Digital Commons Network^™

Lipofilling After Breast Conserving Surgery: A Comprehensive Literature Review Investigating Its Oncologic Safety, Stephanie Cohen, Yurie Sekigami, Theresa Schwartz, Albert Losken, Julie Margenthaler, Abhishek Chatterjee

Open Access Publications

Lipofilling has regenerative properties used to improve deformities after breast conserving surgery. Our hypothesis is that there is inadequate data to ensure that lipofilling does not increase locoregional cancer recurrence after breast conserving surgery. A PRISMA comprehensive literature review was conducted of articles published prior to October 2019 investigating recurrence in patients who underwent lipofilling after breast conserving surgery. All forms of breast conserving surgery, fat grafting, and injection intervals were included. Patients undergoing mastectomy were excluded. Requirements to define lipofilling as "safe" included (I) a defined interval between resection and lipofilling; (II) a minimum follow-up period of 6 years …

Association Of Circulating Ceramides With Cardiac Structure And Function In The Community: The Framingham Heart Study, Chike C Nwabuo, Meredith Duncan, Vanessa Xanthakis, Linda R Peterson, Gary F Mitchell, David Mcmanus, Susan Cheng, Ramachandran S. Vasan

Open Access Publications

Background A higher circulating plasma ceramide ratio (C16:0/C24:0) is associated with an increased risk of heart failure, even after accounting for standard risk factors including lipid markers. However, the pathobiological mechanisms that underlie this association are incompletely understood. We tested the hypothesis that plasma ceramide ratio (C16:0/C24:0) is associated with adverse cardiac remodeling in the community. Methods and Results We evaluated 2652 Framingham Offspring Study participants (mean age, 66±9 years; 55% women) who attended their eighth examination cycle and underwent routine echocardiography and liquid chromatography-tandem mass spectrometry-based assays for circulating ceramide concentrations. We used multivariable linear regression models to relate …

Astrovirus Replication In Human Intestinal Enteroids Reveals Multi-Cellular Tropism And An Intricate Host Innate Immune Landscape, Abimbola O. Kolawole, Andrew B Janowski, David Wang, Christiane E. Wobus, Et Al.

Open Access Publications

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE …

Sequence Specificity Despite Intrinsic Disorder: How A Disease-Associated Val/Met Polymorphism Rearranges Tertiary Interactions In A Long Disordered Protein, Ruchi Lohia, Reza Salari, Grace Brannigan

Open Access Publications

The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) in precursor brain-derived neurotrophic factor (BDNF) is one of the earliest SNPs to be associated with neuropsychiatric disorders, and the underlying molecular mechanism is unknown. Here we report on over 250 μs of fully-atomistic, explicit solvent, temperature replica-exchange molecular dynamics (MD) simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence. The simulations were able to correctly reproduce the location of both local and …

Open-Sourced Civic Annotation Pipeline To Identify And Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes, Erica K Barnell, Adam Waalkes, Matt C Mosior, Kelsi Penewit, Kelsy C Cotto, Arpad M Danos, Lana M Sheta, Katie M Campbell, Kilannin Krysiak, Damian Rieke, Nicholas C Spies, Zachary L Skidmore, Colin C Pritchard, Todd A Fehniger, Ravindra Uppaluri, Ramaswamy Govindan, Malachi Griffith, Stephen J Salipante, Obi L Griffith

Open Access Publications

PURPOSE: Clinical targeted sequencing panels are important for identifying actionable variants for patients with cancer; however, existing approaches do not provide transparent and rationally designed clinical panels to accommodate the rapidly growing knowledge within oncology.

MATERIALS AND METHODS: We used the Clinical Interpretations of Variants in Cancer (CIViC) database to develop an Open-Sourced CIViC Annotation Pipeline (OpenCAP). OpenCAP provides methods to identify variants within the CIViC database, build probes for variant capture, use probes on prospective samples, and link somatic variants to CIViC clinical relevance statements. OpenCAP was tested using a single-molecule molecular inversion probe (smMIP) capture design on 27 …

Optimizing Postprandial Glucose Management In Adults With Insulin-Requiring Diabetes: Report And Recommendations, John (Jack) L. Leahy, Grazia Aleppo, Vivian A. Fonseca, Satish K. Garg, Irl B. Hirsch, Anthony L. Mccall, Janet B. Mcgill, William H. Polonsky

Open Access Publications

Faster-acting insulins, new noninsulin drug classes, more flexible insulin-delivery systems, and improved continuous glucose monitoring devices offer unprecedented opportunities to improve postprandial glucose (PPG) management and overall care for adults with insulin-treated diabetes. These developments led the Endocrine Society to convene a working panel of diabetes experts in December 2018 to assess the current state of PPG management, identify innovative ways to improve self-management and quality of life, and align best practices to current and emerging treatment and monitoring options. Drawing on current research and collective clinical experience, we considered the following issues for the ∼200 million adults worldwide with …

Tic Suppression In Children With Recent-Onset Tics Predicts 1-Year Tic Outcome, Soyoung Kim, Deanna J Greene, Amy Robichaux-Viehoever, Emily C Bihun, Jonathan M Koller, Haley Acevedo, Bradley L Schlaggar, Kevin J Black

Open Access Publications

Successful voluntary tic suppression is a key component of the behavioral interventions that are used to treat tic disorders. This study aimed to examine tic suppression in children with recent-onset tics and determine whether the capacity to suppress tics predicts future tic severity. We tested 45 children (30 male, mean age 7.74 years) with recent-onset tics (mean 3.47 months prior to the first study visit; baseline) and re-examined each child at the 12-month anniversary of the first recognized tic (follow-up). At the baseline visit, children performed a tic suppression task with several conditions: tic freely, inhibit tics given a verbal …

Casein Kinase 1 Family Proteins Promote Slimb-Dependent Expanded Degradation, Alexander D. Fulford, Maxine V. Holder, David Frith, Ambrosius P. Snijders, Nicolas Tapon, Paulo S. Ribeiro

Open Access Publications

Hippo signalling integrates diverse stimuli related to epithelial architecture to regulate tissue growth and cell fate decisions. The Hippo kinase cascade represses the growth-promoting transcription co-activator Yorkie. The FERM protein Expanded is one of the main upstream Hippo signalling regulators in

Inhibition Of 4-Aminobutyrate Aminotransferase Protects Against Injury-Induced Osteoarthritis In Mice, Jie Shen, Cuicui Wang, Jun Ying, Taotao Xu, Audrey Mcalinden, Regis J. O'Keefe

Open Access Publications

Recently we demonstrated that ablation of the DNA methyltransferase enzyme, Dnmt3b, resulted in catabolism and progression of osteoarthritis (OA) in murine articular cartilage through a mechanism involving increased mitochondrial respiration. In this study, we identify 4-aminobutyrate aminotransferase (Abat) as a downstream target of Dnmt3b. Abat is an enzyme that metabolizes γ-aminobutyric acid to succinate, a key intermediate in the tricarboxylic acid cycle. We show that Dnmt3b binds to the Abat promoter, increases methylation of a conserved CpG sequence just upstream of the transcriptional start site, and inhibits Abat expression. Dnmt3b deletion in articular chondrocytes results in reduced methylation of the …

Noninvasive Mapping Of The Electrophysiological Substrate In Cardiac Amyloidosis And Its Relationship To Structural Abnormalities, Michele Orini, Adam J Graham, Ana Martinez-Naharro, Christopher M Andrews, Antonio De Marvao, Ben Statton, Stuart A Cook, Declan P O'Regan, Philip N Hawkins, Yoram Rudy, Marianna Fontana, Pier D Lambiase

Open Access Publications

Background The relationship between structural pathology and electrophysiological substrate in cardiac amyloidosis is unclear. Differences between light-chain (AL) and transthyretin (ATTR) cardiac amyloidosis may have prognostic implications. Methods and Results ECG imaging and cardiac magnetic resonance studies were conducted in 21 cardiac amyloidosis patients (11 AL and 10 ATTR). Healthy volunteers were included as controls. With respect to ATTR, AL patients had lower amyloid volume (51.0/37.7 versus 73.7/16.4 mL, P=0.04), lower myocardial cell volume (42.6/19.1 versus 58.5/17.2 mL, P=0.021), and higher T1 (1172/64 versus 1109/80 ms, P=0.022) and T2 (53.4/2.9 versus 50.0/3.1 ms, P=0.003). ECG imaging revealed differences between cardiac …

Association Of Timing Of Adverse Childhood Experiences And Caregiver Support With Regionally Specific Brain Development In Adolescents, Joan L. Luby, Rebecca Tillman, Deanna M. Barch

Open Access Publications

Importance: Few data are available to inform the associations and timing of the associations between adversity, caregiver support, and brain outcomes. Consideration of timing has important public health implications to inform more precise prevention strategies.

Objective: To evaluate the timing and regional specificity of the association between adverse childhood experiences (ACEs) and caregiver support to structural development of limbic and striatal brain regions in middle childhood and adolescence.

Design, Setting, and Participants: This 15-year developmental, neuroimaging cohort study included 211 children and their caregivers screened from day care centers and preschools in the St Louis, Missouri, metropolitan area during the …

Endobronchial Ultrasound-Guided Intranodal Forceps Biopsy (Ebus-Ifb)-Technical Review, George Cheng, Amit Mahajan, Scott Oh, Sadia Benzaquen, Alexander Chen

Open Access Publications

Endobronchial ultrasound (EBUS) and transbronchial needle aspiration (TBNA) have changed the landscape of pulmonology. Mediastinal structures beyond the confines of airway walls are visualized in real-time with EBUS, leading to improved accuracy of tissue sampling and diagnostic yield. With the development of various needle sizes ranging from 25-G to 19-G, the sampling of lymph nodes is becoming easier and more commonplace. Yet, certain conditions such as sarcoidosis and lymphoma may still be difficult to diagnose via EBUS-TBNA. Furthermore, in the age of targeted therapy, there are more demands on EBUS-TBNA samples for molecular marker testing and next-generation sequencing. Here, we …

Four-Jointed Knock-Out Delays Renal Failure In An Adpkd Model With Kidney Injury, Chiara Formica, Hester Happé, Kimberley Am Veraar, Andrea Vortkamp, Marion Scharpfenecker, Helen Mcneill, Dorien Jm Peters

Open Access Publications

Autosomal Dominant Polycystic Kidney Disease is characterised by the development of fluid-filled cysts in the kidneys which lead to end-stage renal disease (ESRD). In the majority of cases, the disease is caused by a mutation in the Pkd1 gene. In a previous study, we demonstrated that renal injury can accelerate cyst formation in Pkd1 knock-out (KO) mice. In that study, we found that after injury four-jointed (Fjx1), an upstream regulator of planar cell polarity and the Hippo pathway, was aberrantly expressed in Pkd1 KO mice compared to WT. Therefore, we hypothesised a role for Fjx1 in injury/repair and cyst formation. …

Best Practices For Bioinformatic Characterization Of Neoantigens For Clinical Utility, Megan M Richters, Huiming Xia, Katie M Campbell, William E Gillanders, Obi L Griffith, Malachi Griffith

Open Access Publications

Neoantigens are newly formed peptides created from somatic mutations that are capable of inducing tumor-specific T cell recognition. Recently, researchers and clinicians have leveraged next generation sequencing technologies to identify neoantigens and to create personalized immunotherapies for cancer treatment. To create a personalized cancer vaccine, neoantigens must be computationally predicted from matched tumor-normal sequencing data, and then ranked according to their predicted capability in stimulating a T cell response. This candidate neoantigen prediction process involves multiple steps, including somatic mutation identification, HLA typing, peptide processing, and peptide-MHC binding prediction. The general workflow has been utilized for many preclinical and clinical …

Comparative Genomics Of Antibiotic-Resistant Uropathogens Implicates Three Routes For Recurrence Of Urinary Tract Infections, Robert Thänert, Kimberly A Reske, Tiffany Hink, Meghan A Wallace, Bin Wang, Drew J Schwartz, Sondra Seiler, Candice Cass, Carey-Ann D. Burnham, Erik R Dubberke, Jennie H Kwon, Gautam Dantas

Open Access Publications

The rise of antimicrobial resistance in uropathogens has complicated the management of urinary tract infections (UTIs), particularly in patients who are afflicted by recurrent episodes of UTIs. Antimicrobial-resistant (AR) uropathogens persistently colonizing individuals at asymptomatic time points have been implicated in the pathophysiology of UTIs. The dynamics of uropathogen persistence following the resolution of symptomatic disease are, however, mostly unclear. To further our understanding, we determined longitudinal AR uropathogen carriage and clonal persistence of uropathogenic

Sensorimotor Coding Of Vermal Granule Neurons In The Developing Mammalian Cerebellum, Kelly H. Markwalter, Yue Yang, Timothy E. Holy, Azad Bonni

Open Access Publications

The vermal cerebellum is a hub of sensorimotor integration critical for postural control and locomotion, but the nature and developmental organization of afferent information to this region have remained poorly understood

Mucosal Infection Rewires Tnfɑ Signaling Dynamics To Skew Susceptibility To Recurrence, Lu Yu, Valerie P. O'Brien, Jonathan Livny, Denise Dorsey, Nirmalya Bandyopadhyay, Marco Colonna, Michael G. Caparon, Elisha D.O. Roberson, Scott J. Hultgren, Thomas Hannan

Open Access Publications

A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infection resulted in an earlier onset of tumor necrosis factor-alpha (TNFɑ)-mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFɑ signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFɑ depletion studies revealed that transient early-phase TNFɑ signaling in Resolved mice …

A Single-Nuclei Rna Sequencing Study Of Mendelian And Sporadic Ad In The Human Brain, Jorge L Del-Aguila, Zeran Li, Umber Dube, Kathie A Mihindukulasuriya, John P Budde, Maria Victoria Fernandez, Laura Ibanez, Joseph Bradley, Fengxian Wang, Kristy Bergmann, Richard Davenport, John C Morris, David M Holtzman, Richard J Perrin, Bruno A Benitez, Joseph Dougherty, Carlos Cruchaga, Oscar Harari

Open Access Publications

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis heavily impacting the cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian and complex genetic architectures. Using bulk RNA-seq from the parietal lobes and deconvolution methods, we previously reported that brains exhibiting different AD genetic architecture exhibit different cellular proportions. Here, we sought to directly investigate AD brain changes in cell proportion and gene expression using single-cell resolution.

METHODS: We generated unsorted single-nuclei RNA sequencing data from brain tissue. We leveraged the tissue donated from …

Toxoplasma Gondii Infection Drives Conversion Of Nk Cells Into Ilc1-Like Cells, Eugene Park, Swapneel Patel, Qiuling Wang, Prabhakar Andhey, Konstantin Zaitsev, Sophia Porter, Maxwell Hershey, Michael Bern, Beatrice Plougastel-Douglas, Patrick Collins, Marco Colonna, Kenneth M. Murphy, Eugene Oltz, Maxim Artyomov, L David Sibley, Wayne M. Yokoyama

Open Access Publications

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here, we describe

Association Of Baseline Inflammatory Biomarkers With Cancer Mortality In The Regards Cohort, Tomi Akinyemiju, Justin X. Moore, Maria Pisu, Michael Goodman, Virginia J. Howard, Monika Safford, Susan C. Gilchrist, Mary Cushman, Leann Long, Suzanne E. Judd

Open Access Publications

This study examines the association between inflammatory biomarkers and risk of cancer mortality by race. Data were obtained from 1,856 participants in the prospective REGARDS cohort who were cancer-free at baseline, and analyzed in relation to cancer mortality prospectively. Biomarkers were log-transformed and categorized into tertiles due to non-normal distributions, and Cox proportional hazard regression models were utilized to compute hazard ratios with 95% confidence intervals using robust sandwich methods. Individuals in the highest tertile of IL-6 had over a 12-fold increased risk of cancer mortality (HR: 12.97, 95% CI: 3.46-48.63); those in the highest tertile of IL-8 had over …

Sleep Disturbances In Wolfram Syndrome, Amy Licis, Gabriel Davis, Sarah A Eisenstein, Heather M Lugar, Tamara Hershey

Open Access Publications

BACKGROUND: Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients.

METHODS: Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and …

Measurement Repeatability Of 18 F-Fdg Pet/Ct Versus 18 F-Fdg Pet/Mri In Solid Tumors Of The Pelvis, Tyler J Fraum, Kathryn J Fowler, John P Crandall, Richard A Laforest, Amber Salter, Hongyu An, Michael A Jacobs, Perry W Grigsby, Farrokh Dehdashti, Richard L Wahl

Open Access Publications

Knowledge of the within-subject variability of

Quantification Of Image Texture In X-Ray Phase-Contrast-Enhanced Projection Images Of In Vivo Mouse Lungs Observed At Varied Inflation Pressures, Frank J Brooks, Sean P Gunsten, Sunil K Vasireddi, Steven L Brody, Mark A Anastasio

Open Access Publications

To date, there are very limited noninvasive, regional assays of in vivo lung microstructure near the alveolar level. It has been suggested that x-ray phase-contrast enhanced imaging reveals information about the air volume of the lung; however, the image texture information in these images remains underutilized. Projection images of in vivo mouse lungs were acquired via a tabletop, propagation-based, X-ray phase-contrast imaging system. Anesthetized mice were mechanically ventilated in an upright position. Consistent with previously published studies, a distinct image texture was observed uniquely within lung regions. Lung regions were automatically identified using supervised machine learning applied to summary measures …

