Physical profile of Air Force Special Warfare trainees

International Journal of Exercise Science 16(4): 924-931, 2023. Physical fitness testing in the military is commonly used to assess whether service members are physically capable of performing the diverse physical tasks that may be required for their job. Body composition can influence an individual’s ability to physically perform. This study aimed to analyze the general physical profile of U.S. Air Force (USAF) special warfare candidates by assessing body composition results and physical assessment scores collected over the past four years. Male candidates (n = 1036) were 18.2 years to 39.5 years of age (M = 23.5, SD = 3.9) and weighed 78.8 kg (SD = 8.3) with a BMI of 25.0 (SD = 2.0) at 11.8% body fat (SD = 3.3) as measured using bioelectrical impedance. Body composition and fitness scores were similar to those noted in U.S. Navy special warfare candidates as well as individuals in other elite tactical units. These results highlight the normative body composition profile of individuals assessing for advanced military career fields

Translational control of the SigR-directed oxidative stress response in streptomyces via IF3-mediated repression of a noncanonical GTC start codon

The major oxidative stress response in Streptomyces is controlled by the sigma factor SigR and its cognate antisigma factor RsrA, and SigR activity is tightly controlled through multiple mechanisms at both the transcriptional and posttranslational levels. Here we show that sigR has a highly unusual GTC start codon and that this leads to another level of SigR regulation, in which SigR translation is repressed by translation initiation factor 3 (IF3). Changing the GTC to a canonical start codon causes SigR to be overproduced relative to RsrA, resulting in unregulated and constitutive expression of the SigR regulon. Similarly, introducing IF3* mutations that impair its ability to repress SigR translation has the same effect. Thus, the noncanonical GTC sigR start codon and its repression by IF3 are critical for the correct and proper functioning of the oxidative stress regulatory system. sigR and rsrA are cotranscribed and translationally coupled, and it had therefore been assumed that SigR and RsrA are produced in stoichiometric amounts. Here we show that RsrA can be transcribed and translated independently of SigR, present evidence that RsrA is normally produced in excess of SigR, and describe the factors that determine SigR-RsrA stoichiometry.IMPORTANCE In all sigma factor-antisigma factor regulatory switches, the relative abundance of the two proteins is critical to the proper functioning of the system. Many sigma-antisigma operons are cotranscribed and translationally coupled, leading to a generic assumption that the sigma and antisigma factors are produced in a fixed 1:1 ratio. In the case of sigR-rsrA, we show instead that the antisigma factor is produced in excess over the sigma factor, providing a buffer to prevent spurious release of sigma activity. This excess arises in part because sigR has an extremely rare noncanonical GTC start codon, and as a result, SigR translation initiation is repressed by IF3. This finding highlights the potential significance of noncanonical start codons, very few of which have been characterized experimentally. It also emphasizes the limitations of predicting start codons using bioinformatic approaches, which rely heavily on the assumption that ATG, GTG, and TTG are the only permissible start codons

Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma. Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507. Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached. Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted

Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Na\uefve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study

\ua92023 The Authors; Published by the American Association for Cancer Research. PURPOSE: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). PATIENTS AND METHODS: In this open-label, multicenter study, PARP inhibitor-na\uefve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). RESULTS: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1-97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5-43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2-86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. CONCLUSIONS: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified

Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks

Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls γH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes γH2AX spreading. Remarkably, depletion of cohesin leads to an increase of γH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome

Wettability decay in an oil-contaminated waste-mineral mixture with dry-wet cycles

The dependency of soil particle wettability on soil water content implies that soils subjected to drying-wetting cycles become wettable with wetting and water repellent with drying. While this has been demonstrated widely, the results are contradictory when water repellent soils are subjected to a sequence of cycles. Added to this, past wettability measurements were seldom done in batches of samples collected from the field at natural or dry water contents, with little appreciation that slight particle size variations, different drying-wetting histories and fabric (as required by different wettability measurement methods) may alter the results. This note presents soil particle wettability—soil water content relations by means of an index test following staged drying and wetting paths over a period of 8 months for an untreated, oil-contaminated anthropogenic soil (a mixture of slag, coal particles, fly ash and mineral particles) from Barry Docks (UK), a site formally used for oil storage, which is to be remediated and redeveloped for housing. The results revealed a decrease in the water repellency and increasing mineralization and bacterial activity with the wetting and drying cycles.postprin

Neonatal CD8 T-cell Hierarchy Is Distinct from Adults and Is Influenced by Intrinsic T cell Properties in Respiratory Syncytial Virus Infected Mice

Following respiratory syncytial virus infection of adult CB6F1 hybrid mice, a predictable CD8+ T cell epitope hierarchy is established with a strongly dominant response to a Kd-restricted peptide (SYIGSINNI) from the M2 protein. The response to KdM282-90 is ∼5-fold higher than the response to a subdominant epitope from the M protein (NAITNAKII, DbM187-195). After infection of neonatal mice, a distinctly different epitope hierarchy emerges with codominant responses to KdM282-90 and DbM187-195. Adoptive transfer of naïve CD8+ T cells from adults into congenic neonates prior to infection indicates that intrinsic CD8+ T cell factors contribute to age-related differences in hierarchy. Epitope-specific precursor frequency differs between adults and neonates and influences, but does not predict the hierarchy following infection. Additionally, dominance of KdM282-90 –specific cells does not correlate with TdT activity. Epitope-specific Vβ repertoire usage is more restricted and functional avidity is lower in neonatal mice. The neonatal pattern of codominance changes after infection at 10 days of age, and rapidly shifts to the adult pattern of extreme KdM282- 90 -dominance. Thus, the functional properties of T cells are selectively modified by developmental factors in an epitope-specific and age-dependent manner

A step towards mobile arsenic measurement for surface waters.

Surface modified quantum dots (QDs) are studied using a bio-inspired cysteine rich ligand (glutathione, GSH) and their quenching response and selectivity to arsenic examined. As predicted from As(3+) binding with highly crosslinked phytochelatin-(PCn)-like molecules, better arsenic selectivity is obtained for a thicker more 3-dimensional GSH surface layer, with exposed sulfhydryl groups. A detection limit of at least 10 μM can be achieved using CdSe/ZnS core-shell QDs capped with this GSH structure. The system is also demonstrated using a mobile phone camera to record the measurement, producing a detection limit of 5 μM. However, copper remains the main interferent of concern. Water-soluble CdTe QDs show little sensitivity to As(3+) even with a GSH surface, but they remain sensitive to Cu(2+), allowing a copper baseline to be established from the CdTe measurement. Despite anticipating that spectrally non overlapping fluorescence would be required from the two types of QDs to achieve this, a method is demonstrated using RGB channels from a mobile phone and processing the raw data for CdTe QDs, with an emission wavelength of 600 nm, and CdSe/ZnS QDs, with emission maximum of 630 nm. It is shown that As(3+) measurement remains feasible at the WHO guideline value of 10 μg L(-1) up to a copper concentration of around 0.3 μM Cu(2+), which corresponds to the highest recorded level in a selection of large rivers world-wide.This is the author accepted manuscript. The final version is available via RSC at http://pubs.rsc.org/en/Content/ArticleLanding/2015/AN/c4an02368d#!divAbstract

Individual Attachment Style Modulates Human Amygdala and Striatum Activation during Social Appraisal

Adult attachment style refers to individual personality traits that strongly influence emotional bonds and reactions to social partners. Behavioral research has shown that adult attachment style reflects profound differences in sensitivity to social signals of support or conflict, but the neural substrates underlying such differences remain unsettled. Using functional magnetic resonance imaging (fMRI), we examined how the three classic prototypes of attachment style (secure, avoidant, anxious) modulate brain responses to facial expressions conveying either positive or negative feedback about task performance (either supportive or hostile) in a social game context. Activation of striatum and ventral tegmental area was enhanced to positive feedback signaled by a smiling face, but this was reduced in participants with avoidant attachment, indicating relative impassiveness to social reward. Conversely, a left amygdala response was evoked by angry faces associated with negative feedback, and correlated positively with anxious attachment, suggesting an increased sensitivity to social punishment. Secure attachment showed mirror effects in striatum and amygdala, but no other specific correlate. These results reveal a critical role for brain systems implicated in reward and threat processing in the biological underpinnings of adult attachment style, and provide new support to psychological models that have postulated two separate affective dimensions to explain these individual differences, centered on the ventral striatum and amygdala circuits, respectively. These findings also demonstrate that brain responses to face expressions are not driven by facial features alone but determined by the personal significance of expressions in current social context. By linking fundamental psychosocial dimensions of adult attachment with brain function, our results do not only corroborate their biological bases but also help understand their impact on behavior

Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition where loss of motor neurons within the brain and spinal cord leads to muscle atrophy, weakness, paralysis and ultimately death within 3–5 years from onset of symptoms. The specific molecular mechanisms underlying the disease pathology are not fully understood and neuroprotective treatment options are minimally effective. In recent years, stem cell transplantation as a new therapy for ALS patients has been extensively investigated, becoming an intense and debated field of study. In several preclinical studies using the SOD1G93A mouse model of ALS, stem cells were demonstrated to be neuroprotective, effectively delayed disease onset and extended survival. Despite substantial improvements in stem cell technology and promising results in preclinical studies, several questions still remain unanswered, such as the identification of the most suitable and beneficial cell source, cell dose, route of delivery and therapeutic mechanisms. This review will cover publications in this field and comprehensively discuss advances, challenges and future direction regarding the therapeutic potential of stem cells in ALS, with a focus on mesenchymal stem cells. In summary, given their high proliferation activity, immunomodulation, multi-differentiation potential, and the capacity to secrete neuroprotective factors, adult mesenchymal stem cells represent a promising candidate for clinical translation. However, technical hurdles such as optimal dose, differentiation state, route of administration, and the underlying potential therapeutic mechanisms still need to be assessed