Collaborative Assessment of Molecular Geometries and Energies from the Open Force Field.

Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein-ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field.

State estimation for nonlinear state-space transmission models of tuberculosis.

Given the high prevalence of tuberculosis (TB) and the mortality rate associated with the disease, numerous models, such as the Gammaitoni and Nucci (GN) model, were developed to model the risk of transmission. These models typically rely on a quanta generation rate as a measurement of infectivity. Since the quanta generation rate cannot be measured directly, the unique contribution of this work is to develop state estimators to estimate the quanta generation rate from available measurements.

Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial.

Introduction: Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease (ESRD) in the USA and worldwide. Recent experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) may decrease progression of chronic kidney disease. However, a large-scale randomised clinical trial is needed to determine whether PTX can reduce ESRD and death in DKD.

Optimized Lockdown Strategies for Curbing the Spread of COVID-19: A South African Case Study.

To curb the spread of COVID-19, many governments around the world have implemented tiered lockdowns with varying degrees of stringency. Lockdown levels are typically increased when the disease spreads and reduced when the disease abates. A predictive control approach is used to develop optimized lockdown strategies for curbing the spread of COVID-19.

Trifluoromethyloxadiazoles: inhibitors of histone deacetylases for control of Asian soybean rust.

Background: Trifluoromethyloxadiazoles (TFMOs) are selective inhibitors of class II histone deacetylases (HDACs). To date, class II HDACs have not been addressed as target enzymes by commercial fungicides.

Results: Antifungal testing of a broad variety of TFMOs against several important plant pathogens showed activity against only rusts, and especially Phakopsora pachyrhizi, the cause of Asian soybean rust.

A Novel Single-Site Mutation in the Catalytic Domain of Protoporphyrinogen Oxidase IX (PPO) Confers Resistance to PPO-Inhibiting Herbicides.

Protoporphyrinogen oxidase (PPO)-inhibiting herbicides are used to control weeds in a variety of crops. These herbicides inhibit heme and photosynthesis in plants. PPO-inhibiting herbicides are used to control (Palmer amaranth) especially those with resistance to glyphosate and acetolactate synthase (ALS) inhibiting herbicides.

Modeling the Airborne Infection Risk of Tuberculosis for a Research Facility in eMalahleni, South Africa.

A detailed mathematical modeling framework for the risk of airborne infectious disease transmission in indoor spaces was developed to enable mathematical analysis of experiments conducted at the Airborne Infections Research (AIR) facility, eMalahleni, South Africa. A model was built using this framework to explore possible causes of why an experiment at the AIR facility did not produce expected results. The experiment was conducted at the AIR facility from August 31, 2015 to December 4, 2015, in which the efficacy of upper room germicidal ultraviolet (GUV) irradiation as an environmental control was tested.

Effect of cytochrome CYP2C19 metabolizing activity on antidepressant response and side effects: Meta-analysis of data from genome-wide association studies.

Cytochrome (CYP) P450 enzymes have a primary role in antidepressant metabolism and variants in these polymorphic genes are targets for pharmacogenetic investigation. This is the first meta-analysis to investigate how CYP2C19 polymorphisms predict citalopram/escitalopram efficacy and side effects. CYP2C19 metabolic phenotypes comprise poor metabolizers (PM), intermediate and intermediate+ metabolizers (IM; IM+), extensive and extensive+ metabolizers (EM [wild type]; EM+) and ultra-rapid metabolizers (UM) defined by the two most common CYP2C19 functional polymorphisms (rs4244285 and rs12248560) in Caucasians.

Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP).

A key feature of major depressive disorder (MDD) is anhedonia, which is a predictor of response to antidepressant treatment. In order to shed light on its genetic underpinnings, we conducted a genome-wide association study (GWAS) followed by investigation of biological pathway enrichment using an anhedonia dimension for 759 patients with MDD in the GENDEP study. The GWAS identified 18 SNPs associated at genome-wide significance with the top one being an intronic SNP (rs9392549) in PRPF4B (pre-mRNA processing factor 4B) located on chromosome 6 (P = 2.

Interaction between the gene, body mass index and depression: meta-analysis of 13701 individuals.

Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the gene, suggesting its implication in the association between depression and obesity.To confirm these findings by investigating the polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.

Pharmacogenetics of antidepressant response: A polygenic approach.

Background: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait.

Washoff of Residual Photosystem II Herbicides from Sugar Cane Trash under a Rainfall Simulator.

Herbicides are often applied to crop residues, but their fate has not been well studied. We measured herbicide washoff from sugar cane trash during simulated rainfall, at 1, 8, and 40 days after spraying (DAS), to provide insight into herbicide fate and for use in modeling. Herbicides included are commonly used in the sugar industry, either in Australia or in Brazil.

Transcriptomics and the mechanisms of antidepressant efficacy.

The mechanisms by which antidepressants have their effects are not clear and the reasons for variability in treatment outcomes are also unknown. However, there is evidence from candidate gene research that indicates gene expression changes may be involved in antidepressant action. In this study, we examined antidepressant-induced alterations in gene expression on a transcriptome-wide scale, exploring associations with treatment response.

A Pooled Genome-Wide Association Study of Asperger Syndrome.

Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%.

Patterns and determinants of care seeking for obstetric complications in rural northwest Bangladesh: analysis from a prospective cohort study.

Background: In communities with low rates of institutional delivery, little data exist on care-seeking behavior for potentially life-threatening obstetric complications. In this analysis, we sought to describe care-seeking patterns for self-reported complications and near misses in rural Bangladesh and to identify factors associated with care seeking for these conditions.

Methods: Utilizing data from a community-randomized controlled trial enrolling 42,214 pregnant women between 2007 and 2011, we used multivariable multinomial logistic regression to explore the association of demographic and socioeconomic factors, perceived need, and service availability with care seeking for obstetric complications or near misses.

A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder.

Background: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

Background: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD.

Exploring the role of drug-metabolising enzymes in antidepressant side effects.

Rationale: Cytochrome P450 enzymes are important in the metabolism of antidepressants. The highly polymorphic nature of these enzymes has been linked to variability in antidepressant metabolism rates, leading to hope regarding the use of P450 genotyping to guide treatment. However, evidence that P450 genotypic differences underlie the variation in treatment outcomes is inconclusive.

Molecular genetics research in sub-Saharan Africa: how can the international community help?

Background: Opportunities provided by rapidly increasing access to educational resources, clinical and epidemiological data, DNA collections, cheaper technology and financial investment, suggest that researchers in sub-Saharan Africa outside South Africa (SSAOSA) could now join the genomics revolution on equal terms with those in the West.

Findings: Current evidence, however, suggests that, in some cases, various factors may be compromising this development. One interpretation is that urgent practical problems, which may compromise motivation, aspiration and ambition, are blocking opportunity.

The correlation between reading and mathematics ability at age twelve has a substantial genetic component.

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve.

Lipoprotein (A) in clinical practice.

Lipoprotein (a) is a strong and independent risk factor for atherosclerosis severity and a predictor of the risk of ischaemic heart disease and stroke. Many questions are still unanswered in relation to the clinical relevance of the scientific observations on Lp(a) and its application in the realms of cardiovascular prevention. Lp(a), a lipoprotein subtype, is linked to the Apo(a) gene located on chromosome 6q26-27 independently associated with increased risk of coronary artery disease (CAD).

A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study.

Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.

Infrared near-field spectroscopy of trace explosives using an external cavity quantum cascade laser.

Utilizing a broadly-tunable external cavity quantum cascade laser for scattering-type scanning near-field optical microscopy (s-SNOM), we measure infrared spectra of particles of explosives by probing characteristic nitro-group resonances in the 7.1-7.9 µm wavelength range.