Miracle-dz/UniFAR-FTUs huggingface dataset:
Transgenic expression of a T cell epitope in Strongyloides ratti reveals that helminth-specific CD4+ T cells constitute both Th2 and Treg populations

Helminths are distinct from microbial pathogens in both size and complexity, and are the likely evolutionary driving force for type 2 immunity. CD4+ helper T cells can both coordinate worm clearance and prevent immunopathology, but issues of T cell antigen specificity in the context of helminth-induced Th2 and T regulatory cell (Treg) responses have not been addressed. Herein, we generated a novel transgenic line of the gastrointestinal nematode Strongyloides ratti expressing the immunodominant CD4+ T cell epitope 2W1S as a fusion protein with green fluorescent protein (GFP) and FLAG peptide in order to track and study helminth-specific CD4+ T cells. C57BL/6 mice infected with this stable transgenic line (termed Hulk) underwent a dose-dependent expansion of activated CD44hiCD11ahi 2W1S-specific CD4+ T cells, preferentially in the lung parenchyma. Transcriptional profiling of 2W1S-specific CD4+ T cells isolated from mice infected with either Hulk or the enteric bacterial pathogen Salmonella expressing 2W1S revealed that pathogen context exerted a dominant influence over CD4+ T cell phenotype. Interestingly, Hulk-elicited 2W1S-specific CD4+ T cells exhibited both Th2 and Treg phenotypes and expressed high levels of the EGFR ligand amphiregulin, which differed greatly from the phenotype of 2W1S-specific CD4+ T cells elicited by 2W1S-expressing Salmonella. While immunization with 2W1S peptide did not enhance clearance of Hulk infection, immunization did increase total amphiregulin production as well as the number of amphiregulin-expressing CD3+ cells in the lung following Hulk infection. Altogether, this new model system elucidates effector as well as immunosuppressive and wound reparative roles of helminth-specific CD4+ T cells. This report establishes a new resource for studying the nature and function of helminth-specific T cells.
A systematic review of video-modelling interventions for children and adolescents with attention-deficit hyperactivity disorder.

OBJECTIVE To identify, appraise, and synthesise the evidence for video-modelling interventions for individuals with attention-deficit hyperactivity disorder (ADHD). METHOD We searched four electronic databases. Two independent researchers screened abstracts and methodologically assessed data using the Kmet appraisal checklist. RESULTS A total of 15 studies met the inclusion criteria (11 original studies and four follow-up studies). Of the 11 original studies, one was a randomised controlled trial, one was a controlled between-group comparative design, two were one group pre-test post-test studies, one was an experimental 2 × 2 factorial design, and six were single-case experimental design studies. Studies included 1-35 participants with ADHD aged 5-16 years. Three studies targeted behaviour, three targeted social play skills, two targeted social behaviour, one targeted social skills, one targeted goal orientation and friendship quality, targeted and one attention/comprehension of social behaviour. In four studies video-modelling was the whole intervention, with no other intervention components reported. Nine studies reported positive outcomes immediately after intervention, two studies reported mixed findings. All studies were found to have good or strong methodological quality. CONCLUSION There is preliminary evidence to suggest video-modelling may be a promising intervention approach for targeting the social skills and behaviours of individuals with ADHD when used in conjunction with other intervention components. Future studies need to lower the risk of bias and use larger sample sizes before the efficacy of video-modelling interventions can be fully investigated.
Simultaneous feeding of calcium butyrate and tannin extract decreased the incidence of diarrhea and proinflammatory markers in weaned piglets

Objective This study was conducted to investigate the effect of associating calcium butyrate with tannin extract, compared to an antimicrobial on the growth performance, incidence of diarrhea, intestinal histology, immune-expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNF-α) in piglets. Methods Seventy-two piglets (36 barrows and 36 gilts) weaned at 28±2 d and initial body weight of 7.17±1.07 kg were allocated to 3 treatments in a randomized complete block design with 8 replicates per treatment and 3 animals per experimental unit. Treatments were composed of NC, negative control: basal diet without additives; PC, positive control: basal diet + 40 mg/kg of colistin sulfate; or BT, basal diet + calcium butyrate + tannin extract. The butyrate and tannin inclusion levels were 0.15% in the pre-starter phase and 0.075% in the starter phase. Incidence of diarrhea was monitored daily, and on d 14 and 35 of experiment, 1 animal from each experimental unit was slaughtered to collect intestinal samples. Results No significant differences were observed for growth performance. The butyrate- and tannin-based additive resulted in reduced (p<0.05) incidence of diarrhea in piglets during d 1 to 14 and d 1 to 35 in comparison with the other treatments. Piglets that consumed the diet containing the calcium-butyrate and tannin showed a lower (p<0.05) crypt depth in the duodenum than those receiving the NC treatment at 14 d of experimentation. The BT treatment provided a lower (p<0.05) immune-expression of COX-2 at 14 d and TNF-α at 35 d in the duodenum. Conclusion Association between calcium butyrate and tannin extract resulted in a significant decrease in the incidence of diarrhea and inflammatory process in the duodenum of piglets. Therefore, calcium-butyrate combined with tannin could be a part of an alternative program to reduce the use of antimicrobials in the diet of weaned piglets.
Genetic parameters for somatic cell score, milk yield and type traits in Nigerian Dwarf goats

Objective This study was conducted to estimate multi-trait genetic parameters for somatic cell score (SCS), milk yield and type traits in Nigerian Dwarf (ND) goats from the United States. Methods Data from 1,041 ND goats in the United States with kiddings in 95 herds were used to estimate multi-trait genetic parameters for SCS, milk (MILK), fat (FAT), and protein (PROT) yields, and 14 type traits. An 18-trait mixed linear animal model for lactation mean SCS (Log2), MILK, FAT, PROT, and 14 type traits was applied. A factor analytic approach (FA1) in ASReml software was used to obtain convergence. Results Averages for SCS were low (2.85±1.29 Log2), and were 314±110.6, 20.9±7.4, and 14±4.9 kg, respectively, for MILK, FAT, and PROT. Heritabilities for SCS, MILK, FAT, and PROT were 0.32, 0.16, 0.16, and 0.10, respectively. The highest heritabilities for type traits were for stature (0.72), teat diameter (0.49), and rump width (0.48), and the lowest estimates were for dairyness (0.003) and medial suspensory ligament (0.03). Genetic correlations of SCS with MILK, FAT, and PROT were positive but low (0.25, 0.18, and 0.23, respectively). Genetic and phenotypic correlations between MILK, FAT, and PROT were high and positive (≥0.66). Absolute values of genetic correlations involving SCS with type traits were generally low or no different from zero. Most of the phenotypic correlations involving SCS with type traits were low. No serious unfavorable genetic correlations between milk yield traits and SCS or between milk yield traits or SCS and type traits were found. Conclusion Genetic variation exists in the ND breed for most studied traits. The development of selection programs based on these estimates may help accelerate favorable multi-trait genetic changes in this breed.
Gender differences in early stages of language development. Some evidence and possible explanations

It is a common feeling that girls speak earlier than boys; however, whether or not there are gender differences in early language acquisition remains controversial. The present paper aims to review the research on gender effects in early language acquisition and development, to determine whether, and from which age, an advantage for girls does eventually emerge. The focus is on the production of actions and communicative gestures, and early lexical comprehension and production, by girls and boys. The data from various studies that were conducted with direct and indirect tools suggest that some gender differences in actions, gesture, and lexical development depend on the interactions of different factors. Studies differ in terms of age ranges, sample sizes, and tools used, and the girl advantage is often slight and/or not evident at all ages considered. Statistical significance for gender differences appears to depend on the greater individual variability among boys, with respect to girls, which results in a greater number of boys classified as children with poor verbal ability. Biological (e.g., different maturational rates), neuropsychological (e.g., different cognitive strategies in solving tasks), and cultural (e.g., differences in the way parents relate socially to boys and girls) factors appear to interact, to create feedback loops of mutual reinforcement.
QRISK3 Relation to Carotid Plaque is Higher than that of SCORE In Patients with Systemic Lupus Erythematosus.

INTRODUCTION Systemic lupus erythematosus (SLE) has been described as an independent risk factor for the development of cardiovascular (CV) disease. Recently, the QRESEARCH risk estimator version 3 (QRISK3) calculator has been launched for CV risk assessment in the general population. QRISK3 now includes the presence of SLE as one of its variables for calculating CV risk. Our objective was to compare the predictive capacity between QRISK3 and the Systematic Coronary Risk Assessment (SCORE) for the presence of subclinical carotid atherosclerosis in patients with SLE. METHODS 296 patients with SLE were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied. RESULTS There was no correlation between SCORE and QRISK3 in patients with SLE (Rho Spearman r= -0.008, p= 0.90). Although QRISK3 showed a statistically significant correlation with cIMT (Rho Spearman r = 0.420, p= 0.000), this relationship was not found between SCORE and cIMT (Rho Spearman r= -0.005, p= 0.93). The discrimination capacity of QRISK3 for the presence of carotid plaque was statistically significant and superior to that of SCORE (AUC 0.765 [95% CI 0.711-0.820] vs 0.561 [95% CI 0.494-0.629], p= 0.000). CONCLUSION QRISK3 discrimination for subclinical atherosclerosis is higher than that of SCORE. QRISK3, and not SCORE, should be used for the calculation of CV risk in patients with SLE.
GmPIN-dependent polar auxin transport is involved in soybean nodule development

Abstract To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that are fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed the impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that the establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia.
Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer

Although docetaxel (DTX) confers significant survival benefits in patients with castration‐resistant prostate cancer (CRPC), resistance to DTX inevitably occurs. Therefore, clarifying the mechanisms of DTX resistance may improve survival in patients with CRPC. Claspin plays a pivotal role in DNA replication stress and damage responses and is an essential regulator for the S‐phase checkpoint. CLSPN is an oncogenic gene that contributes to tumor proliferation in several human solid tumors. However, the clinical significance of claspin in prostate cancer (PCa) has not been examined. The present study aimed to elucidate the role of claspin and its relationship with DTX resistance in PCa. We immunohistochemically analyzed the expression of claspin in 89 PCa cases, of which 31 (35%) were positive for claspin. Claspin‐positive cases were associated with higher Gleason score, venous invasion, and perineural invasion. Kaplan–Meier analysis showed that high claspin expression was related to poor prostate‐specific antigen (PSA) relapse‐free prognosis. In a public database, high CLSPN expression was associated with poor PSA relapse‐free prognosis, Gleason score, T stage, lymph node metastasis, CRPC, and metastatic PCa. Claspin knockdown by siRNA decreased cell proliferation, upregulated DTX sensitivity, and suppressed the expression of Akt, Erk1/2, and CHK1 phosphorylation in DU145 and PC3 cell lines. Furthermore, claspin expression was much more upregulated in DTX‐resistant DU145 (DU145‐DR) than in parental DU145 cells. Claspin knockdown significantly upregulated the sensitivity to DTX in DU145‐DR cells. These results suggest that claspin plays an important role in PCa tumor progression and DTX resistance.
Clinical and echocardiographic characteristics after six months of sacubitril/valsartan in Chagas heart disease – A case series

Chagas cardiomyopathy is the most prevalent non‐ischaemic cardiomyopathy in Latin America, with high morbidity and mortality even today. Treatment of these patients is based on the use of medications for heart failure. This study evaluated a case series of patients with Chagas heart disease who used sacubitril/valsartan at a referral hospital for this disease in Brazil. After 6 months, there was a symptomatic improvement in these individuals assessed by the New York Heart Association (NYHA) functional class, with a 44.3% reduction in the absolute number of patients classified as III–IV in the period (P = 0.035), but without changes in the parameters on the echocardiogram for reverse ventricular remodelling. There was a high mortality rate and number of hospitalizations. These results emphasize the importance of studying the use of sacubitril/valsartan in Chagas heart disease to better describe its effectiveness considering the particularities of these individuals.
Thyroid hormone receptor β sumoylation is required for thyrotropin regulation and thyroid hormone production

Thyroid hormone receptor β (THRB) is posttranslationally modified by small ubiquitin-like modifier (SUMO). We generated a mouse model with a mutation that disrupted sumoylation at lysine 146 (K146Q) and resulted in desumoylated THRB as the predominant form in tissues. The THRB K146Q mutant mice had normal serum thyroxine (T4), markedly elevated serum thyrotropin-stimulating hormone (TSH; 81-fold above control), and enlargement of both the pituitary and the thyroid gland. The marked elevation in TSH, despite a normal serum T4, indicated blunted feedback regulation of TSH. The THRB K146Q mutation altered the recruitment of transcription factors to the TSHβ gene promoter, compared with WT, in hyperthyroidism and hypothyroidism. Thyroid hormone content (T4, T3, and rT3) in the thyroid gland of the THRB K146Q mice was 10-fold lower (per gram tissue) than control, despite normal TSH bioactivity. The expression of thyroglobulin and dual oxidase 2 genes in the thyroid was reduced and associated with modifications of cAMP response element–binding protein DNA binding and cofactor interactions in the presence of the desumoylated THRB. Therefore, thyroid hormone production had both TSH-dependent and TSH-independent components. We conclude that THRB sumoylation at K146 was required for normal TSH feedback regulation and TH synthesis in the thyroid gland, by a TSH-independent pathway.
Biological Aspects of the Tongue and Oropharyngeal Cavity of the Eurasian Collared Dove (Streptopelia decaocto, Columbiformes, Columbidae): Anatomical, Histochemical, and Ultrastructure Study

Abstract We characterized the morphological and anatomical adaptations of the lingual microstructures of the Eurasian collared dove and discussed their implications for its dietary niche. We analyzed tongues of nine S. decaocto using histological, histochemical, stereomicroscopic, and scanning electron microscopic techniques. Our findings showed that the tongue is relatively short with a tapered apex that carries a terminal lingual nail. However, the lingual body has median scales and is bordered laterally by filiform papillae. Further, the tongue body bears a distinctive papillary crest. The tongue root is nonpapillate and infiltered with orifices of the posterior salivary glands. The bulky laryngeal mound has a circular glottic fissure, carrying a single row of papillae at the rear edge. Concurrently, our histological and histochemical findings demonstrate that the tongue has taste buds, anterior and posterior salivary glands, along with an elongated entoglossum that extends from lingual apex to root. Besides, ovoid and globular mucous glands displayed intense alcianophilic reactions. More substantially, the palate is made up of three palatine ridges with a caudal choanal cleft that was bounded by two rows of palatine papillae. Our data indicate multiple and novel structural variations for the lingual and palatal sculptures coopted for their feeding style.
Posterior wedge osteotomy assisted by O-arm navigation for treating ankylosing spondylitis with thoracolumbar fractures: an early clinical evaluation.

BACKGROUND To explore the feasibility and efficiency of posterior wedge osteotomy assisted by O-arm navigation treatment of ankylosing spondylitis (AS) patients with thoracolumbar fracture. METHODS This is a case series study. A total of 16 cases of AS accompanied by thoracolumbar fractures from January 2012 to July 2015 were retrospectively analyzed. All patients underwent "posterior wedge osteotomy assisted by O-arm navigation". The operation time, blood loss volume, preoperative and postoperative visual analogue scale (VAS), American Spinal Injury Association (ASIA) classification, and spinal imaging parameters [Cobb angle, C7 plumb line (C7PL), and jaw-brow angle] were collected and analyzed. RESULTS The operative time consumption was 120-350 mins and the intra-operative blood loss volume was 200-800 mL. No obvious postoperative complications occurred in any participants. The back pain of all participants was relieved, and the neurological functions of eight participants with spinal cord injury (SCI) were recovered in varying degrees except for one patient with severe SCI. The spinal deformities of the participants were corrected to varying degrees. The fracture sites of 16 participants were all healed, and there was no loosening or detachment of internal fixation during the 6-month follow-up period. CONCLUSIONS Posterior wedge osteotomy assisted by O-arm navigation was shown to be a safe and effective method to treat AS accompanied by thoracolumbar fractures. This treatment strategy can accurately decompress and reduce the fracture and significantly correct the kyphosis, with good surgical effect.
Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis

ABSTRACT Glioblastoma multiforme (GBM) is the most fatal malignancy, and despite extensive treatment, tumors inevitably recur. This study aimed to identify recurrence-associated molecules in GBM. The gene expression profile GSE139533, containing 70 primary and 47 recurrent GBM tissues and their corresponding clinical traits, was downloaded from the Gene Expression Omnibus (GEO) database and used for weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. After identifying the hub genes which differentially expressed in recurrent GBM tissues and in the gene modules correlated with recurrence, data from the Chinese Glioma Genome Atlas (CCGA) and The Cancer Genome Atlas (TCGA) databases were analyzed with GSE43378 to determine the relationship between hub genes and patient prognosis. The diagnostic value of the identified hub genes was verified using 52 GBM tissues. Three gene modules were correlated with recurrence and 2623 genes were clustered in these clinically significant modules. Among these, 13 genes – EHF, TRPM1, FXYD4, CDH15, LHX5, TP73, FBN3, TLX1, C1QL4, COL2A, SEC61G, NEUROD4 and GPR139 – were differentially expressed in recurrent GBM samples; low LHX5 and TLX1 expression predicted poor outcomes. LHX5 and TLX1 expression showed weak positive relationships with Karnofsky performance scale scores. Additionally, LHX5 and TLX1 expression was found to be decreased in our recurrent GBM samples compared with that in primary samples; these genes exhibited high diagnostic value in distinguishing recurrent samples from primary samples. Our findings indicate that LHX5 and TLX1 might be involved in GBM recurrence and act as potential biomarkers for this condition. Graphical abstract
Definition of the immune evasion-replication interface of rabies virus P protein

Rabies virus phosphoprotein (P protein) is a multifunctional protein that plays key roles in replication as the polymerase cofactor that binds to the complex of viral genomic RNA and the nucleoprotein (N protein), and in evading the innate immune response by binding to STAT transcription factors. These interactions are mediated by the C-terminal domain of P (PCTD). The colocation of these binding sites in the small globular PCTD raises the question of how these interactions underlying replication and immune evasion, central to viral infection, are coordinated and, potentially, coregulated. While direct data on the binding interface of the PCTD for STAT1 is available, the lack of direct structural data on the sites that bind N protein limits our understanding of this interaction hub. The PCTD was proposed to bind via two sites to a flexible loop of N protein (Npep) that is not visible in crystal structures, but no direct analysis of this interaction has been reported. Here we use Nuclear Magnetic Resonance, and molecular modelling to show N protein residues, Leu381, Asp383, Asp384 and phosphor-Ser389, are likely to bind to a ‘positive patch’ of the PCTD formed by Lys211, Lys214 and Arg260. Furthermore, in contrast to previous predictions we identify a single site of interaction on the PCTD by this Npep. Intriguingly, this site is proximal to the defined STAT1 binding site that includes Ile201 to Phe209. However, cell-based assays indicate that STAT1 and N protein do not compete for P protein. Thus, it appears that interactions critical to replication and immune evasion can occur simultaneously with the same molecules of P protein so that the binding of P protein to activated STAT1 can potentially occur without interrupting interactions involved in replication. These data suggest that replication complexes might be directly involved in STAT1 antagonism.