Digital Commons Network^™

Neuroendocrine Markers Insulinoma-Associated Protein 1, Chromogranin, Synaptophysin, And Cd56 Show Rare Positivity In Adenocarcinoma Ex-Goblet Cell Carcinoids, Chen Yang, Ivan Gonzalez, Lingxin Zhang, Dengfeng Cao

Open Access Publications

Background: Adenocarcinoma ex-goblet cell carcinoid (AdexGCC) was considered a neuroendocrine adenocarcinoma, despite majority of tumor cells being negative for conventional neuroendocrine markers such as chromogranin and synaptophysin. Recently, insulinoma-associated protein 1 (INSM1) has been identified as a novel neuroendocrine marker that is more sensitive than chromogranin, synaptophysin, and CD56 in pulmonary neuroendocrine tumors.

Methods: We studied this marker in conjunction with chromogranin, synaptophysin, and CD56 in 36 appendiceal AdexGCCs (21 primaries, 15 metastatic).

Results: Primary AdexGCCs showed staining for INSM1, chromogranin, synaptophysin, and CD56 in 13/21 (62%), 18/21 (86%), 18/21 (86%), and 9/19 (47%) cases, respectively. However, the mean proportion …

Apolipoprotein E Associated With Reconstituted High-Density Lipoprotein-Like Particles Is Protected From Aggregation., Ellen Hubin, Philip B Verghese, Nico Van Nuland, Kerensa Broersen

Open Access Publications

Apolipoprotein E (APOE) genotype determines Alzheimer's disease (AD) susceptibility, with the APOE ε4 allele being an established risk factor for late-onset AD. The ApoE lipidation status has been reported to impact amyloid-beta (Aβ) peptide metabolism. The details of how lipidation affects ApoE behavior remain to be elucidated. In this study, we prepared lipid-free and lipid-bound ApoE particles, mimicking the high-density lipoprotein particles found in vivo, for all three isoforms (ApoE2, ApoE3, and ApoE4) and biophysically characterized them. We find that lipid-free ApoE in solution has the tendency to aggregate in vitro in an isoform-dependent manner under near-physiological conditions and that …

Ddr2 Controls Breast Tumor Stiffness And Metastasis By Regulating Integrin Mediated Mechanotransduction In Cafs, Samantha V.H. Bayer, Whitney R. Grither, Audrey Brenot, Priscilla Y. Hwang, Craig E. Barcus, Melanie Ernst, Patrick Pence, Christopher Walter, Amit Pathak, Gregory D. Longmore

Open Access Publications

Biomechanical changes in the tumor microenvironment influence tumor progression and metastases. Collagen content and fiber organization within the tumor stroma are major contributors to biomechanical changes (e., tumor stiffness) and correlated with tumor aggressiveness and outcome. What signals and in what cells control collagen organization within the tumors, and how, is not fully understood. We show in mouse breast tumors that the action of the collagen receptor DDR2 in CAFs controls tumor stiffness by reorganizing collagen fibers specifically at the tumor-stromal boundary. These changes were associated with lung metastases. The action of DDR2 in mouse and human CAFs, and tumors …

Thyroid Hormone Regulates Distinct Paths To Maturation In Pigment Cell Lineages, Lauren M. Saunders, Abhishek K. Mishra, Andrew J. Aman, Victor M. Lewis, Matthew B. Toomey, Jonathan S. Packer, Xiaojie Qiu, Jose L. Mcfaline-Figueroa, Joseph C. Corbo, Cole Trapnell, David M. Parichy

Open Access Publications

Thyroid hormone (TH) regulates diverse developmental events and can drive disparate cellular outcomes. In zebrafish, TH has opposite effects on neural crest derived pigment cells of the adult stripe pattern, limiting melanophore population expansion, yet increasing yellow/orange xanthophore numbers. To learn how TH elicits seemingly opposite responses in cells having a common embryological origin, we analyzed individual transcriptomes from thousands of neural crest-derived cells, reconstructed developmental trajectories, identified pigment cell-lineage specific responses to TH, and assessed roles for TH receptors. We show that TH promotes maturation of both cell types but in distinct ways. In melanophores, TH drives terminal differentiation, …

An Endogenous Peptide Marker Differentiates Sod1 Stability And Facilitates Pharmacodynamic Monitoring In Sod1 Amyotrophic Lateral Sclerosis, Ilya Gertsman, Joanne Wuu, Melissa Mcalonis-Downes, Majid Ghassemian, Karen Ling, Frank Rigo, Frank Bennett, Michael Benatar, Timothy M. Miller, Sandrine Da Cruz

Open Access Publications

The discovery of novel biomarkers has emerged as a critical need for therapeutic development in amyotrophic lateral sclerosis (ALS). For some subsets of ALS, such as the genetic superoxide dismutase 1 (SOD1) form, exciting new treatment strategies, such as antisense oligonucleotide-mediated (ASO-mediated) SOD1 silencing, are being tested in clinical trials, so the identification of pharmacodynamic biomarkers for therapeutic monitoring is essential. We identify increased levels of a 7-amino acid endogenous peptide of SOD1 in cerebrospinal fluid (CSF) of human SOD1 mutation carriers but not in other neurological cases or nondiseased controls. Levels of peptide elevation vary based on the specific …

Celltag Indexing: Genetic Barcode-Based Sample Multiplexing For Single-Cell Genomics, Chuner Guo, Wenjun Kong, Kenji Kamimoto, Guillermo C Rivera-Gonzalez, Xue Yang, Yuhei Kirita, Samantha A Morris

Open Access Publications

High-throughput single-cell assays increasingly require special consideration in experimental design, sample multiplexing, batch effect removal, and data interpretation. Here, we describe a lentiviral barcode-based multiplexing approach, CellTag Indexing, which uses predefined genetic barcodes that are heritable, enabling cell populations to be tagged, pooled, and tracked over time in the same experimental replicate. We demonstrate the utility of CellTag Indexing by sequencing transcriptomes using a variety of cell types, including long-term tracking of cell engraftment and differentiation in vivo. Together, this presents CellTag Indexing as a broadly applicable genetic multiplexing tool that is complementary with existing single-cell technologies.

Cns Myelination And Remyelination Depend On Fatty Acid Synthesis By Oligodendrocytes, Penelope Dimas, Laura Montani, Jorge A. Pereira, Daniel Moreno, Martin Trötzmüller, Joanne Gerber, Clay F. Semenkovich, Harald C. Köfeler, Ueli Suter

Open Access Publications

Oligodendrocytes (OLs) support neurons and signal transmission in the central nervous system (CNS) by enwrapping axons with myelin, a lipid-rich membrane structure. We addressed the significance of fatty acid (FA) synthesis in OLs by depleting FA synthase (FASN) from OL progenitor cells (OPCs) in transgenic mice. While we detected no effects in proliferation and differentiation along the postnatal OL lineage, we found that FASN is essential for accurate myelination, including myelin growth. Increasing dietary lipid intake could partially compensate for the FASN deficiency. Furthermore, FASN contributes to correct myelin lipid composition and stability of myelinated axons. Moreover, we depleted FASN …

Reaching The End Of The Line: Urinary Tract Infections, Kevin O Tamadonfar, Natalie S Omattage, Caitlin N Spaulding, Scott J Hultgren

Open Access Publications

Urinary tract infections (UTIs) cause a substantial health care burden. UTIs (i) are most often caused by uropathogenic

Partial Adaptation To The Value Range In The Macaque Orbitofrontal Cortex, Katherine E. Conen, Camillo Padoa-Schioppa

Open Access Publications

Values available for choice in different behavioral contexts can vary immensely. To compensate for this variability, neuronal circuits underlying economic decisions undergo adaptation. In orbitofrontal cortex (OFC), neurons encode the subjective value of offered and chosen goods in a quasilinear way. Previous experiments found that the gain of the encoding is lower when the value range is wider. However, the parameters OFC neurons adapted to remained unclear. Furthermore, previous studies did not examine additive changes in neuronal responses. Computational considerations indicate that these factors can directly impact choice behavior. Here we investigated how OFC neurons adapt to changes in the …

Genome-Wide Association Study In Finnish Twins Highlights The Connection Between Nicotine Addiction And Neurotrophin Signaling Pathway, Jenni Hällfors, Teemu Palviainen, Ida Surakka, Richa Gupta, Jadwiga Buchwald, Anu Raevuori, Samuli Ripatti, Tellervo Korhonen, Pekka Jousilahti, Pamela A F Madden, Jaakko Kaprio, Anu Loukola

Open Access Publications

The heritability of nicotine dependence based on family studies is substantial. Nevertheless, knowledge of the underlying genetic architecture remains meager. Our aim was to identify novel genetic variants responsible for interindividual differences in smoking behavior. We performed a genome-wide association study on 1715 ever smokers ascertained from the population-based Finnish Twin Cohort enriched for heavy smoking. Data imputation used the 1000 Genomes Phase I reference panel together with a whole genome sequence-based Finnish reference panel. We analyzed three measures of nicotine addiction-smoking quantity, nicotine dependence and nicotine withdrawal. We annotated all genome-wide significant SNPs for their functional potential. First, we …

High-Density Diffuse Optical Tomography For Imaging Human Brain Function, Muriah D Wheelock, Joseph P Culver, Adam T Eggebrecht

Open Access Publications

This review describes the unique opportunities and challenges for noninvasive optical mapping of human brain function. Diffuse optical methods offer safe, portable, and radiation free alternatives to traditional technologies like positron emission tomography or functional magnetic resonance imaging (fMRI). Recent developments in high-density diffuse optical tomography (HD-DOT) have demonstrated capabilities for mapping human cortical brain function over an extended field of view with image quality approaching that of fMRI. In this review, we cover fundamental principles of the diffusion of near infrared light in biological tissue. We discuss the challenges involved in the HD-DOT system design and implementation that must …

Brain Tumors In Neurofibromatosis Type 1, Amanda De Andrade Costa, David H Gutmann

Open Access Publications

As a cancer predisposition syndrome, individuals with neurofibromatosis type 1 (NF1) are at increased risk for the development of both benign and malignant tumors. One of the most common locations for these cancers is the central nervous system, where low-grade gliomas predominate in children. During early childhood, gliomas affecting the optic pathway are most frequently encountered, whereas gliomas of the brainstem and other locations are observed in slightly older children. In contrast, the majority of gliomas arising in adults with NF1 are malignant cancers, typically glioblastoma, involving the cerebral hemispheres. Our understanding of the pathogenesis of NF1-associated gliomas has been …

Regulation Of Cilia Abundance In Multiciliated Cells, Rashmi Nanjundappa, Dong Kong, Kyuhwan Shim, Tim Stearns, Steven L. Brody, Jadranka Loncarek, Moe R. Mahjoub

Open Access Publications

Multiciliated cells (MCC) contain hundreds of motile cilia used to propel fluid over their surface. To template these cilia, each MCC produces between 100-600 centrioles by a process termed centriole amplification. Yet, how MCC regulate the precise number of centrioles and cilia remains unknown. Airway progenitor cells contain two parental centrioles (PC) and form structures called deuterosomes that nucleate centrioles during amplification. Using an ex vivo airway culture model, we show that ablation of PC does not perturb deuterosome formation and centriole amplification. In contrast, loss of PC caused an increase in deuterosome and centriole abundance, highlighting the presence of …

Mutant Huntingtin Enhances Activation Of Dendritic Kv4 K+ Channels In Striatal Spiny Projection Neurons, Luis Carrillo-Reid, Michelle Day, Zhong Xie, Alexandria E. Melendez, Jyothisri Kondapalli, Joshua L. Plotkin, David L. Wokosin, Yu Chen, Geraldine J. Kress, Michael Kaplitt, Ema Ilijic, Jaime N. Guzman, C Savio Chan, D James Surmeier

Open Access Publications

Huntington's disease (HD) is initially characterized by an inability to suppress unwanted movements, a deficit attributable to impaired synaptic activation of striatal indirect pathway spiny projection neurons (iSPNs). To better understand the mechanisms underlying this deficit, striatal neurons in ex vivo brain slices from mouse genetic models of HD were studied using electrophysiological, optical and biochemical approaches. Distal dendrites of iSPNs from symptomatic HD mice were hypoexcitable, a change that was attributable to increased association of dendritic Kv4 potassium channels with auxiliary KChIP subunits. This association was negatively modulated by TrkB receptor signaling. Dendritic excitability of HD iSPNs was rescued …

Down Syndrome Mouse Models Have An Abnormal Enteric Nervous System, Ellen M Schill, Christina M Wright, Alisha Jamil, Jonathan M Lacombe, Randall J Roper, Robert O Heuckeroth

Open Access Publications

Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung Disease (HSCR), a developmental defect where the enteric nervous system (ENS) is missing from distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Post-surgical problems like enterocolitis and soiling are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in two DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including Dscam and Dyrk1a, which …

An Obligatory Role For Club Cells In Preventing Obliterative Bronchiolitis In Lung Transplants, Zhiyi Liu, Fuyi Liao, Davide Scozzi, Yuka Furuya, Kaitlyn N Pugh, Ramsey Hachem, Delphine L Chen, Marlene Cano, Jonathan M Green, Alexander S Krupnick, Daniel Kreisel, Anne Karina T Perl, Howard J Huang, Steven L Brody, Andrew E Gelman

Open Access Publications

Obliterative bronchiolitis (OB) is a poorly understood airway disease characterized by the generation of fibrotic bronchiolar occlusions. In the lung transplant setting, OB is a pathological manifestation of bronchiolitis obliterans syndrome (BOS), which is a major impediment to long-term recipient survival. Club cells play a key role in bronchiolar epithelial repair, but whether they promote lung transplant tolerance through preventing OB remains unclear. We determined if OB occurs in mouse orthotopic lung transplants following conditional transgene-targeted club cell depletion. In syngeneic lung transplants club cell depletion leads to transient epithelial injury followed by rapid club cell-mediated repair. In contrast, allogeneic …

Significance Of Her2 Protein Expression And Her2 Gene Amplification In Colorectal Adenocarcinomas, Xin-Yu Wang, Zhi-Xue Zheng, Yu Sun, Yan-Hua Bai, Yun-Fei Shi, Li-Xin Zhou, Yun-Feng Yao, Ai-Wen Wu, Deng-Feng Cao

Open Access Publications

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas (CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables.

AIM: To correlate HER2 protein expression and

METHODS: About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining (IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated …

Subsequent Event Risk In Individuals With Established Coronary Heart Disease, Riyaz S. Patel, Petra A. Lenzini, Sharon Cresci, Et Al

Open Access Publications

No abstract provided.

A Mixture Of U.S. Food And Drug Administration-Approved Monoaminergic Drugs Protects The Retina From Light Damage In Diverse Models Of Night Blindness, Henri Leinonen, Elliot H. Choi, Anthony Gardella, Vladimir J. Kefalov, Krzysztof Palczewski

Open Access Publications

Purpose: The purpose of this study was to test the extent of light damage in different models of night blindness and apply these paradigms in testing the therapeutic efficacy of combination therapy by drugs acting on the Gi, Gs, and Gq protein-coupled receptors.

Methods: Acute bright light exposure was used to test susceptibility to light damage in mice lacking the following crucial phototransduction proteins: rod transducin (GNAT1), cone transducin (GNAT2), visual arrestin 1 (ARR1), and rhodopsin kinase 1 (GRK1). Mice were intraperitoneally injected with either vehicle or drug combination consisting of metoprolol (β1-receptor antagonist), bromocriptine (dopamine family-2 receptor agonist) and …

Suppression Of Ilc2 Differentiation From Committed T Cell Precursors By E Protein Transcription Factors, Liangyue Qian, Sandra Bajana, Constantin Georgescu, Vincent Peng, Hong-Cheng Wang, Indra Adrianto, Marco Colonna, Jose Alberola-Ila, Jonathan D. Wren, Xiao-Hong Sun

Open Access Publications

Current models propose that group 2 innate lymphoid cells (ILC2s) are generated in the bone marrow. Here, we demonstrate that subsets of these cells can differentiate from multipotent progenitors and committed T cell precursors in the thymus, both in vivo and in vitro. These thymic ILC2s exit the thymus, circulate in the blood, and home to peripheral tissues. Ablation of E protein transcription factors greatly promotes the ILC fate while impairing B and T cell development. Consistently, a transcriptional network centered on the ZBTB16 transcription factor and IL-4 signaling pathway is highly up-regulated due to E protein deficiency. Our results …

Abnormal Oxidative Metabolism In A Quiet Genomic Background Underlies Clear Cell Papillary Renal Cell Carcinoma, Jianing Xu, James J. Hsieh, Et Al

Open Access Publications

No abstract provided.

Astct Consensus Grading For Cytokine Release Syndrome And Neurologic Toxicity Associated With Immune Effector Cells, Daniel W Lee, Armin Ghobadi, John F Dipersio, Et Al

Open Access Publications

Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique …

Conditional Deletion Of Des1 In The Mouse Retina Does Not Impair The Visual Cycle In Cones, Philip D Kiser, Alexander V Kolesnikov, Jianying Z Kiser, Zhiqian Dong, Bhagirath Chaurasia, Liping Wang, Scott A Summers, Thanh Hoang, Seth Blackshaw, Neal S Peachey, Vladimir J Kefalov, Krzysztof Palczewski

Open Access Publications

Cone photoreceptors are essential for vision under moderate to high illuminance and allow color discrimination. Their fast dark adaptation rate and resistance to saturation are believed to depend in part on an intraretinal visual cycle that supplies 11- cis-retinaldehyde to cone opsins. Candidate enzymes of this pathway have been reported, but their physiologic contribution to cone photoresponses remains unknown. Here, we evaluate the role of a candidate retinol isomerase of this pathway, sphingolipid δ4 desaturase 1 (Des1). Single-cell RNA sequencing analysis revealed Des1 expression not only in Müller glia but also throughout the retina and in the retinal pigment epithelium. …

Neurotransmitter Identity Is Acquired In A Lineage-Restricted Manner In The Drosophila Cns, Haluk Lacin, Hui-Min Chen, Xi Long, Robert H. Singer, Tzumin Lee, James W. Truman

Open Access Publications

The vast majority of the adult fly ventral nerve cord is composed of 34 hemilineages, which are clusters of lineally related neurons. Neurons in these hemilineages use one of the three fast-acting neurotransmitters (acetylcholine, GABA, or glutamate) for communication. We generated a comprehensive neurotransmitter usage map for the entire ventral nerve cord. We did not find any cases of neurons using more than one neurotransmitter, but found that the acetylcholine specific gene ChAT is transcribed in many glutamatergic and GABAergic neurons, but these transcripts typically do not leave the nucleus and are not translated. Importantly, our work uncovered a simple …

Skin Cancer Precursor Immunotherapy For Squamous Cell Carcinoma Prevention, Abby R Rosenberg, Mary Tabacchi, Kenneth H Ngo, Michael Wallendorf, Ilana S Rosman, Lynn A Cornelius, Shadmehr Demehri

Open Access Publications

BACKGROUND: Topical calcipotriol plus 5-fluorouracil (5-FU) combination is an effective immunotherapy against actinic keratosis (AK), which is a precursor to squamous cell carcinoma (SCC). However, the long-term effectiveness of calcipotriol plus 5-FU treatment for SCC prevention is unknown.

METHODS: We performed a blinded prospective cohort study on participants of a randomized double-blind clinical trial in which a 4-day course of topical calcipotriol plus 5-FU combination was compared to Vaseline plus 5-FU (control) for AK treatment. SCC and basal cell carcinoma (BCC) incidences were assessed at 1, 2, and 3 years after trial. Tissues were analyzed for calcipotriol plus 5-FU-induced T …

A Novel Pathogenic Variant In Osbpl2 Linked To Hereditary Late-Onset Deafness In A Mongolian Family, Ningjin Wu, Husile Husile, Liqing Yang, Yaning Cao, Xing Li, Wenyan Huo, Haihua Bai, Yangjian Liu, Qizhu Wu

Open Access Publications

BACKGROUND: To investigate the clinical features and the underlying causal gene of a family with hereditary late-onset deafness in Inner Mongolia of China, and to provide evidence for the early genetic screening and diagnosis of this disease.

