Miracle-dz/UniFAR-FTUs huggingface dataset:
Artificial upwelling leads to a large increase in surface dissolved organic matter concentrations

In the face of climate change there is a need to reduce atmospheric CO2 concentrations. Artificial upwelling of nutrient-rich deep waters has been proposed as a method to enhance the biological carbon pump in oligotrophic oceanic regions in order to increase carbon sequestration. However, the fate of the newly produced organic matter, and specifically of its resulting dissolved fraction, is not clearly understood. Here we examine the effect of different upwelling intensities and modes (single pulse versus recurring pulses) on the dissolved organic matter pool (DOM). We introduced nutrient-rich deep water to large scale mesocosms (∼44 m3) in the oligotrophic subtropical North Atlantic and found that artificial upwelling strongly increased DOM concentrations and changed its characteristics. The magnitude of the observed changes was related to the upwelling intensity: more intense treatments led to higher accumulation of dissolved organic carbon (>70 μM of excess DOC over ambient waters for the most intense) and to comparatively stronger changes in DOM characteristics (increased proportions of chromophoric DOM (CDOM) and humic-like fluorescent DOM), suggesting a transformation of the DOM pool at the molecular level. Moreover, the single upwelling pulse resulted in higher CDOM quantities with higher molecular weight than the recurring upwelling mode. Together, our results indicate that under artificial upwelling, large DOM pools may accumulate in the surface ocean without being remineralised in the short-term. Possible reasons for this persistence could be a combination of the molecular diversification of DOM due to microbial reworking, nutrient limitation and reduced metabolic capabilities of the prokaryotic communities inside the mesocosms. Our study demonstrates the importance of the DOC pool when assessing the carbon sequestration potential of artificial upwelling.
Machine learning predictions of MHC-II specificities reveal alternative binding mode of class II epitopes

CD4+ T cells orchestrate the adaptive immune response against pathogens and cancer by recognizing epitopes presented on MHC-II molecules. The high polymorphism of MHC-II genes represents an important hurdle towards accurate prediction and identification of CD4+ T-cell epitopes in different individuals and different species. Here we collected and curated a dataset of 627,013 unique MHC-II ligands identified by mass spectrometry. This enabled us to precisely determine the binding motifs of 88 MHC-II alleles across human, mouse, cattle and chicken. Analysis of these binding specificities combined with X-ray crystallography refined our understanding of the molecular determinants of MHC-II motifs and revealed a widespread reverse binding mode in MHC-II ligands. We then developed a machine learning framework to accurately predict binding specificities and ligands of any MHC-II allele. This tool improves and expands predictions of CD4+ T-cell epitopes, and enabled us to discover and characterize several viral and bacterial epitopes following the aforementioned reverse binding mode.
PRPF31 interacts with PRPH2 confirmed by co-immunoprecipitation and co-localization

Purpose To investigate the potential interaction between PRPF31 and PRPH2. Methods HEK293T and human retinal pigment epithelial cells 19 (APRE-19) were used for our experiments. eGFP and mCherry reporter expression vectors were constructed for PRPF31 and PRPH2, respectively. Immunoblotting and co-immunoprecipitation (Co-IP) were used for gene expression validation and protein interaction. Immunofluorescence staining assay was used to test the co-localization analysis of PRPF31 and PRPH2. Results PRPF31-eGFP and PRPH2-mcherry were highly expressed in HEK293T and APRE-19 cells on fluorescence microscopy and western blot. Co-IP experiments showed that PRPF31 could be pulled down with an anti-PRPH2 antibody. There was co-localization between PRPF31 and PRPH2 in HEK293T, APRE-19 and mouse retina. Conclusion Co-IP and co-localization experiments suggest that PRPF31 interacted with PRPH2.
The value of volunteer surveillance for the early detection of biological invaders

Early detection of invaders requires finding small numbers of individuals across large landscapes. It has been argued that the only feasible way to achieve the sampling effort needed for early detection of an invader is to involve volunteer groups (citizen scientists, passive surveyors, etc.). A key concern is that volunteers may have a considerable false-positive and false-negative rate. The question then becomes whether verification of a report from a volunteer is worth the effort. This question is the topic of this paper. We show that the maximum plausible incidence when the expert samples on its own, , and the maximum plausible incidence when the expert only verifies cases reported by the volunteer surveyor to be infected, , are related as Where θfp and θfn are the false positive and false negative rate of the volunteer surveyor, respectively. We also show that the optimal monitoring programme consists of verifying only the cases reported by the volunteer surveyor if Where TN is the cost of a sample taken by the expert and TX is the cost of an expert verifying a case reported by a volunteer surveyor.
Toxicological study on methanol root bark extract of Acacia sieberiana (Fabaceae) in Wistar rats

Background The plant Acacia sieberiana belongs to the family Fabaceae. It has been used in ethnomedical practice to manage bleeding, rheumatism, pain, pyrexia, kidney diseases, gastrointestinal problems, parasitic and infectious diseases, hepatitis, cough, epilepsy, mouth ulcer and many more. Phytochemical compounds such as ellagic acid, quercetin, isoferulic acid, gallic acid, kaempferol, luteolin, apigenin, glucoside dihydroacacipetalin, acacipetalin and many others were isolated from Acacia sieberiana. Previous pharmacological investigations have reported that the plant has anticancer, antimicrobial, antidiarrhoeal and antitrypanosomal effects. Despite the therapeutic properties of this plant, no safety information is available in the literature. Hence, this work intends to investigate the sub-acute toxicity effects of Acacia sieberiana root bark extract (ASE). The phytochemical and oral median lethal dose (LD50) evaluations on the ASE were done in line with the standard protocols. The sub-acute toxic effects of the ASE (250, 750, and 1,500 mg/kg) were investigated following administration of the ASE daily for 28-consecutive days based on the Organization of Economic Cooperation and Development (OECD) 407 protocols in rats. The weekly body weights were monitored and the rats were euthanized on the 29th day. The blood samples from the animals were obtained for biochemical and haematological determinations. The liver, kidney, lung and heart were removed for histological investigations. Results The ASE revealed triterpenes, tannins, saponins, cardiac glycosides, flavonoids, and alkaloids. The oral LD50 values was >5,000 mg/kg. The ASE remarkably (p<0.05) declined the body weight of the rats in consideration to the control categories. There was also a remarkable (p<0.05) elevation in ALP, urea and lymphocytes. The cardiac histology revealed no abnormalities. However, the liver produced dose-dependent hepatocellular necrosis and vacuolations. Besides, lymphocyte hyperplasia and glomerular necrosis were observed in the kidneys and alveolar congestion in the lungs. Conclusions The ASE is relatively non-toxic on acute administration. In contrast, it could pose slight hepatic and renal toxicity on sub-acute administration.
The assembly yield of complex, heterogeneous structures: A computational toolbox

The self-assembly of complex structures from a set of non-identical building blocks is a hallmark of soft matter and biological systems, including protein complexes, colloidal clusters, and DNA-based assemblies. Predicting the dependence of the equilibrium assembly yield on the concentrations and interaction energies of building blocks is highly challenging, owing to the difficulty of computing the entropic contributions to the free energy of the many structures that compete with the ground state configuration. While these calculations yield well known results for spherically symmetric building blocks, we discovered that they do not hold when the building blocks have internal rotational degrees of freedom. Here we present an approach for solving this problem that works with arbitrary building blocks, including proteins with known structure and complex colloidal building blocks. Our algorithm combines classical statistical mechanics with recently developed computational tools for automatic differentiation. Automatic differentiation allows efficient evaluation of equilibrium averages over configurations that would otherwise be intractable. We demonstrate the validity of our framework by comparison to molecular dynamics simulations of simple examples, and apply it to calculate the yield curves for known protein complexes and for the assembly of colloidal shells.
Secreted Aeromonas GlcNAc binding protein GbpA stimulates epithelial cell proliferation in the zebrafish intestine

In response to microbiota colonization, the intestinal epithelia of many animals exhibit increased rates of cell proliferation. We used gnotobiotic larval zebrafish to identify a secreted factor from the mutualist Aeromonas veronii that is sufficient to promote intestinal epithelial cell proliferation. This secreted A. veronii protein is a homologue of the Vibrio cholerae GlcNAc binding protein GbpA, which was identified as a chitin-binding colonization factor in mice. GbpA was subsequently shown to be a lytic polysaccharide monooxygenase (LPMO) that can degrade recalcitrant chitin. Our phenotypic characterization of gbpA deficient A. veronii found no alterations in the mutant cells’ biogeography in the zebrafish intestine and only a modest competitive disadvantage in chitin-binding and colonization fitness when competed against the wild type strain. These results argue against the model of GbpA being a secreted adhesin that binds simultaneously to bacterial cells and GlcNAc, and instead suggests that GbpA is part of a bacterial GlcNAc utilization program. We show that the host proliferative response to GbpA occurs in the absence of bacteria upon exposure of germ-free zebrafish to preparations of native GbpA secreted from either A. veronii or V. cholerae or recombinant A. veronii GbpA. Furthermore, domain 1 of A. veronii GbpA, containing the predicted LPMO activity, is sufficient to stimulate intestinal epithelial proliferation. We conjecture that intestinal epithelia upregulate their rates of renewal in response to secreted bacterial GbpA proteins as an adaptive strategy for coexisting with bacteria that can degrade glycan constituents of the protective intestinal lining.
The wheat head blight pathogen Fusarium graminearum recruits facultative endohyphal bacteria from the soil, making the fungal-bacterial holobiont nitrogen-fixing and increasing the fungal pathogenicity

In nature, fungal endophytes often have facultative endohyphal bacteria. Can a fungal pathogen such as Fusarium graminearum, pathogenic on wheat, get facultative endohyphal bacteria from soil (FEB) and how does the FEB affect the fungal phenotype? We constructed a growth system/microcosm that allowed a molecularly well-studied F. graminearum isolate, PH-1, to grow through natural soil and then be re-isolated on a gentamicin-containing medium, allowing endohyphal growth of the bacteria while killing eventual bacteria growing on the agar medium. We had labelled the F. graminearum PH-1 with a His1mCherry gene staining the fungal nuclei fluorescent red to confirm re-isolation of the same isolate we sent through the soil. Through qPCR of the 16SrRNA gene in the bacteria using universal primers combined with qPCR of the mCherry gene of DNA from the re-isolated cultures of the Fg-FEB holobionts growing on gentamicin-containing media, it was found that most of the holobiont isolates contained about 10 16SrRNA genes per fungal mCherry gene. The Fg-FEB holobiont isolates were sub-cultured several times, and the FEB content on lab media was stable. Sequencing the 16SrRNA gene from several Fg-FEB holobiont isolates revealed known endophytic bacteria capable of nitrogen fixation. We compared the pathogenicity of one of the Fg-FEB holobionts Fg-S.maltophilia, with the background without FEB and found that it was more pathogenic than without FEB. We could also show that the bacterial 16SrRNA load per fungal His1mCherry gene inside the wheat stayed the same as in culture. Finally, we tested if the Fg-S.maltophilia was capable of nitrogen fixation and could show that it, on a nitrogen-free medium, formed a dense mycelium containing proteins at similar levels as on regular nitrogen-containing media. Our results could indicate that naturally occurring fungal pathogens outside lab conditions might contain facultative endohyphal bacteria, positively affecting their pathogenicity and ecological fitness.
From Doodles to Diagrams to Knots

Summary What closed curves can be drawn in the plane such that they cut the plane into complementary regions that are n-gons, including the outer region, where n is allowed to take some finite number of values? A curve is an (a1, a2, …, an)-curve if the number of edges for its complementary regions all lie in a1, a2 …, an. We show that there are infinitely many curves for (2, n), where n is any odd integer greater than 3, and for (3, n), for any n > 3 relatively prime to 3. We also consider the implications for knot theory, showing that every knot has a (3, 4, 5)-diagram. We ask what values of (a1, a2, …, an) will generate diagrams for every knot.
Case Conceptualizing in Acceptance and Commitment Therapy for Moral Injury: An Active and Ongoing Approach to Understanding and Intervening on Moral Injury

Acceptance and Commitment Therapy for Moral Injury (ACT-MI; 10–11), is an application of Acceptance and Commitment Therapy principles designed to help individuals live their values, even in the presence of moral pain. ACT-MI differs from other emerging treatments for moral injury in that ACT-MI is not based on a traditional syndromal approach to conceptualizing moral injury, which treats moral injury as a collection of signs and symptoms to be reduced. Rather than assuming moral injury causes suffering through a constellation of symptoms that a person has, in ACT-MI, moral injury is defined by what a person does in response to moral pain. Consistent with this framework, we present a unique approach to moral injury case conceptualization that emphasizes function over form, providing clients the opportunity to break free from the patterns of behavior that cause moral injury-related suffering to persist. Rooted in approaches to conceptualizing that have demonstrated utility in extant interventions (e.g., ACT), ACT-MI clinicians conduct ongoing functional analyses to inform case conceptualization and intervention. Functional analysis is used to disrupt the processes maintaining moral injury, as the client and therapist work to identify and intervene on the behaviors reinforcing avoidance and control of painful internal experiences causing moral injury. In the current article, we guide the reader through a framework for applying functional analysis to the conceptualization of moral injury where the reinforcers driving moral injury are explored. We also provide examples of questions that can be used to help uncover the functions of moral injury consistent behavior. Case examples based on our experiences treating moral injury are presented to demonstrate how various types of morally injurious events can evoke different features of moral pain which in turn motivate different repertoires of avoidance and control. These inflexible patterns of avoidance and control create suffering by engaging in behavior designed to escape moral pain, such as social isolation, spiritual disconnection, reduced self-care, suicidal ideation, and substance use. We discuss how to target this suffering using functional analysis to guide treatment decisions, matching interventional processes within ACT-MI to the specific functions that moral injury-related behavior is serving for an individual. We suggest that the use of functional analytic case formulation procedures described herein can assist clients in disrupting behavioral patterns maintaining moral injury and thereby free them to pursue lives of greater meaning and purpose.
Supplementation With Zinc Proteinate Increases the Growth Performance by Reducing the Incidence of Diarrhea and Improving the Immune Function of Dairy Calves During the First Month of Life

Two experiments were conducted to identify the optimal dose of zinc proteinate (ZP) in the diet for dairy calves and then to compare early supplementation with the ZP or zinc methionine (ZM) on the growth performance, incidence of diarrhea, antioxidant status, and immune function of dairy calves during their first month of life. In Experiment 1, forty newborn female Holstein dairy calves were randomly divided into four groups (n = 10): a control group (without ZP supplementation, ZP0) or groups that received ZP supplementation at 40, 80, and 120 mg zinc/day, respectively (ZP40, ZP80, and ZP120). The experiment lasted 14 days, and the growth performance, incidence of diarrhea, and serum zinc concentration were analyzed. In Experiment 2, thirty-six newborn female Holstein dairy calves were randomly allocated to three groups (n = 12): a negative control group (without zinc supplementation, CON), a positive control group (supplemented with 80 mg zinc/day in the form of zinc methionine, ZM), and a ZP group (supplemented with 80 mg zinc/day in the form of ZP). The experiment lasted 28 days, and the growth performance, incidence of diarrhea, serum zinc concentration, serum antioxidant indicators, and concentrations of plasma immunoglobulins and cytokines were determined on days 7, 14, 21, and 28. Results showed that in Experiment 1, supplementation with ZP to yield 80 mg zinc/day increased the ADG (P < 0.01) and serum zinc concentration (P < 0.01), and decreased the F/G (P < 0.01) and the incidence of diarrhea (P < 0.05) during days 1–14. In Experiment 2, compared with the CON group, ZP increased the ADG (P < 0.01), serum zinc concentration (P < 0.01), and plasma immunoglobulin G (IgG; P < 0.01) and IgM (P < 0.01) concentrations, but reduced the incidence of diarrhea (P < 0.01), serum malondialdehyde (P < 0.01), and plasma interleukin-1β (P < 0.01) concentrations during days 1–28. Overall, ZP supplementation to yield 80 mg zinc/day improves the growth performance and immune function, and decrease the incidence of diarrhea of dairy calves, which was comparable to the same dose of zinc in the form of ZM.
Florfenicol-Polyarginine Conjugates Exhibit Promising Antibacterial Activity Against Resistant Strains

Florfenicol was widely used as antibiotic in the livestock and poultry breeding industry, resulting in a serious problem of drug resistance. In order to solve the resistance of florfenicol, this study designed and synthesized a new series of florfenicol-polyarginine conjugates and tested for antimicrobial activities. Drug-sensitive bacteria, gram-negative bacteria Escherichia coli (E. coli) and gram-positive Staphylococcus aureus (S. aureus), were sensitive to several of the compounds tested. These conjugates also showed excellent activity against drug-resistant strains such as methicillin-resistant S. aureus (MRSA) and florfenicol resistant Escherichia coli strains (2017XJ30, 2019XJ20), one of which as E6 had a minimum inhibitory concentration of 12.5 μmol/L. These conjugates did not allow bacteria to develop resistance and also decreased bacterial growth by membrane depolarization and disruption. Additionally, florfenicol succinate (C1) showed certain activity after coupling with arginine. This suggested that conjugating arginine to florfenicol succinate effectively modulated the properties of prodrugs. These new conjugates may provide useful insights for expanding the pool of antibiotics.
Elastic Stable Intramedullary Nailing and Temporary External Fixation for the Treatment of Unstable Femoral Shaft Fractures in Children Aged 5-11 Years Old: A Retrospective Study of 28 Cases

Purpose Unstable femoral shaft fractures (UFSFs) in children aged 5–11 years remain challenging due to their intrinsic instability. The aim of this study was to evaluate the clinical and radiographic outcomes of UFSF in children aged 5 to 11 years managed by the combined use of ESIN and temporary EF. Methods Children with UFSF (long oblique and comminuted) treated by ESIN and temporary EF were retrospectively reviewed. Sex, age at injury, side involved, type of fracture, presence or absence of associated lesions or neurovascular complications, type of treatment, time from trauma to surgery, duration of surgery, radiation exposure and length of postoperative immobilization were collected from the medical charts. Radiological and functional outcomes were evaluated according to Beaty's and Flynn's criteria, respectively. Results A total of 28 consecutive patients with closed or open (Gustilo type I or II) UFSF were reviewed (18 boys and 10 girls). The mean age at injury was 8.7 ± 1.6 years (range, 5–11); the average weight was 38.1 ± 7.6 kg (range, 26–55). The mean hospital stay was 3.7 ± 1.4 days (range, 2–7), and the mean time to EF and ESIN removal was 6.5 ± 1.1 weeks (range, 4–8) and 9.4 ± 1.6 months (range, 6–12), respectively. Twenty-seven out of 28 patients had excellent radiographic outcomes according to Beaty's criteria, and 24/28 had excellent functional outcomes according to Flynn's criteria. Overall, 4 complications (14.3%) were recorded. No statistically significant correlation was found between complication rates and sex, age, weight or fracture characteristics (P < 0.05). Conclusions The combined use of ESIN and temporary EF provides good clinical and radiological outcomes in children with UFSF aged between 5 and 11 years, with a reduced complication rate.