Miracle-dz/UniFAR-FTUs huggingface dataset:
MutS and DNA Function as a Clamp Loader for the MutL Sliding Clamp During Mismatch Repair

DNA mismatch repair (MMR) is accomplished by highly conserved MutS and MutL homologs. MutS proteins recognize mismatch nucleotides and in the presence of ATP form a stable sliding clamp on the DNA. The MutS sliding clamp then promotes the cascade assembly of a MutL sliding clamp, which ultimately coordinates downstream mismatch excision. The MutS clamp-loader mechanics are unknown. Here we have examined a conserved positively charged cleft (PCC) located on the MutL N-terminal domain (NTD) proposed to mediate stable DNA binding events in several MMR models. We show that MutL does not bind DNA in physiological ionic conditions. Instead, the MutS sliding clamps and DNA together exploit the PCC to position the MutL NTD for clamp loading. Once in a sliding clamp form, the MutL PCC aids in UvrD helicase capture but not interactions with MutH during mismatch excision. The MutS-DNA clamp-loader progressions are significantly different from the replication clamp-loaders that attach polymerase processivity factors such as β-clamp and PCNA to the DNA. These studies underlining the breadth of mechanisms for stably linking crucial genome maintenance proteins to the DNA.
Sex differences in the strength of selection under facultative sex

Facultative sex, the ability to reproduce both sexually and asexually, is widespread across the tree of life. In anisogamous species, the frequency of sex modulates selection on traits with sex-specific expression. Current theory on conditional gene expression posits that the strength of selection on loci only expressed by a subset of individuals, and/or in a subset of environments, is proportional to the frequency of expressers in the population. We show here that this assumption does not hold when the subsets in question are males or females (because of the Fisher condition) and is most important in facultatively sexual populations. In this case, the proportion of sexually produced offspring is not determined by male frequency (sex ratio), but on relative female investment in sexual versus asexual reproduction. This breaks the link between the frequency of expressers and selection for loci with sex-specific expression. However, certain conditions can re-establish this link, for example male traits that predict mating success better under strong male-male competition, and sex ratio affecting the relative fecundity of sexual versus asexual females. Our work highlights the importance of the Fisher condition for understanding the efficiency of selection and has implications for differences in the genetic load among sexes.
Innexin function dictates the spatial relationship between distal somatic cells in the Caenorhabditis elegans gonad without impacting the germline stem cell pool

Gap-junctional signaling mediates myriad cellular interactions in metazoans. Yet, how gap junctions control the positioning of cells in organs is not well understood. Innexins compose gap junctions in invertebrates and affect organ architecture. Here, we investigate the roles of gap-junctions in controlling distal somatic gonad architecture and its relationship to underlying germline stem cells in Caenorhabditis elegans. We show that a reduction of soma–germline gap-junctional activity causes displacement of distal sheath cells (Sh1) towards the distal end of the gonad. We confirm, by live imaging, transmission electron microscopy, and antibody staining, that bare regions—lacking somatic gonadal cell coverage of germ cells—are present between the distal tip cell (DTC) and Sh1, and we show that an innexin fusion protein used in a prior study encodes an antimorphic gap junction subunit that mispositions Sh1. We determine that, contrary to the model put forth in the prior study based on this fusion protein, Sh1 mispositioning does not markedly alter the position of the borders of the stem cell pool nor of the progenitor cell pool. Together, these results demonstrate that gap junctions can control the position of Sh1, but that Sh1 position is neither relevant for GLP-1/Notch signaling nor for the exit of germ cells from the stem cell pool.
Myosin-X-dependent assembly of the extracellular matrix limits breast cancer invasion

Institute of Biomedicine, FICAN West Cancer Laboratory, University of Turku, FI20520 Turku, Finland. Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI20520 Turku, Finland. Åbo Akademi University, Faculty of Science and Engineering, Biosciences, FI20520 Turku, Finland. Turku Bioimaging, University of Turku and Åbo Akademi University, FI20520 Turku, Finland. Division of Molecular Pathology, Oncode Institute-Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands. VIB-KU Leuven Center for Cancer Biology, Department of Oncology, Leuven, Belgium. InFLAMES Research Flagship Center, University of Turku, FI20520 Turku, Finland. Department of Pathology, Turku University Hospital, FI20520 Turku, Finland. University of Turku, FI20520 Turku, Finland. Department of Plastic and General Surgery, Turku University Hospital, FI20520 Turku, Finland. Department of Life Technologies, University of Turku, FI20520 Turku, Finland. equal contribution
Study on the Extracting Technology of Alkali-soluble Polysaccharides of P.pulmonarius with Center Combination Design

In this paper,using P.pulmonarius as raw material,on the basis of single factor and center combination designthe optimal extracting technologies of water-soluble and alkali-soluble polysaccharides were probed,and the precipitation properties of the polysaccharides were studied.The results were as the following:The optimal extracting conditions of water-soluble polysaccharides were temperature 89.96℃,time 2.826 h,the ratio of material to water was 1∶69.22. In this condition,the extracting rate of water-soluble polysaccharides was 4.42%. The optimal extracting conditions of alkali-soluble polysaccharides were the concentration of NaOH 1.64 mol/l,time 2.783 h,the ratio of material to NaOH was 1∶43.73. In this condition,the extracting rate of alkali-soluble polysaccharides was 3.97%.
Clinical-Deep Neural Network and Clinical-Radiomics Nomograms for Predicting the Intraoperative Massive Blood Loss of Pelvic and Sacral Tumors

Background Patients with pelvic and sacral tumors are prone to massive blood loss (MBL) during surgery, which may endanger their lives. Purposes This study aimed to determine the feasibility of using deep neural network (DNN) and radiomics nomogram (RN) based on 3D computed tomography (CT) features and clinical characteristics to predict the intraoperative MBL of pelvic and sacral tumors. Materials and Methods This single-center retrospective analysis included 810 patients with pelvic and sacral tumors. 1316 CT and CT enhanced radiomics features were extracted. RN1 and RN2 were constructed by random grouping and time node grouping, respectively. The DNN models were constructed for comparison with RN. Clinical factors associated with the MBL were also evaluated. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) were used to evaluate different models. Results Radscore, tumor type, tumor location, and sex were significant predictors of the MBL of pelvic and sacral tumors (P < 0.05), of which radscore (OR, ranging from 2.109 to 4.706, P < 0.001) was the most important. The clinical-DNN and clinical-RN performed better than DNN and RN. The best-performing clinical-DNN model based on CT features exhibited an AUC of 0.92 and an ACC of 0.97 in the training set, and an AUC of 0.92 and an ACC of 0.75 in the validation set. Conclusions The clinical-DNN and clinical-RN had good performance in predicting the MBL of pelvic and sacral tumors, which could be used for clinical decision-making.
Tunneling of Hydrogen and Deuterium Atoms on Interstellar Ices (I h and ASW)

Model calculations are performed to investigate the kinetic isotope effect of hydrogen and deuterium atom diffusion on hexagonal ice and amorphous solid water. Comparisons with experimental results by Kuwahata et al. (Phys. Rev. Lett., Sep. 2015, 115 (13), 133201) at 10 K are made. The experimentally derived kinetic isotope effect on amorphous solid water is reproduced by transition state theory. The experimentally found kinetic isotope effect on hexagonal ice is much larger than on amorphous solid water and is not reproduced by transition state theory. Additional calculations using model potentials are made for the hexagonal ice, but the experimental kinetic isotope effect is not fully reproduced. A strong influence of temperature is observed in the calculations. The influence of tunnelling is discussed in detail and related to the experiments. The calculations fully support the claims by the Kuwahata et al. (Phys. Rev. Lett., Sep. 2015, 115 (13), 133201) that on amorphous solid water the diffusion is predominantly by thermal hopping while on the polycrystalline ice tunnelling diffusion contributes significantly.
The Impact of Sub-maximal Exercise on Neuropathic Pain, Inflammation, and Affect Among Adults With Spinal Cord Injury: A Pilot Study

Introduction: Persons with spinal cord injury (SCI) often report high levels of neuropathic pain (NP) and poor well-being, which may result from increased inflammation. This study examined the impact of sub-maximal aerobic exercise on NP, inflammation and psychological affect among adults with SCI. Methods: Eight active adults with tetraplegia (n-4, AIS A-C) and paraplegia (n = 4, AIS A-C) performed 30-min of arm-crank aerobic exercise and reported their ratings of perceived exertion (RPE) each minute. Measures of NP, affect, and inflammatory cytokines (IL-6, IL-10, IL-1ra, TNF-α) were taken pre-(T0), immediately post-(T1), and 90-min post-exercise (T2). Results: NP decreased between T0 and T1 for tetraplegics (−60%, d = 0.47; CI = −0.32, 2.02) and paraplegics (−16%, d = 0.15; CI = −0.30, 0.90). Correlations between change in cytokines and change in NP were medium-to large for tetraplegics (rs ranged from −0.820 to 0.965) and paraplegics (rs ranged from −0.598 to 0.833). However, the pattern of correlations between change in cytokines and affect was inconsistent between groups. Lower baseline levels of IL-1ra predicted greater decreases in NP immediately post-exercise (r = 0.83, p = 0.01). Conclusion: Sub-maximal exercise can positively impact NP for some persons with SCI. Further experimental research should identify the optimal exercise intensity to reduce NP for persons with SCI, in addition to understanding biomarkers which may predict changes in NP. Clinical Trial Registration: www.ClinicalTrials. gov, identifier NCT03955523.
Repeated Gait Perturbation Training in Parkinson's Disease and Healthy Older Adults: A Systematic Review and Meta-Analysis

Background: Gait impairments are common in healthy older adults (HOA) and people with Parkinson's disease (PwPD), especially when adaptations to the environment are required. Traditional rehabilitation programs do not typically address these adaptive gait demands in contrast to repeated gait perturbation training (RGPT). RGPT is a novel reactive form of gait training with potential for both short and long-term consolidation in HOA and PwPD. The aim of this systematic review with meta-analysis is to determine whether RGPT is more effective than non-RGPT gait training in improving gait and balance in HOA and PwPD in the short and longer term. Methods: This review was conducted according to the PRISMA-guidelines and pre-registered in the PROSPERO database (CRD42020183273). Included studies tested the effects of any form of repeated perturbations during gait in HOA and PwPD on gait speed, step or stride length. Studies using balance scales or sway measures as outcomes were included in a secondary analysis. Effects of randomized controlled trials (RCT) on RGPT were pooled using a meta-analysis of final measures. Results: Of the 4421 studies, eight studies were deemed eligible for review, of which six could be included in the meta-analysis, totaling 209 participants (159 PwPD and 50 HOA). The studies were all of moderate quality. The meta-analysis revealed no significant effects of RGPT over non-RGPT training on gait performance (SMD = 0.16; 95% CI = −0.18, 0.49; Z = 0.92; P = 0.36). Yet, in some individual studies, favorable effects on gait speed, step length and stride length were observed immediately after the intervention as well as after a retention period. Gait variability and asymmetry, signifying more direct outcomes of gait adaptation, also indicated favorable RGPT effects in some individual studies. Conclusion: Despite some promising results, the pooled effects of RGPT on gait and balance were not significantly greater as compared to non-RGPT gait training in PwPD and HOA. However, these findings could have been driven by low statistical power. Therefore, the present review points to the imperative to conduct sufficiently powered RCT's to verify the true effects of RGPT on gait and balance in HOA and PwPD. Systematic Review Registration: https://www.crd. york.ac. uk/prospero/display_record. php? Identifier: CRD42020183273.
The Potential Effects of Dielectric Barrier Discharge Plasma on the Extraction Efficiency of Bioactive Compounds in Radix Paeoniae Alba

Radix paeoniae alba (RPA) is a kind of herbal medicine of traditional Chinese medicine (TCM) that is widely used for the treatment of liver diseases and rheumatoid arthritis in clinical practice. As a result of the low extraction efficiency of RPA by the conventional method, many patients are given high dosages. In this study, four exposure doses of dielectric barrier discharge (DBD) plasma (0, 60, 120, and 180 s) were applied to modify the extraction efficiency of paeoniflorin, benzoylpaeoniflorin, tannic acid, gallic acid, 2′-hydroxy-4′-methoxyacetophenone, and polysaccharide in RPA. Finally, the application of plasma for 180 s exhibited a 24.6% and 12.0% (p < 0.001) increase of tannic acid and polysaccharide contents, however, a 2.1% (p < 0.05) and 5.4% (p < 0.001) reduction of paeoniflorin and gallic acid composition, respectively, and no significant difference (p > 0.05) in results obtained from benzoylpaeoniflorin and 2′-hydroxy-4′-methoxyacetophenone contents. Our results of scanning electron microscopy (SEM), automatic specific surface area and pore analyzer, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermal gravimetric analysis (TGA) indicated that DBD plasma can etch the surface and undergo graft polymerization by reactive species thereby changing the water/oil holding capacity and eventually changing the extraction efficiency of bioactive compounds in RPA. Overall, our observations provide a scientific foundation for modifying the extraction efficiency of bioactive ingredients related to the pharmacological activities of RPA.
Proteomic Response to Environmental Stresses in the Stolon of a Highly Invasive Fouling Ascidian

Ascidians, particularly those highly invasive ones, are typical fouling organisms to cause significantly negative ecological and economic influence in coastal ecosystems. Stolon, which is the unique structure of some solitary ascidians to complete the essential process of adhesion, possesses extremely high tolerance to environmental stresses during biofouling and invasions. However, the mechanisms underlying environmental tolerance remain largely unknown. Here, we used the quantitative proteomics technology, isobaric tags for relative and absolute quantitation (iTRAQ), to investigate the molecular response to environmental challenges (temperature and salinity) in the stolon of a highly invasive fouling ascidian, Ciona robusta. When compared with the control, a total of 75, 86, 123, and 83 differential abundance proteins were identified under low salinity, high salinity, low temperature, and high temperature stress, respectively. Bioinformatic analyses uncovered the key pathways under both temperature and salinity stresses, including “cytoskeleton,” “signal transduction,” and “posttranslational modification,” which were involved in stolon structure stability, protein synthesis, and stress response activation. Under the low salinity stress, the “extracellular matrix” pathway was identified to play a crucial role by regulating cell signal transduction and protein synthesis. To deal with the high salinity stress, stolon could store more energy by activating “carbohydrate/lipid transport” and “catabolism” pathways. The energy generated by “lipid metabolism” pathway might be beneficial to resist the low temperature stress. The upregulation of “cell cycle” pathway could inhibit cell growth, thus helping stolon conserve more energy against the high temperature stress. Our results here provide valuable references of candidate pathways and associated genes for studying mechanisms of harsh environmental adaptation and developing antifouling strategies in marine and coastal ecosystems.
Leaders’ Windows of Tolerance for Affect Arousal—and Their Effects on Political Decision-making During COVID-19

The recent ‘affect revolution’ in strategic decision-making research has placed greater emphasis on the role of stress and emotions in decision-making, with new theorizing to highlight how leader decisions often differ from rational choice expectations. However, while existing theories add to our understanding of the interplay between affect and cognition, they have not yet explained why affect drives decisions in some situations and not others. Undertheorized connections between leaders’ neurobiological windows of tolerance to affect arousal and their self-regulatory capacity—their capacity to regulate stress and emotions so that these phenomena do not drive resulting decisions—may hold the key to explaining this variation in affect’s influence on decision-making. Furthermore, this article considers how leaders’ windows of tolerance have unique ripple effects in their social environments, thereby affecting their groups’ collective window of tolerance. While regulated leaders can convey a calming and creative influence in their organizations that helps the group access strategic decision-making, dysregulated leaders are likely to convey stress and emotion contagion—which may erode the group’s ability to cooperate, adapt, and learn. It illustrates this argument using evidence from the upper echelons of governmental decision-making, comparing New Zealand Prime Minister Jacinda Ardern’s and US President Donald Trump’s responses to the coronavirus pandemic in their respective nations. It concludes by offering hypotheses for testing the argument in future empirical research.
Implications of Community-Based Management of Marine Reserves in the Philippines for Reef Fish Communities and Biodiversity

Overfishing and destructive fishing practices are major threats to marine biodiversity in the Philippines, where over 1.9 million small-scale fishers are supported by these biodiverse marine communities. Nearly 50% of all marine fish capture in the Philippines is from artisanal fisheries, with much of it not reported or under-reported. Marine reserves, where fishing is prohibited have been created in many local government units to help restore and preserve this biodiversity. The success of these marine reserves is still under serious debate with effective management still representing a significant challenge. The lack of a governance system to centrally managed marine reserves has resulted in non-governmental organizations developing community-based management schemes. Using independent fisheries data from Rare’s Fish Forever program, we applied PERMANOVA, SIMPER and biodiversity index analyses to evaluate the community structure of reef fish in 20 sites within the Philippines. We analyzed the differences in fish assemblage inside and outside of these marine reserves, before and after community-based management had been implemented. We provide evidence that: (i) fish community structure changes within marine reserves after community-based management strategies are implemented; and (ii) community-based management of marine fisheries resources protects and promotes biodiversity inside, and in some cases, outside marine reserves. Variability across sites suggests that other social or ecological factors may be influencing the ability of marine reserves to fully protect biodiversity and marine resources. Small-scale fishers in the Philippines participate in mixed-catch harvests and depend on biodiversity and reef community structure for their livelihoods. Thus, this work has implications on how community-based management strategies for marine reserves and adjacent waters may be beneficial for the sustainability of small-scale fishers.
Overestimated SRB and Missing Girls in China

China’s SRB has been high during the past 4 decades, well exceeding the generally accepted normal range of 102–107 (United Nations Department, 1955). The SRB in China by census data was 107.63, 111.45, 119.92, and 121.21, respectively, in 1982, 1990, 2000, and 2010, and it optimistically declined to 111.30 in the just-released 2020 population census. The high sex ratio at birth (SRB) and its related consequences like missing women and male marriage squeeze have been a hot concern in China. The Chinese government has been aware of this high SRB phenomenon and stipulated a lot of holistic regulations from prohibiting medically unnecessary abortion nationwide to cultivating a girl-friendly social context. SRB was also listed as one evaluation indicator to urge family planning officials to tackle this problem. However, past SRB and missing girls may be overestimated.
Multifocal and Microvascular Involvement in Ischemic Stroke During COVID-19: A Cohort Study With Comparison With Non-COVID-19 Stroke

Introduction: Thromboembolic events, including ischemic stroke, are major complications of coronavirus disease 2019 (COVID-19). The clinical characteristics of COVID-19-related stroke are not clearly defined, and few controlled studies assessed the underlying mechanisms of cerebrovascular complications of COVID-19. This single-center retrospective observational study compared stroke characteristics between patients with and without COVID-19. Methods: This study included all patients hospitalized between March 1, 2020, and April 30, 2020, in Colmar Hospital for ischemic stroke as confirmed by imaging. The characteristics of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by real-time reverse transcriptase polymerase chain reaction or serology were compared with those without SARS-CoV-2 infection. Result: Among 772 patients, nine COVID-19 patients were compared with 50 patients without COVID-19. The following inflammatory and procoagulant marker levels were significantly higher in the COVID-19 group than those in the control group: C-reactive protein, 57.3 ± 43.4 vs. 15.0 ± 30.6 mg/L, p < 0.001; fibrinogen, 5.89 ± 1.75 vs. 4.03 ± 1.26 g/L, p < 0.001; and D-dimer, 4,833.9 ± 6,549.4 vs. 1,028.6 ± 942.6 ng/ml, p < 0.001. The rates of multifocal cerebral territory involvement (4 vs. 7, p = 0.05), microvascular involvement (4 vs. 6, p = 0.04), and thrombophilia (4 vs. 4, p = 0.014) were significantly higher in the COVID-19 group than in the control group, whereas no significant intergroup differences were found in the stroke mechanisms, i.e., cardio-embolic, atherosclerotic, small vessel disease, and cryptogenic. Conclusion: COVID-19-related stroke is characterized by hypercoagulability and hyperinflammation that may favor strokes via microvascular circulation abnormalities, microthrombus formation, and multifocal lesions.