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p40phox-Deficient Mice Exhibit Impaired Bacterial Clearance and Enhanced Pro-Inflammatory Responses during Salmonella enterica serovar Typhimurium Infection

January 3, 2018

Summary: In humans, Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important cause of acute gastroenteritis. A critical step in host defense is the generation of reactive oxygen species (ROS) generated from NADPH oxidase. NADPH oxidase has multiple subunits, and mutations in various subunits may contributed to increased susceptibility to infection. Dr. Hai Ning Shi and colleagues, with the assistance of the Genomics and Cell Biology Core, elucidated the importance of the p40phox subunit of NADPH oxidase, demonstrating that mice lacking p40phox are more susceptible to infection with S. Typhimurium, as evidenced by bacterial dissemination to the liver and spleen … Read More »

Categories: Featured News, Publications Tags: Harvard Medical School

Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with Metabolic Disease

October 17, 2017

Summary Chronic inflammation is thought to contribute to obesity-related insulin resistance.  In obesity, adipocytes are an important source of inflammatory cytokines, but the mechanisms of adipose inflammation in obesity remain unclear.  To determine transcriptional regulators of adipose inflammation, Cowan and colleagues compared transcriptional profiles of primary human adipocytes from obese donors with those from in vitro-derived adipocytes that were genetically identical to the primary adipocytes.  Interferon regulatory factor 1 (IRF1) was identified as a mediator of adipocyte inflammation, as it was upregulated in primary adipocytes compared to genetically identical in vitro-derived adipocytes.  Further investigation demonstrated that IRF1 overexpression in adipocytes … Read More »

Categories: Featured News, Publications Tags: Harvard Medical School

Infant nutritional status and markers of environmental enteric dysfunction are associated with midchildhood anthropometry and blood pressure in Tanzania.

October 17, 2017

Summary Childhood undernutrition and growth impairment remain substantial burdens in Sub-Saharan Africa. Environmental enteric dysfunction (EED), a subclinical condition associated with inflammation and malabsorpition in the small intestine, is associated with growth failure. As several studies have demonstrated that individuals with low weight in early childhood are at risk for cardiometabolic disease later in life, NORCH Associate Director Dr. Christopher P. Duggan, NORCH member Dr. Wafaie Fawzi, and others recently investigated whether EED in infancy is associated with cardiovascular risk measures in mid-childhood. Anti-flagellin IgA is a marker for EED and is significantly higher in Tanzanian infants compared to infants … Read More »

Categories: Featured News, Publications Tags: Harvard Medical School

Maternal Weight Gain During Pregnancy Affects the Infant Fecal Microbiota

May 1, 2017

Summary With support from a NORCH Pilot and Feasibility Grant, Dr. Lauren Fiechtner and others recently reported that gestational weight gain affects the composition and diversity of the infant gut microbiome.   Using data and infant fecal samples from 84 infant-mother pairs, four distinct microbiota profiles were identified:  Bifidobacterium-dominant, Enterobacter/Veillonella-dominant, Bacteroides-dominant, and Escherichia-dominant.  Infants whose mothers had more weight gain during pregnancy were less likely to have a Bacteroides-dominant profile (risk ratio 0.83 [95% CI 0.71-0.96] per 1kg of gestational weight gain).  Further, a larger amount of gestational weight gain predicted lower bacterial diversity. Key Findings The degree of maternal weight … Read More »

Categories: Featured News, Publications Tags: Harvard Medical School

Genetic Risk Factors for Some Diseases Tied to Uric Acid

March 31, 2017

Viva La Familia Nutritional Study We once thought of circulating uric acid levels as mainly a biomarker of kidney disease (or a very rich diet), but research over the past decade suggests that higher than normal levels of uric acid can, in fact, be a cause of some cardiovascular or chronic kidney diseases. Uric acid levels are strongly influenced by a person’s genetics and diet, so understanding genetic risk factors will help to identify who needs to be extra careful about what he or she eats. This is the focus of the Voruganti laboratory at the NRI, which applies nutrigenetics … Read More »

Categories: News, Publications Tags: University of North Carolina at Chapel Hill

Influence of Maternal Breast Milk Ingestion on Acquisition of the Intestinal Microbiome in Preterm Infants

March 11, 2017

Summary The development of the intestinal microbiome in premature infants affects gut maturity and may mediate the risk for necrotizing enterocolitis.  Dr. Gregory and colleagues demonstrate that preterm infants who receive expressed breast milk have greater initial bacterial diversity and more gradual acquisition of diversity compared to those who receive formula.  Supplementation with pasteurized donor human milk partially promoted a microbiome similar to that of breast-milk fed infants. Key Findings Feeding with breast milk appears to have a protective effect against gut immaturity in the preterm infant. Citation Gregory KE, Samuel BS, Houghteling P, Shan G, Ausubel FM, Sadreyev RI, … Read More »

Categories: Publications Tags: Harvard Medical School

An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer

March 4, 2017

Summary Metformin is best known as first line treatment for type 2 diabetes, but in recent years it has become clear that it has anti-cancer properties and prolongs lifespan in a variety of model organisms. In spite of these remarkable effects, the mechanism by which metformin produces them remains elusive. NORCH investigator Dr. Alexander Soukas and colleagues determined that metformin kills human cancer cells and prolongs lifespan in the roundworm C. elegans by a common mechanism involving the nuclear pore complex and a gene of unknown function ACAD10. Metformin’s action on mitochondria leads to “closing” of the nuclear pore, reducing … Read More »

Categories: Publications Tags: Harvard Medical School

Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Bone Mineral Density and Marrow Adipose Tissue

March 2, 2017

Summary Through support from a Pilot & Feasibility award, Dr. Elaine Yu and colleagues investigated changes in bone mineral density (BMD) and marrow adipose tissue (MAT) in 20 adults with morbid obesity undergoing Roux-en-Y gastric bypass (RYGB, n=11) or sleeve gastrectomy (SG, n=10).  At 1 year after surgery, mean weight loss was the same between RYGB and SG groups, and mean calcium, 25-hydroxyvitamin D, and PTH levels were unchanged and with normal in both groups.  P1NP and CTX increased in both RYGB and SG groups, and P1NP increased more in the RYGB group.  There were significant declines from baseline in … Read More »

Categories: Publications Tags: Harvard Medical School

Adipose-Derived Circulating miRNAs Regulate Gene Expression in Other Tissues

March 1, 2017

Summary MicroRNAs (miRNAs) are non-coding RNAs that negatively regulate translation and are involved in multiple cellular processes. A large portion of circulating miRNAs are contained in exosomes. Dr. Kahn and colleagues demonstrated that adipose tissue is an important source of circulating miRNAs by showing that mice with an adipose-tissue-specific knockout of the miRNA processing enzyme Dicer have a significantly decreased number of circulating exosomal miRNAs. Further, fat transplantation from normal mice into mice with fat-specific Dicer knockout restores normal levels of circulating miRNAs.  Humans with decreased fat due to lipodystrophy – both HIV-associated and congenital generalized lipodystrophy – also demonstrate significant reductions … Read More »

Categories: Publications Tags: Harvard Medical School

Choice Architecture to Promote Fruit and Vegetable Purchases by Families Participating in the Special Supplemental Program for Women, Infants, and Children (WIC): Randomized Corner Store Pilot Study

February 28, 2017

Summary Through support from a Pilot & Feasibility award, Dr. Anne Thorndike and colleagues assessed the efficacy of a choice architecture intervention in corner stores to increase fruit and vegetable purchase by families participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).  Six stores were randomly assigned to a choice architecture intervention vs. no intervention.  The intervention consisted of consultation with store owners to determine ways to increase the visibility of fruits and vegetables and to provide necessary resources such as new shelving or containers to achieve this goal.  During the intervention period, WIC fruit and … Read More »

Categories: Publications Tags: Harvard Medical School