Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is Nlrp1b/Nalp1b-dependent.

NOD-like receptors (NLRs) are a group of cytoplasmic molecules that recognize microbial invasion or 'danger signals'. Activation of NLRs can induce rapid caspase-1 dependent cell death termed pyroptosis, or a caspase-1 independent cell death termed pyronecrosis. Bacillus anthracis lethal toxin (LT), is recognized by a subset of alleles of the NLR protein Nlrp1b, resulting in pyroptotic cell death of macrophages and dendritic cells. Here we show that LT induces lysosomal membrane permeabilization (LMP). The presentation of LMP requires expression of an LT-responsive allele of Nlrp1b, and is blocked by proteasome inhibitors and heat shock, both of which prevent LT-mediated pyroptosis. Further the lysosomal protease cathepsin B is released into the cell cytosol and cathepsin inhibitors block LT-mediated cell death. These data reveal a role for lysosomal membrane permeabilization in the cellular response to bacterial pathogens and demonstrate a shared requirement for cytosolic relocalization of cathepsins in pyroptosis and pyronecrosis

The supraclavius muscle is a novel muscular anomaly observed in two cases of thoracic outlet syndrome

Various anomalous muscles and fibrofascial structures have been described in relation to the anatomy of thoracic outlet syndrome. We describe two patients with a previously undescribed muscle anomaly, which originated laterally near the trapezius muscle, coursed across the supraclavicular space deep to the scalene fat pad, and attached obliquely to the superior undersurface of the medial clavicle, which we have termed the “supraclavius” muscle. The significance of the supraclavius muscle is unknown, but its occurrence in patients with thoracic outlet syndrome indicates that it can be associated with narrowing of the anatomic space adjacent to the neurovascular structures

Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families

Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both P<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension

Ethnic-Minority Student Opinion Survey

Note: This report was scanned in 2013 for OSR\u27s archives and the scanning is poor. The subject population for this study was Western\u27s undergraduate ethnic-minority students. Besides all being students of color, respondents were primarily female (62.1% vs. 37.9% male), and mostly between 18 and 25 years of age (83.7%). Most were upper-division undergraduates (juniors/seniors 69.0% vs. 26.7% frosh/sophomores). The survey asked students if they had used any of a list of college services. If respondents had used the service, they were asked to describe their level of satisfaction with it, using a five-point scale ranging from very satisfied to very dissatisfied. The college service used most by respondents was the library (90.6%), followed by computer services (76.1%), student health services (75.2%), and food services (74.4%). The college service used least by respondents was personal counseling (20.5%), followed by student health insurance services (21.4%), job placement services (23.1%), and career planning services (29.1%). The college service receiving the highest percentage of satisfied responses (by users only) was recreation and intramural programs and services (76.8%), followed by computer services (73.0%), cultural programs (71.4%), and student employment services (71.2%). The college service receiving the lowest percentage of satisfied responses was parking services (12.3%), followed by food services (35.6%), student health insurance services (40.0%), and residence hall services (45.2%). Two methods were used to add perspective to these findings. The first was to use a prior OIAT student satisfaction survey, one in which gender and class level ratios were similar but had an ethnicity make-up that was nearly entirely white, non-Hispanics. When comparing the surveys, some results were similar; for example, at about 70%, satisfaction with cultural services was about the same in each survey. On the other hand, some results were quite dissimilar. Services that received considerably higher ratings of satisfaction on the Western Experience Survey than on the Ethnic-minority Students Opinion Survey included residence hall services, college-sponsored social programs, intramurals, and personal counseling. Only two services received higher ratings on the Ethnic-minority Students Opinion Survey than on the Western Experience Survey: academic advising and career advising

The X-ray luminous galaxy cluster XMMU J1007.4+1237 at z=1.56 - The dawn of starburst activity in cluster cores

Observational galaxy cluster studies at z>1.5 probe the formation of the first massive M>10^14 Msun dark matter halos, the early thermal history of the hot ICM, and the emergence of the red-sequence population of quenched early-type galaxies. We present first results for the newly discovered X-ray luminous galaxy cluster XMMU J1007.4+1237 at z=1.555, detected and confirmed by the XMM-Newton Distant Cluster Project (XDCP) survey. We selected the system as a serendipitous weak extended X-ray source in XMM-Newton archival data and followed it up with two-band near-infrared imaging and deep optical spectroscopy. We can establish XMMU J1007.4+1237 as a spectroscopically confirmed, massive, bona fide galaxy cluster with a bolometric X-ray luminosity of Lx=(2.1+-0.4)\times 10^44 erg/s, a red galaxy population centered on the X-ray emission, and a central radio-loud brightest cluster galaxy. However, we see evidence for the first time that the massive end of the galaxy population and the cluster red-sequence are not yet fully in place. In particular, we find ongoing starburst activity for the third ranked galaxy close to the center and another slightly fainter object. At a lookback time of 9.4Gyr, the cluster galaxy population appears to be caught in an important evolutionary phase, prior to full star-formation quenching and mass assembly in the core region. X-ray selection techniques are an efficient means of identifying and probing the most distant clusters without any prior assumptions about their galaxy content.Comment: 6 pages, 3 color figures, accepted for publication in A&