Miracle-dz/UniFAR-FTUs huggingface dataset:
Potent neuroprotection after stroke afforded by a double-knot spider-venom peptide that inhibits acid-sensing ion channel 1a

Significance Six million people die each year from stroke, and 5 million survivors are left with a permanent disability. Moreover, the neuronal damage caused by stroke often triggers a progressive decline in cognitive function that doubles the risk of dementia for stroke survivors. Despite this massive global disease burden, there are no approved drugs for treating the neuronal injury caused to the brain by the oxygen deprivation occurring during an ischemic stroke. The precipitous drop in brain pH resulting from stroke activates acid-sensing ion channel 1a. We show that inhibition of these channels using a “double-knot” spider venom peptide massively attenuates brain damage after stroke and improves behavioral outcomes, even when the peptide is administered 8 h after stroke onset. Stroke is the second-leading cause of death worldwide, yet there are no drugs available to protect the brain from stroke-induced neuronal injury. Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and a key mediator of acidosis-induced neuronal damage following cerebral ischemia. Genetic ablation and selective pharmacologic inhibition of ASIC1a reduces neuronal death following ischemic stroke in rodents. Here, we demonstrate that Hi1a, a disulfide-rich spider venom peptide, is highly neuroprotective in a focal model of ischemic stroke. Nuclear magnetic resonance structural studies reveal that Hi1a comprises two homologous inhibitor cystine knot domains separated by a short, structurally well-defined linker. In contrast with known ASIC1a inhibitors, Hi1a incompletely inhibits ASIC1a activation in a pH-independent and slowly reversible manner. Whole-cell, macropatch, and single-channel electrophysiological recordings indicate that Hi1a binds to and stabilizes the closed state of the channel, thereby impeding the transition into a conducting state. Intracerebroventricular administration to rats of a single small dose of Hi1a (2 ng/kg) up to 8 h after stroke induction by occlusion of the middle cerebral artery markedly reduced infarct size, and this correlated with improved neurological and motor function, as well as with preservation of neuronal architecture. Thus, Hi1a is a powerful pharmacological tool for probing the role of ASIC1a in acid-mediated neuronal injury and various neurological disorders, and a promising lead for the development of therapeutics to protect the brain from ischemic injury.
Mouse Hepatic Tumor Vascular Imaging by Experimental Selective Angiography

Purpose Human hepatocellular carcinoma (HCC) has unique vascular features, which require selective imaging of hepatic arterial perfusion and portal venous perfusion with vascular catheterization for sufficient evaluation. Unlike in humans, vessels in mice are too small to catheterize, and the importance of separately imaging the feeding vessels of tumors is frequently overlooked in hepatic tumor models. The purpose of this study was to perform selective latex angiography in several mouse liver tumor models and assess their suitability. Materials and Methods In several ectopic (Lewis lung carcinoma, B16/F10 melanoma cell lines) and spontaneous liver tumor (Albumin-Cre/MST1fl/fl/MST2fl/fl, Albumin-Cre/WW45fl/fl, and H-ras12V genetically modified mouse) models, the heart left ventricle and/or main portal vein of mice was punctured, and latex dye was infused to achieve selective latex arteriography and/or portography. Results H-ras12V transgenic mice (a HCC and hepatic adenoma model) developed multiple liver nodules that displayed three different perfusion patterns (portal venous or hepatic artery perfusion predominant, mixed perfusion), indicating intra-tumoral vascular heterogeneity. Selective latex angiography revealed that the Lewis lung carcinoma implant model and the Albumin-Cre/WW45fl/fl model reproduced conventional angiography findings of human HCC. Specifically, these mice developed tumors with abundant feeding arteries but no portal venous perfusion. Conclusion Different hepatic tumor models showed different tumor vessel characteristics that influence the suitability of the model and that should be considered when designing translational experiments. Selective latex angiography applied to certain mouse tumor models (both ectopic and spontaneous) closely simulated typical characteristics of human HCC vascular imaging.
Experimental study of coordination patterns during unsteady locomotion in mammals

SUMMARY A framework to study interlimb coordination, which allowed the analysis of all the symmetrical and asymmetrical gaits, was recently proposed. It suggests that gait depends on a common basic pattern controlling the coordination of the forelimbs (fore lag, FL), the coordination of the hindlimbs (hind lag, HL) and the relationship between these two pairs of limbs (pair lag, PL) in an anteroposterior sequence of movement (APS). These three time parameters are sufficient for identifying all steady gaits. We assumed in this work that this same framework could also be used to study non-steady locomotion, particularly the transitions between symmetrical and asymmetrical gaits. Moreover, as the limbs are coordinated in time and also in space during locomotion, we associated three analogous space parameters (fore gap, FG; hind gap, HG and pair gap, PG) to the three time parameters. We studied the interlimb coordination of dogs and cats moving on a runway with a symmetrical gait. In the middle of the runway, the gait was disturbed by an obstacle, and the animal had to change to an asymmetrical coordination to get over it. The time (FL, HL, PL) and space (FG, HG, PG) parameters of each sequence of the trials were calculated. The results demonstrated that the APS method allows quantification of the interlimb coordination during the symmetrical and asymmetrical phases and during the transition between them, in both dogs and cats. The space and time parameters make it possible to link the timing and the spacing of the footfalls, and to quantify the spatiotemporal dimension of gaits in different mammals. The slight differences observed between dogs and cats could reflect their morphological differences. The APS method could thus be used to understand the implication of morphology in interlimb coordination. All these results are consistent with current knowledge in biomechanics and neurobiology, therefore the APS reflects the actual biological functioning of quadrupedal interlimb coordination.
FETAL MORPHINE METABOLISM AND CLEARANCE ARE CONSTANT DURING LATE GESTATION

Fetal metabolism significantly contributes to the clearance of drugs from the fetus. To understand how the changes in fetal metabolism expected in late gestation alter fetal drug clearance, serial measurements of morphine metabolism were made in the fetal baboon over the latter third of gestation. Clearance and metabolism were evaluated in the context of fetal growth, onset of labor, and the administration of classical enzyme induction agents. Morphine, a probe substrate for the enzyme uridine diphosphate glucuronosyltransferase 2B7 (UGT2B7), was continuously infused to chronically catheterized fetal baboons while measuring morphine, morphine-3-β-glucuronide, and morphine-6-β-glucuronide concentrations. In some animals, intermittent infusions of the metabolites provided estimates of metabolite clearance and, hence, the rate of formation of metabolites and metabolic clearance. Overall, metabolic clearance of morphine from the fetus was 27 ± 9.0 ml · min–1 or 32% of total clearance. This is similar to the overall clearance in the adult baboon when standardized to weight. No change in any measure of metabolism or clearance of morphine or its glucuronide metabolites was found with gestational age, the presence of labor, or administration of UGT enzyme induction agents. Interpreting these findings using a physiologically based approach suggests that the intrinsic clearance of the fetal liver toward morphine is of sufficient magnitude that fetal hepatic clearance is flow-limited. The implication of a high intrinsic clearance is for significant placento-hepatic first-pass metabolism when drugs are administered to the mother. The previously held view of the “inadequacy of perinatal glucuronidation” needs to be reconsidered.
A Mathematical Framework to the Computation of the Error Probability of Downlink MIMO Cellular Networks by Using Stochastic Geometry

In this paper, a mathematical framework to the computation of the error probability of downlink cellular networks is introduced. It is based on the Poisson point process (PPP)-based abstraction for modeling the spatial locations of the base stations (BSs), and it exploits results from stochastic geometry for characterizing the distribution of the other-cell interference. The framework is applicable to spatial multiplexing multiple-input-multiple-output (MIMO) systems with an arbitrary number of antennas at the transmitter (Nt) and at the receiver (Nr). If Nt = Nr = 1, the mathematical approach can be used for arbitrary fading distributions on both useful and interfering links. If either Nt > 1 or Nr > 1, it can be applied to arbitrary fading distributions on the useful link and to Rayleigh fading on the interfering links. It is shown that the proposed approach leads to easy-to-compute integral expressions, which reduce to closed-form formulas in some asymptotic regimes. Furthermore, the framework is shown to provide insights for system design and optimization. The accuracy of the mathematical analysis is substantiated through extensive Monte Carlo simulations for various cellular network setups.
Central Modulation of Baroreceptor Reflex Response to Phenylephrine by Dihydropyridines in Rats

The effects of two dihydropyridine derivatives, the calcium channel agonist BAY k 8644 or the antagonist PN 200-110, on the central nervous components of the baroreceptor reflex control of heart rate during activation of baroreceptors by phenylephrine (2 μg i.v.) were studied in pentobarbitalanesthetlzed normotensive (Wistar) rats and spontaneously hypertensive rats (SHR). To rule out an effect on peripheral vessels or on the sinoauricular node (or on both), BAY k 8644 and PN 200-110 were administered intracerebroventricularly (i.c.v.) at doses that did not change blood pressure. Baroreceptor reflex sensitivity was calculated as the slope of the relationship between systolic arterial pressure and heart period. Baroreceptor reflex sensitivity increased with time following the onset of anesthesia. In SHR, injection of BAY k 8644 (3 μg/kg i.c.v.) suppressed the time-dependent Increase in baroreceptor reflex sensitivity. The inhibitory effect of BAY k 8644 (3 μg/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with PN 200-110 (0.6 μg/kg i.c.v.) but not with the solvent, indicating that the central effect of BAY k 8644 occurred at the level of specific dihydropyridine binding sites. In addition, the inhibitory effect of BAY k 8644 (3 μg/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with the muscarink antagonist atropine methylnitrate (80 μg/kg i.c.v.) but not with the solvent. In normotensive rats, the time-dependent increase in baroreceptor reflex sensitivity was not significantly altered by BAY k 8644 (3 μg/kg i.c.v.). These results indicate that dihydropyridines may centrally modulate baroreceptor reflex sensitivity in SHR and suggest that the inhibitory effect of the calcium agonist BAY k 8644 on baroreceptor reflex sensitivity may have been mediated by an enhanced release of acetylcholine.
Habitat filtering and adult dispersal determine the taxonomic composition of stream insects in an urbanizing landscape

Summary Suitability of the local habitat (‘habitat filtering’) and dispersal between stream reaches determines the composition of insect communities, and urban land use may affect both processes. While urban streams are often poor habitats for insects and dispersal between them is often hindered, conservation and restoration activities generally focus solely on the local (in-stream) environment. We determined whether in-stream habitat filtering (a ‘local’ process) or dispersal between reaches (a ‘regional’ process) controlled assemblage composition in a landscape subject to ongoing urban development (‘urbanizing’). We compared models incorporating geographic distance between sites, environmental dissimilarity, and land-use/land-cover attributes of dispersal pathways in an attempt to explain the dissimilarity of stream insect assemblages. Distance and land-use/land-cover attributes were characterised along both overland (straight line) and corridor pathways. Both in-stream habitat filtering and dispersal affected assemblage composition, but habitat had a stronger influence. Overland distance was a better predictor of assemblage dissimilarity than corridor distance, implying stream insect dispersal occurs across catchment boundaries as well as along stream corridors. The best model incorporated land-use/land-cover attributes along dispersal pathways, which supported the idea that urban land-use in the terrestrial environment mediates dispersal. Conservation and restoration strategies for streams in urbanizing landscapes that focus on local habitat quality and ignore dispersal are missing a potentially important mechanism affecting insect assemblage composition. While the primary focus should be on maintaining or improving the local habitat, potential dispersal pathways should also be considered.
Issues in the School-to-Work Transition of Hard of Hearing Adolescents

Career theorists emphasize the importance of the development of career maturity in adolescents if they are to successfully negotiate the school-to-work transition. Transitions of deaf and hard of hearing adolescents may be especially problematic. The authors examine the implications of current labor market trends for young people, in particular those with hearing loss, and review data on employment outcomes for deaf and hard of hearing people. They discuss the environmental and attitudinal barriers that can influence the career outcomes of this population, consider the impact of hearing loss on adolescents' career maturity, and review the studies on this topic in the literature. The article focuses on the experiences of students with significant hearing loss who are educated in regular classes with the support of itinerant teachers, who communicate orally, and who may be defined as hard of hearing. Recommendations for research and practice are provided.
H1N1 Influenza: The Trigger of Diabetic Ketoacidosis in a Young Woman With Ketosis-Prone Diabetes

Abstract:In this study, the authors report a case of new-onset ketosis-prone diabetes in a 21-year-old Chinese woman with H1N1 influenza, who presented with fever, polyuria and loss of appetite for 3 days before admission. She was hospitalized and diagnosed with acute-onset diabetic ketoacidosis for the first time. Her diabetes-associated antibodies were negative. Interestingly, she had an unexplained fever and her white blood cell count was low at admission and remained low for several days. She was believed to have a viral infection, which was found to be H1N1 influenza infection. The literature regarding virus infection and diabetic ketoacidosis is reviewed. The precipitating factors, symptomatology, pathophysiology and management of ketosis-prone diabetes are discussed in the current case report.
Platelet crossmatches of single‐donor platelet concentrates using a latex agglutination assay

A latex agglutination assay was evaluated for the purpose of identifying compatible platelet donors for alloimmunized recipients. Assay reagents were prepared by adsorbing detergent‐solubilized, donor‐specific platelets to polystyrene latex beads. Semiquantitative results for up to 30 donors can be completed in less than 1 hour. These reagents retained their immunoreactivity for at least 3.5 months. A retrospective study has established the assay's upper limit of compatibility. The prospective study evaluated transfusions to a group of multiply transfused patients. Part I evaluated 143 crossmatched, single‐donor platelet transfusions given to 50 patients. In 96 percent of the cases, a positive crossmatch was associated with an unsuccessful transfusion outcome; in 84 percent of the transfusions, a negative crossmatch predicted a satisfactory platelet increment. The overall predictability, sensitivity, and specificity were 87, 62, and 99 percent, respectively. Part II evaluated 105 transfusions given to the 43 patients (of 50) in whom no incidence of fever, sepsis, or bleeding could be documented. A positive crossmatch was 96‐percent efficient in predicting an unsuccessful transfusion, whereas a negative crossmatch was associated with an adequate platelet increment following 89 percent of the transfusions. The overall predictability was 91 percent, the sensitivity was 72 percent, and the specificity was 99 percent. Within‐run and between‐run variations were 6.3 and 6.2 percent, respectively. These results demonstrate that detergent‐solubilized platelet antigens, immobilized on latex particles, can be used in a cost‐effective crossmatching procedure.
Population-Based Study of Birth Prevalence and Factors Associated with Cleft Lip and/or Palate in Taiwan 2002–2009

Background Facial cleft deformities, including cleft lip with or without cleft palate (CL/P) and cleft palate (CP), are common congenital birth anomalies, especially in Asia. This study aimed to analyze the prevalence of CL/P and CP and to identify associated factors in Taiwan. Methods This population-based epidemiological study retrospectively analyzed birth data obtained from the Department of Health in Taiwan for years 2002–2009. Frequency distribution, percentages and related predictors were investigated, and findings were presented by types of cleft deformities. Logistic regression analysis was performed to identify factors associated with cleft deformities. Results Overall prevalence of cleft deformities among 1,705,192 births was 0.1% for CL/P and 0.04% for CP over the 8-year study period. Higher prevalence of CL/P or CP was observed with multiple pregnancies, being male for CL/P, being female for CP, gestational age ≤37 weeks and lower birth weight (<1.5 kg). Both CL/P and CP were significantly associated with gestational age <37 weeks and birth weight<1.5 kg (all P <0.0001). CL/P was significantly associated with multiple parities (P = 0.0004–0.002). Male newborns and female newborns were significantly associated with CL/P and CP, respectively (both P<0.0001). Conclusions Overall prevalence for congenital cleft deformities in study subjects was 0.1%, in keeping with high rates in Asia. Results suggest the need for awareness and early identification of those at high risk for cleft deformities, including newborns with gestational age <37 weeks, weighing <1.5 kg at birth and women with multiple parities, as a potential strategy to counter long-term adverse effects on speech and language in this population.
A Large-Scale RNAi Screen Identifies Deaf1 as a Regulator of Innate Immune Responses in Drosophila

Innate immune signalling pathways are evolutionarily conserved between invertebrates and vertebrates. The analysis of NF-ĸB signalling in Drosophila has contributed important insights into how organisms respond to infection. Nevertheless, significant gaps remain in our understanding of how the activation of intracellular signalling elicits specific transcriptional programs. Here we report a genome-wide RNA interference survey for transcription factors that are required for Toll-dependent immune responses. In addition to the NF-ĸB homologs Dif, Dorsal and factors of the general transcription machinery, we identified Deformed Epidermal Autoregulatory Factor 1 (Deaf1) to be required for the expression of the Toll target gene Drosomycin in cultured cells and in Drosophila in vivo. We show that Deaf1 is required for the survival of flies after fungal, but not E. coli, infection. We determine that Deaf1 acts downstream of the NF-ĸB factors Dorsal and Dif. These results indicate that Deaf1 is an important contributor to innate immune responses in vivo.
Color-Space-Based Visual-MIMO for V2X Communication †

In this paper, we analyze the applicability of color-space-based, color-independent visual-MIMO for V2X. We aim to achieve a visual-MIMO scheme that can maintain the original color and brightness while performing seamless communication. We consider two scenarios of GCM based visual-MIMO for V2X. One is a multipath transmission using visual-MIMO networking and the other is multi-node V2X communication. In the scenario of multipath transmission, we analyze the channel capacity numerically and we illustrate the significance of networking information such as distance, reference color (symbol), and multiplexing-diversity mode transitions. In addition, in the V2X scenario of multiple access, we may achieve the simultaneous multiple access communication without node interferences by dividing the communication area using image processing. Finally, through numerical simulation, we show the superior SER performance of the visual-MIMO scheme compared with LED-PD communication and show the numerical result of the GCM based visual-MIMO channel capacity versus distance.
Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7

Significance The mechanism of action of the artemisinin (ART) class of antimalarial drugs, the most important antimalarial drug class in use today, remains controversial, despite more than three decades of intensive research. We have developed an unbiased chemical proteomic approach using a suite of ART activity-based protein profiling probes to identify proteins within the malaria parasite that are alkylated by ART, including proteins involved in glycolysis, hemoglobin metabolism, and redox defense. The data point to a pleiotropic mechanism of drug action for this class and offer a strategy for investigating resistance mechanisms to ART-based drugs as well as mechanisms of action of other endoperoxide-based drugs. The artemisinin (ART)-based antimalarials have contributed significantly to reducing global malaria deaths over the past decade, but we still do not know how they kill parasites. To gain greater insight into the potential mechanisms of ART drug action, we developed a suite of ART activity-based protein profiling probes to identify parasite protein drug targets in situ. Probes were designed to retain biological activity and alkylate the molecular target(s) of Plasmodium falciparum 3D7 parasites in situ. Proteins tagged with the ART probe can then be isolated using click chemistry before identification by liquid chromatography–MS/MS. Using these probes, we define an ART proteome that shows alkylated targets in the glycolytic, hemoglobin degradation, antioxidant defense, and protein synthesis pathways, processes essential for parasite survival. This work reveals the pleiotropic nature of the biological functions targeted by this important class of antimalarial drugs.