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Πέμπτη 1 Ιουνίου 2017

Chemotherapy for Resected Colorectal Cancer Pulmonary Metastases: Utilization and Outcomes in Routine Clinical Practice

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Publication date: Available online 1 June 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Safiya Karim, Sulaiman Nanji, Kelly Brennan, C.S. Pramesh, Christopher M. Booth
BackgroundThe role of chemotherapy in the setting of resected colorectal cancer pulmonary metastases (CRCPM) is not well defined. Here we describe utilization of peri-operative chemotherapy and outcomes among patients with resected CRCPM in the general population.MethodsAll cases of CRCPM who underwent resection from 2002-2009 were identified using the Ontario Cancer Registry (OCR). Electronic treatment records identified peri-operative chemotherapy delivered within 16 weeks before or after pulmonary metastectomy (PM). Modified Poisson regression was used to evaluate factors associated with chemotherapy delivery. Cox proportional models were used to explore the association between post-operative chemotherapy and cancer-specific (CSS) and overall survival (OS).ResultsThe study population included 420 patients. Thirty-six percent of patients (151/420) received peri-operative chemotherapy. Among these patients, 75% (113/151) received post-operative chemotherapy. Factors that were independently associated with use of post-operative chemotherapy included higher socioeconomic status (SES) and no prior adjuvant chemotherapy (p<0.01). In adjusted analyses post-operative chemotherapy was not associated with improved CSS (HR 0.99, 95% CI 0.67-1.47) or OS (HR 0.93 95%CI 0.66-1.31). In exploratory analyses, among those patients who did not receive previous adjuvant therapy for the primary colorectal cancer, post-operative chemotherapy following lung metastatectomy was associated with HR 0.50 (95%CI 0.27-0.95) for OS and HR 0.59 (95%CI 0.27-1.27) for CSS.ConclusionOne third of patients with resected CRCPM in routine practice receive peri-operative chemotherapy. A randomized controlled trial is warranted to evaluate whether chemotherapy following resection of CRCPM is associated with improved survival.



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Combined spontaneous bacterial empyema and peritonitis in cirrhotic patients with ascites and hepatic hydrothorax

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Anwar Mohamed, Mohammed Atef, Ayman Alsebaey, Mahmoud Musa Elhabshy, Mohsen Salama
Background and study aims: Spontaneous bacterial empyema (SBEM) is an underestimated condition in patients with ascites and hepatic hydrothorax with a high mortality. This study aimed to find whether spontaneous bacterial peritonitis (SBP) is a prerequisite for SBEM. Patients and methods: 3000 HCV-related cirrhotic patients with ascites and hydrothorax were screened for the presence of SBP (ascitic fluid neutrophils >250/mm3) and SBEM (positive pleural fluid culture and neutrophils >250/mm3 or negative pleural fluid culture and neutrophils >500/mm3 with no evidence of pneumonia/parapneumonic effusion on chest radiograph or CT). Results: The prevalence of SBEM in cirrhotic patients was 1.2% (36/3000) unlike SBP (1.6%; 48/3000). SBEM was detected in 51.4% of the patients with hepatic hydrothorax (36/70). A total of 70 patients had concomitant ascites and hydrothorax, namely SBP (n=17), SBEM (n=5), and dual SBP and SBEM (n=31), whereas 17 patients had sterile concomitant ascites and hydrothorax. Age, sex, liver function, kidney function tests, complete blood count, INR, MELD, MELD-Na, blood chemistry, and culture/sensitivity for ascitic and pleural fluid were statistically not different (p>0.05) between SBP and dual SBP and SBEM patients. Escherichia coli and Klebsiella pneumoniae were detected in the culture. From univariate analysis, no predictors of dual SBP and SBEM were detected. Conclusion: SBEM is a part of SBP in cirrhotic patients with ascites and hydrothorax.



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Percutaneous ultrasound-guided fiducial marker placement for liver cancer robotic stereotactic radio-surgery treatment: A comparative analysis of three types of markers and needles

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Maria Marsico, Tommaso Gabbani, Sarah Lunardi, Andrea Galli, Maria Rosa Biagini, Vito Annese
Background and study aimsPercutaneous placement of fiducial markers is required to perform stereotactic body radiation therapy (SBRT) for liver neoplastic lesions. This prospective trial was designed to evaluate the feasibility and safety of percutaneous ultrasound-guided placement of three different types of markers in patients with liver cancer referred for SBRT.Patients and methodsFifty patients underwent percutaneous ultrasound-guided implantation of a fiducial marker in the liver. Three sizes of needles were used: 25 gauge (G), 22G, and 17G. The 25G and 22G needles contained gold anchor markers of 0.28×10mm and 0.4 ×10mm size, respectively. In contrast, the 17G needle contained a gold grain marker of 1×4mm. Each patient received 1–6 markers, depending on lesion size and numbers. Technical feasibility and the occurrence of adverse events were registered. Computed tomography scans were acquired prior to SBRT to evaluate the location, visibility, or complications related to the markers.ResultsA total of 163 needles were used to deliver 163 markers in 50 patients. No major complications occurred. Minor complication occurrence rate was 12%. The total complication occurrence for all type of markers was 8.5%. No complications were observed with the use of the gold anchor marker of 0.4 ×10mm size. Variance analysis of the three markers showed a significant difference in the frequency of complications amongst the three markers (p<0.01).ConclusionPercutaneous ultrasound-guided placement of fiducial markers for SBRT of liver neoplastic lesions is safe and feasible. In our series, the 22G needle showed some advantage in terms of handling and safety when compared with the 25G and 17G needles. In addition, the gold anchor marker of 0.4 ×10mm size displayed a lower percentage of displacement.



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Prevalence of hepatitis C virus genotypes and subtypes in Lebanese population and major high risk groups

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Antoine Abou Rached, Cesar Yaghi, Leda Khalil, Jowana Saba, Walid Ammar
Background and study aimsThe prevalence of hepatitis C in Lebanon is low. It is estimated at 0.2% of the total population. The aim of our study is to evaluate the exact prevalence of each genotype on a large scale population and in each potential source of infection.Patients and methodsWe reviewed all the data in the Ministry of Public Health related to patients who have submitted their file for treatment during a period of 9years ranging from January 2005 till December 2013.ResultsThe genotype distribution in 1031 Lebanese patients was as following: Genotype 1 was the most predominant representing 47% followed by genotype 4 representing 34% then genotype 3 representing14%. Concerning sex distribution and routes of infection, there was a male predominance in intravenous drug users (IVDU), whereas approximately equal distribution was noted in haemodialysis and transfusion groups. A female predominance was noted in the "unknown" mode of infection. Concerning age distribution and routes of infection, a mean age of 27 was noted in the IVDU group, whereas mean age of 60 in the transfusion group and 50 in the haemodialysis group. In patients who acquired the infection post transfusion or during haemodialysis, genotype 1 was the most predominant, whereas in IVDU, genotype 3 was the most predominant. Concerning sub-genotyping: subtype 1b was the most predominant (84%) in genotype 1. in genotype 2 subtype b with 75%, all genotype 3 were subtype a, in genotype 4 subtype a represents 50% of genotype followed by subtype e in 30%.ConclusionOur data concerning Lebanese population demonstrate that genotype 1 is the most prevalent genotype followed by genotype 4. In IVU, we noted genotype-3 and -1 being the most prevalent in relation to clustering in this high risk group. This distribution differs from most surrounding countries and all other Arab countries.



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APRI test and hyaluronic acid as non-invasive diagnostic tools for post HCV liver fibrosis: Systematic review and meta-analysis

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Magdy Amin El Serafy, Abdel Meguid Kassem, Heba Omar, Mohammad Shaaban Mahfouz, Maissa El Said EL Raziky
Background and study aimsHepatitis C virus (HCV) accounts for a sizable proportion of chronic liver disease cases and represents the most common indication for liver transplantation. Precise diagnosis of hepatic fibrosis stage is considered a funnel-neck in proper management and follow-up of HCV-infected patients. Given the possible complications of liver biopsy, a non-invasive method for assessing hepatic fibrosis is needed. This study aimed to evaluate the diagnostic accuracy of APRI and hyaluronic acid as non-invasive diagnostic assessment tools for post HCV liver fibrosis.Patients and methodsSystematic literature searching identified studies performed on Egyptian territory to evaluate APRI and hyaluronic acid as non-invasive tests of fibrosis and using liver biopsy as the reference standard. Meta-analysis was performed for areas with an adequate number of publications. Validation of meta- analysis on APRI was done on a subset of 150 treatment-naïve post-hepatitis C patients.ResultsBoth APRI and hyaluronic acid have superior predictive power for hepatic cirrhosis (F4) than for significant fibrosis (F2-F3). The pooled estimate for sensitivities and specificities of APRI and hyaluronic acid to diagnose F4 were (84% and 82%) and (83% and 89%) respectively. In the subgroup of treatment naïve post-hepatitis C patients, APRI had higher diagnostic performance to diagnose liver cirrhosis with 93.8% sensitivity and 72.4% specificity (AUC; 0.908, 95%CI; 0.851–0.965, p-value; <0.001) compared to its accuracy to diagnose significant hepatic fibrosis with 65.1% sensitivity and 77.8% (AUC; 0.685, 95% CI; 0.59–0.78, p-value; 0.001).ConclusionAPRI score and hyaluronic acid levels are simple and reliable non-invasive markers to detect advanced fibrosis among post-hepatitis C patients.



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Evaluation of gastro-oesophageal reflux disease in wheezy infants using 24-h oesophageal combined impedance and pH monitoring

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Ahmed Abdallah, Tarek El-Desoky, Khalid Fathi, Wagdi Fawzi Elkashef, Ahmed Zaki
Background and study aimsGastro-oesophageal reflux disease (GERD) is incriminated as a cause of non-asthmatic infantile wheeze. To date, no diagnostic test is considered standard for GERD-related airway reflux diagnosis. Oesophageal combined multiple channel intraluminal impedance and pH (MII-pH) monitoring is proposed to be a sensitive tool for evaluation of all GERD including infantile wheeze. We aimed to determine the GERD prevalence amongst wheezy infants in the first year of life using combined MII-pH versus pH monitoring alone and evaluate the sensitivity and specificity of objective MII-pH monitoring parameters in GERD-associated infantile wheeze diagnosis compared to those of lipid-laden macrophage index (LLMI).Patients and methodsThirty-eight wheezy infants below 1year of age were evaluated for GERD using oesophageal combined MII-pH monitoring and LLMI.ResultsTotally, 60.5% of cases had abnormal MII-pH; only 7.9% of them had abnormal pH monitoring. LLMI was significantly higher in wheezy infants with abnormal MII-pH than infants with normal MII-pH monitoring (112±88 versus 70±48; P=0.036). The current definitions of abnormal MII-pH study, reflux index≥10% and distal reflux episodes≥100, had low sensitivity (23%) but high specificity (100% and 96%, respectively) in GERD-related aspiration diagnosis defined by LLMI≥100. Using ROC curves, bolus contact time≥2.4% and proximal reflux episodes≥46 had 61% and 54% sensitivity and 64% and 76% specificity, respectively, in GERD-related aspiration diagnosis.ConclusionCombined MII-pH is superior to pH monitoring in reflux-associated infantile wheeze diagnosis. Objective data including proximal reflux episodes and bolus contact time should be combined with the current parameters used in reflux-associated infantile wheeze diagnosis.



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Relationship between liver injury and serum cytokeratin 18 levels in asymptomatic hepatitis B virus carriers and in patients with chronic hepatitis B infection

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Ayhan Balkan, Nimet Yılmaz, Yasemin Balkan, Irfan Koruk, Mustafa Örkmez, Musa Aydınlı, Mehmet Koruk
Background and study aimsApoptosis represents a well-known mechanism of cell death involved in most chronic liver injuries. Our aim was to investigate the serum fragment level of cytokeratin 18 (CK18), M30, in asymptomatic hepatitis B virus (HBV) carriers and patients with chronic hepatitis B (CHB) and to evaluate the relationship between serum M30 levels and the severity of hepatic injury.Patients and methodsAsymptomatic HBV carriers (n=169), patients with CHB (n=100), and healthy control subjects (n=43) were enrolled in the study. Serum CK18 (M30) levels were analysed in all subjects. Liver biopsy for histopathological assessment was performed in asymptomatic HBV carriers and in patients with CHB infection.ResultsSerum CK18 (M30) levels were significantly higher in asymptomatic HBV carriers (198.77±77.62U/L) than in healthy control subjects (146.92±40.18U/L). Patients with CHB (283.02±147.45U/L) had significantly higher CK18 (M30) levels than asymptomatic HBV carriers (p=0.001). The diagnostic efficacy of CK18 (M30) levels in distinguishing patients with HBeAg-negative CHB from asymptomatic HBV carriers was found to be moderate (c-statistics: 0.695), and the diagnostic cut-off value of CK18 (M30) was 262U/L (specificity: 85%, sensitivity: 48%, positive likelihood ratio: 3.35, and negative likelihood ratio: 0.60). There was a positive correlation between serum CK18 (M30) levels and histological activity index scores in asymptomatic HBV carriers and patients with CHB.ConclusionsSerum CK18 (M30) levels may be a valuable indicator in distinguishing asymptomatic HBV carriers from patients with HBeAg-negative CHB when considered together with ALT and HBV-DNA levels.



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Efficacy and safety of midazolam and ketamine in paediatric upper endoscopy

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Ahmet Basturk, Reha Artan, Aygen Yılmaz
Background and study aimUpper endoscopy can be successfully carried out in children under deep sedation and anaesthesia. However, the best method of upper endoscopy for children who require gastrointestinal intervention has yet to be defined. The aim of this study is to investigate the efficacy and safety of the sedation induced by intravenous midazolam and ketamine during upper endoscopy in children.Patients and methodsThis study included patients ages 3–18years who had undergone upper endoscopy. All subjects received IV midazolam and ketamine. During the intervention, hypoxia, tachycardia, bradycardia, hypertension, and hypotension were recorded. After the intervention, euphoria, dysphoria, vertigo, visual problems (such as diplopia and nystagmus), and emergencies (such as arrhythmia, convulsion, and hallucination), among other findings, were recorded. Older children who were capable of expressing themselves were questioned to help determine these conditions.ResultsThe mean age of the study group was was 11.9±3.42years; 54% of the patients were females, and 46% were males. During the upper endoscopy, hypoxia occurred in 9% of patients, mild hypertension in 14%, hypotension in 5%, tachycardia in 23%, bradycardia in 8%, and flushing-urticaria in 2%. After the upper endoscopy, one of the most common complications was sore throat, which occurred in 24% of patients. Vomiting was observed in 14% of patients, dizziness in 24%, diplopia in 27%, euphoria in 3% (5 patients), dysphoria in 4%, and hallucination in 4%. Of the total patients, 4% required oxygen supply with a face mask.ConclusionThe results of our study showed that the use of IV midazolam and ketamine during upper endoscopy in children was safe and effective.



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Comparative proteome analysis of the hepatopancreas from the Pacific white shrimp Litopenaeus vannamei under long-term low salinity stress

Publication date: 6 June 2017
Source:Journal of Proteomics, Volume 162
Author(s): Chang Xu, Erchao Li, Yan Liu, Xiaodan Wang, Jian G. Qin, Liqiao Chen
Litopenaeus vannamei is a typical euryhaline decapod model to study the osmoregulation mechanism in crustaceans. The proteomic was undertaken using isobaric tags for relative and absolute quantification together with the reverse phase in high-performance liquid chromatography mass spectrometry to quantitatively identify the proteins differentially expressed in the hepatopancreas under low salinity stress (3psu) compared with the control salinity (25psu). 533 proteins and 84 differentially expressed proteins were identified including 58 proteins with the 1.2-fold cut-off value under chronically low salinity stress. Among these proteins, 26 were up-regulated while 32 were down-regulated. 48 out of 58 differentially expressed proteins were annotated in the Uniprot database and were mapped into 38 pathways by KEGG analysis. These proteins were categorized into the pathways for energy metabolism, signaling, immunization and detoxification, lipid and protein metabolism. A more active glycometabolism, positive response detoxification pathway, immunosuppression and positive osmoregulation were identified in L.vannamei under low salinity stress. This study suggests that under chronically low salinity stress, L. vannamei showed low immunity and high demand for energy especially from glycometabolism. Signaling transfer related pathways, especially the Wnt signaling pathways were involved in the process of salinity adaption, but the in-depth mechanism warrants further investigation.SignificanceIn this study, a comprehensive physiological response was studied using proteomics to reveal the underlying mechanism of adaptation to low salinity in L.vannamei, which was the first report on the proteomic response of crustacean to salinity stress. The extensive proteomic investigation on hepatopancreas under low salinity stress provides a new insight into the adaptive mechanism of this euryhaline crustacean species to low salinity.

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A glycoproteomic approach reveals that the S-layer glycoprotein of Lactobacillus kefiri CIDCA 83111 is O- and N-glycosylated

Publication date: 6 June 2017
Source:Journal of Proteomics, Volume 162
Author(s): Gustavo J. Cavallero, Mariano Malamud, Adriana C. Casabuono, M. de los Ángeles Serradell, Alicia S. Couto
In Gram-positive bacteria, such as lactic acid bacteria, general glycosylation systems have not been documented so far. The aim of this work was to characterize in detail the glycosylation of the S-layer protein of Lactobacillus kefiri CIDCA 83111. A reductive β-elimination treatment followed by anion exchange high performance liquid chromatography analysis was useful to characterize the O-glycosidic structures. MALDI-TOF mass spectrometry analysis confirmed the presence of oligosaccharides bearing from 5 to 8 glucose units carrying galacturonic acid. Further nanoHPLC-ESI analysis of the glycopeptides showed two O-glycosylated peptides: the peptide sequence SSASSASSA already identified as a signature glycosylation motif in L. buchneri, substituted on average with eight glucose residues and decorated with galacturonic acid and another O-glycosylated site on peptide 471–476, with a Glc5–8GalA2 structure. As ten characteristic sequons (Asn-X-Ser/Thr) are present in the S-layer amino acid sequence, we performed a PNGase F digestion to release N-linked oligosaccharides. Anion exchange chromatography analysis showed mainly short N-linked chains. NanoHPLC-ESI in the positive and negative ion modes were useful to determine two different peptides substituted with short N-glycan structures. To our knowledge, this is the first description of the structure of N-glycans in S-layer glycoproteins from Lactobacillus species.SignificanceA detailed characterization of protein glycosylation is essential to establish the basis for understanding and investigating its biological role. It is known that S-layer proteins from kefir-isolated L. kefiri strains are involved in the interaction of bacterial cells with yeasts present in kefir grains and are also capable to antagonize the adverse effects of different enteric pathogens. Therefore, characterization of type and site of glycosidic chains in this protein may help to understand these important properties. Furthermore, this is the first description of N-glycosidic chains in S-layer glycoprotein from Lactobacillus spp.

