A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus

Abstract

Aims

SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes.

Methods

We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level.

Results

There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was −6.57 ± 7.34 mg/ml (p = 0.04).

Conclusions

A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

http://ift.tt/2sCEuFg

Circulating anti-Müllerian hormone (AMH) associates with the maturity of boys’ drawings: Does AMH slow cognitive development in males?

Abstract

Purpose

High levels of circulating anti-Müllerian hormone are unique to developing males, but the function of anti-Müllerian hormone in boys is unknown. In mice, anti-Müllerian hormone contributes to the male biases in the brain, but its receptors are present throughout non-sexually dimorphic portions of the brain. In humans, the speed of maturation is the most overt difference between girls and boys. We postulate that this is because anti-Müllerian hormone slows the maturation of the male human brain.

Methods

One hundred and fourty three 5-year or 6-year-old boys and 38 age-matched girls drew a person and donated a blood sample. The children's drawings were blind-scored to generate a maturity index. The level of anti-Müllerian hormone and the other Sertoli cell hormone, inhibin B, were measured by ELISA. The relationship between the children's age, hormones and maturity index were examined by linear regression analysis.

Results

The girls drew more complex and realistic person than the boys (32%, p = 0.001), with their drawings also being larger (39%, p = 0.037) and more coloured-in (235%, p = 0.0005). The maturity index in boys correlated with age (+r = 0.43, p < 0.0005) and anti-Müllerian hormone level (−r = −0.29, p < 0.0005). The association between maturity index and anti-Müllerian hormone level persisted when corrected for age and for inhibin B (r = −0.24, p = 0.0005). The calculated effect of the median level of anti-Müllerian hormone (1 nM) was equal to 0.81 months of development. The size and colouring of the drawings did not correlate with the boys' age, anti-Müllerian hormone or inhibin B.

Conclusions

This exploratory study provides the first indicative evidence that circulating anti-Müllerian hormone may influence the development of the human brain.

http://ift.tt/2sBUXt5

Identification of a flavonoid C-glycoside as potent antioxidant

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Lingrong Wen, Yupeng Zhao, Yueming Jiang, Limei Yu, Xiaofang Zeng, Jiali Yang, Miaomiao Tian, Huiling Liu, Bao Yang
Flavonoids have been documented to have good antioxidant activities in vitro. However, reports on the cellular antioxidant activities of flavonoid C-glycosides are very limited. In this work, an apigenin C-glycoside was purified from Artocarpus heterophyllus by column chromatography and was identified to be 2″-O-β-D-xylosylvitexin by nuclear magnetic resonance spectroscopy. The cellular antioxidant activity and anticancer activity of 2″-O-β-D-xylosylvitexin were evaluated for the first time. The quantitative structure-activity relationship was analysed by molecular modeling. Apigenin presented an unexpected cellular antioxidation behaviour. It had an antioxidant activity at low concentration and a prooxidant activity at high concentration, whereas 2″-O-β-D-xylosylvitexin showed a dose-dependent cellular antioxidant activity. It indicated that C-glycosidation improved the cellular antioxidation performance of apigenin and eliminated the prooxidant effect. The ortho-dihydroxyl at C-3′/C-4′ and C-3 hydroxyl in the flavonoid skeleton play important roles in the antioxidation behaviour. The cell proliferation assay revealed a low cytotoxicity of 2″-O-β-D-xylosylvitexin.

Graphical abstract

http://ift.tt/2sCjONs

Editorial Board

Publication date: August 2017
Source:Free Radical Biology and Medicine, Volume 109





http://ift.tt/2sBWcsf

Introduction to Special Issue “Redox regulation of cardiovascular signaling in health and disease”

Publication date: August 2017
Source:Free Radical Biology and Medicine, Volume 109
Author(s): Santiago Lamas, Thomas Michel




http://ift.tt/2s37gl7

Reconstruction of the composite defect after extended abdominoperineal resection (eAPR): a clinical experience from Italy

Abstract

Background

Abdominalperineal resection (APR) represents the gold standard for lower third of rectum and anal cancer; after this wide excision, it results a large non-collapsible dead space that tends to collect fluid, increasing the risk of infection and wound dehiscence. Moreover, APR is associated to neoadjuvant/adjuvant radiation therapy with further risk of local complications. In this background, flap reconstruction after APR o eAPR represents the best strategy for minimizing tension in skin closure, providing healthy well vascularized and restoring a good functional local anatomy.

Methods

A retrospective study was performed at the Department of Plastic Reconstructive and Aesthetic Surgery at the University Hospital Città della Salute e della Scienza of Turin from March 2013 to November 2016: 11 patients were included in the study: 5 men and 6 women aged 53 to 76 years (mean ± SD age: 66 ± 7 years). All of them received eAPR (extended-APR). Seven patients required a total dose of 20Gy as neoadjuvant radiotherapy treatment and 6 patients needed adjunctive chemotherapy treatment. Skin defects size ranged from 56 to 180 cm2 (mean 114 ± 38 cm2). Skin defect less than 5 cm of maximum width was not included in the study because no major reconstructions were needed. Surgical reconstruction was planned depending on sacrectomy eventually associated to eAPR and defect size too. Planned follow-up was carried out at 1, 3, and 6 months recording clinical data, local and systemic complications, and pain evaluation at sitting position and during normal walking activity.

Results

Wound healing was achieved in all patients within a period of 21 days. Only one patient showed partial flap necrosis and required wound surgical revision with simple skin closure. Another one patient suffered from mild venous congestion and partial flap necrosis was observed: a period of 2 weeks of negative pressure wound therapy and dressing led to complete healing of the defect (both these patients received 20Gy neoadjuvant radiotherapy). Esthetic pleasant results, high patient satisfaction, and no significant motor impairment were recorded among all patients, excepting for just one patient who reports mild walking impairment and pain at sitting position, after the 6th month follow-up. None of the patient referred significant life quality impairment and all of them expressed general high satisfaction concerning reconstructive expectations.

Conclusions

Many flaps can be harvested to fill and close the large defect after eAPR, with respectively advantages and disadvantages, but we found the use composite gluteal flap technique suitable for most of the patients undergoing eAPR, with good functional results and low rates of morbidity and complications.

Level of Evidence: Level IV, therapeutic study.

http://ift.tt/2s2BDrR

A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus

Abstract

Aims

SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes.

Methods

We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level.

Results

There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was −6.57 ± 7.34 mg/ml (p = 0.04).

Conclusions

A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

http://ift.tt/2sCEuFg

Circulating anti-Müllerian hormone (AMH) associates with the maturity of boys’ drawings: Does AMH slow cognitive development in males?

Abstract

Purpose

High levels of circulating anti-Müllerian hormone are unique to developing males, but the function of anti-Müllerian hormone in boys is unknown. In mice, anti-Müllerian hormone contributes to the male biases in the brain, but its receptors are present throughout non-sexually dimorphic portions of the brain. In humans, the speed of maturation is the most overt difference between girls and boys. We postulate that this is because anti-Müllerian hormone slows the maturation of the male human brain.

Methods

One hundred and fourty three 5-year or 6-year-old boys and 38 age-matched girls drew a person and donated a blood sample. The children's drawings were blind-scored to generate a maturity index. The level of anti-Müllerian hormone and the other Sertoli cell hormone, inhibin B, were measured by ELISA. The relationship between the children's age, hormones and maturity index were examined by linear regression analysis.

Results

The girls drew more complex and realistic person than the boys (32%, p = 0.001), with their drawings also being larger (39%, p = 0.037) and more coloured-in (235%, p = 0.0005). The maturity index in boys correlated with age (+r = 0.43, p < 0.0005) and anti-Müllerian hormone level (−r = −0.29, p < 0.0005). The association between maturity index and anti-Müllerian hormone level persisted when corrected for age and for inhibin B (r = −0.24, p = 0.0005). The calculated effect of the median level of anti-Müllerian hormone (1 nM) was equal to 0.81 months of development. The size and colouring of the drawings did not correlate with the boys' age, anti-Müllerian hormone or inhibin B.

