Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in Endogenous Dopamine Induced by Methylphenidate Predict Functional Connectivity in Nonhuman Primates

Dopamine (DA) levels in the striatum are increased by many therapeutic drugs, such as methylphenidate (MPH), which also alters behavioral and cognitive functions thought to be controlled by the PFC dose-dependently. We linked DA changes and functional connectivity (FC) using simultaneous [18F]fallypride PET and resting-state fMRI in awake male rhesus monkeys after oral administration of various doses of MPH. We found a negative correlation between [18F]fallypride nondisplaceable binding potential (BPND) and MPH dose in the head of the caudate (hCd), demonstrating increased extracellular DA resulting from MPH administration. The decreased BPND was negatively correlated with FC between the hCd and the PFC. Subsequent voxelwise analyses revealed negative correlations with FC between the hCd and the dorsolateral PFC, hippocampus, and precuneus. These results, showing that MPH-induced changes in DA levels in the hCd predict resting-state FC, shed light on a mechanism by which changes in striatal DA could influence function in the PFC. SIGNIFICANCE STATEMENT Dopamine transmission is thought to play an essential role in shaping large scale-neural networks that underlie cognitive functions. It is the target of therapeutic drugs, such as methylphenidate (Ritalin), which blocks the dopamine transporter, thereby increasing extracellular dopamine levels. Methylphenidate is used extensively to treat attention deficit hyperactivity disorder, even though its effects on cognitive functions and their underlying neural mechanisms are not well understood. To date, little is known about the link between changes in dopamine levels and changes in functional brain organization. Using simultaneous PET/MR imaging, we show that methylphenidate-induced changes in endogenous dopamine levels in the head of the caudate predict changes in resting-state functional connectivity between this structure and the prefrontal cortex, precuneus, and hippocampus.
Generation of a Primary Hyperoxaluria Type 1 Disease Model Via CRISPR/Cas9 System in Rats.

BACKGROUND Primary hyperoxaluria type 1 (PH1) is an inherited disease caused by mutations in alanine-glyoxylate aminotransferase (AGXT). It is characterized by abnormal metabolism of glyoxylic acid in the liver leading to endogenous oxalate overproduction and deposition of oxalate in multiple organs, mainly the kidney. Patients of PH1 often suffer from recurrent urinary tract stones, and finally renal failure. There is no effective treatment other than combined liver-kidney transplantation. METHODS Microinjection was administered to PH1 rats. Urine samples were collected for urine analysis. Kidney tissues were for Western blotting, quantitative PCR, AGT assays and histological evaluation. RESULTS In this study, we generated a novel PH1 disease model through CRISPR/Cas9 mediated disruption of mitochondrial localized Agxt gene isoform in rats. Agxt-deficient rats excreted more oxalate in the urine than WT animals. Meanwhile, mutant rats exhibited crystalluria and showed a slight dilatation of renal tubules with mild fibrosis in the kidney. When supplied with 0.4% ethylene glycol (EG) in drinking water, mutant rats excreted greater abundance of oxalate and developed severe nephrocalcinosis in contrast to WT animals. Significantly elevated expression of inflammation- and fibrosisrelated genes was also detected in mutants. CONCLUSION These data suggest that Agxt-deficiency in mitochondria impairs glyoxylic acid metabolism and leads to PH1 in rats. This rat strain would not only be a useful model for the study of the pathogenesis and pathology of PH1 but also a valuable tool for the development and evaluation of innovative drugs and therapeutics.
Femural Head Autosegmentation for 3D Radiotherapy Planning: Preliminary Results

Contouring of organs at risk is an important but time consuming part of radiotherapy treatment planning. Several authors proposed methods for automatic delineation but the clinical experts eye remains the gold standard method. In this paper, we present a totally visual software for automated delineation of the femural head. The software was successfully characterized in pelvic CT Scan of prostate patients (n=11). The automatic delineation was compared with manual and approved delineation through blind test evaluated by a panel of seniors radiation oncologists (n=9). Clinical experts evaluated that no any contouring correction were need in 77.8% and 67.8% of manual and automatic delineation respectively. Our results show that the software is robust, the automated delineation was reproducible in all patient, and its performance was similar to manually delineation.
Editorial: which iron preparation for patients with IBD?

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Acibenzolar-S-Methyl Reprograms Apple Transcriptome Toward Resistance to Rosy Apple Aphid

Acibenzolar-S-methyl (ASM) is a chemical compound, which is able to induce resistance in several model and non-model plants, but the end-players of this induced defense remain ill-defined. Here, we test the hypothesis that treatment with ASM can protect apple (Malus × domestica) against the rosy apple aphid (Dysaphis plantaginea) and investigate the defense molecules potentially involved in resistance. We measured aphid life traits and performed behavioral assays to study the effect of ASM on plant resistance against the aphid, and then combined transcriptomic, bioinformatics, metabolic and biochemical analyses to identify the plant compounds involved in resistance. Plants treated with ASM negatively affected several life traits of the aphid and modified its feeding and host seeking behaviors. ASM treatment elicited up-regulation of terpene synthase genes in apple and led to the emission of (E,E)-α-farnesene, a sesquiterpene that was repellent to the aphid. Several genes encoding amaranthin-like lectins were also strongly up-regulated upon treatment and the corresponding proteins accumulated in leaves, petioles and stems. Our results link the production of specific apple proteins and metabolites to the antibiosis and antixenosis effects observed against Dysaphis plantaginea, providing insight into the mechanisms underlying ASM-induced herbivore resistance.
Attachment Style, Openness to Experience, and Social Contact as Predictors of Attitudes Toward Homosexuality

ABSTRACT Considerable research has shown that people generally hold more negative attitudes toward homosexuals. Given this fact, it is important to understand psychological and social correlates of homophobia. With this purpose, the present study investigates attachment styles, openness to experience, and social contact in relation to attitudes toward homosexuals. The findings show that being female, having prior contact with homosexuals, and scoring high in openness to experience predict more favorable attitudes toward homosexuals. The supplementary analyses also support the moderating effect of secure attachment on the relationship between openness to experience and attitudes toward homosexuals. The present study not only extends the related research by examining the interactive effects of attachment style and personality trait, but also provides important implications for researchers, educators, or managers in terms of reducing anti-homosexual attitudes in diverse settings.
Re‐programming of gene expression in the CS8 rice line over‐expressing ADPglucose pyrophosphorylase induces a suppressor of starch biosynthesis

The CS8 transgenic rice (Oryza sativa L.) lines expressing an up-regulated glgC gene produced higher levels of ADPglucose (ADPglc), the substrate for starch synthases. However, the increase in grain weight was much less than the increase in ADPglc levels suggesting one or more downstream rate-limiting steps. Endosperm starch levels were not further enhanced in double transgenic plants expressing both glgC and the maize brittle-1 gene, the latter responsible for transport of ADPglc into the amyloplast. These studies demonstrate that critical processes within the amyloplast stroma restrict maximum carbon flow into starch. RNA-seq analysis showed extensive re-programming of gene expression in the CS8 with 2073 genes up-regulated and 140 down-regulated. One conspicuous gene, up-regulated ~15-fold, coded for a biochemically uncharacterized starch binding domain-containing protein (SBDCP1) possessing a plastid transit peptide. Confocal microscopy and transmission electron microscopy analysis confirmed that SBDCP1 was located in the amyloplasts. Reciprocal immunoprecipitation and pull-down assays indicated an interaction between SBDCP1 and starch synthase IIIa (SSIIIa), which was down-regulated at the protein level in the CS8 line. Furthermore, binding by SBDCP1 inhibited SSIIIa starch polymerization activity in a non-competitive manner. Surprisingly, artificial microRNA gene suppression of SBDCP1 restored protein expression levels of SSIIIa in the CS8 line resulting in starch with lower amylose content and increased amylopectin chains with a higher degree of polymerization. Collectively, our results support the involvement of additional non-enzymatic factors such as SBDCP in starch biosynthesis.
Risky sexual behavior among adolescents: The role of decision-making, problems from cannabis use and externalizing disorder symptoms

ABSTRACT Introduction: Previous research has demonstrated that externalizing symptoms, cannabis use problems, and poor decision-making abilities are each independently related to risky sexual behavior (RSB). However, few studies have examined the joint effect of these factors on RSB among a sample of adolescents. Methods: The current study addresses this gap in the literature by examining how externalizing disorder symptoms, cannabis use, and decision-making abilities interact to predict RSB among a sample of adolescents (n = 204; Mage = 15.5) at-risk for escalation in cannabis use. Poisson regression was used for all analyses, and simple slope difference tests were used for all post-hoc analyses. Results: A greater number of externalizing symptoms, more problems from cannabis use, and more risk disadvantageous choices on the Cups Task (CT) total trials and more risk disadvantageous choices on the CT-gain trials predicted greater RSB endorsement. Findings also highlight significant interactions between cannabis use problems and CT-total and -gain trial performance, as well as between cannabis use problems and externalizing symptoms in predicting RSB.Conclusion: Current treatment and prevention approaches to reduce RSB among adolescents may benefit from incorporating techniques that improve decision-making skills.
Usefulness of the STarT Back Screening Tool to predict pain problems after lumbar spine surgery.

INTRODUCTION The Subgroups for Targeted Treatment (STarT) Back Screening Tool is used in general practice to stratify patients with acute back pain into either a low, medium or a high risk of developing complex pain. This study determines if the STarT Back Screening Tool can identify patients who are at a high risk of developing complex pain after spine surgery. METHODS The STarT Back Screening Tool was administered pre-operatively to a consecutive series of patients who had lumbar spine surgery between 29 October 2012 and 1 February 2013. A visual analogue scale (VAS, 0-100) for back and leg pain was determined pre-operatively and also on the first day after surgery, at discharge, at 4 to 12 weeks after surgery, and one year after surgery. Patients were stratified into those who underwent decompression only for lumbar disc herniation or stenosis and those who underwent decompression and fusion for spondylolisthesis. RESULTS In the decompression group, high-risk patients had poorer pre-operative back and leg pain scores, but similar length of stay, improvements in back or leg pain at 4-12 week and at the one-year follow-up compared with the other groups. The high-risk group experienced a significantly greater improvement in leg pain on the first post-operative day and on the day of discharge. In the decompression and fusion group, high-risk patients had poorer pre-operative back and leg pain scores than the other groups. There were no significant differences in back or leg pain improvement among the three groups at any time point during follow-up. CONCLUSIONS The results of this study show that the STarT Back Screening Tool may be useful for identifying patients who are at a high risk of developing complex pain after spine surgery. FUNDING none. TRIAL REGISTRATION not relevant.
World Kidney Day 2011: Protect Your Kidneys, Save Your Heart

For the Joint International Society of Nephrology (WGC) and International Federation of Kidney Foundations (MCR) World Kidney Day 2011 Steering Committee Willliam G Causer (ISN), Miguel C Riella (IFKF), co-chairmen. Georgi Abraham, Paul Beerkens, John Feehally, Guillermo Garcia Garcia, Jan Lantik, Dan Larsen, Philip Li, Mark Murphy and Bernardo Rodriguez-Iturbe.
A Single siRNA Suppresses Fatal Encephalitis Induced by Two Different Flaviviruses

Background Japanese encephalitis virus (JEV) and West Nile virus (WNV) are neurotropic flaviviruses that can cause acute encephalitis with a high fatality rate. Currently there is no effective treatment for these infections. Methods and Findings We tested RNA interference (RNAi)-based intervention to suppress lethal JE and WN encephalitis in mice. To induce RNAi, we used either lentivirally expressed short hairpin RNA (shRNA) or synthetic short interfering RNA (siRNA). As target, we selected the cd loop-coding sequence in domain II of the viral Envelope protein, which is highly conserved among all flaviviruses because of its essential role in membrane fusion. Using as a target a species-specific sequence in the cd loop that is conserved only among the different strains of either JEV or WNV, we could achieve specific protection against the corresponding virus. However, by targeting a cross-species conserved sequence within the cd loop, we were able to protect mice against encephalitis induced by both viruses. A single intracranial administration of lentivirally delivered shRNA or lipid-complexed siRNA before viral challenge or siRNA treatment after viral challenge was sufficient for protection against lethal encephalitis. Conclusions RNAi-based intervention affords near complete protection from both JEV- and WNV- induced encephalitis in mice. Our results show, to our knowledge for the first time, that siRNA can be used as a broad-spectrum antiviral agent for treating encephalitis caused by multiple related viruses.
Protein gradients on the nucleoid position the carbon-fixing organelles of cyanobacteria

In Brief We describe a novel positioning system that utilizes the cyanobacterial nucleoid to segregate, transport and equidistantly position the carbon-fixation machinery (carboxysomes). Summary Carboxysomes are protein-based bacterial organelles that encapsulate a key enzyme of the Calvin-Benson-Bassham cycle. Previous work has implicated a ParA-like protein (hereafter McdA) as important for spatially organizing carboxysomes along the longitudinal axis of the model cyanobacterium Synechococcus elongatus PCC 7942. Yet, how self-organization of McdA emerges and contributes to carboxysome positioning is unknown. Here, we show that a small protein, termed McdB, localizes to carboxysomes through interactions with carboxysome shell proteins to drive emergent oscillatory patterning of McdA on the nucleoid. Our results demonstrate that McdB directly interacts to stimulate McdA ATPase activity, and indicate that carboxysome-dependent McdA depletion zone formation on the nucleoid is required for directed motion of carboxysomes towards increased concentrations of McdA. We propose that McdA and McdB are a new class of self-organizing proteins that follow a Brownian-ratchet mechanism, challenging the cytoskeletal model of organelle transport, for equidistant positioning of carboxysomes in cyanobacteria. These results have broader implications for understanding spatial organization of protein mega-complexes and organelles in bacteria more broadly.
Extending decision making competence to special populations: a pilot study of persons on the autism spectrum

The area of decision making has much to offer in our effort to understand special populations. This pilot study is an example of just such a project, where we illustrate how traditional decision making tools and tasks can be used to uncover strengths and weaknesses within a growing population of young adults with autism. In this pilot project we extended accounts of autistic behavior such as those derived from “theory of mind” to predict key components of decision making in high-functioning young adults on the autism spectrum. A battery of tests was administered to 15 high-functioning college students with autism spectrum disorder (ASD), focusing on decision making competence (DMC) and other aspects of decision making related to known deficits associated with autism. Data from this group were compared to data from unselected college students receiving the same measures. First, as a test of a key social deficit associated with autism, the target group scored much lower on the Empathy Quotient scale. Traditional elements of decision making competency such as Numeracy and application of decision rules were comparable across groups. However, there were differences in thinking style, with the ASD group showing lesser ability and engagement in intuitive thinking, and they showed lower levels of risk taking. For comparisons within the ASD group, autobiographical reports concerning individual lifestyles and outcomes were used to derive a scale of Social Functioning. The lowest scoring individuals showed the lowest levels of intuitive thinking, the lowest perceived levels of others’ endorsement of socially undesirable behaviors, and the lowest ability to discriminate between “good” and “bad” risks. Results are discussed in terms of interventions that might aid high-functioning young adults with ASD in their everyday decision making.
Expression Profile of Diabetes-Related Genes Associated with Leukocyte Sirtuin 1 Overexpression in Gestational Diabetes

Although compelling evidence indicates that Sirtuin 1 (SIRT1) plays a prominent role in type 2 diabetes, its relationship with gestational diabetes (GDM) remains elusive. This study was aimed at identifying diabetes-related genes and cellular pathways linked to changes of leukocyte SIRT1 expression at the time of GDM diagnosis. For this purpose, 122 GDM patients were screened for leukocyte SIRT1 expression, and two subgroups were distinguished, namely GDM/SIRT1(↑) (n = 30, p < 0.05) and GDM/SIRT1(↔) (n = 92, p > 0.05), with significant and insignificant changes in leukocyte SIRT1 expression compared to a normal glucose tolerant (NGT) group (n = 41), respectively. PCR array analysis identified 11 diabetes-related genes with at least a ± 2-fold difference in expression in GDM/SIRT1(↑) patients (n = 9) vs. NGT controls (n = 7); in addition, significant differences in the expression of four of the six investigated genes were confirmed between the entire GDM/SIRT1(↑) group and the whole NGT group (p < 0.05). Interestingly, of these four genes, only ACLY expression was found to significantly differ between GDM/SIRT1(↑) and GDM/SIRT1(↔). This study demonstrates that under hyperglycemic conditions, leukocyte SIRT1 overexpression is accompanied by an over-abundance of three transcripts and an under-abundance of another; these four govern related metabolism, inflammation, and transport functions, suggesting that such alterations might represent systemic biological adaptations with a unique ACLY under-expression in GDM/SIRT1(↑) women.
In Vitro Cytotoxicity of Folate-Silica-Gold Nanorods on Mouse Acute Lymphoblastic Leukemia and Spermatogonial Cells

Objective The purpose of this study was to evaluate in vitro cytotoxicity of gold nanorods (GNRs) on the viability of spermatogonial cells (SSCs) and mouse acute lymphoblastic leukemia cells (EL4s). Materials and Methods In this experimental study, SSCs were isolated from the neonate mice, following enzymatic digestion and differential plating. GNRs were synthesized, then modified by silica and finally conjugated with folic acid to form F-Si-GNRs. Different doses of F-Si-GNRs (25, 50, 75, 100, 125 and 140 µM) were used on SSCs and EL4s. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay was performed to examine the GNRs toxicity. Flow cytometry was used to confirm the identity of the EL4s and SSCs. Also, the identity and functionality of SSCs were determined by the expression of specific spermatogonial genes and transplantation into recipient testes. Apoptosis was determined by flow cytometry using an annexin V/propidium iodide (PI) kit. Results Flow cytometry showed that SSCs and EL4s were positive for Plzf and H-2kb, respectively. The viability percentage of SSCs and EL4s that were treated with 25, 50, 75, 100, 125 and 140 µM of F-Si-GNRs was 65.33 ± 3.51%, 60 ± 3.6%, 51.33 ± 3.51%, 49 ± 3%, 30.66 ± 2.08% and 16.33 ± 2.51% for SSCs and 57.66 ± 0.57%, 54.66 ± 1.5%, 39.66 ± 1.52%, 12.33 ± 2.51%, 10 ± 1% and 5.66 ± 1.15% for EL4s respectively. The results of the MTT assay indicated that 100 µM is the optimal dose to reach the highest and lowest level of cell death in EL4s and in SSCs, respectively. Conclusion Cell death increased with increasing concentrations of F-Si-GNRs. Following utilization of F-Si-GNRs, there was a significant difference in the extent of apoptosis between cancer cells and SSCs.