bluuebunny/crossref_metadata_2025 huggingface dataset:
THE MANIFESTATION OF MULTI-LEVEL STIGMA IN THE LIVED EXPERIENCES OF TRANSGENDER OLDER ADULTS
Authors: Fabbre Vanessa , Gaveras Eleni
Published: November 2019

Transgender and gender nonconforming (TGNC) older adults experience disparities in mental health outcomes when compared to non-TGNC sexual minority older adults. Stigmatizing experiences are thought to influence these outcomes, but little is known about this process. Recent conceptualizations of stigma draw attention to multiple levels – individual, interpersonal, and structural – experienced by TGNC people of all ages. To explore how multi-level stigma manifests in the lives of TGNC older adults, we conducted a two-phase qualitative content analysis of in-depth biographical interviews with 88 TGNC adults aged 50 and older, from across the United States. Data were obtained from the photography and interview project To Survive on This Shore. Our interpretive analyses suggest that TGNC older adults’ development and well-being are impacted by multiple levels of stigma, which are dynamic and unpredictable, resulting in constant awareness of a changing social environment. Individual level stigma is experienced as ongoing vigilance about aspects of oneself that break gender norms, which is also marked by self-imposed social isolation and fears about accessing older adult services. At the interpersonal level, TGNC older adults navigate unpredictable interpersonal relationships, which manifest as fluctuating levels of love, acceptance, strain, and exclusion. Structural stigma manifests in the awareness of stigmatizing policies and systems but also in the conscious action of TGNC older adults to resist these structures. TGNC older adults promote supportive structural responses to stigma to both improve conditions for younger generations while also reducing experiences of individual and interpersonal stigma for themselves.
VARIABILITY IN ACCESS TO VA’S AID AND ATTENDANCE PENSION BENEFIT: A MIXED-METHODS STUDY
Authors: Thomas Kali S , Corneau Emily , Gidmark Stefanie , Rickard Taylor , Allen Susan
Published: November 2019

The Veterans Benefit Administration’s (VBA) Aid and Attendance enhanced pension benefit (A&A) is available to older, low-income Veterans who require assistance meeting their daily needs. However, reports indicate that A&A is underutilized with only 1/3 of eligible Veterans receiving this benefit. The objective of this mixed methods study is to characterize the variability in A&A enrollment across VA Medical Centers (VAMCs) and determine factors attributable to the variation. Using VA administrative data, we calculated the rate of enrollment in A&A among Veterans receiving pension. We then purposefully sampled 16 Chiefs of Social Work at VAMCs with the highest (n=7) and lowest (n=9) rates of enrollment. Interviews were transcribed, coded, and analyzed using conventional qualitative research methods. The rate of enrollment in A&A varies from <1% to 23% across VAMCs. VAMCs that had higher rates of enrollment were larger and more likely to be located in the South and Mid-Atlantic regions. Respondents at sites with low rates of enrollment indicate that education around the eligibility criteria is needed for VAMC staff. They also report that outreach to Veterans about this benefit is limited. Respondents at VAMCs with high rates of enrollment indicate that the relationships with VBA and Veterans Service Organizations facilitates access. Universally, respondents viewed the A&A benefit positively and note that it helps meet Veterans’ long-term care needs. As the Veteran population continues to age, it is important that VA ensure equal access to A&A for eligible Veterans. Implications of these findings and next steps will be discussed.
SENOLYTIC DRUGS: DISCOVERY, TRANSLATION, AND APPLICATION
Authors: LeBrasseur Nathan
Published: November 2019

Diverse forms of molecular and cellular stress trigger senescence, a state of growth arrest in proliferation-competent cells that is often accompanied by a robust secretory phenotype. Senescent cell burden increases with age in multiple tissues and, plausibly, contributes to the pathogenesis of age-related diseases and geriatric syndromes. Discovery science efforts have identified druggable targets in senescent cells, including key nodes in anti-apoptosis pathways, that distinguish them from non-senescent counterparts and enable pharmacological approaches for their selective elimination. The therapeutic potential of senolytic interventions to improve health- and lifespan has been supported by translational research studies, including murine models of aging, atherosclerosis, osteoporosis, neurodegeneration, pulmonary fibrosis, and frailty. These studies have informed the design of first-in-human clinical trials of senolytic drugs, which have recently begun. The objective of this lecture is to highlight both the progress and challenges of advancing interventions targeting senescent cells from bench to bedside.
BIOMARKER STRATEGIES FOR GEROSCIENCE-GUIDED CLINICAL TRIALS
Authors: Justice Jamie N , Kuchel George A , Barzilai Nir , Kritchevsky Stephen
Published: November 2019

Significant progress in the biology of aging and animal models supports the geroscience hypothesis: by targeting biological aging the onset of age-related diseases can be delayed. Geroscience investigators will test this hypothesis in a multicenter clinical trial, to determine if interventions on biological aging processes can prevent accumulation of multiple age-related diseases and aging phenotypes in older adults. Prodigious activity is underway to develop markers of biological aging, but currently there is no aging biomarker consensus to support geroscience-guided clinical trial outcomes. We convened an expert committee to establish a framework for selection of blood-based biomarkers, emphasizing: feasibility/reliability; aging relevance; ability to predict clinical trial outcomes; and responsiveness to intervention. We applied this framework and identified a short-list of blood-based biomarkers with potential use in multicenter trials on aging. We review progress on efforts to test these candidate biomarkers of aging and development of biomarkers strategy for geroscience-guided clinical trials.
MOBILIZING COMMUNITY PARTNERSHIPS TO ENHANCE HEALTH AND REDUCE INEQUITIES IN MULTICULTURAL COMMUNITIES
Authors: Gardner Daniel S , Giunta Nancy
Published: November 2019

Community-based gerontological research plays an indispensable role in identifying and addressing the strengths, intersectionalities, and socio-structural inequities that shape the lives of older adults in multicultural communities around the world. This symposium highlights the innovative, global scholarship of Silberman Aging: A Hartford Center of Excellence in Diverse Aging, as the Center begins its sixth year. Through community-based research and academic-community collaborations, Center researchers examine challenges affecting the health and wellbeing of diverse and often marginalized aging communities in North America, West Africa, and East Asia. The first paper describes and evaluates a CBPR project that trains community-based natural helping networks to identify and refer older adults with dementia in East Harlem, NY. The second study explores the perceptions and strategies of community-based primary care physicians in Ulaanbaatar, Mongolia in dealing with elder abuse and neglect. The third takes a population health approach to the relationship between social capital and health among older adults in Ghana. Fourth, preliminary results from an evaluation of a nation-wide training initiative that promotes cultural-competencies among aging services providers working with LGBT elders. Finally, we present findings from a CBPR study examining barriers to palliative care among racially and ethnically-diverse community-dwelling older adults with serious illness. Although substantively and methodologically varied, these studies all demonstrate the importance of social networks in health in later life, and underscore the value of community-based research that supports collaboration, empowers communities, and ultimately transforms practice and policy to better meet the diverse needs of older adults around the globe.
EXPLORING PALLIATIVE CARE DISPARITIES IN RACIALLY AND ETHNICALLY DIVERSE COMMUNITY-DWELLING OLDER ADULTS
Authors: Gardner Daniel S , Doherty Meredith
Published: November 2019

Despite the growth and recognized benefits of palliative care for people with serious illness and their families, there are significant racial and ethnic disparities in access to and utilization of services, particularly among older adults living in impoverished, medically-underserved communities. This paper presents preliminary findings from a mixed-method, CBPR study exploring the experiences, supportive care needs, and service use of diverse older adults living with serious illness in an urban, medically-underserved community in the U.S. Systematic analyses of focused, semi-structured interviews with 45 older adults identified cultural, environmental, financial, and structural barriers to palliative care, and identified the critical importance of familial, social, spiritual, and formal networks of support in coping with serious illness and associated symptoms. The investigators describe implications for practice and policy that addresses palliative care disparities, and strategies for engaging with communities to extend culturally-sensitive palliative care to diverse, community-dwelling older adults and their social networks.
IT HURTS AS IF: PAIN LANGUAGE, VISUAL CHARACTERIZATION, AND STORY-TELLING IN HMONG OLDER ADULTS
Authors: Lor Maichou , Vang Xia , Rabago David , Brown Roger , Backonja Miroslav
Published: November 2019

Culture and language affect pain reporting, diagnosis, and treatment. Ethnic subgroup populations, such as the Hmong, are understudied in pain research. The study’s purpose is to qualitatively understand older Hmong adults’ pain expression and their pain communication with providers. Sixty-seven participants were recruited from one healthcare system and community. A directed content analysis revealed that all Hmong participants describe pain using stories with reference to the temporal context, causal attribution, co-occurring symptoms or related experiences, magnitude, and consequences of pain. Several participants also characterized their pain by associating it with visual metaphors as objects and animals. Some participants shared that their stories are often underappreciated by providers, and are therefore not understood by providers. This leads to subsequent feelings of stress, not receiving needed medication or other healthcare, and having less frequent contact with providers or switching providers. These findings have implications for more culturally attentive and appropriate pain care.
DO NOT BECOME A BURDEN: ACTIVATION AND DISENGAGEMENT PRESCRIPTIVE AGE STEREOTYPES
Authors: Couto Clara de Paula , Rothermund Klaus
Published: November 2019

Prescriptive age stereotypes encompass activation (active-aging) and disengagement expectations (succession-consumption-identity). We investigated whether activation and disengagement represent opposite stereotypes or whether they exemplify the overarching norm that older adults should not become a burden to other people and society. Based on data of the Ageing-as-Future project (N=743 German participants, 40-90 years old) our findings support the idea that activation and disengagement represent a single superordinate prescriptive age stereotype: (a) items assessing prescriptive age stereotypes form a single factor comprising activation and disengagement, (b) activation and disengagement show an increase in the strength of personal endorsement over the lifespan, demonstrating an internalization of these stereotypes as people become older, and (c) relations to reference variables show that internalized prescriptive stereotypes are more strongly associated with preparation for age-related changes, reflecting an internalization of the norm that one should take individual responsibility for their age rather than enjoying life in old age.
BESIDES ACTIVE AGING? A TRANQUIL LIFE AFTER RETIREMENT
Authors: Liou Shyhnan
Published: November 2019

This research explores how people think of the time plan after their retirement in rural area in Taiwan. fifty-nine participants in rural communities were interviewed. The findings show patterns of a tranquil life after retirement in three aspects which represent the philosophy mixing in Taiwan (Taoism, Buddhism, and Confucianism). 1). Taking things as they are and following the mandate of heaven(Taoism). 2). the retirement life will not be affected by social changes, and feeling that the pace of life in the society has not changed (Buddhism). 3) When talking about “Future aspirations” and “Future ideal life”, they show concern to their children and posterity. (Confucianism). The findings of tranquil life contribute an alternative way of active ageing with considering the culture. The implications of tranquil life are discussed in the design of elderly education program, technology development to enhance social interaction, and culturally motivated ageing and wisdom.
COMMUNITY NETWORKS ADDRESSING AGING WITH LIFELONG DISABILITIES
Authors: Ansello Edward F
Published: November 2019

Adults aging with lifelong developmental disabilities (I/DD: Down syndrome and other intellectual disabilities, cerebral palsy, etc.) continue to pose a challenge to the Aging Network, developmental services, and healthcare systems. Some funded projects, model programs, and episodic initiatives have helped advance intersystem collaboration but there is still scant federal or state public policy specific to aging with lifelong disabilities. The Area Planning and Services Committee (APSC), a product of three consecutive AoA grants on building and testing intersystem cooperation/collaboration between these systems, is a partnership of community based organizations and academe operating in metro Richmond since 2003. Its successful hands on, interdisciplinary management process has implemented needs assessments, statewide training, staff development, dementia awareness, etc., and been a model for the Virginia Geriatric Education Center (VGEC) Plenary overseeing all GWEP programs. The APSC history informs VGEC GWEP’s incorporating I/DD content into faculty development programs, microlearning, ECHO, and other practitioner training.
Organizational politics and complexity: Coase vs. Arrow, March, and Simon
Authors: Marengo Luigi
Published: November 2019

This article argues that the transaction cost approach to the problem of organizing economic activities is undermined by a neglect of the consequences of the complexity of the interconnections among such activities and, in particular, of the complexity generated by conflict and divergent interests of the agents involved. With the increase of conflict, organizational equilibria cease to exist. Thus hierarchy is, in principle, not necessarily an efficiency increasing remedy to the existence of transaction costs but can be explained also as a way to provide temporary equilibria in the everlasting organizational conflict.
Inter-relationships among key reproductive health indicators in sub-Saharan Africa focusing on the central role of maternal literacy
Authors: Woldegiorgis Mulu Abraha , Meyer Denny , Hiller Janet E , Mekonnen Wubegzier , Bhowmik Jahar
Published: November 2019

Background

Indicators of reproductive health (RH) are expected to be both inter-related and associated with key social determinants. As the provision of RH services is usually integrated, the effort to improve one RH component should influence the other components. However, there is a lack of evidence-based models demonstrating the inter-relationships. The purpose of this study was to examine the inter-relationships among key RH indicators and their relationship with women’s literacy in sub-Saharan Africa (SSA).

Methods

Data were sourced from the most recent demographic and health survey conducted between 2010 and 2016 in 391 provinces of 29 SSA countries. We examined seven RH indicators along with women’s literacy. The unit of analysis was at the provincial level. Structural equation modelling was used to examine the strength of relationships among these indicators and with women’s literacy, using the total standardized effect sizes. Significance tests and 95% confidence intervals (CIs) for these effects were calculated using a bias-corrected bootstrap method.

Results

RH indicators are strongly interrelated and are associated with women’s literacy. The strongest relationship is observed between women’s literacy rate and the contraception prevalence rate, with a total standardized effect size of 0.79 (95% CI 0.74–0.83). The model of inter-relationships developed in this study may guide the design, implementation and evaluation of RH policies and programmes.

Conclusions

The key challenge in reducing fertility in SSA is to reduce people fertility desire. This could mainly be addressed by enhancing integrated approaches especially between the education and health sectors.
An uncommon presentation of a sinister entity
Authors: Naidu Krishanth , Gananadha Sivakumar
Published: November 2019

A case of a female patient presenting with clinical findings ominous for a neoplastic bowel obstruction is reported. Abdominal computed tomography demonstrated a bowel obstruction with evidence of intussusception. Laparotomy revealed an irreducible ileoileal intussusception and segments of the jejunum infiltrated with pigmented deposits. There was no perforation and no evidence of an ulcerating or fungating mass. Intestinal melanoma is not an uncommon sequela of cutaneous melanoma, yet the disease can occur as a primary intestinal process, albeit this is a rarity. Surgical resection is the primary treatment modality and may offer the hope of increased symptom-free survival and overall survival for those patients suffering from metastatic or primary melanoma of the small intestine.
A simple model of time-dependent ionization in Type IIP supernova envelopes
Authors: Potashov M , Yudin A
Published: November 2019

We propose a model kinetic system of the hydrogen atom (two levels plus continuum) under the conditions typical for atmospheres of Type IIP supernovae in the plateau stage. Despite the simplicity of this system, it describes realistically the basic properties of the complete system. Analysis shows that the ionization ‘freeze-out’ effect is always manifest at large times. We give a simple criterion for checking the statistical equilibrium of a system under the given conditions at any time. It is shown that if the system is in non-equilibrium at early times, the time-dependent effect of ionization necessarily exists. We also generalize this criterion to the case of arbitrary multilevel systems. We discuss various factors that affect the strength of the time-dependent effect in the kinetics during the photospheric phase of a supernova explosion.
An fMRI study of inhibitory control and the effects of exposure to violence in Latin-American early adolescents: alterations in frontoparietal activation and performance
Authors: Cará Valentina Metsavaht , Esper Nathalia Bianchini , de Azeredo Lucas Araújo , Iochpe Victoria , Dalfovo Nicole Prigol , Santos Rhaná Carolina , Sanvicente-Vieira Breno , Grassi-Oliveira Rodrigo , Franco Alexandre Rosa , Buchweitz Augusto
Published: November 2019

We used functional magnetic resonance to investigate the effects of exposure to violence on early adolescent brain function in an inhibitory control task. We investigated the association among scores on self-reported exposure to violence, performance and brain activation. Thirty-seven early adolescents (ages 10–14) from a Latin-American urban region participated in the study. Results showed that recent and chronic exposure to violence was associated with less activation of a network of frontal regions, including the anterior cingulate gyrus and the superior frontal cortex; recent exposure to violence was also associated with less activation of the superior parietal lobe. Results also showed that less activation correlated with more prominent deterioration in the performance in the inhibitory control task (increased latency with time). The findings suggest that early adolescence exposure to violence is associated with differences in activation of a neural network commonly associated with executive function and control. The results underscore the urgency of addressing exposure to violence in adolescence, a period of high susceptibility to the environment, and are discussed in the light of the evidence of the effects of violence on adolescent brain function. Executive function training may be a candidate for targeted cognitive interventions aimed at mitigating these effects.
Teleost fish can accurately estimate distance travelled
Authors: Karlsson C. , Willis J.K. , Patel M. , de Perera T. Burt
Published: November 2019

Terrestrial animals compute shortcuts through their environment by integrating self-motion vectors containing distance and direction information. The sensory and neural mechanisms underlying this navigational feat have been extensively documented, but their evolutionary origins remain unexplored. Among extant vertebrates, the teleost fish make up one of the most diverse and earliest-branching phylogenetic groups, and provide a powerful system to study the origins of vertebrate spatial processing. However, how freely-swimming teleost fish collect and compute metric spatial information underwater are unknown. Using the Picasso triggerfish,Rhinecanthus aculeatus, we investigate the functional and mechanistic basis of distance estimation in teleost fish for the first time. We show that a fish can learn and remember distance travelled with remarkable accuracy. By analysing swimming trajectories, we form hypotheses about how distance is represented in the teleost brain, and propose that distance may be encoded by dedicated neural structures in a similar way to terrestrial vertebrates. Finally, we begin exploring the sensory mechanisms underlying distance estimation in fish. Many walking animals use a step counter for odometry. By quantifying finbeat use during our distance task, we show that a functionally equivalent finbeat counter is unlikely to provide reliable and precise distance information in an aquatic environment.
Theoretical relation between axon initial segment geometry and excitability
Authors: Goethals Sarah , Brette Romain
Published: November 2019

In most vertebrate neurons, action potentials are triggered at the distal end of the axon initial segment (AIS). Both position and length of the AIS vary across and within neuron types, with activity, development and pathology. What is the impact of AIS geometry on excitability? Direct empirical assessment has proven difficult because of the many potential confounding factors. Here we carried a principled theoretical analysis to answer this question. We provide a simple formula relating AIS geometry and sodium conductance density to the somatic voltage threshold. A distal shift of the AIS normally produces a (modest) increase in excitability, but we explain how this pattern can reverse if a hyperpolarizing current is present at the AIS, due to resistive coupling with the soma. This work provides a theoretical tool to assess the significance of structural AIS plasticity for electrical function.
Intranasal Glyphosate-Based Herbicide Administration Alters the Redox Balance and the Cholinergic System in the Mouse Brain
Authors: Gallegos Cristina Eugenia , Bartos Mariana , Gumilar Fernanda , Raisman-Vozari Rita , Minetti Alejandra , Baier Carlos Javier
Published: November 2019

Pesticide exposure is associated with cognitive and psychomotor disorders. Glyphosate-based herbicides (GlyBH) are among the most used agrochemicals, and inhalation of GlyBH sprays may arise from frequent aerial pulverizations. Previously, we described that intranasal (IN) administration of GlyBH in mice decreases locomotor activity, increases anxiety, and impairs recognition memory. Then, the aim of the present study was to investigate the mechanisms involved in GlyBH neurotoxicity after IN administration. Adult male CF-1 mice were exposed to GlyBH IN administration (equivalent to 50 mg/kg/day of Gly acid, 3 days a week, during 4 weeks). Total thiol content and the activity of the enzymes catalase, acetylcholinesterase and transaminases were evaluated in different brain areas. In addition, markers of the cholinergic and the nigrostriatal pathways, as well as of astrocytes were evaluated by fluorescence microscopy in coronal brain sections. The brain areas chosen for analysis were those seen to be affected in our previous study. GlyBH IN administration impaired the redox balance of the brain and modified the activities of enzymes involved in cholinergic and glutamatergic pathways. Moreover, GlyBH treatment decreased the number of cholinergic neurons in the medial septum as well as the expression of the α7-acetylcholine receptor in the hippocampus. Also, the number of astrocytes increased in the anterior olfactory nucleus of the exposed mice. Taken together, these disturbances may contribute to the neurobehavioural impairments reported previously by us after IN GlyBH administration in mice.
Toxoplasma Cathepsin Protease B and Aspartyl Protease 1 play recessive roles in endolysosomal protein digestion during infection
Authors: McDonald Christian , Smith David , Di Cristina Manlio , Kannan Geetha , Dou Zhicheng , Carruthers Vern B.
Published: November 2019

The lysosome-like vacuolar compartment (VAC) is a major site of proteolysis in the intracellular parasite Toxoplasma gondii. Previous studies have shown that genetic ablation of a VAC-residing cysteine protease, cathepsin protease L (CPL), resulted in accumulation of undigested protein in the VAC and loss of parasite viability during the chronic stage of infection. However, since the maturation of another VAC localizing protease, cathepsin protease B (CPB), is dependent on CPL, it remained unknown whether these defects result directly from ablation of CPL or indirectly from a lack of CPB maturation. Likewise, although a previously described cathepsin D-like aspartyl protease 1 (ASP1) could also play a role in proteolysis, its definitive residence and function in the Toxoplasma endolysosomal system was not well defined. Here we demonstrate that CPB is not necessary for protein turnover in the VAC and that CPB deficient parasites have normal growth and viability in both the acute and chronic stages of infection. We also show that ASP1 depends on CPL for correct maturation and it resides in the T. gondii VAC where, similar to CPB, it plays a dispensable role in protein digestion. Taken together with previous work, our findings suggest that CPL is the dominant protease in a hierarchy of proteolytic enzymes within the VAC. This unusual lack of redundancy for CPL in T. gondii makes it a single exploitable target for disrupting chronic toxoplasmosis.
Transmission network reconstruction for foot-and-mouth disease outbreaks incorporating farm-level covariates
Authors: Firestone Simon M. , Hayama Yoko , Lau Max S. Y. , Yamamoto Takehisa , Nishi Tatsuya , Bradhurst Richard A. , Demirhan Haydar , Stevenson Mark A. , Tsutsui Toshiyuki
Published: November 2019

Transmission network modelling to infer ‘who infected whom’ in infectious disease outbreaks is a highly active area of research. Outbreaks of foot-and-mouth disease have been a key focus of transmission network models that integrate genomic and epidemiological data. The aim of this study was to extend Lau’s systematic Bayesian inference framework to incorporate additional parameters representing predominant species and numbers of animals held on a farm.

Lau’s Bayesian Markov chain Monte Carlo algorithm was reformulated, verified and pseudo-validated on simulated outbreaks populated with demographic data Japan and Australia. The modified model was then implemented on genomic and epidemiological data from the 2010 outbreak of foot-and-mouth disease in Japan, and outputs compared to those from the SCOTTI model implemented in BEAST2.

The modified model achieved improvements in overall accuracy when tested on the simulated outbreaks. When implemented on the actual outbreak data from Japan, infected farms that held predominantly pigs were estimated to have five times the transmissibility of infected cattle farms and be 49% less susceptible. The farm-level incubation period was 1 day shorter than the latent period, the timing of the seeding of the outbreak in Japan was inferred, as were key linkages between clusters and features of farms involved in widespread dissemination of this outbreak. To improve accessibility the modified model has been implemented as the R package ‘BORIS’ for use in future outbreaks.
Extreme phylogenomic diversity in non-pathogenic Xanthomonas strains associated with citrus
Authors: Bansal Kanika , Kumar Sanjeet , Patil Prabhu B
Published: November 2019