Conclusions

This exploratory study provides the first indicative evidence that circulating anti-Müllerian hormone may influence the development of the human brain.

http://ift.tt/2sBUXt5

Ventilation through an extraglottic tracheal tube: a technique for deep extubation and airway control

Ventilation through an extraglottic tracheal tube: a technique for deep extubation and airway control

Wed, 07 Jun 2017 05:57:03 +0000

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Emergency front-of-neck access: scalpel or cannula

,The parable of Buridan's ass

Wed, 07 Jun 2017 05:46:05 +0000

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Intensity fading MALDI-TOF mass spectrometry and functional proteomics assignments to identify protease inhibitors in marine invertebrates

Publication date: Available online 6 June 2017
Source:Journal of Proteomics
Author(s): Giovanni Covaleda, Sebastian A. Trejo, Emir Salas-Sarduy, Maday Alonso del Rivero, Maria Angeles Chavez, Francesc X. Aviles
Proteases and their inhibitors have become molecules of increasing fundamental and applicative value. Here we report an integrated strategy to identify and analyze such inhibitors from Caribbean marine invertebrates extracts by a fast and sensitive functional proteomics-like approach. The strategy works in three steps: i) multiplexed enzymatic inhibition kinetic assays, ii) Intensity Fading MALDI-TOF MS to establish a link between inhibitory molecules and the related MALDI signal(s) detected in the extract(s), and iii) ISD-CID-T³ MS fragmentation on the parent MALDI signals selected in the previous step, enabling the partial or total top-down sequencing of the molecules. The present study has allowed validation of the whole approach, identification of a substantial number of novel protein protease inhibitors, as well as full or partial sequencing of reference molecular species and of many unknown ones, respectively. Such inhibitors correspond to six protease subfamilies (metallocarboxypeptidases-A and -B, pepsin, papain, trypsin and subtilisin), are small (1–10KDa) disulfide-rich proteins, and have been found at diverse frequencies among the invertebrates (13 to 41%). The overall procedure could be tailored to other enzyme-inhibitor and protein interacting systems, analyzing samples at medium-throughput level and leading to the functional and structural characterization of proteinaceous ligands from complex biological extracts.SignificanceInvertebrate animals, and marine ones among, display a remarkable diversity of species and contained biomolecules. Many of their proteins-peptides have high biological, biotechnological and biomedical potential interest but, because of the lack of sequenced genomes behind, their structural and functional characterization constitutes a great challenge. Here, looking at the small, disulfide-rich, proteinaceous inhibitors of proteases found in them, it is shown that such problem can be significatively facilitated by integrative multiplexed enzymatic assays, affinity-based Intensity-Fading (IF-) MALDI-TOF mass spectrometry (MS), and on-line MS fragmentation, in a fast and easy approach.

Graphical abstract

http://ift.tt/2s2xMuW

The combination of DEX and OND should be recommended in children with a high risk of POV.......Dexamethasone (DEX), ondansetron (OND) and droperidol (DRO) FOR Children undergoing elective surgery under general anaesthesia and considered at high risk for postoperative vomiting (POV)

The combination of DEX and OND should be recommended in children with a high risk of POV.........................................................................................................Dexamethasone (DEX), ondansetron (OND) and droperidol (DRO) FOR Children undergoing elective surgery under general anaesthesia and considered at high risk for postoperative vomiting (POV)

Wed, 07 Jun 2017 05:34:26 +0000

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Psychological Outcomes of Labiaplasty: A Prospective Study.

No abstract available

http://ift.tt/2r3OLIf

Comment to "Evidence-Based Medicine: A Graded Approach to Lower Lid Blepharoplasty".

No abstract available

http://ift.tt/2ryMUPi

Revision Buttock Implantation: Indications, Procedures, and Recommendations.

No abstract available

http://ift.tt/2r3DLec

Response to "Psychological Outcomes of Labiaplasty: A Prospective Study".

No abstract available

http://ift.tt/2rzbujf

Reply to Comment to "A Graded Approach to Lower Lid Blepharoplasty".

No abstract available

http://ift.tt/2r3Cpjq

Tissue Sample Collection From Patients With Head and Neck Cancer and From Healthy Participants

Condition:   Head and Neck Cancer
Interventions:   Other: biologic sample preservation procedure;   Other: medical chart review
Sponsors:   Vanderbilt University Medical Center;   National Cancer Institute (NCI)
Recruiting - verified June 2017

http://ift.tt/2rKjTyz

Chemical Template-assisted Synthesis of Monodisperse Rattle-type Fe3O4@C Hollow Microspheres as Drug Carrier

Publication date: Available online 6 June 2017
Source:Acta Biomaterialia
Author(s): Lin Cheng, Weimin Ruan, Bingfang Zou, Yuanyuan Liu, Yongqiang Wang
A chemical template strategy was put forward to synthesize monodisperse rattle-type magnetic carbon (Fe3O4@C) hollow microspheres. During the synthesis procedure, monodisperse Fe2O3 microspheres were used as chemical template, which released Fe³⁺ ions in acidic solution and initiated the in-situ polymerization of pyrrole into polypyrrole (PPy) shell. With the continual acidic etching of Fe2O3 microspheres, rattle-type Fe2O3@PPy microspheres were generated with the cavity appearing between the PPy shell and left Fe2O3 core, which were then transformed into Fe3O4@C hollow microspheres through calcination in nitrogen atmosphere. Compared with traditional physical template, the shell and cavity of rattle-type hollow microspheres were generated in one step by using the chemical template method, which obviously saved the complex procedures including the coating and removal of middle shells. The experimental results exhibited that the rattle-type Fe3O4@C hollow microspheres with different parameters could be regulated through controlled synthesis of the intermediate Fe2O3@PPy product. Moreover, when the rattle-type Fe3O4@C hollow microspheres were investigated as drug carrier, they manifested sustained-release behaviour of doxorubicin, justifying their promising applications as carriers in drug delivery.Statement of SignificanceThe aim of the present study was first to synthesize rattle-type Fe3O4@C hollow microspheres through a simple synthesis method as a drug carrier. Here a chemical template synthesis of rattle-type hollow microspheres were developed, which saved the complex procedures including the coating and removal of middle shells in traditional physical template. Second, all the influence factors in the reaction processs was systematically investigated to obtain rattle-type Fe3O4@C hollow microspheres with controlled parameters. Third, the rattle-type Fe3O4@C hollow microspheres with controlled parameters were used as durg carriers and investigated for the influence on drug loading and releasing performance.

Graphical abstract

http://ift.tt/2qV5A9j

Colorectal cancer metastatic disease progression in Australia: A population-based analysis

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Qingwei Luo, Dianne L. O'Connell, Clare Kahn, Xue Qin Yu
BackgroundNo previous Australian population-based studies have described or quantified the progression of colorectal cancer (CRC) to metastatic disease. We describe patterns of progression to metastatic disease for an Australian cohort diagnosed with localised or regional CRC.MethodsAll localised and regional CRC cases in the New South Wales Cancer Registry diagnosed during 2000–2007 were followed to December 2011 for subsequent metastases (identified by subsequent disease episode notifications) or CRC death. Cox regression was used to identify factors associated with metastatic progression.ResultsAfter a median 5.3 years follow-up, 26.4% of the 12757 cases initially diagnosed with localised or regional colon cancer had developed metastatic disease, as had 29.5% of the 7154 rectal cancer cases. For both cancer sites, risk of metastatic progression was significantly higher for those initially diagnosed with regional disease (adjusted hazard ratio [aHR] 3.49 for colon, 2.66 for rectal cancer), and for older cases (e.g. aHR for >79years vs <60years: 1.38 for colon, 1.69 for rectal cancer). Risk of disease progression was significantly lower for females, and varied by histology type. For colon cancer, the risk of disease progression decreased over time. For rectal cancer, risk of metastatic progression was significantly higher for those living in more socioeconomically disadvantaged areas compared with those in the least disadvantaged area.ConclusionsAn understanding of the variation in risk of metastatic progression is useful for planning health service requirements, and can help inform decisions about treatment and follow-up for colorectal cancer patients.



http://ift.tt/2qZLn61

A facile coordination-assisted method to fabricate a FRET-based fluorescent probe for ratiometric analysis with improved selectivity

Publication date: November 2017
Source:Sensors and Actuators B: Chemical, Volume 252
Author(s): Wenjing Wang, Yameng Li, Police Vishnuvardhn Reddy, Xuanjun Zhang, Daqiang Yuan
Here we report a facile coordination-assisted method to construct a FRET-based probe that shows ratiometric detection of metal ions with improved selectivity. Probe 2 exhibits good sensitivity and selectivity towards the Fe³⁺ and Al³⁺ over other cations in aqueous acetonitrile solution. Probe 1 can be formed in situ by a convenient addition of Salen-Zn complex, which can further discriminate the Fe³⁺ from Al³⁺ with different ratiometric fluorescence responses.



http://ift.tt/2rSMIuR

Episodic acidification of 5 rivers in Canada's oil sands during snowmelt: A 25-year record

Publication date: 1 December 2017
Source:Science of The Total Environment, Volumes 599–600
Author(s): A.C. Alexander, P.A. Chambers, D.S. Jeffries
Episodic acidification during snowmelt is a natural phenomenon that can be intensified by acidic deposition from heavy industry. In Canada's oil sands region, acid deposition is estimated to be as much as 5% of the Canadian total and large tracks of northeastern Alberta are considered acid-sensitive because of extensive peatland habitats with poorly weathered soils. To identify the frequency, duration and severity of acidification episodes during snowmelt (the predominant hydrological period for delivery of priority pollutants from atmospheric oil sands emissions to surface waters), a 25-year record (1989 to 2014) of automated water quality data (pH, temperature, conductivity) was assembled for 3 rivers along with a shorter record (2012–2014) for another 2 rivers. Acidic episodes (pH<7, ANC<0) were recorded during 39% of all 83 snowmelt events. The severity (duration x magnitude) of episodic acidification increased exponentially over the study period (r²=0.56, P<0.01) and was strongly correlated (P<0.01) with increasing maximum air temperature and weakly correlated with regional land development (P=0.06). Concentrations of aluminum and 11 priority pollutants (Sb, As, Be, Cd, Cr, Cu, Pb, Se, Ag, Tl and Zn) were greatest (P<0.01) during low (<6.5) pH episodes, particularly when coincident with high discharge, such that aluminum and copper concentrations were at times high enough to pose a risk to juvenile rainbow trout (Oncorhynchus mykiss). Although low pH (pH<6.5) was observed during only 8% of 32 acidification episodes, when present, low pH typically lasted 10days. Episodic surface water acidification during snowmelt, and its potential effects on aquatic biota, is therefore an important consideration in the design of long-term monitoring of these typically alkaline (pH=7.72±0.05) rivers.

Graphical abstract

http://ift.tt/2sR4sUx

Spatial patterns and temporal trends of trace metal mass budgets in the western Adriatic sediments (Mediterranean Sea)

Publication date: 1 December 2017
Source:Science of The Total Environment, Volumes 599–600
Author(s): Marilia Lopes-Rocha, Leonardo Langone, Stefano Miserocchi, Patrizia Giordano, Roberta Guerra
Spatial patterns of major (Al, Fe and Ti) and trace metals (Cu, Cr, Mn, Ni, Pb and Zn) measured in surficial sediments collected within the Late-Holocene mud-wedge in the western Adriatic Sea were analyzed to elucidate their sources, transport and mass budgets. Distributions of sedimentary trace metals, their fluvial inputs and accumulation loads reveal along-shore transport towards the southern Adriatic. Pb and to a lower extent Zn accumulation loads over time decreased significantly since 1988 in the North Adriatic, consistently with the implementation of regulations in the Western Europe, whereas Zn accumulation in the Po River prodelta remained unchanged since 1995. The Po River fluvial inputs accounted for half of Cr, Ni, Pb and Zn of the fluvial inputs into the western Adriatic Sea, contributing for the delivery of important amounts of Cr and Ni into the sediments, probably related to the natural occurrence of ultramafic rocks in the North sector. Collectively, ~30% of trace metal fluvial inputs discharged into the North sector are exported to the Central and South sectors. The Po River acts as both a bypass and an accumulation zone. In contrast, trace metal accumulation in the Central sector far exceed trace metal fluvial inputs, which suggested that this area is a preferential sink for particle-reactive river-borne material from the North Adriatic. The North sector shows moderate enrichment of Zn and Pb mainly related to the Po River influence. The anthropogenic fraction of Pb shows a large drop of ~30% from the North sector southwards, whereas Zn proportions remain fairly the same up to the Central sector only decreasing in the South sector.

Graphical abstract

http://ift.tt/2sRb3ya

Chronic corticosterone-induced impaired cognitive flexibility is not due to suppressed adult hippocampal neurogenesis

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): E. Lui, M. Salim, M. Chahal, N. Puri, E. Marandi, J. Quadrilatero, E. Satvat
Hippocampal neurogenesis has been implicated in the etiology of depression. Recent studies suggest new neurons add flexibility to hippocampal-dependent learning and memory. We hypothesized that suppressed hippocampal neurogenesis may contribute to impaired cognitive flexibility associated with depression. The chronic corticosterone (CORT)-induced animal model of depression was used. In Experiment 1, rats received either CORT (40mg/kg) or vehicle injections for 21days and were subjected to Water maze during the last six days of drug treatment. No group differences were found during the spatial learning phase; however, cognitive flexibility, measured by reversal training, was significantly impaired in the CORT-treated rats. The probe test revealed enhanced memory of the new platform location for the CORT-treated rats. Given the time newborn neurons require to mature, we presumed if impaired cognitive flexibility seen in Experiment 1 were due to suppressed neurogenesis, terminating CORT treatment 3days prior to behavioural testing should still induce the impairment. Therefore, Experiment 2 was similar to Experiment 1, except that CORT injections were terminated 3days prior to behavioural assessment. However, not only was spatial learning significantly enhanced in the CORT-treated rats, but there were also no group differences during reversal or probe tests. Bromodeoxyruidine, administered a day after the first drug treatments in both experiments, was quantified and revealed the number of new neurons were the same in both groups in both experiments. Results suggest cognitive flexibility is impaired in the CORT-induced animal model of depression; an effect that is reversible and independent of suppressed hippocampal neurogenesis.



http://ift.tt/2sekD1D

The paracrine effect of cobalt chloride on BMSCs during cognitive function rescue in the HIBD rat

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Ying Dai, Wendi Li, Min Zhong, Jie Chen, Qian Cheng, Youxue Liu, Tingyu Li
Hypoxia–ischemia (HI)-induced perinatal encephalopathy frequently causes chronic neurological morbidities and acute mortality. Bone mesenchymal stem cell (BMSC) transplantation could potentially promote functional and anatomical recovery of ischemic tissue. In vitro hypoxic preconditioning is an effective strategy to improve the survival of BMSCs in ischemic tissue. In this study, cobalt chloride (CoCl2) preconditioned medium from BMSC cultures was injected into the left lateral ventricle of HI rats using a micro-osmotic pump at a flow rate 1.0μl/h for 7 days. The protein levels of HIF-1α and its target genes, vascular endothelial growth factor and erythropoietin, markedly increased after CoCl2 preconditioning in BMSCs. In 7-week-old rats that received CoCl2 preconditioned BMSC medium, results of the Morris water maze test indicated ameliorated spatial working memory function following hypoxia-ischemia damage. Neuronal loss, cellular disorganization, and shrinkage in brain tissue were also ameliorated. Extracellular field excitatory postsynaptic potentials (fEPSPs) in the brain slices of 8-week-old rats were recorded; administration of CoCl2 preconditioned BMSC culture medium induced a progressive increment of baseline and amplitude of the fEPSPs. Immunohistochemical quantification showed that GluR2 protein expression increased. In conclusion, CoCl2 activates HIF-1α signals in BMSCs. CoCl2 preconditioned BMSC culture medium likely effects neuroprotection by inducing long-term potentiation (LTP), which could be associated with GluR2 expression. The paracrine effects of hypoxia preconditioning on BMSCs could have applications in novel cell-based therapeutic strategies for hypoxic and ischemic brain injury.



http://ift.tt/2seCwNY

Cleft palate with/without cleft lip in French children: radiographic evaluation of prevalence, location and coexistence of dental anomalies inside and outside cleft region

Abstract

Introduction

Prevalence of dental anomalies in cleft patients is higher than that in general population. The objectives of this study were to assess the prevalence of dental anomalies and their coexistence in French children with cleft and, then, to investigate the relation between the dental anomalies and the cleft type.

Material and methods

Seventy-four non-syndromic cleft patients (6–16 years old) from Lille Regional University and Mondor-Chenevier Hospitals (France) were included. Clefts were classified as right/left unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP) and cleft palate (CP). Dental anomalies were investigated on panoramic radiographs and categorized as agenesis, supernumerary teeth, incisor rotations, impacted canines and shape anomalies. Prevalence and gender distribution of dental anomalies, mean number of affected teeth per patient, agenesis occurrence and location, and coexistence of dental anomalies were analysed by cleft type.

Results

96.0% of patients presented at least one dental anomaly (agenesis 83.8%, incisor rotations 25.7%, shape anomalies 21.6%, impacted canines 18.9%, supernumerary teeth 8.1%). BCLP patients had a higher number of affected teeth, and left UCLP patients had a higher one compared to right UCLP patients. Distribution of inside (45.3%) and outside (54.7%) cleft region agenesis was similar. Adjacent (31.8%) and not adjacent (33.3%) combined dental anomalies were often encountered.

Conclusions

Dental anomalies were localized inside as well as outside cleft region and were often associated with each other. BCLP patients were more affected.

Clinical relevance

Early radiographic evaluation allows a comprehensive diagnosis of inside and outside cleft region anomalies, required for the multidisciplinary dental treatment.

http://ift.tt/2r3vG9m

Characterization of plastic beach debris finalized to its removal: a proposal for a recycling scheme

Abstract

Characterization of beach debris is crucial to assess the strategy to answer questions such as recycling. With the aim to assess its use in a recycling scheme, in this note, we carried out a physical and chemical characterization of plastic litter from a pilot beach in Central Italy, using the FT-IR spectroscopy and thermoanalysis. Fourteen polymers, having mainly thermoplastic origin, were identified; among them, the most represented are polyethylene (41.7%) and polypropylene (36.9%). Chemical and mechanical degradation were clearly observed by an IR spectrum. The thermogravimetric analysis curve of the plastic blend shows the melting point at 120–140 °C, and degradation occurs almost totally in a one-step process within 300–500 °C. The high heating value of the plastic debris is 43.9 MJ kg⁻¹. Polymer blends obtained by beach debris show mechanical properties similar to the virgin high-density polyethylene polymer. Following the beach plastic debris characterization, a recycling scheme was suggested.

http://ift.tt/2sQMbqw

Effects of different musical frequencies on NPY and Ghrelin secretion in the rat hypothalamus

Publication date: Available online 6 June 2017
Source:Brain Research Bulletin
Author(s): Cristina Russo, Antonella Russo, Rosario Gulino, Rosalia Pellitteri, Stefania Stanzani
It is known that exists a relationship between listening to music and food intake. Hypothalamus appears to integrate the orexigenic properties of a novel peptide, ghrelin (Ghre) that induces food intake through neuropeptide Y (NPY). Ghre stimulates appetite by acting on the ventral hypothalamus, which controls food intake. Ghre is secreted from the stomach and circulates in the bloodstream under fasting conditions, sending a hunger signal from the periphery to the Central Nervous System. The aim of this study was to evaluate, in the rat, the effects of different musical frequencies (432 and 440Hz) on the Ghre and NPY expression in the hypothalamic neurons through immunohistochemistry; in addition, we investigated on the different production of Ghre in the serum through Western blot assay (Wb), in relation to the body weight of animals. Ghre-immunopositive cells were counted, showing a significant increase in music-treated compared to the control (CTR) group. Similarly, music-treated rats showed increased levels of Ghre in the serum compared to CTR animals. Finally, the body weight of animals was affected by music. In particular, music exposure was able to stimulate the body weight increase and, interestingly, the increase was higher when animals were exposed to music at 440Hz. Together, the results strongly support the hypothesis that different musical frequencies could affect food intake by modulating the hypothalamic Ghre expression and its release.



http://ift.tt/2qVaEdw

Functions of AT1 and AT2 angiotensin receptors in the paraventricular nucleus of the rat, correlating single-unit and cardiovascular responses.

Publication date: Available online 6 June 2017
Source:Brain Research Bulletin
Author(s): Mehrangiz Khanmoradi, Ali Nasimi
The paraventricular hypothalamic nucleus (PVN) is a complex structure with both neuroendocrine and autonomic functions including cardiovascular control. The PVN contains angiotensin II (AngII) immunoreactive cells, fibers, as well as AT1 and AT2 receptors of AngII. We microinjected AngII into the PVN of normotensive anesthetized rats and simultaneously recorded blood pressure, heart rate (HR) and single-unit responses. The roles of AT1 and AT2 receptors in these responses were also evaluated. Microinjection of AngII into the PVN produced a short excitatory single-unit response and two types of pressor responses: short duration with a decrease in HR and long with an increase in HR. Microinjection of losartan, an AT1 antagonist, into the PVN produced two response types, attenuation and augmentation of the pressor and firing rate responses to AngII. Microinjection of PD123319, an AT2 antagonist, into the PVN greatly attenuated pressor and single-unit response to AngII, indicating that the pressor response was mediated through AT2 receptors too. In conclusion, microinjection of AngII into the PVN stimulates neurons resulting in an increase in firing rate and consequently produces a short or long pressor response. These responses were mediated through AT1 and AT2 receptors; however, AT1 receptor may produce inhibition too. The results suggest that AngII of the PVN may be a neurotransmitter playing a role in arterial pressure regulation.



http://ift.tt/2sdFvWY

Craniofacial cephalometric morphologies in different cleft types: a retrospective cross-sectional study of 212 patients

Abstract

Objective

The aim of this study was to evaluate and compare the craniofacial cephalometric morphologies among different cleft types in a Spanish population.

Methods

A retrospective cross-sectional study was carried out on 212 patients. The patients were subdivided into four groups according to their cleft types: unilateral cleft lip and palate; bilateral cleft lip and palate; cleft lip; and cleft palate. Angular and linear cephalometric measurements were taken on lateral radiographs.

Results

Unilateral cleft lip and palate was associated with a dolichofacial growth pattern, skeletal Class III with correct maxillary position, and lingual incisor inclination. Bilateral cleft lip and palate was associated with a mesofacial growth pattern, skeletal Class I with protruded maxillary position, and lingual incisor inclination. Cleft palate was associated with a mesofacial growth pattern, skeletal Class III with correct maxillary position, and lingual incisor inclination. Cleft lip was associated with a brachyfacial growth pattern, skeletal Class I with protruded maxillary position, lingual upper incisor inclination, and corrects lower incisor inclination. Significant correlations were observed between cleft types and their craniofacial cephalometric measurements.

Conclusions

The present information can be used for the determination of orthodontic treatment and even future orthognathic surgery planning, a requirement in most cleft patients.

http://ift.tt/2s1RE1e

Associations between mandibular symphysis form and craniofacial structures

Abstract

Objectives

This study aimed to (1) analyze the relationships between mandibular symphysis characteristics (height, prominence, inclination, concavity, and convexity) and facial pattern, skeletal class, lower incisor position, and sex, and (2) determine the associations between the symphysis soft tissue dimensions and the underlying osseous structures.

Methods

Cone-beam computed tomography (CBCT) images were selected for 385 patients (206 women and 179 men). The patients were classified according to their skeletal class and vertical pattern. The lower incisor inclination (IMPA) was recorded. Twelve measurements were taken for each mandibular symphysis using Invivo5 software (Anatomage, San Jose, CA, USA).

Results

Symphyseal measurements were larger in males than in females. Skeletal Class II and III hyperdivergent patients showed the highest symphysis height values. Hypodivergent individuals showed lower symphysis convexity angles. Concavity of the symphysis was greater for Class II hyperdivergent patients. Lower incisor inclination showed a positive correlation with symphysis concavity and inclination. Moderate and weak correlations were found between hard tissue and soft tissue parameters.

Conclusions

Only a few characteristics of symphysis morphology depend on sex, incisor position, skeletal class, and vertical pattern. More significant relationships are found when the vertical pattern and skeletal class are analyzed in combination. The shape of the symphysis soft tissue is not directly correlated with the underlying skeletal structures.

http://ift.tt/2sB3k8f

Evaluation on subcellular partitioning and biodynamics of pulse copper toxicity in tilapia reveals impacts of a major environmental disturbance

Abstract

Fluctuation exposure of trace metal copper (Cu) is ubiquitous in aquatic environments. The purpose of this study was to investigate the impacts of chronically pulsed exposure on biodynamics and subcellular partitioning of Cu in freshwater tilapia (Oreochromis mossambicus). Long-term 28-day pulsed Cu exposure experiments were performed to explore subcellular partitioning and toxicokinetics/toxicodynamics of Cu in tilapia. Subcellular partitioning linking with a metal influx scheme was used to estimate detoxification and elimination rates. A biotic ligand model-based damage assessment model was used to take into account environmental effects and biological mechanisms of Cu toxicity. We demonstrated that the probability causing 50% of susceptibility risk in response to pulse Cu exposure in generic Taiwan aquaculture ponds was ~33% of Cu in adverse physiologically associated, metabolically active pool, implicating no significant susceptibility risk for tilapia. We suggest that our integrated ecotoxicological models linking chronic exposure measurements with subcellular partitioning can facilitate a risk assessment framework that provides a predictive tool for preventive susceptibility reduction strategies for freshwater fish exposed to pulse metal stressors.

http://ift.tt/2s2aTro

Evaluation of FOCUS surface water pesticide concentration predictions and risk assessment of field-measured pesticide mixtures—a crop-based approach under Mediterranean conditions

Abstract

FOCUS models are used in the European regulatory risk assessment (RA) to predict individual pesticide concentrations in edge-of-field surface waters. The scenarios used in higher tier FOCUS simulations were mainly based on Central/North European, and work is needed to underpin the validity of simulated exposure profiles for Mediterranean agroecosystems. In addition, the RA of chemicals are traditionally evaluated on the basis of single substances although freshwater life is generally exposed to a multitude of pesticides. In the present study, we monitored 19 pesticides in surface waters of five locations in the Portuguese 'Lezíria do Tejo' agricultural area. FOCUS step 3 simulations were performed for the South European scenarios to estimate predicted environmental concentrations (PECs). We verified that 44% of the PECs underestimated the measured environmental concentrations (MEC) of the pesticides, showing a non-compliance with the field data. Risk was assessed by comparing the environmental quality standards (EQS) and regulatory acceptable concentrations with their respective MECs. Risk of mixtures was demonstrated in 100% of the samples with insecticides accounting for 60% of the total risk identified. The overall link between the RA and the actual situation in the field must be considerably strengthened, and field studies on pesticide exposure and effects should be carried out to assist the improvement of predictive approaches used for regulatory purposes.

