Miracle-dz/UniFAR-FTUs huggingface dataset:
microRNAs Sculpt Neuronal Communication in a Tight Balance That Is Lost in Neurological Disease

Since the discovery of the first microRNA 25 years ago, microRNAs (miRNAs) have emerged as critical regulators of gene expression within the mammalian brain. miRNAs are small non-coding RNAs that direct the RNA induced silencing complex to complementary sites on mRNA targets, leading to translational repression and/or mRNA degradation. Within the brain, intra- and extracellular signaling events tune the levels and activities of miRNAs to suit the needs of individual neurons under changing cellular contexts. Conversely, miRNAs shape neuronal communication by regulating the synthesis of proteins that mediate synaptic transmission and other forms of neuronal signaling. Several miRNAs have been shown to be critical for brain function regulating, for example, enduring forms of synaptic plasticity and dendritic morphology. Deficits in miRNA biogenesis have been linked to neurological deficits in humans, and widespread changes in miRNA levels occur in epilepsy, traumatic brain injury, and in response to less dramatic brain insults in rodent models. Manipulation of certain miRNAs can also alter the representation and progression of some of these disorders in rodent models. Recently, microdeletions encompassing MIR137HG, the host gene which encodes the miRNA miR-137, have been linked to autism and intellectual disability, and genome wide association studies have linked this locus to schizophrenia. Recent studies have demonstrated that miR-137 regulates several forms of synaptic plasticity as well as signaling cascades thought to be aberrant in schizophrenia. Together, these studies suggest a mechanism by which miRNA dysregulation might contribute to psychiatric disease and highlight the power of miRNAs to influence the human brain by sculpting communication between neurons.
The Eye Opener: Finding and Targeting the Midbrain Lesion

ABSTRACT Lesions of the central nucleus of the third cranial nerve in midbrain leads to bilateral ptosis. We present a case of a 14 year old boy, who was found to have B/L non-correctable ptosis and medial rectus palsy. There was a ring enhancing lesion in the midbrain in contrast MRI which resolved with treatment. The case exemplifies that bilateral ptosis results from the central nucleus involvement of third nerve which has bilateral innervation.
Viruses Utilize Cellular Cues in Distinct Combination to Undergo Systematic Priming and Uncoating

Viral genomes are protected within a proteinaceous shell called “capsid” and, for enveloped viruses, an additional lipid coat. The capsids are generally constructed from a few capsid proteins into helical or icosahedral structures that are, in turn, stabilized by numerous covalent and noncovalent interactions [1]. However, during infection, viruses must uncoat in order to release their genomes into the host. This process is highly dependent on host elements called “cues” [2], which have been previously broadly categorized as (1) receptor- and/or enzyme-based cues, (2) chemical cues, or (3) mechanical cues [3]. In this brief article, we systematically analyze the available information on how 30 different enveloped and nonenveloped viruses exploit these host cues during infection and tabulate the observations in Table 1. By categorizing these cues, a general pattern can be deduced. Specifically, we find that these viruses use a distinct order and combination of the host cues during entry. To illustrate this principle, the mechanism by which four viruses hijack these cues will be highlighted (in Fig 1). We envision such analysis will provide an opportunity for investigators to evaluate whether viruses within the same family—for which the uncoating mechanism is unknown—employ a similar uncoating strategy.
Systolic and Diastolic Left Ventricular Mechanics during and after Resistance Exercise

