The chemical reactivity of acyl glucuronide (AG) has been thought to be associated with the toxic properties of drugs containing carboxylic acid moieties, but there has been no direct evidence showing that AG formation is related to the observed toxicity. In the present study, the cytotoxicity of AGs, especially that associated with the inflammatory response, was investigated. The changes in th...

Inflammasomes are cytosolic multiprotein complexes that sense microbial infection and trigger cytokine production and cell death. However, the molecular components of inflammasomes and what they sense remain poorly defined. Here we demonstrate that 35 amino acids of the carboxyl terminus of flagellin triggered inflammasome activation in the absence of bacterial contaminants or secretion systems...

The selective forces that played a role in the evolution of the musculoskeletal system of the genus Homo have long been debated and remain poorly understood. In this investigation, we introduce a new approach for testing alternative hypotheses. Our analysis is based on the premise that natural selection can be expected to have resulted in muscles that are large enough to achieve necessary level...

Deeper insight into the molecular pathways that orchestrate skeletal myogenesis should enhance our understanding of, and ability to treat, human skeletal muscle disease. It is now widely appreciated that nutrients, such as molecular oxygen (O2), modulate skeletal muscle formation. During early stages of development and regeneration, skeletalmuscle progenitors reside in lowO2environments before ...

Department of Cognitive, Linguistic & Psychological Sciences, Brown University, Providence, RI 02906; Department of Psychiatry, The University of Texas at Austin, Austin, TX 78712; Department of Psychology, New York University, New York, NY 10003; Department of Psychology, Princeton University, Princeton, NJ; Center for Neural Science, New York University, New York, NY 10003; and Emotional Brai...

Background-—Magnetic resonance imaging of carotid plaque can aid in stroke risk stratification in patients with carotid stenosis. However, the prevalence of complicated carotid plaque in patients with cryptogenic stroke is uncertain, especially as assessed by plaque imaging techniques routinely included in acute stroke magnetic resonance imaging protocols. We assessed whether the magnetic reson...

DISRUPTED-IN-SCHIZOPHRENIA (DISC1) has been one of themost intensively studied genetic risk factors for mental illness since it was discovered throughpositionalmappingofa translocationbreakpoint ina largeScottish family where a balanced chromosomal translocationwas found to segregate with schizophrenia and affective disorders. While the evidence for it being central to disease pathogenesis in t...

1KIRTHI SATHYAKUMAR, MD, 1ANURADHA CHANDRAMOHAN, MD, FRCR, 2DIPTI MASIH, MD, 3MARK RANJAN JESUDASAN, MS, 2ANNA PULIMOOD, MD and 1ANU EAPEN, DMRD, DNB Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, India Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India Department of General and Colorectal Surgery, Unit II, Christian Medical College, Vellore...

Motivation: Validation and reproducibility of results is a central and pressing issue in genomics. Several recent embarrassing incidents involving the irreproducibility of high-profile studies have illustrated the importance of this issue and the need for rigorous methods for the assessment of reproducibility. Results: Here, we describe an existing statistical model that is very well suited to ...

At mammalian body temperature, the plague bacillus Yersinia pestis synthesizes lipopolysaccharide (LPS)–lipid A with poor Tolllike receptor 4 (TLR4)–stimulating activity. To address the effect of weak TLR4 stimulation on virulence, we modified Y. pestis to produce a potent TLR4-stimulating LPS. Modified Y. pestis was completely avirulent after subcutaneous infection even at high challenge doses...