Miracle-dz/UniFAR-FTUs huggingface dataset:
Microbial feedbacks optimize ocean iron availability

Significance Marine microbe growth is limited by iron over about half of the global ocean surface. Dissolved iron is quickly lost from the ocean, but its availability to marine microbes may be enhanced by binding with organic molecules which, in turn, are produced by microbes. We hypothesize this forms a reinforcing cycle between biological activity and iron cycling that locally matches the availability of iron and other nutrients, leading to global-scale resource colimitation between macronutrients and micronutrients, and maximizing biological productivity. Idealized models support this hypothesis, depending on the specific relationships between microbial sources and sinks of organic molecules. An evolutionary selection may have occurred which optimizes these characteristics, resulting in “just enough” iron in the ocean. Iron is the limiting factor for biological production over a large fraction of the surface ocean because free iron is rapidly scavenged or precipitated under aerobic conditions. Standing stocks of dissolved iron are maintained by association with organic molecules (ligands) produced by biological processes. We hypothesize a positive feedback between iron cycling, microbial activity, and ligand abundance: External iron input fuels microbial production, creating organic ligands that support more iron in seawater, leading to further macronutrient consumption until other microbial requirements such as macronutrients or light become limiting, and additional iron no longer increases productivity. This feedback emerges in numerical simulations of the coupled marine cycles of macronutrients and iron that resolve the dynamic microbial production and loss of iron-chelating ligands. The model solutions resemble modern nutrient distributions only over a finite range of prescribed ligand source/sink ratios where the model ocean is driven to global-scale colimitation by micronutrients and macronutrients and global production is maximized. We hypothesize that a global-scale selection for microbial ligand cycling may have occurred to maintain “just enough” iron in the ocean.
Interprofessional education in the U.S. military: harnessing simulation for team readiness

ABSTRACT Research into military interprofessional healthcare teams (MIHTs) is rarely reported in the interprofessional literature. MIHTs must effectively collaborate in the low resource and chaotic contexts of humanitarian and combat deployments; however, we have yet to study how MIHTs learn to work in these contexts. To address this gap, we investigated military interprofessional education (MIPE). Using an ethnographic approach, we conducted non-participant observations (n = 30.5 hours) of a specific platoon (n = 32 participants) during an MIPE simulation called Operation Bushmaster – a large-scale immersive simulation of battlefield deployment. Findings indicated three aspects of MIPE: (1) a culture where flailing isn’t failing; (2) the importance of followership; and (3) an interprofessional respect fostered by role adoption. Considering these findings through Dweck’s fixed vs growth mind-set conceptualization, we suggest that – although unusual when compared with traditional IPE – MIPE’s teaching and learning methods provide developmental opportunities for team members. We also suggest why Dweck’s mind-set conceptualizations could be usefully extended from an individual-focus to also include a collaborative-team-focus. We contend that the findings developed from this research could be transferred to civilian contexts so that the lessons learned by those who serve on the war front could inform those who serve at home.
‘High vault-age’: non-coding RNA control of autophagy

RNA-binding proteins typically change the fate of RNA, such as stability, translation or processing. Conversely, we recently uncovered that the small non-coding vault RNA 1-1 (vtRNA1-1) directly binds to the autophagic receptor p62/SQSTM1 and changes the protein's function. We refer to this process as ‘riboregulation'. Here, we discuss this newly uncovered vault RNA function against the background of three decades of vault RNA research. We highlight the vtRNA1-1-p62 interaction as an example of riboregulation of a key cellular process.
Ensemble Stochastic Configuration Networks for Estimating Prediction Intervals: A Simultaneous Robust Training Algorithm and Its Application

Obtaining accurate point prediction of industrial processes’ key variables is challenging due to the outliers and noise that are common in industrial data. Hence the prediction intervals (PIs) have been widely adopted to quantify the uncertainty related to the point prediction. In order to improve the prediction accuracy and quantify the level of uncertainty associated with the point prediction, this article estimates the PIs by using ensemble stochastic configuration networks (SCNs) and bootstrap method. The estimated PIs can guarantee both the modeling stability and computational efficiency. To encourage the cooperation among the base SCNs and improve the robustness of the ensemble SCNs when the training data are contaminated with noise and outliers, a simultaneous robust training method of the ensemble SCNs is developed based on the Bayesian ridge regression and M-estimate. Moreover, the hyperparameters of the assumed distributions over noise and output weights of the ensemble SCNs are estimated by the expectation-maximization (EM) algorithm, which can result in the optimal PIs and better prediction accuracy. Finally, the performance of the proposed approach is evaluated on three benchmark data sets and a real-world data set collected from a refinery. The experimental results demonstrate that the proposed approach exhibits better performance in terms of the quality of PIs, prediction accuracy, and robustness.
The Connecting and Reflecting Experience (CARE): theoretical foundation and development of mentalizing-focused parenting groups

ABSTRACT In underserved communities with limited resources and disproportionately high morbidity and mortality rates, attachment-based, short-term, group interventions that are effective yet simple to disseminate can have a profound public health impact. This paper describes the implementation of a mentalizing-focused group parenting intervention. The Connecting and Reflecting Experience (CARE) serves primary caregivers of children from birth to 18 years within a diverse and impoverished community setting. Families living in communities facing health disparities are at heightened risk for intergenerational cycles of trauma which give rise to myriad public health crises at high societal cost. CARE’s mission is to facilitate the intergenerational transmission of secure attachment which can profoundly reduce rates of psychiatric illness for future generations. The theoretical and empirical bases for the intervention and the evidence base for existing mentalizing-focused parenting interventions are reviewed. The program’s structure and treatment goals are presented in the context of clinical case material.
manta: a Clustering Algorithm for Weighted Ecological Networks

manta comes with unique strengths, such as the abilities to identify nodes that represent an intermediate between clusters, to exploit negative edges, and to assess the robustness of cluster membership. manta does not require parameter tuning, is straightforward to install and run, and can be easily combined with existing microbial network inference tools. ABSTRACT Microbial network inference and analysis have become successful approaches to extract biological hypotheses from microbial sequencing data. Network clustering is a crucial step in this analysis. Here, we present a novel heuristic network clustering algorithm, manta, which clusters nodes in weighted networks. In contrast to existing algorithms, manta exploits negative edges while differentiating between weak and strong cluster assignments. For this reason, manta can tackle gradients and is able to avoid clustering problematic nodes. In addition, manta assesses the robustness of cluster assignment, which makes it more robust to noisy data than most existing tools. On noise-free synthetic data, manta equals or outperforms existing algorithms, while it identifies biologically relevant subcompositions in real-world data sets. On a cheese rind data set, manta identifies groups of taxa that correspond to intermediate moisture content in the rinds, while on an ocean data set, the algorithm identifies a cluster of organisms that were reduced in abundance during a transition period but did not correlate strongly to biochemical parameters that changed during the transition period. These case studies demonstrate the power of manta as a tool that identifies biologically informative groups within microbial networks. IMPORTANCE manta comes with unique strengths, such as the abilities to identify nodes that represent an intermediate between clusters, to exploit negative edges, and to assess the robustness of cluster membership. manta does not require parameter tuning, is straightforward to install and run, and can be easily combined with existing microbial network inference tools.
Early corrective surgery may prevent Baroreflex impairment in congenital heart diseases

Arrhythmias in tetralogy of Fallot (ToF) and transposition of the great arteries (TGA) could be the consequence of reduced baroreflex-sensitivity (BRS). Hypoxia until the first surgical correction in these patients may impair BRS. We aimed to compare the BRS of ToF, TGA and control subjects and test the effect of the timing of operation on BRS. 19 patients with ToF, 22 patients with TGA and 19 healthy controls were enrolled. Carotid pulse pressure (PPc) was similar in ToF and TGA patients but lower in controls. BRS was lower in the ToF group compared to the control or to the TGA groups. The first operation was performed later in patients with ToF than in patients with TGA. Adjustment for PPc attenuated the difference in BRS between ToF and control subjects. Adjustment for age at corrective surgery abolished the difference in BRS between the ToF and the TGA groups. In ToF patients, reduced BRS could be explained by the stiffening of central arteries and the later corrective surgery. Earlier surgical correction may prevent irreversible deterioration of baroreflex-function and arrhythmia development in ToF patients.
Proteins containing ubiquitin-like (Ubl) domains not only bind to 26S proteasomes but also induce their activation

Significance Most protein degradation in eukaryotic cells is catalyzed by the 26S proteasome, which digests proteins marked for destruction by a chain of ubiquitin molecules. Typically, 26S proteasomes are present in cells as inactive particles that can become active when a ubiquitylated substrate binds. Proteasomes are usually viewed as containing a characteristic set of subunits, but, in cells, many important proteins associate transiently with proteasomes to deliver substrates or provide additional activities. Here, we show that a major class of proteasome-binding proteins that contain a ubiquitin-like (Ubl) domain can also enhance the 26S proteasome’s multiple enzymatic activities that are critical for protein degradation. Thus Ubl-containing proteins, in addition to their other functions, have this unexpected regulatory role. During protein degradation by the ubiquitin–proteasome pathway, latent 26S proteasomes in the cytosol must assume an active form. Proteasomes are activated when ubiquitylated substrates bind to them and interact with the proteasome-bound deubiquitylase Usp14/Ubp6. The resulting increase in the proteasome’s degradative activity was recently shown to be mediated by Usp14’s ubiquitin-like (Ubl) domain, which, by itself, can trigger proteasome activation. Many other proteins with diverse cellular functions also contain Ubl domains and can associate with 26S proteasomes. We therefore tested if various Ubl-containing proteins that have important roles in protein homeostasis or disease also activate 26S proteasomes. All seven Ubl-containing proteins tested—the shuttling factors Rad23A, Rad23B, and Ddi2; the deubiquitylase Usp7, the ubiquitin ligase Parkin, the cochaperone Bag6, and the protein phosphatase UBLCP1—stimulated peptide hydrolysis two- to fivefold. Rather than enhancing already active proteasomes, Rad23B and its Ubl domain activated previously latent 26S particles. Also, Ubl-containing proteins (if present with an unfolded protein) increased proteasomal adenosine 5′-triphosphate (ATP) hydrolysis, the step which commits substrates to degradation. Surprisingly, some of these proteins also could stimulate peptide hydrolysis even when their Ubl domains were deleted. However, their Ubl domains were required for the increased ATPase activity. Thus, upon binding to proteasomes, Ubl-containing proteins not only deliver substrates (e.g., the shuttling factors) or provide additional enzymatic activities (e.g., Parkin) to proteasomes, but also increase their capacity for proteolysis.
Detecting TRA-1-60 in cancer via a novel Zr-89 labeled immunoPET imaging agent.

TRA-1-60 (TRA) is a cell-surface antigen implicated in drug resistance, relapse and recurrence. Its expression has been reported in breast, prostate, pancreatic, ovarian tumors and follicular lymphoma, which paved the development of the therapeutic antibody, Bstrongomab (Bsg) and its drug conjugates. Because patient selection is critical to achieve clinical benefit, a non-invasive imaging agent to select TRA+ lesions in patients is needed. Herein, we report the development of the immunopositron emission tomography (immunoPET) radiotracer 89Zr-radiolabeled Bsg and its potential to delineate TRA+ tumors. METHODS Bsg was conjugated to the bifunctional chelator desferrioxamine (DFO) and radiolabeled with [89Zr]Zr-oxalate. [89Zr]Zr-DFO-Bsg was characterized in vitro and evaluated in vivo for uptake and specificity in high and low TRA-expressing BxPC-3 pancreatic and PC-3 prostate cancer models, respectively. Uptake was compared against [89Zr]Zr-DFO-IgG, a non-specific control radiotracer. Immunohistochemical (IHC) staining of patient cancer tissues using Bsg was performed to explore its clinical significance. RESULTS A specific activity of 0.18 ± 0.01 GBq/mg (4.8 ± 0.3 mCi/mg) was obtained for [89Zr]Zr-DFO-Bsg. BxPC-3 xenografts exhibited three-fold higher radiotracer uptake compared to [89Zr]Zr-DFO-IgG. Competitive saturation studies using BxPC-3 xenografts further confirmed tracer specificity. The TRA-specific probe had lower accumulation in PC-3 xenografts. Ex vivo autoradiographs correlated with TRA expression from the histopathology of the resected tumor xenografts. Additionally, patient cancer tissues demonstrated positive staining with Bsg with metastatic lesions exhibiting the highest staining. CONCLUSIONS This study demonstrates the potential of [89Zr]Zr-DFO-Bsg as an imaging agent for non-invasive detection of TRA+ tumors.
Risk factors for myocardial infarction in very young South Asians.

PURPOSE OF REVIEW It is only over the last few decades that the impact of coronary artery disease (CAD) in very young South Asian population has been recognized. There has been a tremendous interest in elucidating the causes behind this phenomenon and these efforts have uncovered several mechanisms that might explain the early onset of CAD in this population. The complete risk profile of very young South Asians being affected by premature CAD still remains unknown. RECENT FINDINGS The existing data fail to completely explain the burden of premature occurrence of CAD in South Asians especially in very young individuals. Results from some studies identified nine risk factors, including low consumption of fruits and vegetables, smoking, alcohol, diabetes, psychosocial factors, sedentary lifestyle, abdominal obesity, hypertension and dyslipidemia as the cause of myocardial infarction in 90% of the patients in this population. Recent large genome-wide association studies have discovered the association of several novel genetic loci with CAD in South Asians. Nonetheless, continued scientific efforts are required to further our understanding of the causal risk factors of CAD in South Asians to address the rising burden of CVD in this vulnerable population. SUMMARY In this review, we discuss established and emerging risk factors of CAD in this population.
miRNA-411 Regulates Chondrocyte Autophagy in Osteoarthritis by Targeting Hypoxia-Inducible Factor 1 alpha (HIF-1α)

Background Osteoarthritis (OA) is the most common joint disease and is characterized by the progressive degeneration of articular cartilage. The molecular basis of OA involves various factors and has not been fully clarified. Autophagy is a conserved catabolic process that involves cellular degradation through the lysosomal machinery. Material/Methods We found that miRNA-411 regulates chondrocyte autophagy in OA by targeting hypoxia-inducible factor 1 alpha (HIF-1α) and identified the related molecular mechanism. OA condition in chondrocyte C28/I2 cells was induced by treatment with interleukin 1 beta (IL-1β). The protein expressions of LC3, p62, HIF-1α, ULK-1, and Beclin-1 were assessed by Western blot analysis, and LC3 expression was assessed by immunofluorescence. Results TargetScan analysis showed that HIF-1α mRNA is directly targeted by miR-411, which was confirmed by luciferase reporter assay. miR-411 mimic decreased HIF-1α levels in chondrocytes while miR-411 inhibitor increased HIF-1α levels in chondrocytes. Furthermore, expression of LC3, ULK-1, P62, and Beclin-1 in chondrocytes was induced by miR-411 inhibitor and was downregulated by miR-411 mimics. In addition, miR-411 mimics reduced the expression level of LC3, as determined by immunofluorescence analysis. Conclusions Our results demonstrate that miR-411 promotes chondrocyte autophagy by targeting HIF-1α, suggesting that regulating HIF-1α by miR-411 might be a therapeutic strategy for OA.
Molecular Imprinting-Based Surface-Enhanced Raman Scattering Sensors.

Molecularly imprinted polymers (MIPs) receive extensive interests, owing to their structure predictability, recognition specificity and application universality as well as robustness, simplicity and inexpensiveness. Surface-enhanced Raman scattering (SERS) is regarded as an ideal optical detection candidate for its unique features of fingerprint recognition, non-destructive property, high sensitivity and rapidity. Accordingly, MIPs based SERS (MIP-SERS) sensors have attracted significant research interest for versatile applications especially in the field of chemo and bio analysis, showing excellent identification and detection performances. Herein, we comprehensively review the recent advances in MIP-SERS sensors construction and applications, including sensing principles and signal enhancement mechanisms, focusing on novel construction strategies and representative applications. Firstly, the basic structure of the MIP-SERS sensors is briefly outlined. Secondly, novel imprinting strategies are highlighted mainly including multi-functional monomer imprinting, dummy template imprinting, living/controlled radical polymerization and stimuli-responsive imprinting. Thirdly, typical application of MIP-SERS sensors in chemo/bio analysis is summarized from both small and macromolecular aspects. Lastly, the challenges and perspectives of the MIP-SERS sensors are proposed, orienting sensitivity improvement and application expanding.
Essential requirement for nicastrin in marginal zone and B-1 B cell development

Significance Follicular B cells generally require T cell help to contribute to adaptive immunity, producing several isotypes of immunoglobulins that carry out distinct effector functions. Two specialized B cell subsets, marginal zone (MZ) and B-1 B cells, arise from different developmental steps and have different functions. They become activated to produce antibodies without T cell help and are the major sources of plasma IgM. We identified a viable missense allele of Ncstn in a forward genetic screen. We discovered that the development of MZ and B-1 B cells, TI antibody response, fur pigmentation, and intestinal homeostasis critically depend on the glycosylation status of NCSTN and the catalytic activity of γ-secretase toward its substrate Notch, a critical receptor in numerous developmental decisions. γ-secretase is an intramembrane protease complex that catalyzes the proteolytic cleavage of amyloid precursor protein and Notch. Impaired γ-secretase function is associated with the development of Alzheimer’s disease and familial acne inversa in humans. In a forward genetic screen of mice with N-ethyl-N-nitrosourea-induced mutations for defects in adaptive immunity, we identified animals within a single pedigree exhibiting both hypopigmentation of the fur and diminished T cell-independent (TI) antibody responses. The causative mutation was in Ncstn, an essential gene encoding the protein nicastrin (NCSTN), a member of the γ-secretase complex that functions to recruit substrates for proteolysis. The missense mutation severely limits the glycosylation of NCSTN to its mature form and impairs the integrity of the γ-secretase complex as well as its catalytic activity toward its substrate Notch, a critical regulator of B cell and T cell development. Strikingly, however, this missense mutation affects B cell development but not thymocyte or T cell development. The Ncstn allele uncovered in these studies reveals an essential requirement for NCSTN during the type 2 transitional-marginal zone precursor stage and peritoneal B-1 B cell development, the TI antibody response, fur pigmentation, and intestinal homeostasis in mice.
Serious video games and virtual reality for prevention and neurorehabilitation of cognitive decline because of aging and neurodegeneration.

PURPOSE OF REVIEW Cognitive decline because of aging and neurodegeneration has become increasingly prevalent. This calls for the implementation of efficacious, motivating, standardized and widely available cognitive interventions for the elderly. In this context, serious video games and virtual reality may represent promising approaches. Here, we review recent research on their potential for cognitive prevention and neurorehabilitation of age-related cognitive decline and mild cognitive impairment (MCI). RECENT FINDINGS The majority of currently available data in this evolving domain lacks the methodological quality to draw reliable conclusions on the potential of novel technology for cognitive training in older people. However, single well designed randomized controlled trials have reported promising effects of cognitive interventions involving serious video games and virtual reality. The cognitive benefits of exergames promoting physical exercise with and without combined cognitive training remain unclear. SUMMARY The immersion into stimulating and motivating environments along with training content based on neuroscientific and neuropsychological models may represent a significant advance as compared with conventional computerized cognitive training. Additional research with sound methodology including sufficient sample sizes, active control groups and meaningful outcome measures of everyday function is needed to elucidate the potential of serious video games and virtual reality in multifactorial neurorehabilitation of cognitive decline in aging and neurodegeneration.
Beta‐blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity rationale and study design of a prospective, randomized, controlled trial (The Preserve‐HR trial)

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta‐blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients.