Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurement of the Absolute Branching FractionsB to D\pi, D^*\pi, D^{**}\pi with aMissing Mass Method

We present branching fraction measurements of charged and neutral B decays to D{pi}{sup -}, D*{pi}{sup -} and D**{pi}{sup -} with a missing mass method, based on a sample of 231 million {Upsilon}(4S) {yields} B{bar B} pairs collected by the BABAR detector at the PEP-II e{sup +}e{sup -} collider. One of the B mesons is fully reconstructed and the other one decays to a reconstructed charged {pi} and a companion charmed meson identified by its recoil mass, inferred by kinematics. Here D** refers to the sum of all the non-strange charm meson states with masses in the range 2.2-2.8 GeV/c{sup 2}.
Expression Ratios of the Anti-Apoptotic BCL2 Family Members Dictate the Selective Addiction of KSHV-Transformed Primary Effusion Lymphoma Cell Lines to MCL1

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes several malignancies in people living with HIV, including primary effusion lymphoma (PEL). PEL cell lines exhibit oncogene addictions to both viral and cellular genes. Using CRISPR screens, we previously identified cellular oncogene addictions in PEL cell lines, including MCL1. MCL1 is a member of the BCL2 family, which functions to prevent intrinsic apoptosis and has been implicated in several cancers. Despite the overlapping functions of the BCL2 family members, PEL cells are only dependent on MCL1 suggesting that MCL1 may have non-redundant functions. To investigate why PEL cells exhibit selective addiction to MCL1, we inactivated the intrinsic apoptosis pathway by engineering BAX/BAK1 double knockout cells. In this context, PEL cells become resistant to MCL1 knockdown or MCL1 inactivation by the MCL1 inhibitor S63845, indicating that the main function of MCL1 in PEL cells is to prevent BAX/BAK1-mediated apoptosis. The selective requirement to MCL1 is due to MCL1 being expressed in excess over the BCL2 family. Ectopic expression of several BCL2 family proteins, as well as the KSHV BCL2 homolog, significantly decreased basal caspase 3/7 activity and buffered against staurosporine-induced apoptosis. Finally, over-expressed BCL2 family members can functionally substitute for MCL1, when it is inhibited by S63845. Together our data indicate that the expression levels of the BCL2 family likely explain why PEL tumor cells are highly addicted to MCL1. Importantly, our results suggest that caution should be taken when considering MCL1i as a monotherapy regimen for PEL, because resistance can easily develop. IMPORTANCE Primary effusion lymphoma (PEL) is caused by Kaposi’s sarcoma-associated herpesvirus. We previously showed that PEL cell lines require the anti-apoptotic protein MCL1 for survival, but not the other BCL2 family proteins. This selective dependence to MCL1 is unexpected as the BCL2 family functions similarly in preventing intrinsic apoptosis. Recently, new roles for MCL1 not shared with the BCL2 family have emerged. Here, we show that non-canonical functions of MCL1 are unlikely essential. Instead, MCL1 mainly functions to prevent apoptosis. The specific requirement to MCL1 is due to MCL1 being expressed in excess over the BCL2 family. Consistent with this model, shifting these expression ratios changes the requirement away from MCL1 and towards the dominant BCL2 family gene. Together, our results indicate that although MCL1 is an attractive chemotherapeutic target to treat PEL, careful consideration must be taken as resistance to MCL1-specific inhibitors easily develops through BCL2 family overexpression.
Tracking N- and C-termini of C. elegans polycystin-1 reveals their distinct targeting requirements and functions in cilia and extracellular vesicles

