Contact heat evoked potentials: reliable acquisition from lower extremities

Publication date: Available online 7 January 2018
Source:Clinical Neurophysiology
Author(s): J Rosner, M Hubli, P Hostettler, PS Scheuren, J Rinert, JLK Kramer, M Hupp, A Curt, CR Jutzeler
ObjectiveTo investigate test-retest reliability of contact heat evoked potentials (CHEPs) from lower extremities using two different stimulation protocols, i.e., normal and increased baseline temperature.MethodsA total of 32 able-bodied subjects were included and a subset (N=22) was retested. CHEPs were recorded from three different dermatomes of the lower extremity (i.e., L2, L5, and S2). Test-retest reliability of CHEPs acquisition after simulation in various lower limb dermatomes using different stimulation protocolswas analyzed.ResultsThe study revealed an improved acquisition of CHEPS employing the increased baseline protocol, particularly when stimulating more distal sites, i.e., dermatome L5 and S2. Based on repeatability coefficients, CHEP latency (N2 potential) emerged as the most robust CHEP parameter. Although CHEP amplitudes (N2P2 complex) and pain ratings were decreased in the retest, amplitudes still showed fair to excellent intraclass correlation coefficients (ICCs) using normal baseline or increased baseline temperature, respectively.ConclusionsThis is the first study to demonstrate that CHEPs acquisition from the lower extremities is improved by increasing the baseline temperature of the thermode.SignificanceThis study highlights the usability of CHEPs as a viable diagnostic method to study small fiber integrity.



http://ift.tt/2D5EjI0

New methods for automatic quantification of microstructural features using digital image processing

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Andrew Campbell, Paul Murray, Evgenia Yakushina, Stephen Marshall, William Ion
Thermal and mechanical processes alter the microstructure of materials, which determines their mechanical properties. This makes reliable microstructural analysis important to the design and manufacture of components. However, the analysis of complex microstructures, such as Ti6Al4V, is difficult and typically requires expert materials scientists to manually identify and measure microstructural features. This process is often slow, labour intensive and suffers from poor repeatability. This paper overcomes these challenges by proposing a new set of automated techniques for 2D microstructural analysis. Digital image processing algorithms are developed to isolate individual microstructural features, such as grains and alpha lath colonies. A segmentation of the image is produced, where regions represent grains and colonies, from which morphological features such as; grain size, volume fraction of globular alpha grains and alpha colony size can be measured. The proposed measurement techniques are shown to obtain similar results to existing manual methods while drastically improving speed and repeatability. The benefits of the proposed approach when measuring complex microstructures are demonstrated by comparing it with existing analysis software. Using a few parameter changes, the proposed techniques are effective on a variety of microstructure types and both SEM and optical microscopy images.

Graphical abstract

http://ift.tt/2Fd191c

The value of detection of S100A8 and ASAH1 in predicting the chemotherapy response for breast cancer patients

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Yu-hong Li, Hai-ting Liu, Jing Xu, Ai-yan Xing, Jie Zhang, Ya-wen Wang, Gang Yin, Peng Gao
Chemotherapy plays an important role in the treatment of breast cancer. However, chemoresistance remains the main obstacle for effective treatment, leading to poor prognosis. This study aims to investigate the value of detection of S100A8 and ASAH1 in predicting the chemotherapy response. Miller and Payne grades were used to assess the chemotherapy response in breast cancers. The expression of S100A8 and ASAH1, as well as ER, PR, HER-2 and Ki-67 were assessed by immunohistochemical staining in 120 cases of non-special type invasive ductal carcinoma (IDC-NOS). S100A8 expression was higher in chemosensitive breast cancers than chemoresistant ones. Moreover, S100A8 expression was significantly correlated with the molecular subtypes and histological grade, but not with patients' age, tumor size and lymph nodes status. However, there was no significant difference in ASAH1 expression between chemoresistant and chemosensitive group. We also found that higher ASAH1 expression was correlated with positive lymph nodes status, but not with age, tumor size, molecular subtypes and histological grade. S100A8 was valuable in predicting chemotherapy response in breast cancers. The expression of ASAH1 was associated significantly with lymph nodes metastasis, indicating that ASAH1 may serve as a biomarker to predict patients' lymph nodes status in breast cancers.



http://ift.tt/2CRA9qg

Atypical multivacuolated lipoblasts and atypical mitoses are not compatible with the diagnosis of spindle cell/pleomorphic lipoma—reply

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Michael Michal, Dmitry V. Kazakov, Kvetoslava Michalova, Michal Michal




http://ift.tt/2AD8fIG

Characteristics of cribriform morular variant of papillary thyroid carcinoma in post-Chernobyl affected region

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Alfred King-yin Lam, Mikhail Fridman
The aim is to study the characteristics of cribriform morular variant of papillary thyroid carcinoma (CMV-PTC) in patients living in radiation-affected area of Belarus. The clinical and pathological features of 35 patients with CMV-PTC from Belarus were studied and compared with those of conventional papillary thyroid carcinoma diagnosed in the same period. The patients with CMV-PTC were all females and were younger at presentation (mean age = 24) than those with conventional papillary thyroid carcinoma. Familial adenomatous polyposis (FAP) was identified in 20% of the patients with CMV-PTC. The majority of the CMV-PTCs (29/35; 83%) were staged as pT1 and were less advanced than conventional papillary thyroid carcinoma. There was no evidence of lymph node metastases or distant metastases. CMV-PTCs were positive for beta-catenin, APC (adenomatous polyposis coli) and p53 proteins. No psammoma bodies were identified on microscopic examination. Over a median follow-up of 9 years, all the patients were alive, there were no cancer recurrence or mortality related to the thyroid cancer. To conclude, patients with CMV-PTC in radiation-affected region behave in an indolent fashion. They had distinctive features that are different from patients with conventional papillary thyroid carcinoma living in the same region.



http://ift.tt/2CRKv9S

Downregulated SASH1 Expression Indicates Poor Clinical Prognosis in Gastric Cancer

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Nan Zhou, Can Liu, Xudong Wang, Qinsheng Mao, Qin Jin, Peng Li
SASH1 (SAM- and SH3-domain containing 1), a novel candidate tumor suppressor, has attracted attention due to its role in intracellular signal transduction and its tumor prognostic value in diverse cancers. Reports have demonstrated that reduced SASH1 expression correlates with tumor proliferation, invasion, and metastasis. However, the expression and prognostic significance of SASH1 in gastric cancer (GC) remain unclear. In this study, 8 paired fresh-frozen GC tissues and corresponding gastric mucosal tissues were examined by Western blot to analyze the protein expression of SASH1. 726 formalin-fixed, paraffin-embedded (FFPE) gastric tissue samples were evaluated by immunohistochemical (IHC) to determine the correlations of SASH1 expression with clinicopathological factors and prognosis. Compared with adjacent noncancerous tissues, SASH1 was significantly downregulated in GC specimens. Analysis using the χ test revealed that low SASH1 expression was significantly associated with advanced TNM stage (P<0.001) in GC. Cox regression multivariable analyses demonstrated that SASH1 expression (P<0.001), TNM stage (P<0.001), preoperative CEA level (P=0.003) and preoperative CA19-9 level (P=0.002) were independent prognostic factors. Our clinical findings suggest that downregulated SASH1 expression could be used as an independent biomarker for poor prognosis in GC.



http://ift.tt/2AAPgP4

Prognostic significance of S100A16 sub-cellular localization in lung adenocarcinoma

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Makoto Kobayashi, Ryo Nagashio, Keita Saito, Clemente Aguilar-Bonavides, Shinichiro Ryuge, Ken Katono, Satoshi Igawa, Benio Tsuchiya, Shi-Xu Jiang, Masaaki Ichinoe, Yoshiki Murakumo, Makoto Saegusa, Yukitoshi Satoh, Yuichi Sato
To discover novel tumor markers for lung adenocarcinoma (AC), we performed proteomics analysis and reported a correlation between S100A16 membranous expression in AC tissues and a poor prognosis. However, some patients with a good prognosis also showed S100A16 membranous staining. We re-evaluated immunohistochemically stained tissues, and found membrane-positive and nucleus- negative expressions to be significantly higher in the presence of the following: male, smoker, positive nodal metastasis, higher p-TNM stage, larger tumor, poorer differentiation, positive for lymphatic invasion, positive for vascular invasion, and positive for pleural invasion (all factors P < 0.05). This pattern of staining was also an independent prognostic factor. Furthermore, we analyzed S100A16 mRNA expression using TCGA and Kaplan-Meier plotter databases, and found that higher S100A16 mRNA expression in AC was significantly correlated with poorer survival. To our knowledge, there has been no comprehensive study focused on both S100A16 protein and mRNA expression levels in AC patients. Our results suggest that the sub-cellular localization of S100A16 and S100A16 mRNA expression levels are promising prognostic markers for AC.



http://ift.tt/2CPmIXY

Uterine Rhabdomyosarcoma in Adults

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Andre Pinto, Ryan M. Kahn, Andrew E. Rosenberg, Brian Slomovitz, Charles Matthew Quick, Michella K. Whisman, Marilyn Huang
Rhabdomyosarcoma (RMS) is an aggressive mesenchymal tumor most commonly diagnosed in the pediatric population, and when occurring in adults, tends to develop in the deep soft tissue of the limbs. Primary uterine RMS comprises an even more restricted subset, with little known or reported when compared to most other gynecologic sarcomas. Our goal with this study was to retrospectively evaluate cases from two academic institutions and describe the main histopathologic findings of this rare gynecologic malignancy. A total of eight cases were identified, consisting of four pleomorphic rhabdomyosarcomas (PRMS), two alveolar rhabdomyosarcomas (ARMS), and two embryonal rhabdomyosarcomas (ERMS). They occurred in patients ranging from 22 to 70 years old, and the most common presenting symptom was vaginal bleeding. Most patients presented with advanced stage at diagnosis, including metastatic disease to lymph nodes and to distant sites. The masses were mostly (6/8) centered in the myometrium, while two cases arose in the cervix (2/8). Histologic characteristics of the tumors were dependent of the RMS subtype, although all cases demonstrated a similar immunohistochemical profile regardless of their subclassification. RMS of the uterus has a very poor prognosis, and data regarding treatment of this rare malignancy is limited, and usually extrapolated from non-uterine sites.



http://ift.tt/2ADkNj5

The Many Faces of Intestinal Tract Gastric Heterotopia; A Series of Four Cases Highlighting Clinical and Pathological Heterogeneity

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Aqsa Nasir, Stuart K. Amateau, Sabina Khan, Ross W. Simpson, Dale C. Snover, Khalid Amin
Gastric heterotopia of the intestinal tract can have a diverse clinicopathologic presentation, resulting in a diagnostic dilemma. We present a series of four cases, two male and two female patients with age range of 31-82 year, found in the duodenum, jejunum, and transverse colon. The most common and rather unusual clinical presentation was iron deficiency anemia, seen in three cases, while one patient presented with abdominal pain. Endoscopically two cases were visualized as pedunculated polyps and two as sessile/plaques like lesions. Polypectomy was performed in three patients and one patient underwent biopsy followed by resection. Two cases showed oxyntic-type epithelium and two cases exhibited pylorictype gastric epithelium. Three patients were relieved of their presenting symptoms after therapeutic procedure with no evidence of recurrence noted on follow-up. Follow-up was not available on one patient. This case series highlights diverse clinicopathologic spectrum of gastric heterotopia. Accurate diagnosis is essential for proper management.



http://ift.tt/2CRo0BS

Diversity and functional evolution of the plasminogen activator system

Publication date: February 2018
Source:Biomedicine & Pharmacotherapy, Volume 98
Author(s): Rishi Kumar Jaiswal, Akhil Kumar Varshney, Pramod Kumar Yadava
The urokinase plasminogen activator system is a family of serine proteases which consists of uPA (urokinase plasminogen activator), uPAR (urokinase type plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1). In addition to their significant roles in activation, these proteases act as key regulators of the tumor microenvironment and are involved in the metastatic process in many cancers. High levels of uPA system proteases in many human cancer predicts poor patient prognosis and strongly indicated a key role of uPA system in cancer metastasis. Individual components of uPA system are found to be differentially expressed in cancer cells compared to normal cells and therefore are potential therapeutic targets. In this review, we present the molecular and cellular mechanisms underlying the role of uPA system in cancer progression. Epithelial to mesenchymal transitions (EMT) is the main cause of the cancer cell metastasis. We have also attempted to relate the role of uPA signaling in EMT of cancer cells.



http://ift.tt/2FbUPqK

Cluster Analysis of Vulnerable Groups in Acute TBI Rehabilitation

Publication date: Available online 6 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Erkut N. Kucukboyaci, Coralynn Long, Michelle Smith, Joseph F. Rath, Tamara Bushnik
ObjectiveTo analyze the complex relationship between various social indicators that contribute to socioeconomic status and healthcare barriers.DesignCluster analysis of historical patient data obtained from inpatient visits.SettingSetting: Inpatient rehabilitation unit in a large, urban university hospitalParticipantsAdult patients receiving acute inpatient care, predominantly for closed head injury.InterventionsNot applicableMain outcome measuresWe examined the membership of TBI patients in various "vulnerable group" (VG) clusters (e.g., homeless, unemployed, racial/ethnic minority) and characterized the rehabilitation outcomes of the patients (e.g., duration of stay, changes in Functional Independence Measure [FIM] scores between admission to inpatient stay and discharge).ResultsAnalysis revealed four major clusters (i.e., Clusters A-D) separated by VG memberships, with distinct durations of stay and FIM gains during their stay. Cluster B, the largest cluster and also consisting of mostly racial/ethnic minorities, had the shortest duration of hospital stay and one of the lowest FIM improvements among the four clusters despite higher FIM scores at admission. In cluster C, also consisting of mostly ethnic minorities with multiple SES vulnerabilities, patients were characterized by low cognitive FIM scores at admission and the longest duration of stay, and they showed good improvement in FIM scores.ConclusionsApplication of clustering techniques to inpatient data identified distinct clusters of patients who may experience differences in their rehabilitation outcome due to their membership in various "at-risk" groups. Results identified patients (i.e., cluster B, with minority patients and Cluster D, with elderly patients) who attain below-average gains in brain injury rehabilitation. Results also suggested that systemic (e.g., duration of stay) or clinical service improvements (e.g., staff's language skills, ability to offer substance abuse therapy, provide appropriate referrals or liaise with intensive social work services or plan subacute rehabilitation phase) could be beneficial for acute settings. Stronger recruitment, training and retention initiatives for bilingual and multiethnic professionals may also be considered to optimize gains from acute inpatient rehabilitation following traumatic brain injury.



http://ift.tt/2qzFvkl

Determining Reliability of a Dual-task Functional Mobility Protocol for Individuals with Lower Extremity Amputations

Publication date: Available online 6 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Courtney Frengopoulos, Michael WC. Payne, Jeffrey Holmes, Ricardo Viana, Susan W. Hunter
ObjectivesTo determine the relative and absolute reliability of a dual-task functional mobility assessment.DesignCross-sectional study.SettingAcademic Rehabilitation Hospital.ParticipantsSixty individuals with lower extremity amputation (LEA) attending an outpatient amputee clinic (age= 58.21±12.59; 80.0% male). Subjects were stratified into three groups: 1) transtibial amputations of vascular etiology (TTA-vas), transtibial amputations of non-vascular etiology (TTA-nonvas); transfemoral or bilateral amputees (TFA/bilat) of any etiology.InterventionsN/AMain Outcome MeasuresTime to complete the L Test measured functional mobility under single- and dual-task conditions. Addition of a cognitive task (serial subtractions by 3s) created dual-task conditions. Single task performance on the cognitive task was also reported. Intra-class correlation coefficients (ICC) measured relative reliability; standard error of measurement (SEM) and minimal detectable change with a 95% confidence interval (MDC95) measured absolute reliability. Bland and Altman plots measured agreement between assessments.ResultsRelative reliability results were excellent for all three groups. Values for the dual-task L Test for those with TTA-vas (n=20, age=60.36±7.84, 90.0% male) were ICC=0.98 (95% CI, 0.94-0.99), with SEM=1.36s and MDC95 of 3.76s; for those with TTA-nonvas (n=20, age=55.85±14.08, 85.0% male), were ICC=0.93 (95% CI, 0.80-0.98), SEM=1.34s and MDC95 of 3.71s; and for those with TFA/bilat group (n=20, age=58.21±14.88, 65.0% male) were ICC=0.998 (95% CI, 0.996-0.999), SEM=1.03s and an MDC95 of 2.85s. Bland-Altman plots indicated that assessments did not vary systematically for each group.ConclusionsThis dual-task assessment protocol achieved approved levels of relative reliability values for the three groups tested. This protocol may be used clinically or in research settings to assess the interaction between cognition and functional mobility in the LEA population.



http://ift.tt/2qB2yLL

Design, synthesis and evaluation against Chikungunya virus of novel small-molecule antiviral agents

Publication date: Available online 6 January 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Roberta Tardugno, Gilda Giancotti, Tine De Burghgraeve, Leen Delang, Johan Neyts, Pieter Leyssen, Andrea Brancale, Marcella Bassetto
Chikungunya virus is a re-emerging arbovirus transmitted to humans by mosquitoes, responsible for an acute flu-like illness associated with debilitating arthralgia, which can persist for several months or become chronic. In recent years, this viral infection has spread worldwide with a previously unknown virulence. To date, no specific antivirals treatments nor vaccines are available against this important pathogen. Starting from the structures of two antiviral hits previously identified in our research group with in silico techniques, this work describes the design and preparation of 31 novel structural analogues, with which different pharmacophoric features of the two hits have been explored and correlated with the inhibition of Chikungunya virus replication in cells. Structure-activity relationships were elucidated for the original scaffolds, and different novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these promising novel structures as antiviral agents against Chikungunya virus.

Graphical abstract

http://ift.tt/2F9vVb5

Amoebal endosymbiont Neochlamydia protects host amoebae against Legionella pneumophila infection by preventing Legionella entry

Publication date: Available online 6 January 2018
Source:Microbes and Infection
Author(s): Chinatsu Maita, Mizue Matsushita, Masahiro Miyoshi, Torahiko Okubo, Shinji Nakamura, Junji Matsuo, Masaharu Takemura, Masaki Miyake, Hiroki Nagai, Hiroyuki Yamaguchi
Acanthamoeba isolated from environmental soil harbors the obligate intracellular symbiont Neochlamydia, which has a critical role in host amoebal defense against Legionella pneumophila infection. Here, by using morphological analysis with confocal laser scanning fluorescence microscopy and transmission electron microscopy, proteome analyses with two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and liquid chromatography–mass spectrometry (LC/MS), and transcriptome analysis with DNA microarray, we explored the mechanism by which the Neochlamydia effected this defense. We observed that when rare uptake did occur, the symbiotic amoebae allowed Legionella to grow normally. However, the symbiotic amoebae had severely reduced uptake of Legionella when compared with the aposymbiotic amoebae. Also, in contrast to amoebae carrying the endosymbiont, the actin cytoskeleton was significantly disrupted by Legionella infection in aposymbiotic amoebae. Furthermore, despite Legionella exposure, there was little change in Neochlamydia gene expression. Taken together, we concluded that the endosymbiont, Neochlamydia prevents Legionella entry to the host amoeba, resulting in the host defense against Legionella infection.



http://ift.tt/2CA94nk

Development of stereotaxic recording system for awake marmosets (Callithrix jacchus)

Publication date: Available online 6 January 2018
Source:Neuroscience Research
Author(s): Masahiro Wakabayashi, Daisuke Koketsu, Hideki Kondo, Shigeki Sato, Kiichi Ohara, Zlata Polyakova, Satomi Chiken, Nobuhiko Hatanaka, Atsushi Nambu
The common marmoset has been proposed as a potential alternative to macaque monkey as a primate model for neuroscience and medical research. Here, we have newly developed a stereotaxic neuronal recording system for awake marmosets under the head-fixed condition by modifying that for macaque monkeys. Using this system, we recorded neuronal activity in the cerebral cortex of awake marmosets and successfully identified the primary motor cortex by intracortical microstimulation. Neuronal activities of deep brain structures, such as the basal ganglia, thalamus, and cerebellum, in awake marmosets were also successfully recorded referring to magnetic resonance images. Our system is suitable for functional mapping of the brain, since the large recording chamber allows access to arbitrary regions over almost the entire brain, and the recording electrode can be easily moved stereotaxically from one site to another. In addition, our system is desirable for neuronal recording during task performance to assess motor skills and cognitive function, as the marmoset sits in the marmoset chair and can freely use its hands. Moreover, our system can be used in combination with cutting-edge techniques, such as two-photon imaging and optogenetic manipulation. This recording system will contribute to boosting neuroscience and medical research using marmosets.



http://ift.tt/2EhYWA8

Presynaptic Calcium Channels

Publication date: Available online 6 January 2018
Source:Neuroscience Research
Author(s): Sumiko Mochida
At the presynaptic terminal, neuronal firing activity induces membrane depolarization and subsequent Ca²⁺ entry through voltage-gated Ca²⁺ (CaV) channels triggers neurotransmitter release from the active zone. Presynaptic Ca²⁺ channels form a large signaling complex, which targets synaptic vesicles to Ca²⁺ channels for efficient release and mediates Ca²⁺ channel regulation. The presynaptic CaV2 channel family (comprising CaV2.1, CaV2.2 and CaV2.3 isoforms) encode the pore-forming α1 subunit. The cytoplasmic regions are the target of regulatory proteins for channel modulation. Modulation of presynaptic Ca²⁺ channels has a powerful influence on synaptic transmission. This article overviews spatial and temporal regulation of Ca²⁺ channels by effectors and sensors of Ca²⁺ signaling, and describes the emerging evidence for a critical role of Ca²⁺ channel regulation in control of synaptic transmission and presynaptic plasticity. Sympathetic superior cervical ganglion neurons in culture expressing CaV2.2 channels represent a well-characterized system for investigating synaptic transmission. The exogenously expressed α1 subunit of the CaV2.1 as well as endogenous CaV2.2 was examined for modulation of channel activity, and thereby regulation of synaptic transmission. The constitutive and Ca²⁺-dependent modulation of CaV2.1 channels coordinately act as spatial and temporal molecular switches to control synaptic efficacy.



