Miracle-dz/UniFAR-FTUs huggingface dataset:
Cross-correlation analysis of cuneothalamic interactions in the rat somatosensory system: influence of receptive field topography and comparisons with thalamocortical interactions.

1. We simultaneously recorded neuronal responses to cutaneous stimulation from matched somatotopic representations in the nucleus cuneatus and ventrobasal complex of intact, halothane-anesthetized rats. A total of 95 cuneate and 86 thalamic neurons representing hairy skin on the forelimb were activated by hair movements produced by air jets at multiple skin sites. Mean responsiveness was higher among neurons in nucleus cuneatus (34.4 spikes per stimulus) than in thalamus (23.7 spikes per stimulus), a result that was consistent with the greater proportion of "sustained" responses recorded in nucleus cuneatus (80%) than in the thalamus (62%). 2. Cross-correlation analysis of 166 pairs of cuneate and thalamic neurons showed that 56 neuron pairs displayed time-locked correlations in activity that were characterized primarily by excitatory interactions (44 pairs) or a combination of excitatory and inhibitory interactions (10 pairs). Unilateral interactions in the cuneothalamic direction (31 pairs) and reverse direction (11 pairs) were observed, as well as multiphasic interactions in both directions (14 pairs). Most excitatory interactions involved intervals of 1-7 ms between successive cuneate and thalamic discharges, whereas most inhibitory influences involved intervals > 7 ms. Connection strength, defined by the ratio of time-linked interactions to the number of cuneate discharges, varied widely among neuron pairs but was largest for interactions involving interspike intervals of < or = 15 ms. 3. The relationship between connection strength and receptive field topography was analyzed in 103 cuneate-thalamic neuron pairs. The region of skin shared by both neurons varied substantially among neuron pairs and the probability of detecting interactions increased proportionately with larger amounts of receptive field overlap. Neuron pairs with moderate (25-50%) amounts of receptive field overlap had connection strengths 3-4 times greater than neuron pairs with minimal (0-25%) overlap. Connection strength was essentially identical, however, for neuron pairs with moderate or large (> 50%) amounts of overlap. 4. Cuneate-thalamic neuron pairs displaying functional connections were usually tested at multiple peripheral sites, but only 37% (18 of 49) of these neuron pairs displayed interactions at more than one stimulation site. Stimulation at different sites altered the timing of interactions in seven neuron pairs, including three that showed timing shifts across time zero in the cross-correlation histogram. In neuron pairs displaying interactions at multiple sites, connection strengths for 67% of the cases were strongest when stimulation was delivered within the region of receptive field overlap. (ABSTRACT TRUNCATED AT 400 WORDS)
Establishing Edoxaban’s Role in Anticoagulation

Purpose This article serves as a review of the current literature regarding the role of edoxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and the treatment of venous thromboembolism (VTE). Summary Until recent years, oral treatment options for both treatment and prevention of VTE and stroke were limited to warfarin. Dabigatran was the first new oral anticoagulant approved in over 50 years followed by rivaroxaban and apixaban. These new oral anticoagulants offer many benefits over warfarin. Edoxaban is the newest member among the oral anticoagulants and exerts its action by direct inhibition of factor Xa. It may offer some advantages in that it is the second Food and Drug Administration-approved once-daily anticoagulant available and does not interact with the cytochrome P450 (CYP450) system. However, there are concerns in patients with AF and preserved renal function (>95 mL/min), as these cohorts experienced a higher incidence of stroke in trials. Conclusion Based on the 3 clinical trials, edoxaban appears to be a safe and effective factor Xa inhibitor in patients with a creatinine clearance of <95 mL/min. It will serve as an alternative anticoagulant for those with a preference for once-daily dosing and/or taking medications that interact with the CYP450 system.
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Cognitive dysfunction is a common finding in schizophrenia. Nevertheless the specific pattern of neuropsychological impairment in schizophrenia compared to other severe mental illnesses has not been intensively studied. Twenty-four patients with schizophrenia belonging to different stages of the disease (11 first-episode patients, 13 patients with multiple episodes), 18 patients with bipolar disorder and 23 healthy control subjects underwent standardized neuropsychological assessment. Statistical analysis of covariance (ANCOVA) demonstrated that, compared to control subjects, patients with schizophrenia performed significantly worse in the trail-making test (P 0.012), verbal fluency (category letter, P 0.004), verbal learning/memory (P 0.005), and the Wisconsin Card Sorting Test (WCST) (P 0.004 for administered trials; P 0.025 for perseverative responses, T value) indicating significant deficits in attention and psychomotor performance, and in particular in verbal working memory and cognitive flexibility for schizophrenic patients. A significant difference between schizophrenic and bipolar patients was found only in the WCST. Schizophrenic patients made significantly more perseverative responses (P 0.002, ANCOVA), indicating a more pronounced and specific deficit in cognitive flexibility and frontally based executive function. In conclusion, these results may suggest a cognitive endophenotype in schizophrenia and underline the role of the prefrontal cortex in schizophrenic pathophysiology.
A Comparison of Surface and Intramuscular Myoelectric Signal Classification

The surface myoelectric signal (MES) has been used as an input to controllers for powered prostheses for many years. As a result of recent technological advances it is reasonable to assume that there will soon be implantable myoelectric sensors which will enable the internal MES to be used as input to these controllers. An internal MES measurement should have less muscular crosstalk allowing for more independent control sites. However, it remains unclear if this benefit outweighs the loss of the more global information contained in the surface MES. This paper compares the classification accuracy of six pattern recognition-based myoelectric controllers which use multi-channel surface MES as inputs to the same controllers which use multi-channel intramuscular MES as inputs. An experiment was designed during which surface and intramuscular MES were collected simultaneously for 10 different classes of isometric contraction. There was no significant difference in classification accuracy as a result of using the intramuscular MES measurement technique when compared to the surface MES measurement technique. Impressive classification accuracy (97%) could be achieved by optimally selecting only three channels of surface MES
Integrated Epstein‐Barr virus (EBV) and chromosomal abnormality in chronic active EBV infection

In order to examine the role of Epstein‐Barr virus (EBV) in the pathogenesis of chronic active EBV infection (CAEBV), we investigated whether or not EBV integration into the human genome is associated with any chromosonal abnormality. We therefore analyzed 4 cases of CAEBV: 2 cases showed a normal karyotype, while one had an oligo‐clonal 6th chromosomal abnormality and the fourth had a clonal 6th deletion (q15q23). In addition, the case with an oligo‐clonal abnormality also had oligo‐clonal EBV terminal repeat (TR) bands, while the case with a clonal abnormality showed a clonal TR band. In contrast, the 2 cases with a normal karyotype showed no clonal band. Two‐color fluorescence in situ hybridization (FISH) was used to detect the integrated EBV and the 6th chromosomal site. The presence of integrated EBV into the 6th chromosome was not frequent in the 2 cases with a normal karyotype, but it was statistically frequent in the case with an oligo‐clonal 6th abnormality. In the case with a clonal 6th deletion, integration in the 6th chromosome was also slightly higher than that in the other chromosomes. In CAEBV, integrated EBV might thus be associated both with chromosomal abnormality and with pathogenesis. Int. J. Cancer 71: 943‐947, 1997. © 1997 Wiley‐Liss Inc.
A model of gastric electrical activity in health and disease