STÖHR, E. J., M. STEMBRIDGE, R. SHAVE, T. J. SAMUEL, K. STONE, and J. I. ESFORMES. Systolic and Diastolic Left Ventricular Mechanics during and after Resistance Exercise.Med. Sci. Sports Exerc. , Vol. 49, No. 10, pp. 2025–2031, 2017. Purpose: To improve the current understanding of the impact of resistance exercise on the heart, by examining the acute responses of left ventricular (LV) strain, twist, and untwisting rate (‘‘LV mechanics’’). Methods: LV echocardiographic images were recorded in systole and diastole before, during and immediately after (7–12 s) double-leg press exercise at two intensities (30% and 60% of maximum strength, one-repetition maximum). Speckle tracking analysis generated LV strain, twist, and untwisting rate data. Additionally, beat-by-beat blood pressure was recorded and systemic vascular resistance (SVR) and LV wall stress were calculated. Results: Responses in both exercise trials were statistically similar (P 9 0.05). During effort, stroke volume decreased, whereas SVR and LV wall stress increased (P G 0.05). Immediately after effort, stroke volume returned to baseline, whereas SVR and wall stress decreased (P G 0.05). Similarly, acute exercise was accompanied by a significant decrease in systolic parameters of LV muscle mechanics (P G 0.05). However, diastolic parameters, including LV untwisting rate, were statistically unaltered (P 9 0.05). Immediately after exercise, systolic LV mechanics returned to baseline levels (P G 0.05) but LV untwisting rate increased significantly (P G 0.05). Conclusions: A single, acute bout of double-leg press resistance exercise transiently reduces systolic LV mechanics, but increases diastolic mechanics after exercise, suggesting that resistance exercise has a differential impact on systolic and diastolic heart muscle function. The findings may explain why acute resistance exercise has been associated with reduced stroke volume but chronic exercise training may result in increased LV volumes.
A Novel Top-k Strategy for Influence Maximization in Complex Networks with Community Structure

In complex networks, it is of great theoretical and practical significance to identify a set of critical spreaders which help to control the spreading process. Some classic methods are proposed to identify multiple spreaders. However, they sometimes have limitations for the networks with community structure because many chosen spreaders may be clustered in a community. In this paper, we suggest a novel method to identify multiple spreaders from communities in a balanced way. The network is first divided into a great many super nodes and then k spreaders are selected from these super nodes. Experimental results on real and synthetic networks with community structure show that our method outperforms the classic methods for degree centrality, k-core and ClusterRank in most cases.
A IMPORTANCIA DO PLANEJAMENTO TRIBUTARIO PARA AS EMPRESAS

Este trabalho aponta e demonstra a importância do planejamento tributario das empresas, de modo a estabelecer opinioes tecnicas de forma eficiente, no intuito de minimizar a incidencia de tributos e otimizar as atividades do mercado consumerista, uma vez que sua real existencia visa o lucro, desencadeando a geracao de empregos e consequentemente gerando um reflexo positivo na sociedade, com uma resposta satisfativa ao mercado em geral. Destarte, evita-se tambem que empresas de pequeno, medio e grande porte tenha suas atividades comprometidas e abaladas pelas demasiadas cobrancas realizadas pelo Fisco, e, portanto, o planejamento tributario tem-se mostrado como uma ferramenta adequada na economia de impostos, nao so por tratar de procedimento legal, mas tambem pelos resultados imediatos que apresenta. Alem disso, necessario e distinguir os conceitos de evasao e de elisao fiscal, para que dessa forma se conheca os caminhos licitos a serem seguidos e garantir o exito no planejamento tributario.
Application of advanced MRI techniques to monitor pharmacologic and rehabilitative treatment in multiple sclerosis: current status and future perspectives

ABSTRACT Introduction: Advances in magnetic resonance imaging (MRI) technology and analyses are improving our understanding of the pathophysiology of multiple sclerosis (MS). Due to their ability to grade the presence of irreversible tissue loss, microstructural tissue abnormalities, metabolic changes and functional plasticity, the application of these techniques is also expanding our knowledge on the efficacy and mechanisms of action of different pharmacological and rehabilitative treatments. Areas covered: This review discusses recent findings derived from the application of advanced MRI techniques to evaluate the structural and functional substrates underlying the effects of pharmacologic and rehabilitative treatments in patients with MS. Current applications as outcome in clinical trials and observational studies, their interpretation and possible pitfalls in their use are discussed. Finally, how these techniques could evolve in the future to improve monitoring of disease progression and treatment response is examined. Expert commentary: The number of treatments currently available for MS is increasing. The application of advanced MRI techniques is providing reliable and specific measures to better understand the targets of different treatments, including neuroprotection, tissue repair, and brain plasticity. This is a fundamental progress to move toward personalized medicine and individual treatment selection.
The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases

The aryl hydrocarbon receptor (AHR) is a nuclear receptor that modulates the response to environmental stimuli. It was recognized historically for its role in toxicology but, in recent decades, it has been increasingly recognized as an important modulator of disease—especially for its role in modulating immune and inflammatory responses. AHR has been implicated in many diseases that are driven by immune/inflammatory processes, including major depressive disorder, multiple sclerosis, rheumatoid arthritis, asthma, and allergic responses, among others. The mechanisms by which AHR has been suggested to impact immune/inflammatory diseases include targeted gene expression and altered immune differentiation. It has been suggested that single nucleotide polymorphisms (SNPs) that are near AHR-regulated genes may contribute to AHR-dependent disease mechanisms/pathways. Further, we have found that SNPs that are outside of nuclear receptor binding sites (i.e., outside of AHR response elements (AHREs)) may contribute to AHR-dependent gene regulation in a SNP- and ligand-dependent manner. This review will discuss the evidence and mechanisms of AHR contributions to immune/inflammatory diseases and will consider the possibility that SNPs that are outside of AHR binding sites might contribute to AHR ligand-dependent inter-individual variation in disease pathophysiology and response to pharmacotherapeutics.
Total flavones of abelmoschus manihot enhances angiogenic ability both in vitro and in vivo

Angiogenesis is a process of new blood vessel formation from pre-existing vessels. It is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. Total flavones of Abelmoschus manihot (TFA) are the major constituents of the traditional Chinese herb Abelmoschus manihot L. Medic. The aim of this study is to investigate the effect of TFA on angiogenic ability using human umbilical vein endothelial cells (HUVECs) in vitro and chick chorioallantoic membrane (CAM) in vivo. HUVECs were treated with TFA at different concentrations. Cell viability, cell cycle progression, cell apoptosis, cell migration and tubular formation were investigated. The expression of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, VEGFR-2) was examined by immunohistochemistry to identify mechanism of action of TFA. CAM model was used to evaluate the effect of TFA on angiogenesis in vivo. Our results showed that TFA promoted HUVECs proliferation in a dose- and time-dependent manner. It increased HUVECs migratory ability and the number of tubular structure, promoted vessel formation in HUVECs culture and CAM model. Furthermore, TFA treatment resulted in a decrease in cell apoptosis and enhanced the expression of VEGF and KDR. Taken together, TFA, as the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic, could enhance angiogenic ability of HUVECs in vitro and CAM in vivo. TFA may be used in the treatment of wound healing and ischemic/reperfusion injuries.
Biased emotional attention in patients with dental phobia

Biased motivated attention towards phobia‐relevant pictures is a typical finding in specific phobia. In the visual system, the allocation of motivated attention is indexed by two event‐related potential components – the Early Posterior Negativity and the Late Positive Potential. Enhanced Early Posterior Negativity and Late Positive Potential amplitudes are reliably observed in specific phobia such as, for instance, snake, spider, or blood‐injection‐injury phobia and to some extent also in dental phobia. However, regarding dental phobia results are sparse and its theoretical concept is not undisputed. To further elucidate the electrophysiological characteristics of dental phobia, we investigated visual emotional processing in dental phobia patients and controls. Subjects viewed neutral, phobia‐irrelevant and phobia‐relevant pictures while magnetoencephalographic and behavioural measures were recorded. All patients reported a history of traumatic experiences and depressive and anxiety symptoms, as well as dissociative and posttraumatic symptoms. In the magnetoencephalography, patients showed generally less evoked neural activation at parietal and temporal regions and a reduced differentiation between picture categories compared to controls. At the behavioural level, patients rated phobia‐relevant pictures as clearly more negative as did controls. In contrast to previous reports, our results suggest that dental phobia cannot be associated with the typical effects of biased motivated attention seen in other specific phobias. Instead, results indicate that dental phobia shares typical characteristics with mild forms of posttraumatic stress disorder.
Effect of early neonatal development and delayed feeding post‐hatch on jejunal and ileal calcium and phosphorus transporter genes expression in broiler chickens1

ABSTRACT Calcium (Ca) and phosphorus (P) are essential minerals involved in many biological processes including bone development and mineralization. Plasma concentration of both minerals is tightly regulated, and Ca and P homeostasis is maintained via intestinal absorption, bone storage and exchange, and renal reabsorption. In the current broiler production systems, chicks are deprived of food and water for up to 72 h due to uneven hatching, hatchery procedures, and transportation time to farms. Post‐hatch (PH) feed delay results in lower body and organ weight, higher feed conversion ratio and mortality, and delayed PH growth and GIT development. Little is known about the effects of early neonatal development and delayed or immediate feeding PH on Ca and P transporters. Therefore, the aim of the present study was to characterize expression patterns of Ca and P transporter genes in small intestine during the first 2 wk PH in chickens fed immediately after hatch (FED) or subjected to 48 h delayed feeding (NOTFED). Expression of all Ca and P transporters in jejunum and ileum was significantly (P < 0.05) affected by age. Among Ca transporter genes, only mRNA expression of Calbidin D28k in jejunum and Ca sensing receptor (CaSR) in ileum were significantly (P < 0.05) affected by delay in feed access. For P transporter genes' expression, only P transporter type III (PIT1) mRNA was significantly affected by age, delay in feed access, and their interaction (P < 0.05). In summary, we have shown, for the first time, early developmental changes of Ca and P transporter genes in broiler chickens. Results suggest that an increase in gene expression of some of the transporters corresponds with the switch from yolk to high starch diet. Overall, our results can be helpful in better understanding of Ca and P homeostasis in broilers.
Detection of Mild Cognitive Impairment Among Community-Dwelling African Americans Using the Montreal Cognitive Assessment.

Objective To establish a cut score for the Montreal Cognitive Assessment (MoCA) that distinguishes mild cognitive impairment (MCI) from normal cognition (NC) in a community-based African American (AA) sample. Methods A total of 135 AA participants, from a larger aging study, diagnosed MCI (n = 90) or NC (n = 45) via consensus diagnosis using clinical history, Clinical Dementia Rating score, and comprehensive neuropsychological testing. Logistic regression models utilized sex, education, age, and MoCA score to predict MCI versus NC. Receiver operating characteristic (ROC) curve analysis determined a cut score to distinguish MCI from NC based on optimal sensitivity, specificity, diagnostic accuracy, and greatest perpendicular distance above the identity line. ROC results were compared with previously published MoCA cut scores. Results The MCI group was slightly older (MMCI = 64.76[5.87], MNC = 62.33[6.76]; p = .033) and less educated (MMCI = 13.07[2.37], MNC = 14.36[2.51]; p = .004) and had lower MoCA scores (MMCI=21.26[3.85], MNC = 25.47[2.13]; p < .001) than the NC group. Demographics were non-significant in regression models. The area under the curve (AUC) was significant (MoCA = .83, p < .01) and an optimal cut score of <24 maximized sensitivity (72%), specificity (84%), and provided 76% diagnostic accuracy. In comparison, the traditional cut score of <26 had higher sensitivity (84%), similar accuracy (76%), but much lower specificity (58%). Conclusions This study provides a MoCA cut score to help differentiate persons with MCI from NC in a community-dwelling AA sample. A cut score of <24 reduces the likelihood of misclassifying normal AA individuals as impaired than the traditional cut score. This study underscores the importance of culturally appropriate norms to optimize the utility of commonly used cognitive screening measures.
Peptide-based PET imaging of the tumor restricted IL13RA2 biomarker

Peptides that target cancer cell surface receptors are promising platforms to deliver diagnostic and therapeutic payloads specifically to cancer but not normal tissue. IL13RA2 is a tumor-restricted receptor found to be present in several aggressive malignancies, including in the vast majority of high-grade gliomas and malignant melanoma. This receptor has been successfully targeted for diagnostic and therapeutic purposes using modified IL-13 ligand and more recently using a specific peptide, Pep-1L. In the current work, we establish the in vitro and in vivo tumor binding properties of radiolabeled Pep-1L, designed for tumor imaging. We radiolabeled Pep-1L with Copper-64 and demonstrated specific cell uptake in the IL13RA2-over expressing G48 glioblastoma cell line having abundant IL13RA2 expression. [64Cu]Pep-1L binding was blocked by unlabeled ligand, demonstrating specificity. To demonstrate in vivo tumor uptake, we intravenously injected into tumor-bearing mice and demonstrated that [64Cu]Pep-1L specifically bound tumors at 24 hours, which was significantly blocked (3-fold) by pre-injecting unlabeled peptide. To further demonstrate specificity of Pep-1L towards IL13RA2 in vivo, we exploited an IL13RA2-inducible melanoma tumor model that does not express receptor at baseline but expresses abundant receptor after treatment with doxycycline. We injected [64Cu]Pep-1L into mice bearing IL13RA2-inducible melanoma tumors and performed in vivo PET/CT and post-necropsy biodistribution studies and found that tumors that were induced to express IL13RA2 receptor by doxycycline pretreatment bound radiolabeled Pep-1L 3-4 fold greater than uninduced tumors, demonstrating receptor specificity. This work demonstrates that [64Cu]Pep-1L selectively binds hIL13RA2-expressing tumors and validates Pep-1L as an effective platform to deliver diagnostics and therapeutics to IL13RA2-expressing cancers.
Genotyping of Enterocytozoon bieneusi in Farmed Blue Foxes (Alopex lagopus) and Raccoon Dogs (Nyctereutes procyonoides) in China

Enterocytozoon bieneusi is the most common species of microsporidia found both in humans and animals. Farmed animals, particularly closely associated to humans, may play an important role of zoonotic reservoir in transmitting this disease to humans. The fur industry is a major economic component in some parts of China. To understand the prevalence, genotype variety and zoonotic risk of E. bieneusi in farmed foxes and raccoon dogs, two species of fur animals, fecal specimens of 110 blue foxes and 49 raccoon dogs from Heilongjiang and Jilin provinces in China were examined by internal transcribed spacer (ITS)-based PCR. E. bieneusi was detected in 16.4% (18/110) blue foxes and 4.1% (2/49) raccoon dogs. Altogether, four genotypes of E. bieneusi were identified, including two known genotypes D (n = 13) and EbpC (n = 5), and two novel genotypes named as CHN-F1 (n = 1) in a fox and CHN-R1 (n = 1) in a raccoon dog. Phylogenetic analysis revealed that all the four genotypes were the members of zoonotic group 1. Genotypes D and EbpC were found in humans previously. The findings of zoonotic genotypes of E. bieneusi in the foxes and raccoon dogs suggest these animals infected with E. bieneusi may pose a threat to human health.
Blocking β‐1,6‐glucan synthesis by deleting KRE6 and SKN1 attenuates the virulence of Candida albicans

β‐1,6‐glucan is an important component of the fungal cell wall. The β‐1,6‐glucan synthase gene KRE6 was thought to be essential in the fungal pathogen Candida albicans because it could not be deleted in previous efforts. Also, the role of its homolog SKN1 was unclear because its deletion caused no defects. Here, we report the construction and characterization of kre6Δ/Δ, skn1Δ/Δ and kre6Δ/Δ skn1Δ/Δ mutants in C. albicans. While deleting KRE6 or SKN1 had no obvious phenotypic consequence, deleting both caused slow growth, cell separation failure, cell wall abnormalities, diminished hyphal growth, poor biofilm formation and loss of virulence in mice. Furthermore, the GPI‐linked cell surface proteins Hwp1 and the invasin Als3 or Ssa1 were not detected in kre6Δ/Δ skn1Δ/Δ mutant. In GMM medium, RT‐qPCR and western blotting revealed a constitutive expression of KRE6 and growth conditions‐associated activation of SKN1. Like many hypha‐specific genes, SKN1 is repressed by Nrg1, but its activation does not involve the transcription factor Efg1. Dysregulation of SKN1 reduces C. albicans ability to damage epithelial and endothelial cells and attenuates its virulence. Given the vital role of β‐1,6‐glucan synthesis in C. albicans physiology and virulence, Kre6 and Skn1 are worthy targets for developing antifungal agents.