Natural disaster and immunological aging in a nonhuman primate.

Weather-related disasters are increasing in frequency and severity, leaving survivors to cope with ensuing mental, financial, and physical hardships. This adversity can exacerbate existing morbidities, trigger new ones, and increase the risk of mortality-features that are also characteristic of advanced age-inviting the hypothesis that extreme weather events may accelerate aging. To test this idea, we examined the impact of Hurricane Maria and its aftermath on immune cell gene expression in large, age-matched, cross-sectional samples from free-ranging rhesus macaques (Macaca mulatta) living on an isolated island. A cross section of macaques was sampled 1 to 4 y before (n = 435) and 1 y after (n = 108) the hurricane. Hurricane Maria was significantly associated with differential expression of 4% of immune-cell-expressed genes, and these effects were correlated with age-associated alterations in gene expression. We further found that individuals exposed to the hurricane had a gene expression profile that was, on average, 1.96 y older than individuals that were not-roughly equivalent to an increase in 7 to 8 y of a human life. Living through an intense hurricane and its aftermath was associated with expression of key immune genes, dysregulated proteostasis networks, and greater expression of inflammatory immune cell-specific marker genes. Together, our findings illuminate potential mechanisms through which the adversity unleashed by extreme weather and potentially other natural disasters might become biologically embedded, accelerate age-related molecular immune phenotypes, and ultimately contribute to earlier onset of disease and death.

Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is a CTG microsatellite expansion (CTGexp) disorder caused by expression of CUGexp RNAs. These mutant RNAs alter the activities of RNA processing factors, including MBNL proteins, leading to re-expression of fetal isoforms in adult tissues and DM1 pathology. While this pathogenesis model accounts for adult-onset disease, the molecular basis of congenital DM (CDM) is unknown. Here, we test the hypothesis that disruption of developmentally regulated RNA alternative processing pathways contributes to CDM disease. We identify prominent alternative splicing and polyadenylation abnormalities in infant CDM muscle, and, although most are also misregulated in adult-onset DM1, dysregulation is significantly more severe in CDM. Furthermore, analysis of alternative splicing during human myogenesis reveals that CDM-relevant exons undergo prenatal RNA isoform transitions and are predicted to be disrupted by CUGexp-associated mechanisms in utero. To test this possibility and the contribution of MBNLs to CDM pathogenesis, we generated mouse Mbnl double (Mbnl1; Mbnl2) and triple (Mbnl1; Mbnl2; Mbnl3) muscle-specific knockout models that recapitulate the congenital myopathy, gene expression, and spliceopathy defects characteristic of CDM. This study demonstrates that RNA misprocessing is a major pathogenic factor in CDM and provides novel mouse models to further examine roles for cotranscriptional/post-transcriptional gene regulation during development.

5th Argentinean Meeting on Evolutionary Biology (RABE V): Report on the "Evo-Devo" Extended Symposium.

Evolutionary developmental biology (Evo-Devo) is flourishing in Latin America, particularly Argentina, where researchers are leveraging this integrative field to unlock the secrets of the region's remarkable biodiversity. A recent symposium held at the 5th Argentinean Meeting on Evolutionary Biology (RABE V) showcased a vibrant Evo-Devo community and the diversity of its research endeavors. The symposium included 3 plenary talks, 3 short talks, and 12 posters, and spanned a range of organisms and approaches. Interestingly, the symposium highlighted a prevalence of "top-down" Evo-Devo studies in the region, where researchers first analyze existing diversity and then propose potential developmental mechanisms. This approach, driven in part by financial constraints and the region's historical focus on natural history, presents a unique opportunity to bridge disciplines like comparative biology, paleontology, and botany. The symposium's success underscores the vital role of Evo-Devo in Latin America, not only for advancing our understanding of evolution but also for providing valuable tools to conserve and manage the region's irreplaceable biodiversity. As Evo-Devo continues to grow in Latin America, fostering collaboration and knowledge exchange within the region and beyond will be crucial for realizing the full potential of this transformative field.

RET 634 germline/gonadal mosaicism generating a second pathogenic amino acid change in multiple endocrine neoplasia type 2A.

Genetic testing for germline RET pathogenic variants, which cause the Multiple Endocrine Neoplasia Type 2 (MEN2) syndrome, has become crucial in managing patients with medullary thyroid carcinoma (MTC). Classically, RET heterozygous missense pathogenic variants are transmitted in a Mendelian autosomal dominant pattern, of which germline/gonadal mosaicism has never been reported. We report the novel occurrence of a MEN2A patient's family in which the siblings inherited three different RET 634 genotypes: wild type (p.Cys634), p.Cys634Gly or p.Cys634Arg heterozygous pathogenic variants. We hypothesized that germline/gonadal mosaicism, derived from an inherited + early somatic mutation in the mother or a double de novo mutation during maternal embryogenesis, led to this rare event in the RET gene. Exome analysis of the proband's deceased mother's paraffin-embedded thyroid tissue confirmed the three nucleotides in the same 634 codon position. For the first time, we describe germline/gonadal mosaicism in RET, generating a second pathogenic amino acid change in the same codon causing MEN2A. Our finding shows that RET parental mosaicism, confirmed by somatic exome sequencing, might explain discrepant genotype cases in siblings with inherited cancers.

The risk of secondary progressive multiple sclerosis is geographically determined but modifiable.

Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients was 39 (95% confidence interval: 37 to 43) years. Higher latitude [median hazard ratio = 1.21, 95% credible interval (1.16, 1.26)], higher national multiple sclerosis prevalence [1.07 (1.03, 1.11)], male sex [1.30 (1.22, 1.39)], older age at onset [1.35 (1.30, 1.39)], higher disability [2.40 (2.34, 2.47)] and frequent relapses [1.18 (1.15, 1.21)] at inclusion were associated with increased hazard of secondary progressive multiple sclerosis. Higher proportion of time on high-to-moderate efficacy therapy substantially reduced the hazard of secondary progressive multiple sclerosis [0.76 (0.73, 0.79)] and reduced the effect of latitude [interaction: 0.95 (0.92, 0.99)]. At the country-level, patients in Oman, Tunisia, Iran and Canada had higher risks of secondary progressive multiple sclerosis relative to the other studied regions. Higher latitude of residence is associated with a higher probability of developing secondary progressive multiple sclerosis. High-to-moderate efficacy immunotherapy can mitigate some of this geographically co-determined risk.

Venous vascular reconstruction of a robotically procured right kidney with two renal veins transplanted into a pediatric recipient.

BACKGROUND: Right versus left kidney donor nephrectomy remains a controversial topic in renal transplantation given the increased incidence of right kidney vascular anomalies and associated venous thrombosis. We present the case of a 3-year-old pediatric recipient with urethral atresia and end-stage kidney disease who received a robotically procured living donor right pelvic kidney with two short same-size renal veins and a short ureter. METHODS: We utilized a completely deceased iliac vein system (common iliac vein with both external and internal veins) to extend the two renal veins. Due to the distance between both renal veins, the external iliac vein was anastomosed to the upper hilum renal vein, and the internal iliac vein was anastomosed to the lower hilum renal vein. The donor's short ureter was anastomosed to the recipient's ureter end-to-side. RESULTS: The patient had immediate graft function and there were no post-operative complications. Renal ultrasound was unremarkable at 48 hours post-transplant. Serum creatinine was 0.5 mg/dL at 3 months post-transplant. CONCLUSION: We demonstrate the successful transplantation of a robotically procured right pelvic donor kidney with two short renal veins using a deceased donor iliac vein system for venous reconstruction without increasing technical complications. This technique of venous reconstruction can be used in right kidneys with similar anatomical variations without affecting graft function.

A comprehensive study on Geranium robertianum L. antibacterial potential.

AIMS: The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined. METHODS AND RESULTS: Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20 mg ml-1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus, enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24 ± 5.78 µg ml-1 for ethanol extract, and 958.01 ± 6.14 µg ml-1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts. CONCLUSIONS: The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms.

The global diet quality score as an indicator of adequate nutrient intake and dietary quality - a nation-wide representative study.

BACKGROUND: The Global Diet Quality Score (GDQS) was developed to be a simple, timely and cost-effective tool to track, simultaneously, nutritional deficiency and non-communicable disease risks from diet in diverse settings. The objective was to investigate the performance of GDQS as an indicator of adequate nutrient intake and dietary quality in a national-representative sample of the Brazilian population. METHODS: Nationally-representative data from 44,744 men and non-pregnant and non-lactating women aging ≥ 10 years, from the Brazilian National Dietary Survey were used. Dietary data were collected through two 24-h recalls (24HR). The GDQS was calculated and compared to a proxy indicator of nutrient adequate intake (the Minimum Dietary Diversity for Women-MDD-W) and to an indicator of high-risk diet for non-communicable diseases (caloric contribution from ultra-processed foods-UPF). To estimate the odds for overall nutrient inadequacy across MDD-W and GDQS quintiles, a multiple logistic regression was applied, and the two metrics' performances were compared using Wald's post-test. RESULTS: The mean GDQS for Brazilians was 14.5 (0-49 possible range), and only 1% of the population had a low-risk diet (GDQS ≥ 23). The GDQS mean was higher in women, elderly individuals and in higher-income households. An inverse correlation was found between the GDQS and UPF (rho (95% CI) = -0.20(-0.21;-0.19)). The odds for nutrient inadequacy were lower as quintiles of GDQS and MDD-W were higher (p-trend < 0.001), and MDD-W had a slightly better performance than GDQS (p-diff < 0.001). Having a low-risk GDQS (≥ 23) lowered the odds for nutrient inadequacy by 74% (95% CI:63%-81%). CONCLUSION: The GDQS is a good indicator of overall nutrient adequacy, and correlates well with UPF in a nationally representative sample of Brazil. Future studies must investigate the relationship between the GDQS and clinical endpoints, strengthening the recommendation to use this metric to surveillance dietary risks.

Renal cell carcinoma with an "uncoiling" tumor thrombus: intraoperative shift from level III to level IV.

BACKGROUND: The gold standard treatment for renal cell carcinoma (RCC) with tumor thrombus (TT) is complete surgical excision. The surgery is complex and challenging to the surgeon, especially with large tumor thrombus extending into the inferior vena cava (IVC) and right atrium. Traditionally, these difficult cases required the use of cardiopulmonary bypass (CPB) with or without deep hypothermic cardiac arrest, but in recent years, different surgical techniques derived from the field of liver transplantation have been used in efforts to avoid CPB. CASE PRESENTATION: We present a case of RCC with TT level IIIc (extending above major hepatic veins) that "uncoiled" intraoperatively into the right atrium after division of the IVC ligament, transforming into a level IV TT. Despite the new TT extension, the surgery was successfully completed exclusively through an abdominal approach without CPB and while using intraoperative transesophageal echocardiography (TEE) monitoring and a cardiothoracic team standby. CONCLUSIONS: This case highlights the need for a multidisciplinary approach and the utility of intraoperative continous TEE monitoring which helped to visualize the change of the TT venous extension, allowing the surgical teamto modify their surgical approach as needed avoiding a catastrophic event.

Biochar mitigates the adverse effects of antimony on methanogenic activity: role as methane production-enhancer.

Antimony, extensively used in energy applications, poses toxicity and contamination concerns, especially in anaerobic environments where its impact on microbial activity is poorly understood. Emerging remedies, like biochar, show promise in soil and water treatment. This study investigates biochar's influence on methanogenic activity under Sb(V) and Sb(III) stress using anaerobic sludge as inoculum and lactate as the carbon source. Sb(III) and Sb(V) were introduced at varied concentrations (5-80 mg/L), with or without biochar, monitoring changes in biogas production, pH, Sb, and lactate levels over time. Experiments with Sb(V) also involved calculating mass balance and electron distribution. Results showcased the following significant enhancements: biochar notably improved COD removal and biogas production in Sb(III) spiked conditions, up to 5-fold and 2-fold increases, respectively. Sb(III) removal reached up to 99% with biochar, while in high Sb(V) concentrations, biochar reduced the adverse effect on biogas production by 96%. Adsorption capacities favored biomass (60.96 mg Sb(III)/gVSS, and 22.4 mg Sb(V)/gVSS) over biochar (3.33 mg Sb(III)/g, and 1.61 mg Sb(V)/g) for both Sb species. This study underscores biochar's potential to mitigate metalloid impact on methanogenic activity while aiding Sb removal from liquid phase, suggesting promising implications for remediation and methane production enhancement strategies.

Is muscle stiffness a determinant for range of motion in the leg muscles?

Previous training studies with comprehensive stretching durations have reported that an increase in range of motion (ROM) can be related to decreases in muscle stiffness. Therefore, the purpose of this study was to analyze the association between the passive muscle stiffness of three muscle groups (triceps surae, quadriceps, hamstrings) to the respective joint ROM. Thirty-six healthy male soccer players volunteered in this study. After a standardized warm-up, the muscle stiffness was tested via shear wave elastography in six muscles (gastrocnemius medialis and lateralis, rectus femoris, semitendinosus, semimembranosus, and biceps femoris long head). The hip extension, hip flexion, and ankle dorsiflexion ROM were also assessed with a modified Thomas test, a sit and reach test, and a standing wall push test, respectively. We found significant moderate to large correlations between hip flexion ROM and muscle stiffness for the semimembranosus (rP = -0.43; P = 0.01), biceps femoris long head (rP = -0.45; P = 0.01), and overall hamstring stiffness (rP = -0.50; P < 0.01). No significant correlations were found for triceps surae (rP = -0.12; P = 0.51 to 0.67) and rectus femoris muscle stiffness (rP = 0.25; P = 0.14) with ankle dorsiflexion and hip extension ROM, respectively. We conclude that muscle stiffness is an important contributor to hip flexion ROM, but less important for hip extension or ankle joint ROM. Additional contributors to ROM might be tendon stiffness or stretch/pain tolerance.

Aryl Hydrocarbon Receptor Agonism Antagonizes the Hypoxia-driven Inflammation in Cystic Fibrosis.

Hypoxia contributes to the exaggerated yet ineffective airway inflammation that fails to oppose infections in cystic fibrosis (CF). However, the potential for impairment of essential immune functions by HIF-1α (hypoxia-inducible factor 1α) inhibition demands a better comprehension of downstream hypoxia-dependent pathways that are amenable for manipulation. We assessed here whether hypoxia may interfere with the activity of AhR (aryl hydrocarbon receptor), a versatile environmental sensor highly expressed in the lungs, where it plays a homeostatic role. We used murine models of Aspergillus fumigatus infection in vivo and human cells in vitro to define the functional role of AhR in CF, evaluate the impact of hypoxia on AhR expression and activity, and assess whether AhR agonism may antagonize hypoxia-driven inflammation. We demonstrated that there is an important interferential cross-talk between the AhR and HIF-1α signaling pathways in murine and human CF, in that HIF-1α induction squelched the normal AhR response through an impaired formation of the AhR:ARNT (aryl hydrocarbon receptor nuclear translocator)/HIF-1ß heterodimer. However, functional studies and analysis of the AhR genetic variability in patients with CF proved that AhR agonism could prevent hypoxia-driven inflammation, restore immune homeostasis, and improve lung function. This study emphasizes the contribution of environmental factors, such as infections, in CF disease progression and suggests the exploitation of hypoxia:xenobiotic receptor cross-talk for antiinflammatory therapy in CF.

Repeat length increases disease penetrance and severity in C9orf72 ALS/FTD BAC transgenic mice.

C9orf72 ALS/FTD patients show remarkable clinical heterogeneity, but the complex biology of the repeat expansion mutation has limited our understanding of the disease. BAC transgenic mice were used to better understand the molecular mechanisms and repeat length effects of C9orf72 ALS/FTD. Genetic analyses of these mice demonstrate that the BAC transgene and not integration site effects cause ALS/FTD phenotypes. Transcriptomic changes in cell proliferation, inflammation and neuronal pathways are found late in disease and alternative splicing changes provide early molecular markers that worsen with disease progression. Isogenic sublines of mice with 800, 500 or 50 G4C2 repeats generated from the single-copy C9-500 line show longer repeats result in earlier onset, increased disease penetrance and increased levels of RNA foci and dipeptide RAN protein aggregates. These data demonstrate G4C2 repeat length is an important driver of disease and identify alternative splicing changes as early biomarkers of C9orf72 ALS/FTD.

The importance of avoiding time-dependent bias when testing the prognostic value of an intervening event - Two acute cellular rejection examples in intestinal transplantation.

In testing the prognostic value of the occurrence of an intervening event (clinical event that occurs posttransplant), 3 proper statistical methodologies for testing its prognostic value exist (time-dependent covariate, landmark, and semi-Markov modeling methods). However, time-dependent bias has appeared in many clinical reports, whereby the intervening event is statistically treated as a baseline variable (as if it occurred at transplant). Using a single-center cohort of 445 intestinal transplant cases to test the prognostic value of first acute cellular rejection (ACR) and severe (grade of) ACR on the hazard rate of developing graft loss, we demonstrate how the inclusion of such time-dependent bias can lead to severe underestimation of the true hazard ratio (HR). The (statistically more powerful) time-dependent covariate method in Cox's multivariable model yielded significantly unfavorable effects of first ACR (P < .0001; HR = 2.492) and severe ACR (P < .0001; HR = 4.531). In contrast, when using the time-dependent biased approach, multivariable analysis yielded an incorrect conclusion for the prognostic value of first ACR (P = .31, HR = 0.877, 35.2% of 2.492) and a much smaller estimated effect of severe ACR (P = .0008; HR = 1.589; 35.1% of 4.531). In conclusion, this study demonstrates the importance of avoiding time-dependent bias when testing the prognostic value of an intervening event.

Sympathetic neural overdrive and diminished exercise capacity in reduced ejection fraction heart failure related to anthracycline-based chemotherapy.

Cardiotoxicity is the most worrying cardiovascular alteration in patients treated with chemotherapy. To improve the understanding regarding the cardiotoxicity, we studied whether 1) patients with cardiac dysfunction related to anthracycline-based chemotherapy have augmented sympathetic nerve activity and decreased exercise capacity and 2) these responses are similar to those observed in patients with heart failure caused by other etiologies. Sixteen patients with heart failure with reduced ejection fraction related to anthracycline-based chemotherapy with or without chest radiation (HFrEFCA), 10 patients with heart failure with reduced ejection not related to cancer therapy (HFrEF), and 16 age- and body mass index (BMI)-matched healthy control subjects were studied. Left ventricular ejection fraction (LVEF, echocardiography), peak oxygen consumption (peak V̇o2, cardiopulmonary exercise test), muscle sympathetic nerve activity (MSNA, microneurography), and forearm blood flow (FBF, venous occlusion plethysmography) were measured. We found that peak oxygen consumption peak V̇o2 and LVEF were significantly reduced in patients with HFrEFCA compared with that of control subjects (P < 0.0001) but similar to those found in patients with HFrEFCA. The sympathetic nerve activity burst frequency and incidence were significantly higher in patients with HFrEFCA than that in control subjects (P < 0.0001). No differences were found between patients with HFrEF and HFrEFCA. Peak V̇o2 was inversely associated with MSNA burst frequency (r = -0.53, P = 0.002) and burst incidence (r = -0.38, P = 0.01) and directly associated with LVEF (r = 0.71, P < 0.0001). Taken together, we conclude that patients who develop heart failure due to anthracycline-based chemotherapy have sympathetic neural overdrive and reduced exercise capacity. In addition, these physiological changes are similar to those observed in patients with HFrEF.NEW & NOTEWORTHY Patients with heart failure with reduced ejection fraction related to anthracycline-based chemotherapy have increased sympathetic nerve activity and decreased exercise capacity. These alterations in autonomic control and physical capacity are similar to those observed in patients with heart failure due to other etiologies. These findings highlight the importance of special care of oncological patients treated with chemotherapy.

Circadian rhythm disrupting behaviours and cancer outcomes in breast cancer survivors: a systematic review.

PURPOSE: Circadian rhythm disruptors (e.g., night-shift work) are risk factors for breast cancer, however studies on their association with prognosis is limited. A small but growing body of research suggests that altered sleep patterns and eating behaviours are potential mechanistic links between circadian rhythm disruptors and breast cancer. We therefore systematically summarised literature examining the influence of circadian rhythm disrupting behaviours on cancer outcomes in women with breast cancer. METHODS: A systematic search of five databases from inception to January 2021 was conducted. Original research published in English, assessing the relationship between post-diagnosis sleep patters and eating behaviours, and breast cancer outcomes were considered. Risk of bias was assessed using the Newcastle-Ottawa Assessment Scale for Cohort Studies. RESULTS: Eight studies published original evidence addressing sleep duration and/or quality (k = 7) and, eating time and frequency (k = 1). Longer sleep duration (≥ 9 h versus [referent range] 6-8 h) was consistently associated with increased risk of all outcomes of interest (HR range: 1.37-2.33). There was limited evidence to suggest that measures of better sleep quality are associated with lower risk of all-cause mortality (HR range: 0.29-0.97). Shorter nightly fasting duration (< 13 h versus ≥ 13 h) was associated with higher risk of all breast cancer outcomes (HR range: 1.21-1.36). CONCLUSION: Our review suggests that circadian rhythm disrupting behaviours may influence cancer outcomes in women with breast cancer. While causality remains unclear, to further understand these associations future research directions have been identified. Additional well-designed studies, examining other exposures (e.g., light exposure, temporal eating patterns), biomarkers, and patient-reported outcomes, in diverse populations (e.g., breast cancer subtype-specific, socio-demographic diversity) are warranted.

Arf6 is required for endocytosis and filamentous actin assembly during angiogenesis in vitro.

OBJECTIVE: Endocytosis is a process vital to angiogenesis and vascular homeostasis. In pathologies where supraphysiological growth factor signaling underlies disease etiology, such as in diabetic retinopathy and solid tumors, strategies to limit chronic growth factor signaling by way of blunting endocytic processes have been shown to have tremendous clinical value. ADP ribosylation factor 6 (Arf6) is a small GTPase that promotes the assembly of actin necessary for clathrin-mediated and clathrin-independent endocytosis. In its absence, growth factor signaling is greatly diminished, which has been shown to ameliorate pathological signaling input in diseased vasculature. However, it is less clear if there are bystander effects related to loss of Arf6 on angiogenic behaviors. Our goal was to provide an analysis of Arf6's function in angiogenic endothelium, focusing on its role in actin and endocytosis as well as sprouting morphogenesis. METHODS: Primary endothelial cells were cultured in both 2D and 3D environments. Here, endothelial cells were fixed and stained for various proteins or transfected with fluorescently-tagged constructs for live-cell imaging. RESULTS: We found that Arf6 localized to both filamentous actin and sites of endocytosis in two-dimensional culture. Loss of Arf6 distorted both apicobasal polarity and reduced the total cellular filamentous actin content, which may be the primary driver underlying gross sprouting dysmorphogenesis in its absence. CONCLUSIONS: Our findings highlight that endothelial Arf6 is a potent mediator of both actin regulation and endocytosis and is required for proper sprout formation.

An inclusive outlook on the fate and persistence of pesticides in the environment and integrated eco-technologies for their degradation.

Intensive and inefficient exploitation of pesticides through modernized agricultural practices has caused severe pesticide contamination problems to the environment and become a crucial problem over a few decades. Due to their highly toxic and persistent properties, they affect and get accumulated in non-target organisms, including microbes, algae, invertebrates, plants as well as humans, and cause severe issues. Considering pesticide problems as a significant issue, researchers have investigated several approaches to rectify the pesticide contamination problems. Several analyses have provided an extensive discussion on pesticide degradation but using specific technology for specific pesticides. However, in the middle of this time, cleaner techniques are essential for reducing pesticide contamination problems safely and environmentally friendly. As per the research findings, no single research finding provides concrete discussion on cleaner tactics for the remediation of contaminated sites. Therefore, in this review paper, we have critically discussed cleaner options for dealing with pesticide contamination problems as well as their advantages and disadvantages have also been reviewed. As evident from the literature, microbial remediation, phytoremediation, composting, and photocatalytic degradation methods are efficient and sustainable and can be used for treatment at a large scale in engineered systems and in situ. However, more study on the bio-integrated system is required which may be more effective than existing technologies.

Cultural contributions to adults' self-rated mental health problems and strengths: 7 culture clusters, 28 societies, 16 906 adults.

BACKGROUND: It is unknown how much variation in adult mental health problems is associated with differences between societal/cultural groups, over and above differences between individuals. METHODS: To test these relative contributions, a consortium of indigenous researchers collected Adult Self-Report (ASR) ratings from 16 906 18- to 59-year-olds in 28 societies that represented seven culture clusters identified in the Global Leadership and Organizational Behavioral Effectiveness study (e.g. Confucian, Anglo). The ASR is scored on 17 problem scales, plus a personal strengths scale. Hierarchical linear modeling estimated variance accounted for by individual differences (including measurement error), society, and culture cluster. Multi-level analyses of covariance tested age and gender effects. RESULTS: Across the 17 problem scales, the variance accounted for by individual differences ranged from 80.3% for DSM-oriented anxiety problems to 95.2% for DSM-oriented avoidant personality (mean = 90.7%); by society: 3.2% for DSM-oriented somatic problems to 8.0% for DSM-oriented anxiety problems (mean = 6.3%); and by culture cluster: 0.0% for DSM-oriented avoidant personality to 11.6% for DSM-oriented anxiety problems (mean = 3.0%). For strengths, individual differences accounted for 80.8% of variance, societal differences 10.5%, and cultural differences 8.7%. Age and gender had very small effects. CONCLUSIONS: Overall, adults' self-ratings of mental health problems and strengths were associated much more with individual differences than societal/cultural differences, although this varied across scales. These findings support cross-cultural use of standardized measures to assess mental health problems, but urge caution in assessment of personal strengths.

Circadian clock proteins and immunity.

Immune parameters change with time of day and disruption of circadian rhythms has been linked to inflammatory pathologies. A circadian-clock-controlled immune system might allow an organism to anticipate daily changes in activity and feeding and the associated risk of infection or tissue damage to the host. Responses to bacteria have been shown to vary depending on time of infection, with mice being more at risk of sepsis when challenged ahead of their activity phase. Studies highlight the extent to which the molecular clock, most notably the core clock proteins BMAL1, CLOCK, and REV-ERBα, control fundamental aspects of the immune response. Examples include the BMAL1:CLOCK heterodimer regulating toll-like receptor 9 (TLR9) expression and repressing expression of the inflammatory monocyte chemokine ligand (CCL2) as well as REV-ERBα suppressing the induction of interleukin-6. Understanding the daily rhythm of the immune system could have implications for vaccinations and how we manage infectious and inflammatory diseases.