Miracle-dz/UniFAR-FTUs huggingface dataset:
MLL methyltransferases regulate H3K4 methylation to ensure CENP-A assembly at human centromeres

The active state of centromeres is epigenetically defined by the presence of CENP-A interspersed with histone H3 nucleosomes. While the importance of dimethylation of H3K4 for centromeric transcription has been highlighted in various studies, the identity of the enzyme(s) depositing these marks on the centromere is still unknown. The MLL (KMT2) family plays a crucial role in RNA polymerase II (Pol II)-mediated gene regulation by methylating H3K4. Here, we report that MLL methyltransferases regulate transcription of human centromeres. CRISPR-mediated down-regulation of MLL causes loss of H3K4me2, resulting in an altered epigenetic chromatin state of the centromeres. Intriguingly, our results reveal that loss of MLL, but not SETD1A, increases co-transcriptional R-loop formation, and Pol II accumulation at the centromeres. Finally, we report that the presence of MLL and SETD1A is crucial for kinetochore maintenance. Altogether, our data reveal a novel molecular framework where both the H3K4 methylation mark and the methyltransferases regulate stability and identity of the centromere.
Alternative polyadenylation factor CPSF6 regulates temperature compensation of the mammalian circadian clock

A defining property of circadian clocks is temperature compensation, characterized by the resilience of their near 24-hour free-running periods against changes in environmental temperature within the physiological range. While temperature compensation is evolutionary conserved across different taxa of life and has been studied within many model organisms, its molecular underpinnings remain elusive. Posttranscriptional regulations such as temperature-sensitive alternative splicing or phosphorylation have been described as underlying reactions. Here, we show that knockdown of cleavage and polyadenylation specificity factor subunit 6 (CPSF6), a key regulator of 3′-end cleavage and polyadenylation, significantly alters circadian temperature compensation in human U-2 OS cells. We apply a combination of 3′-end-RNA-seq and mass spectrometry–based proteomics to globally quantify changes in 3′ UTR length as well as gene and protein expression between wild-type and CPSF6 knockdown cells and their dependency on temperature. Since changes in temperature compensation behavior should be reflected in alterations of temperature responses within one or all of the 3 regulatory layers, we statistically assess differential responses upon changes in ambient temperature between wild-type and CPSF6 knockdown cells. By this means, we reveal candidate genes underlying circadian temperature compensation, including eukaryotic translation initiation factor 2 subunit 1 (EIF2S1).
Long‐term changes in forest response to extreme atmospheric dryness

Atmospheric dryness, as indicated by vapor pressure deficit (VPD), has a strong influence on forest greenhouse gas exchange with the atmosphere. In this study, we used long‐term (10–30 years) net ecosystem productivity (NEP) measurements from 60 forest sites across the world (1003 site‐years) to quantify long‐term changes in forest NEP resistance and NEP recovery in response to extreme atmospheric dryness. We tested two hypotheses: first, across sites differences in NEP resistance and NEP recovery of forests will depend on both the biophysical characteristics (i.e., leaf area index [LAI] and forest type) of the forest as well as on the local meteorological conditions of the site (i.e., mean VPD of the site), and second, forests experiencing an increasing trend in frequency and intensity of extreme dryness will show an increasing trend in NEP resistance and NEP recovery over time due to emergence of long‐term ecological stress memory. We used a data‐driven statistical learning approach to quantify NEP resistance and NEP recovery over multiple years. Our results showed that forest types, LAI, and median local VPD conditions explained over 50% of variance in both NEP resistance and NEP recovery, with drier sites showing higher NEP resistance and NEP recovery compared to sites with less atmospheric dryness. The impact of extreme atmospheric dryness events on NEP lasted for up to 3 days following most severe extreme events in most forests, indicated by an NEP recovery of less than 100%. We rejected our second hypothesis as we found no consistent relationship between trends of extreme VPD with trends in NEP resistance and NEP recovery across different forest sites, thus an increase in atmospheric dryness as it is predicted might not increase the resistance or recovery of forests in terms of NEP.
Berbamine promotes macrophage autophagy to clear Mycobacterium tuberculosis by regulating the ROS/Ca2+ axis

ABSTRACT Drug-resistant tuberculosis (TB) poses a major threat to global TB control; consequently, there is an urgent need to develop novel anti-TB drugs or strategies. Host-directed therapy (HDT) is emerging as an effective treatment strategy, especially for drug-resistant TB. This study evaluated the effects of berbamine (BBM), a bisbenzylisoquinoline alkaloid, on mycobacterial growth in macrophages. BBM inhibited intracellular Mycobacterium tuberculosis (Mtb) growth by promoting autophagy and silencing ATG5, partially abolishing the inhibitory effect. In addition, BBM increased intracellular reactive oxygen species (ROS), while the antioxidant N-acetyl-L-cysteine (NAC) abolished BBM-induced autophagy and the ability to inhibit Mtb survival. Furthermore, the increased intracellular Ca2+ concentration induced by BBM was regulated by ROS, and BAPTA-AM, an intracellular Ca2+-chelating agent, could block ROS-mediated autophagy and Mtb clearance. Finally, BBM could inhibit the survival of drug-resistant Mtb. Collectively, these findings provide evidence that BBM, a Food and Drug Administration (FDA)–approved drug, could effectively clear drug-sensitive and -resistant Mtb through regulating ROS/Ca2+ axis-mediated autophagy and has potential as an HDT candidate for TB therapy. IMPORTANCE It is urgent to develop novel treatment strategies against drug-resistant TB, and HDT provides a promising approach to fight drug-resistant TB by repurposing old drugs. Our studies demonstrate, for the first time, that BBM, an FDA-approved drug, not only potently inhibits intracellular drug-sensitive Mtb growth but also restricts drug-resistant Mtb by promoting macrophage autophagy. Mechanistically, BBM activates macrophage autophagy by regulating the ROS/Ca2+ axis. In conclusion, BBM could be considered as an HDT candidate and may contribute to improving the outcomes or shortening the treatment course of drug-resistant TB. It is urgent to develop novel treatment strategies against drug-resistant TB, and HDT provides a promising approach to fight drug-resistant TB by repurposing old drugs. Our studies demonstrate, for the first time, that BBM, an FDA-approved drug, not only potently inhibits intracellular drug-sensitive Mtb growth but also restricts drug-resistant Mtb by promoting macrophage autophagy. Mechanistically, BBM activates macrophage autophagy by regulating the ROS/Ca2+ axis. In conclusion, BBM could be considered as an HDT candidate and may contribute to improving the outcomes or shortening the treatment course of drug-resistant TB.
Water and Energy Budgets of a Florida Mesoscale Convective System: A Combined Observational and Modeling Study

Abstract Mesoscale water and energy budgets are diagnosed for a squall line during the Convection and Precipitation Electrification Experiment and combined with the results of the two-dimensional Goddard Cumulus Ensemble Model. The fine temporal and spatial resolution of cloud-scale processes contained in the model is used to reduce uncertainty in the diagnosed water budget residual and, thus, to arrive at a good estimate of storm-total rainfall. Profiles of cumulus heating (Q1) and drying (Q2) inferred from the sounding observations are in turn compared with the cloud-scale energy budget terms calculated from the model. This comparison reveals near-agreement in the magnitude and vertical distribution of the peak Q1 and Q2, and also the relative size of the heating and drying at different levels in the column. When the size of the mesoscale convective disturbance is approximately the same as the sounding observation network, it may be wrong to assume that the diagnosed vertical eddy heat transport account.
Stability of a visco-elastic liquid film flowing down an inclined plane

The investigation concerns the stability of an incompressible second-order fluid (visco-elastic) film flowing down an inclined plane under gravity with respect to two-dimensional disturbances. When the elastic parameter is negative as in the case of a solution of polyisobutylene in cetane, surface disturbances (‘soft’ waves) are found to be unstable. The analysis in this case also reveals the existence of growing shear waves (‘hard’ waves) which are highly damped in ordinary Newtonian fluids.
“A Natural Progression”: Australian Women's Attitudes About an Individualized Breast Screening Model

Individualized screening is our logical next step to improve population breast cancer screening in Australia. To explore breast screening participants' views of the current program in Victoria, Australia, examine their openness to change, and attitudes toward an individualized screening model, this qualitative work was performed from a population-based breast screening cohort. This work was designed to inform the development of a decision aid to facilitate women's decisions about participating in individualized screening, and to elicit Australian consumer perspectives on the international movement toward individualized breast screening. A total of 52 women participated in one of four focus groups, and were experienced with screening with 90% of participants having had more than three mammograms. Focus group discussion was facilitated following three main themes: (i) experience of breast screening; (ii) breast cancer risk perception, and (iii) views on individualized screening. Participants had strong, positive, emotional ties to breast screening in its current structure but were supportive, with some reservations, of the idea of individualized screening. There was good understanding about the factors contributing to personalized risk and a wide range of opinions about the inclusion of genetic testing with genetic testing being considered a foreign and evolving domain. Individualized breast screening that takes account of risk factors such as mammographic density, lifestyle, and genetic factors would be acceptable to a population of women who are invested in the current system. The communication and implementation of a new program would be critical to its acceptance and potential success. Reservations may be had in regards to uptake of genetic testing, motivations behind the change, and management of the women allocated to a lower risk category.
Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus.
Regulation of the apical extension morphogenesis tunes the mechanosensory response of microvilliated neurons

Multiple types of microvilliated sensory cells exhibit an apical extension thought to be instrumental in the detection of sensory cues. The investigation of the mechanisms underlying morphogenesis of sensory apparatus is critical to understand the biology of sensation. Most of what we currently know comes from the study of the hair bundle of the inner ear sensory cells, but morphogenesis and function of other sensory microvilliated apical extensions remain poorly understood. We focused on spinal sensory neurons that contact the cerebrospinal fluid (CSF) through the projection of a microvilliated apical process in the central canal, referred to as cerebrospinal fluid-contacting neurons (CSF-cNs). CSF-cNs respond to pH and osmolarity changes as well as mechanical stimuli associated with changes of flow and tail bending. In vivo time-lapse imaging in zebrafish embryos revealed that CSF-cNs are atypical neurons that do not lose their apical attachment and form a ring of actin at the apical junctional complexes (AJCs) that they retain during differentiation. We show that the actin-based protrusions constituting the microvilliated apical extension arise and elongate from this ring of actin, and we identify candidate molecular factors underlying every step of CSF-cN morphogenesis. We demonstrate that Crumbs 1 (Crb1), Myosin 3b (Myo3b), and Espin orchestrate the morphogenesis of CSF-cN apical extension. Using calcium imaging in crb1 and espin mutants, we further show that the size of the apical extension modulates the amplitude of CSF-cN sensory response to bending of the spinal cord. Based on our results, we propose that the apical actin ring could be a common site of initiation of actin-based protrusions in microvilliated sensory cells. Furthermore, our work provides a set of actors underlying actin-based protrusion elongation shared by different sensory cell types and highlights the critical role of the apical extension shape in sensory detection.
Corticostriatal Connectivity during Prosocial Decision-making Relates to Giving Behavior during Adolescence

Abstract Prosocial behavior during adolescence becomes more differentiated based on the recipient of the action as well as the perceived value or benefit, relative to the cost to self, for the recipients. The current study investigated how functional connectivity of corticostriatal networks tracked the value of prosocial decisions as a function of target recipient (caregiver, friend, stranger) and age of the giver, and how they related to giving behavior. Two hundred sixty-one adolescents (9–15 and 19–20 years of age) completed a decision-making task in which they could give money to caregivers, friends, and strangers while undergoing fMRI. Results indicated that adolescents were more likely to give to others as the value of the prosocial decision (i.e., the difference between the benefit to other relative to the cost to self) increased; this effect was stronger for known (caregiver and friends) than unknown targets, and increased with age. Functional connectivity between the nucleus accumbens (NAcc) and OFC increased as the value of the prosocial decisions decreased for strangers, but not for known others, irrespective of choice. This differentiated NAcc-OFC functional connectivity during decision-making as a function of value and target also increased with age. Furthermore, regardless of age, individuals who evinced greater value-related NAcc-OFC functional connectivity when considering giving to strangers relative to known others showed smaller differentiated rates of giving between targets. These findings highlight the role of corticostriatal development in supporting the increasing complexity of prosocial development across adolescence.
Enhanced vortex stability in trapped vortex combustor

Abstract The Trapped Vortex Combustor (TVC) is a new design concept in which cavities are designed to trap a vortex flow structure established through the use of driver air jets located along the cavity walls. TVC offers many advantages when compared to conventional swirl-stabilised combustors. In the present work, numerical investigation of cold flow (non-reacting) through the two-cavity trapped vortex combustor is performed. The numerical simulation involves passive flow through the two-cavity TVC to obtain an optimum cavity size to trap stable vortices inside the second cavity and to observe the characteristics of the two cavity TVC. From the flow attributes, it is inferred that vortex stability is achieved by circulation and the vortex is trapped inside when a second afterbody is added.
Impact of a Ninety Minute Math Block Schedule on Math Achievement of Middle School Students

The purpose of this study was to examine the difference in the Texas Assessment of Knowledge and Skill benchmark test scores between students in a 90-minute consecutive math block and the 90-minute split math block model. Significant differences were found in mean scores for TAKS Math benchmark scores between all students in a 90-minute consecutive math block schedule and a 90-minute split math block schedule. It also found significant differences in mean scores for TAKS Math benchmark scores between ELL students in a 90-minute consecutive math block schedule and a 90-minute split math block schedule. Conclusions were that schedule type had a significant effect on the scores for all students and ELL students. The results of the study provide school administrators with necessary data to determine the type of block model most beneficial for students.
Fuzzy regularisation of deformation fields in image registration

We introduce the use of a variable smoothing kernel, whose width is driven by a fuzzy controller, to regularise a deformation field in the context of image registration. Our experiments show that such a technique outperforms the classical fixed-width regularisation, being capable of removing irregularities in the deformation field while maintaining an adequate adaptive behaviour for localised deformations,
Increasing autobiographical memory specificity: Using kindness meditation to impact features of memory retrieval

Individuals with a history of depression have an increased risk for future episodes. This risk has been linked with impaired features of autobiographical memory retrieval that remain when depressive symptoms abate, including memory specificity, remoteness, valence, and vantage perspective. Rumination has been shown to influence these impairments and can be reduced via compassion training. We therefore investigated the effects of a self-compassion meditation on autobiographical memory retrieval in remitted depression. Baseline data were collected (n = 50) using an extended version of the Autobiographical Memory Test where participants with remitted depression retrieved specific memories from a remote time period (10 cues) and from any time period (10 cues). Valence and vantage perspective were rated. Participants were then randomly allocated to a self-compassion meditation or (control) colouring intervention group. Baseline measures were reassessed after four weeks of the intervention. Results revealed increased retrieval of specific memories in the self-compassion group in comparison to the colouring group, and an increase in positive and field memories across groups while no remoteness changes were observed. This self-compassion meditation demonstrated initial promise as an intervention to influence features of autobiographical memory retrieval in remitted depression. Improvements were shown in specificity, valence, and vantage perspective. Addressing these features with this type of intervention might reduce a cognitive vulnerability to depression and should be investigated in future studies.
Laplacian Behaviour-Based Control for Robot Path Planning using Full-Sweep Successive Over-Relaxation via Nine-Point Laplacian (FSSOR9L)

This paper proposed a behaviour-based paradigm approach to the path planning problem of a mobile robot utilizing fast iteration technique to compute the configuration space rapidly. The technique employs Laplacian Behaviour-Based Control (LBBC) for robust exploration of the configuration space of the robot. The LBBC relies on Laplace’s equation that constraint the potential function in the configuration space of the robot. The solution of Laplace’s equation which represents the potential values in the configuration space is solved using Full-Sweep Successive Over-Relaxation via Nine-Point Laplacian (FSSOR9L) for fast computation. Several experiments were carried out to demonstrate the effectiveness of LBBC using fast FSSOR9L iterative method to compute the potential values rapidly and generate path for the robot successfully even in complex environment.
Habitat complexity and predator odours impact on the stress response and antipredation behaviour in coral reef fish

Mass coral bleaching events coupled with local stressors have caused regional-scale loss of corals on reefs globally. Following the loss of corals, the structural complexity of these habitats is often reduced. By providing shelter, obscuring visual information, or physically impeding predators, habitat complexity can influence predation risk and the perception of risk by prey. Yet little is known on how habitat complexity and risk assessment interact to influence predator-prey interactions. To better understand how prey’s perception of threats may shift in degraded ecosystems, we reared juvenile Pomacentrus chrysurus in environments of various habitat complexity levels and then exposed them to olfactory risk odours before simulating a predator strike. We found that the fast-start escape responses were enhanced when forewarned with olfactory cues of a predator and in environments of increasing complexity. However, no interaction between complexity and olfactory cues was observed in escape responses. To ascertain if the mechanisms used to modify these escape responses were facilitated through hormonal pathways, we conducted whole-body cortisol analysis. Cortisol concentrations interacted with habitat complexity and risk odours, such that P. chrysurus exhibited elevated cortisol levels when forewarned with predator odours, but only when complexity levels were low. Our study suggests that as complexity is lost, prey may more appropriately assess predation risk, likely as a result of receiving additional visual information. Prey’s ability to modify their responses depending on the environmental context suggests that they may be able to partly alleviate the risk of increased predator-prey interactions as structural complexity is reduced.
Simulations of magnetic elds in isolated disk galaxies

Magnetic elds are known to be dynamically important in the interstellar medium of our own Galaxy, and they are ubiquitously observed in diuse gas in the halos of galaxies and galaxy clusters. Yet, magnetic elds have typically been neglected in studies of the formation of galaxies, leaving their global inuence on galaxy formation largely unclear. Here we extend our magnetohydrodynamics (MHD) implementation in the moving-mesh code Arepo to cosmological problems which include radiative cooling and the formation of stars. In particular, we replace our previously employed divergence cleaning approach with a Powell 8-wave scheme, which turns out to be signicantly more stable, even in very dynamic environments. We verify the improved accuracy through simulations of the magneto-rotational instability in accretion disks, which reproduce the correct linear growth rate of the instability. Using this new MHD code, we simulate the formation of isolated disk galaxies similar to the Milky Way using idealized initial conditions with and without magnetic elds. We nd that the magnetic eld strength is quickly amplied