Miracle-dz/UniFAR-FTUs huggingface dataset:
Path Planning with Forests of Random Trees: Parallelization with Super Linear Speedup ; CU-

We propose a new parallelized high-dimensional single-query path planning technique that uses a coupled forest of random trees (i.e., instead of a single tree). We present both theoretical and experimental results that show using forests of random trees can lead to expected super linear speedup, with respect to the number of trees in the forest. In other words, with T trees running in parallel, we expect to get a particular quality result in less than 1/T the time required by a single tree (this is also known as having efficiency greater than 1). Our algorithm works by linking the random sampling and pruning mechanisms of all trees in the forest to the length of the current best path found by any tree. This enables all trees to avoid sampling from large portions of the configuration space that cannot possibly lead to better solutions, and increases speed by enabling trees to prune obsolete nodes. The current best solution is also passed between trees, so that it may be improved by any tree in the forest. Given the potential of super linear speedup, we additionally propose a sequential version of the forest algorithm that works by dividing computation time between each of T trees. We perform a series of experiments and find that both the parallel and sequential versions of the forest algorithm perform well in practice (e.g., vs. a single tree or smaller forests). To demonstrate that our algorithm is generally applicable, experiments are performed using two different state-of-the-art random tree algorithms for the underlying random trees. Theoretical analysis suggest that these results can be duplicated for any random tree path planning algorithm that meets a few requirements stated in the paper.
Long noncoding RNA: multiple players in gene expression

Previously considered as a component of transcriptional noise, long noncoding RNAs (lncRNAs) were neglected as a therapeutic target, however, recently increasing evidence has shown that lncRNAs can participate in numerous biological processes involved in genetic regulation including epigenetic, transcriptional, and post-transcriptional regulation. In this review, we discuss the fundamental functions of lncRNAs at different regulatory levels and their roles in metabolic balance. Typical examples are introduced to illustrate their diverse molecular mechanisms. The comprehensive investigation and identification of key lncRNAs will not only contribute to insights into diseases, such as breast cancer and type II diabetes, but also provide promising therapeutic targets for related diseases.
Triazole Substitution of a Labile Amide Bond Stabilizes Pantothenamides and Improves Their Antiplasmodial Potency

ABSTRACT The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive in vivo. In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC50s) of ∼50 nM, and three others have submicromolar IC50s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds for its ability to interact with the Plasmodium falciparum pantothenate kinase, the first enzyme involved in the conversion of pantothenate to CoA, and show that the compound inhibits the phosphorylation of [14C]pantothenate by the P. falciparum pantothenate kinase, but the inhibition does not correlate with antiplasmodial activity. Furthermore, the compounds are not toxic to human cells and, importantly, are not degraded by pantetheinase.
Use of vitamin D supplements during infancy in an international feeding trial

Abstract Objective To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial. Design Longitudinal study. Setting Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months. Subjects Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia. Results Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements. Conclusions Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Zika virus epidemiology: from Uganda to world pandemic, an update

Abstract Zika virus (ZIKV) infection is an emergent worldwide public health problem. Historically, 84 countries have reported vector-borne ZIKV transmission, 61 of which report on-going transmission. It is a Flavivirus transmitted through arthropods belonging to the Aedes genus. Since 2015, ZIKV infections have increased dramatically; with 1.3 million people infected during 2015 in Brazil alone. This paper's objective is to highlight the conjectural epidemiological points of the virus’ dissemination. The digital archives Pubmed, MEDLINE, EMBASE and Cochrane were searched for papers that assessed aspects of ZIKV transmission and epidemiology. The first isolation occurred in Uganda in 1947. Since then, important outbreaks were documented globally. Consequently, an emergent public health problem arose from a rapidly increasing incidence and its association with the development of neurological diseases such as microcephaly and Guillain–Barré syndrome. Key factors in the successful containment of outbreaks include surveillance of mosquitos in the neighbourhood, an early mosquito control treatment, an assertive information campaign, and the involvement of the local population and healthcare workers. As such, while ZIKV seems to be spreading globally in a similar manner to other arboviruses, such as Dengue and Chikungunya viruses, it can also be rapidly contained due to the pre-existing availability of necessary resources and regulatory tools as control measures. This review aims to provide a description of those characteristics of ZIKV infection that may be useful in the construction of effective outbreak control strategies.
Protracted Regional Dissemination of GIM-1-Producing Serratia marcescens in Western Germany

ABSTRACT The metallo-beta-lactamase GIM-1 has been found in various bacterial host species nearly exclusively in western Germany. However, not much is known about the epidemiology of GIM-1-positive Serratia marcescens. Here we report on a surprisingly protracted regional dissemination. In-hospital transmission was investigated by using conventional epidemiological tools to identify spatiotemporal links. Strain typing was performed using pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). Bayesian phylogeny was used to infer the time axis of the observed occurrence. Thirteen S. marcescens strains from 10 patients from 6 different German hospitals were investigated. Suspected in-hospital transmissions were confirmed by molecular typing at a higher resolution by WGS than by PFGE. A detailed sequence analysis demonstrated the spread of one predominant strain variant but also provided evidence for transfer of the blaGIM-1 gene cassette between different strains. A Bayesian phylogenetic analysis showed that the most recent common ancestor of the identified clonal cluster could be dated back to April 1993 (95% highest posterior density interval, January 1973 to March 2003) and that this strain might have already harbored the blaGIM-1 at that time and, therewith, years before the first detection of this resistance gene in clinical specimens. This study shows a long-standing clonal and plasmid-mediated expansion of GIM-1-producing S. marcescens that might have gone unnoticed in the absence of a standardized and effective molecular screening for carbapenemases. The systematic and early detection of resistance is thus highly advisable, especially for the prevention of potentially long-term dissemination that may progress beyond control.
Vitamin D Combined with Resveratrol Prevents Cognitive Decline in SAMP8 Mice.

BACKGROUND Vitamin D (VD) and resveratrol (RSV) are two nutritional molecules that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. The senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of Alzheimer's disease (AD)-related memory impairment. OBJECTIVE We aimed to explore how the combination of vitamin D with resveratrol would affect memory impairments shown by SAMP8 mice, as well as the potential mechanisms. METHOD SAMP8 mice and their control senescence-accelerated mouse resistant 1 (SAMR1) mice (10 weeks old) were divided into 5 groups, i.e. SAMR1 group, SAMP8 group, SAMP8 mice supplemented with VD group, SAMP8 mice supplemented with RSV group and SAMP8 mice supplemented with both VD and RSV group. At the end of the intervention, Morris water maze (MWM) test was used to assess cognitive function. Hippocampus and parietal cortex were dissected for further analysis. RESULTS The combination of VD and RSV significantly increased time spent in target quadrant and the number of crossing via MWM test. In hippocampus, the combined intervention significantly reduced soluble Aβ42 level and BACE1 protein expression. In cortex, the combined treatment significantly reduced phosphorylation of tau at serine404 and p-p53, as well as enhanced p-CREB protein expression. The combination also significantly reduced GFAP and p-NFκB p65 in both hippocampus and cortex. CONCLUSION The combined intervention might exert greater neuroprotective effects in SAMP8 mice, this might be associated with the fact that the combined intervention could positively affect amyloidogenic pathways, neuroinflammation, tau phosphorylation and probably apoptosis markers.
Can Deliberately Incomplete Gene Sample Augmentation Improve a Phylogeny Estimate for the Advanced Moths and Butterflies (Hexapoda: Lepidoptera)?