The idea of diagnosing gastric dysfunction from noninvasive measurements of gastric electrical activity (GEA) is intuitively appealing, but the predictive accuracy of the cutaneous signal, especially that of its amplitude, is still in question. Mathematical modeling provides a means of investigating, analyzing, and predicting GEA measured percutaneously. In this study, a model of GEA applicable both in health and disease was developed and simulated for a cylindrical body surface. Body-surface maps of the simulated electrogastrogram (EGG) were generated at a 20 by 20 array of sites on the model's surface, and the accuracy of the percutaneous method in detecting simulated gastric electrical abnormalities was determined. The relationship between the amplitude of the simulated surface EGG and the velocity of propagation of the myogenic activity was also investigated. This was compared to a similar investigation of the fluctuations in the amplitude of the surface EGG with the velocity of propagation of the serosal activity measured in humans. The diagnostic accuracy of the measured cutaneous EGG in humans was also determined. The results obtained from the mathematical model show that the amplitude of the electrogastrogram increases with the propagation velocity of GEA. Similar results were obtained from the experimental measurements. The amplitude of the simulated and measured cutaneous signal correlated well (p<0.05) with the phase shift of the simulated and measured activities, (-0.85, -0.54), respectively, Serosal normal activity, tachygastria, and uncoupling mere detected 67%, 90%, and 0% of the time, respectively, at the cutaneous electrode in humans, In simulations, normal activity and tachygastria were accurately detected at all 100 sites on the surface, Uncoupling simulated with 50% of the myogenic sources "diseased" was detected at only 20 of the 400 sites. The results confirm that the amplitude of the cutaneous signal is a function of the velocity of propagation of the myogenic signal. It also confirms that while GEA in health may be accurately predicted from percutaneous recordings, frequency and phase/coupling abnormalities are poorly detected from single-channel electrogastrograms. This suggests the use of multiple-channel surface recordings in clinical electrogastrography. <<ETX>>
Chicken food calls are functionally referential

Male chickens, Gallus gallus domesticus, usually produce characteristic 'food' calls upon discovering edible objects, and are more likely to do so in the presence of a hen. Food calling is thus dependent upon food and modulated by social context, which is consistent with the idea that hens respond because they anticipate a feeding opportunity. An alternative model suggests that female behaviour is not mediated by the predicted presence of food but rather by social information, such as a low probability of male aggression. We conducted two playback experiments to explore the type of information encoded in food-associated vocal signals. Isolated hens were played recorded food calls and we compared their responses with those evoked by ground alarm calls (which have similar acoustic characteristics) and by contact calls (which are produced under similar social circumstances). Hens responded to food call playbacks by fixating downwards with the frontal binocular field. This anticipatory feeding movement was specific to food calls and did not occur in either of the control conditions. Food calls also affected looking downwards selectively. There were no differences between the call types in their effects on social behaviour, such as approach and contact calling, nor were there differences in the nonspecific effects of sound playback, such as orienting towards the loudspeaker or increased locomotor activity. Chicken food calls appear to provide conspecifics with information about the presence of food. This property has not hitherto been demonstrated in any natural system of animal acoustic signals. Copyright 1999 The Association for the Study of Animal Behaviour.
Epstein–Barr Virus-Positive B-Cell Lymphoproliferative Disorders Arising in Immunodeficient Patients Previously Treated With Fludarabine for Low-Grade B-Cell Neoplasms

We describe five patients with treated low-grade B-cell neoplasms who subsequently developed Epstein–Barr virus (EBV)-positive B-cell lymphoproliferative disorders (BLPDs). The low-grade B-cell neoplasms were B-cell chronic lymphocytic leukemia in four patients and splenic marginal zone lymphoma in one patient. All patients had received treatment with fludarabine for the low-grade B-cell neoplasm, and three had also received Campath-1H. The EBV-BLPDs arose 2–12 months after completion of fludarabine therapy and morphologically resembled the EBV-BLPDs that occur in the setting of iatrogenic immunodeficiency. Molecular genetic studies showed that these lesions were clonally distinct from the low-grade B-cell neoplasm in three of four cases assessed. Two patients did not receive therapy for the EBV-BLPD. The lesions regressed spontaneously in both patients but recurred in one. One patient underwent surgical excision and remains without evidence of the EBV-BLPD. One patient received aggressive multiagent chemotherapy with a complete response initially, but the EBV-BLPD recurred after 12 months. One patient received antiviral therapy and responded completely but died 2 months later of an opportunistic infection. We conclude that patients with low-grade B-cell neoplasms treated with fludarabine, possibly in combination with other immune suppressive agents, may subsequently develop EBV-BLPDs that morphologically resemble other iatrogenic immunodeficiency-associated BLPDs. Most are clonally distinct from the underlying low-grade B-cell neoplasm. A subset of these lesions may regress without systemic therapy.
Fermented Alfalfa Meal Instead of “Grain-Type” Feedstuffs in the Diet Improves Intestinal Health Related Indexes in Weaned Pigs

Corn and soybean meal are the two main components in formula feed of farm animals, leading to a serious food competition between humans and livestock. An alternative may be to encourage the utilization of unconventional feedstuff in animal diet. In the current study, we evaluated the utilization of fermented alfalfa meal (FAM) in weaned pigs. Twenty weaned piglets (separately caged) were randomly divided into two groups. Pigs in the control group (CON) were fed corn-soybean meal diet, and part of corn and soya protein concentrate in the diet of another group was replaced by 8% FAM. After 40 days of feeding, the average feed intake of FAM pigs was increased (P > 0.05), and the villus height (VH) of jejunum and duodenum, crypt depth (CD), and VH/CD in FAM pigs was improved compared to the CON group (P < 0.05). The increase (P < 0.05) of goblet cells in the jejunum of FAM pigs was positively correlated with the expression of MUC-2 gene (R = 0.9150). The expression of genes related to immunity (IRAK4, NF-κB, and IL-10) and intestinal barrier (Occludin and MUC-2) in the jejunum, as well as the expression of ZO-1 and MUC-2 in the colon of these pigs, also showed increase (P < 0.05) compared to CON pigs, which was accompanied by the decrease (P < 0.05) of LPS concentration in the serum. The elevated proportion of CD3+ and CD8+ T-lymphocyte subsets in spleen (P < 0.05) confirmed the improvement of systemic immune function in FAM pigs. In addition, FAM pigs have a higher β-diversity of microbial community (P < 0.05) and promoted enrichment of probiotics such as Lactobacillus that positively was correlated with acetate concentration in the colon over CON pigs. In summary, partially replacement of expanded corn and soya protein concentrate with FAM (8%) may benefit the intestinal barrier and immune function of weaned pigs without affecting their growth. Our findings also provide evidence of the feasibility of FAM as a dietary component in pigs to reduce the consumption of grain.
Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase induces orofacial defects in zebrafish.

BACKGROUND Orofacial clefts (OFCs) are common birth defects, which include a range of disorders with a complex etiology affecting formation of craniofacial structures. Some forms of syndromic OFCs are produced by defects in the cholesterol pathway. The principal enzyme of the cholesterol pathway is the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Our aim is to study whether defects of HMGCR function would produce orofacial malformation similar to those found in disorders of cholesterol synthesis. METHODS We used zebrafish hmgcrb mutants and HMGCR inhibition assay using atorvastatin during early and late stages of orofacial morphogenesis in zebrafish. To describe craniofacial phenotypes, we stained cartilage and bone and performed in situ hybridization using known craniofacial markers. Also, we visualized neural crest cell migration in a transgenic fish. RESULTS Our results showed that mutants displayed loss of cartilage and diminished orofacial outgrowth, and in some cases palatal cleft. Late treatments with statin show a similar phenotype. Affected-siblings displayed a moderate phenotype, whereas early-treated embryos had a minor cleft. We found reduced expression of the downstream component of Sonic Hedgehog-signaling gli1 in ventral brain, oral ectoderm, and pharyngeal endoderm in mutants and in late atorvastatin-treated embryos. CONCLUSION Our results suggest that HMGCR loss-of-function primarily affects postmigratory cranial neural crest cells through abnormal Sonic Hedgehog signaling, probably induced by reduction in metabolites of the cholesterol pathway. Malformation severity correlates with the grade of HMGCR inhibition, developmental stage of its disruption, and probably with availability of maternal lipids. Together, our results might help to understand the spectrum of orofacial phenotypes found in cholesterol synthesis disorders. Birth Defects Research (Part A) 106:814-830, 2016. © 2016 Wiley Periodicals, Inc.
Silencing of Soybean Seed Storage Proteins Results in a Rebalanced Protein Composition Preserving Seed Protein Content without Major Collateral Changes in the Metabolome and Transcriptome[W][OA]

The ontogeny of seed structure and the accumulation of seed storage substances is the result of a determinant genetic program. Using RNA interference, the synthesis of soybean (Glycine max) glycinin and conglycinin storage proteins has been suppressed. The storage protein knockdown (SP−) seeds are overtly identical to the wild type, maturing to similar size and weight, and in developmental ontogeny. The SP− seeds rebalance the proteome, maintaining wild-type levels of protein and storage triglycerides. The SP− soybeans were evaluated with systems biology techniques of proteomics, metabolomics, and transcriptomics using both microarray and next-generation sequencing transcript sequencing (RNA-Seq). Proteomic analysis shows that rebalancing of protein content largely results from the selective increase in the accumulation of only a few proteins. The rebalancing of protein composition occurs with small alterations to the seed’s transcriptome and metabolome. The selectivity of the rebalancing was further tested by introgressing into the SP− line a green fluorescent protein (GFP) glycinin allele mimic and quantifying the resulting accumulation of GFP. The GFP accumulation was similar to the parental GFP-expressing line, showing that the GFP glycinin gene mimic does not participate in proteome rebalancing. The results show that soybeans make large adjustments to the proteome during seed filling and compensate for the shortage of major proteins with the increased selective accumulation of other proteins that maintains a normal protein content.
Phase I, pharmacokinetic and pharmacodynamic study of the anti-insulinlike growth factor type 1 Receptor monoclonal antibody CP-751,871 in patients with multiple myeloma.

PURPOSE A phase I first-in-human study was conducted to characterize the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the anti-insulinlike growth factor 1 receptor (IGF-IR) monoclonal antibody CP-751,871. PATIENTS AND METHODS After informed consent and screening, 47 patients with multiple myeloma in relapse or refractory phase were enrolled into 11 dose-escalation cohorts of CP-751,871 at doses from 0.025 to 20 mg/kg for 4 weeks. Patients with less than a partial response to CP-751,871 treatment were eligible to receive CP-751,871 in combination with oral dexamethasone at the discretion of the investigator. Treatment with CP-751,871 and rapamycin with or without dexamethasone was also offered to patients enrolled in the 10 and 20 mg/kg cohorts with less than a partial response to initial therapy with single-agent CP-751,871. RESULTS No CP-751,871-related dose-limiting toxicities were identified. Plasma CP-751,871 concentrations increased with dose and concentration-time profiles were consistent with those of antibodies with target-mediated disposition. Importantly, CP-751,871 administration led to a decrease in granulocyte IGF-IR expression and serum insulinlike growth factor 1 accumulation at high doses, suggesting systemic IGF-IR inhibition. Tumor response was assessed according to the European Group for Blood and Marrow Transplantation criteria. Nine responses were reported in 27 patients treated with CP-751,871 in combination with dexamethasone. Of interest, two of the patients with a partial response were progressing from dexamethasone treatment at study entry. CONCLUSION These data indicate that CP-751,871 is well tolerated and may constitute a novel agent in the treatment of multiple myeloma.
Repair of O6-Benzylguanine by the Escherichia coli Ada and Ogt and the Human O6-Alkylguanine-DNA Alkyltransferases*

O6-Methylguanine is removed from DNA via the transfer of the methyl group to a cysteine acceptor site present in the DNA repair protein O6-alkylguanine-DNA alkyltransferase. The human alkyltransferase is inactivated by the free base O6-benzylguanine, raising the possibility that substantially larger alkyl groups could also be accepted as substrates. However, the Escherichia coli alkyltransferase, Ada-C, is not inactivated by O6-benzylguanine. The Ada-C protein was rendered capable of reaction by the incorporation of two site-directed mutations converting Ala316 to a proline (A316P) and Trp336 to alanine (W336A) or glycine (W336G). These changes increase the space at the active site of the protein where Cys321 is buried and thus permit access of the O6-benzylguanine inhibitor. Reaction of the mutant A316P/W336A-Ada-C with O6-benzylguanine was greatly stimulated by the presence of DNA, providing strong support for the concept that binding of DNA to the Ada-C protein activates the protein. The Ada-C protein was able to repair O6-benzylguanine in a 16-mer oligodeoxyribonucleotide. However, the rate of repair was very slow, whereas the E. coli Ogt, the human alkyltransferase, and the mutant A316P/W336A-Ada-C alkyltransferases reacted very rapidly with this 16-mer substrate and preferentially repaired it when incubated with a mixture of the methylated and benzylated 16-mers. These results show that benzyl groups are better substrates than methyl groups for alkyltransferases provided that steric factors do not prevent binding of the substrate in the correct orientation for alkyl group transfer.