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Nature Genetics

A Leoni Swart, Christopher F Harrison, Ludwig Eichinger, Michael Steinert, Hubert Hilbi
Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella -containing vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of "effector" proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit...
2018: Frontiers in Cellular and Infection Microbiology
Shang Wang, Manmohan Singh, Thuy Tien Tran, John Leach, Salavat R Aglyamov, Irina V Larina, James F Martin, Kirill V Larin
Myocardial infarction (MI) leads to cardiomyocyte loss, impaired cardiac function, and heart failure. Molecular genetic analyses of myocardium in mouse models of ischemic heart disease have provided great insight into the mechanisms of heart regeneration, which is promising for novel therapies after MI. Although biomechanical factors are considered an important aspect in cardiomyocyte proliferation, there are limited methods for mechanical assessment of the heart in the mouse MI model. This prevents further understanding the role of tissue biomechanics in cardiac regeneration...
February 1, 2018: Biomedical Optics Express
David Lopez, Sébastien Ribeiro, Philippe Label, Boris Fumanal, Jean-Stéphane Venisse, Annegret Kohler, Ricardo R de Oliveira, Kurt Labutti, Anna Lipzen, Kathleen Lail, Diane Bauer, Robin A Ohm, Kerrie W Barry, Joseph Spatafora, Igor V Grigoriev, Francis M Martin, Valérie Pujade-Renaud
Corynespora cassiicola is an Ascomycetes fungus with a broad host range and diverse life styles. Mostly known as a necrotrophic plant pathogen, it has also been associated with rare cases of human infection. In the rubber tree, this fungus causes the Corynespora leaf fall (CLF) disease, which increasingly affects natural rubber production in Asia and Africa. It has also been found as an endophyte in South American rubber plantations where no CLF outbreak has yet occurred. The C. cassiicola species is genetically highly diverse, but no clear relationship has been evidenced between phylogenetic lineage and pathogenicity...
2018: Frontiers in Microbiology
Tomas Linder
Fungi are well known for their metabolic versatility, whether it is the degradation of complex organic substrates or the biosynthesis of intricate secondary metabolites. The vast majority of studies concerning fungal metabolic pathways for sulfur assimilation have focused on conventional sources of sulfur such as inorganic sulfur ions and sulfur-containing biomolecules. Less is known about the metabolic pathways involved in the assimilation of so-called "alternative" sulfur sources such as sulfides, sulfoxides, sulfones, sulfonates, sulfate esters and sulfamates...
March 17, 2018: World Journal of Microbiology & Biotechnology
Heather L Howie, Xiaohong Wang, Linda Kapp, Jenna N Lebedev, James C Zimring
There are four subtypes of human IgG with different effector functions. Quantifying the relative amount of each IgG subtype is important for laboratory diagnosis in multiple settings. However, in an evolving landscape of the appreciation of human variability and the need for precision/personalised laboratory diagnosis, it has also been shown that there are numerous natural variants of IgG subtypes, with at least 29 having been described. It has recently been reported that commercially available polyclonal antisera to IgG3 cross react with variants of other IgG subtypes, while available monoclonal anti-IgG3 have a blind-spot for the IgG3-04 variant...
March 17, 2018: Journal of Clinical Pathology
Thomas Rey, Christophe Jacquet
Basic molecular knowledge on plant-pathogen interactions has largely been gained from reverse and forward genetics in Arabidopsis thaliana. However, as this model plant is unable to establish endosymbiosis with mycorrhizal fungi or rhizobia, plant responses to mutualistic symbionts have been studied in parallel in other plant species, mainly legumes. The resulting analyses led to the identification of gene networks involved in various functions, from microbe recognition to signalling and plant responses, thereafter assigned to either mutualistic symbiosis or immunity, according to the nature of the initially inoculated microbe...
March 15, 2018: Current Opinion in Plant Biology
Freek V W Appels, Jan Dijksterhuis, Catherine E Lukasiewicz, Kaspar M B Jansen, Han A B Wösten, Pauline Krijgsheld
Filamentous fungi colonize substrates by forming a mycelium. This network of hyphae can be used as a bio-based material. Here, we assessed the impact of environmental growth conditions and deletion of the hydrophobin gene sc3 on material properties of the mycelium of the mushroom forming fungus Schizophyllum commune. Thermogravimetric analysis showed that Δsc3 mycelium retained more water with increasing temperature when compared to the wild type. The Young's modulus (E) of the mycelium ranged between 438 and 913 MPa when the wild type strain was grown in the dark or in the light at low or high CO2 levels...
