Miracle-dz/UniFAR-FTUs huggingface dataset:
Partial Adaptation to the Value Range in the Macaque Orbitofrontal Cortex

Values available for choice in different behavioral contexts can vary immensely. To compensate for this variability, neuronal circuits underlying economic decisions undergo adaptation. In orbitofrontal cortex (OFC), neurons encode the subjective value of offered and chosen goods in a quasilinear way. Previous experiments found that the gain of the encoding is lower when the value range is wider. However, the parameters OFC neurons adapted to remained unclear. Furthermore, previous studies did not examine additive changes in neuronal responses. Computational considerations indicate that these factors can directly impact choice behavior. Here we investigated how OFC neurons adapt to changes in the value range. We recorded from two male rhesus monkeys during a juice choice task. Each session was divided into two blocks of trials. In each block, juices were offered within a set range of values, and ranges changed between blocks. Across blocks, neuronal responses adapted to both the maximum and the minimum value, but only partially. As a result, the minimum neural activity was elevated in some value ranges relative to others. Through simulation of a linear decision model, we showed that increasing the minimum response increases choice variability, lowering the expected payoff. This effect is modulated by the balance between cells with positive and negative encoding. The presence of these two populations induces a non-monotonic relationship between the value range and choice efficacy, such that the expected payoff is highest for decisions in an intermediate value range. SIGNIFICANCE STATEMENT Economic decisions are thought to rely on the orbitofrontal cortex (OFC). The values available for choice vary enormously in different contexts. Previous work showed that neurons in OFC encode values in a linear way, and that the gain of encoding is inversely related to the range of available values. However, the specific parameters driving adaptation remained unclear. Here we show that OFC neurons adapt to both the maximum and minimum value in the current context. However, adaptation is partial, leading to contextual changes in the response offset. Interestingly, increasing the activity offset negatively affects choices in a simulated network. Partial adaptation may allow the circuit to maintain information about context value at the cost of slightly reduced payoff.
Experimental Hyperglycemia Alters Circulating Concentrations and Renal Clearance of Oxidative and Advanced Glycation End Products in Healthy Obese Humans

The purpose of this investigation was to evaluate the effects of experimental hyperglycemia on oxidative damage (OX), advanced glycation end products (AGEs), and the receptor for AGEs (RAGE) through an in vivo approach. Obese subjects (n = 10; 31.2 ± 1.2 kg·m−2; 56 ± 3 years) underwent 24 h of hyperglycemic clamp (+5.4 mM above basal), where plasma at basal and after 2 h and 24 h of hyperglycemic challenge were assayed for OX (methionine sulfoxide, MetSO, and aminoadipic acid, AAA) and AGE-free adducts (Ne-carboxymethyllysine, CML; Ne-carboxyethyllysine, CEL; glyoxal hydroimidazolone-1, GH-1; methylglyoxal hydroimidazolone-1, MG-H1; and 3-deoxyglucosone hydroimidazolone, 3DG-H) via liquid chromatography–tandem mass spectrometry (LC–MS/MS). Urine was also analyzed at basal and after 24 h for OX and AGE-free adducts and plasma soluble RAGE (sRAGE) isoforms (endogenous secretory RAGE, esRAGE, and cleaved RAGE, cRAGE), and inflammatory markers were determined via enzyme-linked immunosorbent assay (ELISA). Skeletal muscle tissue collected via biopsy was probed at basal, 2 h, and 24 h for RAGE and OST48 protein expression. Plasma MetSO, AAA, CEL, MG-H1, and G-H1 decreased (−18% to −47%; p < 0.05), while CML increased (72% at 24 h; p < 0.05) and 3DG-H remained unchanged (p > 0.05) with the hyperglycemic challenge. Renal clearance of MetSO, AAA, and G-H1 increased (599% to 1077%; p < 0.05), CML decreased (−30%; p < 0.05), and 3DG-H, CEL, and MG-H1 remained unchanged (p > 0.05). Fractional excretion of MetSO, AAA, CEL, G-H1, and MG-H1 increased (5.8% to 532%; p < 0.05) and CML and 3DG-H remained unchanged (p > 0.05). Muscle RAGE and OST48 expression, plasma sRAGE, IL-1β, IL-1Ra, and TNFα remained unchanged (p > 0.05), while IL-6 increased (159% vs. basal; p > 0.05). These findings suggest that individuals who are obese but otherwise healthy have the capacity to prevent accumulation of OX and AGEs during metabolic stress by increasing fractional excretion and renal clearance.
Landscape of Genomic Alterations in Pituitary Adenomas

Purpose: Pituitary adenomas are the second most common primary brain tumor, yet their genetic profiles are incompletely understood. Experimental Design: We performed whole-exome sequencing of 42 pituitary macroadenomas and matched normal DNA. These adenomas included hormonally active and inactive tumors, ones with typical or atypical histology, and ones that were primary or recurrent. Results: We identified mutations, insertions/deletions, and copy-number alterations. Nearly one-third of samples (29%) had chromosome arm-level copy-number alterations across large fractions of the genome. Despite such widespread genomic disruption, these tumors had few focal events, which is unusual among highly disrupted cancers. The other 71% of tumors formed a distinct molecular class, with somatic copy number alterations involving less than 6% of the genome. Among the highly disrupted group, 75% were functional adenomas or atypical null-cell adenomas, whereas 87% of the less-disrupted group were nonfunctional adenomas. We confirmed this association between functional subtype and disruption in a validation dataset of 87 pituitary adenomas. Analysis of previously published expression data from an additional 50 adenomas showed that arm-level alterations significantly impacted transcript levels, and that the disrupted samples were characterized by expression changes associated with poor outcome in other cancers. Arm-level losses of chromosomes 1, 2, 11, and 18 were significantly recurrent. No significantly recurrent mutations were identified, suggesting no genes are altered by exonic mutations across large fractions of pituitary macroadenomas. Conclusions: These data indicate that sporadic pituitary adenomas have distinct copy-number profiles that associate with hormonal and histologic subtypes and influence gene expression. Clin Cancer Res; 23(7); 1841–51. ©2016 AACR.
Naja atra venom peptide reduces pain by selectively blocking the voltage-gated sodium channel Nav1.8

The voltage-gated sodium channel Nav1.8 is preferentially expressed in peripheral nociceptive neurons and contributes to inflammatory and neuropathic pain. Therefore, Nav1.8 has emerged as one of the most promising analgesic targets for pain relief. Using large-scale screening of various animal-derived toxins and venoms for Nav1.8 inhibitors, here we identified μ-EPTX-Na1a, a 62-residue three-finger peptide from the venom of the Chinese cobra (Naja atra), as a potent inhibitor of Nav1.8, exhibiting high selectivity over other voltage-gated sodium channel subtypes. Using whole-cell voltage-clamp recordings, we observed that purified μ-EPTX-Na1a blocked the Nav1.8 current. This blockade was associated with a depolarizing shift of activation and repolarizing shift of inactivation, a mechanism distinct from that of any other gating modifier toxin identified to date. In rodent models of inflammatory and neuropathic pain, μ-EPTX-Na1a alleviated nociceptive behaviors more potently than did morphine, indicating that μ-EPTX-Na1a has a potent analgesic effect. μ-EPTX-Na1a displayed no evident cytotoxicity and cardiotoxicity and produced no obvious adverse responses in mice even at a dose 30-fold higher than that producing a significant analgesic effect. Our study establishes μ-EPTX-Na1a as a promising lead for the development of Nav1.8-targeting analgesics to manage pain.
Cardiomyocyte expression of PPARγ leads to cardiac dysfunction in mice

Three forms of PPARs are expressed in the heart. In animal models, PPARgamma agonist treatment improves lipotoxic cardiomyopathy; however, PPARgamma agonist treatment of humans is associated with peripheral edema and increased heart failure. To directly assess effects of increased PPARgamma on heart function, we created transgenic mice expressing PPARgamma1 in the heart via the cardiac alpha-myosin heavy chain (alpha-MHC) promoter. PPARgamma1-transgenic mice had increased cardiac expression of fatty acid oxidation genes and increased lipoprotein triglyceride (TG) uptake. Unlike in cardiac PPARalpha-transgenic mice, heart glucose transporter 4 (GLUT4) mRNA expression and glucose uptake were not decreased. PPARgamma1-transgenic mice developed a dilated cardiomyopathy associated with increased lipid and glycogen stores, distorted architecture of the mitochondrial inner matrix, and disrupted cristae. Thus, while PPARgamma agonists appear to have multiple beneficial effects, their direct actions on the myocardium have the potential to lead to deterioration in heart function.
Impact of procedural time on clinical and angiographic outcomes in patients with acute ischemic stroke receiving endovascular treatment

Background Procedural time in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy may affect clinical outcomes. We performed a pooled analysis of the effect of procedural time on clinical outcomes using data from three prospective endovascular treatment trials. Objective To examine the relationship between endovascular procedural time and clinical outcomes of patients with AIS following endovascular treatment. Methods We analyzed data from SWIFT, STAR, and SWIFT PRIME studies, including baseline characteristics: National Institutes of Health Stroke Scale (NIHSS) score on admission, intracranial hemorrhage rates, and modified Rankin Scale score at 3 months. The Thrombolysis in Cerebral Infarction (TICI) scale was used to grade postprocedure recanalization. We recorded two procedural time intervals: (1) symptom onset to groin puncture and (2) groin puncture to angiographic recanalization. A multivariate analysis was performed using a logistic regression model to analyze predictors of unfavorable outcome. Results We analyzed 301 patients who had undergone endovascular treatment and had near-complete or complete recanalization (TICI 2b or 3). At 3 months, 122 patients (40.5%) had unfavorable outcomes. The rate of favorable outcomes was significantly higher when the procedural time was <60 min compared with ≥60 min (62% vs 45%, p=0.020). Predictors of unfavorable outcome at 3 months were age (unit 10 years, OR=0.62, 95% CI 0.46 to 0.82, p<0.001), onset to groin puncture time (unit hour, OR=0.61, 95% CI 0.48 to 0.77, p<0.001), groin puncture to recanalization (unit 10 min, OR=0.89, 95% CI 0.80 to 0.99, p=0.032), baseline NIHSS score (20–28 vs 8–10, OR=0.17, 95% CI 0.05 to 0.62, p=0.018), and collaterals (OR=1.48, 95% CI 1.04 to 2.10, p=0.029). Conclusion Procedural time in patients with stroke undergoing mechanical thrombectomy may be an important determinant of favorable outcomes in those with recanalization.
Propulsive design principles in a multi-jet siphonophore

ABSTRACT Coordination of multiple propulsors can provide performance benefits in swimming organisms. Siphonophores are marine colonial organisms that orchestrate the motion of multiple swimming zooids for effective swimming. However, the kinematics at the level of individual swimming zooids (nectophores) have not been examined in detail. We used high-speed, high-resolution microvideography and particle image velocimetry of the physonect siphonophore Nanomia bijuga to study the motion of the nectophores and the associated fluid motion during jetting and refilling. The integration of nectophore and velum kinematics allow for a high-speed (maximum ∼1 m s−1), narrow (1–2 mm) jet and rapid refill, as well as a 1:1 ratio of jetting to refill time. Scaled to the 3 mm nectophore length, jet speeds reach >300 lengths s−1. Overall swimming performance is enhanced by velocity gradients produced in the nectophore during refill, which lead to a high-pressure region that produces forward thrust. Generating thrust during both the jet and refill phases augments the distance traveled by 17% over theoretical animals, which generate thrust only during the jet phase. The details of velum kinematics and associated fluid mechanics elucidate how siphonophores effectively navigate three-dimensional space, and could be applied to exit flow parameters in multijet underwater vehicles. Summary: Colonial siphonophores produce high-speed jets and generate forward thrust during refill using a flexible velum to achieve effective propulsion.
Advances in ultrasound diagnosis in chronic liver diseases

Chronic liver disease is a major disorder worldwide. A better understanding of anatomy, blood flow, and pathophysiology may be a key issue for their proper management. Ultrasound (US) is a simple and non-invasive diagnostic tool in the abdominal field. Doppler mode offers real-time hemodynamic evaluation, and the contrast-enhanced US is one of the most frequently used modalities for the detailed assessment. Further development in digital technology enables threedimensional (3D) visualization of target images with high resolution. This article reviews the wide ranges of application in the abdominal US and describes the recent progress in the diagnosis of chronic liver diseases.
(−)-Epigallocatechin-3-Gallate Protects Against Lithium-Pilocarpine-Induced Epilepsy by Inhibiting the Toll-Like Receptor 4 (TLR4)/Nuclear Factor-κB (NF-κB) Signaling Pathway

Background Temporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in humans, and it is often accompanied by cognitive impairment. In this study, we examined the effects of (−)-Epigallocatechin-3-gallate (EGCG) after SE on behavior in the rat lithium-pilocarpine model of TLE. Material/Methods The rats were randomly divided into 3 groups: (1) the control group, in which 12 rats received no treatment; (2) the epilepsy (EP) group, in which 15 rats were treated with saline after status epilepticus (SE); and (3) the EP+EGCG group, in which 15 rats were treated with EGCG (25 mg/kg/d, intraperitoneal) after SE. The SE model was induced with lithium chloride-pilocarpine, and electroencephalography and a high-definition camera were used to monitor SRS. The Morris water maze test and hippocampal late-phase long-term potentiation (L-LTP) recordings were used to evaluate cognitive impairment, and TLR4, NF-κB, and IL-1β levels were determined using Western blot analysis. Results We concluded that EGCG treatment after SE (1) markedly reduced SRS frequency in pilocarpine-treated rats, (2) improved epilepsy-induced cognitive impairment and reversed epilepsy-induced synaptic dysfunction in L-LTP in vivo, (3) protected hippocampal neurons from damage after SRS, and (4) significantly attenuated the increase in TRL-4 and IL-1β hippocampal levels. The above findings clearly show that EGCG exerts antiepileptogenesis and neuroprotective effects on pilocarpine-induced epilepsy. Conclusions We found that EGCG can suppress seizures and inhibit hippocampal neuronal apoptosis, as well as improving cognitive function of epileptic rats. Our findings suggest that EGCG may a novel adjuvant therapeutic approach in epilepsy by improving epileptic behavior and cognitive dysfunction.
Transcriptome Profiling Reveals Effects of Drought Stress on Gene Expression in Diploid Potato Genotype P3-198

Potato (Solanum tuberosum L.) is one of the three most important food crops worldwide; however, it is strongly affected by drought stress. The precise molecular mechanisms of drought stress response in potato are not very well understood. The diploid potato genotype P3-198 has been verified to be highly resistant to drought stress. Here, a time-course experiment was performed to identify drought resistance response genes in P3-198 under polyethylene glycol (PEG)-induced stress using RNA-sequencing. A total of 1665 differentially expressed genes (DEGs) were specifically identified, and based on gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the transcription factor activity, protein kinase activity, and the plant hormone signal transduction process were significantly enriched. Annotation revealed that these DEGs mainly encode transcription factors, protein kinases, and proteins related to redox regulation, carbohydrate metabolism, and osmotic adjustment. In particular, genes encoding abscisic acid (ABA)-dependent signaling molecules were significantly differentially expressed, which revealed the important roles of the ABA-dependent signaling pathway in the early response of P3-198 to drought stress. Quantitative real-time PCR experimental verification confirmed the differential expression of genes in the drought resistance signaling pathway. Our results provide valuable information for understanding potato drought-resistance mechanisms, and also enrich the gene resources available for drought-resistant potato breeding.
Design, Motivation and Evaluation of a Full-Resolution Optical Tactile Sensor

Human skin is capable of sensing various types of forces with high resolution and accuracy. The development of an artificial sense of touch needs to address these properties, while retaining scalability to large surfaces with arbitrary shapes. The vision-based tactile sensor proposed in this article exploits the extremely high resolution of modern image sensors to reconstruct the normal force distribution applied to a soft material, whose deformation is observed on the camera images. By embedding a random pattern within the material, the full resolution of the camera can be exploited. The design and the motivation of the proposed approach are discussed with respect to a simplified elasticity model. An artificial deep neural network is trained on experimental data to perform the tactile sensing task with high accuracy for a specific indenter, and with a spatial resolution and a sensing range comparable to the human fingertip.
First Report of Tomato Yellow Leaf Curl Geminivirus in Morocco.

In July 1998, shortened internodes, reduced leaf size, leaf curling, and bushy plants were observed in tomato crops in the coastal region near Casablanca, Morocco. The symptoms were similar to those described for tomato yellow leaf curl virus (TYLCV) disease. During September, the disease was present in more than 130 ha of outdoor and protected crops. Economic losses ranged between 20 and 100%. Similar symptoms were observed in tomato crops in the northeastern region of Morocco. During the same period, high populations of Bemisia tabaci (Gennadius) were observed on tomato, sweet pepper, and several weeds, including Sonchus oleraceus L. , Chenopodium sp. , Malva parviflora L. , and Datura stramonium L. Attempts to control whiteflies with insecticides generally were unsuccessful. Using a pair of degenerate primers (3) that are expected to amplify a region of the A component of begomoviruses between the intergenic conserved nonanucleotide sequence and the first 5' quarter of the capsid protein gene, an expected size product of 500 bp was obtained from six tomato leaf samples collected near Casablanca: four were obtained from symptomatic plants and two from apparently symptomless plants. A product of the same size was obtained from a sample of tomato infected with a TYLCV isolate from Reunion Island, France (2), but not from a sample from symptomless tomato plants from Reunion. The polymerase chain reaction (PCR) product obtained from one symptomatic sample from Morocco was cloned and sequenced (2). The resulting sequence (EMBL no. AJ133491) was at least 95.2% identical to sequences of TYLCV isolates from the Dominican Republic (EMBL no. AF024715), Cuba (EMBL no. AJ223505), Israel (EMBL no. X15656; EMBL no. X76319 for the mild clone), Spain (EMBL no. AF071228), and Reunion (EMBL no. AJ010790). Based on sequence comparisons, the tomato leaf sample was infected by a geminivirus isolate belonging to the Israeli species of TYLCV and was most closely related to the Dominican Republic isolate (98.4% nucleotide identity). In symptomless plants from which a 500-bp PCR product was obtained, infection may have been in an early stage. This is consistent with the fact that in the 2-ha field from which tomato samples were collected, only 4% of the plants exhibited TYLCV symptoms at the time of collection, whereas at least 70% of plants showed symptoms later, requiring the farmer to abandon the crop. The presence of the Eastern Mediterranean TYLCV species in a Western Mediterranean country is not a new observation; this virus has been described in Spain and Portugal (1). In Morocco, TYLCV symptoms were observed during the 1996 to 1997 growing season, following importation of grafted tomato plants from the Netherlands, by a farmer from the Casablanca region. References: (1) J. Navas-Castillo et al. Plant Dis. 83:29, 1999. (2) M. Peterschmitt et al. Plant Dis. 83:303, 1999. (3) P. Umaharan et al. Phytopathology 88:1262, 1998.
Sphingosine‐1‐phosphate activates mouse vagal airway afferent C‐fibres via S1PR3 receptors

Sphingosine‐1‐phosphate (S1P) strongly activates mouse vagal C‐fibres in the airways. Airway‐specific nodose and jugular C‐fibre neurons express mRNA coding for the S1P receptor S1PR3. S1P activation of nodose C‐fibres is inhibited by a S1PR3 antagonist. S1P activation of nodose C‐fibres does not occur in S1PR3 knockout mice.
Complex Brain Network Analysis and Its Applications to Brain Disorders: A Survey

It is well known that most brain disorders are complex diseases, such as Alzheimer’s disease (AD) and schizophrenia (SCZ). In general, brain regions and their interactions can be modeled as complex brain network, which describe highly efficient information transmission in a brain. Therefore, complex brain network analysis plays an important role in the study of complex brain diseases. With the development of noninvasive neuroimaging and electrophysiological techniques, experimental data can be produced for constructing complex brain networks. In recent years, researchers have found that brain networks constructed by using neuroimaging data and electrophysiological data have many important topological properties, such as small-world property, modularity, and rich club. More importantly, many brain disorders have been found to be associated with the abnormal topological structures of brain networks. These findings provide not only a new perspective to explore the pathological mechanisms of brain disorders, but also guidance for early diagnosis and treatment of brain disorders. The purpose of this survey is to provide a comprehensive overview for complex brain network analysis and its applications to brain disorders.
Divergent patterns of TDP‐43 and tau pathologies in primary progressive aphasia

To measure postmortem burden of frontotemporal lobar degeneration (FTLD) with TDP‐43 (FTLD‐TDP) or tau (FTLD‐Tau) proteinopathy across hemispheres in primary progressive aphasia (PPA) using digital histopathology and to identify clinicopathological correlates of these distinct proteinopathies.