The authors assessed transmission of SARS-CoV-2 and evaluated the adequacy of symptom-based screening in a skilled nursing facility. More than half of residents with positive test results were ...asymptomatic at the time of testing. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission.
Arabidopsis was transformed with double-stranded RNA interference (dsRNAi) constructs designed to silence three putative callose synthase genes: GLUCAN SYNTHASE-LIKE5 (GSL5), GSL6, and GSL11. Both ...wound callose and papillary callose were absent in lines transformed with GSL5 dsRNAi and in a corresponding sequence-indexed GSL5 T-DNA insertion line but were unaffected in GSL6 and GSL11 dsRNAi lines. These data provide strong genetic evidence that the GSL genes of higher plants encode proteins that are essential for callose formation. Deposition of callosic plugs, or papillae, at sites of fungal penetration is a widely recognized early response of host plants to microbial attack and has been implicated in impeding entry of the fungus. Depletion of callose from papillae in gsl5 plants marginally enhanced the penetration of the grass powdery mildew fungus Blumeria graminis on the nonhost Arabidopsis. Paradoxically, the absence of callose in papillae or haustorial complexes correlated with the effective growth cessation of several normally virulent powdery mildew species and of Peronospora parasitica.
The increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor CAR-T cells), is ...raising questions on their potential immunogenicity and effects on treatment. In this review, we outline the mechanisms of action (MOA) of approved, antibody-based IMD agents, potentially related to their immunogenicity, and discuss the reported incidence of anti-drug antibodies (ADA) as well as their clinical relevance in patients with cancer. In addition, we discuss the impact of the administration route and potential strategies to reduce the incidence of ADA and manage treated patients. Analysis of published reports indicated that the risk of immunogenicity did not appear to correlate with the MOA of anti-programmed death 1 (PD-1)/PD-ligand 1 monoclonal antibodies nor to substantially affect treatment with most of these agents in the majority of patients evaluated to date. Treatment with B-cell depleting agents appears associated with a low risk of immunogenicity. No significant difference in ADA incidence was found between the intravenous and subcutaneous administration routes for a panel of non-oncology IMD antibodies. Additionally, while the data suggest a higher likelihood of immunogenicity for antibodies with T-cell or antigen-presenting cell (APC) targets versus B-cell targets, it is possible to have targets expressed on APCs or T cells and still have a low incidence of immunogenicity.
Lateralization is the functional control of certain behaviors in the brain being processed by either the left or right hemisphere. Behavioral asymmetries can occur at an individual and population ...level, although population-level lateralization is less common amongst solitary species, whereas social species can benefit more from aligning and coordinating their activities. We assessed laterality (individual and population) through turning biases in the eusocial Damaraland mole rat,
We considered factors such as breeding status (queen or subordinate), environment (wild-caught or captive), sex (male or female), colony and body mass. All individuals together demonstrated significant left-turning biases, which was also significant at the population level. Wild-caught animals were more strongly lateralized, had a wider spread over a laterality index and lacked the population-level left-turning bias as compared to captive mole rats. Subordinate animals were more lateralized than queens, demonstrating social status differences in turning biases for social mole rats. This emphasizes the importance of animal handling and context when measuring and interpreting behavioral asymmetries.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations ...for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.
We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.
Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28–4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80–3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10–5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61–5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70–3.00). Sensitivity analyses were consistent with these findings.
In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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There is extensive literature documenting the bioaccumulation of persistent organic pollutants in the marine environment, but relatively little data are available on contamination pathways in ...aquaculture systems such as that for farmed salmon. In recent years, the salmon industry has grown significantly in Europe. This study reports on the determination of a wide range of polychlorinated biphenyls (PCBs), organochlorine pesticides, and polybrominated diphenyl ethers (PBDEs) in farmed and wild European Atlantic salmon fish, aquaculture feeds, and fish oils used to supplement the feeds. The study confirms previous reports of relatively high concentrations of PCBs and indicates moderate concentrations of organochlorine pesticides and PBDEs in farmed Scottish and European salmon. Concentrations of the selected persistent organic pollutants varied among the samples: PCBs (salmon, 145−460 ng/g lipid; salmon feeds, 76−1153 ng/g lipid; fish oils, 9−253 ng/g lipid), S DDTs (salmon, 5−250 ng/g lipid; salmon feeds, 34−52 ng/g lipid; fish oils, 11−218 ng/g lipid), and PBDEs (salmon, 1−85 ng/g lipid: salmon feeds, 8−24 ng/g lipid; fish oils, ND-13 ng/g lipid). Comparison of the samples for all groups of contaminants, except for HCHs, showed an increase in concentration in the order fish oil < feed < salmon. Homologue profiles were similar, with an increase in contribution of hepta- and octa-PCBs in the fish, and profiles of DDTs were similar in all three types of samples. With a constant contribution to the total PCB content, the ICES 7 PCBs appear to be reliable predictors of the PCB contamination profile through all the samples. For PBDEs, BDE 47 dominated the profiles, with no significant difference in the PBDE profiles for the three matrixes. Samples with higher PCB contents generally showed higher levels of the pesticide residues, but this was not the case with the PBDEs, indicating the existence of different pollution sources.
With this study we tested the hypothesis that 6 wk of endurance training increases maximal cardiac output (Qmax) relatively more by elevating blood volume (BV) than by inducing structural and ...functional changes within the heart. Nine healthy but untrained volunteers (Vo2max 47 ± 5 ml·min(-1)·kg(-1)) underwent supervised training (60 min; 4 times weekly at 65% Vo2max for 6 wk), and Qmax was determined by inert gas rebreathing during cycle ergometer exercise before and after the training period. After the training period, blood volume (determined in duplicates by CO rebreathing) was reestablished to pretraining values by phlebotomy and Qmax was quantified again. Resting echography revealed no structural heart adaptations as a consequence of the training intervention. After the training period, plasma volume (PV), red blood cell volume (RBCV), and BV increased (P < 0.05) by 147 ± 168 (5 ± 5%), 235 ± 64 (10 ± 3%), and 382 ± 204 ml (7 ± 4%), respectively. Vo2max was augmented (P < 0.05) by 10 ± 7% after the training period and decreased (P < 0.05) by 8 ± 7% with phlebotomy. Concomitantly, Qmax was increased (P < 0.05) from 18.9 ± 2.1 to 20.4 ± 2.3 l/min (9 ± 6%) as a consequence of the training intervention, and after normalization of BV by phlebotomy Qmax returned to pretraining values (18.1 ± 2.5 l/min; 12 ± 5% reversal). Thus the exercise training-induced increase in BV is the main mechanism increasing Qmax after 6 wk of endurance training in previously untrained subjects.
Pseudogenes have long been labeled as "junk" DNA, failed copies of genes that arise during the evolution of genomes. However, recent results are challenging this moniker; indeed, some pseudogenes ...appear to harbor the potential to regulate their protein-coding cousins. Far from being silent relics, many pseudogenes are transcribed into RNA, some exhibiting a tissue-specific pattern of activation. Pseudogene transcripts can be processed into short interfering RNAs that regulate coding genes through the RNAi pathway. In another remarkable discovery, it has been shown that pseudogenes are capable of regulating tumor suppressors and oncogenes by acting as microRNA decoys. The finding that pseudogenes are often deregulated during cancer progression warrants further investigation into the true extent of pseudogene function. In this review, we describe the ways in which pseudogenes exert their effect on coding genes and explore the role of pseudogenes in the increasingly complex web of noncoding RNA that contributes to normal cellular regulation.
We report a measurement of the CP-violation parameter φ1 obtained in a time-dependent analysis of B0→D¯(*)0h0 decays followed by D¯0→KS0π+π- decay. A model-independent measurement is performed using ...the binned Dalitz plot technique. The measured value is φ1=11.7°±7.8°(stat)±2.1°(syst). Treating sin2φ1 and cos2φ1 as independent parameters, we obtain sin2φ1=0.43±0.27(stat)±0.08(syst) and cos2φ1=1.06±0.33(stat)-0.15+0.21(syst). The results are obtained with a full data sample of 772×106BB¯ pairs collected near the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider.
The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a ...screening trial of individuals at high risk of ovarian cancer.
The coding sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS) after quality-control analysis.
In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P < .001). Mutations in EOC cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). RAD51C mutations were associated with an odds ratio of 5.2 (95% CI, 1.1 to 24; P = .035), and RAD51D mutations conferred an odds ratio of 12 (95% CI, 1.5 to 90; P = .019). We identified 13 RAD51 mutations (0.65%) in unaffected UK_FOCSS participants (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001).
These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing.
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