Digital Commons Network^™

Female Pacific Walruses (Odobenus Rosmarus Divergens) Show Greater Partitioning Of Sea Ice Organic Carbon Than Males: Evidence From Ice Algae Trophic Markers, Chelsea W. Koch, Lee W. Cooper, Ryan J. Woodland, Jacqueline M. Grebmeier, Karen E. Frey, Raphaela Stimmelmayr, Cédric Magen, Thomas A. Brown

Geography

The expected reduction of ice algae with declining sea ice may prove to be detrimental to the Pacific Arctic ecosystem. Benthic organisms that rely on sea ice organic carbon (iPOC) sustain benthic predators such as the Pacific walrus (Odobenus rosmarus divergens). The ability to track the trophic transfer of iPOC is critical to understanding its value in the food web, but prior methods have lacked the required source specificity. We analyzed the H-Print index, based on biomarkers of ice algae versus phytoplankton contributions to organic carbon in marine predators, in Pacific walrus livers collected in 2012, 2014 and 2016 from …

Gut Microbiota Profiles Of Young South Indian Children: Child Sex-Specific Relations With Growth, Nirupama Shivakumar, Ambily Sivadas, Sarita Devi, Farook Jahoor, John Mclaughlin, Craig P Smith, Anura V Kurpad, Arpita Mukhopadhyay

Children’s Nutrition Research Center Staff Publications

Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18-24 month old Indian children were evaluated (n = 41), in relation to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting. The fecal microbiota was enriched in Prevotella 9, Bifidobacterium and Escherichia-Shigella. Weight, weight-for-age Z-scores (WAZ) and weight-for-length Z-scores (WLZ), along with age, acted as covariates of microbiota variation specifically in boys (n = 23). Bifidobacterium longum subsp longum abundance was positively associated with …

Tph2 In The Dorsal Raphe Nuclei Regulates Energy Balance In A Sex-Dependent Manner, Hailan Liu, Chunmei Wang, Meng Yu, Yongjie Yang, Yang He, Hesong Liu, Chen Liang, Longlong Tu, Nan Zhang, Lina Wang, Julia Wang, Feng Liu, Fang Hu, Yong Xu

Children’s Nutrition Research Center Staff Publications

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female …

Rna-Seq Identifies Genes Whose Proteins Are Upregulated During Syncytia Development In Murine C2c12 Myoblasts And Human Bewo Trophoblasts, Christopher Azar, Mark C Valentine, Julie Trausch-Azar, Lisa Rois, Moe Mahjoub, D Michael Nelson, Alan L Schwartz

Open Access Publications

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression, quantitative protein expression, and siRNA knockdown we identified genes and their cognate proteins which are similarly upregulated in two cellular models of mammalian syncytia development (human BeWo cytotrophoblast to syncytiotrophoblast and murine C2C12 myoblast to myotube). These include DYSF, PDE4DIP, SPIRE2, NDRG1, PLEC, GPR146, HSPB8, DHCR7, and HDAC5. These findings provide avenues for further understanding of the mechanisms underlying mammalian placental syncytiotrophoblast development.

Mr Elastography Demonstrates Reduced White Matter Shear Stiffness In Early-Onset Hydrocephalus, M E Wagshul, J P Mcallister, D D Limbrick Jr, S Yang, W Mowrey, J T Goodrich, A Meiri, D M Morales, A Kobets, R Abbott

Open Access Publications

INTRODUCTION: Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures.

METHODS: MRE was collected at two imaging sites …

Neuronal Activity In Dorsal Anterior Cingulate Cortex During Economic Choices Under Variable Action Costs, Xinying Cai, Camillo Padoa-Schioppa

Open Access Publications

The role of the dorsal anterior cingulate cortex (ACCd) in decision making has often been discussed but remains somewhat unclear. On the one hand, numerous studies implicated this area in decisions driven by effort or action cost. On the other hand, work on economic choices between goods (under fixed action costs) found that neurons in ACCd encoded only post-decision variables. To advance our understanding of the role played by this area in decision making, we trained monkeys to choose between different goods (juice types) offered in variable amounts and with different action costs. Importantly, the task design dissociated computation of …

Information Content Differentiates Enhancers From Silencers In Mouse Photoreceptors, Ryan Z. Friedman, David M. Granas, Connie A. Myers, Joseph C. Corbo, Barak A. Cohen, Michael A. White

