It was suggested that the incorporation of more information such as rainfall intensity, land use, and land cover may lead to further improvement of sediment prediction in the future.Previous animal models have illustrated that reduced cortical activity in the developing brain has cascading activity-dependent effects on the microstructural organization of the spinal cord. A limited number of studies have attempted to translate these findings to humans with cerebral palsy (CP). Essentially, the aberrations in sensorimotor cortical activity in those with CP could have an adverse effect on the spinal cord microstructure. To investigate this knowledge gap, we utilized magnetoencephalographic (MEG) brain imaging to quantify motor-related oscillatory activity in fourteen adults with CP and sixteen neurotypical (NT) controls. A subset of these participants also underwent cervical-thoracic spinal cord MRI. Our results showed that the strength of the peri-movement beta desynchronization and the post-movement beta rebound were each weaker in the adults with CP relative to the controls, and these weakened responses were associated with poorer task performance. Additionally, our results showed that the strength of the peri-movement beta response was associated with the total cross-sectional area of the spinal cord and the white matter cross-sectional area. Altogether these results suggest that the altered sensorimotor cortical activity seen in CP may result in activity-dependent plastic changes within the spinal cord microstructure, which could ultimately contribute to the sensorimotor deficits seen in this population.A repeat expansion in C9orf72 is the major cause of both frontotemporal dementia and amyotrophic lateral sclerosis, accounting for approximately 1 in 12 cases of either disease. The expansion is translated to produce five dipeptide repeat proteins (DPRs) which aggregate in patient brain and are toxic in numerous models, though the mechanisms underlying this toxicity are poorly understood. Recent studies highlight nucleocytoplasmic transport impairments as a potential mechanism underlying neurodegeneration in C9orf72-linked disease, although the contribution of DPRs to this remains unclear. We expressed DPRs in HeLa cells, in the absence of repeat RNA. Crucially, we expressed DPRs at repeat-lengths found in patients (> 1000 units), ensuring our findings were relevant to disease. Immunofluorescence imaging was used to investigate the impact of each DPR on the nucleus, nucleocytoplasmic transport machinery and TDP-43 localisation. DPRs impaired the structural integrity of the nucleus, causing nuclear membrane disruption and misshapen nuclei. Ran and RanGAP, two proteins required for nucleocytoplasmic transport, were also mislocalised in DPR-expressing cells. Furthermore, DPRs triggered mislocalisation of TDP-43 to the cytoplasm, and this occurred in the same cells as Ran and RanGAP mislocalisation, suggesting a potential link between DPRs, nucleocytoplasmic transport impairments and TDP-43 pathology.Marine wastes pose a great threat to the ecosystem leading to severe environmental hazards and health issues particularly the shellfish wastes. The shellfish waste which contains half of the amount of chitin can be efficiently transformed into useful products. Various approaches for the hydrolysis of chitin like physical, chemical, and enzymatic processes are there. Still, the use of enzyme chitinase is well documented as an effective and eco-friendly method. The present study summarizes the isolation of chitinase enzyme producing bacteria from different shrimp waste disposal sites in Parangipettai (India), and the possible use of an enzyme hydrolyzate as an immunostimulant to Asian Seabass (Lates calcarifer). The potential chitinase-producing bacteria were identified by 16S rRNA gene sequencing as Stenotrophomonas maltophilia. After purification, the chitinase specific activity was 5.01 (U/ml) and the protein content was 72 mg and the recovery rate was 48.06%. The optimum pH and temperature for the chitinolyction. The control diet-fed fish showed 70% mortality but the chitin derivative supplemented fishes showed only 20% mortality post-infection. The results of the study encompass that the use of chitin-derivate enriched feed further is taken into large-scale approaches thereby benefitting the aquaculture sector.Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season.Metallography is crucial for a proper assessment of material properties. It mainly involves investigating the spatial distribution of grains and the occurrence and characteristics of inclusions or precipitates. This work presents a holistic few-shot artificial intelligence model for Quantitative Metallography, including Anomaly Detection, that automatically quantifies the degree of the anomaly of impurities in alloys. We suggest the following examination process (1) deep semantic segmentation is performed on the inclusions (based on a suitable metallographic dataset of alloys and corresponding tags of inclusions), producing inclusions masks that are saved into a separated dataset. (2) Deep image inpainting is performed to fill the removed inclusions parts, resulting in 'clean’ metallographic images, which contain the background of grains. (3) Grains’ boundaries are marked using deep semantic segmentation (based on another metallographic dataset of alloys), producing boundaries that are ready for further inspection on the distribution of grains’ size. (4) Deep anomaly detection and pattern recognition is performed on the inclusions masks to determine spatial, shape, and area anomaly detection of the inclusions. Finally, the end-to-end model recommends an expert on areas of interest for further examination. The physical result can re-tune the model according to the specific material at hand. Although the techniques presented here were developed for metallography analysis, most of them can be generalized to a broader set of microscopy problems that require automation. All source-codes as well as the datasets that were created for this work, are publicly available at https//github.com/Scientific-Computing-Lab-NRCN/MLography .Altered retinal dopamine and ON-pathway activity may underlie myopia development. It has been shown that the stimulation of the blind spot with short-wavelength light increases the electroretinogram (ERG) b-wave amplitude of myopic eyes and may engage the retinal dopaminergic system. This study evaluated the impact of various durations of blind spot stimulation on the electrophysiological response of the myopic retina and their relationship to axial length. Six myopic individuals underwent three short-wavelength blue light blind spot stimulation protocols (10 s, 1 min, 10 min) using a virtual reality headset. As a control condition, no stimulation was shown for 1 min. The b-wave amplitude of the photopic full-field ERG was measured at baseline and 10, 20, 30, 40, 50, and 60 min after each condition. A significant increase in b-wave amplitude was observed for all stimulation protocols compared to the control. The peak b-wave amplitude was observed 20 min after the 1-min stimulation protocol and 60 min after the 10-min stimulation protocol. A significant positive correlation was found between axial length of the eye and percent change in b-wave amplitude for the 10-min stimulation protocol. A rapid and a delayed b-wave time course responses were observed following 1 min and 10 min of blind spot stimulation, respectively. Overall, these results indicate that light stimulation of the blind spot for various durations elevates ON-bipolar cell activity in the retina and as such is assumed to reduce the myopic response. These findings could have implications for future myopia treatment.Quantification of rill erosion processes is of great importance in both model parameter estimations for process-based rill erosion models and in model performance verification. This study presents a mathematical method to determine a physics-based rill erosion process derived from the feedback relationship of transport capacity and detachment capacity. Experimental data sets were used to determine transport capacities under steep slope gradients of 15°, 20°, and 25° and the detachment capacities. The estimated transport and detachment capacities were then used to determine the sediment delivery processes under different hydraulic regimes. The sediment concentrations along the rill determined with the mathematical method were compared with the experimental measurements to verify the methodology and the mathematics. Results showed that the mathematical model results agreed well with the experimental data in references. The predicted detachment capacity calculated by the new method was capable of predicting saturated, unsaturated, and thawed slope, but incapable of partially thawed soil. This study not only supports the analytical solution to the differential equation of rill erosion, but also verifies that the experimental method was fit well with the mathematical concept. The new method provides a useful and efficient way to quantify rill erosion processes.The continuing evolution of SARS-CoV-2 variants not only causes a long-term global health concerns but also encounters the vaccine/drug effectiveness. The degree of virus infectivity and its clinical outcomes often depend on various biological parameters (e.g., age, genetic factors, diabetes, obesity and other ailments) of an individual along with multiple environmental factors (e.g., air temperature, humidity, seasons). Thus, despite the extensive search for and use of several vaccine/drug candidates, the combinative influence of these various extrinsic and intrinsic risk factors involved in the SARS-CoV-2 virus infectivity has yet to be explored. Previous studies have reported that environment temperature is negatively associated with virus infectivity for SARS-CoV-2. This study elaborates on our previous findings, investigating the link between environmental temperature and other metabolic parameters, such as average total cholesterol and obesity, with the increase in COVID-19 cases. Statistical analysis conducted on a per country basis not only supports the existence of a significant negative correlation between environmental temperature and SARS-CoV-2 infections but also found a strong positive correlation between COVID-19 cases and these metabolic parameters. In addition, a multiphase growth curve model (GCM) was built to predict the contribution of these covariates in SARS-CoV-2 infectivity. These findings, for first time, support the idea that there might be a combinatorial impact of environmental temperature, average total cholesterol, and obesity in the inflation of the SARS-CoV-2 infectivity.It has long been known that the thermal catalyst Cu/ZnO/Al2O3(CZA) can enable remarkable catalytic performance towards CO2 hydrogenation for the reverse water-gas shift (RWGS) and methanol synthesis reactions. However, owing to the direct competition between these reactions, high pressure and high hydrogen concentration (≥75%) are required to shift the thermodynamic equilibrium towards methanol synthesis. Herein, a new black indium oxide with photothermal catalytic activity is successfully prepared, and it facilitates a tandem synthesis of methanol at a low hydrogen concentration (50%) and ambient pressure by directly using by-product CO as feedstock. The methanol selectivities achieve 33.24% and 49.23% at low and high hydrogen concentrations, respectively.Improved risk stratification of patients suspected of prostate cancer prior to biopsy continues to be an unmet clinical need. ExoDx Prostate (IntelliScore) „EPI” is a non-invasive urine test utilizing RNA from exosomes to provide a risk score that correlates with the likelihood of finding high grade prostate cancer at biopsy. Here, we present the results from a prospective clinical validation study of EPI-CE, a CE-marked in-vitro diagnostic (IVD) assay, specifically developed for use in European clinical laboratories. The study (NCT04720599) enrolled patients with ≥ 50 years, PSA 2-10 ng/mL, prior to MRI, who were scheduled for initial biopsy. First catch urine samples were collected from participants without prior digital rectal examination or prostate massage. Exosomal RNA was isolated and expression levels of three biomarkers ERG, PCA3 and SPDEF were analyzed according to the EPI-CE Instructions For Use. In the study cohort of N = 109 patients, EPI-CE was validated to have a Negative Predictive Value of 89%, a Sensitivity of 92% and a superior performance to two commonly used multiparametric risk calculators (PCPT and ERSPC) in both Receiver Operating Characteristics with a higher Area Under the Curve for EPI-CE 0.67 (95% CI 0.56-0.77) versus PCPT 0.59 (95% CI 0.47-0.71) and ERSPC 0.60 (95% CI 0.49-0.72) and higher Net Benefits analysis across a wide range of risk acceptance levels. This is the first clinical study reporting on the performance of EPI-CE. We demonstrate that EPI-CE provides information beyond standard clinical parameters and provides a better risk assessment prior to MRI, of patients suspected of prostate cancer, than the commonly used multiparametric risk calculators.The decision with whom to form a romantic bond is of great importance, yet the biological or behavioral mechanisms underlying this selective process in humans are largely unknown. Classic evolutionary theories of mate selection emphasize immediate and static features such as physical appearance and fertility. However, they do not explain how initial attraction temporally unfolds during an interaction, nor account for mutual physiological or behavioral adaptations that take place when two people become attracted. Instead, recent theories on social bonding emphasize the importance of co-regulation during social interactions (i.e., the social coordination of physiology and behavior between partners), and predict that co-regulation plays a role in bonding with others. In a speed-date experiment of forty-six heterosexual dates, we recorded the naturally occurring patterns of electrodermal activity and behavioral motion in men and women, and calculated their co-regulation during the date. We demonstrate that co-regulation of behavior and physiology is associated with the date outcome when a man and a woman synchronize their electrodermal activity and dynamically tune their behavior to one another, they are more likely to be romantically and sexually attracted to one another. This study supports the hypothesis that co-regulation of sympathetic and behavioral rhythms between a man and a woman serves as a mechanism that promotes attraction.Intracranial human recordings are a valuable and rare resource of information about the brain. Making such data publicly available not only helps tackle reproducibility issues in science, it helps make more use of these valuable data. This is especially true for data collected using naturalistic tasks. Here, we describe a dataset collected from a large group of human subjects while they watched a short audiovisual film. The dataset has several unique features. First, it includes a large amount of intracranial electroencephalography (iEEG) data (51 participants, age range of 5-55 years, who all performed the same task). Second, it includes functional magnetic resonance imaging (fMRI) recordings (30 participants, age range of 7-47) during the same task. Eighteen participants performed both iEEG and fMRI versions of the task, non-simultaneously. Third, the data were acquired using a rich audiovisual stimulus, for which we provide detailed speech and video annotations. This dataset can be used to study neural mechanisms of multimodal perception and language comprehension, and similarity of neural signals across brain recording modalities.Outdoor recreation is increasing and affects habitat use and selection by wildlife. These effects are challenging to study, especially for elusive species with large spatial requirements, as it is hard to obtain reliable proxies of recreational intensity over extensive areas. Commonly used proxies, such as the density of, or distance to, hiking paths, ignore outdoor recreation occurring on other linear feature types. Here we utilized crowdsourced data from the Strava training app to obtain a large-scale proxy for pedestrian outdoor recreation intensity in southeast Norway. We used the proxy and GPS-tracking data from collared Eurasian lynx (Lynx lynx) to investigate how recreation affects habitat selection at the home range scale and local scale by lynx during summer. We fitted resource selection functions at the two scales using conditional logistic regression. Our analysis revealed that lynx avoided areas of recreational activity at the local scale, but not at home range scale. Nonetheless, lynx frequently used areas associated with recreation, and to a greater degree at night than during the day. Our results suggest that local-scale avoidance of recreation and temporal adjustments of habitat use by lynx mitigate the need for a home range-scale response towards recreation. Scale-dependent responses and temporal adjustments in habitat use may facilitate coexistence between humans and large carnivores.Prey spectra (the number and composition of captured arthropods) represent a crucial aspect of carnivorous plant ecology, yet remain poorly studied. Traditional morphology-based approaches for prey identification are time-intensive, require specialists with considerable knowledge of arthropod taxonomy, and are hampered by high numbers of unidentifiable (i.e., heavily digested) prey items. We examined prey spectra of three species of closely-related annual Drosera (Droseraceae, sundews) from tropical northern Australia using a novel DNA metabarcoding approach with in-situ macro photography as a plausibility control and to facilitate prey quantity estimations. This new method facilitated accurate analyses of carnivorous plant prey spectra (even of heavily digested prey lacking characteristic morphological features) at a taxonomic resolution and level of completeness far exceeding morphology-based methods and approaching the 100% mark at arthropod order level. Although the three studied species exhibited significant differences in detected prey spectra, little prey specialisation was observed and habitat or plant population density variations were likely the main drivers of prey spectra dissimilarity.Paradigms of metabolic strategies employed by photoautotrophic