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Proteomic and transcriptomic analysis of saliva components from the hematophagous reduviid Triatoma pallidipennis

Publication date: 6 June 2017
Source:Journal of Proteomics, Volume 162
Author(s): María J. Hernández-Vargas, Jeovanis Gil, Luis Lozano, Martha Pedraza-Escalona, Ernesto Ortiz, Sergio Encarnación-Guevara, Alejandro Alagón, Gerardo Corzo
Species belonging to the Triatominae subfamily are commonly associated with Chagas disease, as they are potential vectors of the parasite Trypanosoma cruzi. However, their saliva contains a cocktail of diverse anti-hemostatic proteins that prevent blood coagulation, vasodilation and platelet aggregation of blood; components with indisputable therapeutic potential. We performed a transcriptomic and proteomic analyses of salivary glands and protein spots from 2DE gels of milked saliva, respectively, from the Mexican Triatoma pallidipennis. Massive sequencing techniques were used to reveal this protein diversity. A total of 78 out of 233 transcripts were identified as proteins in the saliva, divided among 43 of 55 spots from 2DE gels of saliva, identified by LC-MS/MS analysis. Some of the annotated transcripts putatively code for anti-hemostatic proteins, which share sequence similarities with proteins previously described for South American triatomines. The most abundant as well as diverse transcripts and proteins in the saliva were the anti-hemostatic triabins. For the first time, a transcriptomic analysis uncovered other unrelated but relevant components in triatomines, including antimicrobial and thrombolytic polypeptides. Likewise, unique proteins such as the angiotensin-converting enzyme were identified not just in the salivary gland transcriptome but also at saliva proteome of this North American bloodsucking insect.Biological significanceThis manuscript is the first report of the correlation between proteome and transcriptome of Triatoma pallidipennis, which shows for the first time the presence of proteins in this insect that have not been characterized in other species of this family. This information contributes to a better understanding of the multiple host defense mechanisms that are being affected at the moment of blood ingestion by the insect. Furthermore, this report gives a repertoire of possible therapeutic proteins.

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Editorial Board

Publication date: 6 June 2017
Source:Journal of Proteomics, Volume 162





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Organ-specific proteomics of soybean seedlings under flooding and drought stresses

Publication date: 6 June 2017
Source:Journal of Proteomics, Volume 162
Author(s): Xin Wang, Ehsaneh Khodadadi, Baratali Fakheri, Setsuko Komatsu
Organ-specific analyses enrich the understanding of plant growth and development under abiotic stresses. To elucidate the cellular responses in soybean seedlings exposed to flooding and drought stresses, organ-specific analysis was performed using a gel-free/label-free proteomic technique. Physiological analysis indicated that enzyme activities of alcohol dehydrogenase and delta-1-pyrroline-5-carboxylate synthase were markedly increased in leaf and root of plants treated with 6days of flooding and drought stresses, respectively. Proteins related to photosynthesis, RNA, DNA, signaling, and the tricarboxylic acid cycle were predominately affected in leaf, hypocotyl, and root in response to flooding and drought. Notably, the tricarboxylic acid cycle was suppressed in leaf and root under both stresses. Moreover, 17 proteins, including beta-glucosidase 31 and beta-amylase 5, were identified in soybean seedlings under both stresses. The protein abundances of beta-glucosidase 31 and beta-amylase 5 were increased in leaf and root under both stresses. Additionally, the gene expression of beta-amylase 5 was upregulated in leaf exposed to the flooding and drought, and the expression level was highly correlated with the protein abundance. These results suggest that beta-amylase 5 may be involved in carbohydrate mobilization to provide energy to the leaf of soybean seedlings exposed to flooding and drought.Biological significanceThis study examined the effects of flooding and drought on soybean seedlings in different organs using a gel-free/label-free proteomic approach. Physiological responses indicated that enzyme activities of alcohol dehydrogenase and delta-1-pyrroline-5-carboxylate synthase were increased in leaf and root of soybean seedlings exposed to flooding and drought for 6days. Functional analysis of acquired protein profiles exhibited that proteins related to photosynthesis, RNA, DNA, signaling, and the tricarboxylic acid cycle were predominated affected in leaf, hypocotyl, and root under both stresses. Moreover, the tricarboxylic acid cycle was suppressed in leaf and root of stressed soybean seedlings. Additionally, increased protein abundance of beta-amylase 5 was consistent with upregulated gene expression in the leaf under both stresses, suggesting that carbohydrate metabolism might be governed in response to flooding and drought of soybean seedlings.

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Proteome analysis of human embryonic stem cells organelles

Publication date: 6 June 2017
Source:Journal of Proteomics, Volume 162
Author(s): Faezeh Shekari, Hossein Nezari, Mehran Rezaei Larijani, Chia-Li Han, Hossein Baharvand, Yu-Ju Chen, Ghasem Hosseini Salekdeh
As the functions of proteins are associated with their cellular localization, the comprehensive sub-cellular proteome knowledge of human embryonic stem cells (hESCs) is indispensable for ensuring a therapeutic effect. Here, we have utilized a sub-cellular proteomics approach to analyze the localization of proteins in the nucleus, mitochondria, crude membrane, cytoplasm, heavy and light microsomes. Out of 2002 reproducibly identified proteins, we detected 762 proteins in a single organelle whereas 160 proteins were found in all sub-cellular fractions. We verified the localization of identified proteins through databases and discussed the consistency of the obtained results. With regards to the ambiguity in the definition of a membrane protein, we tried to clearly define the plasma membrane, peripheral membrane and membrane proteins by annotation of these proteins in databases, along with predictions of transmembrane helices. Among ten enriched signaling pathways highlighted in our results, non-canonical Wnt signaling were analyzed in greater detail. The functions of three novel hESC membrane proteins (ERBB4, GGT1 and ZDHHC13) have been assessed in terms of pluripotency. Our report is the most comprehensive for organellar proteomics of hESCs.SignificanceMass spectrometric identification of proteins using a TripleTOF 5600 from nucleus, mitochondria, crude membrane, cytoplasm, heavy and light microsomal fractions highlighted the significance of the non-canonical Wnt signaling in human embryonic stem cells.

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Semen proteomics and male infertility

Publication date: 6 June 2017
Source:Journal of Proteomics, Volume 162
Author(s): Meritxell Jodar, Ada Soler-Ventura, Rafael Oliva
Semen is a complex body fluid containing an admixture of spermatozoa suspended in secretions from the testes and epididymis which are mixed at the time of ejaculation with secretions from other accessory sex glands such as the prostate and seminal vesicles. High-throughput technologies have revealed that, contrary to the idea that sperm cells are simply a silent delivery vehicle of the male genome to the oocyte, the sperm cells in fact provide both a specific epigenetically marked DNA together with a complex population of proteins and RNAs crucial for embryogenesis. Similarly, –omic technologies have also enlightened that seminal fluid seems to play a much greater role than simply being a medium to carry the spermatozoa through the female reproductive tract. In the present review, we briefly overview the sperm cell biology, consider the key issues in sperm and seminal fluid sample preparation for high-throughput proteomic studies, describe the current state of the sperm and seminal fluid proteomes generated by high-throughput proteomic technologies and provide new insights into the potential communication between sperm and seminal fluid. In addition, comparative proteomic studies open a window to explore the potential pathogenic mechanisms of infertility and the discovery of potential biomarkers with clinical significance.SignificanceThe review updates the numerous proteomics studies performed on semen, including spermatozoa and seminal fluid. In addition, an integrative analysis of the testes, sperm and seminal fluid proteomes is also included providing insights into the molecular mechanisms that regulate the generation, maturation and transit of spermatozoa. Furthermore, the compilation of several differential proteomic studies focused on male infertility reveals potential pathways disturbed in specific subtypes of male infertility and points out towards future research directions in the field.



