Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiretroviral Pre-exposure Prophylaxis Prevents Vaginal Transmission of HIV-1 in Humanized BLT Mice

Background Worldwide, vaginal transmission now accounts for more than half of newly acquired HIV-1 infections. Despite the urgency to develop and implement novel approaches capable of preventing HIV transmission, this process has been hindered by the lack of adequate small animal models for preclinical efficacy and safety testing. Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection. Methods and Findings We show that the female reproductive tract of humanized bone marrow–liver–thymus (BLT) mice is reconstituted with human CD4+ T and other relevant human cells, rendering these humanized mice susceptible to intravaginal infection by HIV-1. Effects of HIV-1 infection include CD4+ T cell depletion in gut-associated lymphoid tissue (GALT) that closely mimics what is observed in HIV-1–infected humans. We also show that pre-exposure prophylaxis with antiretroviral drugs is a highly effective method for preventing vaginal HIV-1 transmission. Whereas 88% (7/8) of BLT mice inoculated vaginally with HIV-1 became infected, none of the animals (0/5) given pre-exposure prophylaxis of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) showed evidence of infection (Chi square = 7.5, df = 1, p = 0.006). Conclusions The fact that humanized BLT mice are susceptible to intravaginal infection makes this system an excellent candidate for preclinical evaluation of both microbicides and pre-exposure prophylactic regimens. The utility of humanized mice to study intravaginal HIV-1 transmission is particularly highlighted by the demonstration that pre-exposure prophylaxis can prevent intravaginal HIV-1 transmission in the BLT mouse model.
Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans.

Vascular endothelin-receptor stimulation results in vasoconstriction and concomitant production of the vasodilators prostaglandin I2 and nitric oxide. The vascular effects of cyclooxygenase (COx) blockade (diclofenac intravenously) and the subsequent vasoconstrictor response to endothelin-1 (ET-1) infusion 30 min after diclofenac were studied in healthy men. With COx blockade, cardiac output (7%) and splanchnic (14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flow returned to basal value within 30 min. Mean arterial blood pressure increased (4%, P < 0.001). Splanchnic glucose output fell (22%, P < 0.01). Subsequent ET-1 infusion caused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl. Physiol. 77: 121-126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res. Commun. 180: 1298-1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin. Physiol. (Colch.) 13: 653-662, 1993), the same increase in mean arterial blood pressure (4%), decreases in cardiac output (13%) and splanchnic blood flow (38%), but no significant change in splanchnic glucose output. Renal blood flow reduction was potentiated (33 +/- 3 vs. 23 +/- 2%, P < 0.02), with a total reduction corresponding to 43 +/- 3% (P < 0.01 vs. 23 +/- 3%). We conclude that COx inhibition induces renal and splanchnic vasoconstriction. The selectively increased renal vascular responsiveness to ET-1 emphasizes the importance of endogenous arachidonic acid metabolites (i.e., prostaglandin I2) to counteract ET-1-mediated renal vasoconstriction.
Controllable Acoustic Mixing of Fluids in Microchannels for the Fabrication of Therapeutic Nanoparticles

Fifteen years ago, surface acoustic waves (SAW) were found to be able to drive fluids and numerous applications in microfluidics have been developed since. Here, we review the progress made and report on new approaches in setting-up microfluidic, continuous flow acoustic mixing. In a microchannel, chaotic advection is achieved by generation of a SAW driven fluid jet perpendicular to the mean flow direction. Using a high speed video camera and particle image velocimetry, we measure the flow velocities and show that mixing is achieved in a particularly controllable and fast way. The mixing quality is determined as a function of system parameters: SAW power, volume flux and fluid viscosity. Exploring the parameter space of mixing provides a practical guide for acoustic mixing in microchannels and allows for adopting conditions to different solvents, as e.g., required for the generation of nanoscale particles from alcoholic phases. We exemplarily demonstrate the potential of SAW based continuous flow mixing for the production of therapeutic nucleic acid nanoparticles assembled from polymer and lipid solutions.
Predictors of Neuropsychological Test Performance After Pediatric Traumatic Brain Injury

