19 research outputs found
A thirteen-year analysis of Plasmodium falciparum populations reveals high conservation of the mutant pfcrt haplotype despite the withdrawal of chloroquine from national treatment guidelines in Gabon
A multivariable assessment quantifying effects of cohort-level factors associated with combined mortality and culling risk in cohorts of U.S. commercial feedlot cattle
Economic losses due to cattle mortality and culling have a substantial impact on the feedlot industry. Since criteria for culling may vary and may affect measures of cumulative mortality within cattle cohorts, it is important to assess both mortality and culling when evaluating cattle losses over time and among feedlots. To date, there are no published multivariable assessments of factors associated with combined mortality and culling risk. Our objective was to evaluate combined mortality and culling losses in feedlot cattle cohorts and quantify effects of commonly measured cohort-level risk factors (weight at feedlot arrival, gender, and month of feedlot arrival) using data routinely collected by commercial feedlots. We used retrospective data representing 8,904,965 animals in 54,416 cohorts from 16 U.S. feedlots from 2000 to 2007. The sum of mortality and culling counts for each cohort (given the number of cattle at risk) was used to generate the outcome of interest, the cumulative incidence of combined mortality and culling. Associations between this outcome variable and cohort-level risk factors were evaluated using a mixed effects multivariable negative binomial regression model with random effects for feedlot, year, month and week of arrival. Mean arrival weight of the cohort, gender, and arrival month and a three-way interaction (and corresponding two-way interactions) among arrival weight, gender and month were
significantly (P < 0.05) associated with the outcome. Results showed that as the mean arrival weight of the cohort increased, mortality and culling risk decreased, but effects of arrival weight were modified both by the gender of the cohort and the month of feedlot arrival. There was a seasonal pattern in combined mortality and culling risk for light and middleweight male and female cohorts, with a significantly (P < 0.05) higher risk for cattle arriving at the feedlot in spring and summer (MarchâSeptember) than in cattle arriving during fall, and winter months (NovemberâFebruary). Our results quantified effects of covariate patterns that have been heretofore difficult to fully evaluate in smaller scale studies; in addition, they illustrated the importance of utilizing multivariable approaches when quantifying risk factors in heterogeneous feedlot populations. Estimated effects from our model could be useful for managing financial risks associated with adverse health events based on data that are routinely available
Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: Patterning, proliferation, and mitochondrial functions of 22q11 genes
SUMMARY: DiGeorge, or 22q11 Deletion Syndrome (22q11DS), the most common survivable human genetic deletion disorder, is caused by deletion of a minimum of 32 contiguous genes on human chromosome 22, and presumably results from diminished dosage of one, some, or all of these genesâparticularly during development. Nevertheless, the normal functions of 22q11 genes in the embryo or neonate, and their contribution to developmental pathogenesis that must underlie 22q11DS are not well understood. Our data suggests that a substantial number of 22q11 genes act specifically and in concert to mediate early morphogenetic interactions and subsequent cellular differentiation at phenotypically compromised sitesâthe limbs, heart, face and forebrain. When dosage of a broad set of these genes is diminished, early morphogenesis is altered, and initial 22q11DS phenotypes are established. Thereafter, functionally similar subsets of 22q11 genesâespecially those that influence the cell cycle or mitochondrial functionâremain expressed, particularly in the developing cerebral cortex, to regulate neurogenesis and synaptic development. When dosage of these genes is diminished, numbers, placement and connectivity of neurons and circuits essential for normal behavior may be disrupted. Such disruptions likely contribute to vulnerability for schizophrenia, autism, or attention deficit/ hyperactivity disorder seen in most 22q11DS patients
Malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut
Physical contact is important for the interaction between animal cells, but it can represent a major challenge for protists like malaria parasites. Recently, novel filamentous cell-cell contacts have been identified in different types of eukaryotic cells and termed nanotubes due to their morphological appearance. Nanotubes represent small dynamic membranous extensions that consist of F-actin and are considered an ancient feature evolved by eukaryotic cells to establish contact for communication. We here describe similar tubular structures in the malaria pathogen Plasmodium falciparum, which emerge from the surfaces of the forming gametes upon gametocyte activation in the mosquito midgut. The filaments can exhibit a length of > 100 ÎŒm and contain the F-actin isoform actin 2. They actively form within a few minutes after gametocyte activation and persist until the zygote transforms into the ookinete. The filaments originate from the parasite plasma membrane, are close ended and express adhesion proteins on their surfaces that are typically found in gametes, like Pfs230, Pfs48/45 or Pfs25, but not the zygote surface protein Pfs28. We show that these tubular structures represent long-distance cell-to-cell connections between sexual stage parasites and demonstrate that they meet the characteristics of nanotubes. We propose that malaria parasites utilize these adhesive ânanotubesâ in order to facilitate intercellular contact between gametes during reproduction in the mosquito midgut
Anatomy of the 2018 agricultural drought in the Netherlands using in situ soil moisture and satellite vegetation indices
The soil moisture status near the land surface is a key determinant of vegetation productivity. The critical soil moisture content determines the transition from an energy-limited to a water-limited evapotranspiration regime. This study quantifies the critical soil moisture content by comparison of in situ soil moisture profile measurements of the Raam and Twente networks in the Netherlands, with two satellite-derived vegetation indices (near-infrared reflectance of terrestrial vegetation, NIRv, and vegetation optical depth, VOD) during the 2018 summer drought. The critical soil moisture content is obtained through a piece-wise linear correlation of the NIRv and VOD anomalies with soil moisture on different depths of the profile. This non-linear relation reflects the observation that negative soil moisture anomalies develop weeks before the first reduction in vegetation indices: 2-3 weeks in this case. Furthermore, the inferred critical soil moisture content was found to increase with observation depth, and this relationship is shown to be linear and distinctive per area, reflecting the tendency of roots to take up water from deeper layers when drought progresses. The relations of non-stressed towards water-stressed vegetation conditions on distinct depths are derived using remote sensing, enabling the parameterization of reduced evapotranspiration and its effect on gross primary productivity in models to study the impact of a drought on the carbon cycle. </p
ProductivitĂ© de peuplements de forĂȘt tempĂ©rĂ©e feuillue prĂ©sentant diffĂ©rents niveaux de diversitĂ©
Mutations of Transcription Factors in Human with Heart Disease for Understanding the Development and Mechanisms of Congenital Cardiovascular Heart Disease
Inactivation of Bmp4 from the Tbx1 Expression Domain Causes Abnormal Pharyngeal Arch Artery and Cardiac Outflow Tract Remodeling
Maldevelopment of outflow tract and aortic arch arteries is among the most common forms of human congenital heart diseases. Both Bmp4 and Tbx1 are known to play critical roles during cardiovascular development. Expression of these two genes partially overlaps in pharyngeal arch areas in mouse embryos. In this study, we applied a conditional gene inactivation approach to test the hypothesis that Bmp4 expressed from the Tbx1 expression domain plays a critical role for normal development of outflow tract and pharyngeal arch arteries. We showed that inactivation of Bmp4 from Tbx1-expressing cells leads to the spectrum of deformities resembling the cardiovascular defects observed in human DiGeorge syndrome patients. Inactivation of Bmp4 from the Tbx1 expression domain did not cause patterning defects, but affected remodeling of outflow tract and pharyngeal arch arteries. Our further examination revealed that Bmp4 is required for normal recruitment/differentiation of smooth muscle cells surrounding the PAA4 and survival of outflow tract cushion mesenchymal cells