http://ift.tt/2FbRqIm

Exposure- and flux-based assessment of ozone risk to sugarcane plants

Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Bárbara Baêsso Moura, Yasutomo Hoshika, Rafael Vasconcelos Ribeiro, Elena Paoletti
Ozone (O3) is a toxic oxidative air pollutant, with significant detrimental effects on crops. Sugarcane (Saccharum spp.) is an important crop with no O3 risk assessment performed so far. This study aimed to assess O3 risk to sugarcane plants by using exposure-based indices (AOT40 and W126) based on O3 concentrations in the air, and the flux-based index (PODy, where y is a threshold of uptake) that considers leaf O3 uptake and the influence of environmental conditions on stomatal conductance (gsto). Two sugarcane genotypes (IACSP94-2094 and IACSP95-5000) were subjected to a 90-day Free-Air Controlled Experiment (FACE) exposure at three levels of O3 concentrations: ambient (Amb); Amb x1.2; and Amb x1.4. Total above-ground biomass (AGB), stalk biomass (SB) and leaf biomass (LB) were evaluated and the potential biomass production in a clean air was estimated by assuming a theoretical clean atmosphere at 10 ppb as 24 h O3 average. The Jarvis-type multiplicative algorithm was used to parametrize gsto including environmental factors i.e. air temperature, light intensity, air vapor pressure deficit, and minimum night-time temperature. Ozone exposure caused a negative impact on AGB, SB and LB. The O3 sensitivity of sugarcane may be related to its high gsto (∼535 mmol H2O m⁻² s⁻¹). As sugarcane is adapted to hot climate conditions, gsto was restricted when the current minimum air temperature (Tmin) was below ∼14 °C and the minimum night-time air temperature of the previous day (Tnmin) was below ∼7.5 °C. The flux-based index (PODy) performed better than the exposure-based indices in estimating O3 effect on biomass losses. We recommend a y threshold of 2 nmol m⁻² s⁻¹ to incorporate O3 effects on both AGB and SB and 1 nmol m⁻² s⁻¹ on LB. In order not to exceed 4% reduction in the growth of these two sugarcane genotypes, we recommend the following critical levels: 1.09 and 1.04 mmol m⁻² POD2 for AGB, 0.91 and 0.96 mmol m⁻² POD2 for SB, and 3.00 and 2.36 mmol m⁻² POD1 for LB of IACSP95-5000 and IACSP94-2094, respectively.



http://ift.tt/2CQtzAe

Editorial Board

Publication date: January 2018
Source:Biological Psychology, Volume 131





http://ift.tt/2m4tqxX

Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress

Publication date: 2 April 2018
Source:Behavioural Brain Research, Volume 341
Author(s): Dayan Knox, Briana R. Stanfield, Jennifer M. Staib, Nina P. David, Thomas DePietro, Marisa Chamness, Elizabeth K. Schneider, Samantha M. Keller, Caroline Lawless
Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory.



http://ift.tt/2CzOlA2

Mitochondrial Network Responses in Oxidative Physiology and Disease

Publication date: Available online 6 January 2018
Source:Free Radical Biology and Medicine
Author(s): Young-Mi Go, Jolyn Fernandes, Xin Hu, Karan Uppal, Dean P. Jones
Mitochondrial activities are linked directly or indirectly to all cellular functions in aerobic eukaryotes. Omics methods enable new approaches to study functional organization of mitochondria and their adaptive and maladaptive network responses to bioenergetic fuels, physiologic demands, environmental challenges and aging. In this review, we consider mitochondria collectively within a multicellular organism as a macroscale "mitochondriome", functioning to organize bioenergetics and metabolism as an organism utilizes environmental resources and protects against environmental threats. We address complexities of knowledgebase-driven functional mapping of mitochondrial systems and then consider data-driven network mapping using omics methods. Transcriptome-metabolome-wide association study (TMWAS) shows connectivity and organization of nuclear transcription with mitochondrial transport systems in cellular responses to mitochondria-mediated toxicity. Integration of redox and respiratory measures with TMWAS shows central redox hubs separating systems linked to oxygen consumption rate and H2O2 production. Combined redox proteomics, metabolomics and transcriptomics further shows that physiologic network structures can be visualized separately from toxicologic networks. These data-driven integrated omics methods create new opportunities for mitochondrial systems biology.

Graphical abstract

http://ift.tt/2qBSYrO

Soluble protein fraction of human seminal plasma

Publication date: 1 March 2018
Source:Journal of Proteomics, Volume 174
Author(s): Laura Bianchi, Chiara Carnemolla, Viola Viviani, Claudia Landi, Valentina Pavone, Alice Luddi, Paola Piomboni, Luca Bini

Graphical abstract

http://ift.tt/2AB6HyO

Precision of 655nm Confocal Laser Profilometry for 3D surface texture characterisation of natural human enamel undergoing dietary acid mediated erosive wear

Publication date: Available online 6 January 2018
Source:Dental Materials
Author(s): F. Mullan, P. Mylonas, C. Parkinson, D. Bartlett, R.S. Austin
ObjectivesTo assess the precision of optical profilometry for characterising the 3D surface roughness of natural and polished human enamel in order to reliably quantify acid mediated surface roughness changes in human enamel.MethodsForty-two enamel samples were prepared from extracted human molars and either polished flat or left unmodified. To investigate precision, the variability of thirty repeated measurements of five areas of one polished and one natural enamel sample was assessed using 655nm Confocal Laser Profilometry. Remaining samples were subjected to forty-five minutes orange juice erosion and microstructural changes were analysed using Sa roughness change (μm) and qualitatively using surface/subsurface confocal microscopy.ResultsEnamel surface profilometry from the selected areas revealed maximal precision of 5nm for polished enamel and 23nm for natural enamel. After erosion, the polished enamel revealed a 48% increase in mean (SD) Sa roughness of 0.10 (0.07)μm (P<0.05), whereas in contrast the natural enamel revealed a 45% decrease in mean (SD) roughness of −0.32 (0.42)μm (P<0.05). These data were supported by qualitative confocal images of the surface/subsurface enamel.SignificanceThis study demonstrates a method for precise surface texture measurement of natural human enamel. Measurement precision was superior for polished flat enamel in contrast to natural enamel however, natural enamel responds very differently to polished enamel when exposed to erosion challenges. Therefore, thus future studies characterising enamel surface changes following erosion on natural enamel may provide more clinically relevant responses in comparison to polished enamel.



http://ift.tt/2CKRArT

Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer

Publication date: Available online 6 January 2018
Source:Clinical Therapeutics
Author(s): Catherine J. Lucas, Peter Galettis, Shuzhen Song, Nadia Solowij, Stephanie E. Reuter, Jennifer Schneider, Jennifer H. Martin
BackgroundMedicinal cannabis is prescribed under the provision of a controlled drug in the Australian Poisons Standard. However, multiple laws must be navigated in order for patients to obtain access and imported products can be expensive. Dose-response information for both efficacy and toxicity pertaining to medicinal cannabis is lacking. The pharmacokinetic properties of cannabis administered by traditional routes has been described but to date, there is no literature on the pharmacokinetic properties of an intraperitoneal cannabinoid emulsion.Case descriptionA cachectic 56-year-old female with stage IV ovarian cancer and peritoneal metastases presented to hospital with fevers, abdominal distension and severe pain, vomiting, anorexia, dehydration and confusion. The patient reported receiving an intraperitoneal injection, purported to contain 12 g of mixed cannabinoid (administered by a deregistered medical practitioner) two days prior to presentation. Additionally, cannabis oil oral capsules were administered in the hours prior to hospital admission.ResultsTHC concentrations were consistent with the clinical state but not with the known pharmacokinetic properties of cannabis nor of intraperitoneal absorption. THC concentrations at the time of presentation were predicted to be ~60 ng/mL. Evidence suggests that blood THC concentrations >5 ng/mL are associated with substantial cognitive and psychomotor impairment. The predicted time for concentrations to drop <5 ng/mL was 49 days after administration.DiscussionThe unusual pharmacokinetic properties of the case suggest that there is a large amount unknown about cannabis pharmacokinetic properties. The pharmacokinetic properties of a large amount of a lipid soluble compound given intraperitoneally gave insights into the absorption and distribution of cannabinoids, particularly in the setting of metastatic malignancy.



http://ift.tt/2F9KH1k

Letter to the Editor on Nevens et al.

Publication date: Available online 6 January 2018
Source:Radiotherapy and Oncology
Author(s): Olgun Elicin, Roland Giger




http://ift.tt/2F9sLUS

Realizing highly chemoselective detection of H2S in vitro and in vivo with fluorescent probes inside core-shell silica nanoparticles

Publication date: March 2018
Source:Biomaterials, Volume 159
Author(s): Feiyi Wang, Ge Xu, Xianfeng Gu, Zhijun Wang, Zhiqiang Wang, Ben Shi, Cuifen Lu, Xueqing Gong, Chunchang Zhao
Hydrogen sulfide (H2S) is an appealing signaling molecule that plays fundamental roles in health and disease. However, H2S-mediated selective chemical transformations for the construction of imaging probes are limited, retarding the interrogation of H2S-related biological processes. Here, we present an alternative approach for engineering a new generation of efficient probes with a nonchemoselective moiety as a building block. To demonstrate our design concept, we developed a sulfoxide-functionalized BODIPY that exhibited a substantial redshift in its absorption and emission spectra upon reduction with H2S. However, such a probe also showed reactivity toward various competing biothiols under aqueous buffer conditions. To achieve high chemoselectivity, we used core-shell silica nanoparticles as an encapsulation matrix to confine the designed molecule probe within their interiors. The inherent molecular-size sieving character of the porous silica shell was capable of impeding competing biothiols from accessing the molecule probe within the core while allowing the specific reaction with the small target H2S. Thus, this strategy avoided disturbance from coexisting biothiols and achieved highly chemoselective detection in ratiometric and near-infrared (NIR) turn-on fluorescence modes. In light of these promising features, together with fast responsiveness and favorable cellular uptake, such a silica nanocomposite was successfully used to detect the endogenous production of H2S in estrogen-induced cardiomyocytes and living mouse model. To our knowledge, the approach reported here is the first to exploit the usefulness of common thiol-sensitive moieties for building chemoselective probes.

Graphical abstract

http://ift.tt/2D1b7Sm

Injectable thermogel for 3D culture of stem cells

Publication date: March 2018
Source:Biomaterials, Volume 159
Author(s): Madhumita Patel, Hyun Jung Lee, Sohee Park, Yelin Kim, Byeongmoon Jeong
Thermogel is an aqueous polymer solution that undergoes sol-to-gel transition as the temperature increases. Cells, growth factors, and signaling molecules can be incorporated simultaneously during the sol-to-gel transition. The cytocompatible procedure makes the thermogel an excellent platform for 3D culture of stem cells. This review focuses on the crucial questions that need to be addressed to achieve effective differentiation of stem cells into target cells, comprising low modulus, cell adhesion, and controlled supply of the growth factors. Recent progress in the use of thermogel as a 3D culture system of stem cells is summarized, and our perspectives on designing a new thermogel for 3D culture and its eventual application to injectable tissue engineering of stem cells are presented.

Graphical abstract

http://ift.tt/2D1TSjZ

Renal-clearable quaternary chalcogenide nanocrystal for photoacoustic/magnetic resonance imaging guided tumor photothermal therapy

Publication date: March 2018
Source:Biomaterials, Volume 159
Author(s): Longfei Tan, Jing Wan, Weisheng Guo, Caizhang Ou, Tianlong Liu, Changhui Fu, Qiang Zhang, Xiangling Ren, Xing-Jie Liang, Jun Ren, Laifeng Li, Xianwei Meng
Ultrasmall Cu2ZnSnS4 (CZTS) nanocrystals with high near infrared (NIR) photothermal conversion abilities and peroxidase-mimic properties are synthesized and functionalized with bovine serum albumin (BSA) for rapid clearance multifunctional theranostic platform. Due to the presence of Cu (I) of CZTS@BSA, H2O2 could be decomposed to produce highly reactive oxygen species (ROS), catalyzed by intrinsic peroxidase like activity of CZTS. The CZTS@BSA possesses high NIR absorption and excellent photoacoustic (PA) imaging abilities. The as-prepared CZTS@BSA is also reported as an efficient T1 contrast agent for in vivo MR imaging. Therefore, in vivo distribution and rapid renal clearance of CZTS@BSA are successfully tracked by PA/MR dual-modal-imaging and further proved by ICP-MS analysis. Systemic acute toxicity evaluation indicates CZTS@BSA have good biocompatibility to normal tissues and blood. All results reveal that CZTS@BSA could act as a rapid clearance theranostic nanoplatform for dual-modal-imaging guided tumor PTT.



http://ift.tt/2D2Tj9H

Editorial Board

Publication date: March 2018
Source:Biomaterials, Volume 158





http://ift.tt/2CAOkMr

Heterocellular 3D scaffolds as biomimetic to recapitulate the tumor microenvironment of peritoneal metastases in vitro and in vivo

Publication date: March 2018
Source:Biomaterials, Volume 158
Author(s): Emiel De Jaeghere, Elly De Vlieghere, Jasper Van Hoorick, Sandra Van Vlierberghe, Glenn Wagemans, Leen Pieters, Elodie Melsens, Marleen Praet, Jo Van Dorpe, Matthieu N. Boone, Rouba Ghobeira, Nathalie De Geyter, Marc Bracke, Christian Vanhove, Sara Neyt, Geert Berx, Bruno G. De Geest, Peter Dubruel, Heidi Declercq, Wim Ceelen, Olivier De Wever
Peritoneal metastasis is a major cause of death and preclinical models are urgently needed to enhance therapeutic progress. This study reports on a hybrid hydrogel-polylactic acid (PLA) scaffold that mimics the architecture of peritoneal metastases at the qualitative, quantitative and spatial level. Porous PLA scaffolds with controllable pore size, geometry and surface properties are functionalized by type I collagen hydrogel. Co-seeding of cancer-associated fibroblasts (CAF) increases cancer cell adhesion, recovery and exponential growth by in situ heterocellular spheroid formation. Scaffold implantation into the peritoneum allows long-term follow-up (>14 weeks) and results in a time-dependent increase in vascularization, which correlates with cancer cell colonization in vivo. CAF, endothelial cells, macrophages and cancer cells show spatial and quantitative aspects as similarly observed in patient-derived peritoneal metastases. CAF provide long-term secretion of complementary paracrine factors implicated in spheroid formation in vitro as well as in recruitment and organization of host cells in vivo. In conclusion, the multifaceted heterocellular interactions that occur within peritoneal metastases are reproduced in this tissue-engineered implantable scaffold model.



http://ift.tt/2D0Mcyl

2D materials hold key to printing wearable electronics

Publication date: Available online 6 January 2018
Source:Nano Today





http://ift.tt/2qvE3zk