http://ift.tt/2sBeIBf

A comparison between two full-scale MBR and CAS municipal wastewater treatment plants: techno-economic-environmental assessment

Abstract

A holistic assessment procedure has been used in this study for comparing conventional activated sludge (CAS) and membrane bioreactor (MBR) processes for the treatment of municipal wastewater. Technical, social, administrative, economic and environmental impacts have been evaluated based on 1 year of operational data from three full-scale lines (one MBR and two CAS) working in parallel in a large municipal treatment plant. The comparative assessment evidences a slight advantage of the conventional process in the studied case, essentially due to lower costs, complexity and energy consumption. On the other hand, the MBR technology has a better social acceptance and similar overall environmental footprint. Although these results are influenced by site-specific parameters and cannot be generalized, the assessment procedure allowed identifying the most important factors affecting the final scores for each technology and the main differences between the compared technologies. Local conditions can affect the relative importance of the assessed impacts, and the use of weighting factors is proposed for better tailoring the comparative assessment to the local needs and circumstances. A sensitivity analysis on the weighted final scores demonstrated how local factors are very important and must be carefully evaluated in the decision making process.

http://ift.tt/2s1JIx4

Scholar : These new articles for Acta Odontologica Scandinavica are available online

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The online platform for Taylor & Francis Online content New for Acta Odontologica Scandinavica and online now on Taylor & Francis Online: Letter to the Editor Reproducibility of a commercially available subgingival plaque sampling strategy with oligonucleotide probes, common mistake Siamak Sabour http://ift.tt/2rSyv0Q Pages: 1-1 | DOI: 10.1080/00016357.2017.1335431 Original Article Can the Enterococcus faecalis identified in the root canals of primary teeth be a cause of failure of endodontic treatment? Viviane Cancio, Dennis de Carvalho Ferreira, Fernanda Sampaio Cavalcante, Alexandre Soares Rosado, Lúcia Martins Teixeira, Queila Braga Oliveira, Roberta Barcelos http://ift.tt/2rSkJvc, Rogerio Gleiser, Henrique Fragoso Santos http://ift.tt/2sQogYm, Kátia Regina Netto dos Santos & Laura Guimarães Primo Pages: 1-6 | DOI: 10.1080/00016357.2017.1328742 Journal of HIV/AIDS & Social Services – FREE ACCESS Article Collection - click here To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Compromised Survival of Cerebellar Molecular Layer Interneurons Lacking GDNF Receptors GFRα1 or RET Impairs Normal Cerebellar Motor Learning

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Maria Christina Sergaki, Juan Carlos López-Ramos, Stefanos Stagkourakis, Agnès Gruart, Christian Broberger, José María Delgado-García, Carlos F. Ibáñez
The role of neurotrophic factors as endogenous survival proteins for brain neurons remains contentious. In the cerebellum, the signals controlling survival of molecular layer interneurons (MLIs) are unknown, and direct evidence for the requirement of a full complement of MLIs for normal cerebellar function and motor learning has been lacking. Here, we show that Purkinje cells (PCs), the target of MLIs, express the neurotrophic factor GDNF during MLI development and survival of MLIs depends on GDNF receptors GFRα1 and RET. Conditional mutant mice lacking either receptor lose a quarter of their MLIs, resulting in compromised synaptic inhibition of PCs, increased PC firing frequency, and abnormal acquisition of eyeblink conditioning and vestibulo-ocular reflex performance, but not overall motor activity or coordination. These results identify an endogenous survival mechanism for MLIs and reveal the unexpected vulnerability and selective requirement of MLIs in the control of cerebellar-dependent motor learning.

Graphical abstract

Teaser

Sergaki et al. find that conditional mutant mice lacking GDNF receptor GFRα1 or RET lose a quarter of their cerebellar molecular layer interneurons (MLIs), resulting in compromised motor learning but not overall motor coordination. These results identify an endogenous survival mechanism for MLIs and reveal their unexpected vulnerability in the control of cerebellar-dependent motor learning


http://ift.tt/2sQgL3x

Global Hypertranscription in the Mouse Embryonic Germline

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Michelle Percharde, Priscilla Wong, Miguel Ramalho-Santos
Primordial germ cells (PGCs) are vital for inheritance and evolution. Their transcriptional program has been extensively studied and is assumed to be well known. We report here a remarkable global upregulation of the transcriptome of mouse PGCs compared to somatic cells. Using cell-number-normalized genome-wide analyses, we uncover significant transcriptional amplification in PGCs, including mRNAs, rRNA, and transposable elements. Hypertranscription preserves tissue-specific gene expression patterns, correlates with cell size, and can still be detected in E15.5 male germ cells when proliferation has ceased. PGC hypertranscription occurs at the level of nascent transcription, is accompanied by increased translation rates, and is driven by Myc factors n-Myc and l-Myc (but not c-Myc) and by P-TEFb. This study provides a paradigm for transcriptional analyses during development and reveals a major global hyperactivity of the germline transcriptome.

Graphical abstract

Teaser

Percharde et al. find that mouse primordial germ cells are in a state of hypertranscription driven by Myc factors and P-TEFb.


http://ift.tt/2sQn5rL

Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Kasper W. ter Horst, Pim W. Gilijamse, Ruth I. Versteeg, Mariette T. Ackermans, Aart J. Nederveen, Susanne E. la Fleur, Johannes A. Romijn, Max Nieuwdorp, Dongyan Zhang, Varman T. Samuel, Daniel F. Vatner, Kitt F. Petersen, Gerald I. Shulman, Mireille J. Serlie
Hepatic lipid accumulation has been implicated in the development of insulin resistance, but translational evidence in humans is limited. We investigated the relationship between liver fat and tissue-specific insulin sensitivity in 133 obese subjects. Although the presence of hepatic steatosis in obese subjects was associated with hepatic, adipose tissue, and peripheral insulin resistance, we found that intrahepatic triglycerides were not strictly sufficient or essential for hepatic insulin resistance. Thus, to examine the molecular mechanisms that link hepatic steatosis to hepatic insulin resistance, we comprehensively analyzed liver biopsies from a subset of 29 subjects. Here, hepatic cytosolic diacylglycerol content, but not hepatic ceramide content, was increased in subjects with hepatic insulin resistance. Moreover, cytosolic diacylglycerols were strongly associated with hepatic PKCε activation, as reflected by PKCε translocation to the plasma membrane. These results demonstrate the relevance of hepatic diacylglycerol-induced PKCε activation in the pathogenesis of NAFLD-associated hepatic insulin resistance in humans.

Graphical abstract

Teaser

ter Horst et al. show that simple hepatic steatosis in the context of NAFLD does not fully explain hepatic insulin resistance in obese humans. Impaired hepatic insulin action was characterized by accumulation of diacylglycerol subspecies in the cytosol of hepatocytes and translocation of PKCε from the cytosol to the membrane.


http://ift.tt/2sQg22c

Phosphorylation of TXNIP by AKT Mediates Acute Influx of Glucose in Response to Insulin

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Althea N. Waldhart, Holly Dykstra, Anderson S. Peck, Elissa A. Boguslawski, Zachary B. Madaj, Jennifer Wen, Kelsey Veldkamp, Matthew Hollowell, Bin Zheng, Lewis C. Cantley, Timothy E. McGraw, Ning Wu
Growth factors, such as insulin, can induce both acute and long-term glucose uptake into cells. Apart from the rapid, insulin-induced fusion of glucose transporter (GLUT)4 storage vesicles with the cell surface that occurs in muscle and adipose tissues, the mechanism behind acute induction has been unclear in other systems. Thioredoxin interacting protein (TXNIP) has been shown to be a negative regulator of cellular glucose uptake. TXNIP is transcriptionally induced by glucose and reduces glucose influx by promoting GLUT1 endocytosis. Here, we report that TXNIP is a direct substrate of protein kinase B (AKT) and is responsible for mediating AKT-dependent acute glucose influx after growth factor stimulation. Furthermore, TXNIP functions as an adaptor for the basal endocytosis of GLUT4 in vivo, its absence allows excess glucose uptake in muscle and adipose tissues, causing hypoglycemia during fasting. Altogether, TXNIP serves as a key node of signal regulation and response for modulating glucose influx through GLUT1 and GLUT4.

Graphical abstract

Teaser

Waldhart et al. find that TXNIP, an α-arrestin protein, is an adaptor for endocytosis of the glucose transporter GLUT4. Growth factor stimulation induces acute glucose uptake into cells by activating AKT-mediated TXNIP phosphorylation, forcing TXNIP to dissociate from the transporters, thus inhibiting their endocytosis.


http://ift.tt/2sQBMuK

mTOR Inhibition Subdues Milk Disorder Caused by Maternal VLDLR Loss

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): HoangDinh Huynh, Wei Wei, Yihong Wan
It is unknown whether and how very-low density lipoprotein receptors (VLDLRs) impact skeletal homeostasis. Here, we report that maternal and offspring VLDLRs play opposite roles in osteoclastogenesis and bone resorption. VLDLR deletion in the offspring augments osteoclast differentiation by enhancing RANKL signaling, leading to osteoporosis. In contrast, VLDLR deletion in the mother alters milk metabolism, which inhibits osteoclast differentiation and causes osteopetrosis in the offspring. The maternal effects are dominant. VLDLR-null lactating mammary gland exhibits higher mTORC1 signaling and cholesterol biosynthesis. Pharmacological probing reveals that rapamycin, but not statin, treatment of the VLDLR-null mother can prevent both the low bone resorption and our previously described inflammatory fur loss in their offspring. Genetic rescue reveals that maternal mTORC1 attenuation in adipocytes, but not in myeloid cells, prevents offspring osteopetrosis and fur loss. Our studies uncover functions of VLDLR and mTORC1 in lactation and osteoclastogenesis, illuminating key mechanisms and therapeutic insights for bone and metabolic diseases.

Graphical abstract

Teaser

Huynh et al. report that osteoclastogenesis and bone resorption are enhanced by offspring VLDLR deletion due to augmented RANKL signaling but impaired by maternal VLDLR deletion due to excessive mTOR signaling in the lactating mammary gland, providing key insights for VLDLR functions, milk metabolism, and maternal regulation of offspring traits.


http://ift.tt/2sQpvXz

The Alzheimer’s Disease γ-Secretase Generates Higher 42:40 Ratios for β-Amyloid Than for p3 Peptides

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Gabriele Siegel, Hermeto Gerber, Philipp Koch, Oliver Bruestle, Patrick C. Fraering, Lawrence Rajendran
Alzheimer's disease is characterized by intracerebral deposition of β-amyloid (Aβ). While Aβ40 is the most abundant form, neurotoxicity is mainly mediated by Aβ42. Sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases gives rise to full-length Aβ (Aβ1-x) and N-terminally truncated Aβ′ (Aβ11-x) whereas cleavage by α- and γ-secretases leads to the shorter p3 peptides (Aβ17-x). We uncovered significantly higher ratios of 42- versus 40-ending variants for Aβ and Aβ′ than for p3 secreted by mouse neurons and human induced pluripotent stem cell (iPSC)-derived neurons or produced in a cell-free γ-secretase assay with recombinant APP-CTFs. The 42:40 ratio was highest for Aβ′, followed by Aβ and then p3. Mass spectrometry analysis of APP intracellular domains revealed differential processing of APP-C83, APP-C89, and APP-C99 by γ-secretase already at the ε-cleavage stage. This mechanistic insight could aid in developing substrate-targeted modulators of APP-C99 processing to specifically lower the Aβ42:Aβ40 ratio without compromising γ-secretase function.

Graphical abstract

Teaser

Siegel et al. find differences in the γ-secretase-mediated processing of the three major β-secretase- and α-secretase-cleaved C-terminal fragments of amyloid precursor protein (APP-C99, APP-C89, and APP-C83). Mouse and human neurons secrete significantly higher ratios of 42- versus 40-ending variants for Aβ and Aβ′ peptides than for p3 peptides.


http://ift.tt/2sQj2fe

MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Arun K. Rooj, Franz Ricklefs, Marco Mineo, Ichiro Nakano, E. Antonio Chiocca, Agnieszka Bronisz, Jakub Godlewski
Large-scale transcriptomic profiling of glioblastoma (GBM) into subtypes has provided remarkable insight into the pathobiology and heterogeneous nature of this disease. The mechanisms of speciation and inter-subtype transitions of these molecular subtypes require better characterization to facilitate the development of subtype-specific targeting strategies. The deregulation of microRNA expression among GBM subtypes and their subtype-specific targeting mechanisms are poorly understood. To reveal the underlying basis of microRNA-driven complex subpopulation dynamics within the heterogeneous intra-tumoral ecosystem, we characterized the expression of the subtype-enriched microRNA-128 (miR-128) in transcriptionally and phenotypically diverse subpopulations of patient-derived glioblastoma stem-like cells. Because microRNAs are capable of re-arranging the molecular landscape in a cell-type-specific manner, we argue that alterations in miR-128 levels are a potent mechanism of bidirectional transitions between GBM subpopulations, resulting in intermediate hybrid stages and emphasizing highly intricate intra-tumoral networking.

Graphical abstract

Teaser

Rooj et al. find that miR-128-dependent transitions between heterogeneous GSC subtypes lead to molecular rearrangements influencing GSC phenotypes in vitro and in vivo. These transcriptomic transitions, mediated largely by Polycomb repressive complexes, are predictive of GBM patient subtype identity and outcome.


http://ift.tt/2sQoWgg

Regulation of Rvb1/Rvb2 by a Domain within the INO80 Chromatin Remodeling Complex Implicates the Yeast Rvbs as Protein Assembly Chaperones

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Coral Y. Zhou, Caitlin I. Stoddard, Jonathan B. Johnston, Michael J. Trnka, Ignacia Echeverria, Eugene Palovcak, Andrej Sali, Alma L. Burlingame, Yifan Cheng, Geeta J. Narlikar
The hexameric AAA+ ATPases Rvb1 and Rvb2 (Rvbs) are essential for diverse processes ranging from metabolic signaling to chromatin remodeling, but their functions are unknown. While originally thought to act as helicases, recent proposals suggest that Rvbs act as protein assembly chaperones. However, experimental evidence for chaperone-like behavior is lacking. Here, we identify a potent protein activator of the Rvbs, a domain in the Ino80 ATPase subunit of the INO80 chromatin-remodeling complex, termed Ino80INS. Ino80INS stimulates Rvbs' ATPase activity by 16-fold while concomitantly promoting their dodecamerization. Using mass spectrometry, cryo-EM, and integrative modeling, we find that Ino80INS binds asymmetrically along the dodecamerization interface, resulting in a conformationally flexible dodecamer that collapses into hexamers upon ATP addition. Our results demonstrate the chaperone-like potential of Rvb1/Rvb2 and suggest a model where binding of multiple clients such as Ino80 stimulates ATP-driven cycling between hexamers and dodecamers, providing iterative opportunities for correct subunit assembly.

Graphical abstract

Teaser

Rvb1 and Rvb2 (Rvbs) are AAA+ ATPases that have been hypothesized to assemble multi-subunit protein complexes, though this activity has not been experimentally demonstrated. Zhou et al. find that a domain within the chromatin remodeling Ino80 ATPase is a potent activator of Rvb1/Rvb2, creating a metastable dodecamer of Rvb/1Rvb2 that dissociates upon ATP addition.


http://ift.tt/2sQoL4D

Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Alfonso Urbanucci, Stefan J. Barfeld, Ville Kytölä, Harri M. Itkonen, Ilsa M. Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K. Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R. Jeffrey Karnes, Ashley E. Ross, Edward M. Schaeffer, Donald J. Vander Griend, Stefan Knapp, Eva Corey, Felix Y. Feng, Peter S. Nelson, Fahri Saatcioglu, Karen E. Knudsen, Teuvo L.J. Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G. Mills
Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.

Graphical abstract

Teaser

Urbanucci et al. report how upregulated androgen receptor (AR) and AR-targeted bromodomain proteins contribute to genome-wide chromatin relaxation and increased gene transcription in advanced prostate cancer. They show that ATAD2 is a strong tissue biomarker and propose a BROMO-10 gene signature to stratify patients for combination therapies with bromodomain inhibitors.


http://ift.tt/2sQBCDE

PLK1 Activation in Late G2 Sets Up Commitment to Mitosis

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Lilia Gheghiani, Damarys Loew, Bérangère Lombard, Jörg Mansfeld, Olivier Gavet
Commitment to mitosis must be tightly coordinated with DNA replication to preserve genome integrity. While we have previously established that the timely activation of CyclinB1-Cdk1 in late G2 triggers mitotic entry, the upstream regulatory mechanisms remain unclear. Here, we report that Polo-like kinase 1 (Plk1) is required for entry into mitosis during an unperturbed cell cycle and is rapidly activated shortly before CyclinB1-Cdk1. We determine that Plk1 associates with the Cdc25C1 phosphatase and induces its phosphorylation before mitotic entry. Plk1-dependent Cdc25C1 phosphosites are sufficient to promote mitotic entry, even when Plk1 activity is inhibited. Furthermore, we find that activation of Plk1 during G2 relies on CyclinA2-Cdk activity levels. Our findings thus elucidate a critical role for Plk1 in CyclinB1-Cdk1 activation and mitotic entry and outline how CyclinA2-Cdk, an S-promoting factor, poises cells for commitment to mitosis.

Graphical abstract

Teaser

Gheghiani et al. find that Plk1 activity is required for commitment to mitosis during normal cell cycles. Sudden Plk1 activation in late G2 is dependent on CyclinA2-Cdk activity levels and triggers Cdc25C1 phosphorylation, promoting mitotic entry.


http://ift.tt/2sQf3iF

Sonic Hedgehog Activates Phospholipase A2 to Enhance Smoothened Ciliary Translocation

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Angela M. Arensdorf, Miriam E. Dillard, Jacob M. Menke, Matthew W. Frank, Charles O. Rock, Stacey K. Ogden
The G protein-coupled receptor Smoothened (Smo) is the signal transducer of the Sonic Hedgehog (Shh) pathway. Smo signals through G protein-dependent and -independent routes, with G protein-independent canonical signaling to Gli effectors requiring Smo accumulation in the primary cilium. The mechanisms controlling Smo activation and trafficking are not yet clear but likely entail small-molecule binding to pockets in its extracellular cysteine-rich domain (CRD) and/or transmembrane bundle. Here, we demonstrate that the cytosolic phospholipase cPLA2α is activated through Gβγ downstream of Smo to release arachidonic acid. Arachidonic acid binds Smo and synergizes with CRD-binding agonists, promoting Smo ciliary trafficking and high-level signaling. Chemical or genetic cPLA2α inhibition dampens Smo signaling to Gli, revealing an unexpected contribution of G protein-dependent signaling to canonical pathway activity. Arachidonic acid displaces the Smo transmembrane domain inhibitor cyclopamine to rescue CRD agonist-induced signaling, suggesting that arachidonic acid may target the transmembrane bundle to allosterically enhance signaling by CRD agonist-bound Smo.

Graphical abstract

Teaser

Arensdorf et al. report that phospholipase A2 is activated downstream of the G protein-coupled receptor Smoothened to produce arachidonic acid. Arachidonic acid binds the Smoothened transmembrane domain to promote Smoothened ciliary trafficking and high-level signaling. These results identify arachidonic acid as a candidate allosteric regulator of Smoothened.


http://ift.tt/2sQoJK3

MYO6 Regulates Spatial Organization of Signaling Endosomes Driving AKT Activation and Actin Dynamics

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Thomas A. Masters, David A. Tumbarello, Margarita V. Chibalina, Folma Buss
APPL1- and RAB5-positive signaling endosomes play a crucial role in the activation of AKT in response to extracellular stimuli. Myosin VI (MYO6) and two of its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and mediate endosome association with cortical actin filaments. Loss of MYO6 leads to the displacement of these endosomes from the cell cortex and accumulation in the perinuclear space. Depletion of this myosin not only affects endosome positioning, but also induces actin and lipid remodeling consistent with endosome maturation, including accumulation of F-actin and the endosomal lipid PI(3)P. These processes acutely perturb endosome function, as both AKT phosphorylation and RAC-dependent membrane ruffling were markedly reduced by depletion of either APPL1 or MYO6. These results place MYO6 and its binding partners at a central nexus in cellular signaling linking actin dynamics at the cell surface and endosomal signaling in the cell cortex.

Graphical abstract

Teaser

Masters et al. report that MYO6 tethers APPL1 signaling endosomes to the actin cortex. Depletion of MYO6 leads to premature maturation and displacement of these endosomes away from the cell cortex, as well as defective AKT activation and impaired cortical actin dynamics.


http://ift.tt/2sQfPvW

Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Ana Paula Zen Petisco Fiore, Virginia A. Spencer, Hidetoshi Mori, Hernandes F. Carvalho, Mina J. Bissell, Alexandre Bruni-Cardoso
Nuclear actin (N-actin) is known to participate in the regulation of gene expression. We showed previously that N-actin levels mediate the growth and quiescence of mouse epithelial cells in response to laminin-111 (LN1), a component of the mammary basement membrane (BM). We know that BM is defective in malignant cells, and we show here that it is the LN1/N-actin pathway that is aberrant in human breast cancer cells, leading to continuous growth. Photobleaching assays revealed that N-actin exit in nonmalignant cells begins as early as 30 min after LN1 treatment. LN1 attenuates the PI3K pathway leading to upregulation of exportin-6 (XPO6) activity and shuttles actin out of the nucleus. Silencing XPO6 prevents quiescence. Malignant cells are impervious to LN1 signaling. These results shed light on the crucial role of LN1 in quiescence and differentiation and how defects in the LN1/PI3K/XPO6/N-actin axis explain the loss of tissue homeostasis and growth control that contributes to malignant progression.

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Teaser

Fiore et al. show that laminin-111 (LN1) induces a drastic decrease of nuclear actin in human mammary epithelial cells in a process mediated by XPO6 and required for acquisition of cellular quiescence. The LN1/XPO6/N-actin pathway is abnormal in malignant cells that are unresponsive to LN1 and proliferate uncontrollably.


http://ift.tt/2sQmXIN

Hepatocyte ABCA1 Deletion Impairs Liver Insulin Signaling and Lipogenesis

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Chia-Chi C. Key, Mingxia Liu, C. Lisa Kurtz, Soonkyu Chung, Elena Boudyguina, Timothy A. Dinh, Alexander Bashore, Peter E. Phelan, Barry I. Freedman, Timothy F. Osborne, Xuewei Zhu, Lijun Ma, Praveen Sethupathy, Sudha B. Biddinger, John S. Parks
Plasma membrane (PM) free cholesterol (FC) is emerging as an important modulator of signal transduction. Here, we show that hepatocyte-specific knockout (HSKO) of the cellular FC exporter, ATP-binding cassette transporter A1 (ABCA1), leads to decreased PM FC content and defective trafficking of lysosomal FC to the PM. Compared with controls, chow-fed HSKO mice had reduced hepatic (1) insulin-stimulated Akt phosphorylation, (2) activation of the lipogenic transcription factor Sterol Regulatory Element Binding Protein (SREBP)-1c, and (3) lipogenic gene expression. Consequently, Western-type diet-fed HSKO mice were protected from steatosis. Surprisingly, HSKO mice had intact glucose metabolism; they showed normal gluconeogenic gene suppression in response to re-feeding and normal glucose and insulin tolerance. We conclude that: (1) ABCA1 maintains optimal hepatocyte PM FC, through intracellular FC trafficking, for efficient insulin signaling; and (2) hepatocyte ABCA1 deletion produces a form of selective insulin resistance so that lipogenesis is suppressed but glucose metabolism remains normal.

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Teaser

Key et al. find that deletion of hepatocyte ABCA1 leads to decreased lysosomal free-cholesterol trafficking to the plasma membrane and attenuated cholesterol biosynthesis, resulting in decreased insulin signaling to mTORC1 and attenuated lipogenesis. However, gluconeogenesis remains responsive. Mice lacking hepatocyte ABCA1 are resistant to high-fat-diet-induced hepatosteatosis.


http://ift.tt/2sQgE87

Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Alexandra Clemente-Perez, Stefanie Ritter Makinson, Bryan Higashikubo, Scott Brovarney, Frances S. Cho, Alexander Urry, Stephanie S. Holden, Matthew Wimer, Csaba Dávid, Lief E. Fenno, László Acsády, Karl Deisseroth, Jeanne T. Paz
Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT) gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers. We dissociated the connectivity, physiology, and circuit functions of neurons within rodent nRT, based on parvalbumin (PV) and somatostatin (SOM) expression, and validated the existence of such populations in human nRT. We found that PV, but not SOM, cells are rhythmogenic, and that PV and SOM neurons are connected to and modulate distinct thalamocortical circuits. Notably, PV, but not SOM, neurons modulate somatosensory behavior and disrupt seizures. These results provide a conceptual framework for how nRT may gate incoming information to modulate brain-wide rhythms.

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Teaser

Clemente-Perez et al. deconstruct the nucleus reticularis thalami (nRT) at the cellular, circuit, and behavioral levels. They find that parvalbumin- and somatostatin-expressing neurons in nRT have distinct cellular and circuit properties, segregate along predominantly non-overlapping neuronal pathways, and differentially modulate thalamocortical rhythmogenesis, somatosensory behavior, and generalized seizures.


http://ift.tt/2sQ68he

Dorsal-CA1 Hippocampal Neuronal Ensembles Encode Nicotine-Reward Contextual Associations

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Li Xia, Stephanie K. Nygard, Gabe G. Sobczak, Nicholas J. Hourguettes, Michael R. Bruchas
Natural and drug rewards increase the motivational valence of stimuli in the environment that, through Pavlovian learning mechanisms, become conditioned stimuli that directly motivate behavior in the absence of the original unconditioned stimulus. While the hippocampus has received extensive attention for its role in learning and memory processes, less is known regarding its role in drug-reward associations. We used in vivo Ca²⁺ imaging in freely moving mice during the formation of nicotine preference behavior to examine the role of the dorsal-CA1 region of the hippocampus in encoding contextual reward-seeking behavior. We show the development of specific neuronal ensembles whose activity encodes nicotine-reward contextual memories and that are necessary for the expression of place preference. Our findings increase our understanding of CA1 hippocampal function in general and as it relates to reward processing by identifying a critical role for CA1 neuronal ensembles in nicotine place preference.

