The incidence of pediatric nephrolithiasis has been steadily increasing for the past several decades, with a concomitant concerning increase in health care costs and burden to children with this ...disease. Recent population-based studies have also demonstrated a change in the current trends of pediatric nephrolithiasis that is characterized by a significant increase in the number of girls now being affected. While changes in diet and lifestyle, obesity prevalence, and even imaging practices have been proposed to contribute to the recent increase in pediatric nephrolithiasis, a definite underlying cause remains elusive. This situation is complicated by the fact that, unlike in adults, the trends occurring in pediatric nephrolithiasis have not been studied rigorously, which contributes to the paucity of data in children. The level of concern with the increasing incidence is raised by factors unique to pediatric nephrolithiasis that could expose an affected child to more complications. Factors such as variable clinical presentation, high recurrence of kidney stones associated with abnormalities of metabolism and the urinary tract, and the possible presence of rare genetic kidney stone diseases would require physicians to comprehensively evaluate patients presenting with kidney stones. The goal of evaluation is to identify modifiable risk factors and abnormalities for which targeted therapy can be prescribed. The goals of medical and surgical treatments are to eliminate the burden of kidney stones and prevent recurrence while simultaneously minimizing complications from interventions. Patients at high risk may benefit from a specialized kidney stone clinic staffed by a pediatric nephrologist, urologist, dietitian, and clinical nurse. Such a multidisciplinary clinic can help provide the medical and surgical support needed for patients at high risk and offer key opportunities to learn more about pediatric nephrolithiasis, thereby fueling the much-needed research in this field.
Population scale sweeps of viral pathogens, such as SARS-CoV-2, require high intensity testing for effective management. Here, we describe "Systematic Parallel Analysis of RNA coupled to Sequencing ...for Covid-19 screening" (C19-SPAR-Seq), a multiplexed, scalable, readily automated platform for SARS-CoV-2 detection that is capable of analyzing tens of thousands of patient samples in a single run. To address strict requirements for control of assay parameters and output demanded by clinical diagnostics, we employ a control-based Precision-Recall and Receiver Operator Characteristics (coPR) analysis to assign run-specific quality control metrics. C19-SPAR-Seq coupled to coPR on a trial cohort of several hundred patients performs with a specificity of 100% and sensitivity of 91% on samples with low viral loads, and a sensitivity of >95% on high viral loads associated with disease onset and peak transmissibility. This study establishes the feasibility of employing C19-SPAR-Seq for the large-scale monitoring of SARS-CoV-2 and other pathogens.
Because few ice core records from the Himalayas exist, understanding of the onset and timing of the human impact on the atmosphere of the “roof of the world” remains poorly constrained. We report a ...continuous 500-y trace metal ice core record from the Dasuopu glacier (7,200 m, central Himalayas), the highest drilling site on Earth. We show that an early contamination from toxic trace metals, particularly Cd, Cr, Mo, Ni, Sb, and Zn, emerged at high elevation in the Himalayas at the onset of the European Industrial Revolution (∼1780 AD). This was amplified by the intensification of the snow accumulation (+50% at Dasuopu) likely linked to the meridional displacement of the winter westerlies from 1810 until 1880 AD. During this period, the flux and crustal enrichment factors of the toxic trace metals were augmented by factors of 2 to 4 and 2 to 6, respectively. We suggest this contamination was the consequence of the long-range transport and wet deposition of fly ash from the combustion of coal (likely from Western Europe where it was almost entirely produced and used during the 19th century) with a possible contribution from the synchronous increase in biomass burning emissions from deforestation in the Northern Hemisphere. The snow accumulation decreased and dry winters were reestablished in Dasuopu after 1880 AD when lower than expected toxic metal levels were recorded. This indicates that contamination on the top of the Himalayas depended primarily on multidecadal changes in atmospheric circulation and secondarily on variations in emission sources during the last 200 y.
Fine particulate air pollution <2.5 μm in diameter (PM
) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have ...recognized PM
as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM
can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention.
The bacterium Caulobacter crescentus is a popular model for the study of cell cycle regulation and senescence. The large prolate siphophage phiCbK has been an important tool in C. crescentus biology, ...and has been studied in its own right as a model for viral morphogenesis. Although a system of some interest, to date little genomic information is available on phiCbK or its relatives.
Five novel phiCbK-like C. crescentus bacteriophages, CcrMagneto, CcrSwift, CcrKarma, CcrRogue and CcrColossus, were isolated from the environment. The genomes of phage phiCbK and these five environmental phage isolates were obtained by 454 pyrosequencing. The phiCbK-like phage genomes range in size from 205 kb encoding 318 proteins (phiCbK) to 280 kb encoding 448 proteins (CcrColossus), and were found to contain nonpermuted terminal redundancies of 10 to 17 kb. A novel method of terminal ligation was developed to map genomic termini, which confirmed termini predicted by coverage analysis. This suggests that sequence coverage discontinuities may be useable as predictors of genomic termini in phage genomes. Genomic modules encoding virion morphogenesis, lysis and DNA replication proteins were identified. The phiCbK-like phages were also found to encode a number of intriguing proteins; all contain a clearly T7-like DNA polymerase, and five of the six encode a possible homolog of the C. crescentus cell cycle regulator GcrA, which may allow the phage to alter the host cell's replicative state. The structural proteome of phage phiCbK was determined, identifying the portal, major and minor capsid proteins, the tail tape measure and possible tail fiber proteins. All six phage genomes are clearly related; phiCbK, CcrMagneto, CcrSwift, CcrKarma and CcrRogue form a group related at the DNA level, while CcrColossus is more diverged but retains significant similarity at the protein level.
Due to their lack of any apparent relationship to other described phages, this group is proposed as the founding cohort of a new phage type, the phiCbK-like phages. This work will serve as a foundation for future studies on morphogenesis, infection and phage-host interactions in C. crescentus.
1. Activity patterns of arthropods lead to consistent changes in community composition in many ecosystems, but this daily turnover in community membership is poorly characterised. This study used ...passive collection methods of ground and air active arthropods, feeding guild assignment, and body size measurements to characterise changes in a terrestrial arthropod community between consecutive 4‐h time intervals.
2. We found that arthropod communities are highly structured in time, with the time of sample collection significantly affecting family richness, relative abundance, abundance of feeding guilds, community dissimilarity, community turnover rates, and average body sizes within taxonomic orders.
3. Community dissimilarity is periodic on two timescales, 12 and 24 h. Morning and evening communities were similar to each other and supported a unique assemblage that occurred during the transition from highly dissimilar night and day arthropod communities.
4. The results offered support for previous findings that night‐active arthropods are generally larger than day‐active ones, with the pattern holding for some but not all orders.
5. These findings demonstrate that species‐specific daily activity patterns influence community composition in a predictable manner, with characteristic repeating time communities within a single habitat.
Arthropod communities are highly structured in time and vary over the course of the day in a predictable manner, with characteristic repeating time communities within a single habitat.
Time of sample collection significantly affects family richness, relative abundance, abundance of feeding guilds, community dissimilarity, community turnover rates, and average body size with several orders.
Morning and evening communities were similar to each other and supported a unique assemblage that occurred during the transition from highly dissimilar night and day arthropod communities.
Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of CKD. The discovery of monogenic causes of SRNS has revealed specific pathogenetic pathways, but these monogenic causes do not ...explain all cases of SRNS.
To identify novel monogenic causes of SRNS, we screened 665 patients by whole-exome sequencing. We then evaluated the
functional significance of two genes and the mutations therein that we discovered through this sequencing and conducted complementary studies in podocyte-like
nephrocytes.
We identified conserved, homozygous missense mutations of
in two families with early-onset NS and a homozygous missense mutation of
in two siblings with SRNS. GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5. Coimmunoprecipitation assays indicated interaction between GAPVD1 and ANKFY1 proteins, which also colocalized when expressed in HEK293T cells. Silencing either protein diminished the podocyte migration rate. Compared with wild-type GAPVD1 and ANKFY1, the mutated proteins produced upon ectopic expression of
or
bearing the patient-derived mutations exhibited altered binding affinity for active RAB5 and reduced ability to rescue the knockout-induced defect in podocyte migration. Coimmunoprecipitation assays further demonstrated a physical interaction between nephrin and GAPVD1, and immunofluorescence revealed partial colocalization of these proteins in rat glomeruli. The patient-derived
mutations reduced nephrin-GAPVD1 binding affinity. In
, silencing
impaired endocytosis and caused mistrafficking of the nephrin ortholog.
Mutations in
and probably in
are novel monogenic causes of NS. The discovery of these genes implicates RAB5 regulation in the pathogenesis of human NS.
Sensitive, rapid, and accessible diagnostics continue to be critical to track the COVID-19 pandemic caused by the SARS-CoV-2 virus. RT-qPCR is the gold standard test, and comparison of methodologies ...and reagents, utilizing patient samples, is important to establish reliable diagnostic pipelines.
Here, we assessed indirect methods that require RNA extraction with direct RT-qPCR on patient samples. Four different RNA extraction kits (Qiagen, Invitrogen, BGI and Norgen Biotek) were compared. For detection, we assessed two recently developed Taqman-based modules (BGI and Norgen Biotek), a SYBR green-based approach (NEB Luna Universal One-Step Kit) with published and newly-developed primers, and clinical results (Seegene STARMag RNA extraction system and Allplex 2019-nCoV RT-qPCR assay). We also tested and optimized direct, extraction-free detection using these RT-qPCR systems and performed a cost analysis of the different methods evaluated here.
Most RNA isolation procedures performed similarly, and while all RT-qPCR modules effectively detected purified viral RNA, the BGI system provided overall superior performance (lower detection limit, lower Ct values and higher sensitivity), generating comparable results to original clinical diagnostic data, and identifying samples ranging from 65 copies to 2.1 × 10
copies of viral genome/μl. However, the BGI detection system is more expensive than other options tested here. With direct RT-qPCR, simply adding an RNase inhibitor greatly improved detection, without the need for any other treatments (e.g. lysis buffers or boiling). The best direct methods detected ~ 10 fold less virus than indirect methods, but this simplified approach reduced sample handling, as well as assay time and cost.
With extracted RNA, the BGI RT-qPCR detection system exhibited superior performance over the Norgen system, matching initial clinical diagnosis with the Seegene Allplex assay. The BGI system was also suitable for direct, extraction-free analysis, providing 78.4% sensitivity. The Norgen system, however, still accurately detected samples with a clinical Ct < 33 from extracted RNA, provided significant cost savings, and was superior to SYBR green assays that exhibited reduced specificity.
The Truncated Disk of CoKu Tau/4 D’Alessio, Paola; Hartmann, Lee; Calvet, Nuria ...
The Astrophysical journal,
03/2005, Letnik:
621, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We present a model of a dusty disk with an inner hole that accounts for the Spitzer Space Telescope Infrared Spectrograph observations of the low-mass pre-main-sequence star CoKu Tau/4. We have ...modeled the mid-infrared spectrum (between 8 and 25 mu m) as arising from the inner wall of a disk. Our model disk has an evacuated inner zone of radius similar to 10 AU, with a dusty inner "wall" of half-height similar to 2 AU that is illuminated at normal incidence by the central star. The radiative equilibrium temperature decreases from the inner disk edge outward through the optically thick disk; this temperature gradient is responsible for the emission of the silicate bands at 10 and 20 mu m. The observed spectrum is consistent with being produced by Fe-Mg amorphous glassy olivine and/or pyroxene, with no evidence of a crystalline component. The mid-infrared spectrum of CoKu Tau/4 is reminiscent of that of the much older star TW Hya, where it has been suggested that the significant clearing of its inner disk is due to planet formation. However, no inner disk remains in CoKu Tau/4, consistent with the star being a weak-emission (nonaccreting) T Tauri star. The relative youth of CoKu Tau/4 ( similar to 1 Myr) may indicate much more rapid planet formation than typically assumed.
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