Miracle-dz/UniFAR-FTUs huggingface dataset:
Mate selection among online daters in Shanghai: Why does education matter?

Prior studies of assortative mating have shown that people tend to marry someone of the same educational level, but why individuals value a mate’s education and the process of mate selection itself remain a black box in predominantly quantitative studies. With online dating’s growing popularity, research needs to examine how online daters navigate dating markets given educational preferences they hold and “freedom of choice” offered by technologies. This study aims to investigate individuals’ educational preferences and how educational preferences shape mate selection processes in online dating. In-depth interviews were conducted with 29 university-educated, heterosexual online daters (13 men, 16 women) in Shanghai. Data were analyzed through a combination of abductive and inductive coding strategies. Results showed that both educational levels and university prestige were primary mate selection criteria in online dating. Both genders considered educational sorting essential for achieving cultural matching, but only men emphasized the importance of spouse’s education for their future children’s education. Furthermore, guided by their educational preferences, online daters deliberately chose dating platforms and screened dating candidates. We argue that online daters’ emphasis on university prestige is rooted in China’s hierarchical higher education system, and gendered rationales for educational preferences stem from ingrained gender roles in Chinese families. Seemingly “personal” preferences are therefore shaped by cultural norms and institutional contexts. Moreover, results suggest that online dating may reinforce social closure among China’s educational elites.
An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow

Glucose homeostasis is the tight control of glucose in the blood. This complex control is important and not yet sufficiently understood, due to its malfunction in serious diseases like diabetes. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. Over the last 10 years, this model has been used to insert new insights from the intra-cellular level into the larger whole-body perspective. However, the original cell-organ-body translation has during these years never been updated, despite several critical shortcomings, which also have not been resolved by other modelling efforts. For this reason, we here present an updated multi-level model. This model provides a more accurate sub-division of how much glucose is being taken up by the different organs. Unlike the original model, we now also account for the different dynamics seen in the different organs. The new model also incorporates the central impact of blood flow on insulin-stimulated glucose uptake. Each new improvement is clear upon visual inspection, and they are also supported by statistical tests. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. We hope that this model will serve as an improved basis for future data integration, useful for research and drug developments within diabetes.
General Auditory and Speech-Specific Contributions to Cortical Envelope Tracking Revealed Using Auditory Chimeras

In recent years research on natural speech processing has benefited from recognizing that low-frequency cortical activity tracks the amplitude envelope of natural speech. However, it remains unclear to what extent this tracking reflects speech-specific processing beyond the analysis of the stimulus acoustics. In the present study, we aimed to disentangle contributions to cortical envelope tracking that reflect general acoustic processing from those that are functionally related to processing speech. To do so, we recorded EEG from subjects as they listened to auditory chimeras, stimuli composed of the temporal fine structure of one speech stimulus modulated by the amplitude envelope (ENV) of another speech stimulus. By varying the number of frequency bands used in making the chimeras, we obtained some control over which speech stimulus was recognized by the listener. No matter which stimulus was recognized, envelope tracking was always strongest for the ENV stimulus, indicating a dominant contribution from acoustic processing. However, there was also a positive relationship between intelligibility and the tracking of the perceived speech, indicating a contribution from speech-specific processing. These findings were supported by a follow-up analysis that assessed envelope tracking as a function of the (estimated) output of the cochlea rather than the original stimuli used in creating the chimeras. Finally, we sought to isolate the speech-specific contribution to envelope tracking using forward encoding models and found that indices of phonetic feature processing tracked reliably with intelligibility. Together these results show that cortical speech tracking is dominated by acoustic processing but also reflects speech-specific processing. SIGNIFICANCE STATEMENT Activity in auditory cortex is known to dynamically track the energy fluctuations, or amplitude envelope, of speech. Measures of this tracking are now widely used in research on hearing and language and have had a substantial influence on theories of how auditory cortex parses and processes speech. But how much of this speech tracking is actually driven by speech-specific processing rather than general acoustic processing is unclear, limiting its interpretability and its usefulness. Here, by merging two speech stimuli together to form so-called auditory chimeras, we show that EEG tracking of the speech envelope is dominated by acoustic processing but also reflects linguistic analysis. This has important implications for theories of cortical speech tracking and for using measures of that tracking in applied research.
The active repertoire of Escherichia coli peptidoglycan amidases varies with physiochemical environment

Nearly all bacteria are encased in a peptidoglycan cell wall, an essential crosslinked matrix of polysaccharide strands and short peptide stems. In the Gram-negative model organism Escherichia coli, more than forty cell wall synthases and autolysins coordinate the growth and division of the peptidoglycan sacculus in the periplasm. The precise contribution of many of these enzymes to cell wall metabolism remains unclear due to significant apparent redundancy, particularly among the cell wall autolysins. E. coli produces three major LytC-type-N-acetylmuramoyl-L-alanine amidases, which share a role in separating the newly formed daughter cells during cytokinesis. Here, we reveal two of the three amidases exhibit growth medium-dependent changes in activity. Specifically, we report acidic growth conditions stimulate AmiB—and to a lesser extent, AmiC—activity. Combining computational and genetic analysis, we demonstrate that low pH-dependent stimulation of AmiB requires three periplasmic amidase activators: EnvC, NlpD, and YgeR. Altogether, our findings support overlapping, but not redundant, roles for the E. coli amidases in cell separation and illuminate the physiochemical environment as an important mediator of cell wall enzyme activity. IMPORTANCE Penicillin and related β-lactam antibiotics targeting the bacterial cell wall synthesis are among the most commonly prescribed antimicrobials worldwide. However, rising rates of antibiotic resistance and tolerance jeopardize their continued clinical use. Development of new cell wall active therapeutics, including those targeting cell wall autolysins, has been stymied in part due to high levels of apparent enzymatic redundancy. In this study, we report a subset of E. coli amidases involved in cell separation during cell division are not redundant and instead are preferentially active during growth in distinct pH environments. Specifically, we discover E. coli amidases AmiB and AmiC are activated by acidic pH. Three semi-redundant periplasmic regulators—NlpD, EnvC, and YgeR—collectively mediate low pH-dependent stimulation of amidase activity. This discovery contributes to our understanding of how the cell wall remains robust across diverse environmental conditions and reveals opportunities for the development of condition-specific antimicrobial agents.
eEF1A2 controls local translation and actin dynamics in structural synaptic plasticity

Synaptic plasticity involves structural modifications in dendritic spines. Increasing evidence suggests that structural plasticity is modulated by local protein synthesis and actin remodeling in a synapsis-specific manner. However, the precise molecular mechanisms connecting synaptic stimulation to these processes in dendritic spines are still unclear. In the present study, we demonstrate that the configuration of phosphorylation sites in eEF1A2, an essential translation elongation factor in neurons, is a key modulator of structural plasticity in dendritic spines. A mutant that cannot be phosphorylated stimulates translation but reduces actin dynamics and spine density. By contrast, the phosphomimetic variant loosens its association with F-actin and becomes inactive as a translation elongation factor. Metabotropic glutamate receptor signaling triggers a transient dissociation of eEF1A2 from its GEF protein in dendritic spines, in a phospho-dependent manner. We propose that eEF1A2 establishes a crosstalk mechanism that coordinates local translation and actin dynamics during spine remodeling.
Information Confusion Reveals an Innate Limit of the Information Processing by Neurons

Information experiences complex transformation processes in the brain, involving various errors. A daunting and critical challenge in neuroscience is to understand the origin of these errors and their effects on neural information processing. While previous efforts have made substantial progresses in studying the information errors in bounded, unreliable and noisy transformation cases, it still remains elusive whether the neural system is inherently error-free under an ideal and noise-free condition. This work brings the controversy to an end with a negative answer. We propose a novel neural information confusion theory, indicating the widespread presence of information confusion phenomenon after the end of transmission process, which originates from innate neuron characteristics rather than external noises. Then, we reformulate the definition of zero-error capacity under the context of neuroscience, presenting an optimal upper bound of the zero-error transformation rates determined by the tuning properties of neurons. By applying this theory to neural coding analysis, we unveil the multi-dimensional impacts of information confusion on neural coding. Although it reduces the variability of neural responses and limits mutual information, it controls the stimulus-irrelevant neural activities and improves the interpretability of neural responses based on stimuli. Together, the present study discovers an inherent and ubiquitous precision limitation of neural information transformation, which shapes the coding process by neural ensembles. These discoveries reveal that the neural system is intrinsically error-prone in information processing even in the most ideal cases. Author summary One of the most central challenges in neuroscience is to understand the information processing capacity of the neural system. Decades of efforts have identified various errors in nonideal neural information processing cases, indicating that the neural system is not optimal in information processing because of the widespread presences of external noises and limitations. These incredible progresses, however, can not address the problem about whether the neural system is essentially error-free and optimal under ideal information processing conditions, leading to extensive controversies in neuroscience. Our work brings this well-known controversy to an end with a negative answer. We demonstrate that the neural system is intrinsically error-prone in information processing even in the most ideal cases, challenging the conventional ideas about the superior neural information processing capacity. We further indicate that the neural coding process is shaped by this innate limit, revealing how the characteristics of neural information functions and further cognitive functions are determined by the inherent limitation of the neural system.
Imeglimin amplifies glucose-stimulated insulin release from diabetic islets via a distinct mechanism of action

Pancreatic islet β-cell dysfunction is characterized by defective glucose-stimulated insulin secretion (GSIS) and is a predominant component of the pathophysiology of diabetes. Imeglimin, a novel first-in-class small molecule tetrahydrotriazine drug candidate, improves glycemia and GSIS in preclinical models and clinical trials in patients with type 2 diabetes; however, the mechanism by which it restores β-cell function is unknown. Here, we show that Imeglimin acutely and directly amplifies GSIS in islets isolated from rodents with Type 2 diabetes via a mode of action that is distinct from other known therapeutic approaches. The underlying mechanism involves increases in the cellular nicotinamide adenine dinucleotide (NAD+) pool – potentially via the salvage pathway and induction of nicotinamide phosphoribosyltransferase (NAMPT) along with augmentation of glucose-induced ATP levels. Further, additional results suggest that NAD+ conversion to a second messenger, cyclic ADP ribose (cADPR), via cyclic ADP ribose hydrolase (CD38) is required for Imeglimin’s effects in islets, thus representing a potential link between increased NAD+ and enhanced glucose-induced Ca2+ mobilization which - in turn - is known to drive insulin granule exocytosis. Collectively, these findings implicate a novel mode of action for Imeglimin that explains its ability to effectively restore β-cell function and provides for a new approach to treat patients suffering from Type 2 diabetes.
Experience-dependent alteration of mnemonic representation in early visual cortex and intraparietal sulcus

The ability to discriminate between stimuli relies on a chain of neural operations associated with perception, memory and decision-making. Accumulating studies show learning-dependent plasticity in perception or decision-making, yet whether perceptual learning modifies mnemonic processing remains unclear. Here, we trained participants on an orientation discrimination task, while using fMRI and TMS to separately examine training-induced changes in working memory (WM) representation. Although fMRI decoding revealed orientation-specific neural patterns during delay period in early visual cortex (V1) before, but not after, training, neurodisruption of V1 during delay period led to behavioral deficit in both phases. In contrast, both fMRI decoding and disruptive effect of TMS showed that intraparietal sulcus (IPS) represent WM content after, but not before, training. These results suggest that sensory engagement for WM is relatively independent of training but the coding format may be altered, whereas the involvement of parietal area in WM depends on training.
Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19

SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection, whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines. GRAPHIC ABSTRACT HIGHLIGHTS Human lung organoids with mixed proximodistal epithelia are created Proximal airway cells are critical for viral infectivity Distal alveolar cells are important for emulating host response Both are required for the overzealous response in severe COVID-19 IN BRIEF An integrated stem cell-based disease modeling and computational approach demonstrate how both proximal airway epithelium is critical for SARS-CoV-2 infectivity, but distal differentiation of alveolar pneumocytes is critical for simulating the overzealous host response in fatal COVID-19.
Persistence of the ground beetle (Coleoptera: Carabidae) microbiome to diet manipulation

Host-associated microbiomes can play important roles in the ecology and evolution of their insect hosts, but bacterial diversity in many insect groups remains poorly understood. Here we examine the relationship between host environment, host traits, and microbial diversity in three species in the ground beetle family (Coleoptera: Carabidae), a group of roughly 40,000 species that synthesize a wide diversity of defensive compounds. This study found that the ground beetle microbiome is consistent across different host food sources. We used 16S amplicon sequencing to profile three species that are phylogenetically distantly related, trophically distinct, and whose defensive chemical secretions differ: Anisodactylus similis LeConte, 1851, Pterostichus serripes (LeConte, 1875), and Brachinus elongatulus Chaudoir, 1876. Wild-caught beetles were compared to individuals maintained in the lab for two weeks on carnivorous, herbivorous, or starvation diets. Soil environment but not diet had a significant effect on bacterial diversity and composition. The three carabid species have patterns of microbial diversity similar to those previously found in other insect hosts. Metagenomic samples from two highly active tissue types — guts, and pygidial gland secretory cells (which produce defensive compounds) — were processed and sequenced separately from those of the remaining body. The observed similarity of the pygidial gland secretory cell microbiome across hosts suggests the possibility that it may be a conserved community, possibly due to functional interactions related to defensive chemistry. These results provide a baseline for future studies of the role of microbes in the diversification of defensive chemical biosynthesis in carabids.
App-SpaM: phylogenetic placement of short reads without sequence alignment

Phylogenetic placement is the task of placing a query sequence of unknown taxonomic origin into a given phylogenetic tree of a set of reference sequences. Several approaches to phylogenetic placement have been proposed in recent years. The most accurate of them need a multiple alignment of the reference sequences as input. Most of them also need alignments of the query sequences to the multiple alignment of the reference sequences. A major field of application of phylogenetic placement is taxonomic read assignment in metagenomics. Herein, we propose App-SpaM, an efficient alignment-free algorithm for phylogenetic placement of short sequencing reads on a tree of a set of reference genomes. App-SpaM is based on the Filtered Spaced Word Matches approach that we previously developed. Unlike other methods, our approach neither requires a multiple alignment of the reference genomes, nor alignments of the queries to the reference sequences. Moreover, App-SpaM works not only on assembled reference genomes, but can also take reference taxa as input for which only unassembled read sequences are available. The quality of the results achieved with App-SpaM is comparable to the best available approaches to phylogenetic placement. However, since App-SpaM is not based on sequence alignment, it is between one and two orders of magnitude faster than those existing methods.
Antimicrobial stewardship in children: Where to from here?

Antimicrobial resistance (AMR) is an ever‐developing global threat and children are becoming increasingly affected. In addition to established antimicrobial stewardship (AMS) measures, it is important to recognise the need for a paediatric focus to manage the physiological and pathological differences unique to children. Most studies on paediatric AMS are drawn from resource‐rich, hospital settings. They support interventions including AMS programmes, bundled groups of interventions, guidelines and education initiatives. These must be tailored to specific institutions, populations and resources as translating interventions between these may not be effective. There are knowledge gaps in paediatric AMS, which pose challenges to designing both interventions and research in this area. These include quantifying antimicrobial consumption, defining AMS outcomes and understanding the development of AMR. Finding answers to fill these gaps needs urgent attention. There is also a need to think outside the box to improve AMS in children. Potential opportunities include intravenous antibiotics at home via hospital‐in‐the‐home programmes, earlier switching to oral antibiotics, repurposing old antibiotics and re‐evaluating children labelled as having antibiotic allergy. Using all of the possibilities available gives us the best chance of staying ahead of the relentless march of AMR in children.
“You Think Differently After Playing This Sport”: Experiences of Collegiate Goalball Players

The inclusion of athletes with and without disabilities in disability sport, known as reverse integration, has received limited attention in the literature. The purpose of this study was to understand players’ experiences in collegiate goalball. One-on-one semistructured interviews were conducted with two males (one with visual impairment, one without impairment) and four females (one with visual impairment, three without impairment) who participated in collegiate goalball programs. Interpretative thematic analysis helped uncover the meaning in participants’ goalball experiences. Reverse integration was used as a conceptual framework to guide the interpretation of participant experiences. Four main themes were extracted from the data: (a) the disability advantage, (b) the building of team cohesion, (c) the disappearing disability, and (d) enjoyment and pride. Participation in collegiate goalball allowed students to see disability as an asset and question assumptions regarding teammates’ abilities. This study highlights the potential value of providing opportunities for people with and without a disability to participate in sport together.
Factor Exposure Variation and Mutual Fund Performance

We investigated the relationship between a mutual fund’s variation in factor exposures and its future performance. Using a dynamic state-space version of the Carhart (1997) four-factor model to capture factor variations, we found that funds with volatile factor exposures underperform funds with stable factor exposures by 147 bps a year. This underperformance is explained neither by volatile factor loadings of a fund’s equity holdings nor by a fund’s forced trading through investor flows. We conclude that fund managers voluntarily attempt to time factors but are unsuccessful at doing so. Disclosure: The authors report no conflicts of interest. Editor’s Note Submitted 13 February 2020 Accepted 5 August 2020 by Stephen J. Brown