The cilium acts as an antenna receiving and sending signals, the latter via extracellular vesicles (EVs). In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 (PC1) and polycystin-2 (PC2) localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. However, the functions of the polycystins on cilia and EVs remain enigmatic. We used our C. elegans model and endogenously fluorescent-tagged LOV-1/polycystin-1 to study LOV-1 processing, trafficking, transport, EV biogenesis, and function in living animals. Super resolution, real time imaging reveals that LOV-1 is processed into N-terminal and C-terminal forms via a conserved GPCR proteolytic site (GPS). The LOV-1 NTM is secreted into the extracellular matrix and not localized to ciliary tip EVs. In contrast, LOV-1 CTM and PKD-2 are co-trafficked, co-transported, and co-localized in cilia and on environmentally-released ciliary EVs. LOV-1 CTM requires PKD-2 for ciliary EV localization, while PKD-2 localizes to ciliary EVs independent of LOV-1. We find that LOV-1 but not PKD-2 is required for chemosensation of an ascaroside mating pheromone. These findings indicate that the polycystins LOV-1 and PKD-2 function together and independently and provide insight to how cargo selected and packaged in ciliary EVs.
Comparing Inference under the MSC versus the MSC-with-Recombination

Accurate inference of population parameters plays a pivotal role in unravelling the evolutionary histories. While recombination has been universally accepted as a fundamental process in the evolution of sexually reproducing organisms, it remains challenging to model it exactly. Thus, existing coalescent-based approaches make different assumptions or approximations to facilitate phylogenetic inference, which can potentially bring about biases in estimates of evolutionary parameters when recombination is present. In this article, we evaluate the performance of population parameters estimation using three classes of methods: StarBEAST2, SNAPP, and diCal2. We performed whole-genome simulations in which recombination rates, mutation rates, and levels of ILS were varied. We show that StarBEAST2 using short or medium-sized loci is robust to realistic rates of recombination, which is in agreement with previous studies. SNAPP, as expected, is generally unaffected by recombination events. Most surprisingly, diCal2, a method that is designed to explicitly account for recombination, performs considerably worse than other methods under comparison.
RTK signalling promotes epithelial columnar cell shape and apical junction maintenance in human lung progenitor cells

Multipotent epithelial progenitor cells can be expanded from human embryonic lungs as organoids. and maintained in a self-renewing state using a defined medium. The organoid cells are columnar, resembling the cell morphology of the developing lung tip epithelium in vivo. Cell shape dynamics and fate are tightly coordinated during development. We therefore used the organoid system to identify signalling pathways that maintain the columnar shape of human lung tip progenitors. We found that EGF, FGF7 and FGF10 have distinct functions in lung tip progenitors. FGF7 activates MAPK/ERK and PI3K/AKT signalling and is sufficient to promote columnar cell shape in primary tip progenitors. Inhibitor experiments show that MAPK/ERK and PI3K/AKT signalling are key downstream pathways, regulating cell proliferation, columnar cell shape and cell junctions. We identified integrin signalling as a key pathway downstream of MAPK/ERK in the tip progenitors; disrupting integrin alters polarity, cell adhesion and tight junction assembly. By contrast, stimulation with FGF10 or EGF alone is not sufficient to maintain organoid columnar cell shape. This study employs organoids to provide insight into the cellular mechanisms regulating human lung development. Summary statement RTK signalling activated MAPK/ERK and PI3K/AKT signalling regulates the shape and junctional structure of human lung epithelial progenitor cells during branching.
Adaptive Encoding Speed in Working Memory

Humans can adapt when complex patterns unfold at a faster or slower pace, for instance when remembering a grocery list that is dictated at an increasingly fast rate. Integrating information over such timescales crucially depends on working memory, but although recent findings have shown that working memory capacity can be flexibly adapted, such adaptations have not yet been demonstrated for encoding speed. In a series of experiments, we found that young adults encoded at a faster rate when they were adapted to overall and recent stimulus duration. Interestingly, our participants were unable to use explicit cues to speed up encoding, even though these cues were objectively more informative than statistical information. Our findings suggest that adaptive tuning of encoding speed in working memory is a fundamental but largely implicit mechanism underlying our ability to keep up with the pace of our surroundings.
Erotic cue exposure increases physiological arousal, biases choices towards immediate rewards and attenuates model-based reinforcement learning

