bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of PCR-based Tumor Testing in the Evaluation of Lynch Syndrome–associated Endometrial Cancer
Authors: Bruegl Amanda S. , Kernberg Annessa , Broaddus Russell R.
Published: August 2017

Lynch syndrome (LS) is a hereditary cancer syndrome caused by a germline mutation in a DNA mismatch repair gene, usually MLH1, MSH2, MSH6, or PMS2. The most common cancers associated with LS are colorectal adenocarcinoma and endometrial carcinoma. Identification of women with LS-associated endometrial cancer is important, as these women and their affected siblings and children are at-risk of developing these same cancers. Germline testing of all endometrial cancer patients is not cost effective, and screening using young age of cancer diagnosis and/or presence of family history of syndrome-associated is underutilized and ineffective. Therefore, most groups now advocate for tumor tissue testing to screen for LS, with germline testing targeted to women with abnormal tissue testing results. Immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 is used in many clinical laboratories for this tumor screening step, as immunohistochemistry is relatively inexpensive and is technically more accessible for smaller clinical labs. PCR-based tissue testing, whereas technically more challenging, does play an important role in the identification of these patients. MLH1 methylation analysis identifies women with tumor MLH1 loss who likely have sporadic endometrial cancer and do not need heightened cancer prevention surveillance. High levels of microsatellite instability have been identified in tumors with retained positive expression of mismatch repair proteins. Somatic sequencing of mismatch repair genes from tumor DNA, whereas not currently available in most clinical laboratories, is helpful in resolution of cases in which germline sequencing fails to identify a mutation in a mismatch repair gene. The tumor tissue testing approach can help to identify most women at-risk for germline mutations in a LS gene, but not all patients will be captured using this approach. Clinical suspicion can still play a pivotal role in accurately identifying a subset of these patients.
The Surgeon’s Fist with the Thumb Up to Guide the Design and Inset of the Osteoseptocutaneous Fibula Flap in Mandibular Reconstruction
Authors: AL Deek Nidal F. , Tsao Chung-Kan , Wei Fu-Chan
Published: August 2017

Successful reconstruction of an oromandibular defect with the osteoseptocutaneous fibula flap necessitates flawless design and inset, which is an experience-demanding endeavor. Laterality of the fibula flap has been thought to pose a certain challenge to reconstruction. To address this concern and guide flap design and inset, the authors proposed using the surgeon’s fist with the thumb up to replicate key anatomical landmarks of the fibula flap: the peroneal vessels and proximal bone end, and the posterior crural septum including the septal vessels, the skin, and the lateral surface of the fibula bone. This method facilities recipient vessels selection and skin paddle design, orientation, and inset to avoid complications regardless of laterality.
Smaller Diameter Anastomotic Coupling Devices Have Higher Rates of Venous Thrombosis in Microvascular Free Tissue Transfer
Authors: Hanson Summer E. , Mitchell Matthew B. , Palivela Nihanth , Peng S. Andrew , Feng Lei , Largo Rene D. , Butler Charles E. , Garvey Patrick B.
Published: August 2017

Background:

Smaller anastomotic coupling devices may increase the risk of complications in free flap reconstructions; however, the relationship between coupler size and venous thrombosis rates has not been adequately evaluated. The authors hypothesized that smaller diameter coupling devices are associated with higher rates of venous thrombosis than larger diameter devices in free tissue transfer.

Methods:

The authors reviewed a prospectively maintained database for all patients who underwent microsurgical free tissue transfer at their institution from 2001 to 2013. The primary outcome measured was venous thrombosis, and the primary objective was to assess the relationship between venous coupler diameter and the rate of venous thrombosis. The secondary objective was to compare venous thrombosis rates between coupled and hand-sewn venous anastomoses.

Results:

A total of 5643 consecutive free flap reconstructions were evaluated; 3257 (57.7 percent) had coupled venous anastomoses. The 1.5-mm-diameter coupler had an overall thrombosis rate of 6.9 percent, significantly higher than that of all other coupler sizes (p = 0.04). In multivariable regression with generalized estimating equations analysis, both use of a 1.5-mm coupler (OR, 7.75; 95 percent CI, 3.20 to 18.76; p < 0.0001) and preoperative radiation therapy (OR, 1.62; 95 percent CI, 1.04 to 2.52; p = 0.03) were significant independent predictors of venous thrombosis.

Conclusions:

The authors found a significantly higher rate of venous thrombosis with the 1.5-mm-diameter coupler than with larger diameter devices or hand-sewn venous anastomoses. This evidence suggests that surgeons should choose an outflow vessel that does not require a coupler diameter smaller than 2.0 mm or perform a hand-sewn anastomosis in situations where this is not possible.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Upper Extremity Innervation Patterns and Clinical Implications for Nerve and Tendon Transfer
Authors: Lee Ellen Y. , Sebastin Sandeep J. , Cheah Andre , Kumar V. P. , Lim Aymeric Y. T.
Published: August 2017

Background:

The authors previously studied the intramuscular innervation of 150 upper limb muscles and demonstrated that certain patterns of intramuscular innervation allowed muscles to be split into compartments with independent function. This study aims to determine the location, extramuscular course, and number of motor nerve branches of upper limb peripheral nerves. The authors want to combine this information with their previous work to create a blueprint of upper limb neuromuscular anatomy that would be useful in reconstructive surgery.

Methods:

Ten fresh frozen cadaveric upper limbs were dissected. The origin of branches from the peripheral nerve trunk, their course, and the number of motor nerves per muscle were determined. The authors reviewed all the images of the Sihler-stained muscles from their earlier study.

Results:

Motor nerve branches arise at the intersection of nerve trunk and muscle belly and are clustered near the origin of muscle groups. Two patterns of extramuscular innervation were noted, with one group having a single motor nerve and another group with consistently more than one motor nerve. A modified classification of muscles was proposed based on the orientation of muscle fibers to the long axis of the limb, the number of muscle compartments, and the number of heads of origin or the tendons of insertion.

Conclusions:

Motor nerve clusters can be located based on fixed anatomical landmarks. Muscles with multiple motor nerves have morphology that allows them to be split into individual compartments. The authors created a muscle and nerve blueprint that helps in planning nerve and split muscle transfers.
Identifying climate drivers of infectious disease dynamics: recent advances and challenges ahead
Authors: Metcalf C. Jessica E. , Walter Katharine S. , Wesolowski Amy , Buckee Caroline O. , Shevliakova Elena , Tatem Andrew J. , Boos William R. , Weinberger Daniel M. , Pitzer Virginia E.
Published: August 2017

Climate change is likely to profoundly modulate the burden of infectious diseases. However, attributing health impacts to a changing climate requires being able to associate changes in infectious disease incidence with the potentially complex influences of climate. This aim is further complicated by nonlinear feedbacks inherent in the dynamics of many infections, driven by the processes of immunity and transmission. Here, we detail the mechanisms by which climate drivers can shape infectious disease incidence, from direct effects on vector life history to indirect effects on human susceptibility, and detail the scope of variation available with which to probe these mechanisms. We review approaches used to evaluate and quantify associations between climate and infectious disease incidence, discuss the array of data available to tackle this question, and detail remaining challenges in understanding the implications of climate change for infectious disease incidence. We point to areas where synthesis between approaches used in climate science and infectious disease biology provide potential for progress.
Sperm competition games when males invest in paternal care
Authors: Requena Gustavo S. , Alonzo Suzanne H.
Published: August 2017

Sperm competition games investigate how males partition limited resources between pre- and post-copulatory competition. Although extensive research has explored how various aspects of mating systems affect this allocation, male allocation between mating, fertilization and parental effort has not previously been considered. Yet, paternal care can be energetically expensive and males are generally predicted to adjust their parental effort in response to expected paternity. Here, we incorporate parental effort into sperm competition games, particularly exploring how the relationship between paternal care and offspring survival affects sperm competition and the relationship between paternity and paternal care. Our results support existing expectations that (i) fertilization effort should increase with female promiscuity and (ii) paternal care should increase with expected paternity. However, our analyses also reveal that the cost of male care can drive the strength of these patterns. When paternal behaviour is energetically costly, increased allocation to parental effort constrains allocation to fertilization effort. As paternal care becomes less costly, the association between paternity and paternal care weakens and may even be absent. By explicitly considering variation in sperm competition and the cost of male care, our model provides an integrative framework for predicting the interaction between paternal care and patterns of paternity.
OligoMiner: A rapid, flexible environment for the design of genome-scale oligonucleotidein situhybridization probes
Authors: Beliveau Brian J. , Kishi Jocelyn Y. , Nir Guy , Sasaki Hiroshi M. , Saka Sinem K. , Nguyen Son C. , Wu Chao-ting , Yin Peng
Published: August 2017

Oligonucleotide (oligo)-based fluorescence in situ hybridization (FISH) has emerged as an important tool for the study of chromosome organization and gene expression and has been empowered by the commercial availability of highly complex pools of oligos. However, a dedicated bioinformatic design utility has yet to be created specifically for the purpose of identifying optimal oligo FISH probe sequences on the genome-wide scale. Here, we introduce OligoMiner, a rapid and robust computational pipeline for the genome-scale design of oligo FISH probes that affords the scientist exact control over the parameters of each probe. Our streamlined method uses standard bioinformatic file formats, allowing users to seamlessly integrate existing and new utilities into the pipeline as desired, and introduces a novel method for evaluating the specificity of each probe molecule that connects simulated hybridization energetics to rapidly generated sequence alignments using supervised learning. We demonstrate the scalability of our approach by performing genome-scale probe discovery in numerous model organism genomes and showcase the performance of the resulting probes with both diffraction-limited and single-molecule super-resolution imaging of chromosomal and RNA targets. We anticipate this pipeline will make the FISH probe design process much more accessible and will more broadly facilitate the design of pools of hybridization probes for a variety of applications.
Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer Samples into Molecular Subtypes
Authors: Ragulan Chanthirika , Eason Katherine , Fontana Elisa , Nyamundanda Gift , Patil Yatish , Poudel Pawan , Lawlor Rita T. , Rio Maguy Del , Si-Lin Koo , Siew Tan Wah , Sclafani Francesco , Begum Ruwaida , Mendes Larissa S. Teixeira , Martineau Pierre , Scarpa Aldo , Tan Iain Beehuat , Cunningham David , Sadanandam Anguraj
Published: August 2017

Previously, we classified colorectal cancers (CRCs) into five CRCA subtypes with different prognoses and potential treatment responses, using a 786-gene signature. We merged our subtypes and those described by five other groups into four consensus molecular subtypes (CMS) that are similar to CRCA subtypes. Here we demonstrate the analytical development and application of a custom NanoString platform-based biomarker assay to stratify CRC into subtypes. To reduce costs, we switched from the standard protocol to a custom modified protocol (NanoCRCA) with a high Pearson correlation coefficient (>0.88) between protocols. Technical replicates were highly correlated (>0.96). The assay included a reduced robust 38-gene panel from the 786-gene signature that was selected using an in-laboratory developed computational pipeline of class prediction methods. We applied our NanoCRCA assay to untreated CRCs including fresh-frozen and formalin-fixed paraffin-embedded (FFPE) samples (n=81) with matched microarray or RNA-Seq profiles. We further compared the assay results with CMS classification, different platforms (microarrays/RNA-Seq) and gene-set classifiers (38 and 786 genes). NanoCRCA classified fresh-frozen samples (n=39; not including those showing a mixture of subtypes) into all five CRCA subtypes with overall high concordance across platforms (89.7%) and with CMS subtypes (84.6%), independent of tumour cellularity. This analytical validation of the assay shows the association of subtypes with their known molecular, mutational and clinical characteristics. Overall, our modified NanoCRCA assay with further clinical assessment may facilitate prospective validation of CRC subtypes in clinical trials and beyond.

Novelty and Impact

We previously identified five gene expression-based CRC subtypes with prognostic and potential predictive differences using a 786-gene signature and microarray platform. Subtype-driven clinical trials require a validated assay suitable for routine clinical use. This study demonstrates, for the first time, how molecular CRCA subtype can be detected using NanoString Technology-based biomarker assay (NanoCRCA) suitable for clinical validation. NanoCRCA is suitable for analysing FFPE samples, and this assay may facilitate patient stratification within clinical trials.
Co-occurring soil bacteria exhibit a robust competitive hierarchy and lack of non-transitive interactions
Authors: Higgins Logan M. , Friedman Jonathan , Shen Hao , Gore Jeff
Published: August 2017

Microbial communities are typically incredibly diverse, and this diversity is thought to play a key role in community function. However, explaining how this diversity can be maintained is a major challenge in ecology. Temporal fluctuations and spatial structure in the environment likely play a key role, but it has also been suggested that the structure of interactions within the community may act as a stabilizing force for species diversity. In particular, if competitive interactions are non-transitive as in the classic rock-paper-scissors game, they can contribute to the maintenance of species diversity; on the other hand, if they are predominantly hierarchical, any observed diversity must be maintained via other mechanisms. Here, we investigate the network of pairwise competitive interactions in a model community consisting of 20 strains of naturally co-occurring soil bacteria. We find that the interaction network is strongly hierarchical and lacks significant non-transitive motifs, a result that is robust across multiple environments. Moreover, in agreement with recently proposed community assembly rules, the full 20-strain competition resulted in extinction of all but three of the most highly competitive strains, indicating that higher order interactions do not play a major role in structuring this community. The lack of non-transitivity and higher order interactionsin vitroindicates that other factors, such as temporal or spatial heterogeneity, must be at play in enabling these strains to coexist in nature.
Whole Root Transcriptomic Analysis Reveals a Role for Auxin Pathways in Resistance toRalstonia solanacearumin Tomato
Authors: French Elizabeth , Kim Bong Suk , Rivera-Zuluaga Katherine , Iyer-Pascuzzi Anjali S.
Published: August 2017

The soilborne pathogenRalstonia solanacearumis the causal agent of bacterial wilt, and causes significant crop loss in the Solanaceae family. The pathogen first infects roots, which are a critical source of resistance in tomato (Solanum lycopersicumL.). Roots of both resistant and susceptible plants are colonized by the pathogen, yet rootstocks can provide significant levels of resistance. Currently, mechanisms of this ‘root-mediated resistance’ remain largely unknown. To identify the molecular basis of this resistance, we analyzed the genome-wide transcriptional response of roots of resistant (Hawaii 7996) and susceptible (West Virginia700) tomatoes at multiple time points after inoculation withR. solanacearum. We found that defense pathways in roots of the resistant Hawaii7996 are activated earlier and more strongly than roots of susceptible West Virginia700. Further, auxin signaling and transport pathways are suppressed in roots of the resistant variety. Functional analysis of an auxin transport mutant in tomato confirmed a role for auxin pathways in bacterial wilt. Together, our results suggest that roots mediate resistance toR. solanacearumthrough genome-wide transcriptomic changes that result in strong activation of defense genes and alteration of auxin pathways.
MicrobiomeDB: a systems biology platform for integrating, mining and analyzing microbiome experiments
Authors: Oliveira Francislon S. , Brestelli John , Cade Shon , Zheng Jie , Iodice John , Fischer Steve , Aurrecoechea Cristina , Kissinger Jessica C. , Brunk Brian P. , Stoeckert Christian J. , Fernandes Gabriel R. , Roos David S. , Beiting Daniel P.
Published: August 2017

MicrobiomeDB (http://microbiomeDB.org) is a data discovery and analysis platform that empowers researchers to fully leverage experimental variables to interrogate microbiome datasets. MicrobiomeDB was developed in collaboration with the Eukaryotic Pathogens Bioinformatics Resource Center (http://EuPathDB.org) and leverages the infrastructure and user interface of EuPathDB, which allows users to constructin silicoexperiments using an intuitive graphical ‘strategy’ approach. The current release of the database integrates microbial census data with sample details for nearly 14,000 samples originating from human, animal and environmental sources, including over 9,000 samples from healthy human subjects in the Human Microbiome Project (http://portal.ihmpdcc.org/). Query results can be statistically analyzed and graphically visualized via interactive web applications launched directly in the browser, providing insight into microbial community diversity and allowing users to identify taxa associated with any experimental covariate.
An atlas of genetic associations in UK Biobank
Authors: Canela-Xandri Oriol , Rawlik Konrad , Tenesa Albert
Published: August 2017

Genome-wide association studies have revealed many loci contributing to the variation of complex traits, yet the majority of loci that contribute to the heritability of complex traits remain elusive. Large study populations with sufficient statistical power are required to detect the small effect sizes of the yet unidentified genetic variants. However, the analysis of huge cohorts, like UK Biobank, is complicated by incidental structure present when collecting such large cohorts. For instance, UK Biobank comprises 107,162 third degree or closer related participants. Traditionally, GWAS have removed related individuals because they comprised an insignificant proportion of the overall sample size, however, removing related individuals in UK Biobank would entail a substantial loss of power. Furthermore, modelling such structure using linear mixed models is computationally expensive, which requires a computational infrastructure that may not be accessible to all researchers. Here we present an atlas of genetic associations for 118 non-binary and 599 binary traits of 408,455 related and unrelated UK Biobank participants of White-British descent. Results are compiled in a publicly accessible database that allows querying genome-wide association summary results for 623,944 genotyped and HapMap2 imputed SNPs, as well downloading whole GWAS summary statistics for over 30 million imputed SNPs from the Haplotype Reference Consortium panel. Our atlas of associations (GeneATLAS,http://geneatlas.roslin.ed.ac.uk) will help researchers to query UK Biobank results in an easy way without the need to incur in high computational costs.
Large-scale cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets
Authors: Lam Max , Trampush Joey W. , Yu Jin , Knowles Emma , Davies Gail , Liewald David C. , Starr John M. , Djurovic Srdjan , Melle Ingrid , Sundet Kjetil , Christoforou Andrea , Reinvang Ivar , DeRosse Pamela , Lundervold Astri J. , Steen Vidar M. , Espeseth Thomas , Räikkönen Katri , Widen Elisabeth , Palotie Aarno , Eriksson Johan G. , Giegling Ina , Konte Bettina , Roussos Panos , Giakoumaki Stella , Burdick Katherine E. , Payton Antony , Ollier William , Chiba-Falek Ornit , Attix Deborah K. , Need Anna C. , Cirulli Elizabeth T. , Voineskos Aristotle N. , Stefanis Nikos C. , Avramopoulos Dimitrios , Hatzimanolis Alex , Arking Dan E. , Smyrnis Nikolaos , Bilder Robert M. , Freimer Nelson A. , Cannon Tyrone D. , London Edythe , Poldrack Russell A. , Sabb Fred W. , Congdon Eliza , Conley Emily Drabant , Scult Matthew A. , Dickinson Dwight , Straub Richard E. , Donohoe Gary , Morris Derek , Corvin Aiden , Gill Michael , Hariri Ahmad R. , Weinberger Daniel R. , Pendleton Neil , Bitsios Panos , Rujescu Dan , Lahti Jari , Hellard Stephanie Le , Keller Matthew C. , Andreassen Ole A. , Deary Ian J. , Glahn David C. , Malhotra Anil K. , Lencz Todd
Published: August 2017

Neurocognitive ability is a fundamental readout of brain function, and cognitive deficits are a critical component of neuropsychiatric disorders, yet neurocognition is poorly understood at the molecular level. In the present report, we present the largest genome-wide association studies (GWAS) of cognitive ability to date (N=107,207), and further enhance signal by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with cognitive ability, 34 of which were novel. A total of 350 genes were implicated, and this list showed significant enrichment for genes associated with Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis of gene results implicated the biological process of neurogenesis, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker; and LY97241, a potassium channel inhibitor. Transcriptome-wide analysis revealed that the implicated genes were strongly expressed in neurons, but not astrocytes or oligodendrocytes, and were more strongly associated with fetal brain expression than adult brain expression. Several tissue-specific gene expression relationships to cognitive ability were observed (for example, DAG1 levels in the hippocampus). Finally, we report novel genetic correlations between cognitive ability and disparate phenotypes such as maternal age at first birth and number of children, as well as several autoimmune disorders.
Impairment of zebrafish reproduction upon exposure to TDCPP
Authors: Liu Xiecheng , Jia Guofeng
Published: August 2017

TDCPP is one of the most common organophosphate flame retardant, which has been widely used in many products. It has been detected in the environment and biota; however, its potential affect to the wildlife and human health remains largely unknown. In this study, we aimed to investigate the effect of long-term exposure to TDCPP on fish reproduction. Zebrafish eggs were treated with various concentration of TDCPP (0, 1, 10 and 100 μg/L) from 1 day post-fertilization (hpf) to 6 months. The fecundity of female fish was significantly decreased as indicated by reduced embryos production. The egg quality was decreased and the malformation rates were increased in the F1 generation. Taken together, long-term exposure to TDCPP affects the reproduction of zebrafish.
Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort
Authors: Strawbridge Rona J. , Ward Joey , Cullen Breda , Tunbridge Elizabeth M. , Hartz Sarah , Bierut Laura , Horton Amy , Bailey Mark E. S. , Graham Nicholas , Ferguson Amy , Lyall Donald M. , Mackay Daniel , Pidgeon Laura M. , Cavanagh Jonathan , Pell Jill P. , O’Donovan Michael , Escott-Price Valentina , Harrison Paul J. , Smith Daniel J.
Published: August 2017

Risk-taking behaviour is a key component of several psychiatric disorders and could influence lifestyle choices such as smoking, alcohol use and diet. As a phenotype, risk-taking behaviour therefore fits within a Research Domain Criteria (RDoC) approach, whereby identifying genetic determinants of this trait has the potential to improve our understanding across different psychiatric disorders. Here we report a genome wide association study in 116 255 UK Biobank participants who responded yes/no to the question “Would you consider yourself a risk-taker?” Risk-takers (compared to controls) were more likely to be men, smokers and have a history of psychiatric disorder. Genetic loci associated with risk-taking behaviour were identified on chromosomes 3 (rs13084531) and 6 (rs9379971). The effects of both lead SNPs were comparable between men and women. The chromosome 3 locus highlightsCADM2, previously implicated in cognitive and executive functions, but the chromosome 6 locus is challenging to interpret due to the complexity of the HLA region. Risk-taking behaviour shared significant genetic risk with schizophrenia, bipolar disorder, attention deficit hyperactivity disorder and post-traumatic stress disorder, as well as with smoking and total obesity. Despite being based on only a single question, this study furthers our understanding of the biology of risk-taking behaviour, a trait which has a major impact on a range of common physical and mental health disorders.
Positively selected effector genes and their contribution to virulence in the smut fungusSporisorium reilianum
Authors: Schweizer Gabriel , Münch Karin , Mannhaupt Gertrud , Schirawski Jan , Kahmann Regine , Dutheil Julien Y.
Published: August 2017

Plants and fungi display a broad range of interactions in natural and agricultural ecosystems ranging from symbiosis to parasitism. These ecological interactions result in coevolution between genes belonging to different partners. A well-understood example are secreted fungal effector proteins and their host targets, which play an important role in pathogenic interactions. Biotrophic smut fungi (Basidiomycota) are well-suited to investigate the evolution of plant pathogens, because several reference genomes and genetic tools are available for these species. Here, we used the genomes ofSporisorium reilianumf. sp.zeaeandS. reilianumf. sp.reilianum, two closely related formae speciales infecting maize and sorghum, respectively, together with the genomes ofUstilago hordei,Ustilago maydisandSporisorium scitamineumto identify and characterize genes displaying signatures of positive selection. We identified 154 gene families having undergone positive selection during species divergence in at least one lineage, among which 77% were identified in the two investigated formae speciales ofS. reilianum. Remarkably, only 29% of positively selected genes encode predicted secreted proteins. We assessed the contribution to virulence of nine of these candidate effector genes inS. reilianumf. sp.zeaeby deleting individual genes, including a homologue of the effector genepit2previously characterized inU. maydis. Only thepit2deletion mutant was found to be strongly reduced in virulence. Additional experiments are required to understand the molecular mechanisms underlying the selection forces acting on the other candidate effector genes, as well as the large fraction of positively selected genes encoding predicted cytoplasmic proteins.
A variant of the Morris water task for assessing learning and memory processes in mice
Authors: Mehla Jogender , Faraji Jamshid , Saito Takashi , Saido Takaomi C , Mohajerani Majid H. , McDonald Robert J.
Published: August 2017

The Morris water task (MWT) is commonly used to assess rodent spatial learning and memory. Our goal was to develop a 3-phase variant of the hidden goal water task to assess old and new spatial memories acquired in the same context using various measures of spatial learning in C57BL/6 mice. In the first phase, mice were pre-trained to an initially hidden location. The second phase consisted of a massed training session to a new location in the same apparatus and context. The final phase consisted of a competition test between the original and new platform locations.AppNL-G-F/NL-G-Fmice, a novel transgenic mouse model for Alzheimer’s disease (AD), were also used as an independent variable to validate this 3-phase variant of MWT. The results of the present study showed that C57 mice acquired and retained both the old and new location representations; however,AppNL-G-F/NL-G-Fmice retained a recently acquired spatial memory but did not remember the old location acquired in the same apparatus and context. The results showed that C57 mice can show precise place learning and memory with the right amount of training and acquire and retain multiple spatial memory locations in the same environment whereas this ability was impaired inAppNL-G-F/NL-G-Fmice. In the visible platform test, however, all groups of mice showed normal sensorimotor ability and motivation. These findings indicate that this new version of the MWT provides a robust way for assessment of old and new memories in mice. This paradigm could also be exploited to assess manipulations of neural circuits implicated in learning and memory processes as well as for research investigating human brain diseases.
Concept and in-silico assessment of an algorithm for monitoring cytosolic fluorescent aggregates in cells
Authors: Garcés Suárez Yasel , Pérez Koldenkova Vadim , Matsuda Tomoki , Guerrero Adán , Nagai Takeharu
Published: August 2017

Autophagy is an evolutionary conserved pathway, by which eukaryotic cells degrade long-living cellular proteins and intracellular organelles, to maintain a pool of available nutrients. Impaired autophagy has been associated to important pathophysiological conditions, and this is the reason why several techniques have been developed for its correct assessment and monitoring. Fluorescence microscopy is one of these tools, which relies on the detection of specific fluorescence changes of targeted GFP-based reporters in dot-like organelles in which autophagy is executed. Currently, several procedures exist to count and segment this punctate structures in the resulting fluorescence images, however, they are either based on subjective criteria, or no information is available related to them. Here we present the concept of an algorithm for a semi-automatic detection and segmentation in 2D fluorescence images of spot-like structures similar to those observed under induction of autophagy. By evaluating the algorithm on more than 20000 simulated images of cells containing a variable number of punctate structures of different sizes and different levels of applied noise, we demonstrate its high robustness of puncta detection, even on a high noise background. We further demonstrate this feature of our algorithm by testing it in experimental conditions of a high non-specific background signal. We conclude that our algorithm is a suitable tool to be tested in biologically-relevant contexts.
Disruption of the interfacial membrane leads toMagnaporthe oryzaeeffector re-location and lifestyle switch during rice blast disease
Authors: Jones Kiersun , Zhu Jie , Jenkinson Cory B. , Kim Dong Won , Khang Chang Hyun
Published: August 2017

The hemibiotrophic fungusMagnaporthe oryzaeproduces invasive hyphae enclosed in a plant-derived interfacial membrane, known as the extra-invasive hyphal membrane (EIHM), in living rice cells. Little is known about when the EIHM is disrupted and how the disruption contributes to blast disease. Here we show that EIHM disruption correlates with the hyphal growth stage in first-invaded susceptible rice cells. Our approach utilized GFP secreted from invasive hyphae as an EIHM integrity reporter. Secreted-GFP accumulated in the EIHM compartment but appeared in the rice cytoplasm when the EIHM integrity was compromised. Live-cell imaging of secreted-GFP and various fluorescent reporters revealed that EIHM disruption led to rice vacuole rupture and cell death limited to the invaded cell with closed plasmodesmata. We report that EIHM disruption and host cell death are landmarks delineating three distinct infection phases (early biotrophic, late biotrophic, and transient necrotrophic phases) within the first-invaded cell before reestablishment of biotrophy in second-invaded cells.M. oryzaeeffectors exhibited phase-specific localizations, including entry of the apoplastic effector Bas4 into the rice cytoplasm during the late biotrophic phase. Understanding how the phase-specific dynamics are regulated and linked to host susceptibility will offer potential targets that can be exploited to control blast disease.
Reward sensitivity following boredom and cognitive effort: A high-powered neurophysiological investigation
Authors: Milyavskaya Marina , Inzlicht Michael , Johnson Travis , Larson Michael
Published: August 2017

What do people feel like doing after they have exerted cognitive effort or are bored? Here, we empirically test whether people are drawn to rewards (at the neural level) following cognitive effort and when bored. This elucidates the experiences and consequences of engaging in cognitive effort, and compares it to the consequences of experiencing boredom, an affective state with predicted similar motivational consequences. Event-related potentials were recorded after participants (N=243) were randomized into one of three conditions – boredom (observing strings of numbers), cognitive effort (adding 3 to each digit of a four-digit number), or control. In the subsequent task, we focused on the feedback negativity (FN) to assess the brain’s immediate response to the presence or absence of reward. Phenomenologically, participants in the boredom condition reported more fatigue than those in the cognitive effort condition. Results suggest participants in the boredom condition exhibited larger FN amplitude than participants in the control condition, while the cognitive effort condition was neither different from boredom nor control. The neural and methodological implications for ego depletion research, including issues of replicability, are discussed.
Persistent effects of acute stress on fear and drug-seeking in a novel model of the comorbidity between post-traumatic stress disorder and addiction
Authors: Pizzimenti Christie L. , Navis Tom M. , Lattal K. Matthew
Published: August 2017

Even following long periods of abstinence, individuals with anxiety disorders have high rates of relapse to drugs of abuse. Although many current models of relapse demonstrate effects of acute stress on drug-seeking, most of these studies examine stressful experiences that occur in close temporal and physical proximity to the reinstatement test. Here, we assess the effects of a stressful experience in one context on fear and drug-seeking in a different context. We adapt the stress-enhanced fear learning procedure to examine impacts on drug-seeking long after the stressful experience occurred. We find massive footshock in a distinct environment produced an acute increase in corticosterone, long-term hyper-responsivity to a single shock in different contexts with extensive histories of drug-seeking behaviors, enhancements in cocaine-induced conditioned place preference in mice, and persistent enhancements in cue-induced reinstatement of methamphetamine-seeking behavior in rats. Together, these experiments demonstrate that an acute trauma causes persistent changes in responsivity to mild stressors and drug-seeking behavior in other contexts, which mirrors aspects of the comorbidity between post-traumatic stress disorder and substance use disorders. These behavioral approaches provide novel procedures for investigating basic mechanisms underlying this comorbidity and they provide powerful tools for testing preclinical pharmacological and behavioral interventions.
Developmental pathway genes and neural plasticity underlying emotional learning and stress-related disorders
Authors: Maheu Marissa E. , Ressler Kerry J.
Published: August 2017

The manipulation of neural plasticity as a means of intervening in the onset and progression of stress-related disorders retains its appeal for many researchers, despite our limited success in translating such interventions from the laboratory to the clinic. Given the challenges of identifying individual genetic variants that confer increased risk for illnesses like depression and post-traumatic stress disorder, some have turned their attention instead to focusing on so-called “master regulators” of plasticity that may provide a means of controlling these potentially impaired processes in psychiatric illnesses. The mammalian homolog ofTailless(TLX), Wnt, and the homeoprotein Otx2 have all been proposed to constitute master regulators of different forms of plasticity which have, in turn, each been implicated in learning and stress-related disorders. In the present review, we provide an overview of the changing distribution of these genes and their roles both during development and in the adult brain. We further discuss how their distinct expression profiles provide clues as to their function, and may inform their suitability as candidate drug targets in the treatment of psychiatric disorders.
Characterization of the amplificatory effect of norepinephrine in the acquisition of Pavlovian threat associations
Authors: Díaz-Mataix Lorenzo , Piper Walter T. , Schiff Hillary C. , Roberts Clark H. , Campese Vincent D. , Sears Robert M. , LeDoux Joseph E.
Published: August 2017

The creation of auditory threat Pavlovian memory requires an initial learning stage in which a neutral conditioned stimulus (CS), such as a tone, is paired with an aversive one (US), such as a shock. In this phase, the CS acquires the capacity of predicting the occurrence of the US and therefore elicits conditioned defense responses. Norepinephrine (NE), through β-adrenergic receptors in the amygdala, enhances threat memory by facilitating the acquisition of the CS–US association, but the nature of this effect has not been described. Here we show that NE release, induced by the footshock of the first conditioning trial, promotes the subsequent enhancement of learning. Consequently, blocking NE transmission disrupts multitrial but not one-trial conditioning. We further found that increasing the time between the conditioning trials eliminates the amplificatory effect of NE. Similarly, an unsignaled footshock delivered in a separate context immediately before conditioning can enhance learning. These results help define the conditions under which NE should and should not be expected to alter threat processing and fill an important gap in the understanding of the neural processes relevant to the pathophysiology of stress and anxiety disorders.
Neurobiological correlates of state-dependent context fear
Authors: Meyer Mariah A.A. , Corcoran Kevin A. , Chen Helen J. , Gallego Sonia , Li Guanguan , Tiruveedhula Veda V. , Cook James M. , Radulovic Jelena
Published: August 2017

Retrieval of fear memories can be state-dependent, meaning that they are best retrieved if the brain states at encoding and retrieval are similar. Such states can be induced by activating extrasynaptic γ-aminobutyric acid type A receptors (GABAAR) with the broad α-subunit activator gaboxadol. However, the circuit mechanisms and specific subunits underlying gaboxadol's effects are not well understood. Here we show that gaboxadol induces profound changes of local and network oscillatory activity, indicative of discoordinated hippocampal–cortical activity, that were accompanied by robust and long-lasting state-dependent conditioned fear. Episodic memories typically are hippocampus-dependent for a limited period after learning, but become cortex-dependent with the passage of time. In contrast, state-dependent memories continued to rely on hippocampal GABAergic mechanisms for memory retrieval. Pharmacological approaches with α-subunit-specific agonists targeting the hippocampus implicated the prototypic extrasynaptic subunits (α4) as the mediator of state-dependent conditioned fear. Together, our findings suggest that continued dependence on hippocampal rather than cortical mechanisms could be an important feature of state-dependent memories that contributes to their conditional retrieval.
In operando quantitation of Li concentration for a commercial Li-ion rechargeable battery using high-energy X-ray Compton scattering
Authors: Suzuki Kosuke , Suzuki Ayahito , Ishikawa Taiki , Itou Masayoshi , Yamashige Hisao , Orikasa Yuki , Uchimoto Yoshiharu , Sakurai Yoshiharu , Sakurai Hiroshi
Published: August 2017

Compton scattering is one of the most promising probes for quantitating Li under in operando conditions, since high-energy X-rays, which have high penetration power, are used as the incident beam and the Compton-scattered energy spectrum has specific line-shapes for each element. An in operando quantitation method to determine the Li composition in electrodes has been developed by using line-shape (S-parameter) analysis of the Compton-scattered energy spectrum. In this study, S-parameter analysis has been applied to a commercial coin cell Li-ion rechargeable battery and the variation of the S-parameters during the charge/discharge cycle at the positive and negative electrodes has been obtained. By using calibration curves for Li composition in the electrodes, the change in Li composition of the positive and negative electrodes has been determined using the S-parameters simultaneously.
Diffusion of innovation among Malaysian manufacturing SMEs
Authors: Mamun Abdullah Al
Published: August 2017

Purpose

The purpose of this paper is to examine the attributes of innovation adoption and its effects on the performance of Malaysian manufacturing SMEs.

Design/methodology/approach

Quantitative data were collected from 360 randomly selected manufacturing SMEs through structured interviews.

Findings

The findings of the study confirmed that, in Malaysian manufacturing SMEs, the degree of persuasion (i.e. relative advantages, compatibility, complexity, trialability and observability), strategic orientation (i.e. consumer, market and entrepreneurship) and firm antecedents (i.e. prior condition, knowledge and risk orientation) have significant effects on the innovation (i.e. product, process and service) adoption and performance of SMEs.

Practical implications

For policymakers, this study emphasizes the areas to focus on the development of an effective innovation ecosystem for an innovation-led economy. Because SMEs operate with limited resources and capacity, the programs and policies for innovation support systems must focus on providing new innovation information, cost-benefit analyses for new innovation adoption, innovation adoption processes and how new innovations affect performance.

Originality/value

The paper examines an important, but under-researched issue – designed and tested a model under the premises of the DOI and organizational diffusion of innovation theories which improve the knowledge and understanding about the innovation adoption by manufacturing SMEs.
Entrepreneurial intentions of young women in the Arab world
Authors: Mehtap Salime , Pellegrini Massimiliano M. , Caputo Andrea , Welsh Dianne H.B.
Published: August 2017

Purpose

Female entrepreneurship is a growing segment in the context of developing countries and has the potential to become a driving force for economic development. However, research suggests that females are less inclined toward entrepreneurship when compared to their male counterparts. This fact is related to a complex mix of causes such as the belief that entrepreneurship is a male domain, certain conditions within the economic and social environment and a general lack of confidence with regards to succeeding in such activities. Barriers to female entrepreneurship are prevalent in the patriarchal Arab world. The purpose of this paper is to measure the perceptions of female Jordanian business students with regards to the socio-cultural barriers to entrepreneurship. It also looks at the conduciveness of the education they are receiving in terms of new venture creation.

Design/methodology/approach

A sample of 254 female business students from two universities in Jordan was asked to evaluate various factors within the entrepreneurial ecosystem, including the business education they are currently receiving. A factor analysis has been performed to show which relevant elements may prevent young women from engaging with entrepreneurial activities. A comparison of perceptions about the educational system has also been presented to understand how a supportive educational environment may affect the previous analysis.

Findings

The results indicated that a strong supportive education system to some extent may reduce the perception of potential barriers for entrepreneurship but the overall impact can be limited. Conversely, an educational system lacking a supportive environment and concrete initiatives can deeply affect and worsen the fears of engaging in entrepreneurship amongst female students.

Originality/value

The role of women in the Arab world is quite marked and the reluctance of women to take a more decisive engagement in entrepreneurship may be reinforced by conservative, societal traditions. A supportive education system has the potential to act as a catalyst to encourage active female participation in the entrepreneurial domain, thus helping to spur economic development in the region.