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Teaser

Xia et al. find that nicotine contextual learning (place preference) recruits specific CA1 neuronal ensembles within drug-paired contexts and that these ensembles are also reactivated in drug-paired contexts in the absence of nicotine. These findings indicate that CA1 ensembles integrate nicotine-contextual information for subsequent cued-behavioral responses.


http://ift.tt/2sQeXHP

Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Zachary M. Carico, Kingshuk Roy Choudhury, Baojun Zhang, Yuan Zhuang, Michael S. Krangel
Adaptive immunity depends on diverse T cell receptor repertoires generated by variable, diversity, and joining (V[D]J) recombination. Here, we define the principles by which combinatorial diversity is generated in the murine Tcra repertoire. Tcra and Tcrd gene segments share the Tcra-Tcrd locus, with interspersed Vα and Vδ segments undergoing Vδ-Dδ-Jδ rearrangement in CD4⁻CD8⁻ thymocytes and then multiple rounds of Vα-Jα rearrangement in CD4⁺CD8⁺ thymocytes. We document stepwise, highly coordinated proximal-to-distal progressions of Vα and Jα use on individual Tcra alleles, limiting combinatorial diversity. This behavior is supported by an extended chromatin conformation in CD4⁺CD8⁺ thymocytes, with only nearby Vα and Jα segments contacting each other. Tcrd rearrangements can use distal Vδ segments due to a contracted Tcra-Tcrd conformation in CD4⁻CD8⁻ thymocytes. These rearrangements expand the Tcra repertoire by truncating the Vα array to permit otherwise disfavored Vα-Jα combinations. Therefore, recombination events at two developmental stages with distinct chromatin conformations synergize to promote Tcra repertoire diversity.

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Teaser

A diverse Tcra repertoire is essential for robust adaptive immunity. Carico et al. demonstrate that the Tcra repertoire is intrinsically limited by a processive recombination program. Tcrd recombination overcomes this constraint to broaden Vα-Jα combinatorial diversity, and it is important for the development of MAIT cells, an innate-like αβ T cell subset.


http://ift.tt/2sQrHhw

NLRP6 Protects Il10−/− Mice from Colitis by Limiting Colonization of Akkermansia muciniphila

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Sergey S. Seregin, Natasha Golovchenko, Bryan Schaf, Jiachen Chen, Nicholas A. Pudlo, Jonathan Mitchell, Nielson T. Baxter, Lili Zhao, Patrick D. Schloss, Eric C. Martens, Kathryn A. Eaton, Grace Y. Chen




http://ift.tt/2sQf31Y

Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-Mediated Oxidative Antimicrobial Offense

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Philipp Wiemann, Adi Perevitsky, Fang Yun Lim, Yana Shadkchan, Benjamin P. Knox, Julio A. Landero Figueora, Tsokyi Choera, Mengyao Niu, Andrew J. Steinberger, Marcel Wüthrich, Rachel A. Idol, Bruce S. Klein, Mary C. Dinauer, Anna Huttenlocher, Nir Osherov, Nancy P. Keller




http://ift.tt/2rS75Z6

Cycling around Lysine Modifications

Publication date: Available online 6 June 2017
Source:Trends in Biochemical Sciences
Author(s): Surinder Kumar, David B. Lombard
Recent studies have revealed the existence of a plethora of previously unknown protein acyl-lysine modifications, affecting the functions of targets involved in diverse cellular processes. A recent study from the Hirschey laboratory has provided new chemical insights into the mechanisms of protein acylation.



http://ift.tt/2sefNkS

Scholar : These new articles for Computer-Aided Design and Applications are available online

The online platform for Taylor & Francis Online content New for Computer-Aided Design and Applications and online now on Taylor & Francis Online: Original Articles Adaptive eigensystem truncation for spectral shape signatures Reed M. Williams http://ift.tt/2sQk62x & Horea T. Ilieş Pages: 1-8 | DOI: 10.1080/16864360.2017.1287679 Read selected content from the Journal of Structural Integrity and Maintenance for free! http://ift.tt/2coiFom To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Africa Review are available online

The online platform for Taylor & Francis Online content New for Africa Review and online now on Taylor & Francis Online: Original Articles Feasibility of funding peace operation in Africa: understanding the challenges of Southern African development community standby force (SADCSF) Emeka Austin Ndaguba & Charles Okonkwo Pages: 1-14 | DOI: 10.1080/09744053.2017.1329807 Interested in the political-economic topics surrounding China? You wouldn't want to miss this exclusive collection. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

A novel dianionic amino acid ionic liquid-coated PEG 4000 modified Fe3O4 nanocomposite for the magnetic solid-phase extraction of trypsin

Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Qin Yang, Yuzhi Wang, Hongmei Zhang, Kaijia Xu, Xiaoxiao Wei, Panli Xu, Yigang Zhou
A novel magnetic extractant, PEG 4000 modified Fe3O4nanomaterial that coated with dianionic amino acid ionic liquid (Fe3O4@PEG@DAAAIL), was successfully synthesized and characterized. X-ray diffraction (XRD), transmission electron microscope (TEM), vibrating sample magnetometer (VSM), fourier transform infrared spectrometry (FT-IR), thermal gravimetric analysis (TGA) and zeta potentials were used to confirm that the novel nanocomposite was successfully synthesized. Subsequently, the prepared Fe3O4@PEG@DAAAIL nanocomposite was used as the extractant for trypsin coupled with magnetic solid-phase extraction (MSPE). The concentrations of trypsin in the supernatant were detected by UV–vis spectrophotometer at 278nm. The extraction ability turned out to be better than the other four kinds of extractants prepared in this work. Furthermore, the influence of a series of factors, such as extraction time and temperature, initial trypsin concentration, the value of pH and ionic strength, was systematically investigated. Under the optimal extraction condition, the extraction capacity for trypsin could reach up to 718.73mg/g, absolutely higher than that of other adsorbents reported. This satisfactory extraction capacity could be maintained unchangeable after at least eight days, and kept over 90% of initial extraction capacity after eight recycles. What's more, the activity of trypsin after extraction retained 92.29% of initial activity, verifying the biocompatibility of the prepared extractant. Finally, the developed Fe3O4@PEG@DAAAIL-MSPE method was successfully applied to the real sample analysis with satisfactory results. All of above proves the potential value of Fe3O4@PEG@DAAAIL-MSPE in the analysis of biomass.

Graphical abstract

http://ift.tt/2rS6Ey2

Silver triangular nanoplates as an high efficiently FRET donor-acceptor of upconversion nanoparticles for ultrasensitive “Turn on-off” protamine and trypsin sensor

Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Hongyu Chen, Aijin Fang, Youyu Zhang, Shouzhuo Yao
Silver triangular nanoplates (STNPs) as a high efficient fluorescence quenching reagent of upconversion nanoparticles (UCNPs) was used to constract a novel label-free fluorescence nanosensor for ultrasensitive detection of protamine and trypsin based on fluorescence resonance energy transfer (FRET) between STNPs and UCNPs. In this assay, the negatively charged STNPs can bind with positively charged UCNPs through electrostatic interaction, and then quenched the fluorescence of UCNPs. When protamine was added to the mixture of UCNPs-STNPs, the STNPs interacted with protamine and then detached from the surface of UCNPs and aggregated, which result in the recovery of the fluorescence of UCNPs. Trypsin could catalyze the hydrolysis of protamine and effectively quench the fluorescence recovered by protamine. By measuring the changes of the fluorescence of UCNPs, the concentrations of protamine and trypsin were determined. Under the optimized conditions, the linear response range was obtained from 10 to 500ng/mL, 5–80ng/mL and with the low detection limit of 3.1ng/mL and 1.8ng/mL for protamine and trypsin, respectively. Meanwhile, the nanosensor shows good selectivity, sensitivity and can be successfully applied to detection of protamine and trypsin in serum samples.

Graphical abstract

http://ift.tt/2rSfSKx

Scholar : These new articles for Advances in School Mental Health Promotion are available online

The online platform for Taylor & Francis Online content New for Advances in School Mental Health Promotion and online now on Taylor & Francis Online: Original Articles The Student Check-Up: effects of paraprofessional-delivered Motivational Interviewing on academic outcomes Gerald G. Strait, Eric Ryan Lee, Sam McQuillin, John Terry, Michelle Cebada & Julia Englund Strait Pages: 1-15 | DOI: 10.1080/1754730X.2017.1333915 Routledge Psychology 2017 sponsor of BPS #PsychCrunch podcasts. Access 25 journal articles: http://bit.ly/psychcrunch2017 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.