March 16, 2018: Scientific Reports
Dominik Brado, Adetayo Emmanuel Obasa, George Mondinde Ikomey, Ruben Cloete, Kamalendra Singh, Susan Engelbrecht, Ujjwal Neogi, Graeme Brendon Jacobs
HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatment-naive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2...
March 16, 2018: Scientific Reports
Neda Nemat-Gorgani, Hugo G Hilton, Brenna M Henn, Meng Lin, Christopher R Gignoux, Justin W Myrick, Cedric J Werely, Julie M Granka, Marlo Möller, Eileen G Hoal, Makoto Yawata, Nobuyo Yawata, Lies Boelen, Becca Asquith, Peter Parham, Paul J Norman
The functions of human NK cells in defense against pathogens and placental development during reproduction are modulated by interactions of killer cell Ig-like receptors (KIRs) with HLA-A, -B and -C class I ligands. Both receptors and ligands are highly polymorphic and exhibit extensive differences between human populations. Indigenous to southern Africa are the KhoeSan, the most ancient group of modern human populations, who have highest genomic diversity worldwide. We studied two KhoeSan populations, the Nama pastoralists and the ≠Khomani San hunter-gatherers...
March 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Christian Greunke, Elke Regina Duell, Paul Michael D'Agostino, Anna Glöckle, Katharina Lamm, Tobias Alexander Marius Gulder
Specialized metabolites from bacteria are an important source of inspiration for drug development. The genes required for the biosynthesis of such metabolites in bacteria are usually organized in so-called biosynthetic gene clusters (BGCs). Using modern bioinformatic tools, the wealth of genomic data can be scanned for such BGCs and the expected products can often structurally be predicted in silico. This facilitates the directed discovery of putatively novel bacterial metabolites. However, the production of these molecules often requires genetic manipulation of the BGC for activation or the expression of the pathway in a heterologous host...
March 13, 2018: Metabolic Engineering
James R Smith, Jaboury Ghazoul, David F R P Burslem, Akira Itoh, Eyen Khoo, Soon Leong Lee, Colin R Maycock, Satoshi Nanami, Kevin Kit Siong Ng, Chris J Kettle
Documenting the scale and intensity of fine-scale spatial genetic structure (FSGS), and the processes that shape it, is relevant to the sustainable management of genetic resources in timber tree species, particularly where logging or fragmentation might disrupt gene flow. In this study we assessed patterns of FSGS in three species of Dipterocarpaceae (Parashorea tomentella, Shorea leprosula and Shorea parvifolia) across four different tropical rain forests in Malaysia using nuclear microsatellite markers. Topographic heterogeneity varied across the sites...
2018: PloS One
Yuval B Simons, Kevin Bullaughey, Richard R Hudson, Guy Sella
Human genome-wide association studies (GWASs) are revealing the genetic architecture of anthropomorphic and biomedical traits, i.e., the frequencies and effect sizes of variants that contribute to heritable variation in a trait. To interpret these findings, we need to understand how genetic architecture is shaped by basic population genetics processes-notably, by mutation, natural selection, and genetic drift. Because many quantitative traits are subject to stabilizing selection and because genetic variation that affects one trait often affects many others, we model the genetic architecture of a focal trait that arises under stabilizing selection in a multidimensional trait space...
March 16, 2018: PLoS Biology
Antony T Vincent, Steve J Charette, Jean Barbeau
The Gram-negative bacterium Pseudomonas aeruginosa is found in several habitats, both natural and human-made, and is particularly known for its recurrent presence as a pathogen in the lungs of patients suffering from cystic fibrosis, a genetic disease. Given its clinical importance, several major studies have investigated the genomic adaptation of P. aeruginosa in lungs and its transition as acute infections become chronic. However, our knowledge about the diversity and adaptation of the P. aeruginosa genome to non-clinical environments is still fragmentary, in part due to the lack of accurate reference genomes of strains from the numerous environments colonized by the bacterium...
March 16, 2018: Genome Génome / Conseil National de Recherches Canada
Ruili Shi, Pengju Wang, Lingli Tang, Xiaoming Huang, Yonggang Chen, Yan Su, Jijun Zhao
Using a genetic algorithm incorporated in density functional theory, we explore the ground state structures of fluoride anion-water clusters F-(H2O)n with n = 1-10. The F-(H2O)n clusters prefer structures in which the F- anion remains at the surface of the structure and coordinates with four water molecules, as the F-(H2O)n clusters have strong F--H2O interactions as well as strong hydrogen bonds between H2O molecules. The strong interaction between the F- anion and adjacent H2O molecule leads to a longer O-H distance in the adjacent molecule than in an individual water molecule...
March 16, 2018: Journal of Physical Chemistry. A
Ruchita Dixit, Sowmya Nettem, Simerjit S Madan, Htoo Htoo Kyaw Soe, Adinegara Bl Abas, Leah D Vance, Patrick J Stover
BACKGROUND: Sickle cell disease (SCD) is a group of disorders that affects haemoglobin, which causes distorted sickle- or crescent-shaped red blood cells. It is characterized by anaemia, increased susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with SCD, it is hypothesized that they are at an increased risk for folate deficiency...
March 16, 2018: Cochrane Database of Systematic Reviews
Alejandra M Petrilli, Cristina Fernández-Valle
Schwannomas are benign nerve tumors that occur sporadically in the general population and in those with neurofibromatosis type 2 (NF2), a tumor predisposition genetic disorder. NF2-associated schwannomas and most sporadic schwannomas are caused by inactivating mutations in Schwann cells in the neurofibromatosis type 2 gene (NF2) that encodes the merlin tumor suppressor. Despite their benign nature, schwannomas and especially vestibular schwannomas cause considerable morbidity. The primary available therapies are surgery or radiosurgery which usually lead to loss of function of the compromised nerve...
2018: Methods in Molecular Biology
Olivier Turc, François Tardieu
Abortion of reproductive organs is a major limiting factor of yield under water deficit, but is also a trait selected for by evolutionary processes. Youngest reproductive organs must be prone to abortion so older organs can finish their development in case of limited resources. Water deficit increases natural abortion via two developmentally-driven processes, namely a signal from the first fertilized ovaries and a simultaneous arrest of the expansive growth of all ovaries at a precise stage. In maize (Zea mays) subjected to water deficits typically encountered in dryland agriculture, these developmental mechanisms account for 90 % of drought-associated abortion and are irreversible three days after silk emergence...
March 13, 2018: Journal of Experimental Botany
Minjing Zou, Ali S Alzahrani, Ali Al-Odaib, Mohammad A Alqahtani, Omer Babiker, Roua A Al-Rijjal, Huda A BinEssa, Walaa E Kattan, Anwar F Al-Enezi, Ali Al Qarni, Manar S A Al-Faham, Essa Y Baitei, Afaf Alsagheir, Brian F Meyer, Yufei Shi
Context: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, affecting one in 3000-4000 newborns. Since the introduction of a newborn screening program in 1988, more than 300 cases have been identified. The underlying genetic defects have not been systematically studied. Objective: To identify mutation spectrum of CH-causing genes. Methods: Fifty-five patients from 47 families were studied by next-generation-exome sequencing...
March 12, 2018: Journal of Clinical Endocrinology and Metabolism
Yehuda Ben-Shahar
Manganese (Mn) is an essential trace element that acts as a metal co-factor in diverse biochemical and cellular functions. However, chronic environmental exposure to high levels of Mn is a well-established risk factor for the etiology of severe, atypical parkinsonian syndrome (manganism) via its accumulation in the basal ganglia, pallidum, and striatum brain regions, which is often associated with abnormal dopamine, GABA, and glutamate neural signaling. Recent studies have indicated that chronic Mn exposure at levels that are below the risk for manganism can still cause behavioral, cognitive, and motor dysfunctions via poorly understood mechanisms at the molecular and cellular levels...
2018: Frontiers in Genetics
Zi-Ru Chen, Lu Kuang, Yi-Qun Gao, Ya-Ling Wang, David E Salt, Dai-Yin Chao
Zinc (Zn) is an essential element for plant growth and development, and Zn derived from crop plants in the diet is also important for human health. Here, we report that genetic variation in Heavy Metal-ATPase 4 ( HMA4 ) controls natural variation in leaf Zn content. Investigation of the natural variation in leaf Zn content in a world-wide collection of 349 Arabidopsis thaliana wild collected accessions identified two accessions, Van-0 and Fab-2, which accumulate significantly lower Zn when compared with Col-0...
2018: Frontiers in Plant Science
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