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Corrigendum to “Quantitative proteomics and integrative network analysis identified novel genes and pathways related to osteoporosis” [J. Proteomics 142 (16 June 2016) 45–52]

Publication date: 6 June 2017
Source:Journal of Proteomics, Volume 162
Author(s): Yong Zeng, Lan Zhang, Wei Zhu, Chao Xu, Hao He, Yu Zhou, Yao-Zhong Liu, Qing Tian, Ji-Gang Zhang, Fei-Yan Deng, Hong-Gang Hu, Li-Shu Zhang, Hong-Wen Deng




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Plasma-induced selectivity in bone cancer cells death

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Cristina Canal, Raul Fontelo, Ines Hamouda, Jordi Guillem-Marti, Uros Cvelbar, Maria-Pau Ginebra
BackgroundCurrent therapies for bone cancers - either primary or metastatic – are difficult to implement and unfortunately not completely effective. An alternative therapy could be found in cold plasmas generated at atmospheric pressure which have already demonstrated selective anti-tumor action in a number of carcinomas and in more relatively rare brain tumors. However, its effects on bone cancer are still unknown.MethodsHerein, we employed an atmospheric pressure plasma jet (APPJ) to validate its selectivity towards osteosarcoma cell line vs. osteoblasts & human mesenchymal stem cells.ResultsCytotoxicity following direct interaction of APPJ with cells is comparable to indirect interaction when only liquid medium is treated and subsequently added to the cells, especially on the long-term (72h of cell culture). Moreover, following contact of the APPJ treated medium with cells, delayed effects are observed which lead to 100% bone cancer cell death through apoptosis (decreased cell viability with incubation time in contact with APPJ treated medium from 24h to 72h), while healthy cells remain fully viable and unaffected by the treatment.ConclusionsThe high efficiency of the indirect treatment indicates that an important role is played by the reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the gaseous plasma stage and then transmitted to the liquid phase, which overall lead to lethal and selective action towards osteosarcoma cells. These findings open new pathways for treatment of metastatic bone disease with a minimally invasive approach.

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Preliminary Results of a Simplified Breast MRI Protocol to Characterize Breast Lesions

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Publication date: Available online 1 June 2017
Source:Academic Radiology
Author(s): Valeria Romeo, Renato Cuocolo, Raffaele Liuzzi, Albina Riccardi, Antonello Accurso, Alessandra Acquaviva, Roberta Buonocore, Massimo Imbriaco
Rationale and ObjectivesThis study aimed to investigate whether a simplified breast magnetic resonance imaging (MRI) protocol consisting of a localizer, one precontrast sequence, and three time-point postcontrast sequences (at 28 seconds, 84 seconds and 252 seconds after the contrast agent administration) is suitable for the characterization of breast lesions as compared to a full diagnostic protocol (FDP). This study also aimed to review the current literature concerning abbreviated breast MRI protocols and offer an alternative protocol.Materials and MethodsBreast magnetic resonance (MR) examinations with detected breast lesions of 98 patients were retrospectively evaluated. Two expert radiologists in consensus reviewed the simplified breast protocol (SBP) first and only thereafter the regular FDP, recording a diagnosis for each detected lesion for both protocols. Receiver operating characteristic curve analysis was performed to determine the diagnostic performance of the SBP compared to the standard FDP. A revision of the previously reported abbreviated breast magnetic resonance protocols was also carried out.ResultsA total of 180 lesions were identified; of these, 110 (61%) were malignant and 70 (39%) were benign. Of the 110 malignant lesions, 86 (78%) were invasive ductal carcinoma, 18 (16%) were invasive lobular carcinoma, and 6 (6%) were ductal carcinoma in situ. Areas under the curve for the receiver operating characteristic curves for the SBP vs the FDP were equivalent (0.98 vs 0.99, respectively; P = 0.76). The SBP could be performed in approximately 6 minutes and 58 seconds, compared to 14 minutes and 48 seconds for the FDP.ConclusionsAn SBP protocol including a late postcontrast time point is accurate for the characterization of breast lesions and was comparable to the standard FDP protocol, allowing a potential reduction of the total acquisition and interpretation times.



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Measuring contact area in a sliding human finger-pad contact

Abstract

Background/Purpose

The work outlined in this paper was aimed at achieving further understanding of skin frictional behaviour by investigating the contact area between human finger-pads and flat surfaces.

Methods

Both the static and the dynamic contact areas (in macro- and micro-scales) were measured using various techniques, including ink printing, optical coherence tomography (OCT) and Digital Image Correlation (DIC).

Results

In the studies of the static measurements using ink printing, the experimental results showed that the apparent and the real contact area increased with load following a piecewise linear correlation function for a finger-pad in contact with paper sheets. Comparisons indicated that the OCT method is a reliable and effective method to investigate the real contact area of a finger-pad and allow micro-scale analysis. The apparent contact area (from the DIC measurements) was found to reduce with time in the transition from the static phase to the dynamic phase while the real area of contact (from OCT) increased.

Conclusions

The results from this study enable the interaction between finger-pads and contact object surface to be better analysed, and hence improve the understanding of skin friction.



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A Study of the Combination of Cetuximab and Methotrexate in Recurrent or Metastatic Cancer of the Head and Neck

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: Cetuximab;   Drug: Methotrexate
Sponsors:   Radboud University;   Merck Serono International SA;   Leiden University Medical Center;   Academisch Ziekenhuis Maastricht;   Erasmus Medical Center;   Medisch Spectrum Twente;   Medical Center Haaglanden;   Elisabeth-TweeSteden Ziekenhuis;   Medical Centre Leeuwarden;   Erasmus Medical Center, Rotterdam
Recruiting - verified May 2017

http://ift.tt/2rLbg9R

Is long-term postoperative monitoring of microsurgical flaps still necessary?

Autologous microsurgical flap reconstruction has become commonplace in most plastic surgery units, and the success rates of this procedure have markedly increased over recent years. However, the possibility of flap failure still needs to be considered. A review of the literature reveals that the critical period for flap-threatening complications is the first 24-to-48 postoperative hours; however, the window for the onset of these complications remains open for up to 7 days postoperatively. Here, we focus on the timing of flap complications, aiming to elucidate the time period over which meticulous flap monitoring can still contribute positively to flap salvage rates.

http://ift.tt/2rx1yal

The Dorsal Frontoparietal Network: A Core System for Emulated Action

Publication date: Available online 1 June 2017
Source:Trends in Cognitive Sciences
Author(s): Radek Ptak, Armin Schnider, Julia Fellrath
The dorsal frontoparietal network (dFPN) of the human brain assumes a puzzling variety of functions, including motor planning and imagery, mental rotation, spatial attention, and working memory. How can a single network engage in such a diversity of roles? We propose that cognitive computations relying on the dFPN can be pinned down to a core function underlying offline motor planning: action emulation. Emulation creates a dynamic representation of abstract movement kinematics, sustains the internal manipulation of this representation, and ensures its maintenance over short time periods. Based on these fundamental characteristics, the dFPN has evolved from a pure motor control network into a domain-general system supporting various cognitive and motor functions.



http://ift.tt/2qGIDqi

Influence of broadleaf forest vegetation on atmospheric deposition of airborne radionuclides

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Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): Miodrag Krmar, Dragan Radnović, Jan Hansman, Predrag Repić
The activities of airborne radionuclides 7Be and unsupported 210Pb (210Pbus) were measured in moss samples taken from 17 different locations. The objective was to estimate the influence of the broadleaf forest vegetation on atmospheric deposition of airborne radionuclides attached to aerosols. Two moss samples were collected at each location: within the forest stand (inside the area of the tree canopy projection) and within forest openings (outside the area of the tree canopy projection). Samples were taken in the spring season, before the leaves of trees came forth and in the autumn season, right before fall defoliation. A measurement indicates an absence of variation in 210Pbus concentration, however spring/autumn ratios of 7Be concentrations in mosses showed the expected seasonal difference in 7Be deposition. It was also noted that atmospheric deposition of 7Be at the forest openings was about two times higher than deposition in the forest. Using very simplified models, these measurements can be used to get estimation at how long 7Be and aerosols can reside on the leaves before precipitation eventually wash it to the ground mosses. It was estimated that the mean residence time of aerosols in the leaves was up to 50 days.



http://ift.tt/2s0id6O

Potein Kinase D Signaling in Cancer: A Friend or Foe?

