Medicine and Health Sciences Commons^™

Tgf-Β Drives The Conversion Of Conventional Nk Cells Into Uterine Tissue-Resident Nk Cells To Support Murine Pregnancy, Josselyn D Barahona, Liping Yang, D Michael Nelson, Wayne M Yokoyama

2020-Current year OA Pubs

Tissue microenvironments shape lymphocyte differentiation to align immune function with local physiological demands. Uterine natural killer (NK) cells are critical for reproductive success, yet the molecular cues in the uterus that instruct their specialized identities remain incompletely understood. Here, we identify a TGF-β-dependent differentiation pathway by which circulating conventional NK cells convert into uterine tissue-resident NK cells during murine pregnancy. Loss of TGF-β receptor II expression in

Trends In Lung Cancer Survival: Superior Outcomes In Us Veterans Compared With The General Population, Nikki E Rossetti, Brendan T Heiden, Steven Tohmasi, Nahom Seyoum, Theodore Thomas, Whitney S Brandt, Sara Malone, Yan Yan, Ana Baumann, Su-Hsin Chang, Daniel Kreisel, Ruben Nava, Bryan Meyers, Benjamin Kozower, Varun Puri, Et Al.

2020-Current year OA Pubs

BACKGROUND: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality in the United States, but survival outcomes are shifting with evolving therapies and screening. Recent findings suggest that survival improvements vary across health-care systems, with favorable trends observed in the Veterans Health Administration (VHA). We sought to compare NSCLC survival trends across US health systems.

METHODS: We conducted a retrospective cohort study of patients with NSCLC (2007-2019) using data from the VHA and the National Cancer Database (NCDB), representing the non-VHA US general population. The primary exposure was health system (VHA vs non-VHA), and the primary outcome …

Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks

2020-Current year OA Pubs

The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high

Long-Term Inactivation Mediated By Different Fgf-A Homologues On Heterologously Expressed Nav1.2 Currents, Yenisleidy Lorenzo-Ceballos, Pedro L Martinez-Espinosa, Xiao-Ming Xia, Christopher J Lingle

2020-Current year OA Pubs

A-isoforms of cytosolic growth factor homologous factors (FGF11-14) mediate long-term inactivation (LTI) of voltage-dependent sodium (NaV) channels. LTI is a rapid onset process that is competitive with the fast inactivation (IF) intrinsic to NaV channels, with little or no interconversion between inactivated states. Since recovery from LTI is orders of magnitude slower than recovery from IF, repetitive depolarizations lead to use-dependent accumulation of NaV channels in slow recovery states, thereby limiting NaV availability during trains of action potentials. Of the two or more N-terminal splice variants of the various FGF homologues, LTI specifically arises only from the A-isoform of each …

Subunit Composition Of The Katp Channels That Modulate Contractility Of Skeletal Muscle During Fatigue, Rosa Scala, Yuezhou Chen, Berk Mizrak, Gretchen A Meyer, Colin G Nichols

2020-Current year OA Pubs

ATP-sensitive potassium (KATP) channels are among the most expressed ion channels in skeletal muscle sarcolemma. While all KATP subunits can be detected in skeletal muscles, transcripts are enriched for KCNJ11 and ABCC9, suggesting that noncanonical Kir6.2/SUR2A assembly may constitute the majority of sarcolemmal KATP channels, but there has been no systematic dissection of KATP makeup in skeletal muscles. Here, we used a unique collection of murine lines selectively lacking specific channel-forming subunits (knockout, KO), and combined a genetic and pharmacological approach to determine which subunits of KATP channels are functionally relevant for skeletal muscle contraction. Under fatiguing conditions, isometric tetanic …

A Conserved Mechanism For Dimerization And Activation Of Superfamily 1a Uvrd-Family Helicases, Binh Nguyen, Kacey N Mersch, Ankita Chadda, Eric A Galburt, Timothy M Lohman

2020-Current year OA Pubs

DNA helicases are ATP-dependent motor proteins that catalyze duplex DNA unwinding and are involved in DNA repair, recombination, and replication restart. Prominent members of the non-hexameric SF1A UvrD-family helicases are Escherichia coli UvrD, Rep, Bacillus stearothermophilus PcrA, and Mycobacterium tuberculosis (Mtb) UvrD1. SF1A monomers are processive 3'-to-5' single-stranded DNA translocases but need to be activated to become DNA helicases. One mechanism of activation is dimerization. Whereas Rep, UvrD, and PcrA form non-covalent dimers, the Mtb UvrD1 helicase forms a redox-dependent covalent dimer. Dimerization of Mtb UvrD1 occurs between the same regulatory domain (2B) within each subunit stabilized by a disulfide …

Improving Infant Health Equity: What Have We Learned, What Do We Do, Dewayne M Pursley, F Sessions Cole

2020-Current year OA Pubs

The United States neonatal and infant mortality rates have declined substantially over the last six decades. Despite these reductions, significant racial disparities in mortality and other important outcomes have persisted. While increased risk of preterm birth is a major contributor to these differences, racial inequities in risk-adjusted outcomes such as gestational age-specific and major congenital anomaly-associated mortality remain. Race-specific differences in inter- and intra-neonatal intensive care unit (NICU) practices associated with worse outcomes for infants of color suggest opportunities for reducing these disparate health outcomes during and after NICU hospitalization. Identifying NICU-based contributing factors and implementing factor-specific improvement strategies can …

Cardiorespiratory Signatures Of Necrotizing Enterocolitis: A 4-Nicu Study Of Very Low Birth Weight Infants, Sherry L Kausch, Zachary A Vesoulis, Colm P Travers, Carie Taveras, Rachel Benz, Amanda Duncan, Angela K S Gummadi, Katy N Krahn, Rakesh Sahni, Joseph Isler, Namasivayam Ambalavanan, J Randall Moorman, Douglas E Lake, Karen D Fairchild, Brynne A Sullivan

2020-Current year OA Pubs

BACKGROUND: Necrotizing enterocolitis (NEC) is a disorder in very low birth weight (VLBW, < 1500 g) infants, associated with significant morbidity and mortality. Earlier detection of NEC may improve outcomes. We hypothesized that NEC's physiological signature resembles that of sepsis and that our model developed for sepsis, the Pulse Oximetry Warning System (POWS), would also predict NEC.

OBJECTIVES: Assess relationships between continuous heart rate (HR) and oxygen saturation (SpO

METHODS: In a retrospective multicenter analysis, we studied VLBW infants at four level IV NICUs, identifying cases of late-onset sepsis (LOS) and NEC (Bell stages 2 or 3). Using HR and SpO

RESULTS: Among 3914 infants evaluated, 5% had NEC and 13% had LOS. Cardiorespiratory data analysis showed that HR/SpO

CONCLUSION: NEC shares a cardiorespiratory signature with LOS. POWS predicted NEC with a dynamic rise before clinical diagnosis.

IMPACT: A cardiorespiratory early warning score analyzing …

Beyond Lactate: Real-Time Resuscitation Targets For Septic Shock During Critical Care Transport, James L Li, Aaron J Lacy, Michael J Defilippo

2020-Current year OA Pubs

No abstract provided.

A Call To Investigate The Association Between Histoplasmosis And Fatigue, Christian Hendrix, Julio Zuniga-Moya, Andrej Spec, Patrick Mazi

2020-Current year OA Pubs

Historically, infections are subjectively associated with fatigue, a common yet poorly delineated syndrome. The impact on patient quality of life is the ultimate justification to evaluate fatigue in patients with infections. While fungal infections are subjectively associated with fatigue, there are minimal quantifiable fungal research outcomes that evaluate histoplasmosis and fatigue.

Evaluation Of The Impact Of A Pathology Trainee-Driven Manual Review Process For Reference Testing At A Large Academic Center, Carly Maucione, Christopher W Farnsworth, Mark A Zaydman

2020-Current year OA Pubs

BACKGROUND: Increasing reliance on and complexity of laboratory testing necessitates laboratory stewardship initiatives to ensure appropriate test ordering, especially as reference testing costs continue to rise. Prospective manual review processes, although demanding of resources, have been shown to be cost-effective, but literature addressing the value of such a process is lacking.

METHODS: The pathology trainee-driven manual review process of 444 chemistry and microbiology tests on approval at a large academic center was reviewed. Data were extracted from an internal-use call-log and analyzed for test volumes, cancellation rates, and cost savings. A hypergeometric distribution was used to model random variation in …

Modern Molecular Profiling Recontextualizes The Nrg/Rtog 0539 Trial And Reveals Hidden High-Risk And Radiotherapy-Resistant Meningiomas, Leeor S Yefet, Clifford Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Meningiomas exhibit clinical heterogeneity. Radiotherapy (RT) remains the only adjuvant therapy, but tumor-control is variable, and biomarkers are limited. NRG/RTOG-0539 is the first prospective phase 2 trial to stratify meningioma patients for adjuvant RT based on clinical risk. Here, we apply modern molecular tools to this cohort and identify correlates of RT response.

METHODS: Tumor tissue from 100 RTOG-0539 patients was profiled using DNA methylation arrays, RNA sequencing, and whole-exome sequencing. Recurrence scores, Molecular Groups, gene expression, and copy number alterations were compared across clinical groups and between RT responders and non-responders; non-response was defined as progression or death …

Enhancing Validation Of Case-Control Omics Signatures Through "Minimalist" Single-Subject Analysis (N-Of-1 Trials): Proof Of Concept In Sepsis, Liam S Wilson, Nima Pouladi, Rachel F Nelson, Elizabeth A Middleton, Neal D Tolley, Mahdieh Shabanian, Colleen Kenost, Robert A Campbell, Matthew T Rondina, Yves A Lussier

2020-Current year OA Pubs

OBJECTIVE: To evaluate if a single-subject study (S3) design, utilizing paired transcriptome samples from the same patient (eg, "sepsis" vs "recovered"), can replicate transcriptomic signatures from small case-control studies, addressing challenges in patient accrual for rare or sub-stratified diseases.

METHODS: We generated a sepsis gene signature (SGS) comprising 300 differentially expressed genes (DEGs; FDR <  5%) from a human sepsis case-control cohort using general linear models (GLMs). Reproducibility of SGS was assessed through three approaches applied to sub-sampled independent datasets: single-subject analyses (N-of-1-MixEnrich), anticipated to perform better; conventional paired-sample GLM analyses; and a traditional case-control GLM analysis.

RESULTS: SGS reproducibility in GLM analyses was inconsistent at smaller cohort sizes (∼80% reproducibility; n = 5) but stabilized at cohort sizes >6. Remarkably, the single-subject-study approach consistently reproduced SGS in each of the 18 subjects individually (100% reproducibility; n = 1).

DISCUSSION: Conventional GLMs are …

Cumulative Dose Of Chemotherapy And Survival Outcomes In Children With Average-Risk Medulloblastoma Treated On Children's Oncology Group Study Acns0331, Erin Wright, Catherine Billups, Sarah Rush, Yimei Li, Anna Janns, Jeff M Michalski, Ralph Salloum, Peter De Blank

2020-Current year OA Pubs

BACKGROUND: Although survival outcomes for average-risk (AR) medulloblastoma remain excellent, patients experience significant long-term toxicities. To evaluate the effect of therapy dose modifications among children with AR medulloblastoma, we examined the association of cumulative chemotherapy dose with overall survival (OS) and event-free survival (EFS) for patients treated on Children's Oncology Group (COG) study ACNS0331.

METHODS: A cohort of children enrolled on ACNS0331 (medulloblastoma confirmed by methylation, received standard dose craniospinal radiation, and completed all cycles of chemotherapy) were evaluated for cumulative chemotherapy dose intensity continuously and categorically (≥75% or < 75% of planned dose). Cox proportional hazards regression models were used to examine associations of proportion of planned chemotherapy received with outcome. A secondary analysis separately evaluated each of the 4 molecular subgroups: Wnt-activated (WNT), Sonic Hedgehog Activated (SHH), group 3 and group 4.

RESULTS: Two hundred thirty-five children were followed for a median of …

Characteristics Of Mortality In Hiv-Negative Cryptococcosis Patients: Analysis Of A Cohort Of 743 Patients, Kai Dai, Xinyao Jian, Chongliang Luo, Siguang Wang, Qiyu Pan, Xiaofeng Xu, Jia Liu, Fuhua Peng, Yong Chen, Ying Jiang

2020-Current year OA Pubs

BACKGROUND: Reports of cryptococcosis among patients without human immunodeficiency virus (HIV) infection are increasing. However, there is still a lack of data regarding the mortality characteristics in this population.

METHOD: The clinical, laboratory, imaging data from 743 HIV-negative patients with cryptococcosis were analyzed. Kaplan-Meier analysis was used to estimate all-cause mortality at 2-week, 10-week, and 1-year, with comparisons between groups using log-rank tests. Risk factor analysis was conducted using Cox models. Additionally, a meta-analysis was conducted on four recent large-scale cohort studies to investigate the differences in 2-week mortality of HIV-negative cryptococcosis across different regions. Statistical analyses were performed using …

Extending The Fundamental Theorem Of Biomedical Informatics For The Ai Era, Philip R O Payne, Jonathan H Chen, Christopher A Longhurst

2020-Current year OA Pubs

BACKGROUND: Charles Friedman's Fundamental Theorem of Biomedical Informatics holds that a person working in partnership with an information resource outperforms that same person unassisted. Since its publication, advances in artificial intelligence (AI), adaptive learning systems, and large-scale data infrastructures have transformed the biomedical ecosystem, extending informatics beyond clinical care into domains such as public health, consumer health, translational science, and the broader life sciences. Such expansion has further underscored the importance of the Fundamental Theorem while also elucidating ways it can be expanded to meet current needs.

OBJECTIVE: To reassess and extend the Fundamental Theorem for the AI era in …

Laser Interstitial Thermal Therapy Enhances Bidirectional Blood-Brain Barrier Permeability In Glioblastoma, Ryan T Cleary, Yiwei Fu, David Giles, Jinyun Yuan, Diogo P Moniz Garcia, Danny Palmer, Rowland H Han, Timothy Woodiwiss, Alicia B Yang, Dimitrios Mathios, Hong Chen, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for glioblastoma that increases blood-brain barrier (BBB) permeability. However, the mechanisms and spatiotemporal features of this effect remain unclear. It is also unknown whether LITT promotes release of circulating tumor DNA (ctDNA).

METHODS: Using our previously developed LITT mouse model, we employed single-cell RNA-sequencing (scRNA-seq) to investigate gene expression changes in endothelial cells following LITT in the naive mouse brain. Brains were also harvested at multiple time points to assess LITT effects on tight junction (TJ) integrity and transcytosis via immunofluorescence and transmission electron microscopy. Human glioblastoma tissues were …

Diagnostic Stewardship Of Respiratory Cultures Using Clinical Decision Support In The Picu, Anna C Sick-Samuels, John C Lin, Rebecca G Same, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Endotracheal aspirate culture (EAC) practices for evaluation of ventilator-associated infections (VAI) vary widely across pediatric hospitals, and overuse can contribute to overdiagnosis and overtreatment for VAI. Diagnostic stewardship strategies to optimize EAC testing practices may reduce overtesting and unnecessary antibiotic treatment.

OBJECTIVE: To evaluate the association of diagnostic stewardship of EACs using clinical decision support with culture rates, antibiotic use, and patient outcomes across a multicenter collaborative of pediatric intensive care units (PICUs).

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter cohort study with a pre-post study design among the BrighT STAR (Testing Stewardship for Antibiotic Reduction) Quality Improvement …

Patient-Centered Approach To Surgical Prevention Of Ovarian Cancer: A Nonrandomized Clinical Trial, Karen H Lu, Andrea R Hagemann, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Risk-reducing salpingo-oophorectomy (RRSO) is an effective option to prevent ovarian cancer in high-risk individuals, but adverse effects from premature menopause are a barrier to uptake. Interval salpingectomy with delayed oophorectomy (ISDO) may be an effective alternative.

OBJECTIVE: To evaluate the association of ISDO vs RRSO and sexual function and menopausal symptoms.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, nonrandomized (patient preference) clinical trial was performed among Women Choosing Surgical Prevention participants with a pathogenic or likely pathogenic germline variant conferring an increased risk for ovarian cancer. Patients from 9 US centers were enrolled from June 2, 2016, to October …

Prescribed Short-Acting Hormonal Contraceptive Use Among Premenopausal Females, Israel Bacha, Suleepon Uttamapinan, Hannah Harsanyi, Abigail Liberty, Lin Yang, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Hormonal contraceptive use has important implications for both reproductive and general health. However, the patterns and trends of short-acting hormonal contraceptive use among US premenopausal females remain insufficiently characterized.

OBJECTIVE: To evaluate trends in and factors associated with prescribed short-acting hormonal contraceptive use among US premenopausal females.

DESIGN, SETTING, AND PARTICIPANTS: Serial, cross-sectional analyses were conducted using US nationally representative data from the National Health and Nutrition Examination Survey (NHANES), including 10 survey cycles between 1999 to 2000 and 2017 to 2020 (before the COVID-19 pandemic). Participants included noninstitutionalized premenopausal females aged 15 years to younger than 60 years …

Maternal Health And Sociodemographic Characteristics Influence Infant Growth To 24 Months In The Tunza Mwana Cohort: A Prospective Cohort Study, David Taylor Hendrixson, Mark J Manary, Et Al.

2020-Current year OA Pubs

Upstream pathways influencing child growth are complex. Weight-for-age z-score (WAZ) reflects both ponderal and linear growth and can identify children at high mortality risk. Using data from a prospective cohort of 326 mother-child pairs in Kenya, we evaluated whether associations between maternal exposures and child growth outcomes in early and later childhood. Growth trajectories were examined using locally weighted scatterplot smoothing and piecewise linear mixed-effect models with a knot at age 3 months. Poisson regression models examined associations between maternal characteristics and child underweight (WAZ <  -2) and stunting (LAZ <  -2) before and after 3 months. Mean WAZ increased to a peak at 3 months before declining steadily through 24 months. Lower maternal education (adjusted β [aβ] -0.18; 95% CI: -0.24, -0.13), household crowding (aβ -0.2; 95% CI: -0.28, -0.11), lower wealth quintile (aβ -0.04; 95% CI: -0.06, -0.02) and multiparity (aβ -0.16; 95% CI: -0.23, -0.1) were associated with lower monthly rate of change in WAZ prior to age 3 months. Younger maternal age was associated with an increased monthly rate of change in WAZ (aβ = 0.13; 95% CI: 0.08, 0.18) before 3 months and decreased monthly WAZ (aβ -0.02; 95% CI: -0.03, -0.01) after 3 months. Preterm birth was associated with increased risk of underweight in both periods (aRR 2.77; 95% CI: 1.39-5.50). Maternal mental health, intimate partner violence and adverse childhood experiences were not significantly associated with child growth. Maternal nutritional, socio-economic and household-level factors shape early growth, emphasising the need for cross-sectoral programs to support growth.

Multi-Center Comparison Of Corticotropin Releasing Hormone Vs. Desmopressin Stimulation Responses In Inferior Petrosal Sinus Sampling For Cushing's Disease, Samuel A Tenhoeve, Julie M Silverstein, Albert H Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Inferior petrosal sinus sampling (IPSS) is important for confirming Cushing's Disease (CD). Due to lack of corticotropin releasing hormone (CRH) availability, desmopressin/DDAVP is being used as the alternative stimulating agent but has limited data regarding testing cutoffs.

DESIGN: We compared the stimulation profiles of desmopressin and CRH in patients with CD.

METHODS: Data from the multi-center Registry of Adenomas of the PItuitary and Related Disorders (RAPID) was evaluated. 93 patients with CD confirmed by pathology or biochemical remission that underwent IPSS testing prior to surgical resection (desmopressin [n = 57], CRH [n = 36] or both [n = 1]). …

Delayed Diagnosis Of A Rare Metabolic Disorder In Adulthood, Isaiah K Mensah, Angie Carreno Martinez, Taylor Wilson, Miguel Valdez, Maria Laura Duque Lasio

2020-Current year OA Pubs

No abstract provided.

Elevated Phagocytic Capacity Directs Innate Spinal Cord Repair, Dana Klatt Shaw, Vishnu Muraleedharan Saraswathy, Anthony R Mcadow, Lili Zhou, Dongkook Park, Ridim Mote, Amulya Saini, Ashley J Douthitt, Katerina Stepankova, Brittney Unverzagt, Cédric G Geoffroy, Aaron N Johnson, Mayssa H Mokalled

2020-Current year OA Pubs

Immune cells elicit a continuum of transcriptional states after spinal cord injury (SCI). In mammals, inefficient debris clearance and chronic inflammation impede recovery and overshadow pro-regenerative immune functions. We found that zebrafish SCI elicits transient immune activation and efficient debris clearance. Transcriptomics and genetic ablation showed zebrafish macrophages are highly phagocytic and required for regeneration. Comparisons between zebrafish and mammalian macrophages identified transcription and immune response regulator (tcim) as an immune-enriched regenerative gene. Deletion of zebrafish tcim impairs phagocytosis and regeneration and activates a pro-inflammatory signature in leukocytes. Tcim expression in zebrafish and mouse macrophages establishes its conserved roles by …

Bottlebrush Polymer Conjugates For Enhanced Antisense Oligonucleotide Therapy In Myotonic Dystrophy Type 1, Yao Li, Gyu Seong Heo, Yongjian Liu, Et Al.

2020-Current year OA Pubs

Oligonucleotides are a promising class of genetic medicine for myotonic dystrophy type 1 (DM1), the most common adult-onset muscular dystrophy. However, poor muscle distribution of nucleic acid drugs following systemic administration has hindered drug development, and no curative treatment currently exists. DM1 pathology requires drug localization to the nucleus, where pathogenic mutant RNA is sequestered, posing additional challenges after cellular internalization regarding endosomal escape and nuclear uptake. Here, we show that a locked nucleic acid oligonucleotide targeting mutant CUG repeat RNA tracts, conjugated to a bottlebrush polymer, exhibits improved muscle distribution and potent correction of DM1-associated splicing dysregulation in a …

Chiari Malformation Type 1 Is Associated With A Smaller Fourth Ventricle Volume - A Multi-Cohort Replication Study, Jarod L Roland, Thanda Meehan, Alexandra Gabliani, Scott Marek, Nico Dosenbach, Joshua S Shimony, Nilay Jakati, Yi Li, Leo Sugrue, Jennifer M Strahle, Chenyang Lu, David D Limbrick, Gabe Haller

2020-Current year OA Pubs

Chiari Malformation Type 1 (CM1) is canonically defined by ectopic position of the cerebellar tonsils with additional anatomic variations described inconsistently. Effect on fourth ventricle volume is controversial with prior studies reporting disparate results and methodologically limited to single institution series that hinder generalizability. This limitation was addressed utilizing multiple data sources, longitudinal replication, and reproducible methods using both FreeSurfer and the deep learning-based DL+DiReCT tools for automated volumetrics. First, we analyzed a local retrospective clinical cohort of individuals with CM1 and controls. Using data from the Adolescent Brain Cognitive Development (ABCD) Study, we analyzed volumes at baseline then replicated …

Broadly Reactive Human Monoclonal Antibodies Targeting Influenza A Nucleoprotein Lack Protective Activity In Vivo, Walter N Harrington, David C Brice, Aaron J Schmitz, Jackson S Turner, Rafael Brent, Philip A Mudd, Ali H Ellebedy, Richard J Webby

2020-Current year OA Pubs

The antibody response to influenza virus infection targets numerous viral proteins, with those specific for the hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins being the most extensively studied. Antibodies to HA and NA function as independent immune correlates of protection and form the basis of most vaccine approaches. In contrast, the contribution of antibodies to other viral proteins such as the nucleoprotein (NP) remains unclear, and existing studies have reached conflicting conclusions. In this work, we examined three human monoclonal NP antibodies isolated from plasmablasts of two individuals naturally infected with influenza A virus (IAV) during the 2018-2019 influenza season. …

Patterns Of Brain-Wide Associations Reflect Socioeconomics, Scott Marek, Meghan Rose Donohue, Nicole R Karcher, Caroline P Hoyniak, Roselyne J Chauvin, Ashley C Meyer, John Miller, Andrew N Van, Anxu Wang, Noah J Baden, Vahdeta Suljic, Kristen M Scheidter, Julia Monk, Forrest I Whiting, Nadeshka J Ramirez-Perez, Samuel R Krimmel, Athanasia Metoki, Rebecca F Schwarzlose, Steven E Petersen, Joan Luby, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Previous brain-wide association studies (BWAS) have linked specific environmental and behavioral variables to brain variability. In this work, we mapped 649 variables to children's brains and compared the resultant BWAS maps with each other and with neurobiological reference patterns. Socioeconomic status (SES) showed the strongest brain-wide associations. The SES associations were strongest in motor and sensory but not cognitive regions, a pattern shared across many BWAS maps, including intelligence quotient (IQ). A single, common BWAS brain pattern existed across variables that was most reflective of a child's socioeconomics. Adjusting for SES weakened brain-IQ associations, eliminating the BWAS motor and sensory …

Opposing Regulation By Rev1 Of Dna Polymerase Zeta Activity On Damaged Versus Undamaged Dna, Rachel Bezalel-Buch, Carrie Stith, Alena V Makarova, Sara K Binz, Peter M Burgers

2020-Current year OA Pubs

The Rev1 deoxycytidyl transferase functions as a scaffold protein for DNA polymerase ζ (Pol ζ)-mediated translesion synthesis (TLS). Biochemical studies with yeast enzymes indicate that Rev1 plays a dual regulatory role in TLS, stimulating Pol ζ activity at sites of damage but inhibiting its activity on undamaged DNA. An evolutionary conserved N-terminal alpha-helical motif (M1), located 10-20 amino acids upstream of Rev1's single BRCT domain, is required for the inhibitory activity of Rev1 on undamaged DNA. Mutations in the M1 motif result in a stimulation of Pol ζ replication activity on both undamaged and damaged DNA. Yeast cells carrying a …

Growth In Early Infancy Drives Optimal Brain Functional Connectivity Which Predicts Cognitive Flexibility In Later Childhood, Chiara Bulgarelli, Anna Blasi, Samantha Mccann, Bosiljka Milosavljevic, Giulia Ghillia, Ebrima Mbye, Ebou Touray, Tijan Fadera, Lena Acolatse, Sophie E Moore, Sarah Lloyd-Fox, Clare E Elwell, Adam T Eggebrecht, Bright Study Team

2020-Current year OA Pubs

Functional brain network organisation, measured by functional connectivity (FC), reflects key neurodevelopmental processes for healthy development. Early exposure to adversity, for example undernutrition, affects neurodevelopment, observable via disrupted FC, and leads to poorer outcomes from preschool age onwards. We assessed longitudinally the impact of early growth trajectories on developmental FC in a rural Gambian population from age 5-24 months. To investigate how these early trajectories relate to later childhood outcomes, we assessed cognitive flexibility at 3-5 years. We observed that early physical growth before the fifth month of life drove optimal developmental trajectories of FC that in turn predicted cognitive …