Miracle-dz/UniFAR-FTUs huggingface dataset:
A new method for phosphate purification for oxygen isotope ratio analysis in freshwater and soil extracts using solid-phase extraction with zirconium-loaded resin.

RATIONAL Phosphate (PO4 ) oxygen isotope (δ18 OPO4 ) analysis is increasingly applied to elucidate phosphorus (P) cycling. Due to its usefulness, analytical methods continue to be developed and improved to increase processing efficiency and applicability to various sample types. A new pretreatment procedure to obtain clean Ag3 PO4 using solid-phase extraction (SPE) with zirconium-loaded resin (ZrME), which can selectively adsorb PO4 is presented and evaluated here. METHODS Our method comprises 1) PO4 concentration, 2) PO4 separation by SPE, 3) cations removal, 4) Cl- removal, and 5) formation of Ag3 PO4 . The method was tested by comparing the resulting δ18 OPO4 of KH2 PO4 reagent, soil extracts (NaHCO3 , NaOH, and HCl), freshwater, and seawater with data obtained using a conventional pretreatment method. RESULT PO4 recovery of our method ranged from 79.2% to 97.8% for KH2 PO4 , soil extracts, and freshwater. Although the recovery rate indicated incomplete desorption of PO4 from the ZrME columns, our method produced high-purity of Ag3 PO4 and accurate δ18 OPO4 values (i.e., consistent with those obtained using conventional pretreatment methods). However, for seawater, the PO4 recovery was low (1.1%), probably due to the high concentration of F- and SO4 2- which interfere with PO4 adsorption on the columns. Experiments indicate that the ZrME columns could be regenerated and used repeatedly at least three times. CONCLUSION We demonstrated the utility of ZrME for purification of PO4 from freshwater and soil extracts for δ18 OPO4 analysis. Multiple samples could be processed in three days using this method increasing sample throughput and potentially facilitating more widespread use of δ18 OPO4 analysis to deepen our understanding of P-cycling in natural environments.
Highly sensitive and rapid detection of SARS‐CoV‐2 via a portable CRISPR‐Cas13a‐based lateral flow assay

To rapidly identify individuals infected with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) and control the spread of coronavirus disease (COVID‐19), there is an urgent need for highly sensitive on‐site virus detection methods. A clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein (Cas)‐based molecular diagnostic method was developed for this purpose. Here, a CRISPR system‐mediated lateral flow assay (LFA) for SARS‐CoV‐2 was established based on multienzyme isothermal rapid amplification, CRISPR‐Cas13a nuclease, and LFA. To improve the limit of detection (LoD), the crispr RNA, amplification primer, and probe were screened, in addition to concentrations of various components in the reaction system. The LoD of CRISPR detection was improved to 0.25 copy/μl in both fluorescence‐ and immunochromatography‐based assays. To enhance the quality control of the CRISPR‐based LFA method, glyceraldehyde‐3‐phosphate dehydrogenase was detected as a reference using a triple‐line strip design in a lateral flow strip. In total, 52 COVID‐19‐positive and 101 COVID‐19‐negative clinical samples examined by reverse transcription polymerase chain reaction (RT‐PCR) were tested using the CRISPR immunochromatographic detection technique. Results revealed 100% consistency, indicating the comparable effectiveness of our method to that of RT‐PCR. In conclusion, this approach significantly improves the sensitivity and reliability of CRISPR‐mediated LFA and provides a crucial tool for on‐site detection of SARS‐CoV‐2.
The human gut microbiota and glucose metabolism: a scoping review of key bacteria and the potential role of SCFAs

ABSTRACT The gut microbiota plays a fundamental role in human nutrition and metabolism and may have direct implications for type 2 diabetes and associated preconditions. An improved understanding of relations between human gut microbiota and glucose metabolism could lead to novel opportunities for type 2 diabetes prevention, but human observational studies reporting on such findings have not been extensively reviewed. Here, we review the literature on associations between gut microbiota and markers and stages of glucose dysregulation and insulin resistance in healthy adults and in adults with metabolic disease and risk factors. We present the current evidence for identified key bacteria and their potential roles in glucose metabolism independent of overweight, obesity, and metabolic drugs. We provide support for SCFAs mediating such effects and discuss the role of diet, as well as metabolites derived from diet and gut microbiota interactions. From 5983 initially identified PubMed records, 45 original studies were eligible and reviewed. α Diversity and 45 bacterial taxa were associated with selected outcomes. Six taxa were most frequently associated with glucose metabolism: Akkermansia muciniphila, Bifidobacterium longum, Clostridium leptum group, Faecalibacterium prausnitzii, and Faecalibacterium (inversely associated) and Dorea (directly associated). For Dorea and A. muciniphila, associations were independent of metabolic drugs and body measures. For A. muciniphila and F. prausnitzii, limited evidence supported SCFA mediation of potential effects on glucose metabolism. We conclude that observational studies applying metagenomics sequencing to identify species-level relations are warranted, as are studies accounting for confounding factors and investigating SCFA and postprandial glucose metabolism. Such advances in the field will, together with mechanistic and prospective studies and investigations into diet–gut microbiota interactions, have the potential to bring critical insight into roles of gut microbiota and microbial metabolites in human glucose metabolism and to contribute toward the development of novel prevention strategies for type 2 diabetes, including precision nutrition.
S100A8/A9 drives the formation of procoagulant platelets through GPIbα

Abstract S100A8/A9, also known as “calprotectin” or “MRP8/14,” is an alarmin primarily secreted by activated myeloid cells with antimicrobial, proinflammatory, and prothrombotic properties. Increased plasma levels of S100A8/A9 in thrombo-inflammatory diseases are associated with thrombotic complications. We assessed the presence of S100A8/A9 in the plasma and lung autopsies from patients with COVID-19 and investigated the molecular mechanism by which S100A8/A9 affects platelet function and thrombosis. S100A8/A9 plasma levels were increased in patients with COVID-19 and sustained high levels during hospitalization correlated with poor outcomes. Heterodimeric S100A8/A9 was mainly detected in neutrophils and deposited on the vessel wall in COVID-19 lung autopsies. Immobilization of S100A8/A9 with collagen accelerated the formation of a fibrin-rich network after perfusion of recalcified blood at venous shear. In vitro, platelets adhered and partially spread on S100A8/A9, leading to the formation of distinct populations of either P-selectin or phosphatidylserine (PS)-positive platelets. By using washed platelets, soluble S100A8/A9 induced PS exposure but failed to induce platelet aggregation, despite GPIIb/IIIa activation and alpha-granule secretion. We identified GPIbα as the receptor for S100A8/A9 on platelets inducing the formation of procoagulant platelets with a supporting role for CD36. The effect of S100A8/A9 on platelets was abolished by recombinant GPIbα ectodomain, platelets from a patient with Bernard-Soulier syndrome with GPIb-IX-V deficiency, and platelets from mice deficient in the extracellular domain of GPIbα. We identified the S100A8/A9-GPIbα axis as a novel targetable prothrombotic pathway inducing procoagulant platelets and fibrin formation, in particular in diseases associated with high levels of S100A8/A9, such as COVID-19.
Recurring Cholinergic Inputs Induce Local Hippocampal Plasticity through Feedforward Disinhibition

Abstract The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Recent experiments showed that recurring cholinergic activation of α7 nACh receptors expressed in oriens-lacunosum-moleculare (OLMα2) interneurons can directly induce LTP in Schaffer collateral (SC)–CA1 synapses. Here, we pair in vitro studies with biophysically based modeling to uncover the underlying mechanisms. According to our model, α7 nAChR activation increases OLM GABAergic activity. This results in the inhibition of the fast-spiking interneurons that provide feedforward inhibition onto CA1 pyramidal neurons. This disinhibition, paired with tightly timed SC stimulation, can induce potentiation at the excitatory synapses of CA1 pyramidal neurons. Our work details the role of cholinergic modulation in disinhibition-induced hippocampal plasticity. It relates the timing of cholinergic pairing found experimentally in previous studies with the timing between disinhibition and hippocampal stimulation necessary to induce potentiation and suggests the dynamics of the involved interneurons plays a crucial role in determining this timing.
Pre‐domestication bottlenecks of the cultivated seaweed Gracilaria chilensis

Gracilaria chilensis is the main cultivated seaweed in Chile. The low genetic diversity observed in the Chilean populations has been associated with the over‐exploitation of natural beds and/or the founder effect that occurred during post‐glacial colonization from New Zealand. How these processes have affected its evolutionary trajectory before farming and incipient domestication is poorly understood. In this study, we used 2232 single nucleotide polymorphisms (SNPs) to assess how the species' evolutionary history in New Zealand (its region of origin), the founder effect linked to transoceanic dispersion and colonization of South America, and the recent over‐exploitation of natural populations have influenced the genetic architecture of G. chilensis in Chile. The contrasting patterns of genetic diversity and structure observed between the two main islands in New Zealand attest to the important effects of Quaternary glacial cycles on G. chilensis. Approximate Bayesian Computation (ABC) analyses indicated that Chatham Island and South America were colonized independently near the end of the Last Glacial Maximum and emphasized the importance of coastal and oceanic currents during that period. Furthermore, ABC analyses inferred the existence of a recent and strong genetic bottleneck in Chile, matching the period of over‐exploitation of the natural beds during the 1970s, followed by rapid demographic expansion linked to active clonal propagation used in farming. Recurrent genetic bottlenecks strongly eroded the genetic diversity of G. chilensis prior to its cultivation, raising important challenges for the management of genetic resources in this incipiently domesticated species.
Macrophages take up VLDL-sized emulsion particles through caveolae-mediated endocytosis and excrete part of the internalized triglycerides as fatty acids

Triglycerides are carried in the bloodstream as part of very low-density lipoproteins (VLDLs) and chylomicrons, which represent the triglyceride-rich lipoproteins. Triglyceride-rich lipoproteins and their remnants contribute to atherosclerosis, possibly by carrying remnant cholesterol and/or by exerting a proinflammatory effect on macrophages. Nevertheless, little is known about how macrophages process triglyceride-rich lipoproteins. Here, using VLDL-sized triglyceride-rich emulsion particles, we aimed to study the mechanism by which VLDL triglycerides are taken up, processed, and stored in macrophages. Our results show that macrophage uptake of VLDL-sized emulsion particles is dependent on lipoprotein lipase (LPL) and requires the lipoprotein-binding C-terminal domain but not the catalytic N-terminal domain of LPL. Subsequent internalization of VLDL-sized emulsion particles by macrophages is carried out by caveolae-mediated endocytosis, followed by triglyceride hydrolysis catalyzed by lysosomal acid lipase. It is shown that STARD3 is required for the transfer of lysosomal fatty acids to the ER for subsequent storage as triglycerides, while NPC1 likely is involved in promoting the extracellular efflux of fatty acids from lysosomes. Our data provide novel insights into how macrophages process VLDL triglycerides and suggest that macrophages have the remarkable capacity to excrete part of the internalized triglycerides as fatty acids.
Longitudinal mediation by perceived burden of the pathway from thwarted belonging to suicidal ideation

Abstract Introduction Whereas the interpersonal theory of suicide entails the assumption that thwarted belongingness and perceived burdensomeness are equally important, mutually moderating, proximal causes of active ideation, evidence suggests these may not be co‐moderating processes. We tested an alternative perspective, hypothesizing that burden mediates the longitudinal relationship of thwarted belonging with active ideation. Methods A 6‐week, four‐wave prospective online survey was completed by 298 undergraduates. We tested cross‐sectional and cross‐lagged panel models (CLPM, with and without random effects) with belonging, burden, and ideation at 2‐week lags, and post hoc models with burden as a concurrent mediator of ideation. Results Approximately 28% of undergraduates reported active ideation at baseline. Cross‐sectionally, thwarted belonging had no direct influence on ideation but indirectly affected ideation via burden. This result was not confirmed in the 2‐week CLPM analyses. In post hoc analyses, we found belonging operated indirectly via later burden to influence contemporaneous ideation. Conclusions Findings suggest thwarted belonging influences active ideation indirectly via perceived burden. The effect of burden as a mediator appears to depend on its temporal proximity to ideation. Future research should delimit the period during which perceived burden is an active mediator, accommodate dual‐process approaches, and explore other mediation alternatives to co‐moderation.
Lateralization of Autonomic Output in Response to Limb-Specific Threat

Abstract In times of stress or danger, the autonomic nervous system (ANS) signals the fight or flight response. A canonical function of ANS activity is to globally mobilize metabolic resources, preparing the organism to respond to threat. Yet a body of research has demonstrated that, rather than displaying a homogenous pattern across the body, autonomic responses to arousing events, as measured through changes in electrodermal activity (EDA), can differ between right and left body locations. Surprisingly, an attempt to identify a function of ANS asymmetry consistent with its metabolic role has not been investigated. In the current study, we investigated whether asymmetric autonomic responses could be induced through limb-specific aversive stimulation. Participants were given mild electric stimulation to either the left or right arm while EDA was monitored bilaterally. In a group-level analyses, an ipsilateral EDA response bias was observed, with increased EDA response in the hand adjacent to the stimulation. This effect was observable in ∼50% of individual participants. These results demonstrate that autonomic output is more complex than canonical interpretations suggest. We suggest that, in stressful situations, autonomic outputs can prepare either the whole-body fight or flight response, or a simply a limb-localized flick, which can effectively neutralize the threat while minimizing global resource consumption. These findings are consistent with recent theories proposing evolutionary leveraging of neural structures organized to mediate sensory responses for processing of cognitive emotional cues.
Rapid adaptation of predictive models during language comprehension: Aperiodic EEG slope, individual alpha frequency and idea density modulate individual differences in real-time model updating

Predictive coding provides a compelling, unified theory of neural information processing, including for language. However, there is insufficient understanding of how predictive models adapt to changing contextual and environmental demands and the extent to which such adaptive processes differ between individuals. Here, we used electroencephalography (EEG) to track prediction error responses during a naturalistic language processing paradigm. In Experiment 1, 45 native speakers of English listened to a series of short passages. Via a speaker manipulation, we introduced changing intra-experimental adjective order probabilities for two-adjective noun phrases embedded within the passages and investigated whether prediction error responses adapt to reflect these intra-experimental predictive contingencies. To this end, we calculated a novel measure of speaker-based, intra-experimental surprisal (“speaker-based surprisal”) as defined on a trial-by-trial basis and by clustering together adjectives with a similar meaning. N400 amplitude at the position of the critical second adjective was used as an outcome measure of prediction error. Results showed that N400 responses attuned to speaker-based surprisal over the course of the experiment, thus indicating that listeners rapidly adapt their predictive models to reflect local environmental contingencies (here: the probability of one type of adjective following another when uttered by a particular speaker). Strikingly, this occurs in spite of the wealth of prior linguistic experience that participants bring to the laboratory. Model adaptation effects were strongest for participants with a steep aperiodic (1/f) slope in resting EEG and low individual alpha frequency (IAF), with idea density (ID) showing a more complex pattern. These results were replicated in a separate sample of 40 participants in Experiment 2, which employed a highly similar design to Experiment 1. Overall, our results suggest that individuals with a steep aperiodic slope adapt their predictive models most strongly to context-specific probabilistic information. Steep aperiodic slope is thought to reflect low neural noise, which in turn may be associated with higher neural gain control and better cognitive control. Individuals with a steep aperiodic slope may thus be able to more effectively and dynamically reconfigure their prediction-related neural networks to meet current task demands. We conclude that predictive mechanisms in language are highly malleable and dynamic, reflecting both the affordances of the present environment as well as intrinsic information processing capabilities of the individual.
Unequal Efficacy of Different Infarct Location in Predicting Futile Recanalization of Patients With Acute Ischemic Stroke

Objectives Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) caused by large vessel occlusion, while futile recanalization is the main factor influencing the prognosis. The present study aimed to investigate the efficacy of different infarct sites in predicting futile recanalization of patients with AIS. Methods Data were obtained from two multicenter, prospective, randomized, and controlled trials, which were concurrently conducted in China. Cases achieving a successful recanalization and with complete data of preoperative Alberta Stroke Program Early CT score (ASPECTS) and 90-day follow-up were included. The ASPECTS subregions were used to mark different infarct locations in the two cerebral hemispheres. First, the distribution of each ASPECTS subregion in the left and right hemispheres and the whole brain was analyzed, respectively. Then, the regions associated with futile recanalization were initially assessed by a univariate model. Afterward, a multivariate logistic regression model was used to identify the efficacy of different infarct sites in predicting futile recanalization. Results A total of 336 patients were included in this study with a median age of 65 years (IQR: 51–74), of whom 210 (62.50%) patients were male, and 189 (56.25%) met the definition of futile recanalization. The correlation between each ASPECTS subregion and poor outcome was different when it was restricted to a specific cerebral hemisphere. Moreover, in the left hemisphere, the internal capsule region (OR: 1.42, 95%CI: 1.13–1.95, P = 0.03) and the M3 region (OR: 2.26, 95%CI: 1.36–3.52, P = 0.001), and in the right hemisphere, M6 region (OR: 2.24, 95%CI: 1.32–3.36, P = 0.001) showed significantly higher efficacy in predicting futile recanalization. Conclusion The efficacy of different infarct locations in predicting futile recanalization is different. Different preoperative patterns of the high-efficiency regions in the infarction core or penumbra can guide the thrombectomy decision-making.
Network design problem considering system time minimization and road safety maximization: formulation and solution approaches

ABSTRACT This paper discusses the network design problem (NDP), solved for travel time minimization and road safety maximization. Similarly to other NDP models, the model is formulated as a bi-level multi-objective optimization problem. The estimation of the system time benefit and safety benefit is performed using previously developed methods. Two different approaches are applied and discussed for solving the problem: the constrained multi-objective optimization and the multi-objective genetic algorithm. Both approaches are tested on a real-size network, using a large set of candidate projects. The paper presents a discussion regarding the different optimal solutions obtained, emphasizing the relative attractiveness of the candidate projects.
Reading Jael with Women from a Traumatized Community

The story of Jael is interpreted in many different ways; the two main ones are that she is a hero to Israel, or she is a deceitful murderer. An incident that occurred in the Cape Flats, South Africa, some years ago throws light on local women’s interpretation of the Jael story. In the contemporary incident, a woman killed her son, but was viewed by women in the community not as a murderer but as a fellow-sufferer. In this study, women in the community and women in prison (some for murder) read the Jael text, act out the story, and share their views of what was happening in the biblical text. It is clear that contemporary women living in a violent community can contribute to a better understanding of the Jael text through their many parallel experiences.