Salt ups antibiotic resistance
Acinetobacter baumannii – a bacterial pathogen nicknamed “Iraqibacter” because of the number of infections it has caused in soldiers wounded in Iraq – is rapidly becoming a leading cause of hospital-acquired infections. A. baumannii easily acquires resistance to antibiotics, making it notoriously difficult to treat.
Eric Skaar, Ph.D., Indriati Hood and colleagues sought to identify signals in the hospital setting or human host that contribute to antibiotic resistance in A. baumannii. They found that exposure to sodium chloride (salt) – at physiological levels found in the human body – increases A. baumannii resistance to four different classes of antibiotics. Sodium chloride triggers a gene expression program that increases the production of proteins that “pump” antibiotics out of the bacteria. The findings, reported in the journal Antimicrobial Agents and Chemotherapy, suggest that simply growing inside the human body may make A. baumannii resistant to antibiotics and hinder treatment of infections. Identifying the bacterial systems that sense and respond to sodium chloride could point to novel therapeutic targets.
— Leigh MacMillan
Stressful signals in the amygdala
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Psychiatry resident Sachin Patel, M.D., Ph.D., and colleagues examined the effect of restraint stress on endocannabinoid function in the mouse basolateral amygdala (BLA), a brain region that regulates stress responses and emotion. They found that repeated, but not acute, restraint stress prolonged depolarization-induced suppression of inhibition, a measure of endocannabinoid activity. Repeated restraint stress also increased 2-arachidonyoylglycerol (2-AG) – one of two main types of endocannabinoid – and its precursors in the BLA. The results, published in the December issue of Neuropsychopharmacology, suggest that these adaptations could contribute to stress-induced aggravation of neuropsychiatric disorders.
— Melissa Marino
Beta-cell bump
During pregnancy, the mass of insulin-producing beta-cells in the pancreas increases by about 50 percent to meet physiologic demands. Placental lactogens (PL) stimulate beta-cell proliferation, but the molecular regulators responding to PL are unknown. Understanding how beta-cell mass changes could lead to strategies for enhancing beta-cell proliferation as a treatment for gestational and type 2 diabetes.
Hongjie Zhang, M.D., Ph.D., Jia Zhang, Maureen Gannon, Ph.D., and colleagues examined the role of FoxM1 – a protein they previously showed was important for beta-cell mass expansion during normal growth – in pregnancy-induced beta-cell proliferation. They examined virgin, pregnant and postpartum control mice and mice missing the FoxM1 gene in the pancreas. Beta-cell proliferation did not increase during pregnancy in the mutant mice, resulting in gestational diabetes as pregnancy progressed. In addition, they found that PL works through FoxM1 to stimulate beta-cell proliferation. The findings, reported in the January issue of Diabetes, are the first to identify FoxM1 as a downstream effector of PL in beta-cell proliferation in vivo.
— Leigh MacMillan
Atf4: Good for growing bones
During early fetal development, our fragile skeletons are made of cartilage. In the long bones, this cartilage is gradually replaced with bone through the process of endochondral ossification. Previously, Xiangli Yang, Ph.D., and colleagues found that mice deficient in the transcription factor Atf4 had severe skeletal defects, overall short stature and short limbs, suggesting a defect in endochondral bone formation. Because this process relies on the proliferation and differentiation of chondrocytes (cartilage cells), the researchers examined Atf4’s function in these cells.
In the Dec. 15 issue of Development, the Vanderbilt Center for Bone Biology investigators report that Atf4 deletion disrupts development of the growth plate (the cartilage plate near the ends of growing long bones) and subsequent ossification. Additionally, they found that Atf4 is required for the expression of Indian Hedgehog, a protein that regulates skeletal development. The results suggest that Atf4 may pace long bone growth by controlling proliferation and differentiation of growth plate chondrocytes and may offer new insights into skeletal repair and disorders of skeletal development, such as dwarfism.
— Melissa Marino
We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.
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