Publication date: Available online 31 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Adhiraj Roy, Jing Ye, Fan Deng, Qiming Jane Wang
Protein kinase D is a family of evolutionarily conserved serine/threonine kinases that belongs to the Ca++/Calmodulin-dependent kinase superfamily. Signal transduction pathways mediated by PKD can be triggered by a variety of stimuli including G protein-coupled receptor agonists, growth factors, hormones, and cellular stresses. The regulatory mechanisms and physiological roles of PKD have been well documented including cell proliferation, survival, migration, angiogenesis, regulation of gene expression, and protein/membrane trafficking. However, its precise roles in disease progression, especially in cancer, remain elusive. A plethora of studies documented the cell- and tissue-specific expressions and functions of PKD in various cancer-associated biological processes, while the causes of the differential effects of PKD have not been thoroughly investigated. In this review, we have discussed the structural-functional properties, activation mechanisms, signaling pathways and physiological functions of PKD in the context of human cancer. Additionally, we have provided a comprehensive review of the reported tumor promoting or tumor suppressive functions of PKD in several major cancers types and discussed the discrepancies that have been raised on PKD as a major regulator of malignant transformation.



http://ift.tt/2qMDxrE

Preparation of acellular scaffold for corneal tissue engineering by supercritical carbon dioxide extraction technology

Publication date: Available online 1 June 2017
Source:Acta Biomaterialia
Author(s): Yi-Hsun Huang, Fan-Wei Tseng, Wen-Hsin Chang, I-Chen Peng, Dar-Jen Hsieh, Shu-Wei Wu, Ming-Long Yeh
In this study, we developed a novel method using supercritical carbon dioxide (SCCO2) to prepare acellular porcine cornea (APC). Under gentle extraction conditions using SCCO2 technology, hematoxylin and eosin staining showed that cells were completely lysed, and cell debris, including nuclei, was efficiently removed from the porcine cornea. The SCCO2-treated corneas exhibited intact stromal structures and appropriate mechanical properties. Moreover, no immunological reactions and neovascularization were observed after lamellar keratoplasty in rabbits. All transplanted grafts and animals survived without complications. The transplanted APCs were opaque after the operation but became transparent within 2 weeks. Complete re-epithelialization of the transplanted APCs was observed within 4 weeks. In conclusion, APCs produced by SCCO2 extraction technology could be an ideal and useful scaffold for corneal tissue engineering.Statement of significanceWe decellularized the porcine cornea using SCCO2 extraction technology and investigated the characteristics, mechanical properties, and biocompatibility of the decellularized porcine cornea by lamellar keratoplasty in rabbits. To the best of our knowledge, this is the first report describing the use of SCCO2 extraction technology for preparation of acellular corneal scaffold. We proved that the cellular components of porcine corneas had been efficiently removed, and the biomechanical properties of the scaffold were well preserved by SCCO2 extraction technology. SCCO2-treated corneas maintained optical transparency and exhibited appropriate strength to withstand surgical procedures. In vivo, the transplanted corneas showed no evidence of immunological reactions and exhibited good biocompatibility and long-term stability. Our results suggested that the APCs developed by SCCO2 extraction technology could be an ideal and useful scaffold for corneal replacement and corneal tissue engineering.

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http://ift.tt/2skejmw

Nanostructured Raspberry-like Gelatin Microspheres for Local Delivery of Multiple Biomolecules

Publication date: Available online 1 June 2017
Source:Acta Biomaterialia
Author(s): Mani Diba, Bram Pape, Alexey Klymov, Yang Zhang, Jiankang Song, Dennis W.P.M. Löwik, Hajar Seyednejad, Sander C.G. Leeuwenburgh
Multicompartment particles, which are particles composed of smaller building units, have gained considerable interest during the past decade to facilitate simultaneous and differential delivery of several biomolecules in various applications. Supercritical carbon dioxide (CO2) processing is an industrial technology widely used for large-scale synthesis and processing of materials. However, the application of this technology for production of multicompartment particles from colloidal particles has not yet been explored. Here, we report the formation of raspberry-like gelatin (RLG) microparticles composed of gelatin nanoparticles as colloidal building blocks through supercritical CO2 processing. We show that these RLG microparticles exhibit a high stability upon dispersion in aqueous media without requiring chemical cross-linking. We further demonstrate that these microparticles are cytocompatible and facilitate differential release of two different model compounds. The strategy presented here can be utilized as a cost-effective route for production of various types of multicompartment particles using colloidal particles with suitable interparticle interactions.Statement of singnificanceMulticompartment particles have gained considerable interest during the past decade to facilitate simultaneous and differential delivery of multiple biomolecules in various biomedical applications. Nevertheless, common methods employed for the production of such particles are often complex and only offer small-scale production. Here, we report the formation of raspberry-like gelatin (RLG) microparticles composed of gelatin nanoparticles as colloidal building blocks through supercritical CO2 processing. We show that these microparticles are cytocompatible and facilitate differential release of two model compounds with different molecular sizes, promising successful applications in various biomedical areas. Summarizing, this paper presents a novel strategy that can be utilized as a cost-effective route for production of various types of multicompartment particles using a wide range of colloidal building blocks.

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A Multi-defense Strategy: Enhancing Bactericidal Activity of a Medical Grade Polymer with a Nitric Oxide Donor and Surface-immobilized Quaternary Ammonium Compound

Publication date: Available online 1 June 2017
Source:Acta Biomaterialia
Author(s): Jitendra Pant, Jing Gao, Marcus J. Goudie, Sean Hopkins, Jason Locklin, Hitesh Handa
Although the use of biomedical devices in hospital-based care is inevitable, unfortunately, it is also one of the leading causes of the nosocomial infections, and thus demands development of novel antimicrobial materials for medical device fabrication. In the current study, a multi-defense mechanism against Gram-positive and Gram-negative bacteria is demonstrated by combining a NO releasing agent with a quaternary ammonium antimicrobial that can be covalently grafted to medical devices. Antibacterial polymeric composites were fabricated by incorporating a nitric oxide (NO) donor, S-nitroso-N-acetyl-penicillamine (SNAP) in CarboSil® polymer and top coated with surface immobilized benzophenone based quaternary ammonium antimicrobial (BPAM) small molecule. The results suggest that SNAP and BPAM have a different degree of toxicity towards Gram-positive and Gram-negative bacteria, and the SNAP-BPAM combination is effective in reducing both types of adhered viable bacteria equally well. SNAP-BPAM combinations reduced the adhered viable Pseudomonas aeruginosa by 99.0% and Staphylococcus aureus by 99.98% as compared to the control CarboSil films. Agar diffusion tests demonstrate that the diffusive nature of NO kills bacteria beyond the direct point of contact which the non-leaching BPAM cannot achieve alone. This is important for potential application in biofilm eradication. The live-dead bacteria staining shows that the SNAP-BPAM combination has more attached dead bacteria (than live) as compared to the controls. The SNAP-BPAM films have increased hydrophilicity and higher NO flux as compared to the SNAP films useful for preventing blood protein and bacterial adhesion. Overall the combination of SNAP and BPAM imparts different attributes to the polymeric composite that can be used in the fabrication of antimicrobial surfaces for various medical device applications.Statement of SignificanceA significant increase in the biomedical device related infections (BDRIs), inability of the currently existing antimicrobial strategies to combat them and a proportional rise in the associated morbidity demands development of novel antimicrobial surfaces. Some of the major challenges associated with the currently used therapeutics are: antibiotic resistance and cytotoxicity. In the current study, engineered polymeric composites with multi-defense mechanism were fabricated to kill bacteria via both active and passive mode. This was done by incorporating a nitric oxide (NO) donor S-nitroso-N-acetypenicillamine (SNAP) in a medical grade polymer (CarboSil®) and a benzophenone based quaternary ammonium antimicrobial small molecule (BPAM) was surface immobilized as the top layer. The developed biomaterial was tested with Gram-positive and Gram-negative strains and was found to be effective against both the strains resulting in up to 99.98% reduction in viable bacterial count. This preventative strategy can be used to fabricate implantable biomedical devices (such as catheters, stents, extracorporeal circuits) to not only significantly limit biofilm formation but also to reduce the antibiotic dose which are usually given post infections.

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Considering the indirect effects of colonialism: Example from a Great Plains middle ground

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Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Sarah Trabert
Historically, there have been many archaeological and ethnographic works that examined the impacts of colonialism on indigenous peoples where direct contact took place. More recently, archaeological scholarship has drawn increasing attention towards examining the far-reaching effects that colonialism had on indigenous peoples by considering communities on the periphery of colonial control. Here, I argue that it is the indirect or down-the-line effects of colonialism that can best inform us of the extent and intensity of social, economic, and demographic change seen in regions adjacent to colonial centers. This paper considers methodological frameworks utilized in several regions and applies elements of these models to the Great Plains of North America to examine the ways indigenous social networks and Spanish colonialism forever changed the lives of people living hundreds of miles away from actual colonies. Evidence of blended technological and manufacturing styles at sites in western Kansas point to a creolized Puebloan/Plains Apache community that formed as a direct result of the indirect effects of Spanish colonial activities, highlighting the significant role of the Central Plains middle ground for many Native peoples.



http://ift.tt/2qHbXkl

Water, centering, and the beginning of time at Middle Preclassic Nixtun-Ch'ich', Petén, Guatemala

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Prudence M. Rice, Timothy W. Pugh
What determines a site's location? In the ceremonial core of the lowland Maya site of Nixtun-Ch'ich', Guatemala, a large depression lies east of an E-Group (quasi-solar-"observatory") architectural complex. Excavations in this depression (Fosa Y) revealed a large, deep—and thus far bottomless—cavity in the limestone filled with water-deposited sediments containing Terminal Early and Middle Preclassic (∼1000–400BCE) pottery and other remains. The upper periphery of Fosa Y was lined with amphitheater-like stone terraces, which framed a rich late Middle Preclassic ritual midden. Interpretations of the role of Fosa Y and adjacent constructions relate to deep structures of Mesoamerican belief systems, from Olmec to Aztec, concerning water, mountains, solar stations, the Underworld, and Creation. Fosa Y was likely a natural sinkhole (cenote), rather than human-made, and thus a powerful and deeply symbolic feature of the terrain for the earliest settlers and a compelling setting for integrative community rituals. It centered the east-west axis of this unusual, gridded, early city and its sacred landscape.