Open Access Publications

Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF cone-rod homeobox (CRX) in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both …

Bladder Exposure To Gardnerella Activates Host Pathways Necessary For Escherichia Coli Recurrent Uti, Valerie P O'Brien, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic

Antibiotic-Driven Intestinal Dysbiosis In Pediatric Short Bowel Syndrome Is Associated With Persistently Altered Microbiome Functions And Gut-Derived Bloodstream Infections, Robert Thänert, Anna Thänert, Jocelyn Ou, Adam Bajinting, Carey-Ann D Burnham, Holly J Engelstad, Maria E Tecos, I Malick Ndao, Carla Hall-Moore, Colleen Rouggly-Nickless, Mike A Carl, Deborah C Rubin, Nicholas O Davidson, Phillip I Tarr, Barbara B Warner, Gautam Dantas, Brad W Warner

Open Access Publications

Surgical removal of the intestine, lifesaving in catastrophic gastrointestinal disorders of infancy, can result in a form of intestinal failure known as short bowel syndrome (SBS). Bloodstream infections (BSIs) are a major challenge in pediatric SBS management. BSIs require frequent antibiotic therapy, with ill-defined consequences for the gut microbiome and childhood health. Here, we combine serial stool collection, shotgun metagenomic sequencing, multivariate statistics and genome-resolved strain-tracking in a cohort of 19 patients with surgically-induced SBS to show that antibiotic-driven intestinal dysbiosis in SBS enriches for persistent intestinal colonization with BSI causative pathogens in SBS. Comparing the gut microbiome composition of …

Rubella Virus Infected Macrophages And Neutrophils Define Patterns Of Granulomatous Inflammation In Inborn And Acquired Errors Of Immunity, Ludmila Perelygina, Amy Musiek, Et Al

Open Access Publications

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, …

Prevalence And Correlates Of Sex Selling And Sex Purchasing Among Adults Seeking Treatment For Cocaine Use Disorder, Emma C Lathan, Judy H Hong, Angela M Heads, Nicholas C Borgogna, Joy M Schmitz

Faculty, Staff and Student Publications

Exchange sex places individuals with cocaine use disorder (CUD) at particularly high risk for deleterious safety and health outcomes. A substance use treatment provider who is aware of a patient's exchange sex behavior is better able to provide appropriate screening, care, and/or referral to risk reduction services. However, little is known about exchange sex, especially purchasing, among treatment-seeking adults with CUD. The current study examined the prevalence and correlates of sex selling and sex purchasing among treatment-seeking men and women with CUD (

Mir-9-1 Suppresses Cell Proliferation And Promotes Apoptosis By Targeting Uhrf1 In Lung Cancer, Cheng-You Jia, Wei Xiang, Ji-Bin Liu, Geng-Xi Jiang, Feng Sun, Jian-Jun Wu, Xiao-Li Yang, Rui Xin, Yi Shi, Dan-Dan Zhang, Wen Li, Zavuga Zuberi, Jie Zhang, Gai-Xia Lu, Hui-Min Wang, Pei-Yao Wang, Fei Yu, Zhong-Wei Lv, Yu-Shui Ma, Da Fu

Faculty, Staff and Student Publications

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 …

Risk Factors For Amyotrophic Lateral Sclerosis: A Regional United States Case-Control Study., Angeline S Andrew, Walter G Bradley, Daniel Peipert, Tanya Butt, Kwadwo Amoako, Erik P Pioro, Rup Tandan, John Novak, Adam Quick, K Doug Pugar, Komal Sawlani, Bashar Katirji, Todd A Hayes, Pamela Cazzolli, Jiang Gui, Paul Mehta, D Kevin Horton, Elijah W Stommel

Ambulatory and Primary Care Articles

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. To learn more about sporadic ALS etiology, we recruited n = 188 ALS patients from northern New England and Ohio and matched controls 2:1 from the general population of the same regions. Questionnaires evaluated the association between a variety of lifestyle, behavioral (ie, hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency. Head trauma was associated with increased ALS risk (adjusted …

Women Have A Lower Risk Of Nonalcoholic Fatty Liver Disease But A Higher Risk Of Progression Vs Men: A Systematic Review And Meta-Analysis, Maya Balakrishnan, Parth Patel, Sydney Dunn-Valadez, Cecilia Dao, Vinshi Khan, Hiba Ali, Laith El-Serag, Ruben Hernaez, Amy Sisson, Aaron P Thrift, Yan Liu, Hashem B El-Serag, Fasiha Kanwal

Library Staff Publications

BACKGROUND & AIMS: The risk of nonalcoholic fatty liver disease (NAFLD) and its progression may differ between men and women. We conducted a systematic review and meta-analysis to determine the relationship between sex and NAFLD, nonalcoholic steatohepatitis (NASH), and advanced NAFLD fibrosis.

METHODS: Studies reporting sex-stratified NAFLD prevalence among population-based samples and either NASH or advanced fibrosis among patients with biopsy-proven NAFLD were identified from MEDLINE, EMBASE, and Cochrane databases through December 2017. We calculated pooled relative risk ratios comparing women vs men for each outcome.

RESULTS: Our final analysis comprised 54 studies. Samples sizes were 62,239 for the NAFLD …

Clip And Massively Parallel Functional Analysis Of Celf6 Reveal A Role In Destabilizing Synaptic Gene Mrnas Through Interaction With 3' Utr Elements, Michael A Rieger, Dana M King, Haley Crosby, Yating Liu, Barak A Cohen, Joseph D Dougherty

Open Access Publications

CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. Using a massively parallel reporter assay framework, we test the consequence of CELF6 expression on target sequences, with and without mutating putative binding motifs. Where CELF6 exerts an effect on sequences, it is largely to decrease RNA abundance, which is reversed by mutating UGU-rich motifs. This is also the case for CELF3-5, …

Multiomics Characterization Of Preterm Birth In Low- And Middle-Income Countries., Fyezah Jehan, Sunil Sazawal, Abdullah H. Baqui, Muhammad Imran Nisar, Usha Dhingra, Rasheda Khanam, Muhammad Ilyas, Arup Dutta, Dipak K. Mitra, Usma Mehmood, Saikat Deb, Arif Mahmud, Aneeta Hotwani, Said Mohammed Ali, Sayedur Rahman, Ambreen Nizar, Shaali Makame Ame, Mamun Ibne Moin, Sajid Muhammad, Aishwarya Chauhan, Nazma Begum, Waqasuddin Khan, Sayan Das, Salahuddin Ahmed, Tarik Hasan, Javairia Khalid, Syed Jafar Raza Rizvi, Mohammed Hamad Juma, Nabidul Haque Chowdhury, Furqan Kabir, Fahad Aftab, Abdul Quaiyum, Alexander Manu, Sachiyo Yoshida, Rajiv Bahl, Anisur Rahman, Jesmin Pervin, Jennifer Winston, Patrick Musonda, Jeffrey S. A. Stringer, James A. Litch, Mohammad Sajjad Ghaemi, Mira N. Moufarrej, Kévin Contrepois, Songjie Chen, Ina A. Stelzer, Natalie Stanley, Alan L. Chang, Ghaith Bany Hammad, Ronald J. Wong, Candace Liu, Cecele C. Quaintance, Anthony Culos, Camilo Espinosa, Maria Xenochristou, Martin Becker, Ramin Fallahzadeh, Edward Ganio, Amy S. Tsai, Dyani Gaudilliere, Eileen S. Tsai, Xiaoyuan Han, Kazuo Ando, Martha Tingle, Ivana Maric, Paul H. Wise, Virginia D. Winn, Maurice L. Druzin, Ronald S. Gibbs, Gary L. Darmstadt, Jeffrey C. Murray, Gary M. Shaw, David K. Stevenson, Michael P. Snyder, Stephen R. Quake, Martin S. Angst, Brice Gaudilliere, Nima Aghaeepour

All Dugoni School of Dentistry Faculty Articles

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies.

Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB.

Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in …

Neonatal Mouse Gut Metabolites Influence Cryptosporidium Parvum Infection In Intestinal Epithelial Cells, Kelli L Vandussen, Lisa J Funkhouser-Jones, Marianna E Akey, Deborah A Schaefer, Kevin Ackman, Michael W Riggs, Thaddeus S Stappenbeck, L David Sibley

Open Access Publications

The protozoan parasite

Stem Cell And Niche Regulation In Human Short Bowel Syndrome, Vered A Gazit, Elzbieta A Swietlicki, Miranda U Liang, Adam Surti, Raechel Mcdaniel, Mackenzie Geisman, David M Alvarado, Matthew A Ciorba, Grant Bochicchio, Obeid Ilahi, John Kirby, William J Symons, Nicholas O Davidson, Marc S. Levin, Deborah C Rubin

Open Access Publications

Loss of functional small bowel surface area following surgical resection for disorders such as Crohn's disease, intestinal ischemic injury, radiation enteritis, and in children, necrotizing enterocolitis, atresia, and gastroschisis, may result in short bowel syndrome, with attendant high morbidity, mortality, and health care costs in the United States. Following resection, the remaining small bowel epithelium mounts an adaptive response, resulting in increased crypt cell proliferation, increased villus height, increased crypt depth, and enhanced nutrient and electrolyte absorption. Although these morphologic and functional changes are well described in animal models, the adaptive response in humans is less well understood. Clinically the …

Pomalidomide, Dexamethasone, And Daratumumab In Relapsed Refractory Multiple Myeloma After Lenalidomide Treatment., David S Siegel, Gary J Schiller, Christy Samaras, Michael Sebag, Jesus Berdeja, Siddhartha Ganguly, Jeffrey Matous, Kevin Song, Christopher S Seet, Giampaolo Talamo, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, William E Pierceall, Weiyuan Chung, Faiza Zafar, Amit Agarwal, Nizar J Bahlis

Articles, Abstracts, and Reports

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. …

Aging, But Not Sex And Genetic Diversity, Impacts The Pathobiology Of Bacterial Endophthalmitis, Pawan Kumar Singh, Sukhvinder Singh, Robert Emery Wright, Ramandeep Rattan, Ashok Kumar

Obstetrics, Gynecology and Women's Health Services Articles

Purpose: Age, sex, and genetics are important biological variables in determining an individual's susceptibility or response to infectious agents; however, their role has not been evaluated in intraocular infections. In this study, we comprehensively examined the impact of these host biological factors in the pathogenesis of experimental bacterial endophthalmitis.

Methods: Endophthalmitis was induced by intravitreal injection of bacteria (Staphylococcus aureus) in the eyes of male and female C57BL/6 mice of different ages: group I (young, 6-8 weeks), group II (mid-age, 18-20 weeks), and group III (old, 1 year). Highly heterogeneous outbred J:DO mice were used for genetic diversity analysis. Eyes …

Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring

Open Access Publications

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task …

Stat1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity In Obesity, Aaron R Cox, Natasha Chernis, David A Bader, Pradip K Saha, Peter M Masschelin, Jessica B Felix, Robert Sharp, Zeqin Lian, Vasanta Putluri, Kimal Rajapakshe, Kang Ho Kim, Dennis T Villareal, Reina Armamento-Villareal, Huaizhu Wu, Cristian Coarfa, Nagireddy Putluri, Sean M Hartig

Faculty, Staff and Students Publications

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1a-KO) enhanced mitochondrial function …

Sequence Analysis In Bos Taurus Reveals Pervasiveness Of X-Y Arms Races In Mammalian Lineages, Jennifer F Hughes, Colin Kremitzki, Catrina Fronick, Tina A Graves-Lindsay, Lucinda Fulton, Wesley C Warren, Richard K Wilson, Et Al.

2020-Current year OA Pubs

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X-Y crossing-over unleashed a second dynamic: selfish X-Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of

Differences In Gynecologic Tumor Development In Amhr2-Cre Mice With Krasg12d Or Krasg12v Mutations, Eucharist H S Kun, Yvonne T M Tsang, Sophia Lin, Sophia Pan, Tejas Medapalli, Anais Malpica, Joanne S Richards, David M Gershenson, Kwong-Kwok Wong

Faculty, Staff and Students Publications

How different KRAS variants impact tumor initiation and progression in vivo has not been thoroughly examined. We hypothesize that the ability of either KRASG12D or KRASG12V mutations to initiate tumor formation is context dependent. Amhr2-Cre mice express Cre recombinase in tissues that develop into the fallopian tubes, uterus, and ovaries. We used these mice to conditionally express either the KRASG12V/+ or KRASG12D/+ mutation. Mice with the genotype Amhr2-Cre Pten(fl/fl) KrasG12D/+(G12D mice) had abnormal follicle structures and developed low-grade serous ovarian carcinomas with 100% penetrance within 18 weeks. In contrast, mice with …

A Review Of Volatile Organic Compound Contamination In Post-Industrial Urban Centers: Reproductive Health Implications Using A Detroit Lens, Carol J. Miller, Melissa Runge-Morris, Andrea E. Cassidy-Bushrow, Jennifer K. Straughen, Timothy M. Dittrich, Tracie R. Baker, Michael C. Petriello, Gil Mor, Douglas M. Ruden, Brendan F. O'Leary, Sadaf Teimoori, Chandra M. Tummala, Samantha Heldman, Manisha Agarwal, Katherine Roth, Zhao Yang, Bridget B. Baker

Public Health Sciences Articles

Volatile organic compounds (VOCs) are a group of aromatic or chlorinated organic chemicals commonly found in manufactured products that have high vapor pressure, and thus vaporize readily at room temperature. While airshed VOCs are well studied and have provided insights into public health issues, we suggest that belowground VOCs and the related vapor intrusion process could be equally or even more relevant to public health. The persistence, movement, remediation, and human health implications of subsurface VOCs in urban landscapes remain relatively understudied despite evidence of widespread contamination. This review explores the state of the science of subsurface movement and remediation …

Altered Capicua Expression Drives Regional Purkinje Neuron Vulnerability Through Ion Channel Gene Dysregulation In Spinocerebellar Ataxia Type 1, Ravi Chopra, David D Bushart, John P Cooper, Dhananjay Yellajoshyula, Logan M Morrison, Haoran Huang, Hillary P Handler, Luke J Man, Warunee Dansithong, Daniel R Scoles, Stefan M Pulst, Harry T Orr, Vikram G Shakkottai

2020-Current year OA Pubs

Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 co-repressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, …

Central Nervous System Pathology In Preclinical Mps Iiib Dogs Reveals Progressive Changes In Clinically Relevant Brain Regions, Martin T Egeland, Marta M Tarczyluk-Wells, Melissa M Asmar, Evan G Adintori, Roger Lawrence, Elizabeth M Snella, Jackie K Jens, Brett E Crawford, Jill C M Wait, Emma Mccullagh, Jason Pinkstaff, Jonathan D Cooper, N Matthew Ellinwood

2020-Current year OA Pubs

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B) is an autosomal recessive lysosomal storage disorder caused by the deficiency of alpha-N-acetylglucosaminidase activity, leading to increased levels of nondegraded heparan sulfate (HS). A mouse model has been useful to evaluate novel treatments for MPS IIIB, but has limitations. In this study, we evaluated the naturally occurring canine model of MPS IIIB for the onset and progression of biochemical and neuropathological changes during the preclinical stages (onset approximately 24-30 months of age) of canine MPS IIIB disease. Even by 1 month of age, MPS IIIB dogs had elevated HS levels in brain …

Mitigating Toxic Stress In Children Affected By Conflict And Displacement, Anushka Ataullahjan, Muthanna Samara, Theresa S. Betancourt, Zulfiqar Ahmed Bhutta

Woman and Child Health

Anushka Ataullahjan and colleagues describe the myriad stressors related to conflict and displacement experienced by children and how best to reduce their negative effect

A Praziquantel Treatment Study Of Immune And Transcriptome Profiles In Schistosoma Haematobium-Infected Gabonese Schoolchildren, Lucja A Labuda, Ayola A Adegnika, Bruce A Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D Manurung, Jeannot F Zinsou, Hermelijn H Smits, Peter G Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh

2020-Current year OA Pubs

BACKGROUND: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.

METHODS: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.

RESULTS: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were …

Heterotopic Autotransplantation Of Ovarian Tissue In A Large Animal Model: Effects Of Cooling And Vegf., Samara S Souza, Benner G Alves, Kele A Alves, Fabiana A S Brandão, Danielle C C Brito, Melba O Gastal, Ana P R Rodrigues, José R Figueireod, Dárcio I A Teixeira, Eduardo L Gastal

Peer-reviewed Articles

Heterotopic and orthotopic ovarian tissue autotransplantation techniques, currently used in humans, will become promising alternative methods for fertility preservation in domestic and wild animals. Thus, this study describes for the first time the efficiency of a heterotopic ovarian tissue autotransplantation technique in a large livestock species (i.e., horses) after ovarian fragments were exposed or not to a cooling process (4°C/24 h) and/or VEGF before grafting. Ovarian fragments were collected in vivo via an ultrasound-guided biopsy pick-up method and surgically autografted in a subcutaneous site in both sides of the neck in each mare. The blood flow perfusion at the transplantation …