Computational psychiatry focuses on identifying core cognitive processes that appear altered across a broad range of psychiatric disorders. Temporal discounting of future rewards and model-based control during reinforcement learning have proven as two promising candidates. Despite its trait-like stability, temporal discounting has been suggested to be at least partly under contextual control. For example, highly arousing cues such as erotic pictures were shown to increase discounting, although overall evidence to date remains somewhat mixed. Whether model-based reinforcement learning is similarly affected by arousing cues is unclear. Here we tested cue-reactivity effects (erotic pictures) on subsequent temporal discounting and model-based reinforcement learning in a within-subjects design in n=39 healthy male participants. Self-reported and physiological arousal (cardiac activity and pupil dilation) were assessed before and during cue exposure. Arousal was increased during exposure of erotic vs. neutral cues both on the subjective and autonomic level. Erotic cue exposure nominally increased discounting as reflected by reduced choices of delayed options. Hierarchical drift diffusion modeling (DDM) linked increased discounting to a shift in the starting point bias of evidence accumulation towards immediate options. Model-based control during reinforcement learning was reduced following erotic cues according to model-agnostic analysis. Notably, DDM linked this effect to attenuated forgetting rates of unchosen options, leaving the model-based control parameter unchanged. Our findings replicate previous work on cue-reactivity effects in temporal discounting and for the first time show similar effects in model-based reinforcement learning. Our results highlight how environmental cues can impact core human decision processes and reveal that comprehensive drift diffusion modeling approaches can yield novel insights in reward-based decision processes.
XerC Is Required for the Repair of Antibiotic- and Immune-Mediated DNA Damage in Staphylococcus aureus

To survive in the host environment, pathogenic bacteria need to be able to repair DNA damage caused by both antibiotics and the immune system. The SOS response is a key bacterial pathway to repair DNA double-strand breaks and may therefore be a good target for novel therapeutics to sensitize bacteria to antibiotics and the immune response. ABSTRACT To survive in the host environment, pathogenic bacteria need to be able to repair DNA damage caused by both antibiotics and the immune system. The SOS response is a key bacterial pathway to repair DNA double-strand breaks and may therefore be a good target for novel therapeutics to sensitize bacteria to antibiotics and the immune response. However, the genes required for the SOS response in Staphylococcus aureus have not been fully established. Therefore, we carried out a screen of mutants involved in various DNA repair pathways to understand which were required for induction of the SOS response. This led to the identification of 16 genes that may play a role in SOS response induction and, of these, 3 that affected the susceptibility of S. aureus to ciprofloxacin. Further characterization revealed that, in addition to ciprofloxacin, loss of the tyrosine recombinase XerC increased the susceptibility of S. aureus to various classes of antibiotics, as well as to host immune defenses. Therefore, the inhibition of XerC may be a viable therapeutic approach to sensitize S. aureus to both antibiotics and the immune response.
Magnetocaloric effect in itinerant electron metamagnetic systems La(Fe1-xCOx)11.9Si1.1

The NaZn13-type compounds La(Fe1−xCox)11.9Si1.1 (x=0.04, 0.06, 0.08) were successfully synthesized, in which the Si content is the limit that can be reached by arc-melting technique. TC is tunable from 243 to 301 K with Co doping from x=0.04 to 0.08. Great magnetic entropy change ΔS in a wide temperature range from ∼230 to ∼320K has been observed. The adiabatic temperature change ΔTad upon changing magnetic field was also directly measured. ΔTad of sample x=0.06 reaches ∼2.4K upon a field change from 0 to 1.1 T. The temperature hysteresis upon phase transition is small, ∼1K, for all samples. The influence of Co doping on itinerant electron metamagnetic transition and magnetic entropy change is discussed.
Statistical Learning of Distractor Suppression Downregulates Prestimulus Neural Excitability in Early Visual Cortex

Visual attention is highly influenced by past experiences. Recent behavioral research has shown that expectations about the spatial location of distractors within a search array are implicitly learned, with expected distractors becoming less interfering. Little is known about the neural mechanism supporting this form of statistical learning. Here, we used magnetoencephalography (MEG) to measure human brain activity to test whether proactive mechanisms are involved in the statistical learning of distractor locations. Specifically, we used a new technique called rapid invisible frequency tagging (RIFT) to assess neural excitability in early visual cortex during statistical learning of distractor suppression while concurrently investigating the modulation of posterior alpha band activity (8–12 Hz). Male and female human participants performed a visual search task in which a target was occasionally presented alongside a color-singleton distractor. Unbeknown to the participants, the distracting stimuli were presented with different probabilities across the two hemifields. RIFT analysis showed that early visual cortex exhibited reduced neural excitability in the prestimulus interval at retinotopic locations associated with higher distractor probabilities. In contrast, we did not find any evidence of expectation-driven distractor suppression in alpha band activity. These findings indicate that proactive mechanisms of attention are involved in predictive distractor suppression and that these mechanisms are associated with altered neural excitability in early visual cortex. Moreover, our findings indicate that RIFT and alpha band activity might subtend different and possibly independent attentional mechanisms. SIGNIFICANCE STATEMENT What we experienced in the past affects how we perceive the external world in the future. For example, an annoying flashing light might be better ignored if we know in advance where it usually appears. This ability of extracting regularities from the environment is called statistical learning. In this study, we explore the neuronal mechanisms allowing the attentional system to overlook items that are unequivocally distracting based on their spatial distribution. By recording brain activity using MEG while probing neural excitability with a novel technique called RIFT, we show that the neuronal excitability in early visual cortex is reduced in advance of stimulus presentation for locations where distracting items are more likely to occur.
Gene interaction perturbation network deciphers a high-resolution taxonomy in colorectal cancer

Molecular subtypes of colorectal cancer (CRC) are currently identified via the snapshot transcriptional profiles, largely ignoring the dynamic changes of gene expressions. Conversely, biological networks remain relatively stable irrespective of time and condition. Here, we introduce an individual-specific gene interaction perturbation network-based (GIN) approach and identify six GIN subtypes (GINS1-6) with distinguishing features: (i) GINS1 (proliferative, 24%∼34%), elevated proliferative activity, high tumor purity, immune-desert, PIK3CA mutations, and immunotherapeutic resistance; (ii) GINS2 (stromal-rich, 14%∼22%), abundant fibroblasts, immune-suppressed, stem-cell-like, SMAD4 mutations, unfavorable prognosis, high potential of recurrence and metastasis, immunotherapeutic resistance, and sensitive to fluorouracil-based chemotherapy; (iii) GINS3 (KRAS-inactivated, 13%∼20%), high tumor purity, immune-desert, activation of EGFR and ephrin receptors, chromosomal instability (CIN), fewer KRAS mutations, SMOC1 methylation, immunotherapeutic resistance, and sensitive to cetuximab and bevacizumab; (iv) GINS4 (mixed, 10%∼19%), moderate level of stromal and immune activities, transit-amplifying-like, and TMEM106A methylation; (v) GINS5 (immune-activated, 12%∼24%), stronger immune activation, plentiful tumor mutation and neoantigen burden, microsatellite instability and high CpG island methylator phenotype, BRAF mutations, favorable prognosis, and sensitive to immunotherapy and PARP inhibitors; (vi) GINS6, (metabolic, 5%∼8%), accumulated fatty acids, enterocyte-like, and BMP activity. Overall, the novel high-resolution taxonomy derived from an interactome perspective could facilitate more effective management of CRC patients.
Rising above the noise: The influence of population dynamics on the evolution of acoustic signaling

Acoustic signaling is employed by many sexually reproducing species to select for mates and enhance fitness. However, signaling in dense populations can create an auditory background, or chorus, which can interfere with a signal receiver’s phonotactic selectivity, or the ability to distinguish signals. Feedback between the strength of an individual’s signal, phonotactic selectivity, and population size, may interactin complex ways to impact the evolution of the signaling trait within a population, potentially leading to the emergence of silence. Here we formulate a general model that captures the dynamic feedback between individual acoustic signalers, phonotactic selectivity, and the populationlevel chorus to explore the eco-evolutionary dynamics of an acoustic trait. We find that population dynamics has a significant influence on the evolutionary dynamics of the signaling trait, and that very sharp transitions separate conspicuous from silent populations. Our framework also reveals that increased phonotactic selectivity promotes the stability of signaling populations. We suggest that understanding the relationship between factors influencing population size such as environmental productivity, as well as factors influencing phonotactic selectivity such as anthropogenic noise, are central to understanding the complex mosaic of acoustically signaling and silent populations.
Two-Dimensional Riemann Problem for a Hyperbolic System of Nonlinear Conservation Laws: I. Four-J Cases

Abstract The Riemann problem for a two-dimensional 2 × 2 hyperbolic system of nonlinear conservation laws has been. solved analytically. The solutions reveal a variety of geometric structures; 57 exact solutions and the corresponding criteria have been obtained. A kind of new nonlinear hyperbolic wave which we call delta shock appears in some solutions. The delta shock is a discontinuity surface which is the support of a Dirac δ-function.
D-mannose ameliorates age-associated cellular senescence in the bladder urothelium and NLRP3/Gasdermin/IL-1β -driven pyroptotic epithelial cell shedding

Aging is a risk factor for disease via increased susceptibility to infection, decreased ability to maintain homeostasis, inefficiency in combatting stress, and decreased regenerative capacity. Multiple diseases including urinary tract infection (UTI), are more prevalent with age; however, the mechanisms underlying how aging affects the urinary tract mucosa and the reason why aging correlates with disease are poorly understood. Here, we show that, relative to young (8-12 weeks) mice, the urothelium of aged (18-24 months) female mice accumulates large lysosomes with decreased acid phosphatase activity and shows overall decreased autophagic flux. Aged bladders exhibit basally high accumulation of reactive oxygen species (ROS) and dampened redox response. Furthermore, the aged urothelium exhibits a canonical senescence-associated secretory phenotype (SASP) at baseline with continuous NLRP3-inflammasome- and Gasdermin D (GSDMD)-dependent pyroptotic cell death. Accordingly, we find that aged mice chronically exfoliate epithelial cells. When infected with uropathogenic E. coli, infected aged mice harbor more bacterial reservoirs post-infection and are prone to spontaneous recurrent UTI. Finally, treatment of aged mice with D-Mannose, a natural bioactive monosaccharide, rescues autophagy flux, reverses SASP, and limits pyroptotic epithelial shedding. Thus, normal aging dramatically affects bladder physiology with aging alone increasing baseline cellular stress and susceptibility to infection. Additionally, our results suggest that mannose supplementation could serve as a senotherapeutic to limit age-associated urothelial dysfunction.
Beta-cell Metabolic Activity Rather than Gap Junction Structure Dictates Subpopulations in the Islet Functional Network

Diabetes is caused by dysfunction of electrically coupled heterogeneous β-cells within the pancreatic islet. Functional networks have been used to represent cellular synchronization and study β-cells subpopulations, which play an important role in driving dynamics. The mechanism by which highly synchronized β-cell subpopulations drive islet function is not clear. We used experimental and computational techniques to investigate the relationship between functional networks, structural (gap-junction) networks, and underlying β-cell dynamics. Highly synchronized subpopulations in the functional network were differentiated by metabolic dynamics rather than structural coupling. Consistent with this, metabolic similarities were more predictive of edges in the islet functional network. Finally, removal of gap junctions, as occurs in diabetes, caused decreases in the efficiency and clustering of the functional network. These results indicate that metabolism rather than structure drives connections in the function network, deepening our interpretation of functional networks and the formation of functional sub-populations in dynamic tissues such as the islet.