Miracle-dz/UniFAR-FTUs huggingface dataset:
A Connection between Lysine and Serotonin Metabolism in Rice Endosperm1[OPEN]

Serotonin biosynthesis is dramatically elevated, and closely linked with dark-brown color of the endosperm, in high-lysine rice. Cereal endosperms produce a vast array of metabolites, including the essential amino acid lysine (Lys). Enhanced accumulation of Lys has been achieved via metabolic engineering in cereals, but the potential connection between metabolic engineering and Lys fortification is unclear. In mature seeds of engineered High Free Lysine (HFL) rice (Oryza sativa), the endosperm takes on a characteristic dark-brown appearance. In this study, we use an integrated metabolomic and transcriptomic approach combined with functional validation to elucidate the key metabolites responsible for the dark-brown phenotype. Importantly, we found that serotonin biosynthesis was elevated dramatically and closely linked with dark-brown endosperm color in HFL rice. A functional connection between serotonin and endosperm color was confirmed via overexpression of TDC3, a key enzyme of serotonin biosynthesis. Furthermore, we show that both the jasmonate signaling pathway and TDC expression were strongly induced in the late stage of endosperm development of HFL rice, coinciding with serotonin accumulation and dark-brown pigmentation. We propose a model for the metabolic connection between Lys and serotonin metabolism in which elevated 2-aminoadipate from Lys catabolism may play a key role in the connection between the jasmonate signaling pathway, serotonin accumulation, and the brown phenotype in rice endosperm. Our data provide a deeper understanding of amino acid metabolism in rice. In addition, the finding that both Lys and serotonin accumulate in HFL rice grains should promote efforts to create a nutritionally favorable crop.
Muscle-tendon length and force affect human tibialis anterior central aponeurosis stiffness in vivo

Significance Muscle-force production and energy consumption are highly dependent on stiffness of the connecting tendinous tissues (tendon and aponeurosis). Although reduced tendinous tissue stiffness favors greater elastic energy recovery, it permits muscle fiber shortening during fixed-end contractions, which is economically unfavorable for force production. Here, we provide in vivo evidence that the longitudinal central aponeurosis stiffness of human tibialis anterior increases not only with force but also with muscle-tendon unit length. Such a mechanism is likely to be beneficial for different movement scenarios for a range of lower limb muscles. These findings are important for interpreting and modeling muscle-force production and energy consumption during movement and understanding muscle and tendon injury mechanics. The factors that drive variable aponeurosis behaviors in active versus passive muscle may alter the longitudinal stiffness of the aponeurosis during contraction, which may change the fascicle strains for a given muscle force. However, it remains unknown whether these factors can drive variable aponeurosis behaviors across different muscle-tendon unit (MTU) lengths and influence the subsequent fascicle strains during contraction. Here, we used ultrasound and elastography techniques to examine in vivo muscle fascicle behavior and central aponeurosis deformations of human tibialis anterior (TA) during force-matched voluntary isometric dorsiflexion contractions at three MTU lengths. We found that increases in TA MTU length increased both the length and apparent longitudinal stiffness of the central aponeurosis at low and moderate muscle forces (P < 0.01). We also found that increased aponeurosis stiffness was directly related to reduced magnitudes of TA muscle fascicle shortening for the same change in force (P < 0.01). The increase in slope and shift to longer overall lengths of the active aponeurosis force–length relationship as MTU length increased was likely due to a combination of parallel lengthening of aponeurosis and greater transverse aponeurosis strains. This study provides in vivo evidence that human aponeurosis stiffness is increased from low to moderate forces and that the fascicle strains for a given muscle force are MTU length dependent. Further testing is warranted to determine whether MTU length-dependent stiffness is a fundamental property of the aponeurosis in pennate muscles and evaluate whether this property can enhance muscle performance.
Improving guideline concordance in multidisciplinary teams: preliminary results of a cluster-randomized trial evaluating the effect of a web-based audit and feedback intervention with outreach visits

Despite their widespread use, audit and feedback (A&F) interventions show variable effectiveness on improving professional performance. Based on known facilitators of successful A&F interventions, we developed a web-based A&F intervention with indicator-based performance feedback, benchmark information, action planning and outreach visits. The goal of the intervention was to engage with multidisciplinary teams to overcome barriers to guideline concordance and to improve overall team performance in the field of cardiac rehabilitation (CR). To assess its effectiveness we conducted a cluster-randomized trial in 18 CR clinics (14,847 patients) already working with computerized decision support (CDS). Our preliminary results showed no increase in concordance with guideline recommendations regarding prescription of CR therapies. Future analyses will investigate whether our intervention did improve team performance on other quality indicators.
Dicer and Argonaute Genes Involved in RNA Interference in the Entomopathogenic Fungus Metarhizium robertsii

ABSTRACT RNA interference (RNAi) is a gene-silencing mechanism that plays an important role in gene regulation in a number of eukaryotic organisms. Two core components, Dicer and Argonaute, are central in the RNAi machinery. However, the physiological roles of Dicer and Argonaute in the entomopathogenic fungus Metarhizium robertsii have remained unclear. Here, the roles of genes encoding Dicer (M. robertsiidcl1 [Mrdcl1] and Mrdcl2) and Argonaute (Mrago1 and Mrago2) proteins in M. robertsii were investigated. The results showed that the Dicer-like protein MrDCL2 and Argonaute protein MrAGO1 are the major components of the RNAi process occurring in M. robertsii. The Dicer and Argonaute genes were not involved in the regulation of growth and diverse abiotic stress response in M. robertsii under the tested conditions. Moreover, our results showed that the Dicer and Argonaute gene mutants demonstrated reduced abilities to produce conidia, compared to the wild type (WT) and the gene-rescued mutant. In particular, the conidial yields in the Δdcl2 and Δago1 mutants were reduced by 55.8% and 59.3%, respectively, compared with those from the control strains. Subsequently, for the WT and Δdcl2 mutant strains, digital gene expression (DGE) profiling analysis of the stage of mycelium growth and conidiogenesis revealed that modest changes occur in development or metabolism processes, which may explain the reduction in conidiation in the Δdcl2 mutant. In addition, we further applied high-throughput sequencing technology to identify small RNAs (sRNAs) that are differentially expressed in the WT and the Δdcl2 mutant and found that 4 known microRNA-like small RNAs (milRNAs) and 8 novel milRNAs were Mrdcl2 dependent in M. robertsii. IMPORTANCE The identification and characterization of components in RNAi have contributed significantly to our understanding of the mechanism and functions of RNAi in eukaryotes. Here, we found that Dicer and Argonaute genes play an important role in regulating conidiation in M. robertsii. Our study also demonstrates that diverse small RNA pathways exist in M. robertsii. The study provides a theoretical platform for exploration of the functions of Dicer and Argonaute genes involved in RNAi in fungi.
Humanized Mouse Models for Transplant Immunology

Our understanding of the molecular pathways that control immune responses, particularly immunomodulatory molecules that control the extent and duration of an immune response, have led to new approaches in the field of transplantation immunology to induce allograft survival. These molecular pathways are being defined precisely in murine models and translated into clinical practice; however, many of the newly available drugs are human‐specific reagents. Furthermore, many species‐specific differences exist between mouse and human immune systems. Recent advances in the development of humanized mice, namely, immunodeficient mice engrafted with functional human immune systems, have led to the availability of a small animal model for the study of human immune responses. Humanized mice represent an important preclinical model system for evaluation of new drugs and identification of the mechanisms underlying human allograft rejection without putting patients at risk. This review highlights recent advances in the development of humanized mice and their use as preclinical models for the study of human allograft responses.
Discordant Temporal Turnovers of Sediment Bacterial and Eukaryotic Communities in Response to Dredging: Nonresilience and Functional Changes

ABSTRACT To study the stability and succession of sediment microbial and macrobenthic communities in response to anthropogenic disturbance, a time-series sampling was conducted before, during, and 1 year after dredging in the Guan River in Changzhou, China, which was performed with cutter suction dredgers from 10 April to 20 May 2014. The microbial communities were analyzed by sequencing bacterial 16S rRNA and eukaryotic 18S rRNA gene amplicons with Illumina MiSeq, and the macrobenthic community was identified using a morphological approach simultaneously. The results indicated that dredging disturbance significantly altered the composition and structures of sediment communities. The succession rates of communities were estimated by comparing the slopes of time-decay relationships. The temporal turnover of microeukaryotes (w = 0.3251, P < 0.001 [where w is a measure of the rate of log(species turnover) across log(time)]) was the highest, followed by that of bacteria (w = 0.2450, P < 0.001), and then macrobenthos (w = 0.1273, P < 0.001). During dredging, the alpha diversities of both bacterial and microeukaryotic communities were more resistant, but their beta diversities were less resistant than that of macrobenthos. After recovery for 1 year, all three sediment communities were not resilient and had reached an alternative state. The alterations in sediment community structure and stability resulted in functional changes in nitrogen and carbon cycling in sediments. Sediment pH, dissolved oxygen, redox potential, and temperature were the most important factors influencing the stability of sediment communities and ecosystem multifunctionality. This study suggests that discordant temporal turnovers and nonresilience of sediment communities under dredging resulted in functional changes, which are important for predicting sediment ecosystem functions under anthropogenic disturbances. IMPORTANCE Understanding the temporal turnover and stability of biotic communities is crucial for predicting the responses of sediment ecosystems to dredging disturbance. Most studies to date focused on the bacterial or macrobenthic community, only at two discontinuous time points, before and after dredging, and hence, it was difficult to analyze the community succession. This study first compared the stabilities and temporal changes of sediment bacterial, microeukaryotic, and macrobenthic communities at a continuous time course. The results showed that discordant responses of the three communities are mainly related to their different biological inherent attributes, and sensitivities to sediment geochemical variables change with dredging, resulting in changes in sediment ecosystem multifunctionality.
Hepatocellular Carcinoma in a β-Thalassemia Intermedia Patient: Yet Another Case in the Expanding Epidemic

Abstract The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is increasing, the two well recognized HCC risk factors in thalassemia being iron overload and chronic hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, whereas chronic hepatitis leads to necroinflammation that can accelerate progression to HCC. We hereby report the case of a non transfused, hepatitis C-negative, β-thalassemia intermedia (β-TI) patient from our practice who had evidence of significant iron overload, suggesting the importance of increased iron burden as a HCC risk factor in this patient population. As such, screening thalassemia patients using magnetic resonance imaging (MRI)-based liver iron concentration (LIC) measurement and liver ultrasound is strongly recommended for early detection of iron overload and HCC, respectively. Data appears to be lacking on HCC treatment outcomes in patients who have thalassemia, but an approach tailored to each patient’s comorbidities is key to treatment success. The prognosis of these patients can be improved by multicenter studies investigating novel HCC therapeutic targets in the thalassemia realm.
Burden of severe neonatal jaundice: a systematic review and meta-analysis

Context To assess the global burden of late and/or poor management of severe neonatal jaundice (SNJ), a common problem worldwide, which may result in death or irreversible brain damage with disabilities in survivors. Population-based data establishing the global burden of SNJ has not been previously reported. Objective Determine the burden of SNJ in all WHO regions, as defined by clinical jaundice associated with clinical outcomes including acute bilirubin encephalopathy/kernicterus and/or exchange transfusion (ET) and/or jaundice-related death. Data sources PubMed, Scopus and other health databases were searched, without language restrictions, from 1990 to 2017 for studies reporting the incidence of SNJ. Study selection/data extraction Stratification was performed for WHO regions and results were pooled using random effects model and meta-regression. Results Of 416 articles including at least one marker of SNJ, only 21 reported estimates from population-based studies, with 76% (16/21) of them conducted in high-income countries. The African region has the highest incidence of SNJ per 10 000 live births at 667.8 (95% CI 603.4 to 738.5), followed by Southeast Asian, Eastern Mediterranean, Western Pacific, Americas and European regions at 251.3 (132.0 to 473.2), 165.7 (114.6 to 238.9), 9.4 (0.1 to 755.9), 4.4 (1.8 to 10.5) and 3.7 (1.7 to 8.0), respectively. The incidence of ET per 10 000 live births was significantly higher for Africa and Southeast Asian regions at 186.5 (153.2 to 226.8) and 107.1 (102.0 to 112.5) and lower in Eastern Mediterranean (17.8 (5.7 to 54.9)), Americas (0.38 (0.21 to 0.67)), European (0.35 (0.20 to 0.60)) and Western Pacific regions (0.19 (0.12 to 0.31). Only 2 studies provided estimates of clear jaundice-related deaths in infants with significant jaundice [UK (2.8%) and India (30.8%). Conclusions Limited but compelling evidence demonstrates that SNJ is associated with a significant health burden especially in low-income and middle-income countries.
The emergent algebraic structure of RNNs and embeddings in NLP

We examine the algebraic and geometric properties of a uni-directional GRU and word embeddings trained end-to-end on a text classification task. A hyperparameter search over word embedding dimension, GRU hidden dimension, and a linear combination of the GRU outputs is performed. We conclude that words naturally embed themselves in a Lie group and that RNNs form a nonlinear representation of the group. Appealing to these results, we propose a novel class of recurrent-like neural networks and a word embedding scheme.
A First-Trimester Biomarker Panel for Predicting the Development of Gestational Diabetes

Objective: Serum markers measured early in pregnancy have been associated with the later diagnosis of gestational diabetes mellitus (GDM). This study aims to explore the performance of a panel of first-trimester biochemical markers for the prediction of GDM. Methods: A case–control study was performed that included 12 women who developed GDM and 60 controls matched for maternal and gestational age at blood collection. Levels of pregnancy-associated plasma protein A (PAPP-A), soluble endoglin, pregnancy protein 13, and adiponectin (Adipo) were measured on residual sera used in first-trimester screening for Down syndrome. Data were analyzed by nonparametric methods. A receiver operating characteristic curve was used to calculate the detection rate (DR) obtained with a panel of significant predictors for GDM. Results: Multiples of the median values for Adipo and PAPP-A were significantly reduced in GDM cases versus matched controls. Combination of Adipo and PAPP-A yielded a DR of 63.6% at a false-positive rate of 10%. Addition of body mass index (BMI) to this panel increased DR to 72.7%. Conclusion: This study suggests that first-trimester screening with Adipo, PAPP-A, and BMI may effectively identify women at high risk for the development of GDM.
Activation of Akt characterizes estrogen receptor positive human breast cancers which respond to anthracyclines

Anthracyclines are key components of human breast cancer chemotherapy. Here, we explored the role of Akt signaling in anthracycline resistance. The antitumor activity of doxorubicin and Akt inhibitor A-443654 alone or combined was examined in estrogen receptor (ER) positive and negative human breast cancer cell lines. Further, we examined mRNA changes induced by anthracyclines in locally advanced breast cancers biopsied before and after treatment in two clinical trials. Doxorubicin increased Akt phosphorylation in ER positive MCF7 and T47D cell lines, with no effect in ER negative MDA-MB231 breast cancer cells. A-443654 was significantly more cytotoxic in doxorubicin-resistant compared to doxorubicin-naïve MCF7. This difference was not observed in MDA-MB231. Among 24 patients, AKT1 gene expression increased 24 hrs after the initial epirubicin exposure in ER positive tumors responding to therapy (n=6), as compared to ER positive non-responders (n=7) or ER negative tumors (n=11). In contrast, AKT1 mRNA changes after 16 weeks of doxorubicin were unrelated to clinical response and ER status (n=30). In conclusion, rapid Akt activation was observed in ER positive breast cancers which responded to anthracyclines. Increased cytotoxicity of A-443654 in doxorubicin-resistant MCF7 cells indicates a possible role for Akt inhibitors in ER positive breast cancers where chemoresistance evolves.
Measuring attention in very old adults using the Test of Everyday Attention

ABSTRACT There is a need for validated measures of attention for use in longitudinal studies of older populations. We studied 249 participants aged 80 to 101 years using the population-based MOBILIZE Boston Study. Four subscales of the Test of Everyday Attention (TEA) were included, measuring attention switching, selective, sustained and divided attention and a neuropsychological battery including validated measures of multiple cognitive domains measuring attention, executive function and memory. The TEA previously has not been validated in persons aged 80 and older. Among participants who completed the TEA, scores on other attentional measures strongly with TEA domains (R=.60-.70). Proportions of participants with incomplete TEA subscales ranged from 8% (selective attention) to 19% (attentional switching). Reasons for not completing TEA tests included failure to comprehend test instructions despite repetition and practice. These results demonstrate the challenges and potential value of the Test of Everyday Attention in studies of very old populations.
Antimicrobial activity of copaiba oil (Copaifera ssp.) on oral pathogens: Systematic review

Copaifera ssp. produces an oil‐resin that presents antiinflammatory, antitumor, antiseptic, germicidal, antifungal, and antibacterial activity. This systematic review aimed to analyze the antimicrobial action of Copaiba oil against oral pathogens, when compared to that of control substances. A search on Medline/PubMed, LILACS, SciELO, EMBASE, and SCOPUS databases were performed up to March 2017. To be included, the studies needed to perform any antimicrobial activity essay, using copaiba oil and a control substance. The antimicrobial effect of each substance, in each study, was extracted. Eleven studies were included, and several copaiba species were used. All studies showed that copaiba oil, regardless of its species, presented a bactericidal and/or bacteriostatic effect in in vitro analyzes. Only one study showed that the antimicrobial effect of the Copaifera officinalis was similar to the one found in chlorhexidine. A higher risk of bias was detected in most of the included studies. The studies demonstrated that the antimicrobial activity of copaiba oil, in most cases, is lower than chlorhexidine, which is considered the gold standard. However, there is great potential against oral bacteria. Further high quality studies are warranted in order to assess the efficacy of copaiba oil on oral pathogens.
The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local TH17 Responses

ABSTRACT The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro. In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses.