Extrapulmonary Tuberculosis among Somalis in Minnesota1

To analyze extrapulmonary tuberculosis in Somalis living in Minnesota, we reviewed surveillance and public health case management data on tuberculosis cases in ethnic Somalis in Minnesota from 1993 through 2003. The presence of these recent immigrants substantially affects the local epidemiology and clinical manifestation of tuberculosis

The polyamine diaminodecane (DA-10) produces a voltage-dependent flickery block of single NMDA receptor channels

Receptor binding assays have shown that diaminodecane (DA-10) reduced binding of open channel blockers to the (NMDA) subtype of postsynaptic glutamate receptor through an interaction with the polyamine regulatory site. Because the action of DA-10 was opposite to that of the polyamine agonist spermine and was reversed by polyamine antagonists, DA-10 has been classified as an inverse agonist at the polyamine site. Using whole-cell voltage-clamp and single-channel recordings from cultured rat cortical neurons, we show that at negative holding potentials DA-10 (1-300 [mu]M) reduced NMDA receptor whole cell current (IC50 = 34 [mu]M) and produced a flickery block of NMDA single-channel currents. The flickery block of NMDA single channels was voltage-dependent and not reversed by the polyamine antagonist diethylenetriamine (DET). Potential mechanisms for the flickery block of NMDA single channel currents are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29844/1/0000191.pd

Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons

Gabapentin (GBP) is a cyclic [gamma]-aminobutyric acid (GABA) analog and investigational antiepileptic drug which is effective in the treatment of a variety of human and experimental seizures. GBP's antiepileptic mechanism of action is not known. The present studies tested for effects of GBP on inhibitory (GABA and glycine) and excitatory ( (NMDA) and non-NMDA) amino acid neurotransmitter receptors, on repetitive firing of sodium (Na+) action potentials, and on voltage-dependent calcium (Ca2+) channel currents in cultured rodent neurons using intracellular, whole cell, or single channel recording techniques. GBP did not have a significant effect in any experiment when tested at or above concentrations that are therapeutic in humans except for a variable enhancement of NMDA-evoked depolarizations. These results suggest that the antiepileptic activity of GBP is not due to direct effects at receptors for inhibitory or excitatory amino acids or on voltage-dependent Na+ or Ca2+ channels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30530/1/0000162.pd

Design of the PACIFIC study: A randomized controlled trial evaluating a novel treatment for adults with overweight and obesity.

The majority of adults in the United States have overweight or obesity which is associated with significant health and psychological consequences. Behavioral Weight Loss (BWL) is the current gold-standard weight-loss program for adults but recidivism rates continue to be disturbingly high. Given the health consequences of excess weight and the lack of long-term effectiveness of BWL, it is important to identify novel weight-loss programs. We developed the ROC (Regulation of Cues) program to reduce overeating through improvement in sensitivity to appetitive cues and decreased responsivity to external food cues. This study is a 4-arm randomized control trial designed to evaluate the efficacy of ROC, ROC combined with BWL, BWL alone and an active comparator over 24 months. Study recruitment completed in November 2017. Two hundred and seventy-one participants were randomized (mean age = 46.97 years; 82% female, mean BMI = 34.59; 20% Hispanic) and assessments were conducted at baseline, mid-treatment (6 months) and post-treatment (12 months). At this time, participants are completing 6- (18 months) and 12-month (24 months) follow-ups. Targeting novel mechanisms is critically important to improve weight-loss programs. Through this trial, we hope to identify treatments for adults with overweight and obesity to facilitate long-term weight loss and improved health

Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant

Zonisamide is a novel anticonvulsant that prevents seizures in laboratory animals and in man. Zonisamide (3 [mu]g/ml and above) blocked the sustained firing of action potentials induced by depolarizing steps of current injected across the membrane of intracellularly recorded spinal cord neurons. Responses to GABA and glutamate were not altered by zonisamide, and spontaneous synaptically evoked activity was not reduced until higher concentrations of zonisamide (10[mu]g/ml) were applied.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28029/1/0000468.pd

Fast Benchtop Fabrication of Laminar Flow Chambers for Advanced Microscopy Techniques

Background: Fluid handling technology is acquiring an ever more prominent place in laboratory science whether it is in simple buffer exchange systems, perfusion chambers, or advanced microfluidic devices. Many of these applications remain the providence of laboratories at large institutions with a great deal of expertise and specialized equipment. Even with the expansion of these techniques, limitations remain that frequently prevent the coupling of controlled fluid flow with other technologies, such as coupling microfluidics and high-resolution position and force measurements by optical trapping microscopy. Method: Here we present a method for fabrication of multiple-input laminar flow devices that are optically clear [glass] on each face, chemically inert, reusable, inexpensive, and can be fabricated on the benchtop in approximately one hour. Further these devices are designed to allow flow regulation by a simple gravity method thus requiring no specialized equipment to drive flow. Here we use these devices to perform total internal reflection fluorescence microscopy measurements as well as position sensitive optical trapping experiments. Significance: Flow chamber technology needs to be more accessible to the general scientific community. The method presented here is versatile and robust. These devices use standard slides and coverslips making them compatible with nearly all types and models of light microscopes. These devices meet the needs of groups doing advanced optical trapping experiments, but could also be adapted by nearly any lab that has a function for solution flow coupled with microscopy

The amphibians and reptiles of Luzon Island, Philippines, VIII: the herpetofauna of Cagayan and Isabela Provinces, northern Sierra Madre Mountain Range

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.We provide the first report on the herpetological biodiversity (amphibians and reptiles) of the northern Sierra Madre Mountain Range (Cagayan and Isabela provinces), northeast Luzon Island, Philippines. New data from extensive previously unpublished surveys in the Municipalities of Gonzaga, Gattaran, Lasam, Santa Ana, and Baggao (Cagayan Province), as well as fieldwork in the Municipalities of Cabagan, San Mariano, and Palanan (Isabela Province), combined with all available historical museum records, suggest this region is quite diverse. Our new data indicate that at least 101 species are present (29 amphibians, 30 lizards, 35 snakes, two freshwater turtles, three marine turtles, and two crocodilians) and now represented with well-documented records and/or voucher specimens, confirmed in institutional biodiversity repositories. A high percentage of Philippine endemic species constitute the local fauna (approximately 70%). The results of this and other recent studies signify that the herpetological diversity of the northern Philippines is far more diverse than previously imagined. Thirty-eight percent of our recorded species are associated with unresolved taxonomic issues (suspected new species or species complexes in need of taxonomic partitioning). This suggests that despite past and present efforts to comprehensively characterize the fauna, the herpetological biodiversity of the northern Philippines is still substantially underestimated and warranting of further study

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.

Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex