Miracle-dz/UniFAR-FTUs huggingface dataset:
CMG helicase can use ATPγS to unwind DNA: Implications for the rate-limiting step in the reaction mechanism

Significance The rate-limiting step of hexameric replicative helicases is ill-understood and this study on the eukaryotic replicative helicase CMG identifies that the catalytic ATP hydrolysis step is not the rate-limiting step, implying that a conformational change may be rate-limiting for DNA-unwinding activity. The results support a “staircase” model of CMG movement along DNA, requiring a large conformational change after ATP hydrolysis. Many studies use ATPγS to “preload” CMG onto DNA. However, this study demonstrates that ATPγS hydrolysis fuels CMG to unwind DNA. To achieve preloading without unwinding, the current study provides an alternative nucleotide analog, AMP-PNP, that is not hydrolyzable and efficiently preloads CMG onto DNA. The adenosine triphosphate (ATP) analog ATPγS often greatly slows or prevents enzymatic ATP hydrolysis. The eukaryotic CMG (Cdc45, Mcm2 to 7, GINS) replicative helicase is presumed unable to hydrolyze ATPγS and thus unable to perform DNA unwinding, as documented for certain other helicases. Consequently, ATPγS is often used to “preload” CMG onto forked DNA substrates without unwinding before adding ATP to initiate helicase activity. We find here that CMG does hydrolyze ATPγS and couples it to DNA unwinding. Indeed, the rate of unwinding of a 20- and 30-mer duplex fork of different sequences by CMG is only reduced 1- to 1.5-fold using ATPγS compared with ATP. These findings imply that a conformational change is the rate-limiting step during CMG unwinding, not hydrolysis. Instead of using ATPγS for loading CMG onto DNA, we demonstrate here that nonhydrolyzable adenylyl-imidodiphosphate (AMP-PNP) can be used to preload CMG onto a forked DNA substrate without unwinding.
Obstetrical and Perinatal Outcomes in Female Survivors of Childhood and Adolescent Cancer: A Population-Based Cohort Study.

BACKGROUND The likelihood of pregnancy and risk of obstetrical or perinatal complications is inadequately documented in female survivors of pediatric cancer. METHODS We assembled a population-based cohort of female survivors of cancer diagnosed at < 21 years in Ontario, Canada between 1985-2012. Survivors were matched 1:5 to women without prior cancer. Multivariable Cox proportional hazards and modified Poisson models assessed the likelihood of a recognized pregnancy and perinatal and maternal complications. RESULTS 4,062 survivors were matched to 20,308 comparisons. Median (interquartile range [IQR]) age was 11 (4-15) years at cancer diagnosis and 25 (19-31) years at follow-up. By age 30, the cumulative incidence of achieving a recognized pregnancy was 22.3% (95% confidence interval [CI] = 20.7%-23.9%) among survivors' vs 26.6% (95% CI = 25.6%-27.3%) among comparisons (hazard ratio [HR] = 0.80, 95% CI = 0.75-0.86). A lower likelihood of pregnancy was associated with a brain tumour, alkylator chemotherapy, cranial radiation, and hematopoietic stem cell transplantation (HSCT). Pregnant survivors were as likely as cancer-free women to carry a pregnancy >20 weeks' (relative risk [RR] = 1.01, 95% CI = 0.98-1.04). Survivors had a higher relative risk of severe maternal morbidity (RR = 2.31, 95% CI = 1.59-3.37), cardiac morbidity (RR = 4.18, 95% CI = 1.89-9.24) and preterm birth (RR = 1.57, 95% CI = 1.29-1.92). Preterm birth was more likely in survivors treated with HSCT (allogenic: RR = 8.37, 95% CI = 4.83-14.48; autologous: RR = 3.72, 95% CI = 1.66-8.35). CONCLUSION Survivors of childhood or adolescent cancer are less likely to achieve a pregnancy and once pregnant, are at higher risk for severe maternal morbidity and preterm birth.
What can we learn from over a decade of testing bats in New South Wales to exclude infection with Australian bat lyssaviruses?

Australian Bat lyssaviruses (ABLV) are known to be endemic in bats in New South Wales (NSW), Australia. These viruses pose a public health risk because they cause a fatal disease in humans that is indistinguishable from classical rabies infection. All potentially infectious contact between bats and humans, or between bats and domestic animals, should be investigated to assess the risk of virus transmission by submitting the bat for testing to exclude ABLV infection. The aim of this study was to establish the prevalence of ABLV infection in bats submitted for testing in NSW and to document any trends or changes in submission and bat details. We examined all submissions of samples for ABLV testing received by the NSW Department of Primary Industries Virology Laboratory for the 13‐year period between 1 May 2008 and 30 April 2021. Fifty‐four (4.9%) ABLV‐infected bats were detected, with some clustering of positive results. This is greater than the prevalence estimated from wild‐caught bats. All bats should be considered a potential source of ABLV. In particular, flying‐foxes with rabies‐like clinical signs, and with known or possible human interaction, pose the highest public health risk because they are more likely to return a positive result for ABLV infection. This review of ABLV cases in NSW will help veterinarians to recognise the clinical presentations of ABLV infection in bats and emphasises the importance of adequate rabies vaccination for veterinarians.
Wearable Pressure Sensors for Pulse Wave Monitoring

Cardiovascular diseases remain the leading cause of death worldwide. The rapid development of flexible sensing technologies and wearable pressure sensors have attracted keen research interest and have been widely used for long‐term and real‐time cardiovascular status monitoring. Owing to compelling characteristics, including light weight, wearing comfort, and high sensitivity to pulse pressures, physiological pulse waveforms can be precisely and continuously monitored by flexible pressure sensors for wearable health monitoring. Herein, an overview of wearable pressure sensors for human pulse wave monitoring is presented, with a focus on the transduction mechanism, microengineering structures, and related applications in pulse wave monitoring and cardiovascular condition assessment. The conceptualizations and methods for the acquisition of physiological and pathological information related to the cardiovascular system are outlined. The biomechanics of arterial pulse waves and the working mechanism of various wearable pressure sensors, including triboelectric, piezoelectric, magnetoelastic, piezoresistive, capacitive, and optical sensors, are also subject to systematic debate. Exemple applications of pulse wave measurement based on microengineering structured devices are then summarized. Finally, a discussion of the opportunities and challenges that wearable pressure sensors face, as well as their potential as a wearable intelligent system for personalized healthcare is given in conclusion.
A muscle cell‐macrophage axis involving matrix metalloproteinase 14 facilitates extracellular matrix remodeling with mechanical loading

The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. For successful adaptation to mechanical loading, remodeling processes must occur. In a large cohort of older adults, transcriptomics revealed that genes involved in ECM remodeling, including matrix metalloproteinase 14 (MMP14), were the most upregulated following 14 weeks of progressive resistance exercise training (PRT). Using single‐cell RNA‐seq, we identified macrophages as a source of Mmp14 in muscle following a hypertrophic exercise stimulus in mice. In vitro contractile activity in myotubes revealed that the gene encoding cytokine leukemia inhibitory factor (LIF) is robustly upregulated and can stimulate Mmp14 expression in macrophages. Functional experiments confirmed that modulation of this muscle cell‐macrophage axis facilitated Type I collagen turnover. Finally, changes in LIF expression were significantly correlated with MMP14 expression in humans following 14 weeks of PRT. Our experiments reveal a mechanism whereby muscle fibers influence macrophage behavior to promote ECM remodeling in response to mechanical loading.
Proteomic Correlates of Enhanced Daptomycin Activity following β-Lactam Preconditioning in Daptomycin-Resistant, Methicillin-Resistant Staphylococcus aureus

Clinical treatment options for daptomycin (DAP)-resistant (DAP-R), methicillin-resistant Staphylococcus aureus (MRSA) infections are relatively limited. Current therapeutic strategies often take advantage of potential synergistic activity of DAP plus β-lactams; however, the mechanisms underlying their combinatorial efficacy are likely complex and remain incompletely understood. ABSTRACT Clinical treatment options for daptomycin (DAP)-resistant (DAP-R), methicillin-resistant Staphylococcus aureus (MRSA) infections are relatively limited. Current therapeutic strategies often take advantage of potential synergistic activity of DAP plus β-lactams; however, the mechanisms underlying their combinatorial efficacy are likely complex and remain incompletely understood. We recently showed that in vitro β-lactam passaging can resensitize DAP-R strains to a DAP-susceptible (DAP-S) phenotype. To further investigate the implications of selected β-lactam pretreatments on DAP plus β-lactam combination efficacy, we utilized DAP-R strain D712. We studied six such combinations, featuring β-lactams with a broad range of penicillin-binding protein-targeting profiles (PBP-1 to -4), using DAP-R strain D712. Of note, preconditioning with each β-lactam antibiotic (sequential exposures), followed by DAP exposure, yielded significantly enhanced in vitro activity compared to either DAP treatment alone or simultaneous exposures to both antibiotics. To explore the underpinnings of these outcomes, proteomic analyses were performed, with or without β-lactam preconditioning. Relative proteomic quantitation comparing β-lactam pretreatments (versus untreated controls) identified differential modulation of several well-known metabolic, cellular, and biosynthetic processes, i.e., the autolytic and riboflavin biosynthetic pathways. Moreover, these differential proteomic readouts with β-lactam preconditioning were not PBP target specific. Taken together, these studies suggest that the cellular response to β-lactam preconditioning in DAP-R MRSA leads to distinct and complex changes in the proteome that appear to resensitize such strains to DAP-mediated killing.
Climate change could reduce and spatially reconfigure cocoa cultivation in the Brazilian Amazon by 2050

Cocoa is a plant with origins in northwestern South America with high relevance in the global economy. Evidence indicates that cocoa is sensitive to a dry climate, under which crop production is reduced. Projections for future climate change scenarios suggest a warmer and drier climate in the Amazon basin. In this paper, we quantify the potential effects in cocoa production due to its edaphoclimatic suitability changes to the Brazilian Amazon biome and account for regional differences in planning occupation territories. We modeled the suitability of cocoa’s geographical distribution using an ensemble of 10 correlative models that were run in the “biomod2” library and projected to two future climate scenarios (RCPs 4.5 and 8.5) by 2050. Combining information on climate and soil suitability and installed infrastructure in the macro-regions of the Brazilian Amazon. We defined a zoning system to indicate how cocoa production may respond to climate change according to the current and future suitability model. Our results suggest that a reduction in precipitation and an increase in temperature may promote a reduction in the suitability of cocoa production in the Brazilian Amazon biome. In addition of the areas suitable for cocoa plantation, we found a 37.05% and 73.15% decrease in the areas suitable for intensification and expansion zones under RCP 4.5 and 8.5, respectively, compared with the current scenario. We conclude that there may be a need to expand land to cocoa production in the future, or else it will be necessary to plant a cocoa variety resistant to new climatic conditions. Besides, we recommend procedures to combat illegal deforestation to prevent the most critical climate change scenarios from occurring.
Dropout during a 12-week transitional exercise-based cardiac rehabilitation programme: a mixed-methods prospective cohort study.

AIMS Investigate the dropout rate during a 12-week transitional exercise-based cardiac rehabilitation (exCR) programme focusing on a halfway transition phase between hospital and the municipality-based cardiac rehabilitation. Secondly, investigate patient characteristics associated with dropout at the transition. METHODS AND RESULTS Patients with coronary heart disease, heart failure, or heart valve surgery referred to exCR were included in a prospective cohort study conducted between 1 March 2018 and 28 February 2019 at Zealand University Hospital. Exercise-based cardiac rehabilitation was initiated at the hospital with a halfway transitional to local healthcare centres in the municipalities. Dropouts were identified every third week through telephone interviews. A Kaplan-Meier time-to-event analysis was used to investigate time to dropout, while multiple logistic regression assessed associations between patient characteristics and dropout at the transition. Of 560 patients eligible for exCR, 279 participated in the study. Fourteen patients were lost to follow-up and 103 dropped out, resulting in a dropout rate of 39% [95% confidence interval (CI) 33-45%]. Of the 103 dropouts, 72 patients (70%) dropped out at the transition. In the adjusted analysis, patients attached to the labour market were associated with dropout at the transition [odds ratio (OR) = 6.31 (95% CI 2.04-19.54)]. Furthermore, odds of dropping out at transition were reduced for each extra exercise session attended [OR = 0.79 (95% CI 0.66-0.94)]. CONCLUSION The transition phase constitutes a critical dropout period in exCR, in which increased attention on patient adherence is needed. In clinical practice, communication and strategies addressing patient retention across settings could be essential to prevent dropout in transitional exCR.
Performance of Three Tests for SARS-CoV-2 on a University Campus Estimated Jointly with Bayesian Latent Class Modeling

Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been vitally important during the COVID-19 pandemic. There are a variety of methods for testing for this virus, and it is important to understand their accuracy in choosing which one might be best suited for a given application. ABSTRACT Accurate tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical in efforts to control its spread. The accuracy of tests for SARS-CoV-2 has been assessed numerous times, usually in reference to a gold standard diagnosis. One major disadvantage of that approach is the possibility of error due to inaccuracy of the gold standard, which is especially problematic for evaluating testing in a real-world surveillance context. We used an alternative approach known as Bayesian latent class modeling (BLCM), which circumvents the need to designate a gold standard by simultaneously estimating the accuracy of multiple tests. We applied this technique to a collection of 1,716 tests of three types applied to 853 individuals on a university campus during a 1-week period in October 2020. We found that reverse transcriptase PCR (RT-PCR) testing of saliva samples performed at a campus facility had higher sensitivity (median, 92.3%; 95% credible interval [CrI], 73.2 to 99.6%) than RT-PCR testing of nasal samples performed at a commercial facility (median, 85.9%; 95% CrI, 54.7 to 99.4%). The reverse was true for specificity, although the specificity of saliva testing was still very high (median, 99.3%; 95% CrI, 98.3 to 99.9%). An antigen test was less sensitive and specific than both of the RT-PCR tests, although the sample sizes with this test were small and the statistical uncertainty was high. These results suggest that RT-PCR testing of saliva samples at a campus facility can be an effective basis for surveillance screening to prevent SARS-CoV-2 transmission in a university setting. IMPORTANCE Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been vitally important during the COVID-19 pandemic. There are a variety of methods for testing for this virus, and it is important to understand their accuracy in choosing which one might be best suited for a given application. To estimate the accuracy of three different testing methods, we used a data set collected at a university that involved testing the same samples with multiple tests. Unlike most other estimates of test accuracy, we did not assume that one test was perfect but instead allowed for some degree of inaccuracy in all testing methods. We found that molecular tests performed on saliva samples at a university facility were similarly accurate as molecular tests performed on nasal samples at a commercial facility. An antigen test appeared somewhat less accurate than the molecular tests, but there was high uncertainty about that.
Horticultural innovation by viral-induced gene regulation of carotenogenesis

Abstract Multipartite viral vectors provide a simple, inexpensive and effective biotechnological tool to transiently manipulate (i.e. reduce or increase) gene expression in planta and characterise the function of genetic traits. The development of virus-induced gene regulation (VIGR) systems usually involve the targeted silencing or overexpression of genes involved in pigment biosynthesis or degradation in plastids, thereby providing rapid visual assessment of success in establishing RNA- or DNA-based VIGR systems in planta. Carotenoids pigments provide plant tissues with an array of yellow, orange, and pinkish-red colours. VIGR-induced transient manipulation of carotenoid-related gene expression has advanced our understanding of carotenoid biosynthesis, regulation, accumulation and degradation, as well as plastid signalling processes. In this review, we describe mechanisms of VIGR, the importance of carotenoids as visual markers of technology development, and knowledge gained through manipulating carotenogenesis in model plants as well as horticultural crops not always amenable to transgenic approaches. We outline how VIGR can be utilised in plants to fast-track the characterisation of gene function(s), accelerate fruit tree breeding programs, edit genomes, and biofortify plant products enriched in carotenoid micronutrients for horticultural innovation.
An experimental investigation of a simulated online intergenerational friendship

ABSTRACT Reducing ageism is a significant social issue. The current study involved a novel experimental examination of whether a one-time simulated online intergenerational friendship would reduce ageism. Undergraduate participants were randomly assigned to complete an interpersonal closeness exercise (the “fast friends” procedure, Aron et al., 1997; Lytle & Levy, 2015) with a confederate who used a script to answer the fast friends questions, during which they either did not reveal their age (control condition) or revealed being an older adult (age 65; experimental condition). Results indicate that experimental (vs. control) participants reported less ageism and more positive behavior (friendlier responses). These findings suggest that positive online intergenerational contact may help combat ageism. As intergenerational contact was limited before the COVID-19 pandemic and even more so during the pandemic, facilitating online intergenerational contact may be a particularly worthwhile ageism reduction strategy. Further implications of these findings and future directions are discussed.
Hexavalent Chromium Induced Toxicological, Physiological and Biochemical Alterations in Sesbania sesban L. Seedlings

Hexavalent Chromium Induced Toxicological, Physiological and Biochemical Alterations in Sesbania sesban L. Seedlings Widespread use of chromium in several industrial and mining activities leads to the release of toxic hexavalent chromium (Cr6+) to environment. Screening and identification of hyperaccumulators for possible phytoremediation of Cr6+ from these contaminated sites has gained utmost importance in recent years. A pot culture experiment was conducted to observe the possible phytotoxic effects of Cr6+ in an agroforestry species, i.e. Sesbania sesban L. , commonly known as sesban. Cr6+ showed significant growth retardation in 21 days old sesban seedlings, which includes 80% inhibition in seed germination at 10,000 ppm, 59.6% germination index.
The antipsychotic aripiprazole induces peripheral antinociceptive effects through PI3Kγ/NO/cGMP/KATP pathway activation

Aripiprazole is an antipsychotic drug used to treat schizophrenia and bipolar disorder. Recently, its peripheral analgesic component was evaluated, however, the mechanism involved in this effect is not fully established. Therefore, the aim of the study was to obtain pharmacological evidence for the involvement of the nitric oxide system in the peripheral antinociceptive effect induced by aripiprazole.
Implementation intentions speed up young adults’ responses to prospective memory targets in everyday life

Prospective memory (PM), which is the ability to remember to do something in the future, is vitally important for successful everyday functioning. Although young adults demonstrate high PM abilities in laboratory settings, their abilities to complete intended actions in naturalistic settings are surprisingly low. The present study tested the effectiveness of various encoding techniques in improving young adults’ performance in everyday life. Ninety-two participants were asked to remember to take photographs of receipts for a duration of seven days. The task instructions were either given alone or followed by: (a) the if-then statement, (b) visualising the task, or (c) the combination of the if-then statement plus visualisation. The if-then statement alone significantly speeded up responses to the prospective memory targets, i.e., less time elapsed between getting a receipt and taking a photograph of it. With no effect of the if-then statement on the proportion of correct PM responses, the results may suggest that the if-then statement strengthened the PM cue-intention association but did not influence the PM cue saliency.
Influence of taste stimulation on sucking pressure in newborn infants at term

Abstract Purpose To verify the influence of a taste stimulus on the suction pressure, during the non-nutritive sucking (SNN), in newborns, healthy and with weight appropriate to the gestational age. Methods Quasi-experimental study of the non-randomized clinical trial type with a convenience sample of 60 newborns (NB), 30 allocated in the study group (EG) and 30 in the control group (CG). The NB were evaluated for sucking pressure during the SNN in a pacifier. For the EG, a gustatory stimulus was added to the pacifier, moistened with colostrum. The CG did not receive any stimulus, other than the pacifier itself. The average, minimum and maximum pressures were measured with the equipment S-Flex®. Results The SG presented mean and maximum sucking pressure significantly higher than the CG. In addition, there was a statistically significant difference between the groups for the second measurement of mean sucking pressure. Conclusion The results showed that the NB of the SG presented sucking pressures, average and maximum, significantly higher, when compared to the CG. The use of a taste stimulus associated with SNN modified the sucking pressure and seems to enhance oral skills.