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Altered reward sensitivity in female offspring of cocaine-exposed fathers

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Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Delaney K. Fischer, Richard C. Rice, Arlene Martinez Rivera, Mary Donohoe, Anjali M. Rajadhyaksha
Recent rodent studies have demonstrated that parental cocaine exposure can influence offspring behavior, supporting the idea that environmental insults can impact subsequent generations. However, studies on the effects of paternal cocaine exposure are limited and multiple inconsistencies exist. In the current study, we behaviorally characterize the effects of paternal cocaine exposure in a C57BL/6J intergenerational mouse model. Male sires were administered cocaine hydrochloride (20mg/kg) or saline (0.01mL/g) once a day for 75days, and bred with drug naïve females twenty-four hours after the final injection. Offspring, separated by sex, were tested in a battery of behaviors. We found that paternal cocaine exposure altered sensitivity to the rewarding and stimulant effects of psychostimulants and natural reward (sucrose) in female offspring; female cocaine-sired offspring showed blunted cocaine preference using cocaine conditioned place preference (CPP) at a low dose (5mg/kg), but displayed similar preference at a higher dose (10mg/kg) compared to saline-sired controls. Additionally, cocaine-sired female offspring exhibited higher psychomotor sensitivity to cocaine (10mg/kg) and amphetamine (2mg/kg) and consumed more sucrose. Cocaine-sired males exhibited increased psychomotor effects of cocaine and amphetamine. Male offspring also displayed an anxiety-like phenotype. No effect of paternal cocaine exposure was observed on depressive-like, learning and memory or social behavior in male or female offspring. Collectively, our findings show that paternal, chronic cocaine exposure induces intergenerational behavioral effects in male and female offspring with greatest impact on sensitivity to psychostimulants and sucrose in females.



http://ift.tt/2suG3nQ

Socially induced plasticity in sensorimotor gating in the African cichlid fish Astatotilapia burtoni

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Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Heike Neumeister, Mila Adelman, William Gallagher, Jiangtao Gou, Karin Merrins, Melissa Perkowski, Stephanie Shih, Beth Terranova, Thomas Preuss
Deficits in prepulse inhibition (PPI), social defeat and social withdrawal are hallmark features of several neurological and neuropsychiatric disorders. However, the link between social environment and PPI i.e., the possible role of social defeat in driving PPI plasticity, is far from clear. Here we explored these questions in the African cichlid fish Astatotilapia burtoni, where males exist as two distinct yet reversible phenotypes. In fish communities, DOMs exhibit frequent aggressive and territorial behaviors, threatening and attacking SUBs, which respond either by engaging in fights and fleeing, or by avoiding interaction with DOMs altogether. Social phenotypes were selected using focal observations of dominant and submissive behaviors. Tests of auditory PPI showed markedly decreased PPI in SUBs as compared to DOMs at prepulse/pulse interstimulus interval of ISI 50ms. Interestingly, further analysis showed the PPI reduction in SUBs was driven by males with low social interactivity. Testing males before and after social transitions revealed increasing and decreasing PPI in ascending and descending males, respectively. In an open field paradigm, SUBs also showed higher levels of wall hugging (thigmotaxis) and freezing when compared to DOMs i.e., an increase in anxiety-related behavior. Together the results suggest distinct yet reversible behavioral PPI phenotypes in A. burtoni males, and that social defeat drives PPI plasticity. The fact that PPI deficits are readily reversible by status change implies PPI plasticity may reflect an adaptive response to challenges in the social environment.



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Time dependent effect of chronic embryonic exposure to ethanol on zebrafish: Morphology, biochemical and anxiety alterations

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Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Nurul Farhana Ramlan, Nurul Syafida Asma Mohd Sata, Siti Norhidayah Hassan, Noraini Abu Bakar, Syahida Ahmad, Syaizwan Zahmir Zulkifli, Che Azurahanim Che Abdullah, Wan Norhamidah Wan Ibrahim
Exposure to ethanol during critical period of development can cause severe impairments in the central nervous system (CNS). This study was conducted to assess the neurotoxic effects of chronic embryonic exposure to ethanol in the zebrafish, taking into consideration the time dependent effect. Two types of exposure regimen were applied in this study. Withdrawal exposure group received daily exposure starting from gastrulation until hatching, while continuous exposure group received daily exposure from gastrulation until behavioural assessment at 6dpf (days post fertilization). Chronic embryonic exposure to ethanol decreased spontaneous tail coiling at 24hpf (hour post fertilization), heart rate at 48hpf and increased mortality rate at 72hpf. The number of apoptotic cells in the embryos treated with ethanol was significantly increased as compared to the control. We also measured the morphological abnormalities and the most prominent effects can be observed in the treated embryos exposed to 1.50% and 2.00%. The treated embryos showed shorter body length, larger egg yolk, smaller eye diameter and heart edema as compared to the control. Larvae received 0.75% continuous ethanol exposure exhibited decreased swimming activity and increased anxiety related behavior, while withdrawal ethanol exposure showed increased swimming activity and decreased anxiety related behavior as compared to the respective control. Biochemical analysis exhibited that ethanol exposure for both exposure regimens altered proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. Our results indicated that time dependent effect of ethanol exposure during development could target the biochemical processes thus leading to induction of apoptosis and neurobehavioral deficits in the zebrafish larvae. Thus it raised our concern about the safe limit of alcohol consumption for pregnant mother especially during critical periods of vulnerability for developing nervous system.



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Spectral and temporal properties of calls reveal deficits in ultrasonic vocalizations of adult Fmr1 knockout mice

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Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Samantha L. Hodges, Suzanne O. Nolan, Conner D. Reynolds, Joaquin N. Lugo
The Fmr1 knockout (KO) mouse has commonly been used to investigate communication impairments, one of the key diagnostic symptoms observed in Fragile X syndrome (FXS) and Autism spectrum disorder (ASD). Many studies have found alterations in ultrasonic vocalizations (USVs) in neonatal Fmr1 KO mice, however, there is limited research investigating whether these deficits continue into adulthood. In the present study, we examine differences in female urine-induced ultrasonic vocalizations, scent marking behavior, odor discrimination, and open field activity in adult male Fmr1 KO and wildtype (WT) mice. Overall, we found extensive alterations between genotypes in both spectral and temporal properties of ultrasonic vocalizations. There was no difference in the average number of calls emitted by both genotypes, however, Fmr1 KO mice emitted calls of a higher frequency, decreased amplitude, and shorter duration than WT mice. Spectrographic analyses revealed statistically significant differences between genotypes in the types of calls emitted. Contrastingly, we found no differences in scent marking behavior, a form of social communication, or in odor discrimination and activity levels of the mice. The results corroborate previous studies emphasizing the importance of qualitative differences observed in vocalization behavior of Fmr1 KO mice, rather than quantitative measurements such as number of calls emitted. Overall, the study confirms the presence of abnormalities in vocalization behavior in adult Fmr1 KO mice that we believe are consistent with communication deficits seen in the syndrome.



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Modulation of synaptic plasticity by short-term aerobic exercise in adult mice

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Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): G. D'Arcangelo, T. Triossi, A. Buglione, G. Melchiorri, V. Tancredi
Physiological effects of different types, of continuous and interval aerobic training, have been largely described and studied in the adult man. It was previously indicated that interval training plays an important role in maximizing both peripheral muscle and central cardiorespiratory adaptations, permitting significant functional improvement even in healthy sedentary subjects. Since the outcome of different aerobic training trials on cognitive processes had never been evaluated, we compared, on an experimental mouse model, the effects of four training exercise protocols, named respectively C100, I100, C50 and I50 depending on the volume and on the type of training proposed, continuous or interval method. Therefore, to asses quantitative and qualitative functional changes, we analyzed several physical parameters before and after 6 weeks training in all four groups with respect to the control sedentary animals and we studied synaptic plasticity, by extracellular in vitro recordings, in hippocampal mouse slices, a region involved in learning and memory processes. We found that all four protocols of exercise applied in this study exerted positive effects on both physical and training parameters inducing weight augmentation, strength endurance and aerobic endurance increase, and potentiation of motor coordination. However, the improvement observed failed to induce an enhancement in synaptic plasticity in three out of four exercise protocols and only in the slices from mice trained with the interval 50% volume exercise the long term potentiation (LTP) increased with respect to the sedentary group. These findings suggest that motor activity exerts positive effects on cognitive processes provided that certain principles are respected, such as the training load and the elements of which it is composed, in order to plan the right quantitative and qualitative parameters and the appropriate recovery periods.



http://ift.tt/2rZQa7e

Characterization of long-term gait deficits in mouse dMCAO, using the CatWalk system

Publication date: 28 July 2017
Source:Behavioural Brain Research, Volume 331
Author(s): E. Caballero-Garrido, J.C. Pena-Philippides, Z. Galochkina, E. Erhardt, T. Roitbak
Evaluation of functional outcome is widely used across species to assess the recovery process following various pathological conditions, including spinal cord injury, musculo-skeletal injury, mithochondrial disease, neuropathic cancer, Huntington's disease, chronic pain, cortical lesion, and olivocerebellar degeneration among others. The Stroke Therapy Academic Industry Roundtable (STAIR) recommends multiple endpoints for behavioral studies in pre-clinical stroke research, to demonstrate their clinical relevance. One of the more challenging tasks in experimental stroke research is measuring long-term functional outcome in mice. It is, however, becoming more important, since transgenic mice are increasingly used for modeling human neurological disorders. Using CatWalk, we characterized long-lasting gait/locomotion deficits following mouse distal middle cerebral artery occlusion (dMCAO). The post-dMCAO assessment was performed at 7, 14, 21, and 28days after experimental ischemia. When compared to sham-operated mice, dMCAO animals displayed a statistically significant decrease in Spatial parameters (such as Paw Area), while the Temporal parameters (Stand, Initial and Terminal Dual Stances) were significantly increased for three weeks after surgery. Kinetic parameters were significantly decreased in dMCAO animals at 7days after dMCAO. The Interlimb coordination group of parameters displayed the strongest deficits at 21days. While CatWalk variables were altered in all paws, the degree of change was greatest for the parameters measured from the Right Front Paw (contralateral to the lesion). All parameters measured in dMCAO and Sham-operated groups reached similar levels at four weeks after the experimental insult, which reflects a spontaneous post-ischemic recovery. Based on our investigation, we conclude that CatWalk represents a relevant and sensitive analysis, which allows long-term characterization of animal functional recovery in the dMCAO model of experimental ischemia.

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http://ift.tt/2qGyWIn

Is centrally induced alveolar bone loss in a large animal model preventable by peripheral hormone substitution?

Abstract

Objectives

Alveolar bone structures are mostly investigated in small animal models. The majority of these studies examined local influences on the alveolar bone, but only a few examined systemic influencing factors. The hypothalamic-pituitary axis is known to be essential for a vital bone balance. The aim of this study was to analyse the effects that selective hormone treatments have on alveolar bone structure and quality in a sheep model for alveolar bone loss, induced by hypothalamic-pituitary disconnection (HPD).

Methods

Thirty sheep were randomly selected into six groups of five each: control (C), ovariectomy—OVX (O), O + HPD (OH), OH with oestrogen treatment (OHE), OH with thyroxine (T4) treatment (OHT), and OH with a combined treatment of oestrogen and thyroxine (OHTE). After OVX and HPD procedures and an additional 9-month observation/treatment period, structural bone analyses of the mandible were performed by contact radiography, micro-CT, and static histomorphometry.

Results

The HPD procedure caused structural alveolar bone parameters to decrease significantly compared to controls (C). Treatment with oestrogen (OHE) was protective and bone structure was maintained at baseline levels. Thyroxine treatment (OHT) promoted significant bone loss, but the combined treatment (OHTE) improved bone structure and volume parameters even above baseline levels.

Conclusions

Alveolar bone homeostasis significantly underlies systemic regulatory systems. Centrally induced (HPD) bone loss can be prevented by combined peripheral treatment with oestrogen and thyroxine.

Clinical relevance

These results demonstrate the significance of a balanced hormonal regulatory system for steady bone remodelling and maintenance of healthy alveolar bone.



http://ift.tt/2qH6WrU

Scholar : These new articles for Annals of the American Association of Geographers are available online

Taylor & Francis Online - The new journals and reference work platform for Taylor & Francis
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Methods, Models, and GIS

System Effects: A Hybrid Methodology for Exploring the Determinants of Food In/Security
Luke K. Craven
Pages: 1-17 | DOI: 10.1080/24694452.2017.1309965


The Application of a Geographically Weighted Principal Component Analysis for Exploring Twenty-three Years of Goat Population Change across Mongolia
Narumasa Tsutsumida http://ift.tt/2qGxLZp, Paul Harris http://ift.tt/2rZJpSS & Alexis Comber http://ift.tt/2qGJ5om
Pages: 1-15 | DOI: 10.1080/24694452.2017.1309968


Nature and Society

The Land Sparing Complex: Environmental Governance, Agricultural Intensification, and State Building in the Brazilian Amazon
Gregory M. Thaler
Pages: 1-20 | DOI: 10.1080/24694452.2017.1309966


Big Food and Little Data: The Slow Harvest of Corporate Food Supply Chain Sustainability Initiatives
Susanne Freidberg
Pages: 1-18 | DOI: 10.1080/24694452.2017.1309967


Find out more about the issues and challenges in Governing Asia. This collection includes free access papers on security challenges, the Abe and Modi administration, reflections on the Chinese Governance and more. Browse today!

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Cytosolic Proteostasis Networks of the Mitochondrial Stress Response

Publication date: Available online 1 June 2017
Source:Trends in Biochemical Sciences
Author(s): Davide D'Amico, Vincenzo Sorrentino, Johan Auwerx
Mitochondrial stress requires timely intervention to prevent mitochondrial and cellular dysfunction. Re-establishing the correct protein homeostasis is crucial for coping with mitochondrial stress and maintaining cellular homeostasis. The best-characterized adaptive pathways for mitochondrial stress involve a signal originating from stressed mitochondria that triggers a nuclear response. However, recent findings have shown that mitochondrial stress also affects a complex network of protein homeostasis pathways in the cytosol. We review how mitochondrial dysregulation affects cytosolic proteostasis by regulating the quantity and quality of protein synthesis, protein stability, and protein degradation, leading to an integrated regulation of cellular metabolism and proliferation. This mitochondria to cytosol network extends the current model of the mitochondrial stress response, with potential applications in the treatment of mitochondrial disease.



http://ift.tt/2sjMFGj

Advances on the Transfer of Lipids by Lipid Transfer Proteins

Publication date: Available online 1 June 2017
Source:Trends in Biochemical Sciences
Author(s): Louise H. Wong, Alenka Čopič, Tim P. Levine
Transfer of lipid across the cytoplasm is an essential process for intracellular lipid traffic. Lipid transfer proteins (LTPs) are defined by highly controlled in vitro experiments. The functional relevance of these is supported by evidence for the same reactions inside cells. Major advances in the LTP field have come from structural bioinformatics identifying new LTPs, and from the development of countercurrent models for LTPs. However, the ultimate aim is to unite in vitro and in vivo data, and this is where much progress remains to be made. Even where in vitro and in vivo experiments align, rates of transfer tend not to match. Here we set out some of the advances that might test how LTPs work.



http://ift.tt/2rKKNJE

Determination of carbamazepine and 12 degradation products in various compartments of an outdoor aquatic mesocosm by reliable analytical methods based on liquid chromatography-tandem mass spectrometry

Abstract

The aims of this work are to develop suitable analytical methods to determine the widely used anticonvulsant carbamazepine and 12 of its degradation/transformation products in water, sediment, fish (Gasterosteus aculeatus) and mollusc (Dreissena polymorpha). Protocols based on solid phase extraction for water, pressurized-liquid extraction for sediments and QuEChERS (quick easy cheap efficient rugged and safe) extraction for both organisms followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) are developed, validated and finally applied to samples collected during a 6-month experiment in outdoor mesocosms. Very low detection limits are reached, allowing environmentally realistic doses (namely, 0.05, 0.5 and 5 μg/L nominal concentrations) to be employed. The results indicate several metabolites and/or transformation products in each compartment investigated, with concentrations sometimes being greater than that of the parent carbamazepine. Biotic degradation of carbamazepine is demonstrated in water, leading to 10,11-dihydrocarbamazepine and 10,11-epoxycarbamazepine. In sediment, the degradation results in the formation of acridine, and 2- and 3-hydroxycarbamazepine. Finally, in both organisms, a moderate bioaccumulation is observed together with a metabolization leading to 10,11-epoxycarbamazepine in fish and 2-hydroxycarbamazepine in mollusc. Acridone is also present in fish. This study provides new and interesting data, helping to elucidate how chronic exposure to carbamazepine at relevant concentrations may affect impact freshwater ecosystems.



http://ift.tt/2rq7YpG

Synthesis, X-ray single crystal structure, likelihood of occurrence of intermolecular contacts, spectroscopic investigation and DFT quantum chemical calculations of zwitterionic complex: 1-Ethylpiperaziniumtrichlorozincate (II)

Publication date: 15 October 2017
Source:Journal of Molecular Structure, Volume 1146
Author(s): S. Soudani, E. Jeanneau, C. Jelsch, F. Lefebvre, C. Ben Nasr
The synthesis and the X-ray structure of the Zn(II) zwitterionic complex:1-ethylpiperaziniumtrichlorozincate (II) are described. In the atomic arrangement, the ZnCl3N entities, grouped in pairs, are deployed along the b-axis to form layers. The organic entities are inserted between these layers through NH⋯Cl and CH⋯Cl hydrogen bonds to form infinite three-dimensional network. The 3D Hirshfeld surfaces were investigated for intermolecular interactions. The optimized geometry, Mulliken charge distribution, molecular electrostatic potential (MEP) maps and thermodynamic properties have been calculated using the Lee-Yang-Parr correlation functional B3LYP with the LanL2DZ basis set. The HOMO and LUMO energy gap and chemical reactivity parameters were made. The 13C and 15N CP-MAS NMR spectra are in agreement with the X-ray crystal structure. The vibrational absorption bands were identified by infrared spectroscopy. DFT calculations allowed the attribution of the NMR peaks and of the IR bands.



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Zinc(II) bis(dipyrromethenate)s crystal solvates with dimethyl sulfoxide Composition, stability and spectral-luminescent properties

Publication date: November 2017
Source:Sensors and Actuators B: Chemical, Volume 251
Author(s): A.A. Ksenofontov, G.B. Guseva, E.V. Antinа, I.A. Khodov, A.I. Vyugin
It was found that 3,3′-, 2,3′ and 2,2′-zinc(II) bis(dipyrromethenate)s ([Zn2L2]) form stable supramolecular complexes of the composition [Zn2L2(DMSO)n] (n=1 or 2) with dimethyl sulfoxide (DMSO). The [Zn2L2(DMSO)n] are stable in the solid phase and solutions. Composition, stability, and spectral-luminescent properties of the [Zn2L2(DMSO)n] crystal solvates were studied by means of FTIR, PXRD, 1H NMR, DOSY, absorption and fluorescence analyses. Spectroscopic studies showed that the quantum yields (φ) of [Zn2L2(DMSO)n] are lower (to ∼1.6–3.6 times) than quantum yields (φо) of [Zn2L2] in cyclohexane. Quantum-chemical study allowed to suggest the most likely mechanism of the DMSO molecules coordination on the coordinating centers of [Zn2L2]. It is demonstrated, that the high-energy coordination interactions (Zn − O) in [Zn2L2(DMSO)n] are the main cause of the fluorescence quenching of [Zn2L2] in the presence of DMSO. Fluorescence quenching of [Zn2L2] in the DMSO presence is based on the photoinduced electron transfer (PeT) mechanism. The obtained results are interesting for the development of new [Zn2L2] fluorescent sensors of the DMSO molecules.

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Simple biosynthesis of zinc oxide nanoparticles using nature's source, and it's in vitro bio-activity

Publication date: 15 October 2017
Source:Journal of Molecular Structure, Volume 1146
Author(s): Elham Zare, Shahram Pourseyedi, Mehrdad Khatami, Esmaeel Darezereshki
Nanoparticles with antimicrobial activity, especially as a new class of biomedical materials for use in increasing the level of public health in daily life have emerged. In this study, green synthesis of zinc oxide) ZnO(nanoparticles was studied by Cuminum cyminum (cumin) as novel natural source and zinc nitrate [Zn(NO3)2] as Zn2+ source. The results showed that parameters such as concentration, time, temperature and pH have a direct impact on the synthesis of zinc nanoparticles and change in any of the factors causing the change in the process of synthesis. The properties of synthesized nanoparticles were examined by UV–visible Spectrophotometer, X-ray diffraction spectroscopy and transmission electron microscopy (TEM). The UV–visible spectroscopy presented the absorption peak in the range of 370 nm. Transmission electron microscopy images of synthesized nanoparticles are mainly spherical or oval with an average size of about 7 nm. The effect of antimicrobial nanoparticles calculated using disk diffusion method and broth MIC and MBC in different strains of bacteria, which showed that gram positive and negative were sensitive to zinc oxide nanoparticles. The sensitivity of gram-negative bacteria was more.

Graphical abstract

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Effects of Multicomponent Training of Cognitive Control on Cognitive Function and Brain Activation in Older Adults

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Publication date: Available online 1 June 2017
Source:Neuroscience Research
Author(s): Hoyoung Kim, Jeanyung Chey, Sanghun Lee
The aim of this study was to investigate the changes in cognitive functions and brain activation after multicomponent training of cognitive control in non-demented older adults, utilizing neuropsychological tests and fMRI. We developed and implemented a computerized Multicomponent Training of Cognitive Control (MTCC), characterized by task variability and adaptive procedures, in order to maximize training effects in cognitive control and transfer to other cognitive domains. Twenty-seven community-dwelling adults, aged 64-77 years, without any history of neurological or psychiatric problems, participated in this study (14 in the training group and 13 in the control group). The MTCC was administered to the participants assigned to the training group for 8 weeks, while those in the control group received no training. Neuropsychological tests and fMRI were administered prior to and after the training. Trained participants showed improvements in cognitive control, recognition memory and general cognitive functioning. Furthermore, the MTCC led to an increased brain activation of the regions adjacent to the baseline cognitive control-related areas in the frontoparietal network. Future studies are necessary to confirm our hypothesis that MTCC improves cognitive functioning of healthy elderly individuals by expanding their frontoparietal network that is involved in cognitive control.



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Zonisamide ameliorates levodopa-induced dyskinesia and reduces expression of striatal genes in Parkinson model rats

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Publication date: Available online 31 May 2017
Source:Neuroscience Research
Author(s): Mitsuaki Oki, Satoshi Kaneko, Satoshi Morise, Norihiro Takenouchi, Takanori Hashizume, Ayako Tsuge, Masataka Nakamura, Reika Wate, Hirofumi Kusaka
To investigate the difference in results according to the mode of levodopa administration and the effect of zonisamide (ZNS), we analyzed the mRNA expression of dopaminergic and non-dopaminergic receptors in the striatum of Parkinson model rats in relation to the development of levodopa-induced dyskinesia (LID). Unilateral Parkinson model rats were subdivided into 4 groups and treated as follows: no medication (group N), continuous levodopa infusion (group C), intermittent levodopa injection (group I), and intermittent levodopa and ZNS injection (group Z). Two weeks after the treatment, LID was observed in group I and Z, but less severe in group Z. The level of both D1 and D2 receptor mRNAs was elevated in groups I and Z, but only D2 receptor mRNA expression was elevated in group C. Adenosine A2A receptor mRNA showed increased expression only in group I. The level of endocannabinoid CB1 receptor mRNA was elevated in groups N, C, and I, but not in group Z. Intermittent injection of levodopa caused LID, in association with elevated expression of D1 and A2A receptors. ZNS ameliorated the development of LID and inhibited up-regulation of A2A and CB1 receptors. Modulation of these receptors may lead to therapeutic approaches for dyskinesia.



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Social memory engram in the hippocampus

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Publication date: Available online 1 June 2017
Source:Neuroscience Research
Author(s): Teruhiro Okuyama
Social memory is one of the crucial components of episodic memories. Gregarious animals living in societies utilize social memory to exhibit the appropriate social behaviors such as aggression, avoidance, cooperative behavior, and even mating behavior. However, the neural mechanisms underlying social memory in the hippocampus remains mysterious. Here, I review some evidence from work done in rodents and primates on the brain region(s) and circuits encoding and/or retrieving social memory, as well as a storage for social memory (i.e. social memory engram neurons). Based on our recent findings that neural ensemble in ventral CA1 sub-region of the hippocampus possesses social memory engram, I would discuss the neural network for social information processing in order to encode social memory; and its evolutionary conservation between rodents and human.



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Scholar : These new articles for Amyloid are available online

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New for Amyloid and online now on Taylor & Francis Online:

Letter to the Editor

Cardiac light-chain deposition disease relapsing in the transplanted heart
Alberto Aimo, Giuseppe Vergaro, Angela Pucci, Sonia Bernazzali, Massimo Maccherini, Gabriele Buda, Claudio Passino, Giampaolo Merlini & Michele Emdin
Pages: 1-3 | DOI: 10.1080/13506129.2017.1334196


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Scholar : These new articles for Acta Orthopaedica are available online

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New for Acta Orthopaedica and online now on Taylor & Francis Online:

Research-article

Preoperative psychosocial risk factors for poor outcomes at 1 and 5 years after total knee replacement
A cohort study of 266 patients
| Open Access
Vikki Wylde, Lea Trela-Larsen, Michael R Whitehouse & Ashley W Blom
Pages: 1-7 | DOI: 10.1080/17453674.2017.1334180


Time trends in pediatric fracture incidence in Sweden during the period 1950–2006 | Open Access
Vasileios Lempesis, Björn E Rosengren, Jan-Åke Nilsson, Lennart Landin, Carl Johan Tiderius & Magnus K Karlsson
Pages: 1-6 | DOI: 10.1080/17453674.2017.1334284


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

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Original Article

High percentage of oral lichen planus and lichenoid lesion in oral squamous cell carcinomas
Hellevi M. A. Ruokonen, Aino Juurikivi, Timo Kauppila, Anna Maria Heikkinen & Riitta Seppänen-Kaijansinkko
Pages: 1-4 | DOI: 10.1080/00016357.2017.1332777


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