Abstract This paper addresses the question of whether one can economically improve the robustness of a molecular phylogeny estimate by increasing gene sampling in only a subset of taxa, without having the analysis invalidated by artifacts arising from large blocks of missing data. Our case study stems from an ongoing effort to resolve poorly understood deeper relationships in the large clade Ditrysia ( > 150,000 species) of the insect order Lepidoptera (butterflies and moths). Seeking to remedy the overall weak support for deeper divergences in an initial study based on five nuclear genes (6.6 kb) in 123 exemplars, we nearly tripled the total gene sample (to 26 genes, 18.4 kb) but only in a third (41) of the taxa. The resulting partially augmented data matrix (45% intentionally missing data) consistently increased bootstrap support for groupings previously identified in the five-gene (nearly) complete matrix, while introducing no contradictory groupings of the kind that missing data have been predicted to produce. Our results add to growing evidence that data sets differing substantially in gene and taxon sampling can often be safely and profitably combined. The strongest overall support for nodes above the family level came from including all nucleotide changes, while partitioning sites into sets undergoing mostly nonsynonymous versus mostly synonymous change. In contrast, support for the deepest node for which any persuasive molecular evidence has yet emerged (78–85% bootstrap) was weak or nonexistent unless synonymous change was entirely excluded, a result plausibly attributed to compositional heterogeneity. This node (Gelechioidea + Apoditrysia), tentatively proposed by previous authors on the basis of four morphological synapomorphies, is the first major subset of ditrysian superfamilies to receive strong statistical support in any phylogenetic study. A “more-genes-only” data set (41 taxa×26 genes) also gave strong signal for a second deep grouping (Macrolepidoptera) that was obscured, but not strongly contradicted, in more taxon-rich analyses.
The ‘known’ genetic potential for microbial communities to degrade organic phosphorus is reduced in low‐pH soils

In soil, bioavailable inorganic orthophosphate is found at low concentrations and thus limits biological growth. To overcome this phosphorus scarcity, plants and bacteria secrete numerous enzymes, namely acid and alkaline phosphatases, which cleave orthophosphate from various organic phosphorus substrates. Using profile hidden Markov modeling approaches, we investigated the abundance of various non specific phosphatases, both acid and alkaline, in metagenomes retrieved from soils with contrasting pH regimes. This analysis uncovered a marked reduction in the abundance and diversity of various alkaline phosphatases in low‐pH soils that was not counterbalanced by an increase in acid phosphatases. Furthermore, it was also discovered that only half of the bacterial strains from different phyla deposited in the Integrated Microbial Genomes database harbor alkaline phosphatases. Taken together, our data suggests that these ‘phosphatase lacking’ isolates likely increase in low‐pH soils and future research should ascertain how these bacteria overcome phosphorus scarcity.
In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease

Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics.
SaxA-Mediated Isothiocyanate Metabolism in Phytopathogenic Pectobacteria

ABSTRACT Pectobacteria are devastating plant pathogens that infect a large variety of crops, including members of the family Brassicaceae. To infect cabbage crops, these plant pathogens need to overcome the plant's antibacterial defense mechanisms, where isothiocyanates are liberated by hydrolysis of glucosinolates. Here, we found that a Pectobacterium isolate from the gut of cabbage root fly larvae was particularly resistant to isothiocyanate and even seemed to benefit from the abundant Brassica root metabolite 2-phenylethyl isothiocyanate as a nitrogen source in an ecosystem where nitrogen is scarce. The Pectobacterium isolate harbored a naturally occurring mobile plasmid that contained a sax operon. We hypothesized that SaxA was the enzyme responsible for the breakdown of 2-phenylethyl isothiocyanate. Subsequently, we heterologously produced and purified the SaxA protein and characterized the recombinant enzyme. It hydrolyzed 2-phenylethyl isothiocyanate to yield the products carbonyl sulfide and phenylethylamine. It was also active toward another aromatic isothiocyanate but hardly toward aliphatic isothiocyanates. It belongs to the class B metal-dependent beta-lactamase fold protein family but was not, however, able to hydrolyze beta-lactam antibiotics. We discovered that several copies of the saxA gene are widespread in full and draft Pectobacterium genomes and therefore hypothesize that SaxA might be a new pathogenicity factor of the genus Pectobacterium, possibly compromising food preservation strategies using isothiocyanates.
Ethnic density of regions and psychiatric disorders among ethnic minority individuals

Background: Ethnic minorities form an increasingly large proportion of Canada’s population. Living in areas of greater ethnic density may help protect mental health among ethnic minorities through psychosocial pathways such as accessibility to culturally appropriate provision of mental health care, less discrimination and a greater sense of belonging. Mood and anxiety disorders are common psychiatric disorders. Aim: This study examined whether ethnic density of regions was related to mood and anxiety disorders among ethnic minorities in Canada. Method: Responses by ethnic minority individuals to the 2011–2014 administrations of the Canadian Community Health Survey (n = 33,201) were linked to health region ethnic density data. Multilevel logistic regression was employed to model the odds of having mood and/or anxiety disorders associated with increasing region-level ethnic density and to examine whether sense of community belonging helped explain variance in such associations. Analyses were adjusted for individual-level demographic factors as well as region-level socio-economic factors. Results: Higher ethnic density related to lower odds of mood and/or anxiety disorders for Canadian-born (but not foreign-born) ethnic minorities. Sense of community belonging did not help explain such associations, but independently related to lower odds of mood and/or anxiety disorders. These findings remained after adjusting for regional population density and after excluding (rural/remote) regions of very low ethnic density. Conclusion: Ethnic density of regions in Canada may be an important protective factor against mental illness among Canadian-born ethnic minorities. It is important to better understand how, and for which specific ethno-cultural groups, ethnic density may influence mental health.
Chemical regulation of body feather microbiota in a wild bird

The microbiota has a broad range of impacts on host physiology and behaviour, pointing out the need to improve our comprehension of the drivers of host–microbiota composition. Of particular interest is whether the microbiota is acquired passively, or whether and to what extent hosts themselves shape the acquisition and maintenance of their microbiota. In birds, the uropygial gland produces oily secretions used to coat feathers that have been suggested to act as an antimicrobial defence mechanism regulating body feather microbiota. However, our comprehension of this process is still limited. In this study, we for the first time coupled high‐throughput sequencing of the microbiota of both body feathers and the direct environment (i.e., the nest) in great tits with chemical analyses of the composition of uropygial gland secretions to examine whether host chemicals have either specific effects on some bacteria or nonspecific broad‐spectrum effects on the body feather microbiota. Using a network approach investigating the patterns of co‐occurrence or co‐exclusions between chemicals and bacteria within the body feather microbiota, we found no evidence for specific promicrobial or antimicrobial effects of uropygial gland chemicals. However, we found that one group of chemicals was negatively correlated to bacterial richness on body feathers, and a higher production of these chemicals was associated with a poorer body feather bacterial richness compared to the nest microbiota. Our study provides evidence that chemicals produced by the host might function as a nonspecific broad‐spectrum antimicrobial defence mechanism limiting colonization and/or maintenance of bacteria on body feathers, providing new insight about the drivers of the host's microbiota composition in wild organisms.
A score‐type test for heterogeneity in zero‐inflated models in a stratified population

We propose a score‐type statistic to evaluate heterogeneity in zero‐inflated models for count data in a stratified population, where heterogeneity is defined as instances in which the zero counts are generated from two sources. Evaluating heterogeneity in this class of models has attracted considerable attention in the literature, but existing testing procedures have primarily relied on the constancy assumption under the alternative hypothesis. In this paper, we extend the literature by describing a score‐type test to evaluate homogeneity against general alternatives that do not neglect the stratification information under the alternative hypothesis. The limiting null distribution of the proposed test statistic is a mixture of chi‐squared distributions that can be well approximated by a simple parametric bootstrap procedure. Our numerical simulation studies show that the proposed test can greatly improve efficiency over tests of heterogeneity that ignore the stratification information. An empirical application to dental caries data in early childhood further shows the importance and practical utility of the methodology in using the stratification profile to detect heterogeneity in the population. Copyright © 2014 John Wiley & Sons, Ltd.