Miracle-dz/UniFAR-FTUs huggingface dataset:
Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4+ T cell decline and increased immune activation during acute infection

HIV-1 transmission is associated with a severe bottleneck in which a limited number of variants from a pool of genetically diverse quasispecies establishes infection. The IAVI protocol C cohort of discordant couples, female sex workers, other heterosexuals and men who have sex with men (MSM) present varying risks of HIV infection, diverse HIV-1 subtypes and represent a unique opportunity to characterize transmitted/founder viruses (TF) where disease outcome is known. To identify the TF, the HIV-1 repertoire of 38 MSM participants’ samples was sequenced close to transmission (median 21 days post infection, IQR 18–41) and assessment of multivariant infection done. Patient derived gag genes were cloned into an NL4.3 provirus to generate chimeric viruses which were characterized for replicative capacity (RC). Finally, an evaluation of how the TF virus predicted disease progression and modified the immune response at both acute and chronic HIV-1 infection was done. There was higher prevalence of multivariant infection compared with previously described heterosexual cohorts. A link was identified between multivariant infection and replicative capacity conferred by gag, whereby TF gag tended to be of lower replicative capacity in multivariant infection (p = 0.02) suggesting an overall lowering of fitness requirements during infection with multiple variants. Notwithstanding, multivariant infection was associated with rapid CD4+ T cell decline and perturbances in the CD4+ T cell and B cell compartments compared to single variant infection, which were reversible upon control of viremia. Strategies aimed at identifying and mitigating multivariant infection could contribute toward improving HIV-1 prognosis and this may involve strategies that tighten the stringency of the transmission bottleneck such as treatment of STI. Furthermore, the sequences and chimeric viruses help with TF based experimental vaccine immunogen design and can be used in functional assays to probe effective immune responses against TF.
Palladium (II)–Salan Complexes as Catalysts for Suzuki–Miyaura C–C Cross-Coupling in Water and Air. Effect of the Various Bridging Units within the Diamine Moieties on the Catalytic Performance

Water-soluble salan ligands were synthesized by hydrogenation and subsequent sulfonation of salens (N,N’-bis(slicylidene)ethylenediamine and analogues) with various bridging units (linkers) connecting the nitrogen atoms. Pd (II) complexes were obtained in reactions of sulfosalans and [PdCl4]2−. Characterization of the ligands and complexes included extensive X-ray diffraction studies, too. The Pd (II) complexes proved highly active catalysts of the Suzuki–Miyaura reaction of aryl halides and arylboronic acid derivatives at 80 °C in water and air. A comparative study of the Pd (II)–sulfosalan catalysts showed that the catalytic activity largely increased with increasing linker length and with increasing steric congestion around the N donor atoms of the ligands; the highest specific activity was 40,000 (mol substrate) (mol catalyst × h)−1. The substrate scope was explored with the use of the two most active catalysts, containing 1,4-butylene and 1,2-diphenylethylene linkers, respectively.
Incidence of motor neuron disease/amyotrophic lateral sclerosis in South Africa: a 4‐year prospective study

Little is known about the epidemiological features of amyotrophic lateral sclerosis (ALS) in sub‐Saharan Africa, and data from the region are limited to clinical series or case reports. The aim of the study was to investigate the incidence rate and presentation of ALS in an ethnically diverse region of South Africa.
Non-Empirical Large-Scale Search for Optical Metasurfaces

Metasurfaces are artificially designed, on-top, thin structures on bulk substrates, realizing various functions in recent years. Most metasurfaces have been conceived of for attaining optical functions, based on elaborate human knowledge-based designs for complex structures. Here, we introduce a method for a non-empirical, large-scale structural search to find optical metasurfaces, which enable us to access intended functions without depending on human knowledge and experience. This method is different from the optimization and modification reported so far. To illustrate the outputs in the non-empirical search, we show unpredictable, optically high-performance, all-dielectric metasurfaces found in the machine search. As an extension of the finding of a higher order diffractive structure, we furthermore show a light-focusing metadevice, which is diffraction-limited and has the unique feature that the focal length is almost invariant even when the distance from the incident spot to the metadevice largely varies.
Associations of the LPL S447X and Hind III Polymorphism with Type 2 Diabetes Mellitus Risk: A Meta-Analysis

Abstract The present study was aimed to evaluate the association of lipoprotein lipase (LPL) gene (S447X and Hind III) polymorphisms and T2DM. Relevant studies were identified through systematic search PubMed, Cochrane Library, Embase, Wanfang, CNKI databases. A total of 22 studies (8 studies for LPL S447X and 14 studies for Hind III) were included. The results showed that the LPL S447X polymorphism was associated with the low risk of T2DM under dominant and allelic genetic models. Subgroup analysis by ethnicity showed that the LPL S447X polymorphism was associated with a decreased risk of T2DM in the Asian population (under dominant, heterozygous and allelic genetic models). In addition, we found that X allele carriers of S447X polymorphism is associated with low levels of TC, TG, and LDL. In subgroup analysis, Hind III polymorphism was associated with low risk of T2DM in Asian populations (under dominant, heterozygote, allele genetic models). Moreover, the carriers of H allele of Hind III have lower levels of TG, and higher levels of HDL-C. This meta-analysis demonstrated that 447X carriers and H allele in LPL gene associated with low risk of T2DM, which may due to in part to the change of serum level of TC, TG, LDL, and HDL.
Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection

Whether dietary omega-3 (n-3) polyunsaturated fatty acid (PUFA) confers cardiac benefit in cardiometabolic disorders is unclear. We test whether dietary α-linolenic acid (ALA) enhances myocardial resistance to ischemia-reperfusion (I-R) and responses to ischemic preconditioning (IPC) in type 2 diabetes (T2D); and involvement of conventional PUFA-dependent mechanisms (caveolins/cavins, kinase signaling, mitochondrial function, and inflammation). Eight-week male C57Bl/6 mice received streptozotocin (75 mg/kg) and 21 weeks high-fat/high-carbohydrate feeding. Half received ALA over six weeks. Responses to I-R/IPC were assessed in perfused hearts. Localization and expression of caveolins/cavins, protein kinase B (AKT), and glycogen synthase kinase-3β (GSK3β); mitochondrial function; and inflammatory mediators were assessed. ALA reduced circulating leptin, without affecting body weight, glycemic dysfunction, or cholesterol. While I-R tolerance was unaltered, paradoxical injury with IPC was reversed to cardioprotection with ALA. However, post-ischemic apoptosis (nucleosome content) appeared unchanged. Benefit was not associated with shifts in localization or expression of caveolins/cavins, p-AKT, p-GSK3β, or mitochondrial function. Despite mixed inflammatory mediator changes, tumor necrosis factor-a (TNF-a) was markedly reduced. Data collectively reveal a novel impact of ALA on cardioprotective dysfunction in T2D mice, unrelated to caveolins/cavins, mitochondrial, or stress kinase modulation. Although evidence suggests inflammatory involvement, the basis of this “un-conventional” protection remains to be identified.
Status and prospects of marine NIS detection and monitoring through (e)DNA metabarcoding

In coastal ecosystems, non-indigenous species (NIS) are recognized as a major threat to biodiversity, ecosystem functioning and socio-economic activities. Here we present a systematic review on the use of metabarcoding for NIS surveillance in marine and coastal ecosystems, through the analysis of 42 publications. Metabarcoding has been mainly applied to environmental DNA (eDNA) from water samples, but also to DNA extracted from bulk organismal samples. DNA extraction kits have been widely used and the 18S rRNA and the COI genes the most employed markers, but less than half of the studies targeted more than one marker loci. The Illumina MiSeq platform has been used in >50% of the publications. Current weaknesses include potential occurrence of false negatives due to the primer-biased or faulty DNA amplification and the incompleteness of reference libraries. This is particularly concerning in the case of NIS surveillance, where proficiency in species level detection is critical. Until these weaknesses are resolved, ideally NIS metabarcoding should be supported by complementary approaches, such as morphological analysis or more targeted molecular approaches (e.g. qPCR, ddPCR). Even so, metabarcoding has already proved to be a highly sensitive tool to detect small organisms or undifferentiated life stages across a wide taxonomic range. In addition, it also seems to be very effective in ballast water management and to improve the spatial and temporal sampling frequency of NIS surveillance in marine and coastal ecosystems. Although specific protocols may be required for species-specific NIS detection, for general monitoring it would be vital to settle on a standard protocol able to generate comparable results among surveillance campaigns and regions of the globe, seeking the best approach for detecting the broadest range of species, while minimizing the chances of a false positive or negative detection.
Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats

Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes.
Comparison of DL-Methionine, DL-Methionine-Na, DL-Methionine Hydroxy Analogue-Ca, and DL-Methionine Hydroxy Analogue-Free Acid with Layers

Abstract Two 12-week trials with laying hens were conducted to compare the effectiveness of DL-methionine, DL-methionine-Na, DL-methionine hydroxy analogue-Ca (MHA-Ca) and DL-methionine hydroxy analogue-free acid (MHA-FA) with a practical type basal diet deficient in sulfur amino acids. In the first experiment, DL-MHA-Ca was compared with DL-methionine at molar equivalent methionine levels of . 05, . 10, . 15, and . 20%. On a composite basis, feed conversion efficiency of the DL-methionine fed birds was slightly but significantly superior to that of the MHA-Ca fed birds. In the second experiment, DL-methionine, DL-methionine-Na and MHA-FA were tested, each at molar equivalent methionine levels of . 05 and . 10%. DL-Methionine and DL-methionine-Na produced similar laying hen performance; performance of hens fed the MHA-FA supplemental diets was distinctly inferior to that of birds fed the other two methionine sources.
Cross-talk of signalling cascades in the modulation of presynaptic extracellular signal-regulated protein kinase 1 and 2 function

Activation of extracellular signal-regulated protein kinases (ERK1/2) has emerged as a key signalling event in the modulation of presynaptic plasticity by neurotrophic factors. In this study, we investigated the cross-talk between presynaptic signalling pathways activating PKA or PKC and ERK signalling, underlying the modulation of neurotransmitter release. Purified, isolated cerebrocortical nerve terminals and phosphorylation state-specific antibodies were used to carry out this research. Stimulation of PKA by cAMP, produced in response to p-adrenoreceptor activation by isoproterenol, or direct stimulation of adenylyl cyclase by forskolin, resulted in a substantial increase in ERK phosphorylation/activity. Similarly, stimulation of PKC, by PDBu, also led to stimulation of ERK phosphorylation/activity. Metabotropic glutamate receptor activation by the Group I agonist DHPG, however, led to ERK1/2 phosphorylation which showed a Ca2+ -dependency, though the role of PKC was less clearly defined. A key effector molecule for the regulation of neurotransmitter release by ERK activation is the small synaptic vesicle (SSV) protein synapsin I, which, through alteration in its phosphorylation-state, modulates SSV-actin cytoskeleton interactions and thereby controls the distribution of SSVs between release pools. Accordingly, with both PKA and PKC activation of ERKs, the downstream stimulation of synapsin phosphorylation at specific ERK-dependent sites was also detected. These results suggest that, together with the established roles of PKA and PKC acting on ion- channel targets to modulate of presynaptic excitability and/or voltage-dependent Ca-entry, downstream of these loci, the two kinase cascades may converge at the level of SSV mobilization to regulate the efficacy of glutamate release from cerebrocortical nerve terminals.
Nascent nephrons during human embryonic development: Spatial distribution and relationship with urinary collecting system

The two major components of the metanephros, the urinary collecting system (UCS) and nephron, have different developmental courses. Nephron numbers vary widely between species and individuals and are determined during fetal development. Furthermore, the development of nascent nephrons may contribute to the expansion of the proximal part of the UCS. This study investigated the distribution of nascent nephrons and their interrelationship with UCS branches during human embryogenesis. We obtained samples from 31 human embryos between Carnegie stages (CSs) 19 and 23 from the Kyoto Collection at the Congenital Anomaly Research Center of Kyoto University in Japan. Serial histological sections of the metanephros with the UCS were digitalized and computationally reconstructed for morphological and quantitative analyses. The three‐dimensional (3D) coordinates for the positions of all UCS branch points, end points, attachment points to nascent nephrons (APs), and renal corpuscles (RCs) were recorded and related to the developmental phase. Phases were categorized from phase 1 to phase 5 according to the histological analysis. The UCS branching continued until RCs first appeared (at CS19). End branches with attached nascent nephrons (EB‐AP[+]) were observed after CS19 during the fifth generation or higher during the embryonic period. The range of end branch and EB‐AP(+) generation numbers was broad, and the number of RCs increased with the embryonic stage, reaching 273.8 ± 104.2 at CS23. The number of RCs connected to the UCS exceeded the number not connected to the UCS by CS23. The 3D reconstructions revealed RCs to be distributed around end branches, close to the surface of the metanephros. The RCs connected to the UCS were located away from the surface. The APs remained near the end point, whereas connecting ducts that become renal tubules were found to elongate with maturation of the RCs. Nascent nephrons in RC phases 3‐5 were preferentially attached to the end branches at CS22 and CS23. The mean generation number of EB‐AP(−) was higher than that of EB‐AP(+) in 19 of 22 metanephros and was statistically significant for eight metanephros at CS22 and CS23. The ratio of the deviated branching pattern was almost constant (29%). The ratio of the even branching pattern with EB‐AP(+) and EB‐AP(+) to the total even branching pattern increased with CS (9.2% at CS21, 19.2% at CS22, and 45.4% at CS23). Our data suggest the following: EB‐AP(+) may not branch further at the tip (i.e., by tip splitting), but branching beneath the AP (lateral branching) continues throughout the embryonic stages. Our study provides valuable data that can further the understanding of the interactions between the UCS and nascent nephrons during human embryogenesis.
Tissue‐engineered vessel derived from human fibroblasts with an electrospun scaffold

Advanced cardiovascular disease often requires surgical revascularization for small diameter arterial bypass procedures, and there is a need for alternative grafts in those patients lacking autologous vein. A decellularized biological vessel with the characteristics of a small artery and the ability to remodel in vivo could replace currently available bypass grafts. In this study, a biodegradable electrospun scaffold was specifically designed to be placed in a biomimetic perfusion system to generate a tissue‐engineered vessel from human dermal fibroblasts. The polyglycolic acid electrospun scaffold was co‐electrosprayed with a sacrificial porogen microparticle, polyethylene oxide, to increase porosity and pore size. After a 10‐week culture period in the biomimetic system, the tissue‐engineered vessel derived from human fibroblasts was further processed with decellularization to form an allogeneic tissue‐engineered vessel. The tissue‐engineered vessel had a similar morphology by histological staining for collagen and elastin before and after decellularization. The mechanical properties (burst pressure, ultimate tensile strength, and elastic modulus) remained stable after decellularization and were on the same magnitude as a human saphenous vein. The decellularization processing demonstrated no loss of collagen, near complete removal of DNA, and no presence of intracellular proteins. The decellularized tissue‐engineered vessel supported the growth of endothelial cells on the surface, and fibroblasts were able to migrate into the midportion of the matrix. Therefore, an electrospun scaffold provides a versatile biomaterial to create a decellularized tissue‐engineered vessel derived from human dermal fibroblasts with morphological and mechanical properties for use as a small diameter vascular graft.
Different trapping schemes and variable disturbance intensity do not affect hatching success of Whiskered Terns Chlidonias hybrida

Capsule In the Whiskered Tern Chlidonias hybrida, hatching success was similar at nests where both parents were caught during the same trapping session and nests where parents were caught on different days. Trapping both mates during the same session may represent an efficient approach to reduce fieldwork effort, but it should be preceded by a pilot study, confirming that it does not affect breeding success.
Minimising effort in large-scale surveys of terrestrial birds: an example from the English uplands

In 1990 a complete survey of the south Pennines in England (covering 725 km2) was used to estimate the population sizes of ten species of upland breeding birds. We investigate whether survey effort could have been reduced by using a sample based approach. Random sampling could have produced large reductions in survey effort for Curlew Numenius arquata, Golden Plover Pluvialis apricaria and Red Grouse Lagopus lagopus scoticus, which tended to be relatively evenly distributed across the region. A random sample of less than 50% of the study area could estimate the populations of these species to within 10% of the value obtained through the complete survey. Whinchat Saxicola rubetra and Twite Acanthis flavirostris tended to be locally common and so over 80% of the study area would need to be surveyed to provide equivalent population estimates for these species. Regression sampling could not reduce survey effort significantly in comparison with random sampling, because species-environment correlations tended to be relatively low. The largest reduction in survey effort occurred for Golden Plover in association with the distance to the moor edge in which a 41% regression sample had an equivalent accuracy to a 47% random sample. Stratified sampling could produce the largest reductions in survey effort when the allocation of survey effort to individual strata was related both to strata size and to the variation of bird numbers within strata. Reductions in survey effort of over 25% in comparison with random sampling were obtained for Dunlin Calidris alpina stratified by percent moorland, and Twite stratified by northing. No single environmental variable could provide the most efficient means of stratification for all species. We discuss the choice of sampling strategy for different bird species and given different survey objectives, and consider how the results obtained in the south Pennines may be used to determine appropriate sampling strategies in other regions.
Machine-Learning Based Temperature Compensation For Guided WaveImaging In Structural Health Monitoring

In Guided Wave (GW) Structural Health Monitoring (SHM), a baseline, i.e. a set of measurements taken on the inspected structure in a pristine state, is often required to separate the contributions of the defect(s) from the other propagating wave packets. Due to the sensitivity of GWs to Environmental and Operational Conditions (OECs), most GW-SHM techniques are limited in terms of range of applicability [1]. More specifically, the inspection of the unknown state must be conducted under the same EOCs as the ones of the pristine state. Besides measuring baselines on the structure under all the EOCs of interest, which is prohibitively expensive, a potential solution is to compensate the EOC effects on the measured signals. Several solutions in the literature, such as Baseline Signal Stretch [2] and Dynamic Time Warping [3], have been proposed to solve this problem, but are somewhat limited in terms of amplitude of compensation or range of application. In this paper, a model-based machine learning procedure to compensate the measured signals in an unknown state and known EOCs is presented. The compensation model is trained on experimental data acquired at various temperatures on a structure representative of the one of interest. In other words, an experiment under various EOCs must be conducted on a simplified version of the structure with at least two transducers. Material and transducers of the simplified experiment must be identical to the ones of the real structure, but the actual geometry might differ. The compensated signals are then used to conduct guided wave imaging, allowing immediate defect detection and localization. Results are shown for both aluminum and composite panels.