marine picocyanobacteria have been challenged in recent years. Based on genomic annotations, picocyanobacteria are predicted to assimilate organic nutrients via ATP-binding cassette importers, a process mediated by substrate-binding proteins. We report the functional characterisation of a modified sugar-binding protein, MsBP, from a marine Synechococcus strain, MITS9220. Ligand screening of MsBP shows a specific affinity for zinc (KD ~ 1.3 μM) and a preference for phosphate-modified sugars, such as fructose-1,6-biphosphate, in the presence of zinc (KD ~ 5.8 μM). Our crystal structures of apo MsBP (no zinc or substrate-bound) and Zn-MsBP (with zinc-bound) show that the presence of zinc induces structural differences, leading to a partially-closed substrate-binding cavity. The Zn-MsBP structure also sequesters several sulphate ions from the crystallisation condition, including two in the binding cleft, appropriately placed to mimic the orientation of adducts of a biphosphate hexose. Combined with a previously unseen positively charged binding cleft in our two structures and our binding affinity data, these observations highlight novel molecular variations on the sugar-binding SBP scaffold. Our findings lend further evidence to a proposed sugar acquisition mechanism in picocyanobacteria alluding to a mixotrophic strategy within these ubiquitous photosynthetic bacteria.Many studies had established the chronic kidney disease (CKD) prediction models, but most of them were conducted on the general population and not on patients with type 2 diabetes, especially in Asian populations. This study aimed to develop a risk prediction model for CKD in patients with type 2 diabetes from the Diabetes Care Management Program (DCMP) in Taiwan. This research was a retrospective cohort study. We used the DCMP database to set up a cohort of 4,601 patients with type 2 diabetes without CKD aged 40-92 years enrolled in the DCMP program of a Taichung medical center in 2002-2016. All patients were followed up until incidences of CKD, death, and loss to follow-up or 2016. The dataset for participants of national DCMP in 2002-2004 was used as external validation. The incident CKD cases were defined as having one of the following three conditions ACR data greater than or equal to 300 (mg/g); both eGFR data less than 60 (ml/min/1.73 m2) and ACR data greater than or equal to 30 (mg/g); and eGFR data lively, and were 0.76, 0.77, and 0.76 in the sample for external validation, respectively. The value of Harrell’s c-statistics was 0.76 (0.74, 0.78). The proposed model is the first CKD risk prediction model for type 2 diabetes patients in Taiwan. The 1-, 3-, and 5-year CKD risk prediction models showed good prediction accuracy. The model can be used as a guide for clinicians to develop medical plans for future CKD preventive intervention in Chinese patients with type 2 diabetes.Amid accelerating threats to species and ecosystems, technology advancements to monitor, protect, and conserve biodiversity have taken on increased importance. While most innovations stem from adaptation of off-the-shelf devices, these tools can fail to meet the specialized needs of conservation and research or lack the support to scale beyond a single site. Despite calls from the conservation community for its importance, a shift to bottom-up innovation driven by conservation professionals remains limited. We surveyed practitioners, academic researchers, and technologists to understand the factors contributing to or inhibiting engagement in the collaborative process of technology development and adoption for field use and identify emerging technology needs. High cost was the main barrier to technology use across occupations, while development of new technologies faced barriers of cost and partner communication. Automated processing of data streams was the largest emerging need, and respondents focused mainly on applications for individual-level monitoring and automated image processing. Cross-discipline collaborations and expanded funding networks that encourage cyclical development and continued technical support are needed to address current limitations and meet the growing need for conservation technologies.Visual perception is one of the basic tools for exploring the world. However, in schizophrenia, this modality is disrupted. So far, there has been no clear answer as to whether the disruption occurs primarily within the brain or in the precortical areas of visual perception (the retina, visual pathways, and lateral geniculate nucleus [LGN]). A web-based comprehensive search of peer-reviewed journals was conducted based on various keyword combinations including schizophrenia, saliency, visual cognition, visual pathways, retina, and LGN. Articles were chosen with respect to topic relevance. Searched databases included Google Scholar, PubMed, and Web of Science. This review describes the precortical circuit and the key changes in biochemistry and pathophysiology that affect the creation and characteristics of the retinal signal as well as its subsequent modulation and processing in other parts of this circuit. Changes in the characteristics of the signal and the misinterpretation of visual stimuli associated with them may, as a result, contribute to the development of schizophrenic disease.We investigated visual processing and adaptation in 22q11.2 deletion syndrome (22q11.2DS), a condition characterized by an increased risk for schizophrenia. Visual processing differences have been described in schizophrenia but remain understudied early in the disease course. Electrophysiology was recorded during a visual adaptation task with different interstimulus intervals to investigate visual processing and adaptation in 22q11.2DS (with (22q+) and without (22q-) psychotic symptoms), compared to control and idiopathic schizophrenia groups. Analyses focused on early windows of visual processing. While increased amplitudes were observed in 22q11.2DS in an earlier time window (90-140 ms), decreased responses were seen later (165-205 ms) in schizophrenia and 22q+. 22q11.2DS, and particularly 22q-, presented increased adaptation effects. We argue that while amplitude and adaptation in the earlier time window may reflect specific neurogenetic aspects associated with a deletion in chromosome 22, amplitude in the later window may be a marker of the presence of psychosis and/or of its chronicity/severity.Current methods to assess asthma and guide inhaled corticosteroid (ICS) dose titration mainly centre on patient-reported symptoms and lung function assessments. However, these methods correlate only weakly with airway inflammation making them unreliable predictors of future exacerbations and ICS requirement. Fractional Exhaled Nitric Oxide (FeNO) is a simple non-invasive objective measure of airways inflammation used predominantly in specialist clinics. Previous qualitative studies have mainly focused on the acceptability of FeNO in secondary care and there is limited insight to support clinicians and patients using FeNO in primary care asthma reviews. This study aimed to explore adult patient with asthma and primary care health care professional (HCP) views on introducing FeNO as part of routine asthma reviews. Twenty-three health care professionals and 22 patients were interviewed over the phone or online. Both groups reported that current asthma reviews are often seen as tick-box exercises and that introducing the FeNO test would make reviews more tailored to the individual patient, rather than relying on subjective patient reports of asthma control. Adults with asthma also highlighted support more open communication and their understanding of asthma, as they desired to feel more engaged in decisions and conversations about their asthma. HCPs reported valuing patient education and empowerment over a paternalistic approach, when time and resources allow. They also recognised FeNO to provide an objective measure of inflammation that could support them in the education and empowerment of patients. FeNO was seen by both groups as a potentially valuable addition to current asthma reviews mainly led by nurses, both for increasing their understanding of current risk of exacerbation and also to provide more tailored and personalised asthma management to patients. Our findings highlighted the need for open and clear communication about how to interpret FeNO results.The refractive index and its variation with temperature, i.e. the thermo-optic coefficient, are basic optical parameters for all those semiconductors that are used in the fabrication of linear and non-linear opto-electronic devices and systems. Recently, 4H single-crystal silicon carbide (4H-SiC) and gallium nitride (GaN) have emerged as excellent building materials for high power and high-temperature electronics, and wide parallel applications in photonics can be consequently forecasted in the near future, in particular in the infrared telecommunication band of λ = 1500-1600 nm. In this paper, the thermo-optic coefficient (dn/dT) is experimentally measured in 4H-SiC and GaN substrates, from room temperature to 480 K, at the wavelength of 1550 nm. Specifically, the substrates, forming natural Fabry-Perot etalons, are exploited within a simple hybrid fiber free-space optical interferometric system to take accurate measurements of the transmitted optical power in the said temperature range. It is found that, for both semiconductors, dn/dT is itself remarkably temperature-dependent, in particular quadratically for GaN and almost linearly for 4H-SiC.While research focus remains mainly on psychotic symptoms, it is questionable whether we are placing enough emphasis on improving the quality of life (QoL) of schizophrenia patients. To date, the predictive power of QoL remained limited. Therefore, this study aimed to accurately predict the QoL within schizophrenia using supervised learning methods. The authors report findings from participants of a large randomized, double-blind clinical trial for schizophrenia treatment. Potential predictors of QoL included all available and non-redundant variables from the dataset. By optimizing parameters, three linear LASSO regressions were calculated (N = 697, 692, and 786), including 44, 47, and 41 variables, with adjusted R-squares ranging from 0.31 to 0.36. Best predictors included social and emotion-related symptoms, neurocognition (processing speed), education, female gender, treatment attitudes, and mental, emotional, and physical health. These results demonstrate that machine learning is an excellent predictive tool to process clinical data. It appears that the patient’s perception of their treatment has an important impact on patients’ QoL and that interventions should consider this aspect.Trial registration ClinicalTrials.gov Identifier NCT00014001.Traditional carrier screening has been utilized for the detection of carriers of genetic disorders. Since a comprehensive assessment of the carrier frequencies of recessive conditions in the Southern Chinese population is not yet available, we performed a secondary analysis on the spectrum and carrier status for 315 genes causing autosomal recessive disorders in 1543 Southern Chinese individuals with next-generation sequencing data, 1116 with exome sequencing and 427 with genome sequencing data. Our data revealed that 1 in 2 people (47.8% of the population) was a carrier for one or more recessive conditions, and 1 in 12 individuals (8.30% of the population) was a carrier for treatable inherited conditions. In alignment with current American College of Obstetricians and Gynecologists (ACOG) pan-ethnic carrier recommendations, 1 in 26 individuals were identified as carriers of cystic fibrosis, thalassemia, and spinal muscular atrophy in the Southern Chinese population. When the >1% expanded carrier screening rate recommendation by ACOG was used, 11 diseases were found to meet the criteria in the Southern Chinese population. Approximately 1 in 3 individuals (35.5% of the population) were carriers of these 11 conditions. If the 1 in 200 carrier frequency threshold is used, and additional seven genes would meet the criteria, and 2 in 5 individuals (38.7% of the population) would be detected as a carrier. This study provides a comprehensive catalogue of the carrier spectrum and frequency in the Southern Chinese population and can serve as a reference for careful evaluation of the conditions to be included in expanded carrier screening for Southern Chinese people.Hadal trenches are the deepest and most remote regions of the ocean. The 11-kilometer deep Challenger Deep is the least explored due to the technical challenges of sampling hadal depths. It receives organic matter and heavy metals from the overlying water column that accumulate differently across its V-shaped topography. Here, we collected sediments across the slope and bottom-axis of the Challenger Deep that enable insights into its in situ microbial communities. Analyses of 586 metagenome-assembled genomes retrieved from 37 metagenomes show distinct diversity and metabolic capacities between bottom-axis and slope sites. 26% of prokaryotic 16S rDNA reads in metagenomes were novel, with novelty increasing with water and sediment depths. These predominantly heterotrophic microbes can recycle macromolecules and utilize simple and complex hydrocarbons as carbon sources. Metagenome and metatranscriptome data support reduction and biotransformation of arsenate for energy gain in sediments that present a two-fold greater accumulation of arsenic compared to non-hadal sites. Complete pathways for anaerobic ammonia oxidation are predominantly identified in genomes recovered from bottom-axis sediments compared to slope sites. Our results expand knowledge of microbially-mediated elemental cycling in hadal sediments, and reveal differences in distribution of processes involved in nitrogen loss across the trench.Drought is a major cause of agricultural losses worldwide. Climate change will intensify drought episodes threatening agricultural sustainability. Gaining insights into drought response mechanisms is vital for crop adaptation to climate emergency. To date, only few studies report comprehensive analyses of plant metabolic adaptation to drought. Here, we present a multifactorial metabolomic study of early-mid drought stages in the model plant Arabidopsis thaliana. We sampled root and shoot tissues of plants subjected to water withholding over a six-day time course, including brassinosteroids receptor mutants previously reported to show drought tolerance phenotypes. Furthermore, we sequenced the root transcriptome at basal and after 5 days drought, allowing direct correlation between metabolic and transcriptomic changes and the multi-omics integration. Significant abiotic stress signatures were already activated at basal conditions in a vascular-specific receptor overexpression (BRL3ox). These were also rapidly mobilized under drought, revealing a systemic adaptation strategy driven from inner tissues of the plant. Overall, this dataset provides a significant asset to study drought metabolic adaptation and allows its analysis from multiple perspectives.Plant nucleotide-binding and leucine-rich repeat domain proteins (NLRs) are immune sensors that recognize pathogen effectors. Here, we show that molecular engineering of the integrated decoy domain (ID) of an NLR can extend its recognition spectrum to a new effector. We relied for this on detailed knowledge on the recognition of the Magnaporthe oryzae effectors AVR-PikD, AVR-Pia, and AVR1-CO39 by, respectively, the rice NLRs Pikp-1 and RGA5. Both receptors detect their effectors through physical binding to their HMA (Heavy Metal-Associated) IDs. By introducing into RGA5_HMA the AVR-PikD binding residues of Pikp-1_HMA, we create a high-affinity binding surface for this effector. RGA5 variants carrying this engineered binding surface perceive the new ligand, AVR-PikD, and still recognize AVR-Pia and AVR1-CO39 in the model plant N. benthamiana. However, they do not confer extended disease resistance specificity against M. oryzae in transgenic rice plants. Altogether, our study provides a proof of concept for the design of new effector recognition specificities in NLRs through molecular engineering of IDs.Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We find that editing can stabilize or destabilize secondary structures formed between RCMs via correcting AC mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provide experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlight the complexity of cross-talk in RNA processing and its contributions to tumorigenesis.The planar assembly of twisted bilayer graphene (tBLG) hosts multitude of interaction-driven phases when the relative rotation is close to the magic angle (θm = 1.1∘). This includes correlation-induced ground states that reveal spontaneous symmetry breaking at low temperature, as well as possibility of non-Fermi liquid (NFL) excitations. However, experimentally, manifestation of NFL effects in transport properties of twisted bilayer graphene remains ambiguous. Here we report simultaneous measurements of electrical resistivity (ρ) and thermoelectric power (S) in tBLG for several twist angles between θ ~ 1.0 - 1.7∘. We observe an emergent violation of the semiclassical Mott relation in the form of excess S close to half-filling for θ ~ 1.6∘ that vanishes for θ ≳ 2∘. The excess S (≈2 μV/K at low temperatures T ~ 10 K at θ ≈ 1.6∘) persists upto ≈40 K, and is accompanied by metallic T-linear ρ with transport scattering rate (τ-1) of near-Planckian magnitude τ-1 ~ kBT/ℏ. Closer to θm, the excess S was also observed for fractional band filling (ν ≈ 0.5). The combination of non-trivial electrical transport and violation of Mott relation provides compelling evidence of NFL physics intrinsic to tBLG.The presence of phosphate from different origins (inorganic, bioorganic) is found more and more in calcium carbonate-based biominerals. Phosphate is often described as being responsible for the stabilization of the transient amorphous calcium carbonate phase. In order to specify the composition of the mineral phase deposited at the onset of carbonated shell formation, the present study investigates, down to the nanoscale, the growing shell from the European abalone Haliotis tuberculata, using a combination of solid state nuclear magnetic resonance, scanning transmission electron microscope and spatially-resolved electron energy loss spectroscopy techniques. We show the co-occurrence of inorganic phosphate with calcium and carbonate throughout the early stages of abalone shell formation. One possible hypothesis is that this first-formed mixed mineral phase represents the vestige of a shared ancestral mineral precursor that appeared early during Evolution. In addition, our findings strengthen the idea that the final crystalline phase (calcium carbonate or phosphate) depends strongly on the nature of the mineral-associated proteins in vivo.Although the mammalian intestinal epithelium manifests robust regenerative capacity after various cytotoxic injuries, the underlying mechanism has remained unclear. Here we identify the cyclin-dependent kinase inhibitor p57 as a specific marker for a quiescent cell population located around the +4 position of intestinal crypts. Lineage tracing reveals that the p57+ cells serve as enteroendocrine/tuft cell precursors under normal conditions but dedifferentiate and act as facultative stem cells to support regeneration after injury. Single-cell transcriptomics analysis shows that the p57+ cells undergo a dynamic reprogramming process after injury that is characterized by fetal-like conversion and metaplasia-like transformation. Population-level analysis also detects such spatiotemporal reprogramming widely in other differentiated cell types. In intestinal adenoma, p57+ cells manifest homeostatic stem cell activity, in the context of constitutively activated spatiotemporal reprogramming. Our results highlight a pronounced plasticity of the intestinal epithelium that supports maintenance of tissue integrity in normal and neoplastic contexts.Due to epistasis, the same mutation can have drastically different phenotypic consequences in different individuals. This phenomenon is pertinent to precision medicine as well as antimicrobial drug development, but its general characteristics are largely unknown. We approach this question by genome-wide assessment of gene essentiality polymorphism in 16 Saccharomyces cerevisiae strains using transposon insertional mutagenesis. Essentiality polymorphism is observed for 9.8% of genes, most of which have had repeated essentiality switches in evolution. Genes exhibiting essentiality polymorphism lean toward having intermediate numbers of genetic and protein interactions. Gene essentiality changes tend to occur concordantly among components of the same protein complex or metabolic pathway and among a group of over 100 mitochondrial proteins, revealing molecular machines or functional modules as units of gene essentiality variation. Most essential genes tolerate transposon insertions consistently among strains in one or more coding segments, delineating nonessential regions within essential genes.RNA excited states represent a class of high-energy-level and thus low-populated conformational states of RNAs that are sequestered within the free energy landscape until being activated by cellular cues. In recent years, there has been growing interest in structural and functional studies of these transient states, but the rational design of excited states remains unexplored. Here we developed a method to design small hairpin RNAs with predefined excited states that exchange with ground states through base pair reshuffling, and verified these transient states by combining NMR relaxation dispersion technique and imino chemical shift prediction. Using van’t Hoff analysis and accelerated molecular dynamics simulations, a mechanism of multi-step sequential transition has been revealed. The efforts made in this study will expand the scope of RNA rational design, and also contribute towards improved predictions of RNA secondary structure.Parkinson’s disease (PD) is a multi-stage neurodegenerative disorder with largely unknown etiology. Recent findings have identified PD-associated autoimmune features including roles for T cells. To further characterize the role of T cells in PD, we performed RNA sequencing on PBMC and peripheral CD4 and CD8 memory T cell subsets derived from PD patients and age-matched healthy controls. When the groups were stratified by their T cell responsiveness to alpha-synuclein (α-syn) as a proxy for an ongoing inflammatory autoimmune response, the study revealed a broad differential gene expression profile in memory T cell subsets and a specific PD associated gene signature. We identified significant enrichment of transcriptomic signatures previously associated with PD, including for oxidative stress, phosphorylation, autophagy of mitochondria, cholesterol metabolism and inflammation, and the chemokine signaling proteins CX3CR1, CCR5, and CCR1. In addition, we identified genes in these peripheral cells that have previously been shown to be involved in PD pathogenesis and expressed in neurons, such as LRRK2, LAMP3, and aquaporin. Together, these findings suggest that features of circulating T cells with α-syn-specific responses in PD patients provide insights into the interactive processes that occur during PD pathogenesis and suggest potential intervention targets.Although pivotal trials with varying populations and study methods suggest higher efficacy for mRNA than adenoviral Covid-19 vaccines, not many studies have directly compared vaccine effectiveness in the population. Here, we conduct a head-to-head comparison of BNT162b2 versus ChAdOx1 against Covid-19. We analyse 235,181 UK Biobank participants aged 50 years or older and vaccinated with one or two doses of BNT162b2 or ChAdOx1. People are followed from the vaccination date until 18/10/2021. Inverse probability weighting is used to minimise confounding and the Cox models to derive hazard ratio. We find that, compared with one dose of ChAdOx1, vaccination with BNT162b2 is associated with a 28% (95% CI, 12-42) decreased risk of SARS-CoV-2 infection. Also, two doses of BNT162b2 vs ChAdOx1 confers 30% (95% CI, 25-35) and 29% (95% CI, 10-45) lower risks of both infection and hospitalisation during the study period when the Delta variant is dominant. Furthermore, the comparative protection against the infection persists for at least six months among the fully vaccinated, suggesting no differential waning between the two vaccines. These findings can inform evidence-based Covid-19 vaccination campaigns and booster strategies.HitRS is a two-component system that responds to cell envelope damage in the human pathogen Bacillus anthracis. Here we identify an RNA-binding protein, KrrA, that regulates HitRS function by modulating the stability of the hitRS mRNA. In addition to hitRS, KrrA binds to over 70 RNAs and, directly or indirectly, affects the expression of over 150 genes involved in multiple processes, including genetic competence, sporulation, RNA turnover, DNA repair, transport, and cellular metabolism. KrrA does not exhibit detectable nuclease activity in vitro, and thus the mechanism by which it modulates mRNA stability remains unclear.Acute cardiac injury has been observed in a subset of COVID-19 patients, but the molecular basis for this clinical phenotype is unknown. It has been hypothesized that molecular mimicry may play a role in triggering an autoimmune inflammatory reaction in some individuals after SARS-CoV-2 infection. Here we investigate if linear peptides contained in proteins that are primarily expressed in the heart also occur in the SARS-CoV-2 proteome. Specifically, we compared the library of 136,704 8-mer peptides from 144 human proteins (including splicing variants) to 9926 8-mers from all the viral proteins in the reference SARS-CoV-2 proteome. No 8-mers were exactly identical between the reference human proteome and the reference SARS-CoV-2 proteome. However, there were 45 8-mers that differed by only one amino acid when compared to the reference SARS-CoV-2 proteome. Interestingly, analysis of protein-coding mutations from 141,456 individuals showed that one of these 8-mers from the SARS-CoV-2 Replicase polyprotein 1a/1ab (KIALKGGK) is identical to an MYH6 peptide encoded by the c.5410 C > A (Q1804K) genetic variation, which has been observed at low prevalence in Africans/African Americans (0.08%), East Asians (0.3%), South Asians (0.06%), and Latino/Admixed Americans (0.003%). Furthermore, analysis of 4.85 million SARS-CoV-2 genomes from over 200 countries shows that viral evolution has already resulted in 20 additional 8-mer peptides that are identical to human heart-enriched proteins encoded by reference sequences or genetic variants. Whether such mimicry contributes to cardiac inflammation during or after COVID-19 illness warrants further experimental evaluation. We suggest that SARS-CoV-2 variants harboring peptides identical to human cardiac proteins should be investigated as „viral variants of cardiac interest”.Palbociclib 3-weeks-on/1-week-off, combined with hormonal therapy, is approved for hormone receptor positive (HR+)/HER2-negative (HER2-) advanced/metastatic breast cancer (MBC). Neutropenia is the most frequent adverse event (AE). We aim to determine whether an alternative 5-days-on/2-days-off weekly schedule reduces grade 3 and above neutropenia (G3 + ANC) incidence. In this single-arm phase II trial, patients with HR+/HER2- MBC received palbociclib 125 mg, 5-days-on/2-days-off, plus letrozole or fulvestrant per physician, on a 28-day cycle (C), as their first- or second-line treatment. The primary endpoint was G3 + ANC in the first 29 days (C1). Secondary endpoints included AEs, efficacy, and serum thymidine kinase 1 (sTK1) activity. At data-cutoff, fifty-four patients received a median of 13 cycles (range 2.6-43.5). The rate of G3 + ANC was 21.3% (95% CI 11.2-36.1%) without G4 in C1, and 40.7% (95% CI 27.9-54.9%), including 38.9% G3 and 1.8% G4, in all cycles. The clinical benefit rate was 80.4% (95% CI 66.5-89.7%). The median progression-free survival (mPFS) (95% CI) was 19.75 (12.11-34.89), 33.5 (17.25-not reached [NR]), and 11.96 (10.43-NR) months, in the overall, endocrine sensitive or resistant population, respectively. High sTK1 at baseline, C1 day 15 (C1D15), and C2D1 were independently prognostic for shorter PFS (p = 9.91 × 10-4, 0.001, 0.007, respectively). sTK1 decreased on C1D15 (p = 4.03 × 10-7), indicating target inhibition. Rise in sTK1 predicted progression, with the median lead time of 59.5 (inter-quartile range -206.25-0) days. Palbociclib, 5-days-on/2-days-off weekly, met its primary endpoint with reduced G3 + ANC, without compromising efficacy. sTK1 is prognostic and shows promise in monitoring the palbociclib response. ClinicalTrials.gov# NCT3007979.To investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8, HIF-1α, EPAS-1, and TSP-1 SNPs and their role on progression-free survival (PFS) in metastatic breast cancer (MBC) patients treated with bevacizumab plus first-line paclitaxel or with paclitaxel alone. Analyses were performed on germline DNA, and SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction (MDR) methodology was applied to investigate the interaction between SNPs. The present study was an explorative, ambidirectional cohort study 307 patients from 11 Oncology Units were evaluated retrospectively from 2009 to 2016, then followed prospectively (NCT01935102). Two hundred and fifteen patients were treated with paclitaxel and bevacizumab, whereas 92 patients with paclitaxel alone. In the bevacizumab plus paclitaxel group, the MDR software provided two pharmacogenetic interaction profiles consisting of the combination between specific VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes. Median PFS for favorable genetic profile was 16.8 vs. the 10.6 months of unfavorable genetic profile (p = 0.0011). Cox proportional hazards model showed an adjusted hazard ratio of 0.64 (95% CI, 0.5-0.9; p = 0.004). Median OS for the favorable genetic profile was 39.6 vs. 28 months of unfavorable genetic profile (p = 0.0103). Cox proportional hazards model revealed an adjusted hazard ratio of 0.71 (95% CI, 0.5-1.01; p = 0.058). In the 92 patients treated with paclitaxel alone, the results showed no effect of the favorable genetic profile, as compared to the unfavorable genetic profile, either on the PFS (p = 0.509) and on the OS (p = 0.732). The pharmacogenetic statistical interaction between VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes may identify a population of bevacizumab-treated patients with a better PFS.