Xanthomonas are primarily known as a group of phytopathogens infecting diverse plants. Recent molecular studies reveal existence of novel species and strains of Xanthomonas that follow non-pathogenic (NPX) lifestyle. Presently, we report whole genome sequence of four NPX reported from Citrus sp. (NPXc). Taxonogenomic analysis revealed surprising diversity as each of the three isolates were found to be novel genomospecies that together form a Citri associated non-pathogenic Xanthomonas species complex (NPXc complex). Interestingly, this NPXc complex is related to another non-pathogenic species, X. sontii from rice (NPXr). On the other hand, the fourth NPXc isolate was found to be related to NPX isolates from walnut (NPXw), altogether they form a potential taxonomic outlier of pathogenic X. arboricola species. Interestingly, their pathogenic counterparts, X. citri and X. arboricola are known to cause similar symptoms in diverse fruit plants. Further, genomic investigation of well-characterized pathogenicity clusters in NPXc isolates revealed lifestyle specific gene content dynamics. Majorly, genes essential for virulence (T3SS, effectors, T6SS, biofilm cluster etc.) and adaptation (gum, rpf, iron uptake and utilization, T2SS (xps) and variable repertoire of cell wall degrading enzymes) could be depicted by comparative genomics of Xanthomonas community comprising of diverse lifestyle isolates. Overall, present analysis confers that non-pathogenic isolates of diverse host phylogenomically converge and are evolving in parallel to their pathogenic counterparts. Hence, there is a need to understand the world of NPX isolates from diverse and economically important hosts. Genomic knowledge and resource will be invaluable in both basic and applied research of genus Xanthomonas.
Conjunctive Representations that Integrate Stimuli, Responses, and Rules are Critical for Action Selection
Authors: Kikumoto Atsushi , Mayr Ulrich
Published: November 2019

People can use abstract rules to flexibly configure and select actions for specific situations. Yet how exactly rules shape actions towards specific sensory and/or motor requirements remains unclear. One possibility is that rules become integrated with sensory/response features in a non-linear, conjunctive manner (e.g., event files; Hommel, 1998) to drive rule-guided action selection. To dynamically track such conjunctive representations during action selection, we applied a time-resolved representational similarity analysis to the spectral-temporal profiles of the EEG signal, while participants selected actions based on varying rules. Across two experiments, we found that action selection engages conjunctive representations binding action rules to specific sensory/motor settings throughout the entire selection period. The strength of conjunctions was the most important predictor of trial-by-trial variability in response times (RTs) and was closely, and selectively, related to an important behavioral indicator of event files—the partial-overlap priming pattern. Thus, conjunctive representations were functionally dissociated from their constituent action features and play a critical role during flexible selection of action.
Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder
Authors: Huang Kunling , Wu Yuchang , Shin Junha , Zheng Ye , Siahpirani Alireza Fotuhi , Lin Yupei , Ni Zheng , Chen Jiawen , You Jing , Keles Sunduz , Wang Daifeng , Roy Sushmita , Lu Qiongshi
Published: November 2019

Recent advances in consortium-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in autism spectrum disorder (ASD), but our understanding of their etiologic roles, especially the interplay with rare variants, is incomplete. In this work, we introduce an analytical framework to quantify the transmission disequilibrium of genetically regulated gene expression from parents to offspring. We applied this framework to conduct a transcriptome-wide association study (TWAS) on 7,805 ASD proband-parent trios, and replicated our findings using 35,740 independent samples. We identified 31 associations at the transcriptome-wide significance level. In particular, we identified POU3F2 (p=2.1e-7), a transcription factor (TF) mainly expressed in developmental brain. TF targets regulated by POU3F2 showed a 2.1-fold enrichment for known ASD genes (p=4.6e-5) and a 2.7-fold enrichment for loss-of-function de novo mutations in ASD probands (p=7.1e-5). These results provide a clear example of the connection between ASD genes affected by very rare mutations and an unlinked key regulator affected by common genetic variations.
Conversion of a defensive toxin-antitoxin system into an offensive T6SS effector in Burkholderia
Authors: Yadav Sunil Kumar , Magotra Ankita , Krishnan Aiswarya , Ghosh Srayan , Kumar Rahul , Das Joyati , Jha Gopaljee
Published: November 2019

Bacteria use various kinds of toxins to either inhibit the growth of co-habiting bacteria or when needed control their own growth. Here we report that Burkholderia and certain other bacteria have altered the potential defensive function of Tox-REase-5 domain containing toxins into offensive function. The Burkholderia gladioli strain NGJ1 encodes such toxins as type VI secretion system (T6SS) effectors (Tse) and potentially deploys them to kill co-habiting rice endophytic bacteria. Notably, the immunity (Tsi) proteins associated with Tse effectors demonstrate functional similarity with the antitoxin of type II toxin-antitoxin (TA) system. Genome analysis of diverse bacteria revealed that various Tse orthologs are either encoded as TA or T6SS effectors. In addition, potential evolutionary events associated with conversion of TA into T6SS effectors have been delineated. Our results indicate that the transposition of IS3 elements has led to the operonic fusion of certain T6SS related genes with TA genes resulting in their conversion into T6SS effectors. Such a genetic change has enabled bacteria to utilize novel toxins to precisely target co-habiting bacteria.
Paradoxical role of AT-rich interactive domain 1A in restraining pancreatic carcinogenesis
Authors: Ferri-Borgogno Sammy , Barui Sugata , McGee Amberly , Griffiths Tamara , Singh Pankaj K , Piett Cortt G , Ghosh Bidyut , Bhattacharyya Sanchari , Singhi Aatur , Pradhan Kith , Verma Amit , Nagel Zac , Maitra Anirban , Gupta Sonal
Published: November 2019

Background & Aims

ARID1A is postulated to be a tumor suppressor gene owing to loss-of-function mutations in human pancreatic ductal adenocarcinomas (PDAC). However, its role in pancreatic pathogenesis is not clear despite recent studies using genetically engineered mouse (GEM) models. We aimed at further understanding of its direct functional role in PDAC, using a combination of GEM model, PDAC cell lines.

Methods

Pancreas-specific mutant Arid1a-driven GEM model (Ptf1a-Cre;KrasG12D;Arid1af/f or “KAC”) was generated by crossing Ptf1a-Cre;KrasG12D (“KC”) mice with Arid1af/f mice and characterized histologically with timed necropsies. Arid1a was also deleted using CRISPR-Cas9 system in established PDAC cell lines to study the immediate effects of Arid1a loss in isogenic models. Cells lines with or without Arid1a expression were developed from respective autochthonous PDAC GEM models, compared functionally using various culture assays, and subjected to RNA-sequencing for comparative gene expression analysis. DNA damage repair was analyzed in cultured cells using immunofluorescence and COMET assay.

Results

Arid1a is critical for early progression of mutant Kras-driven pre-malignant lesions into PDAC, as evident by lower Ki-67 and higher apoptosis staining in “KAC” as compared to “KC” mice. Enforced deletion of Arid1a in established PDAC cell lines caused suppression of cellular growth and migration, accompanied by compromised DNA damage repair. Despite early development of relatively indolent cystic precursor lesions called intraductal papillary mucinous neoplasms (IPMNs), a subset of “KAC” mice developed aggressive PDAC in later ages. PDAC cells obtained from older autochthonous “KAC” mice revealed epigenetic changes underlying the various compensatory mechanisms to overcome the growth suppressive effects of Arid1a loss.

Conclusions

Arid1a is an essential survival gene whose loss impairs cellular growth, and thus, its expression is critical during early stages of pancreatic tumorigenesis in mouse models.
Characterisation of protein isoforms encoded by theDrosophilaGlycogen Synthase Kinase 3 geneshaggy
Authors: Korona Dagmara , Nightingale Daniel J. H. , Fabre Bertrand , Nelson Michael , Fischer Bettina , Johnson Glynnis , Lees Jonathan , Hubbard Simon , Lilley Kathryn , Russell Steven
Published: November 2019

TheDrosophila shaggygene (sgg, GSK-3) encodes multiple protein isoforms with serine/threonine kinase activity and is a key player in diverse developmental signalling pathways. Currently it is unclear whether different Sgg proteoforms are similarly involved in signalling or if different proteoforms have distinct functions. We used CRISPR/Cas9 genome engineering to tag eight different Sgg proteoform classes and determined their localization during embryonic development. We performed proteomic analysis of the two major proteoform classes and generated mutant lines for both of these for transcriptomic and phenotypic analysis. We uncovered distinct tissue-specific localization patterns for all of the tagged proteoforms we examined, most of which have not previously been characterised directly at the protein level, including one proteoform initiating with a non-standard codon. Collectively this suggests complex developmentally regulated splicing of thesggprimary transcript. Further, affinity purification followed by mass spectrometric analyses indicate a different repertoire of interacting proteins for the two major proteoform classes we examined, one with ubiquitous expression (Sgg-PB) and one with nervous system specific expression (Sgg-PA). Specific mutation of these proteoforms shows that Sgg-PB performs the well characterised maternal and zygotic segmentations functions of thesgglocus, while Sgg-PA mutants show adult lifespan and locomotor defects consistent with its nervous system localisation. Our findings provide new insights into the role of GSK-3 proteoforms and intriguing links with the GSK-3α and GSK-3β encoded by independent vertebrate genes. Our analysis suggests that different protein isoforms generated by alternative splicing perform distinct functions.
Stochastic analysis of optimal production of infectious progeny in Chlamydia
Authors: Enciso German , Tan Ming , Wan Frederic Y.M.
Published: November 2019

Recent data collected on the Chlamydia Trachomatis life cycle show an initial period of no RB-to-EB conversion. This and other features of the observed bacterial life cycle are postulated to be consequences of the bacteria’s drive for Darwinian survival. Stochastic optimal control models formulated herein in fact lead to an initial conversion holiday that support this proposition.
Exploring High-Dimensional Biological Data with Sparse Contrastive Principal Component Analysis
Authors: Boileau Philippe , Hejazi Nima S. , Dudoit Sandrine
Published: November 2019

Motivation

Statistical analyses of high-throughput sequencing data have re-shaped the biological sciences. In spite of myriad advances, recovering interpretable biological signal from data corrupted by technical noise remains a prevalent open problem. Several classes of procedures, among them classical dimensionality reduction techniques and others incorporating subject-matter knowledge, have provided effective advances; however, no procedure currently satisfies the dual objectives of recovering stable and relevant features simultaneously.

