Maize (Zea mays L.) is one of the most important cereal crops and a model for the study of genetics, evolution, and domestication. To better understand maize genome organization and to build a ...framework for genome sequencing, we constructed a sequence-ready fingerprinted contig-based physical map that covers 93.5% of the genome, of which 86.1% is aligned to the genetic map. The fingerprinted contig map contains 25,908 genic markers that enabled us to align nearly 73% of the anchored maize genome to the rice genome. The distribution pattern of expressed sequence tags correlates to that of recombination. In collinear regions, 1 kb in rice corresponds to an average of 3.2 kb in maize, yet maize has a 6-fold genome size expansion. This can be explained by the fact that most rice regions correspond to two regions in maize as a result of its recent polyploid origin. Inversions account for the majority of chromosome structural variations during subsequent maize diploidization. We also find clear evidence of ancient genome duplication predating the divergence of the progenitors of maize and rice. Reconstructing the paleoethnobotany of the maize genome indicates that the progenitors of modern maize contained ten chromosomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anthropogenic releases of mercury (Hg)
are a human health issue
because the potent toxicant methylmercury (MeHg), formed primarily by microbial methylation of inorganic Hg in aquatic ecosystems, ...bioaccumulates to high concentrations in fish consumed by humans
. Predicting the efficacy of Hg pollution controls on fish MeHg concentrations is complex because many factors influence the production and bioaccumulation of MeHg
. Here we conducted a 15-year whole-ecosystem, single-factor experiment to determine the magnitude and timing of reductions in fish MeHg concentrations following reductions in Hg additions to a boreal lake and its watershed. During the seven-year addition phase, we applied enriched Hg isotopes to increase local Hg wet deposition rates fivefold. The Hg isotopes became increasingly incorporated into the food web as MeHg, predominantly from additions to the lake because most of those in the watershed remained there. Thereafter, isotopic additions were stopped, resulting in an approximately 100% reduction in Hg loading to the lake. The concentration of labelled MeHg quickly decreased by up to 91% in lower trophic level organisms, initiating rapid decreases of 38-76% of MeHg concentration in large-bodied fish populations in eight years. Although Hg loading from watersheds may not decline in step with lowering deposition rates, this experiment clearly demonstrates that any reduction in Hg loadings to lakes, whether from direct deposition or runoff, will have immediate benefits to fish consumers.
Previous approaches to comparing gene and chromosome organization between two genomes have been based on genetic maps or genomic sequences. We have developed a system to align an FPC-based physical ...map to a genomic sequence based on BAC end sequences and sequence-tagged hybridization markers and to align two FPC maps to one another based on shared markers and fingerprints. The system, called SyMAP (Synteny Mapping and Analysis Program), consists of an algorithm to compute synteny blocks and Web-based graphics to visualize the results. The approach to calculating the anchors (corresponding elements on the respective maps) maximizes the inclusion of anchors with different rates of divergence. Chains (putative syntenic sets of anchors) are computed using a dynamic programming algorithm, which includes off-diagonal anchors that result from map coordinate errors and small inversions. As the gap parameters (the distances allowed between anchors in a chain) can vary over different data sets and be difficult to set manually, they are automatically computed per data set. The criterion for a chain to be acceptable is based on the number of anchors and the Pearson correlation coefficient. Neighboring chains are merged into synteny blocks for display. This algorithm has been tested with three data sets that vary in the number of BACs, BAC end sequences, hybridization markers, distance between anchors, and number and antiquity of genome duplication events. The Web-based graphics uses Java for a highly interactive display that allows the user to interrogate the evidence of synteny.
Infection is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Our object was to better define the epidemiology and outcomes of infections after HCT.
...This was a prospective, multicenter cohort study of HCT recipients and conducted from 2006 to 2011. The study included 4 US transplant centers and 444 HCT recipients. Data were prospectively collected for up to 30 months after HCT using a standardized data collection tool.
The median age was 53 years, and median follow up was 413 (range, 5-980) days. The most common reason for HCT was hematologic malignancy (87%). The overall crude mortality was 52%. Death was due to underlying disease in 44% cases and infection in 21%. Bacteremia occurred in 231 (52%) cases and occurred early posttransplant (median day 48). Gram-negative bloodstream infections were less frequent than Gram-positive, but it was associated with higher mortality (45% vs 13%,
= .02).
infection developed in 148 patients (33%) at a median of 27 days post-HCT. There were 53 invasive fungal infections (IFIs) among 48 patients (11%). The median time to IFI was 142 days. Of 155 patients with cytomegalovirus (CMV) infection, 4% had CMV organ involvement. Varicella zoster infection (VZV) occurred in 13 (4%) cases and was disseminated in 2. Infection with respiratory viruses was seen in 49 patients.
pneumonia was rare (1%), and there were no documented cases of nocardiosis, toxoplasmosis, endemic mycoses, or mycobacterial infection. This study lacked standardized antifungal and antiviral prophylactic strategies.
Infection remains a significant cause of morbidity and mortality after HCT. Bacteremias and
infection are frequent, particularly in the early posttransplant period. The rate of IFI is approximately 10%. Organ involvement with CMV is infrequent, as are serious infections with VZV and herpes simplex virus, likely reflecting improved prevention strategies.
Background: Complex Trauma (CT) is a term used to refer to multiple or prolonged traumatic experiences. Such experiences are often first encountered during childhood and may impact key developmental ...periods. CT is a risk for a broad range of deleterious physical, psychological, social, and occupational outcomes. The diagnosis of Complex Posttraumatic Stress Disorder (C-PTSD) has been proposed to capture the symptomatology resulting from CT exposure.
In Australia, there are few publicly funded services that target, and are purposely designed to support, the mental health needs of young people with symptoms of complex post-traumatic stress (C-PTSD). The Tern Programme has been designed as a purpose-built model of care for providing mental health support to young people with C-PTSD.
Methods: This implementation trial will involve a longitudinal examination of Tern participants for a fixed 24-month period. Participants will be recruited from the young people referred to Tern at headspace centres in regional Australia where Tern operates. Eligible participants will have reported a history of complex trauma, and present with symptoms of C-PTSD. All participants will be invited to complete a series of surveys during their participation in the programme. Survey items will assess C-PTSD symptom change, quality of life and occupational functioning.
The Tern model of care is delivered in a semi-structured format to accommodate a person-centred flexible approach. Fidelity will be monitored through the completion of a clinician post-session checklist and through group supervision.
Discussion: This study will provide the first quantitative data on the new Tern model of care and evaluate mental health and functional outcomes of its participants. If effective, Tern may be suitable for replication in other Australian or international youth mental health services where complex post-traumatic stress is prevalent.
Trial Registration: Australia and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000079842p. Prospectively registered on 29 January 2021.
Abbreviations: CT = Complex Trauma; C-PTSD = Complex Posttraumatic Stress Disorder
Tern represents a new model of care incorporating a flexible, person-centred approach to C-PTSD treatment whilst providing for the complex needs of young people as well as the wellbeing of the staff delivering the intervention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define ...characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.
We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality.
We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 30% of 69, respiratory 69 19% of 358, wound nine 14% of 66, urine six 7% of 88; p=0·0012) and geographical region (Middle East 15 29% of 52, south and central America 20 27% of 73, USA 60 19% of 308, Australia and Singapore three 11% of 28, China seven 6% of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 69% of 127, Australia and Singapore 32 57% of 56, China 54 32% of 171, Middle East 27 30% of 91, USA ten 2% of 527; p<0·0001). KPC-2 (n=103 49%) and VIM-2 (n=75 36%) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 22% of 120 vs 19 12% of 153; difference 9%, 95% CI 3–16) and adjusted (difference 7%, 95% CI 1–14) analyses.
The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms.
National Institutes of Health.
Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We ...extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10
). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10
) and the risk of type 2 diabetes (P=6.1×10
) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10
). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10
), and pentose and glucuronate interconversions (P=3.0×10
) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.
Methylmercury contamination of fisheries from centuries of industrial atmospheric emissions negatively impacts humans and wildlife worldwide. The response of fish methylmercury concentrations to ...changes in mercury deposition has been difficult to establish because sediments/soils contain large pools of historical contamination, and many factors in addition to deposition affect fish mercury. To test directly the response of fish contamination to changing mercury deposition, we conducted a whole-ecosystem experiment, increasing the mercury load to a lake and its watershed by the addition of enriched stable mercury isotopes. The isotopes allowed us to distinguish between experimentally applied mercury and mercury already present in the ecosystem and to examine bioaccumulation of mercury deposited to different parts of the watershed. Fish methylmercury concentrations responded rapidly to changes in mercury deposition over the first 3 years of study. Essentially all of the increase in fish methylmercury concentrations came from mercury deposited directly to the lake surface. In contrast, <1% of the mercury isotope deposited to the watershed was exported to the lake. Steady state was not reached within 3 years. Lake mercury isotope concentrations were still rising in lake biota, and watershed mercury isotope exports to the lake were increasing slowly. Therefore, we predict that mercury emissions reductions will yield rapid (years) reductions in fish methylmercury concentrations and will yield concomitant reductions in risk. However, a full response will be delayed by the gradual export of mercury stored in watersheds. The rate of response will vary among lakes depending on the relative surface areas of water and watershed.
Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants ...associated with onset of ESKD in individuals with type 1 diabetes at advanced kidney disease stage.
Gene-based exome array analyses of 15,449 genes in five large incidence cohorts of individuals with type 1 diabetes and proteinuria were analyzed for survival time to ESKD, testing the top gene in a sixth cohort (
=2372/1115 events all cohorts) and replicating in two retrospective case-control studies (
=1072 cases, 752 controls). Deep resequencing of the top associated gene in five cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models.
Protein coding variants in the hydroxysteroid 17-
dehydrogenase 14 gene (
), predicted to affect protein structure, had a net protective effect against development of ESKD at exome-wide significance (
=4196;
value=3.3 × 10
). The
gene and encoded enzyme were robustly expressed in healthy human kidney, maximally in proximal tubular cells. Paradoxically, gene and protein expression were attenuated in human diabetic proximal tubules and in mouse kidney injury models. Expressed
gene and protein levels remained low without recovery after 21 days in a murine ischemic reperfusion injury model. Decreased gene expression was found in other CKD-associated renal pathologies.
gene is mechanistically involved in diabetic kidney disease. The encoded sex steroid enzyme is a druggable target, potentially opening a new avenue for therapeutic development.
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