Yersinia pestis was introduced to Brazil during the third plague pandemic and currently exists in several recognized foci. There is currently limited available phylogeographic data regarding Y. pestis in Brazil. We generated whole genome sequences for 411 Y. pestis strains from six Brazilian foci to investigate the phylogeography of Y. pestis in Brazil; these strains were isolated from 1966 to 1997. All 411 strains were assigned to a single monophyletic clade within the 1.ORI population, indicating a single Y. pestis introduction was responsible for the successful establishment of endemic foci in Brazil. There was a moderate level of genomic diversity but little population structure among the 411 Brazilian Y. pestis strains, consistent with a radial expansion wherein Y. pestis spread rapidly from the coast to the interior of Brazil and became ecologically established. Overall, there were no strong spatial or temporal patterns among the Brazilian strains. However, strains from the same focus tended to be more closely related and strains isolated from foci closer to the coast tended to fall in more basal positions in the whole genome phylogeny than strains from more interior foci. Overall, the patterns observed in Brazil are similar to other locations affected during the 3rd plague pandemic such as in North America and Madagascar.

High optical resolution in microscopy usually goes along with costly hardware components, such as lenses, mechanical setups and cameras. Several studies proved that Single Molecular Localization Microscopy can be made affordable, relying on off-the-shelf optical components and industry grade CMOS cameras. Recent technological advantages have yielded consumer-grade camera devices with surprisingly good performance. The camera sensors of smartphones have benefited of this development. Combined with computing power smartphones provide a fantastic opportunity for "imaging on a budget". Here we show that a consumer cellphone is capable of optical super-resolution imaging by (direct) Stochastic Optical Reconstruction Microscopy (dSTORM), achieving optical resolution better than 80 nm. In addition to the use of standard reconstruction algorithms, we used a trained image-to-image generative adversarial network (GAN) to reconstruct video sequences under conditions where traditional algorithms provide sub-optimal localization performance directly on the smartphone. We believe that "cellSTORM" paves the way to make super-resolution microscopy not only affordable but available due to the ubiquity of cellphone cameras.

Information on extrapulmonary TB (EPTB) patients is limited in many African countries including Ghana. The study objective was to describe the epidemiology of EPTB patients diagnosed from different categories of health facilities in Accra, Ghana compared to pulmonary TB (PTB) patients and identify risk factors for mortality among EPTB patients.

Seabirds and pinnipeds play an important role in biogeochemical cycling by transferring nutrients from aquatic to terrestrial environments. Indeed, soils rich in animal depositions have generally high organic carbon, nitrogen and phosphorus contents. Several studies have assessed bacterial diversity in Antarctic soils influenced by marine animals; however most have been conducted in areas with significant human impact. Thus, we chose Cape Shirreff, Livingston Island, an Antarctic Specially Protected Area designated mainly to protect the diversity of marine vertebrate fauna, and selected sampling sites with different types of animals coexisting in a relatively small space, and where human presence and impact are negligible. Using 16S rRNA gene analyses through massive sequencing, we assessed the influence of animal concentrations, via their modification of edaphic characteristics, on soil bacterial diversity and composition. The nutrient composition of soils impacted by Antarctic fur seals and kelp gulls was more similar to that of control soils (i.e. soils without visible presence of plants or animals), which may be due to the more active behaviour of these marine animals compared to other species. Conversely, the soils from concentrations of southern elephant seals and penguins showed greater differences in soil nutrients compared to the control. In agreement with this, the bacterial communities of the soils associated with these animals were most different from those of the control soils, with the soils of penguin colonies also possessing the lowest bacterial diversity. However, all the soils influenced by the presence of marine animals were dominated by bacteria belonging to Gammaproteobacteria, particularly those of the genus Rhodanobacter. Therefore, we conclude that the modification of soil nutrient composition by marine vertebrates promotes specific groups of bacteria, which could play an important role in the recycling of nutrients in terrestrial Antarctic ecosystems.

Contact networks can be used to assess disease spread potential within a population. However, the data required to generate the networks can be challenging to collect. One method of collecting this type of data is by using radio-frequency identification (RFID) tags. The OpenBeacon RFID system generally consists of tags and readers. Communicating tags should be within 10m of the readers, which are powered by an external power source. The readers are challenging to implement in agricultural settings due to the lack of a power source and the large area needed to be covered.

Cardiorespiratory fitness is inversely associated with a high risk of cardiovascular disease, all-cause mortality, and mortality attributable to various cancers. It is often estimated indirectly using mathematical formulas for estimating oxygen uptake. Cardiopulmonary exercise testing, especially oxygen uptake, represents the "gold standard" for assessing exercise capacity. The purpose of this report was to develop reference standards for exercise capacity by establishing cardiorespiratory fitness values derived from cardiopulmonary exercise testing in a Brazilian population. We focused on oxygen uptake standards and compared the maximal oxygen uptake [mLO2·kg-1·min-1] values with those in the existing literature.

The rapid increase in transcriptome data provides an opportunity to access the complex regulatory mechanisms in cellular systems through gene association network (GAN). Nonetheless, GANs derived from single datasets generally allow us to envisage only one side of the regulatory network, even under the particular condition of study. The circumstance is well demonstrated by inconsistent GANs of individual datasets proposed for similar experimental conditions, which always leads to ambiguous interpretation. Here, pan- and core-gene association networks (pan- and core-GANs), analogous to the pan- and core-genome concepts, are proposed to increase the power of inference through the integration of multiple, diverse datasets. The core-GAN represents the consensus associations of genes that were inferred from all individual networks. On the other hand, the pan-GAN represents the extensive gene-gene associations that occurred in each individual network. The pan- and core-GANs prospects were demonstrated based on three time series microarray datasets in leaves of Arabidopsis thaliana grown under diurnal conditions. We showed the overall performance of pan- and core-GANs was more robust to the number of data points in gene expression data compared to the GANs inferred from individual datasets. In addition, the incorporation of multiple data broadened our understanding of the biological regulatory system. While the pan-GAN enabled us to observe the landscape of gene association system, core-GAN highlighted the basic gene-associations in essence of the regulation regulating starch metabolism in leaves of Arabidopsis.

Surveys indicate that patients, particularly those suffering from chronic conditions, strongly benefit from the information found in social networks and online forums. One challenge in accessing online health information is to differentiate between factual and more subjective information. In this work, we evaluate the feasibility of exploiting lexical, syntactic, semantic, network-based and emotional properties of texts to automatically classify patient-generated contents into three types: "experiences", "facts" and "opinions", using machine learning algorithms. In this context, our goal is to develop automatic methods that will make online health information more easily accessible and useful for patients, professionals and researchers.

Citizen science and data collected from various volunteers have an interesting potential in aiding the understanding of many biological and ecological processes. We describe a mobile application that allows the public to map and report occurrences of the odonata species (dragonflies and damselflies) found in the Czech Republic. The application also helps in species classification based on observation details such as date, GPS coordinates, and the altitude, biotope, suborder, and colour. Dragonfly Hunter CZ is a free Android application built on the open-source framework NativeScript using the JavaScript programming language which is now fully available on Google Play. The server side is powered by Apache Server with PHP and MariaDB SQL database. A mobile application is a fast and accurate way to obtain data pertaining to the odonata species, which can be used after expert verification for ecological studies and conservation basis like Red Lists and policy instruments. We expect it to be effective in encouraging Citizen Science and in promoting the proactive reporting of odonates. It can also be extended to the reporting and monitoring of other plant and animal species.

Rift Valley fever (RVF) is one of the major viral zoonoses in Africa, affecting humans and several domestic animal species. The epidemics in eastern Africa occur in a 5-15 year cycle coinciding with abnormally high rainfall generally associated to the warm phase of the El Niño event. However, recently, evidence has been gathered of inter-epidemic transmission. An open-source, easily applicable, accessible and modifiable model was built to simulate the transmission dynamics of RVF. The model was calibrated using data collected in the Kilombero Valley in Tanzania with people and cattle as host species and Ædes mcintoshi, Æ. ægypti and two Culex species as vectors. Simulations were run over a period of 27 years using standard parameter values derived from two previous studies in this region. Our model predicts low-level transmission of RVF, which is in line with epidemiological studies in this area. Emphasis in our simulation was put on both the dynamics and composition of vector populations in three ecological zones, in order to elucidate the respective roles played by different vector species: the model output did indicate the necessity of Culex involvement and also indicated that vertical transmission in Ædes mcintoshi may be underestimated. This model, being built with open-source software and with an easy-to-use interface, can be adapted by researchers and control program managers to their specific needs by plugging in new parameters relevant to their situation and locality.

Folate metabolism is essential for DNA synthesis and a validated drug target in fast-growing cell populations, including tumors and malaria parasites. Genome data suggest that Plasmodium has retained its capacity to generate folates de novo. However, the metabolic plasticity of folate uptake and biosynthesis by the malaria parasite remains unresolved. Here, we demonstrate that Plasmodium uses an aminodeoxychorismate synthase and an aminodeoxychorismate lyase to promote the biogenesis of the central folate precursor para-aminobenzoate (pABA) in the cytoplasm. We show that the parasite depends on de novo folate synthesis only when dietary intake of pABA by the mammalian host is restricted and that only pABA, rather than fully formed folate, is taken up efficiently. This adaptation, which readily adjusts infection to highly variable pABA levels in the mammalian diet, is specific to blood stages and may have evolved to avoid folate competition between the parasite and its host.

Rare mutations in TARDBP, the gene encoding TDP-43, cause amyotrophic lateral sclerosis (ALS), and TDP-43 pathology is seen in a large majority of ALS patients, suggesting a central pathogenic role of this regulatory protein. The consequences of TARDBP mutations on TDP-43 function and the mechanism by which mutant TDP-43 causes neurodegeneration remain uncertain. Here, we characterize a series of knockin mice carrying disease-associated TARDBP mutations. We demonstrate that TDP-43M337V and TDP-43G298S are functional, each rescuing the lethality of TDP-43 loss of function. In a subset of aged heterozygous knockin mice, we observe the earliest signs of selective motor neuron degeneration, demonstrating that physiological levels of mutant TDP-43 are sufficient to initiate disease. Furthermore, aged homozygous mutants develop selective, asymmetric motor neuron pathology, providing in vivo evidence of TDP-43 dose-dependent neurotoxicity. These knockin mice represent a faithful in vivo model of early-stage ALS and enable future exploration of TDP-43-associated neurodegeneration.

MicroRNA (miRNA) processing begins with Drosha cleavage, the fidelity of which is critical for downstream processing and mature miRNA target specificity. To understand how pri-miRNA sequence and structure influence Drosha cleavage, we studied the maturation of three pri-miR-9 paralogs, which encode the same mature miRNA but differ in the surrounding scaffold. We show that pri-miR-9-1 has a unique Drosha cleavage profile due to its distorted and flexible stem structure. Cleavage of pri-miR-9-1, but not pri-miR-9-2 or pri-miR-9-3, generates an alternative miR-9 with a shifted seed sequence that expands the scope of its target RNAs. Analyses of low-grade glioma patient samples indicate that the alternative-miR-9 has a potential role in tumor progression. Furthermore, we provide evidence that distortion of pri-miRNA stems induced by asymmetric internal loops correlates with Drosha cleavage at non-canonical sites. Our studies reveal that pri-miRNA paralogs can have distinct functions via differential Drosha processing.

The 26S proteasome is the central ATP-dependent protease in eukaryotes and is essential for organismal health. Proteasome assembly is mediated by several dedicated, evolutionarily conserved chaperone proteins. These chaperones associate transiently with assembly intermediates but are absent from mature proteasomes. Chaperone eviction upon completion of proteasome assembly is necessary for normal proteasome function, but how they are released remains unresolved. Here, we demonstrate that the Nas6 assembly chaperone, homolog of the human oncogene gankyrin, is evicted from nascent proteasomes during completion of assembly via a conformation-specific allosteric interaction of the Rpn5 subunit with the proteasomal ATPase ring. Subsequent ATP binding by the ATPase subunit Rpt3 promotes conformational remodeling of the ATPase ring that evicts Nas6 from the nascent proteasome. Our study demonstrates how assembly-coupled allosteric signals promote chaperone eviction and provides a framework for understanding the eviction of other chaperones from this biomedically important molecular machine.

Both endoplasmic reticulum (ER) stress and autophagy involve in the pathological process of Parkinson's disease (PD). But the relationship between them is not clear in PD. A 6-OHDA-induced parkinsonian rat is recognized as a standard model for many years, and it can be used in experimental study. The glucose regulated protein 78 (GRP78) is a master regulator of ER stress, and the C/EBP homologous binding protein (CHOP) is an indicator of the UPR signaling. Besides, the Beclin-1 is also well known as a regulator of autophagy, and P62 is a specific marker to monitor autophagy. Therefore, we investigated the expressions of GRP78, CHOP, Beclin-1 and P62 in 6-OHDA-induced parkinsonian rat. Unilateral 6-OHDA injection into medial forebrain bundle was used except sham-operated rats. The rats were randomly divided into 6 groups: a sham-operated group; a model group; a 3-methyladenine (3-MA) group, administered 3-MA---autophagy inhibitor; a rapamycin group, administered rapamycin---autophagy inducer; a 4-phenylbutyric acids (4-PBA) group, administered 4-PBA---ER stress inhibitor; a tunicamycin (TM) group, administered TM---ER stress inducer. The results showed that the expressions of GRP78, CHOP and Beclin-1 increased, P62 decreased in model group; the expressions of GRP78 and CHOP were unchanged in 3-MA group and rapamycin group; but the expression of Beclin-1 decreased and P62 increased in 4-PBA group, while the expression of Beclin-1 increased and P62 decreased in TM group. These data suggest that ER stress and autophagy occurred in 6-OHDA-induced parkinsonian rat, and ER stress might induce autophagy. The result is important for the pathological mechanism of PD.

Improved capacity of genomics and biotechnology has greatly enhanced genetic studies in different areas. Genomic selection exploits the genotype-to-phenotype relationship at the whole-genome level and is being implemented in many crops. Here we show that design-thinking and data-mining techniques can be leveraged to optimize genomic prediction of hybrid performance. We phenotyped a set of 276 maize hybrids generated by crossing founder inbreds of nested association mapping populations for flowering time, ear height, and grain yield. With 10 296 310 SNPs available from the parental inbreds, we explored the patterns of genomic relationships and phenotypic variation to establish training samples based on clustering, graphic network analysis, and genetic mating scheme. Our analysis showed that training set designs outperformed random sampling and earlier methods that either minimize the mean of prediction error variance or maximize the mean of generalized coefficient of determination. Additional analyses of 2556 wheat hybrids from an early-stage hybrid breeding system and 1439 rice hybrids from an established hybrid breeding system validated the approaches. Together, we demonstrated that effective genomic prediction models can be established with a training set 2%-13% of the size of the whole set, enabling an efficient exploration of enormous inference space of genetic combinations.

AGel amyloidosis, formerly known as familial amyloidosis of the Finnish-type, is caused by pathological aggregation of proteolytic fragments of plasma gelsolin. So far, four mutations in the gelsolin gene have been reported as responsible for the disease. Although D187N is the first identified variant and the best characterized, its structure has been hitherto elusive. Exploiting a recently-developed nanobody targeting gelsolin, we were able to stabilize the G2 domain of the D187N protein and obtained, for the first time, its high-resolution crystal structure. In the nanobody-stabilized conformation, the main effect of the D187N substitution is the impairment of the calcium binding capability, leading to a destabilization of the C-terminal tail of G2. However, molecular dynamics simulations show that in the absence of the nanobody, D187N-mutated G2 further misfolds, ultimately exposing its hydrophobic core and the furin cleavage site. The nanobody's protective effect is based on the enhancement of the thermodynamic stability of different G2 mutants (D187N, G167R and N184K). In particular, the nanobody reduces the flexibility of dynamic stretches, and most notably decreases the conformational entropy of the C-terminal tail, otherwise stabilized by the presence of the Ca2+ ion. A Caenorhabditis elegans-based assay was also applied to quantify the proteotoxic potential of the mutants and determine whether nanobody stabilization translates into a biologically relevant effect. Successful protection from G2 toxicity in vivo points to the use of C. elegans as a tool for investigating the mechanisms underlying AGel amyloidosis and rapidly screen new therapeutics.

The use of titanium suboxides, known as Magnéli phase TiOx, is expected to increase in the near future due to their desirable properties. In order to use Magnéli phase TiOx nanoparticles safely, it is necessary to know how nanoparticles interact with biological systems. In this study, the cytotoxicity of three different Magnéli TiOx nanoparticles was evaluated using human lung A549 cells and the results were compared with hazard data on two different TiO₂ nanoparticles whose biological interactions have already been extensively studied. After A549 cells were exposed to nanoparticles, the metabolic activity was measured by the Resazurin assay, the amount of cellular proteins was measured by the Coomassie Blue assay, and lysosomal integrity was measured by the Neutral Red Uptake assay. In order to investigate possible modes of particle actions, intracellular Ca2+ level, reactive oxygen species (ROS) production, and photo-oxidative disruptions of lysosomal membranes were assessed. All experiments were performed in serum-containing and in serum-deprived cell culture mediums. In addition, the photocatalytic activity of Magnéli TiOx and TiO₂ nanoparticles was measured. The results show that Magnéli TiOx nanoparticles increase intracellular Ca2+ but not ROS levels. In contrast, TiO₂ nanoparticles increase ROS levels, resulting in a higher cytotoxicity. Although Magnéli TiOx nanoparticles showed a lower UV-A photocatalytic activity, the photo-stability of the lysosomal membranes was decreased by a greater extent, possibly due to particle accumulation inside lysosomes. We provide evidence that Magnéli TiOx nanoparticles have lower overall biological activity when compared with the two TiO₂ formulations. However, some unique cellular interactions were detected and should be further studied in line with possible Magnéli TiOx application. We conclude that Magnéli phase nanoparticles could be considered as low toxic material same as other forms of titanium oxide particles.

The development of biomaterials with the potential to accelerate wound healing is a great challenge in biomedicine. In this study, four types of samples including pepsin soluble collagen sponge (PCS), acid soluble collagen sponge (ACS), bovine collagen electrospun I (BCE I) and bovine collagen electrospun II (BCE II) were used as wound dressing materials. We showed that the PCS, ACS, BCE I and BCE II treated rats increased the percentage of wound contraction, reduced the inflammatory infiltration, and accelerated the epithelization and healing. PCS, ACS, BCE I, and BCE II significantly enhanced the total protein and hydroxyproline level in rats. ACS could induce more fibroblasts proliferation and differentiation than PCS, however, both PCS and ACS had a lower effect than BCE I and BCE II. PCS, ACS, BCE I, and BCE II could regulate deposition of collagen, which led to excellent alignment in the wound healing process. There were similar effects on inducing the level of cytokines including EGF, FGF, and vascular endothelial marker CD31 among these four groups. Accordingly, this study disclosed that collagens (PCS and ACS) from tilapia skin and bovine collagen electrospun (BCE I and BCE II) have significant bioactivity and could accelerate wound healing rapidly and effectively in rat model.

Trait variation among natural populations and their cultivated relatives occurs due to evolutionary forces, including selection and drift. In the present study, we analyzed these forces at the locus level in a global barley diversity set using population genetics analysis. Genome-wide outlier loci detection found a locus on chromosome 2H at which a common single nucleotide polymorphism (SNP) marker SCRI_RS_170235 accounted for the highest diversity index (Fst) values between cultivars and landraces and between cultivars and wild accessions. For a population wide genetic analysis, we developed a Polymerase Chain Reaction (PCR)-based cleaved amplified polymorphic marker at the identified locus. Marker genotyping of 115 genotypes identified a characteristic distribution of polymorphisms among the cultivated, landraces, and wild barley accessions. Using this marker, we screened a library of wild barley introgression lines (IL) and selected IL S42IL-109 that carried the wild introgression of the outlier locus in cultivar 'Scarlett' background. A plethora of phenotypic evaluation was performed between the S42IL109 and 'Scarlett' to dissect the putative effect of the identified outlier locus. Comparison of S42IL109 and 'Scarlett' revealed significant difference in the development of phyllochron two (Phyl-2), phyllochron three (Phyl-3), and phyllochron four (Phyl-4). Across the three phyllochrons, it was consistently observed that S42IL109 developed successive leaves in a shorter time span, by one to two days, compared to 'Scarlett'. These data suggest that outlier locus may influence phyllochron variation which underwent positive selection in barley.