The influence of neurological and demographic variables on neuropsychological test performance was examined in 100 9-to 16-year-old children with traumatic brain injury (TBI). Regression analyses were conducted to determine the relative contributions of coma, neuroimaging findings, ethnicity, socioeconomic status, and gender to variance in performance on the Wechsler Intelligence Scale for Children—Third Edition (WISC-III), California Verbal Learning Test—Children’s Version (CVLT-C), and the Children’s Category Test. Both neurological and demographic variables contributed to performance on various WISC-III factor index scores as well as the CVLT-C. No evidence for a moderating effect of demographic variables was found, but speed of information processing mediated the effect of neurological and demographic variables on CLVT-C performance. It is concluded that demographic variables have an incremental effect on the neuropsychological test performance of children with TBI above and beyond the influence of injury severity.
Chromosomal localization of the 18S-28S and 5S rRNA genes and (TTAGGG)n sequences of butterfly lizards (Leiolepis belliana belliana and Leiolepis boehmei, Agamidae, Squamata)

Chromosomal mapping of the butterfly lizards Leiolepis belliana belliana and L. boehmei was done using the 18S-28S and 5S rRNA genes and telomeric (TTAGGG)n sequences. The karyotype of L. b. belliana was 2n = 36, whereas that of L. boehmei was 2n = 34. The 18S-28S rRNA genes were located at the secondary constriction of the long arm of chromosome 1, while the 5S rRNA genes were found in the pericentromeric region of chromosome 6 in both species. Hybridization signals for the (TTAGGG)n sequence were observed at the telomeric ends of all chromosomes, as well as interstitially at the same position as the 18S-28S rRNA genes in L. boehmei. This finding suggests that in L. boehmei telomere-to-telomere fusion probably occurred between chromosome 1 and a microchromosome where the 18S-28S rRNA genes were located or, alternatively, at the secondary constriction of chromosome 1. The absence of telomeric sequence signals in chromosome 1 of L. b. belliana suggested that its chromosomes may have only a few copies of the (TTAGGG)n sequence or that there may have been a gradual loss of the repeat sequences during chromosomal evolution.
Sequence Determinants of GLUT1-mediated Accelerated-exchange Transport

Background: The human equilibrative glucose transporter GLUT1 catalyzes accelerated-exchange transport, but the related isoform GLUT4 does not. Results: Substitution of GLUT1 transmembrane helix 6 into GLUT4 permits GLUT4 to catalyze accelerated-exchange, whereas GLUT4 helix 6 prevents accelerated-exchange in GLUT1. Conclusion: Transmembrane helix 6 sequence determines accelerated-exchange behavior. Significance: Transmembrane helices external to the transport pathway influence transport behavior. The class 1 equilibrative glucose transporters GLUT1 and GLUT4 are structurally similar but catalyze distinct modes of transport. GLUT1 exhibits trans-acceleration, in which the presence of intracellular sugar stimulates the rate of unidirectional sugar uptake. GLUT4-mediated uptake is unaffected by intracellular sugar. Using homology-scanning mutagenesis in which domains of GLUT1 are substituted with equivalent domains from GLUT4 and vice versa, we show that GLUT1 transmembrane domain 6 is both necessary and sufficient for trans-acceleration. This region is not directly involved in GLUT1 binding of substrate or inhibitors. Rather, transmembrane domain 6 is part of two putative scaffold domains, which coordinate membrane-spanning amphipathic helices that form the sugar translocation pore. We propose that GLUT1 transmembrane domain 6 restrains import when intracellular sugar is absent by slowing transport-associated conformational changes.
Single Channel Recordings Reveal Differential β2 Subunit Modulations Between Mammalian and Drosophila BKCa(β2) Channels

Large-conductance Ca2+- and voltage-activated potassium (BK) channels are widely expressed in tissues. As a voltage and calcium sensor, BK channels play significant roles in regulating the action potential frequency, neurotransmitter release, and smooth muscle contraction. After associating with the auxiliary β2 subunit, mammalian BK(β2) channels (mouse or human Slo1/β2) exhibit enhanced activation and complete inactivation. However, how the β2 subunit modulates the Drosophila Slo1 channel remains elusive. In this study, by comparing the different functional effects on heterogeneous BK(β2) channel, we found that Drosophila Slo1/β2 channel exhibits “paralyzed”-like and incomplete inactivation as well as slow activation. Further, we determined three different modulations between mammalian and Drosophila BK(β2) channels: 1) dSlo1/β2 doesn’t have complete inactivation. 2) β2(K33,R34,K35) delays the dSlo1/Δ3-β2 channel activation. 3) dSlo1/β2 channel has enhanced pre-inactivation than mSlo1/β2 channel. The results in our study provide insights into the different modulations of β2 subunit between mammalian and Drosophila Slo1/β2 channels and structural basis underlie the activation and pre-inactivation of other BK(β) complexes.
Neonatal outcome and congenital malformations in children born after in-vitro fertilization.

BACKGROUND To evaluate the neonatal outcome and the prevalence of congenital malformations in children born after IVF in northern Finland we carried out a population-based study with matched controls. METHODS Firstly, 304 IVF children born in 1990-1995 were compared with 569 controls, representing the general population in proportion of multiple births, randomly chosen from the Finnish Medical Birth Register (FMBR) and matched for sex, year of birth, area of residence, parity, maternal age and social class. Secondly, plurality matched controls (n = 103) for IVF twins (n =103) were randomly chosen from the FMBR and analysed separately. Additionally, IVF singletons (n = 153) were compared with singleton controls (n = 287). Mortality rates were compared with national figures from FMBR. RESULTS Most mortality rates were twice as high as national figures in the general population. When compared with the control group representing the general population, the incidences of preterm birth [odds ratio (OR) 5.6, 95% confidence interval (CI) 3.7-8.6], very low birth weight (OR 6.2, 95% CI 2.0-19.0), low birth weight (OR 9.8, 95% CI 5.6-17.3), neonatal morbidity (OR 2.4, 95% CI 1.7-3.4) and hospitalization (OR 3.2, 95% CI 2.2-4.6) were significantly higher in the IVF group. The prevalence of heart malformations was four-fold in the IVF population than in the controls representing the general population (OR 4.0, 95% CI 1.4-11.7). CONCLUSIONS Neonatal outcome after IVF is worse than in the general population with similar maternal age, parity and social standing, mainly due to the large proportion of multifetal births after IVF. The higher prevalence of heart malformations does not solely arise from multiplicity but from other causes. In order to improve neonatal outcome after IVF, the number of embryos transferred should be limited to a minimum.
Alignment versus variation methods for clustering microarray time-series data

In the past few years, it has been shown that traditional clustering methods do not necessarily perform well on time-series data because of the temporal relationships involved in such data — this makes it a particularly difficult problem. In this paper, we compare two clustering methods that have been introduced recently, especially for gene expression time-series data, namely, multiple-alignment (MA) clustering and variation-based co-expression detection (VCD) clustering approaches. Both approaches are based on a transformation of the data that takes into account the temporal relationships, and have been shown to effectively detect groups of co-expressed genes. We investigate the performances of the MA and VCD approaches on two microarray time-series data sets and discuss their strengths and weaknesses. Our experiments show the superior accuracy of MA over VCD when finding groups of co-expressed genes.
The Mechanisms of the Atlantic Meridional Overturning Circulation Slowdown Induced by Arctic Sea Ice Decline

We explore the mechanisms by which Arctic sea ice decline affects the Atlantic meridional overturning circulation (AMOC) in a suite of numerical experiments perturbing the Arctic sea ice radiative budget within a fully coupled climate model. The imposed perturbations act to increase the amount of heat available to melt ice, leading to a rapid Arctic sea ice retreat within 5 years after the perturbations are activated. In response, the AMOC gradually weakens over the next ~100 years. The AMOC changes can be explained by the accumulation in the Arctic and subsequent downstream propagation to the North Atlantic of buoyancy anomalies controlled by temperature and salinity. Initially, during the first decade or so, the Arctic sea ice loss results in anomalous positive heat and salinity fluxes in the subpolar North Atlantic, inducing positive temperature and salinity anomalies over the regions of oceanic deep convection. At first, these anomalies largely compensate one another, leading to a minimal change in upper ocean density and deep convection in the North Atlantic. Over the following years, however, more anomalous warm water accumulates in the Arctic and spreads to the North Atlantic. At the same time, freshwater that accumulates from seasonal sea ice melting over most of the upper Arctic Ocean also spreads southward, reaching as far as south of Iceland. These warm and fresh anomalies reduce upper ocean density and suppress oceanic deep convection. The thermal and haline contributions to these buoyancy anomalies, and therefore to the AMOC slowdown during this period, are found to have similar magnitudes. We also find that the related changes in horizontal wind-driven circulation could potentially push freshwater away from the deep convection areas and hence strengthen the AMOC, but this effect is overwhelmed by mean advection.
Water management practices and anthropogenic carbon sources alter the patterns of CH4 and CO2 emissions from inland waters

Recent estimates have confirmed that inland waters emit a considerable amount of CH4 and CO2 to the atmosphere at the regional and global scale. But these estimates are based on extrapolated measured data and lack of data from inland waters in arid and semi-arid regions and carbon sources from wastewater treatment plants (WWTPs) as well insufficient resolution of the spatiotemporal variability of these emissions. Through this study, we analyzed monthly hydrological, meteorological and water quality data from three irrigation and drinking water reservoirs in the lower Jordan River basin and estimated the atmospheric emission rates of CO2. We investigated the effect of WWTPs on surrounding aquatic systems in term of CH4 and CO2 emission by presenting seasonally resolved data for dissolved concentrations of both gases in the effluents and in the receiving streams at nine WWTPs in Germany. We investigated spatiotemporal variability of CH4 and CO2 emission from aquatic ecosystems by using of simple low-cost tools for measuring CO2 flux and bubble release rate from freshwater systems. Our estimates showed that reservoirs in semi-arid regions are oversaturated with CO2 and acted as net sources to the atmosphere. The magnitude of observed fluxes at the three water reservoirs in Jordan is comparable to those from tropical reservoirs (3.3 g CO2 m-2 d-1). The CO2 emission rate from these reservoirs is linked to changes of water surface area, which is the result of water management practices. WWTPs have been shown to discharge a considerable amount of CH4 (30.9±40.7 kg yr-1) and CO2 (0.06±0.05 Gg yr-1) to their surrounding streams, and emission rates of CH4 and CO2 from these streams are significantly enhanced by effluents of WWTPs up to 1.2 and 8.6 times, respectively. Our results showed that both diffusive flux and bubble release rate varied in time and space, and both of emission pathways should be included and variability should be resolved adequately in further sampling and measuring strategies. We conclude that future emission measurements and estimates from inland waters may consider water management practices, carbon sources from WWTPs as well spatial and temporal variability of emission.
Localization of Nitric Oxide Synthase in Human Trophoblast Cells: Role of Nitric Oxide in Trophoblast Proliferation and Differentiation

PROBLEM: There are conflicting reports about the isoform of nitric oxide synthase (NOS) present in trophoblast cells. In this study, we have examined the presence of different NOS isoforms in trophoblast cells. In addition, the role of nitric oxide (NO) in trophoblast function has also been studied by investigating the possible role of nitric oxide in trophoblast proliferation and differentiation. METHOD OF STUDY: NOS isoforms in primary‐term trophoblast and JEG‐3 cells were identified by immunocytochemistry. The intracellular localization of this enzyme was determined by confocal laser scanning microscopy. Trophoblast proliferation was studied by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrasolium bromide (MTT) conversion assay and cellular differentiation was monitored by human chorionic gonodotropin (hCG) and progesterone secretion, measured by radioimmunoassay. RESULTS: The immunoreactive NOS was present in human trophoblast cells of normal term placenta and JEG‐3 cells (a choriocarcinoma cell line) maintained in culture. Nicotinamide adenine dinucleotide phosphate (NADPH)‐dependent diaphorase activity overlapped with the immunostaining of NOS. Specific antibodies against the different isoforms of NOS detected the presence of neuronal‐type NOS (nNOS) only. The other two isoforms, i.e., eNOS (endothelial) and iNOS (macrophage specific) were completely absent. The nNOS was localized in cell cytoplasm. In culture, JEG‐3 cells normally undergo proliferation and cytotrophoblast cells in primary culture differentiate to form hormone‐secreting syncytial cells. Sodium nitroprusside (SNP), a nitric oxide donor, when added to the culture, significantly increased proliferation of JEG‐3 cells and inhibited the differentiation of cytotrophoblast cells. The arrest by SNP in the formation of syncytial cells was further evidenced by the low secretion profile of hCG and progesterone. CONCLUSIONS: Our findings suggest for the first time the presence of nNOS in the human trophoblast cells and a previously unrecognized role of NO in trophoblast proliferation and differentiation.
Winter grazing system and supplementation during late gestation influence performance of beef cows and steer progeny1

ABSTRACT A 2 × 2 factorial study evaluated effects of cow wintering system and last trimester CP supplementation on performance of beef cows and steer progeny over a 3-yr period. Pregnant composite cows (Red Angus × Simmental) grazed winter range (WR; n = 4/yr) or corn residue (CR; n = 4/yr) during winter and within grazing treatment received 0.45 kg/d (DM) 28% CP cubes (PS; n = 4/yr) or no supplement (NS; n = 4/yr). Offspring steer calves entered the feedlot 14 d postweaning and were slaughtered 222 d later. Precalving BW was greater (P = 0.02) for PS than NS cows grazing WR, whereas precalving BCS was greater (P < 0.001) for cows grazing CR compared with WR. Calf birth BW was greater (P = 0.02) for CR than WR and tended to be greater (P = 0.11) for PS than NS cows. Prebreeding BW and BCS were greater (P ≤ 0.001) for CR than WR cows and PS than NS (P = 0.006) cows. At weaning, CR cows were heavier (P < 0.001) than WR cows but had similar BCS (P = 0.74). Cow weaning BW and BCS were not affected (P > 0.32) by PS. Calf weaning BW was less (P = 0.01) for calves from NS cows grazing WR compared with all other treatments. Pregnancy rate was unaffected by treatment (P > 0.39). Steer ADG, 12th-rib fat, yield grade, and LM area (P > 0.10) were similar among all treatments. However, final BW and HCW (P = 0.02) were greater for steers from PS-WR than NS-WR cows. Compared with steers from NS cows, steers from PS cows had greater marbling scores (P = 0.004) and a greater (P = 0.04) proportion graded USDA Choice or greater. Protein supplementation of dams increased the value of calves at weaning (P = 0.03) and of steers at slaughter regardless of winter grazing treatment (P = 0.005). Calf birth and weaning BW were increased by grazing CR during the winter. Calf weaning BW was increased by PS of the dam if the dam grazed WR. Compared with steers from NS cows, steer progeny from PS cows had a greater quality grade with no (P = 0.26) effect on yield grade. These data support a late gestation dam nutrition effect on calf production via fetal programming.
Inhibitory Control Supports Referential Context Use in Language Production and Comprehension

Using referential context in language (e.g., saying “blue pen” when two different-colored pens are visible) makes communication efficient. But it is still unclear which general cognitive processes support the use of context in conversation. Research on pragmatic use in language implicates working memory and inhibitory control; however, no studies have shown evidence of a shared cognitive mechanism in both production and comprehension within an individual. The current study asked a) whether referential context use is supported by the same cognitive mechanisms in production and comprehension, b) which processes are implicated, and c) whether the nature of the context itself affects processing. Participants completed a referential communication eye-tracking task in which a disambiguating adjective was either necessary or over-informative, as well as a cognitive test battery. The results implicated inhibitory control in both production and comprehension (although the comprehension results were more variable), suggesting a shared underlying cognitive mechanism across domains.
The impact of DHT routing geometry on resilience and proximity

The various proposed DHT routing algorithms embody several different underlying routing geometries. These geometries include hypercubes, rings, tree-like structures, and butterfly networks. In this paper we focus on how these basic geometric approaches affect the resilience and proximity properties of DHTs. One factor that distinguishes these geometries is the degree of flexibility they provide in the selection of neighbors and routes. Flexibility is an important factor in achieving good static resilience and effective proximity neighbor and route selection. Our basic finding is that, despite our initial preference for more complex geometries, the ring geometry allows the greatest flexibility, and hence achieves the best resilience and proximity performance.