METHODS: Family data were collected to draw a pedigree. Audiological testing and physical examination of the family members were conducted following questionnaire. Genomic DNA was extracted from peripheral blood of 5 family members (3 patients and 2 normal control) and subjected to whole genome sequencing for identifying deafness casual genes. The pathogenic variant in the deafness gene was further confirmed by Sanger sequencing. …

Follicular Lymphoma Patients With Kir2dl2 And Kir3dl1 And Their Ligands (Hla-C1 And Hla-Bw4) Show Improved Outcome When Receiving Rituximab, Amy K Erbe, Wei Wang, Lakeesha Carmichael, Anna Hoefges, Bartosz Grzywacz, Patrick K Reville, Erik A Ranheim, Jacquelyn A Hank, Kyungmann Kim, Songwon Seo, Eneida A Mendonca, Yiqiang Song, Vaishalee P Kenkre, Fangxin Hong, Randy D Gascoyne, Elisabeth Paietta, Sandra J Horning, Jeffrey S Miller, Brad Kahl, Paul M Sondel

Open Access Publications

BACKGROUND: The ECOG-ACRIN Cancer Research Group evaluated rituximab treatment schedules for patients with newly-diagnosed low-tumor-burden follicular-lymphoma (FL). All patients received 4-weekly rituximab treatments as induction therapy. Clinically-responding patients were randomized to receive rituximab every 13 weeks ("maintenance") vs. no additional rituximab until progression ("non-maintenance"). Based on "time-to-rituximab-failure (TTRF)", the study-committee reported there was no overall-benefit for maintenance rituximab in this setting. Tumor-reactive mAbs, like rituximab, trigger natural killer (NK) cells. NK-cell responses are regulated, in part, by interactions between killer immunoglobulin-like receptors (KIRs) on NK cells and their interactions with KIR-ligands. In a separate study of children with neuroblastoma treated …

Homozygous Frameshift Mutations In Fat1 Cause A Syndrome Characterized By Colobomatous-Microphthalmia, Ptosis, Nephropathy And Syndactyly., Najim Lahrouchi, Aman George, Ilham Ratbi, Ronen Schneider, Siham C Elalaoui, Shahida Moosa, Sanita Bharti, Ruchi Sharma, Mones Abu-Asab, Felix Onojafe, Najlae Adadi, Elisabeth M Lodder, Fatima-Zahra Laarabi, Yassine Lamsyah, Hamza Elorch, Imane Chebbar, Alex V Postma, Vassilios Lougaris, Alessandro Plebani, Janine Altmueller, Henriette Kyrieleis, Vardiella Meiner, Helen Mcneill, Kapil Bharti, Stanislas Lyonnet, Bernd Wollnik, Alexandra Henrion-Caude, Amina Berraho, Friedhelm Hildebrandt, Connie R Bezzina, Brian P Brooks, Abdelaziz Sefiani

Open Access Publications

A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic …

Association Of The Infant Gut Microbiome With Early Childhood Neurodevelopmental Outcomes: An Ancillary Study To The Vdaart Randomized Clinical Trial, Joanne E. Sordillo, Susan Korrick, Nancy Laranjo, Vincent Carey, George M. Weinstock, Diane R. Gold, George O'Connor, Megan Sandel, Leonard B. Bacharier, Avraham Beigelman, Robert Zeiger, Augusto A. Litonjua, Scott T. Weiss

Open Access Publications

Importance: In animal models, the early life gut microbiome influences later neurodevelopment. Corresponding data in human populations are lacking.

Objective: To study associations between the gut microbiome in infants and development at preschool age measured by the Ages and Stages Questionnaire, third edition (ASQ-3).

Design, Setting, and Participants: This ancillary cohort study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART) used data from 715 participants who had development assessed at 3 years of age by the ASQ-3, which included scores in 5 domains (gross motor skills, fine motor skills, problem solving, communication, and personal and social skills). A total …

Staying Awake To Stay Alive: A Circuit Controlling Starvation-Induced Waking, Krishna Melnattur, Paul Shaw

Open Access Publications

The balance of sleep and wake is plastic and changes to meet environmental demands. Mechanisms that allow an animal to suppress sleep and maintain waking in potentially adverse situations could serve adaptive functions in evolution. The fruit fly, Drosophila melanogaster, is well poised as a system in which to explore these questions. The environment changes sleep and wake in flies, e.g., starvation induces waking in Drosophila as it does in many animals. Further, the sophisticated neurobiological toolkit available to Drosophila researchers gives the fly a great advantage as a system to investigate the precise neurobiological mechanisms underlying these adaptive changes. …