Dithiopyr and dinitroanilines are preemergence-applied, mitotic-inhibiting herbicides used to control goosegrass Eleusine indica (L.) Gaertn. in turfgrass. A suspected resistant E. indica population ...was collected from a golf course putting green and was evaluated for possible resistance to dithiopyr and prodiamine. After dose–response evaluation, the α-tubulin gene was sequenced for known target-site mutations that have been reported to confer resistance to mitotic-inhibiting herbicides. A mutation was discovered that resulted in an amino acid substitution at position 136 from leucine to phenylalanine (Leu-136-Phe). Previous research has indicated that Leu-136-Phe does confer resistance to dinitroaniline herbicides. The level of resistance indicated by regression models and I50 values indicates that there is 54.1-, 4.7-, >100-, and >100-fold resistance to dithiopyr, prodiamine, pendimethalin, and oryzalin, respectively, when compared with the susceptible population based on seedling emergence response and 88.4-, 7.8-, >100-, and >100-fold resistance to dithiopyr, prodiamine, pendimethalin, and oryzalin, respectively, when compared with the susceptible population based on biomass reduction response. This is the first report of less resistance to prodiamine compared with pendimethalin or oryzalin due to a target-site α-tubulin mutation and the first report of a target-site α-tubulin mutation associated with dithiopyr resistance.
Depression is a highly prevalent condition with devastating personal and public health consequences that often first manifests during adolescence. Though extensively studied, the pathogenesis of ...depression remains poorly understood, and efforts to stratify risks and identify optimal interventions have proceeded slowly. A major impediment has been the reliance on an all-or-nothing categorical diagnostic scheme based solely on whether a patient endorses an arbitrary number of common symptoms for a sufficiently long period. This approach masks the well-documented heterogeneity of depression, a disorder that is highly variable in presentation, severity, and course between individuals and is frequently comorbid with other psychiatric conditions. In this targeted review, we outline the limitations of traditional diagnosis-based research and instead advocate an alternative approach centered around symptoms as unique dimensions of clinical dysfunction that span across disorders and more closely reflect underlying neurobiological abnormalities. In particular, we highlight anhedonia-the reduced ability to anticipate and experience pleasure-as a specific, quantifiable index of reward dysfunction and an ideal candidate for dimensional investigation. Anhedonia is a core symptom of depression but also a salient feature of numerous other conditions, and its severity varies widely within clinical and even healthy populations. Similarly, reward dysfunction is a hallmark of depression but is evident across many psychiatric conditions. Reward function is especially relevant in adolescence, a period characterized by exaggerated reward-seeking behaviors and rapid maturation of neural reward circuitry. We detail extensive work by our research group and others to investigate the neural and systemic factors contributing to reward dysfunction in youth, including our cumulative findings using multiple neuroimaging and immunological measures to study depressed adolescents but also trans-diagnostic cohorts with diverse psychiatric symptoms. We describe convergent evidence that reward dysfunction: (a) predicts worse clinical outcomes, (b) is associated with functional and chemical abnormalities within and beyond the neural reward circuitry, (c) is linked to elevated peripheral levels of inflammatory biomarkers, and (d) manifests early in the course of illness. Emphasis is placed on high-resolution neuroimaging techniques, comprehensive immunological assays, and data-driven analyses to fully capture and characterize the complex, interconnected nature of these systems and their contributions to adolescent reward dysfunction.
Abstract
Background
No studies have explored the association between pneumococcal nasopharyngeal density and severe pneumonia using the World Health Organization (WHO) 2013 definition. In Lao ...People’s Democratic Republic (Lao PDR), we determine the association between nasopharyngeal pneumococcal density and severe pneumonia in children.
Methods
A prospective observational study was undertaken at Mahosot Hospital, Vientiane, from 2014 to mid-2018. Children <5 years admitted with acute respiratory infections (ARIs) were included. Clinical and demographic data were collected alongside nasopharyngeal swabs for pneumococcal quantification by lytA real-time quantitative polymerase chain reaction. Severe pneumonia was defined using the 2013 WHO definition. For pneumococcal carriers, a logistic regression model examined the association between pneumococcal density and severe pneumonia, after adjusting for potential confounders including demographic and household factors, 13-valent pneumococcal conjugate vaccine status, respiratory syncytial virus co-detection, and preadmission antibiotics.
Results
Of 1268 participants with ARI, 32.3% (n = 410) had severe pneumonia and 36.9% (n = 468) had pneumococcal carriage. For pneumococcal carriers, pneumococcal density was positively associated with severe pneumonia (adjusted odds ratio, 1.4 95% confidence interval, 1.1–1.8; P = .020).
Conclusions
Among children with ARIs and pneumococcal carriage, pneumococcal carriage density was positively associated with severe pneumonia in Lao PDR. Further studies may determine if pneumococcal density is a useful marker for pneumococcal conjugate vaccine impact on childhood pneumonia.
No studies have explored the association between pneumococcal nasopharyngeal density and severe pneumonia using the World Health Organization 2013 definition. Among children with acute respiratory infections and pneumococcal carriage, pneumococcal carriage density was positively associated with severe pneumonia in Laos.
Imidazolium ionic liquids (IILs) have a range of biotechnological applications, including as pretreatment solvents that extract cellulose from plant biomass for microbial fermentation into ...sustainable bioenergy. However, residual levels of IILs, such as 1-ethyl-3-methylimidazolium chloride (C
C
imCl), are toxic to biofuel-producing microbes, including the yeast
strains isolated from diverse ecological niches differ in genomic sequence and in phenotypes potentially beneficial for industrial applications, including tolerance to inhibitory compounds present in hydrolyzed plant feedstocks. We evaluated >100 genome-sequenced
strains for tolerance to C
C
imCl and identified one strain with exceptional tolerance. By screening a library of genomic DNA fragments from the C
C
imCl-tolerant strain for improved IIL tolerance, we identified
, which encodes a plasma membrane multidrug efflux pump, and a previously uncharacterized gene that we named
(
), which encodes a predicted membrane protein. Analyses of
sequences from our panel of
strains together with growth phenotypes implicated two single nucleotide polymorphisms (SNPs) that associated with IIL tolerance and sensitivity. We confirmed these phenotypic effects by transferring the
SNPs into a C
C
imCl-sensitive yeast strain using CRISPR/Cas9 genome editing. Further studies indicated that these SNPs affect Sge1 protein stability and cell surface localization, influencing the amount of toxic IILs that cells can pump out of the cytoplasm. Our results highlight the general potential for discovering useful biotechnological functions from untapped natural sequence variation and provide functional insight into emergent
alleles with reduced capacities to protect against IIL toxicity.
Childhood environments are critical in shaping cognitive neurodevelopment. With the increasing availability of large-scale neuroimaging datasets with deep phenotyping of childhood environments, we ...can now build upon prior studies that have considered relationships between one or a handful of environmental and neuroimaging features at a time. Here, we characterize the combined effects of hundreds of inter-connected and co-occurring features of a child’s environment (“exposome”) and investigate associations with each child’s unique, multidimensional pattern of functional brain network organization (“functional topography”) and cognition. We apply data-driven computational models to measure the exposome and define personalized functional brain networks in pre-registered analyses. Across matched discovery (n=5139, 48.5% female) and replication (n=5137, 47.1% female) samples from the Adolescent Brain Cognitive Development study, the exposome was associated with current (ages 9–10) and future (ages 11–12) cognition. Changes in the exposome were also associated with changes in cognition after accounting for baseline scores. Cross-validated ridge regressions revealed that the exposome is reflected in functional topography and can predict performance across cognitive domains. Importantly, a single measure capturing a child’s exposome could more accurately and parsimoniously predict cognition than a wealth of personalized neuroimaging data, highlighting the importance of children’s complex, multidimensional environments in cognitive neurodevelopment.
•Complex childhood environments captured by the “exposome” are related to cognition.•Changes in the exposome are associated with changes in cognition over two years.•The exposome is reflected in personalized functional brain network organization.•Cross-validated ridge regressions trained on the exposome predict future cognition.
The primary aim of this study was to evaluate the current state of point-of-care ultrasound (POCUS) integration in undergraduate medical education (UME) at MD-granting medical schools in the United ...States.
In 2020, 154 clinical ultrasound directors and curricular deans at MD-granting medical schools were surveyed. The 25-question survey collected data about school characteristics, barriers to POCUS training implementation, and POCUS curriculum details. Descriptive analysis was conducted using frequency and percentage distributions.
One hundred twenty-two (79%) of 154 schools responded to the survey, of which 36 were multicampus. Sixty-nine (57%) schools had an approved POCUS curriculum, with 10 (8%) offering a longitudinal 4-year curriculum. For a majority of schools, POCUS instruction was required during the first year (86%) and second year (68%). Forty-two (61%) schools were teaching fundamentals, diagnostic, and procedural ultrasound. One hundred fifteen (94%) schools identified barriers to implementing POCUS training in UME, which included lack of trained faculty (63%), lack of time in current curricula (54%), and lack of equipment (44%). Seven (6%) schools identified no barriers.
Over half of the responding medical schools in the United States had integrated POCUS instruction into their UME curricula. Despite this, a very small portion had a longitudinal curriculum and multiple barriers existed for implementation, with the most common being lack of trained faculty. The data from this study can be used by schools planning to add or expand POCUS instruction within their current curricula.
Epigenetic modifications on DNA and histones regulate gene expression by modulating chromatin accessibility to transcription machinery. Here we identify methionine as a key nutrient affecting ...epigenetic reprogramming in CD4+ T helper (Th) cells. Using metabolomics, we showed that methionine is rapidly taken up by activated T cells and serves as the major substrate for biosynthesis of the universal methyl donor S-adenosyl-L-methionine (SAM). Methionine was required to maintain intracellular SAM pools in T cells. Methionine restriction reduced histone H3K4 methylation (H3K4me3) at the promoter regions of key genes involved in Th17 cell proliferation and cytokine production. Applied to the mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis), dietary methionine restriction reduced the expansion of pathogenic Th17 cells in vivo, leading to reduced T cell-mediated neuroinflammation and disease onset. Our data identify methionine as a key nutritional factor shaping Th cell proliferation and function in part through regulation of histone methylation.
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•Activated T cells use exogenous methionine to synthesize the methyl donor SAM•Methionine restriction reduces intracellular SAM and H3K4me3 levels in T cells•Methionine restriction limits the expansion of inflammatory Th17 cells•EAE onset and severity are reduced by dietary methionine restriction
CD4+ T helper (Th) cells are central drivers of autoimmune pathology in diseases such as multiple sclerosis. Roy and Chen et al. identify methionine as an essential nutrient for Th cell epigenetic programming and demonstrate that dietary methionine restriction impacts T cell-mediated autoimmunity through effects on Th17 cell proliferation and cytokine production.
The Modular Optical Underwater Survey System Amin, Ruhul; Richards, Benjamin L; Misa, William F X E ...
Sensors (Basel, Switzerland),
10/2017, Letnik:
17, Številka:
10
Journal Article
Recenzirano
Odprti dostop
The Pacific Islands Fisheries Science Center deploys the Modular Optical Underwater Survey System (MOUSS) to estimate the species-specific, size-structured abundance of commercially-important fish ...species in Hawaii and the Pacific Islands. The MOUSS is an autonomous stereo-video camera system designed for the in situ visual sampling of fish assemblages. This system is rated to 500 m and its low-light, stereo-video cameras enable identification, counting, and sizing of individuals at a range of 0.5-10 m. The modular nature of MOUSS allows for the efficient and cost-effective use of various imaging sensors, power systems, and deployment platforms. The MOUSS is in use for surveys in Hawaii, the Gulf of Mexico, and Southern California. In Hawaiian waters, the system can effectively identify individuals to a depth of 250 m using only ambient light. In this paper, we describe the MOUSS's application in fisheries research, including the design, calibration, analysis techniques, and deployment mechanism.
Symptoms of borderline personality disorder (BPD) often manifest during adolescence, but the underlying relationship between these debilitating symptoms and the development of functional brain ...networks is not well understood. Here, we aimed to investigate how multivariate patterns of functional connectivity are associated with borderline personality traits in large samples of young adults and adolescents.
We used functional magnetic resonance imaging data from young adults and adolescents from the HCP-YA (Human Connectome Project Young Adult) (n = 870, ages 22–37 years, 457 female) and the HCP-D (Human Connectome Project Development) (n = 223, ages 16–21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five-Factor Inventory. A ridge regression model with cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with age-related changes in connectivity.
Multivariate functional connectivity patterns significantly predicted out-of-sample BPD scores in unseen data in young adults (HCP-YA ppermuted = .001) and older adolescents (HCP-D ppermuted = .001). Regional predictive capacity was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD scores aligned with those associated with development in youth.
Individual differences in functional connectivity in developmentally sensitive regions are associated with borderline personality traits.
Virulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus. We investigated the mechanisms of virulence loss at the whole genome level using Babesia bovis as a ...model apicomplexan in which genetically related attenuated parasites can be reliably derived from virulent parental strains in the natural host. We expected virulence loss to be accompanied by consistent changes at the gene level, and that such changes would be shared among attenuated parasites of diverse geographic and genetic background.
Surprisingly, while single nucleotide polymorphisms in 14 genes distinguished all attenuated parasites from their virulent parental strains, all non-synonymous changes resulted in no deleterious amino acid modification that could consistently be associated with attenuation (or virulence) in this hemoparasite. Interestingly, however, attenuation significantly reduced the overall population's genome diversity with 81% of base pairs shared among attenuated strains, compared to only 60% of base pairs common among virulent parental parasites. There were significantly fewer genes that were unique to their geographical origins among the attenuated parasites, resulting in a simplified population structure among the attenuated strains.
This simplified structure includes reduced diversity of the variant erythrocyte surface 1 (ves) multigene family repertoire among attenuated parasites when compared to virulent parental strains, possibly suggesting that overall variance in large protein families such as Variant Erythrocyte Surface Antigens has a critical role in expression of the virulence phenotype. In addition, the results suggest that virulence (or attenuation) mechanisms may not be shared among all populations of parasites at the gene level, but instead may reflect expansion or contraction of the population structure in response to shifting milieus.
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