Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular detection of equine infectious anemia virus in clinically normal, seronegative horses in an endemic area of Mexico

Equine infectious anemia (EIA) is a highly infectious disease in members of the Equidae family, caused by equine infectious anemia virus (EIAV). The disease severity ranges from subclinical to acute or chronic, and causes significant economic losses in the equine industry worldwide. Serologic tests for detection of EIAV infection have some concerns given the prolonged seroconversion time. Therefore, molecular methods are needed to improve surveillance programs for this disease. We attempted detection of EIAV in 6 clinical and 42 non-clinical horses in Nuevo Leon State, Mexico, using the agar gel immunodiffusion (AGID) test for antibody detection, and nested and hemi-nested PCR for detection of proviral DNA. We found that 6 of 6, 5 of 6, and 6 of 6 clinical horses were positive by AGID, nested PCR, and hemi-nested PCR, respectively, whereas 0 of 42, 1 of 42, and 9 of 42 non-clinical horses were positive by these tests, respectively. BLAST analysis of the 203-bp 5′-LTR/tat segment of PCR product revealed 83–93% identity with EIAV isolates in GenBank and reference strains from other countries. By phylogenetic analysis, our Mexican samples were grouped in a different clade than other sequences reported worldwide, indicating that the LRT/tat region represents an important target for the detection of non-clinical horses.
The role of GDP-l-galactose phosphorylase in the control of ascorbate biosynthesis

Abstract The enzymes involved in l-ascorbate biosynthesis in photosynthetic organisms (the Smirnoff–Wheeler [SW] pathway) are well established. Here, we analyzed their subcellular localizations and potential physical interactions and assessed their role in the control of ascorbate synthesis. Transient expression of C terminal-tagged fusions of SW genes in Nicotiana benthamiana and Arabidopsis thaliana mutants complemented with genomic constructs showed that while GDP-d-mannose epimerase is cytosolic, all the enzymes from GDP-d-mannose pyrophosphorylase (GMP) to l-galactose dehydrogenase (l-GalDH) show a dual cytosolic/nuclear localization. All transgenic lines expressing functional SW protein green fluorescent protein fusions driven by their endogenous promoters showed a high accumulation of the fusion proteins, with the exception of those lines expressing GDP-l-galactose phosphorylase (GGP) protein, which had very low abundance. Transient expression of individual or combinations of SW pathway enzymes in N. benthamiana only increased ascorbate concentration if GGP was included. Although we did not detect direct interaction between the different enzymes of the pathway using yeast-two hybrid analysis, consecutive SW enzymes, as well as the first and last enzymes (GMP and l-GalDH) associated in coimmunoprecipitation studies. This association was supported by gel filtration chromatography, showing the presence of SW proteins in high-molecular weight fractions. Finally, metabolic control analysis incorporating known kinetic characteristics showed that previously reported feedback repression at the GGP step, combined with its relatively low abundance, confers a high-flux control coefficient and rationalizes why manipulation of other enzymes has little effect on ascorbate concentration.
H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation

In plants, genome stability is maintained during DNA replication by the H3.1K27 methyltransferases ATXR5 and ATXR6, which catalyze the deposition of K27me1 on replicationdependent H3.1 variants. Loss of H3.1K27me1 in atxr5 atxr6 double mutants leads to heterochromatin defects, including transcriptional de-repression and genomic instability, but the molecular mechanisms involved remain largely unknown. In this study, we identified the conserved histone acetyltransferase GCN5 as a mediator of transcriptional de-repression and genomic instability in the absence of H3.1K27me1. GCN5 is part of a SAGA-like complex in plants that requires ADA2b and CHR6 to mediate the heterochromatic defects of atxr5 atxr6 mutants. Our results show that Arabidopsis GCN5 acetylates multiple lysine residues on H3.1 variants in vitro, but that H3.1K27 and H3.1K36 play key roles in inducing genomic instability in the absence of H3.1K27me1. Overall, this work reveals a key molecular role for H3.1K27me1 in maintaining genome stability by restricting histone acetylation in plants.
Medicago truncatula Yellow Stripe-Like7 encodes a peptide transporter participating in symbiotic nitrogen fixation.

Yellow Stripe-Like (YSL) proteins are a family of plant transporters that are typically involved in transition metal homeostasis. Three of the four YSL clades (I, II, and IV) transport metals complexed with the non-proteinogenic amino acid nicotianamine or its derivatives. No such capability has been shown for any member of clade III but the link between these YSLs and metal homeostasis could be masked by functional redundancy. We studied the role of the clade III YSL protein MtSYL7 in Medicago truncatula nodules. MtYSL7, which encodes a plasma membrane-bound protein, is mainly expressed the pericycle and cortex cells of the root nodules. Yeast complementation assays revealed that MtSYL7 is able to transport short peptides. Medicago truncatula transposon insertion mutants with decreased expression of MtYSL7 had lower nitrogen fixation rates and showed reduced plant growth whether grown in symbiosis with rhizobia or not. YSL7 mutants accumulated more copper and iron in the nodules, which is likely to result from the increased expression of iron uptake and delivery genes in roots. Taken together, these data suggest that MtYSL7 plays an important role in the transition metal homeostasis of nodules and in symbiotic nitrogen fixation. This article is protected by copyright. All rights reserved.
Human osteoclastogenesis in Epstein-Barr virus-induced erosive arthritis in humanized NOD/Shi-scid/IL-2Rγnull mice

Many human viruses, including Epstein-Barr virus (EBV), do not infect mice, which is challenging for biomedical research. We have previously reported that EBV infection induces erosive arthritis, which histologically resembles rheumatoid arthritis, in humanized NOD/Shi-scid/IL-2Rγnull (hu-NOG) mice; however, the underlying mechanisms are not known. Osteoclast-like multinucleated cells were observed during bone erosion in this mouse model, and therefore, we aimed to determine whether the human or mouse immune system activated bone erosion and analyzed the characteristics and origin of the multinucleated cells in hu-NOG mice. Sections of the mice knee joint tissues were immunostained with anti-human antibodies against certain osteoclast markers, including cathepsin K and matrix metalloproteinase-9 (MMP-9). Multinucleated cells observed during bone erosion stained positively for human cathepsin K and MMP-9. These results indicate that human osteoclasts primarily induce erosive arthritis during EBV infections. Human osteoclast development from hematopoietic stem cells transplanted in hu-NOG mice remains unclear. To confirm their differentiation potential into human osteoclasts, we cultured bone marrow cells of EBV-infected hu-NOG mice and analyzed their characteristics. Multinucleated cells cultured from the bone marrow cells stained positive for human cathepsin K and human MMP-9, indicating that bone marrow cells of hu-NOG mice could differentiate from human osteoclast progenitor cells into human osteoclasts. These results indicate that the human immune response to EBV infection may induce human osteoclast activation and cause erosive arthritis in this mouse model. Moreover, this study is the first, to our knowledge, to demonstrate human osteoclastogenesis in humanized mice. We consider that this model is useful for studying associations of EBV infections with rheumatoid arthritis and human bone metabolism.
Redox regulation of chloroplast metabolism

Abstract Regulation of enzyme activity based on thiol-disulfide exchange is a regulatory mechanism in which the protein disulfide reductase activity of thioredoxins (TRXs) plays a central role. Plant chloroplasts are equipped with a complex set of up to 20 TRXs and TRX-like proteins, the activity of which is supported by reducing power provided by photosynthetically reduced ferredoxin (FDX) with the participation of a FDX-dependent TRX reductase (FTR). Therefore, the FDX–FTR–TRXs pathway allows the regulation of redox-sensitive chloroplast enzymes in response to light. In addition, chloroplasts contain an NADPH-dependent redox system, termed NTRC, which allows the use of NADPH in the redox network of these organelles. Genetic approaches using mutants of Arabidopsis (Arabidopsis thaliana) in combination with biochemical and physiological studies have shown that both redox systems, NTRC and FDX-FTR-TRXs, participate in fine-tuning chloroplast performance in response to changes in light intensity. Moreover, these studies revealed the participation of 2-Cys peroxiredoxin (2-Cys PRX), a thiol-dependent peroxidase, in the control of the reducing activity of chloroplast TRXs as well as in the rapid oxidation of stromal enzymes upon darkness. In this review, we provide an update on recent findings regarding the redox regulatory network of plant chloroplasts, focusing on the functional relationship of 2-Cys PRXs with NTRC and the FDX–FTR–TRXs redox systems for fine-tuning chloroplast performance in response to changes in light intensity and darkness. Finally, we consider redox regulation as an additional layer of control of the signaling function of the chloroplast.
Adsorption of Zn on Synthetic Hydroxyapatite from Aqueous Solution

The aim of this paper was to discuss the changes in the double electrical layer at the hydroxyapatite /electrolyte solution interface during zinc ions adsorption. The second aim was establishing the relations between time and adsorption on this material. Hydroxyapatite of a determined specific surface area was prepared by the wet method, characterized by XRD methods, scanning and atomic microscopes. Moreover, the specific surface area was characterized and the grain sizes were determined. Studies of adsorption were carried out using 65Zn isotopes and ionic solutions containing this ion depending on concentration and pH of the solution. Zn adsorption isotherms on hydroxyapatite were determined. The effect of the presence of zinc ions on grain sizes surface charge density and zeta potential was discussed.
Rates of photoisomerization of trans-stilbene in isolated and solvated molecules: experiments on the deuterium isotope effect and RRKM behavior

In this paper the dynamics of the photoisomerization of trans-stilbene and related molecules are considered. New measurements of the deuterium isotope effect on reaction rates are presented, and details of RRKM behavior in isolated and solvated trans-stilbene are discussed. From measurements of fluorescence decay rates as a function of the excess vibrational energy in jet-cooled trans-stilbene-d/sup 12/, an energy threshold to the rates is found at ca. 1200-cm/sup -1/ excess energy in the first excited singlet state. The threshold behavior is similar to that which occurs in the photoisomerization of trans-stilbene-h/sup 12/. The overall magnitudes of the perdeuterio rates are smaller, however, than the perprotio ones. As with trans-stilbene-h/sup 12/ the measured rates are found to be slower than those calculated by standard RRKM theory. Nevertheless, the observed slowing of the rates upon deuteration is predicted by the theory. The results and their interpretation are discussed in light of the results of other jet studies of trans-stilbene derivatives and of studies of the photoisomerization reaction in solution. The role of intramolecular vibrational energy redistribution and the nonadiabatic influences on the reaction are also discussed. 53 references, 4 figures, 3 tables.
Aggregate stability as affected by short and long-term tillage systems and nutrient sources of a hapludox in southern Brazil

The ability of a soil to keep its structure under the erosive action of water is usually high in natural conditions and decreases under frequent and intensive cultivation. The effect of five tillage systems (NT = no-till; CP = chisel plowing and one secondary disking; CT = primary and two secondary distings; CTb = CT with crop residue burning; and CTr = CT with removal of crop residues from the field), combined with five nutrient sources (C = control, no nutrient application; MF = mineral fertilizers according to technical recommendations for each crop; PL = 5 Mg ha-1 y-1 fresh matter of poultry litter; CM = 60 m3 ha-1 y-1 slurry cattle manure; and SM = 40 m3 ha-1 y-1 slurry swine manure) on wet-aggregate stability was determined after nine years (four sampled soil layers) and on five sampling dates in the 10th year (two sampled soil layers) of the experiment. The size distribution of the air-dried aggregates was strongly affected by soil bulk density, and greater values of geometric mean diameter (GMDAD) found in some soil tillage or layer may be partly due to the higher compaction degree. After nine years, the GMDAD on the surface was greater in NT and CP compared to conventional tillage systems (CT, CTb and CTr), due to the higher organic matter content, as well as less soil mobilization. Aggregate stability in water, on the other hand, was affected by the low variation in previous gravimetric moisture of aggregates, which contributed to a high coefficient of variation of this attribute. The geometric mean diameter of water-stable aggregates (GMDWS) was highest in the 0.00-0.05 m layer in the NT system, in the layers 0.05-0.10 and 0.12-0.17 m in the CT, and values were intermediate in CP. The stability index (SI) in the surface layers was greater in treatments where crop residues were kept in the field (NT, CP and CT), which is associated with soil organic matter content. No differences were found in the layer 0.27-0.32 m. The effect of nutrient sources on GMDAD and GMDWS was small and did not affect SI.
In silico approach of secondary metabolites from Brazilian herbal medicines to search for potential drugs against SARS‐CoV‐2

The new severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of secondary metabolites related to Brazilian herbal medicines was performed as a strategy for the discovery of new antiviral agents. To confirm this potential, an in silico screening of the identified compounds identified was also evaluated. The review was performed by the PubMed database and the selected natural compounds were subjected to in silico analysis such as QSAR, molecular docking and ADMET. 497 secondary metabolites were identified from 23 species. The in silico assays indicated 19 potential anti‐SARS‐CoV‐2 compounds, being triterpenes and phenolic compounds. The indicated compounds showed a high affinity with proteins considered as the main molecular targets against SARS‐CoV‐2 and parameters indicated low toxicity. In addition to Brazilian medicinal plants, these compounds can be found in other species and they can be a base for the synthesis of other anti‐COVID‐19 drugs. Therefore, this review is important to conduct researches that address the emerging need for drugs in COVID‐19 treatment.
The combination of fibrinogen concentrations and the platelet-to-lymphocyte ratio predicts survival in patients with advanced lung adenocarcinoma treated with EGFR-TKIs

Objective This study aimed to identify a predictive marker of response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant advanced lung adenocarcinoma. Methods A cohort of 190 patients with EGFR-mutant advanced lung adenocarcinoma was analyzed. Receiver operating characteristic curve analysis was used to evaluate the optimal cutoffs for fibrinogen levels, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) for predicting progression-free survival (PFS). Univariate and multivariate survival analyses were performed to identify factors correlated with PFS and overall survival (OS). Results High NLR was associated with worse performance status. In univariate analysis, fibrinogen levels, NLR, and PLR were correlated with OS and PFS. In multivariate analysis, all three variables remained predictive of OS, whereas only fibrinogen levels and PLR were independent prognostic factors for PFS. Furthermore, the combination of fibrinogen levels and PLR (F-PLR score) could stratify patients into three groups with significantly different prognoses, and the score was independently predictive of survival. Conclusion The F-PLR score predicted the prognosis of patients with EGFR-mutant advanced lung adenocarcinoma who received EGFR-TKIs, and this score may serve as a convenient blood-based marker for identifying high-risk patients.
Place of Death and Density of Homecare Resources: A Nationwide Study in Japan

Background Although more than half of the population of Japan wants to spend their last days at home, approximately only 10% are able to do so. This study examined the associations between death at home and healthcare facility density by municipality based on the analysis of nationwide observed data in Japan. Methods We used data on deaths at home and healthcare resources in municipalities across Japan for the fiscal years 2014 and 2017. The proportions of deaths at home by municipality were used as the dependent variable, while healthcare resources (e.g., hospital density) divided by the population of older people in each municipality and municipality-level income were used as independent variables. We applied a fixed-effects regression analysis to examine the association of healthcare resources and municipality-level income with death at home. Results Clinics providing home medical care and facilities providing visiting nursing services were positively associated with death at home, with coefficients (95% confidence intervals) of 2.14 (1.12 to 3.15) and 2.19 (0.99 to 3.39), respectively. Stratified analysis showed that these associations were observed in higher income-level municipalities but not in lower income-level municipalities. Conclusion Municipalities with a higher density of home care services had higher rates of death at home, whereas municipalities with a higher density of hospitals had lower rates. We recommend the development of policy that allows hospitals to be converted into home care providers so that more people can spend time in peace at home at the end of their lives.
Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone

A substantial proportion of patients with chronic hepatitis B (CHB) who do not fit into any of the usual immune states are considered to be in the ‘grey zone (GZ)’. We aimed to investigate the distribution and characteristics of GZ in a large cohort of CHB patients. Four thousand seven hundred and fifty‐nine consecutive treatment‐naïve CHB patients were enrolled. The immune states were defined based on AASLD 2018 Hepatitis B Guidance. GZ CHB patients were classified into four groups: HBeAg positive, normal ALT levels and serum HBV DNA ≤106 IU/ml (GZ‐A); HBeAg positive, elevated ALT levels and serum HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg negative, normal ALT levels and serum HBV DNA ≥2 × 103 IU/ml (GZ‐C); HBeAg negative, elevated ALT levels and serum HBV DNA ≤2 × 103 IU/ml (GZ‐D). The distributions of different immune states were: 233 (4.90%) patients in immune‐tolerant phase, 941 (19.77%) patients in HBeAg‐positive immune active phase, 1,717 (36.08%) patients in inactive phase and 546 (11.47%) patients in HBeAg‐negative immune active phase. Of note, 1,322 (27.78%) patients did not fit into any of above phases and were defined as the GZ. A high proportion of patients in GZ‐B had advanced fibrosis (33.3%) or cirrhosis (25.8%). Older age, HBeAg‐positive status and higher ALT levels were independently risk factors of advanced disease in GZ CHB patients. Therefore, our results revealed that more than a quarter of CHB patients were classified into the GZ and a high proportion of patients in GZ‐B had advanced fibrosis or even cirrhosis.
A network meta-analysis of direct factor Xa inhibitors for the treatment of cancer-associated venous thromboembolism

Introduction Treatment of cancer-associated venous thromboembolism (CAVTE) remains challenging. The aim of this study was to assess the outcomes of direct acting oral anticoagulants (DOAs) for the treatment of CAVTE. Materials and methods A network meta-analysis of randomized clinical trials comparing DOAs (Apixaban, Rivaroxaban, and Edoxaban) versus Dalteparin for the treatment of CAVTE was performed. Outcomes of interest included, VTE recurrence, all-cause mortality, event-free survival, major bleeding, and clinically relevant non-major bleeding (CRNMB). Analysis was based on a random effects model and Bayesian Markov-chain Monte Carlo method was used for indirect comparisons. Results Four RCTs involving 2894 patients were included. Overall certainty of evidence was moderate regarding all outcomes. DOAs exhibited lower risk of VTE (RR 0.62; 95% CI 0.44, 0.87; P = 0.007), similar risk of major bleeding (RR 1.33; 95% CI 0.84, 2.11; P = 0.23), and higher risk of CRNMB (RR 1.66, 95% CI 1.08, 2.56; P = 0.02), compared with Dalteparin. Risk of all-cause mortality and event-free survival were similar between groups with RR 0.99 (95% CI 0.84, 1.16) and RR 1.03 (95% CI 0.94, 1.13), respectively. Apixaban ranked first for recurrent VTE (42.4%) and major bleeding (62.3%) and Dalteparin ranked first for CRNMB (54.7%). Rivaroxaban ranked best considering all-cause mortality (58.7%); Apixaban ranked best for event-free survival (83.6%). Conclusions DOAs presented a reduced risk of recurrent VTE with similar risk of major bleeding compared to Dalteparin. However, a higher risk of CRNMB is expected when this cohort of patients are treated with DOAs instead of Dalteparin.
Clinical factors predictive of mortality in acute leukemia patients with febrile neutropenia.

BACKGROUND Acute leukemia is mainly treated with chemotherapy leading to febrile neutropenia (FN). There is limited data on clinical factors predictive of mortality in adults with acute leukemia and FN. METHODS This was a retrospective cohort study and enrolled adult patients, diagnosed as acute leukemia, and developed FN. The eligible patients were admitted and followed up with mortality as the primary outcome. A stepwise, multivariate logistic regression analysis was used to find predictors for mortality. RESULTS There were 203 patients met the study criteria. Of those, 14 patients died (6.89%). AML was the most common type of acute leukemia with FN (64.04%). There were five remaining factors in the final model: AML, FN at admission, prolong broad spectrum antibiotics, lower respiratory tract infection, and Aspergillosis. Only lower respiratory tract infection was significant with adjusted odds ratio of 7.794 (95% CI of 1.549, 39.212). The Hosmer-Lemeshow Chi square was 2.74 (p value 0.907). The lower respiratory tract infection group had higher proportions of Gram negative and fungus than the non-lower respiratory tract infection group; specifically E. coli (p 0.003), and Aspergillus (P < 0.001). CONCLUSIONS There were two independent predictors of mortality in acute leukemia patients with FN: septic shock and lower respiratory tract infection regardless of leukemia type or pathogen. E. coli and Aspergillus were more common in those with lower respiratory tract infection than those without. No specific pathogens were found in cases of septic shock.