Analysis Of An Improved Cyanophora Paradoxa Genome Assembly, Dana C Price, Ursula W Goodenough, Robyn Roth, Jae-Hyeok Lee, Thamali Kariyawasam, Marek Mutwil, Camilla Ferrari, Fabio Facchinelli, Steven G Ball, Ugo Cenci, Cheong Xin Chan, Nicole E Wagner, Hwan Su Yoon, Andreas P M Weber, Debashish Bhattacharya

Open Access Publications

Glaucophyta are members of the Archaeplastida, the founding group of photosynthetic eukaryotes that also includes red algae (Rhodophyta), green algae, and plants (Viridiplantae). Here we present a high-quality assembly, built using long-read sequences, of the ca. 100 Mb nuclear genome of the model glaucophyte Cyanophora paradoxa. We also conducted a quick-freeze deep-etch electron microscopy (QFDEEM) analysis of C. paradoxa cells to investigate glaucophyte morphology in comparison to other organisms. Using the genome data, we generated a resolved 115-taxon eukaryotic tree of life that includes a well-supported, monophyletic Archaeplastida. Analysis of muroplast peptidoglycan (PG) ultrastructure using QFDEEM shows that PG is …

Precision Delivery Of Ras-Inhibiting Sirna To Kras Driven Cancer Via Peptide-Based Nanoparticles, Matthew S. Strand, Bradley A. Krasnick, Hua Pan, Xiuli Zhang, Ye Bi, Candace Brooks, Christopher Wetzel, Narendra Sankpal, Timothy Fleming, S Peter Goedegebuure, David G. Denardo, William E. Gillanders, William G. Hawkins, Samuel A. Wickline, Ryan C. Fields

Open Access Publications

Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfering RNA (siRNA) is a promising modality for anti-neoplastic therapy due to its precision and wide range of potential therapeutic targets. Unfortunately, siRNA therapy is limited by low serum half-life, vulnerability to intracellular digestion, and transient …

Spinal V2b Neurons Reveal A Role For Ipsilateral Inhibition In Speed Control, Rebecca A. Callahan, Richard Roberts, Mohini Sengupta, Yukiko Kimura, Shin-Ichi Higashijima, Martha W. Bagnall

Open Access Publications

The spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal alternation between left and right sides or flexors and extensors. However, recent work has shown that inhibition also increases coincident with excitation during contraction. Here, using larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines we define two stable subclasses with distinct neurotransmitter and morphological properties. These V2b subclasses synapse directly onto motor neurons with differential targeting …

Ml277 Specifically Enhances The Fully Activated Open State Of Kcnq1 By Modulating Vsd-Pore Coupling, Panpan Hou, Jingyi Shi, Kelli Mcfarland White, Yuan Gao, Jianmin Cui

Open Access Publications

Upon membrane depolarization, the KCNQ1 potassium channel opens at the intermediate (IO) and activated (AO) states of the stepwise voltage-sensing domain (VSD) activation. In the heart, KCNQ1 associates with KCNE1 subunits to form I

Relationship Between Duration And Extent Of Oedema And Visual Acuity Outcome With Ranibizumab In Diabetic Macular Oedema: A Post Hoc Analysis Of Protocol I Data, Srinivas R Sadda, Joanna Campbell, Pravin U Dugel, Nancy M Holekamp, Szilárd Kiss, Anat Loewenstein, Albert J Augustin, Vanessa Shih, Xiaoshu Xu, Charles C Wykoff, Scott M Whitcup

Open Access Publications

BACKGROUND/OBJECTIVES: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO).

SUBJECTS/METHODS: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each …

A Sparse Covarying Unit That Describes Healthy And Impaired Human Gut Microbiota Development, Arjun S Raman, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Sathish Subramanian, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an "ecogroup" of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of …

Effects Of Microbiota-Directed Foods In Gnotobiotic Animals And Undernourished Children, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Vanderlene L Kung, Jiye Cheng, Robert Y Chen, Sathish Subramanian, Carrie A Cowardin, Martin F Meier, David O'Donnell, Michael Talcott, Larry D Spears, Clay F Semenkovich, Christopher Sawyer, Richard D Head, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF …