Novel Secretion Apparatus Maintains Spore Integrity and Developmental Gene Expression in Bacillus subtilis

Sporulation in Bacillus subtilis involves two cells that follow separate but coordinately regulated developmental programs. Late in sporulation, the developing spore (the forespore) resides within a mother cell. The regulation of the forespore transcription factor σG that acts at this stage has remained enigmatic. σG activity requires eight mother-cell proteins encoded in the spoIIIA operon and the forespore protein SpoIIQ. Several of the SpoIIIA proteins share similarity with components of specialized secretion systems. One of them resembles a secretion ATPase and we demonstrate that the ATPase motifs are required for σG activity. We further show that the SpoIIIA proteins and SpoIIQ reside in a multimeric complex that spans the two membranes surrounding the forespore. Finally, we have discovered that these proteins are all required to maintain forespore integrity. In their absence, the forespore develops large invaginations and collapses. Importantly, maintenance of forespore integrity does not require σG. These results support a model in which the SpoIIIA-SpoIIQ proteins form a novel secretion apparatus that allows the mother cell to nurture the forespore, thereby maintaining forespore physiology and σG activity during spore maturation

Diatom control of the autotrophic community and particle export in the eastern Bering Sea during the recent cold years (2008–2010)

The southeastern Bering Sea has exhibited shifts in climate since the start of the 21st century. The regional climate shifts are manifested in the duration and areal extent of seasonal sea-ice coverage. During a recent cold period (2008–2010) with extensive spring sea-ice cover over the southeastern shelf of the Bering Sea, a total of 77 water column and 24 sediment trap profiles were collected over the shelf and shelf break and analyzed for autotrophic pigment concentrations and elemental (carbon, nitrogen, phosphorus, and silicon) concentrations in suspended and exported particulate material. These results are used to establish the seasonal succession of the autotrophic community and the control that both phytoplankton and zooplankton exert on export production. In spring (April to mid-June), total chlorophyll a (TChl a) concentrations were generally low (i.e., \u3c 1 μg L–1); however, localized phytoplankton blooms near the marginal ice zone (MIZ) lead to elevated spring average TChl a concentrations (i.e., \u3e5 μg L–1). In summer (mid-June to late July), photic zone chlorophyll a concentrations were typically \u3c1 μg L–1 over the shelf and at the shelf break. Diatoms represented the greatest contribution to TChl a (regional averages of 71%–96% in spring and 25%–75% in summer) and autotrophic biomass in spring and summer. This algal class also represented 50%–99% of TChl a associated with particles sinking from the photic zone. The relatively high proportion of phaeophorbide a in sediment trap material indicates that sinking of zooplankton fecal pellets facilitate the export of particles through the water column. Further, zooplankton grazing may be an important process that returns regenerated nutrients to the water column based on the elemental composition of suspended and sinking particles. In colder than average years, the emergence of diatom blooms in the spring MIZ supports the production of abundant large zooplankton, which are a primary food source for juvenile pelagic fishes of economically important species. Therefore, processes in colder than average years may be essential for the transfer of particulate organic carbon from the surface waters and the success of the economically important pelagic fisheries

The Stellar Populations of Stripped Spiral Galaxies in the Virgo Cluster

(Abridged) We present an analysis of the stellar populations of the gas-stripped outer disks of ten Virgo Cluster spiral galaxies, utilizing SparsePak integral field spectroscopy on the WIYN 3.5m telescope and GALEX UV photometry. The galaxies in our sample show evidence for being gas-stripped spiral galaxies, with star formation within a truncation radius, and a passive population beyond the truncation radius. We find that all of the galaxies with spatially truncated star formation have outer disk stellar populations consistent with star formation ending within the last 500 Myr. The synthesis of optical spectroscopy and GALEX observations demonstrate that star formation was relatively constant until the quenching time, after which the galaxies passively evolved. Large starbursts at the time of quenching are excluded for all galaxies. For approximately half of our galaxies, timescales derived from our observations are consistent with galaxies being stripped in or near the cluster core, where simple ram-pressure estimates can explain the stripping. However, the other half of our sample galaxies were clearly stripped outside the cluster core. Such galaxies provide evidence that the intra-cluster medium is not static and smooth. For three of our sample galaxies, our stripping timescales agree with those from the gas stripping simulations, suggesting that star formation is quenched near the time of peak pressure. While the stripping of star-forming gas in the outer disk creates a passive population in our galaxies, there is still normal star formation in the center of our sample galaxies. It may be that Virgo is not massive enough to completely strip these spiral galaxies and, in a more dynamically active cluster or a cluster with a higher density ICM, such a process would lead to passive spirals and/or S0s.Comment: 17 pages, 19 figures, accepted for publication in AJ. Replaced submission corrects Table names and matches figure style of Journal articl

An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.

BackgroundType 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed.MethodsWe conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals.ResultsA total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed.ConclusionsTeplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.)

AEGIS: Demographics of X-ray and Optically Selected AGNs

We develop a new diagnostic method to classify galaxies into AGN hosts, star-forming galaxies, and absorption-dominated galaxies by combining the [O III]/Hbeta ratio with rest-frame U-B color. This can be used to robustly select AGNs in galaxy samples at intermediate redshifts (z<1). We compare the result of this optical AGN selection with X-ray selection using a sample of 3150 galaxies with 0.3<z<0.8 and I_AB<22, selected from the DEEP2 Galaxy Redshift Survey and the All-wavelength Extended Groth Strip International Survey (AEGIS). Among the 146 X-ray sources in this sample, 58% are classified optically as emission-line AGNs, the rest as star-forming galaxies or absorption-dominated galaxies. The latter are also known as "X-ray bright, optically normal galaxies" (XBONGs). Analysis of the relationship between optical emission lines and X-ray properties shows that the completeness of optical AGN selection suffers from dependence on the star formation rate and the quality of observed spectra. It also shows that XBONGs do not appear to be a physically distinct population from other X-ray detected, emission-line AGNs. On the other hand, X-ray AGN selection also has strong bias. About 2/3 of all emission-line AGNs at L_bol>10^44 erg/s in our sample are not detected in our 200 ks Chandra images, most likely due to moderate or heavy absorption by gas near the AGN. The 2--7 keV detection rate of Seyfert 2s at z~0.6 suggests that their column density distribution and Compton-thick fraction are similar to that of local Seyferts. Multiple sample selection techniques are needed to obtain as complete a sample as possible.Comment: 24 pages, 14 figures, submitted to ApJ. Version 2 matches the ApJ accepted version. Sec 3 was reorganized and partly rewritten with one additional figure (Fig.3

Integrating depth of invasion in T classification improves the prognostic performance of the American Joint Committee on Cancer primary tumor staging system for cutaneous squamous cell carcinoma of the head and neck

BACKGROUND: The last revision of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual included a specific system for cutaneous squamous cell carcinoma (CSCC) of the head and neck. Here, we assessed the prognostic performance of six candidate modified T-classification models in head and neck CSCC patients. METHODS: Analysis of 916 patients with head and neck CSCC given treatment with curative intent at The University of Texas MD Anderson Cancer Center between 1995 and 2019 was performed. The main outcome was disease-specific survival (DSS), and the impact of depth of invasion (DOI) was analyzed using multivariable regression models. Candidate models were developed using the optimal DOI cut points for each AJCC T classification based on goodness of fit of the model and the simplicity of the model. Staging systems were compared using Harrell\u27s concordance index. RESULTS: Median age was 70 years (range, 19-97years) and median follow-up time of 22 months (range, 1-250months). The median DOI was 6.0 mm (range, 0.1-70.0 mm). The five-year DSS rate was 80.7% (95%CI, 77.4-83.7%). We found significant association between DOI (hazard ratio, 1.21 [95%CI: 1.01-1.43]) and DSS on multivariable analysis. Based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves, model 6 surpassed the AJCC staging system. CONCLUSIONS: Incorporation of DOI in the current AJCC staging system improves discrimination of T classifications in head and neck CSCC patients. LAY SUMMARY: The current staging system for head and neck cutaneous squamous cell carcinoma demonstrates wide prognostic variability and provides suboptimal risk stratification. Incorporation of depth of invasion in the T-classification system improves risk prediction and patient counseling. PRECIS: We propose improved head and neck cutaneous squamous cell carcinoma T staging that will include depth of invasion and should be considered in future versions of the American Joint Committee on Cancer after external validation

beta-alanine supplementation improves tactical performance but not cognitive function in combat soldiers

Background: There are no known studies that have examined beta-alanine supplementation in military personnel. Considering the physiological and potential neurological effects that have been reported during sustained military operations, it appears that beta-alanine supplementation may have a potential benefit in maintaining physical and cognitive performance during high-intensity military activity under stressful conditions. The purpose of this study was to examine the effect of 28 days of beta-alanine ingestion in military personnel while fatigued on physical and cognitive performance. Methods: Twenty soldiers (20.1 +/- 0.9 years) from an elite combat unit were randomly assigned to either a beta-alanine ( BA) or placebo (PL) group. Soldiers were involved in advanced military training, including combat skill development, navigational training, self-defense/hand-to-hand combat and conditioning. All participants performed a 4-km run, 5-countermovement jumps using a linear position transducer, 120-m sprint, a 10-shot shooting protocol with assault rifle, including overcoming a misfire, and a 2-min serial subtraction test to assess cognitive function before (Pre) and after ( Post) 28 days of supplementation. Results: The training routine resulted in significant increases in 4-km run time for both groups, but no between group differences were seen (p = 0.597). Peak jump power at Post was greater for BA than PL (p = 0.034), while mean jump power for BA at Post was 10.2% greater (p = 0.139) than PL. BA had a significantly greater (p = 0.012) number of shots on target at Post (8.2 +/- 1.0) than PL (6.5 +/- 2.1), and their target engagement speed at Post was also significantly faster (p = 0.039). No difference in serial subtraction performance was seen between the groups (p = 0.844). Conclusion: Results of this study indicate that 4-weeks of beta-alanine ingestion in young, healthy soldiers did not impact cognitive performance, but did enhance power performance, marksmanship and target engagement speed from pre-ingestion levels

Caught in the Act: Strong, Active Ram Pressure Stripping in Virgo Cluster Spiral NGC 4330

We present a multi-wavelength study of NGC 4330, a highly-inclined spiral galaxy in the Virgo Cluster which is a clear example of strong, ongoing ICM-ISM ram pressure stripping. The HI has been removed from well within the undisturbed old stellar disk, to 50% - 65% of R_25. Multi-wavelength data (WIYN BVR and H-alpha, VLA 21-cm HI and radio continuum, and GALEX NUV and FUV) reveal several one-sided extraplanar features likely caused by ram pressure at an intermediate disk-wind angle. At the leading edge of the interaction, the H-alpha and dust extinction curve sharply out of the disk in a remarkable and distinctive "upturn" feature that may be generally useful as a diagnostic indicator of active ram pressure. On the trailing side, the ISM is stretched out in a long tail which contains 10% of the galaxy's total HI emission, 6 - 9% of its NUV-FUV emission, but only 2% of the H-alpha. The centroid of the HI tail is downwind of the UV/H-alpha tail, suggesting that the ICM wind has shifted most of the ISM downwind over the course of the past 10 - 300 Myr. Along the major axis, the disk is highly asymmetric in the UV, but more symmetric in H-alpha and HI, also implying recent changes in the distributions of gas and star formation. The UV-optical colors indicate very different star formation histories for the leading and trailing sides of the galaxy. On the leading side, a strong gradient in the UV-optical colors of the gas-stripped disk suggests that it has taken 200-400 Myr to strip the gas from a radius of >8 to 5 kpc, but on the trailing side there is no age gradient. All our data suggest a scenario in which NGC 4330 is falling into cluster center for first time and has experienced a significant increase in ram pressure over the last 200-400 Myr.Comment: AJ accepted; 22 pages, 25 figures, version with full-resolution figures available at http://www.astro.yale.edu/abramso

An Analysis of Public Attitudes Toward the Insanity Defense

Results from a public opinion survey of knowledge, attitudes, and support for the insanity defense indicate that people dislike the insanity defense for both retributive and utilitarian reasons: they want insane law-breakers punished, and they believe that insanity defense procedures fail to protect the public. However, people vastly overestimate the use and success of the insanity plea. Several attitudinal and demographic variables that other researchers have found to be associated with people\u27s support for the death penalty and perceptions of criminal sentencing are also related to support for the insanity defense. Implications for public policy are discussed

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts