Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression and distribution of GABA and GABAB‐receptor in the rat adrenal gland

The inhibitory effects of gamma‐aminobutyric acid (GABA) in the central and peripheral nervous systems and the endocrine system are mediated by two different GABA receptors: GABAA‐receptor (GABAA‐R) and GABAB‐receptor (GABAB‐R). GABAA‐R, but not GABAB‐R, has been observed in the rat adrenal gland, where GABA is known to be released. This study sought to determine whether both GABA and GABAB‐R are present in the endocrine and neuronal elements of the rat adrenal gland, and to investigate whether GABAB‐R may play a role in mediating the effects of GABA in secretory activity of these cells. GABA‐immunoreactive nerve fibers were observed in the superficial cortex. Some GABA‐immunoreactive nerve fibers were found to be associated with blood vessels. Double‐immunostaining revealed GABA‐immunoreactive nerve fibers in the cortex were choline acetyltransferase (ChAT)‐immunonegative. Some GABA‐immunoreactive nerve fibers ran through the cortex toward the medulla. In the medulla, GABA‐immunoreactivity was seen in some large ganglion cells, but not in the chromaffin cells. Double‐immunostaining also showed GABA‐immunoreactive ganglion cells were nitric oxide synthase (NOS)‐immunopositive. However, neither immunohistochemistry combined with fluorescent microscopy nor double‐immunostaining revealed GABA‐immunoreactivity in the noradrenaline cells with blue‐white fluorescence or in the adrenaline cells with phenylethanolamine N‐methyltransferase (PNMT)‐immunoreactivity. Furthermore, GABA‐immunoreactive nerve fibers were observed in close contact with ganglion cells, but not chromaffin cells. Double‐immunostaining also showed that the GABA‐immunoreactive nerve fibers were in close contact with NOS‐ or neuropeptide tyrosine (NPY)‐immunoreactive ganglion cells. A few of the GABA‐immunoreactive nerve fibers were ChAT‐immunopositive, while most of the GABA‐immunoreactive nerve fibers were ChAT‐immunonegative. Numerous ChAT‐immunoreactive nerve fibers were observed in close contact with the ganglion cells and chromaffin cells in the medulla. The GABAB‐R‐immunoreactivity was found only in ganglion cells in the medulla and not at all in the cortex. Immunohistochemistry combined with fluorescent microscopy and double‐immunostaining showed no GABAB‐R‐immunoreactivity in noradrenaline cells with blue‐white fluorescence or in adrenaline cells with PNMT‐immunoreactivity. These immunoreactive ganglion cells were NOS‐ or NPY‐immunopositive on double‐immunostaining. These findings suggest that GABA from the intra‐adrenal nerve fibers may have an inhibitory effect on the secretory activity of ganglion cells and cortical cells, and on the motility of blood vessels in the rat adrenal gland, mediated by GABA‐Rs.
Diversity of Babesia and Rickettsia species in questing Ixodes ricinus: a longitudinal study in urban, pasture, and natural habitats.

In a previous study, our group investigated the Babesia spp. prevalence in questing Ixodes ricinus ticks from nine city parks in South Germany in the years 2009 and 2010. We showed predominant prevalence of B. venatorum (in previous literature also known as Babesia sp. EU1), especially in those parks in a more natural condition and with occurrence of large wild animals, such as roe deer. To obtain longitudinal data and to broaden the knowledge about this pathogen, further investigations were carried out in 2011 and 2012 in four of those city parks. Two additional habitat types were chosen for comparison of prevalence data and species analysis focusing on occurrence of potential reservoir hosts. A total of 10,303 questing I. ricinus were collected in four city parks, a pasture, and a natural area in Bavaria, and a representative number of samples were investigated for prevalence of DNA of Babesia spp. (n=4381) and Rickettsia spp. (n=2186) by PCR. In the natural and pasture area, a significantly higher Babesia spp. prevalence compared to the urban area was detected. The natural area revealed sequences of B. microti, B. venatorum, and B. capreoli. In the pasture and urban habitat, predominantly B. venatorum was found, whereas B. capreoli was less frequent and only one B. microti-infected tick was found. All B. microti sequences were 100% identical to the zoonotic Jena/Germany strain. For Rickettsia spp. , the significantly highest prevalence was also detected in the natural and pasture areas, whereas lower prevalence was found in the urban area. Sequence analysis revealed R. helvetica (98%) and R. monacensis (2%). Prevalence rates and occurrence of Babesia spp. and Rickettsia spp. differed in urban, pasture and natural sites, most likely depending on the habitat structure (natural or cultivated) and therefore on the appearance and availability of reservoir hosts like roe deer or small mammals.
Association of Sleep Habits With Accidents and Near Misses in United States Transportation Operators

Objective: To explore sleep risk factors and their association with adverse events in transportation operators. Methods: Self-reported sleep-related behaviors were analyzed in transportation operators (drivers, pilots, and rail operators) aged 26 to 78 years who completed the National Sleep Foundation's 2012 “Planes, Trains, Automobiles, and Sleep” survey. Regression analyses were used to assess the associations of various sleep-related variables with the combined outcome of self-reported accidents and near misses. Results: Age- and body mass–adjusted predictors of accidents/near misses included an accident while commuting (odds ratio [OR] = 4.6; confidence interval [CI], 2.1 to 9.8), driving drowsy (OR = 4.1; CI, 2.5 to 6.7), and Sheehan Disability Scale score greater than 15 (OR = 3.5; CI, 2.2 to 5.5). Sleeping more than 7 hours nightly was protective for accident/near misses (OR = 0.6; CI, 0.4 to 0.9). Conclusion: Recognized risk factors for poor sleep or excessive daytime sleepiness were significantly associated with self-reported near misses and/or accidents in transportation operators.
High-Throughput Reliable Multicast in Multi-Hop Wireless Mesh Networks

This paper presents a cross-layer approach for enabling high-throughput reliable multicast in multi-hop wireless mesh networks. The building block of our approach is a multicast routing metric, called the expected multicast transmission count (EMTX). EMTX is designed to capture the combined effects of MAC-layer retransmission-based reliability, wireless broadcast advantage, and link quality awareness. The EMTX of single-hop transmission of a multicast packet from a sender is the expected number of multicast transmissions (including retransmissions) required for its next-hop recipients to receive the packet successfully. We formulate the EMTX-based multicast problem with the objective of minimizing the sum of EMTX over all forwarding nodes in the multicast tree, aiming to reduce network bandwidth consumption while ensure high end-to-end packet delivery ratio for the multicast traffic. We provide rigorous mathematical formulations and methods to find near-optimal solutions of the problem computationally efficiently. We present centralized and distributed algorithms, and demonstrate their effectiveness in tackling the EMTX-based multicast problem with a combination of theoretical and numerical results. Simulation experiments show that, in comparison with two baseline approaches, EMTX-based multicast routing reduces the number of hop-by-hop transmissions per packet by up to 40 percent and yet improves the multicast throughput by up to 24 percent.
Climate Envelope Modeling and Dispersal Simulations Show Little Risk of Range Extension of the Shipworm, Teredo navalis (L.), in the Baltic Sea

The shipworm, Teredo navalis, is absent from most of the Baltic Sea. In the last 20 years, increased frequency of T. navalis has been reported along the southern Baltic Sea coasts of Denmark, Germany, and Sweden, indicating possible range-extensions into previously unoccupied areas. We evaluated the effects of historical and projected near-future changes in salinity, temperature, and oxygen on the risk of spread of T. navalis in the Baltic. Specifically, we developed a simple, GIS-based, mechanistic climate envelope model to predict the spatial distribution of favourable conditions for adult reproduction and larval metamorphosis of T. navalis, based on published environmental tolerances to these factors. In addition, we used a high-resolution three-dimensional hydrographic model to simulate the probability of spread of T. navalis larvae within the study area. Climate envelope modeling showed that projected near-future climate change is not likely to change the overall distribution of T. navalis in the region, but will prolong the breeding season and increase the risk of shipworm establishment at the margins of the current range. Dispersal simulations indicated that the majority of larvae were philopatric, but those that spread over a wider area typically spread to areas unfavourable for their survival. Overall, therefore, we found no substantive evidence for climate-change related shifts in the distribution of T. navalis in the Baltic Sea, and no evidence for increased risk of spread in the near-future.
Cap-binding protein 4EHP effects translation silencing by microRNAs

Significance miRNAs are important components of gene regulatory networks and affect all aspects of cell biology by controlling the stability and translation efficiency of their target mRNAs. Here, we identified the mRNA cap-binding eIF4E-related protein 4EHP as an effector of miRNA-mediated translation repression. Through screening for protein interactions in cells via the BioID method, we identified 4EHP as a component of the CCR4–NOT/DDX6/4E-T axis. Direct interaction between 4E-T and 4EHP increases the latter’s cap-binding affinity, suggesting that this interaction potentiates its competition with the eIF4F complex for binding to the mRNA 5′ cap. Our findings suggest that 4EHP facilitates the formation of a closed-loop structure between the 3′ UTR of the mRNA and its 5′ cap, which causes repression of mRNA translation. MicroRNAs (miRNAs) play critical roles in a broad variety of biological processes by inhibiting translation initiation and by destabilizing target mRNAs. The CCR4–NOT complex effects miRNA-mediated silencing, at least in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is unknown. Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component of the miRNA-mediated silencing machinery. We demonstrate that the cap-binding activity of 4EHP contributes to the translational silencing by miRNAs through the CCR4–NOT complex. Our results show that 4EHP competes with eIF4E for binding to 4E-T, and this interaction increases the affinity of 4EHP for the cap. We propose a model wherein the 4E-T/4EHP interaction engenders a closed-loop mRNA conformation that blocks translational initiation of miRNA targets.
Possible Role of Minor H Antigens in the Persistence of Donor Chimerism after Stem Cell Transplantation; Relevance for Sustained Leukemia Remission

Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.
Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice

ABSTRACT An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI). The frequency distribution of respiratory syncytial virus (RSV)-the main cause of severe cases of bronchiolitis and pneumonia in children-was studied in all collected samples. The mechanism through which CB2 affects clinical outcomes in case of RSV infection was studied in Balb/c mice model using AM630 as a CB2 antagonist. The potential therapeutic effect of CB2 activation during RSV infection was studied using a selective agonist, JWH133. The CB2 Q63R variation was associated with increased risk of hospitalization in children with ARTI. Children carrying the QQ genotype were more prone to developing severe ARTI (OR = 3.275, 95% CI: 1.221–8.705; p = 0.019). Of all the children enrolled in the study, 83 patients (46.1%) were found positive for RSV infection. The associated risk of developing severe ARTI following RSV infection increased more than two-fold in children carrying the Q allele (OR = 2.148, 95% CI: 1.092–4.224; p = 0.026). In mice, the blockade of CB2 by AM630 during RSV infection enhanced the influx of BAL cells and production of cytokines/chemokines while exaggerating lung pathology. CB2 activation by JWH133 reduces the influx of BAL cells and production of cytokines/chemokines while alleviating lung pathology. Collectively, CB2 is associated with RSV severity during infancy and may serve as a therapeutic target in RSV infection through the alleviation of virus-associated immunopathology.
Associations between Green Space and Health in English Cities: An Ecological, Cross-Sectional Study

Green space has been identified as a modifiable feature of the urban environment and associations with physiological and psychological health have been reported at the local level. This study aims to assess whether these associations between health and green space are transferable to a larger scale, with English cities as the unit of analysis. We used an ecological, cross-sectional study design. We classified satellite-based land cover data to quantify green space coverage for the 50 largest cities in England. We assessed associations between city green space coverage with risk of death from all causes, cardiovascular disease, lung cancer and suicide between 2002 and 2009 using Poisson regression with random effect. After adjustment for age, income deprivation and air pollution, we found that at the city level the risk of death from all causes and a priori selected causes, for men and women, did not significantly differ between the greenest and least green cities. These findings suggest that the local health effects of urban green space observed at the neighbourhood level in some studies do not transfer to the city level. Further work is needed to establish how urban residents interact with local green space, in order to ascertain the most relevant measures of green space.
Disaggregating Census Data for Population Mapping Using Random Forests with Remotely-Sensed and Ancillary Data

High resolution, contemporary data on human population distributions are vital for measuring impacts of population growth, monitoring human-environment interactions and for planning and policy development. Many methods are used to disaggregate census data and predict population densities for finer scale, gridded population data sets. We present a new semi-automated dasymetric modeling approach that incorporates detailed census and ancillary data in a flexible, “Random Forest” estimation technique. We outline the combination of widely available, remotely-sensed and geospatial data that contribute to the modeled dasymetric weights and then use the Random Forest model to generate a gridded prediction of population density at ~100 m spatial resolution. This prediction layer is then used as the weighting surface to perform dasymetric redistribution of the census counts at a country level. As a case study we compare the new algorithm and its products for three countries (Vietnam, Cambodia, and Kenya) with other common gridded population data production methodologies. We discuss the advantages of the new method and increases over the accuracy and flexibility of those previous approaches. Finally, we outline how this algorithm will be extended to provide freely-available gridded population data sets for Africa, Asia and Latin America.
Improved List-Decodability of Random Linear Binary Codes

There has been a great deal of work establishing that random linear codes are as list-decodable as uniformly random codes, in the sense that a random linear binary code of rate <inline-formula> <tex-math notation="LaTeX">$1 - {H}(\text {p}) - \epsilon $ </tex-math></inline-formula> is <inline-formula> <tex-math notation="LaTeX">$( {p},\text {O}(1/\epsilon))$ </tex-math></inline-formula>-list-decodable with high probability. In this work, we show that such codes are <inline-formula> <tex-math notation="LaTeX">$( {p}, {H}( {p})/\epsilon + 2)$ </tex-math></inline-formula>-list-decodable with high probability, for any <inline-formula> <tex-math notation="LaTeX">$ {p} \in (0, 1/2)$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$\epsilon > 0$ </tex-math></inline-formula>. In addition to improving the constant in known list-size bounds, our argument—which is quite simple—works simultaneously for all values of p, while previous works obtaining <inline-formula> <tex-math notation="LaTeX">$ {L} = \text {O}(1/\epsilon)$ </tex-math></inline-formula> patched together different arguments to cover different parameter regimes. Our approach is to strengthen an existential argument of (Guruswami, Håstad, Sudan and Zuckerman, IEEE Trans. IT, 2002) to hold with high probability. To complement our upper bound for random linear codes, we also improve an argument of (Guruswami, Narayanan, IEEE Trans. IT, 2014) to obtain an essentially tight lower bound of <inline-formula> <tex-math notation="LaTeX">$1/\epsilon $ </tex-math></inline-formula> on the list size of uniformly random codes; this implies that random linear codes are in fact <italic>more</italic> list-decodable than uniformly random codes, in the sense that the list sizes are strictly smaller. To demonstrate the applicability of these techniques, we use them to (a) obtain more information about the distribution of list sizes of random linear codes and (b) to prove a similar result for random linear rank-metric codes.
The TyrR Transcription Factor Regulates the Divergent akr-ipdC Operons of Enterobacter cloacae UW5

The TyrR transcription factor regulates genes involved in the uptake and biosynthesis of aromatic amino acids in Enterobacteriaceae. Genes may be positively or negatively regulated depending on the presence or absence of each aromatic amino acid, all three of which function as cofactors for TyrR. In this report we detail the transcriptional control of two divergently transcribed genes, akr and ipdC, by TyrR, elucidated by promoter fusion expression assays and electrophoretic mobility shift assays to assess protein-DNA interactions. Expression of both genes was shown to be controlled by TyrR via interactions with two TyrR boxes located within the akr-ipdC intergenic region. Expression of ipdC required TyrR bound to the proximal strong box, and is strongly induced by phenylalanine, and to a lesser extent by tryptophan and tyrosine. Down-regulation of akr was reliant on interactions with the weak box, and may also require a second, as yet unidentified protein for further repression. Tyrosine enhanced repression of akr. Electrophoretic mobility shift assays demonstrated that TyrR interacts with both the strong and weak boxes, and that binding of the weak box in vitro requires an intact adjacent strong box. While the strong box shows a high degree of conservation with the TyrR binding site consensus sequence, the weak box has atypical spacing of the two half sites comprising the palindromic arms. Site-directed mutagenesis demonstrated sequence-specific interaction between TyrR and the weak box. This is the first report of TyrR-controlled expression of two divergent protein-coding genes, transcribed from independent promoters. Moreover, the identification of a predicted aldo-keto reductase as a member of the TyrR regulon further extends the function of the TyrR regulon.
Perception of Antiretroviral Generic Medicines: One-Day Survey of HIV-Infected Patients and Their Physicians in France

Background In the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physicians Methods and Findings 556 out of 703 (79%) adult HIV+ outpatients and 116 physicians in 33 clinics were included in a multicentric cross-sectional survey performed in September 2013. Patients completed a self-questionnaire on their perception and acceptability of generics. Physicians completed a questionnaire on their acceptability of switching antiretroviral to generic. Socio-demographic data, medical history and HIV history were collected. Among the 556 patients with a median HIV duration of 13 years, 77% were France native, 59% in active employment, 100% covered by social insurance, 95% on antiretroviral therapy. Seventy-six percent of the patients accepted generics and 55% trusted them overall. Antiretroviral generics were accepted by 44% of them but only by 17% if the pill burden was going to increase. The factor significantly associated with acceptability of antiretroviral generics was acceptance of generics per se (p<0.001). Among the 116 physicians following a median of 100 HIV-patients/year, 75% would prescribe generics, dropping to 26% if the combo had to be broken. Factors significantly associated with willingness to prescribe antiretroviral generics were the absence of concern regarding the chemical entity (OR = 0.33), being aware that the patient would accept generics for other pathologies (OR = 2.04) and would accept antiretroviral generics (OR = 1.94). No factor related to sociodemographic conditions, HIV status or comorbidities was associated with the acceptability of antiretroviral generics. Conclusions Acceptability of antiretroviral generics in this French population was mostly dictated by the patient’s and physician’s knowledge and use of generics overall. It should be improved with an efficient information of both patients and physicians.