bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression-like phenotype by deletion of α7 nicotinic acetylcholine receptor: Role of BDNF-TrkB in nucleus accumbens
Authors: Zhang Ji-chun , Yao Wei , Ren Qian , Yang Chun , Dong Chao , Ma Min , Wu Jin , Hashimoto Kenji 
Published: November 2016

AbstractThe α7 subtype of nicotinic acetylcholine receptor (nAChR) plays a role in the inflammation which is implicated in depression. This study was undertaken to examine the role of α7 nAChR in depression using α7 nAChR knock-out (KO) mice. Serum levels of tumor necrosis factor-α and interlukin-1β in KO mice were higher than wild-type mice, suggesting an inflammatory process in KO mice. α7 nAChR KO mice showed depression-like phenotype. Furthermore, KO mice showed increased brain-derived neurotrophic factor (BDNF) and its receptor TrkB signaling, as well as increased synaptogenesis and spine density in the nucleus accumbens (NAc), although BDNF-TrkB signaling and synaptogenesis were not altered in the prefrontal cortex and hippocampus. Systemic administration of the TrkB antagonist ANA-12, but not the TrkB agonist 7,8-dihydroxyflavone and the selective serotonin reuptake inhibitor fluoxetine, showed a rapid antidepressant effect in KO mice by normalizing increased synaptogenesis in the NAc. In addition, bilateral infusion of ANA-12 into NAc promoted a rapid antidepressant effect in KO mice by normalizing increased synaptogenesis in the NAc. These findings suggest that increased BDNF-TrkB signaling and synaptogenesis in the NAc by deletion of α7 nAChR plays a key role in depression.
Random mutagenesis of the hyperthermophilic archaeon Pyrococcus furiosus using in vitro mariner transposition and natural transformation
Authors: Guschinskaya Natalia , Brunel Romain , Tourte Maxime , Lipscomb Gina L. , Adams Michael W. W. , Oger Philippe , Charpentier Xavier 
Published: November 2016

AbstractTransposition mutagenesis is a powerful tool to identify the function of genes, reveal essential genes and generally to unravel the genetic basis of living organisms. However, transposon-mediated mutagenesis has only been successfully applied to a limited number of archaeal species and has never been reported in Thermococcales. Here, we report random insertion mutagenesis in the hyperthermophilic archaeon Pyrococcus furiosus. The strategy takes advantage of the natural transformability of derivatives of the P. furiosus COM1 strain and of in vitro Mariner-based transposition. A transposon bearing a genetic marker is randomly transposed in vitro in genomic DNA that is then used for natural transformation of P. furiosus. A small-scale transposition reaction routinely generates several hundred and up to two thousands transformants. Southern analysis and sequencing showed that the obtained mutants contain a single and random genomic insertion. Polyploidy has been reported in Thermococcales and P. furiosus is suspected of being polyploid. Yet, about half of the mutants obtained on the first selection are homozygous for the transposon insertion. Two rounds of isolation on selective medium were sufficient to obtain gene conversion in initially heterozygous mutants. This transposition mutagenesis strategy will greatly facilitate functional exploration of the Thermococcales genomes.
Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity
Authors: Cao Jian-Meng , Cheng Xiao-Ning , Li Shang-Qi , Heller Stefan , Xu Zhi-Gang , Shi De-Li 
Published: November 2016

AbstractThe unconventional myosin MYO18A that contains a PDZ domain is required for muscle integrity during zebrafish development. However, the mechanism by which it functions in myofibers is not clear. The presence of a PDZ domain suggests that MYO18A may interact with other partners to perform muscle-specific functions. Here we performed double-hybrid screening and co-immunoprecipitation to identify MYO18A-interacting proteins, and have identified p190RhoGEF and Golgin45 as novel partners for the MYO18A PDZ domain. We have also identified Lurap1, which was previously shown to bind MYO18A. Functional analyses indicate that, similarly as myo18a, knockdown of lurap1, p190RhoGEF and Golgin45 by morpholino oligonucleotides disrupts dystrophin localization at the sarcolemma and produces muscle lesions. Simultaneous knockdown of myo18a with either of these genes severely disrupts myofiber integrity and dystrophin localization, suggesting that they may function similarly to maintain myofiber integrity. We further show that MYO18A and its interaction partners are required for adhesion of myoblasts to extracellular matrix, and for the formation of the Golgi apparatus and organization of F-actin bundles in myoblast cells. These findings suggest that MYO18A has the potential to form a multiprotein complex that links the Golgi apparatus to F-actin, which regulates muscle integrity and function during early development.
Serotonergic modulation of ‘waiting impulsivity’ is mediated by the impulsivity phenotype in humans
Authors: Neufang S , Akhrif A , Herrmann C G , Drepper C , Homola G A , Nowak J , Waider J , Schmitt A G , Lesch K-P , Romanos M 
Published: November 2016

AbstractIn rodents, the five-choice serial reaction time task (5-CSRTT) has been established as a reliable measure of waiting impulsivity being defined as the ability to regulate a response in anticipation of reinforcement. Key brain structures are the nucleus accumbens (NAcc) and prefrontal regions (for example, pre- and infralimbic cortex), which are, together with other transmitters, modulated by serotonin. In this functional magnetic resonance imaging study, we examined 103 healthy males while performing the 5-CSRTT measuring brain activation in humans by means of a paradigm that has been widely applied in rodents. Subjects were genotyped for the tryptophan hydroxylase-2 (TPH2; G-703T; rs4570625) variant, an enzyme specific for brain serotonin synthesis. We addressed neural activation patterns of waiting impulsivity and the interaction between the NAcc and the ventromedial prefrontal cortex (vmPFC) using dynamic causal modeling. Genetic influence was examined via interaction analyses between theTPH2genotype (GG homozygotes vs T allele carriers) and the degree of impulsivity as measured by the 5-CSRTT. We found that the driving input of the vmPFC was reduced in highly impulsive T allele carriers (reflecting a reduced top-down control) in combination with an enhanced response in the NAcc after correct target processing (reflecting an augmented response to monetary reward). Taken together, we found a high overlap of our findings with reports from animal studies in regard to the underlying cognitive processes, the brain regions associated with waiting impulsivity and the neural interplay between the NAcc and vmPFC. Therefore, we conclude that the 5-CSRTT is a promising tool for translational studies.
Neuropathology of mood disorders: do we see the stigmata of inflammation?
Authors: Mechawar N , Savitz J 
Published: November 2016

AbstractA proportion of cases with mood disorders have elevated inflammatory markers in the blood that conceivably may result from stress, infection and/or autoimmunity. However, it is not yet clear whether depression is a neuroinflammatory disease. Multiple histopathological and molecular abnormalities have been found postmortem but the etiology of these abnormalities is unknown. Here, we take an immunological perspective of this literature. Increases in activated microglia or perivascular macrophages in suicide victims have been reported in the parenchyma. In contrast, astrocytic markers generally are downregulated in mood disorders. Impairment of astrocytic function likely compromises the reuptake of glutamate potentially leading to excitotoxicity. Inflammatory cytokines and microglia/macrophage-derived quinolinic acid (QA) downregulate the excitatory amino acid transporters responsible for this reuptake, while QA has the additional effect of inhibiting astroglial glutamine synthetase, which converts glutamate to glutamine. Given that oligodendroglia are particularly vulnerable to inflammation, it is noteworthy that reductions in numbers or density of oligodendrocyte cells are one of the most prominent findings in depression. Structural and/or functional changes to GABAergic interneurons also are salient in postmortem brain samples, and may conceivably be related to early inflammatory insults. Although the postmortem data are consistent with a neuroimmune etiology in a subgroup of depressed individuals, we do not argue that all depression-associated abnormalities are reflective of a neuroinflammatory process or even that all immunological activity in the brain is deleterious. Rather, we highlight the pervasive role of immune signaling pathways in brain function and provide an alternative perspective on the current postmortem literature.
Altered gray matter organization in children and adolescents with ADHD: a structural covariance connectome study
Authors: Griffiths K R , Grieve S M , Kohn M R , Clarke S , Williams L M , Korgaonkar M S 
Published: November 2016

AbstractAlthough multiple studies have reported structural deficits in multiple brain regions in attention-deficit hyperactivity disorder (ADHD), we do not yet know if these deficits reflect a more systematic disruption to the anatomical organization of large-scale brain networks. Here we used a graph theoretical approach to quantify anatomical organization in children and adolescents with ADHD. We generated anatomical networks based on covariance of gray matter volumes from 92 regions across the brain in children and adolescents with ADHD (n=34) and age- and sex-matched healthy controls (n=28). Using graph theory, we computed metrics that characterize both the global organization of anatomical networks (interconnectivity (clustering), integration (path length) and balance of global integration and localized segregation (small-worldness)) and their local nodal measures (participation (degree) and interaction (betweenness) within a network). Relative to Controls, ADHD participants exhibited altered global organization reflected in more clustering or network segregation. Locally, nodal degree and betweenness were increased in the subcortical amygdalae in ADHD, but reduced in cortical nodes in the anterior cingulate, posterior cingulate, mid temporal pole and rolandic operculum. In ADHD, anatomical networks were disrupted and reflected an emphasis on subcortical local connections centered around the amygdala, at the expense of cortical organization. Brains of children and adolescents with ADHD may be anatomically configured to respond impulsively to the automatic significance of stimulus input without having the neural organization to regulate and inhibit these responses. These findings provide a novel addition to our current understanding of the ADHD connectome.
Sex and the shifting biodiversity dynamics of marine animals in deep time
Authors: Bush Andrew M. , Hunt Gene , Bambach Richard K. 
Published: November 2016

Significance
Fertilization mechanisms explain broad patterns in the taxonomic distribution of diversity in marine animals, as argued previously for land plants. We argue that fertilization via copulation (or some other significant interaction among adults) permits additional mechanisms of reproductive isolation and smaller population sizes relative to fertilization via the broadcasting of sperm into the water, thus enhancing diversification potential. Maximum-likelihood modeling of paleontological data indicates that the diversity of sperm broadcasters has been limited by diversity-dependent factors for the last 450 million years. In contrast, animals that copulate, etc., were also limited until the Cretaceous and then radiated dramatically, coincident with apparent major changes in marine productivity. Fertilization may have acted synergistically with ecological specialization in promoting diversification, particularly in predators.
ESA-UbiSite: accurate prediction of human ubiquitination sites by identifying a set of effective negatives
Authors: Wang Jyun-Rong , Huang Wen-Lin , Tsai Ming-Ju , Hsu Kai-Ti , Huang Hui-Ling , Ho Shinn-Ying 
Published: November 2016

Abstract

Motivation
Numerous ubiquitination sites remain undiscovered because of the limitations of mass spectrometry-based methods. Existing prediction methods use randomly selected non-validated sites as non-ubiquitination sites to train ubiquitination site prediction models.

Results
We propose an evolutionary screening algorithm (ESA) to select effective negatives among non-validated sites and an ESA-based prediction method, ESA-UbiSite, to identify human ubiquitination sites. The ESA selects non-validated sites least likely to be ubiquitination sites as training negatives. Moreover, the ESA and ESA-UbiSite use a set of well-selected physicochemical properties together with a support vector machine for accurate prediction. Experimental results show that ESA-UbiSite with effective negatives achieved 0.92 test accuracy and a Matthews’s correlation coefficient of 0.48, better than existing prediction methods. The ESA increased ESA-UbiSite’s test accuracy from 0.75 to 0.92 and can improve other post-translational modification site prediction methods.

Availability and Implementation
An ESA-UbiSite-based web server has been established at http://iclab.life.nctu.edu.tw/iclab_webtools/ESAUbiSite/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Agent-based re-engineering of ErbB signaling: a modeling pipeline for integrative systems biology
Authors: Das Arya A , Ajayakumar Darsana T , Jacob Elizabeth 
Published: November 2016

Abstract

Motivation
Experiments in systems biology are generally supported by a computational model which quantitatively estimates the parameters of the system by finding the best fit to the experiment. Mathematical models have proved to be successful in reverse engineering the system. The data generated is interpreted to understand the dynamics of the underlying phenomena. The question we have sought to answer is that – is it possible to use an agent-based approach to re-engineer a biological process, making use of the available knowledge from experimental and modelling efforts? Can the bottom-up approach benefit from the top-down exercise so as to create an integrated modelling formalism for systems biology? We propose a modelling pipeline that learns from the data given by reverse engineering, and uses it for re-engineering the system, to carry out in-silico experiments.

Results
A mathematical model that quantitatively predicts co-expression of EGFR-HER2 receptors in activation and trafficking has been taken for this study. The pipeline architecture takes cues from the population model that gives the rates of biochemical reactions, to formulate knowledge-based rules for the particle model. Agent-based simulations using these rules, support the existing facts on EGFR-HER2 dynamics. We conclude that, re-engineering models, built using the results of reverse engineering, opens up the possibility of harnessing the power pack of data which now lies scattered in literature. Virtual experiments could then become more realistic when empowered with the findings of empirical cell biology and modelling studies.

Availability and Implementation
Implemented on the Agent Modelling Framework developed in-house. C ++ code templates available in Supplementary material.

Supplementary information
Supplementary data are available at Bioinformatics online.
Invasive Systemic Infection After Hospital Treatment for Diabetic Foot Ulcer: Risk of Occurrence and Effect on Survival
Authors: Chen Shey-Ying , Giurini John M , Karchmer Adolf W 
Published: November 2016

Abstract

Background
Diabetic foot ulcers (DFUs) threaten limbs and prompt hospitalization. After hospitalization, remote-site invasive systemic infection related to DFU (DFU-ISI) may occur. The characteristics of DFU-ISIs and their effect on mortality risk have not been defined.

Methods
We conducted a retrospective cohort study of 819 diabetic patients hospitalized for treatment of 1212 unique DFUs during a 9-year period. We defined the index ulcer as that present at the first (index) DFU admission to our hospital. We defined DFU-ISI as a nonfoot infection that occurred after the index hospitalization and was caused by a microorganism concomitantly or previously cultured from the index ulcer. We determined the frequency, risk factors, and mortality risk associated with DFU-ISIs.

Results
After 1212 index DFU hospitalizations, 141 patients had 172 DFU-ISIs. Of the initial 141 DFU-ISIs, 64% were bacteremia, 13% deep abscesses, 10% pneumonia, 7% endocarditis, and 6% skeletal infections. Methicillin-resistant Staphylococcus aureus (MRSA) caused 57% of the ISIs. Patients with initial DFU cultures yielding MRSA and protracted open ulcers had a high 24-month cumulative probability of DFU-ISI (31%) and all-cause mortality rate (13%). Analysis with Cox regression modeling showed that complicated ulcer healing (hazard ratio, 3.812; 95% confidence interval, 2.434–5.971) and initial DFU culture yielding MRSA (2.030; 1.452–2.838) predicted DFU-ISIs and that DFU-ISIs were associated with increased mortality risk (1.987; 1.106–3.568).

Conclusions
DFU-ISIs are important late complications of DFUs. Prevention of DFU-ISIs should be studied prospectively. Meanwhile, clinicians should aggressively incorporate treatment to accelerate ulcer healing and address MRSA into the care of diabetic patients with foot ulcers.
Microangiopathic Hemolytic Anemia Due to Malignancy in Pregnancy
Authors: Happe Sarah K. , Zofkie Amanda C. , Nelson David B. 
Published: November 2016

BACKGROUND:
Microangiopathic disorders during pregnancy remain a diagnostic challenge because these conditions often imitate more common obstetric diseases.

CASE:
A 31-year-old multigravid woman delivered at term with a postpartum course complicated by laboratory indices consistent with hemolysis, elevated liver enzymes, and low platelet count syndrome. After clinical recovery, she was readmitted 2 weeks after delivery with presumptive pyelonephritis. Persistent hemolysis and worsening thrombocytopenia suggested a diagnosis of thrombotic microangiopathy, which did not respond to plasma exchange. Directed bone biopsy revealed metastatic signet ring cell adenocarcinoma.

CONCLUSION:
Microangiopathic hemolytic anemia is rarely the initial clinical manifestation of malignancy. Given the similar features of several common obstetric complications, additional diagnostic measures may be necessary to refine the diagnosis in cases unresponsive to standard obstetric management.
Hip Dislocation and Dystocia in Early Medieval Times
Authors: Malgosa Assumpció , Carrascal Susana , Piga Giampaolo , Isidro Albert 
Published: November 2016

BACKGROUND:
In ancient times, maternal mortality would occur frequently, particularly during labor. Evidence of dystocia resulting in the death of a pregnant woman is very infrequent in paleopathologic literature, with only a few cases being demonstrated.

CASE:
In the early medieval site of Casserres, the skeleton of a young woman with a fetus in the pelvic region was found. Some abnormal findings of the maternal skeleton were evaluated, including a sacral anomaly, femoral head wound, the rare position of the lower left limb with the femoral head dislodged anteriorly and cephalad from the socket, and a fibular fracture.

CONCLUSION:
Examining the anomalies all together, a case of anterior hip dislocation related to a McRoberts-like maneuver performed during labor is a plausible explanation of the findings.
Social Contributors to Glycemic Control in Gestational Diabetes Mellitus
Authors: Colicchia Laura C. , Parviainen Kristiina , Chang Judy C. 
Published: November 2016

OBJECTIVE:
To evaluate the association of social factors with glycemic control in women with gestational diabetes mellitus (GDM).

METHODS:
A survey instrument assessing social support, access to healthy food, cooking and meal preparation, chaotic lifestyle, employer support, and physical and emotional responses to food was developed and administered to women with GDM at maternal–fetal medicine office visits. Validated scales were used to measure social support and life chaos (defined as organization, instability, and the ability to plan and prepare for the future). Glycemic control and pregnancy outcome were ascertained by chart review. Multivariable logistic regression was used to quantify the association of these factors with the primary outcome of satisfactory glycemic control, defined as greater than 70% of blood sugars within goal.

RESULTS:
We approached 145 women, of whom 111 agreed to participate (76.5%). Seventy-seven percent of patients (86/111) achieved satisfactory glycemic control. Chaotic lifestyle (Confusion, Hubbub and Order Scale score 12.5±2.9 for those with good control, 16.3±3.9 for poor control; odds ratio [OR] 0.71, 95% confidence interval [CI] 0.59–0.85) and receipt of food stamps (11/86 [12.9%] for good control and 10/25 [40%] for poor control; OR 0.22, 95% CI 0.08–0.62) were associated with decreased likelihood of achieving glycemic control. Being married (67/86 [77.9%] for good control and 12/25 [48.0%] for poor control; OR 3.82, 95% CI 1.49–9.74) and regular exercise (49/86 [57.0%] for good control and 5/25 [20.0%] for poor control; OR 5.03, 95% CI 1.72–14.72) increased the likelihood of achieving glycemic control. Transportation time to food stores, home cooking, and social support were not associated with glycemic control or pregnancy outcomes.

CONCLUSION:
Social factors are associated with glycemic control in GDM and may be modifiable to improve glucose control.
Extensor Tendon Injury Associated With Dorsal Entry Flexible Nailing of Radial Shaft Fractures in Children: A Report of 5 New Cases and Review of the Literature
Authors: Murphy Hamadi A. , Jain Viral V. , Parikh Shital N. , Wall Eric J. , Cornwall Roger , Mehlman Charles T. 
Published: November 2016

Background:
Extensor pollicis longus (EPL) tendon injury following the dorsal approach to elastic stable intramedullary nailing (ESIN) of the radius has been reported in a growing number of cases in the literature. This study includes 5 new cases from our institution as well as a comprehensive review of previously reported cases from the literature.

Methods:
We conducted a retrospective chart review of all patients undergoing ESIN between January 1, 2004 and December 31, 2013 at our institution. Those patients with an EPL injury or rupture were identified and clinical data collected included operative technique, diagnosis, treatment, and outcomes data. In addition, we performed a systematic review of the literature using Pubmed MEDLINE database, the Chochrane database, Scopus, Web of Science, and Embase. A total of 28 cases of EPL injury following ESIN of the radius were identified in the literature and the relevant data were extracted from those studies.

Results:
All 33 pediatric cases of EPL tendon injury occurred after entry to the radial canal was obtained by the dorsal approach to ESIN. EPL injury was diagnosed an average of 10 weeks following the index procedure. Extensor indicis pollicis to EPL transfer was performed in 13 patients, tendon release/lysis of adhesions in 5, EPL repair in 2, EPL graft reconstruction from palmaris longus tendon in 1, 3 patients refused further intervention, and treatment was unreported in 7 cases. By 12-month follow-up, all operatively treated patients had a good functional outcome with near anatomic extension at the thumb interphalangeal joint, no pain, and no further complication.

Conclusions:
EPL tendon injury was found to be a complication unique to the dorsal entry approach for ESIN of the radius. The lateral approach appears to offer a safer alternative with regard to the EPL tendon. We suggest that physicians consider the risk of EPL tendon injury when planning for ESIN of the radius, and make an effort to avoid direct injury when using a dorsal approach.

Level of Evidence:
Level III—therapeutic.