Results

Inspired by recent proposals for making use of control data in the removal of unwanted variation, we propose a variant of principal component analysis, sparse contrastive principal component analysis, that extracts sparse, stable, interpretable, and relevant biological signal. The new methodology is compared to competing dimensionality reduction approaches through a simulation study as well as via analyses of several publicly available protein expression, microarray gene expression, and single-cell transcriptome sequencing datasets.

Availability

A free and open-source software implementation of the methodology, the scPCA R package, is made available via the Bioconductor Project. Code for all analyses presented in the paper is also available via GitHub.
Double-rotator and valve plate distribution radial piston pump
Authors: Dong Peng , Zhao Shengdun , Fan Shuqin , Zhu Muzhi , Zhang Peng
Published: November 2019

Purpose

The drive shaft and the distribution shaft of a traditional radial piston pump are in a cantilever state. To solve this problem, this paper aims to present a radial piston pump with through shaft driving and valve plate distribution.

Design/methodology/approach

The working principle of the pump is discussed in detail. In this radial piston pump, valve plate distribution parts are designed to distribute oil to the piston chambers, and the distribution shaft is replaced. A bearing is installed between the stator and rotator to reduce the friction. The transmission shaft is supported by two bearings to ensure smooth operation. The support force of the transmission shaft is optimized. In addition, the flow pulsation principle is presented. To accomplish the change, the displacement of the radial piston pump, the proportional control system is designed.

Findings

After completing the machining and assembly of the pump, an experimental study was carried out. The results show that the output flow of the pump is basically the same as the theoretical flow.

Originality/value

The friction between the slipping shoes and the stator is greatly reduced due to the function of rolling bearings. The higher stability of the driveshaft is obtained for the reason of double-sided support. The radial piston pump has a novel structural design in reducing the friction between the shoes and the stator and improving the stability of the transmission shaft.
Open innovation: from technology exploitation to creation of superior performance
Authors: Zanjirchi Seyed Mahmoud , Jalilian Negar , Shahmohamadi Mehrjardi Marzieh
Published: November 2019

Purpose

Nowadays, to develop innovative activities in research and development units, it is desirable to rely on the concept of open innovation to take actions towards the identification of external capabilities of an organization and external knowledge acquisition. Therefore, this study aims to evaluate the impact of external technology acquisition (ETA), external technology exploitation (ETE) and culture of innovation (IC) on open innovation (OI) using SEM approach and then examine the amount of the impact of open innovation on organizational performance (OP) and value creation (VC).

Design/methodology/approach

This study was an applied survey in terms of research purpose and data collection method. The statistical population included all companies in Yazd Science and Technology Park (STP). To collect the data, 109 questionnaires were distributed. The content validity of the questionnaire was confirmed by experts’ comments, and Cronbach’s alpha coefficient was calculated equal to 0.873 for reliability.

Findings

The results indicated, ETA, ETE and IC had significant and positive effects on OI, and OI by itself had a significant and positive impact on OP and VC. However, the hypothesis of the significant and positive effect of VC on OP was rejected.

Originality/value

Considering the importance of innovative activities of companies in STPs and the role of OI in achieving the goals of idea-driven companies, the present study evaluated the effects of factors affecting the fulfillment of OI in companies based in STPs in the Yazd province of Iran.
ZeNXL express logistics: route optimization
Authors: Dhaigude Amol S , Ray Soham , Konwar Dhrubojit
Published: November 2019

Learning outcomes

This case has four major learning outcomes using hands-on spreadsheet tool. First is to introduce and apply the Clarke and Wright’s Savings algorithm. Second is to conduct a cost-benefit analysis in transportation set up. Third is to find out the optimal route to be taken to fulfill given demand while satisfying time and capacity constraints. Finally, one has to optimize the number of vehicles required for daily operations.

Case overview/synopsis

Dhruvam, the protagonist of the case, working at ZeNXL, a third-party logistics service provider, was assigned the task of reducing the operational cost of the company as part of the new service offering called “Route optimization.” This new offering would help optimize vehicle delivery routes to meet daily customer demand. The launch of the new service offering was due in the next 10 days with client LG Electronics to be the first beneficiary.

Complexity academic level

MBA-1 (Logistics Management), MBA-2 (Route Optimization). This case provides an opportunity for instructors to introduce vehicle routing and scheduling as part of logistics management. Students are expected to use the data given in the case and exhibits to develop the optimal routes (using Clarke and Wright’s Savings algorithm) and conduct cost-benefit analysis. This case also provides insights on the challenges associated with start-up operations.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 9: Operations and Logistics