Microvascular Perfusion Abnormalities of the Thalamus in Painful but Not Painless Diabetic Polyneuropathy: A clue to the pathogenesis of pain in type 1 diabetes

OBJECTIVE The pathogenesis of painful diabetic neuropathy (DN) remains undetermined, with both central and peripheral mechanisms implicated. This study investigates whether thalamic perfusion abnormalities occur in painful DN. RESEARCH DESIGN AND METHODS Eighteen subjects with type 1 diabetes (no DN = 6, painful DN = 5, painless DN = 7) and six healthy volunteers (HV) were recruited. Microvascular perfusion characteristics (relative cerebral blood volume [rCBV], flow [rCBF], and transit time [ttFM]) of the thalamus and caudate nucleus were assessed using magnetic resonance perfusion imaging. The caudate nucleus was chosen to serve as an in vivo control region. RESULTS Subjects with painful DN had significantly greater thalamic rCBV (means [SD]; painful DN, 228.7 [19.5]; no DN, 202.3 [25.8]; painless DN, 216.5 [65.5]; HV, 181.9 [51.7]; P = 0.04) and the longest ttFM(s) (painful DN, 38.4 [3.6]; no DN, 35.3 [13.2]; painless DN, 35.9 [13.7]; HV, 33.7 [14.9]; P = 0.07). There was no significant difference in markers of caudate nucleus perfusion. CONCLUSIONS Painful DN is associated with increased thalamic vascularity. This may provide an important clue to the pathogenesis of pain in DN

Coronavirus 2019 Disease (COVID‐19), Systemic Inflammation, and Cardiovascular Disease

n/

Impaired Redox Signaling in Huntington’s Disease: Therapeutic Implications

Huntington’s disease (HD) is a neurodegenerative disease triggered by expansion of polyglutamine repeats in the protein huntingtin. Mutant huntingtin (mHtt) aggregates and elicits toxicity by multiple mechanisms which range from dysregulated transcription to disturbances in several metabolic pathways in both the brain and peripheral tissues. Hallmarks of HD include elevated oxidative stress and imbalanced redox signaling. Disruption of antioxidant defense mechanisms, involving antioxidant molecules and enzymes involved in scavenging or reversing oxidative damage, have been linked to the pathophysiology of HD. In addition, mitochondrial function is compromised in HD leading to impaired bioenergetics and elevated production of free radicals in cells. However, the exact mechanisms linking redox imbalance to neurodegeneration are still elusive. This review will focus on the current understanding of aberrant redox homeostasis in HD and potential therapeutic interventions

Symplectic cohomology and q-intersection numbers

Given a symplectic cohomology class of degree 1, we define the notion of an equivariant Lagrangian submanifold. The Floer cohomology of equivariant Lagrangian submanifolds has a natural endomorphism, which induces a grading by generalized eigenspaces. Taking Euler characteristics with respect to the induced grading yields a deformation of the intersection number. Dehn twists act naturally on equivariant Lagrangians. Cotangent bundles and Lefschetz fibrations give fully computable examples. A key step in computations is to impose the "dilation" condition stipulating that the BV operator applied to the symplectic cohomology class gives the identity. Equivariant Lagrangians mirror equivariant objects of the derived category of coherent sheaves.Comment: 32 pages, 9 figures, expanded introduction, added details of example 7.5, added discussion of sign

Observed multivariable signals of late 20th and early 21st century volcanic activity

The relatively muted warming of the surface and lower troposphere since 1998 has attracted considerable attention. One contributory factor to this “warming hiatus” is an increase in volcanically induced cooling over the early 21st century. Here we identify the signals of late 20th and early 21st century volcanic activity in multiple observed climate variables. Volcanic signals are statistically discernible in spatial averages of tropical and near-global SST, tropospheric temperature, net clear-sky short-wave radiation, and atmospheric water vapor. Signals of late 20th and early 21st century volcanic eruptions are also detectable in near-global averages of rainfall. In tropical average rainfall, however, only a Pinatubo-caused drying signal is identifiable. Successful volcanic signal detection is critically dependent on removal of variability induced by the El Nino–Southern Oscillation.National Science Foundation (U.S.) (Grant AGS-1342810

Benign mesenteric lymphangioma presenting as acute pancreatitis: a case report

Benign mesenteric lymphangiomas are rare intra-abdominal cysts which may be asymptomatic or present with a variety of abdominal symptoms including an acute abdomen. We are however not aware of any reports in the literature linking mesenteric lymphangioma to acute pancreatitis. We present the case of a 62-year-old man who was admitted with signs and symptoms of acute pancreatitis and a palpable abdominal mass. Computerised tomography (CT) of his abdomen confirmed the presence of a mesenteric cystic mass. He underwent a laparotomy at which a large thin walled mass filled with a chylous fluid was resected. Histological analysis of this cyst showed it to be a benign mesenteric lymphangioma

DUF2285 is a novel helix-turn-helix domain variant that orchestrates both activation and antiactivation of conjugative element transfer in proteobacteria.

Horizontal gene transfer is tightly regulated in bacteria. Often only a fraction of cells become donors even when regulation of horizontal transfer is coordinated at the cell population level by quorum sensing. Here, we reveal the widespread 'domain of unknown function' DUF2285 represents an 'extended-turn' variant of the helix-turn-helix domain that participates in both transcriptional activation and antiactivation to initiate or inhibit horizontal gene transfer. Transfer of the integrative and conjugative element ICEMlSymR7A is controlled by the DUF2285-containing transcriptional activator FseA. One side of the DUF2285 domain of FseA has a positively charged surface which is required for DNA binding, while the opposite side makes critical interdomain contacts with the N-terminal FseA DUF6499 domain. The QseM protein is an antiactivator of FseA and is composed of a DUF2285 domain with a negative surface charge. While QseM lacks the DUF6499 domain, it can bind the FseA DUF6499 domain and prevent transcriptional activation by FseA. DUF2285-domain proteins are encoded on mobile elements throughout the proteobacteria, suggesting regulation of gene transfer by DUF2285 domains is a widespread phenomenon. These findings provide a striking example of how antagonistic domain paralogues have evolved to provide robust molecular control over the initiation of horizontal gene transfer

Chemical Heterogeneity on Mercury's Surface Revealed by the MESSENGER X-Ray Spectrometer

We present the analysis of 205 spatially resolved measurements of the surface composition of Mercury from MESSENGER's X-Ray Spectrometer. The surface footprints of these measurements are categorized according to geological terrain. Northern smooth plains deposits and the plains interior to the Caloris basin differ compositionally from older terrain on Mercury. The older terrain generally has higher Mg/Si, S/Si, and Ca/Si ratios, and a lower Al/Si ratio than the smooth plains. Mercury's surface mineralogy is likely dominated by high-Mg mafic minerals (e.g., enstatite), plagioclase feldspar, and lesser amounts of Ca, Mg, and/or Fe sulfides (e.g., oldhamite). The compositional difference between the volcanic smooth plains and the older terrain reflects different abundances of these minerals and points to the crystallization of the smooth plains from a more chemically evolved magma source. High-degree partial melts of enstatite chondrite material provide a generally good compositional and mineralogical match for much of the surface of Mercury. An exception is Fe, for which the low surface abundance on Mercury is still higher than that of melts from enstatite chondrites and may indicate an exogenous contribution from meteoroid impacts

A Clinical Trial to Validate Event-Related Potential Markers of Alzheimer\u27s Disease in Outpatient Settings

INTRODUCTION: We investigated whether event-related potentials (ERP) collected in outpatient settings and analyzed with standardized methods can provide a sensitive and reliable measure of the cognitive deficits associated with early Alzheimer\u27s disease (AD). METHODS: A total of 103 subjects with probable mild AD and 101 healthy controls were recruited at seven clinical study sites. Subjects were tested using an auditory oddball ERP paradigm. RESULTS: Subjects with mild AD showed lower amplitude and increased latency for ERP features associated with attention, working memory, and executive function. These subjects also had decreased accuracy and longer reaction time in the target detection task associated with the ERP test. DISCUSSION: Analysis of ERP data showed significant changes in subjects with mild AD that are consistent with the cognitive deficits found in this population. The use of an integrated hardware/software system for data acquisition and automated data analysis methods make administration of ERP tests practical in outpatient settings