91 research outputs found

    Reference Conditions and Spatial Dynamics in a Southwestern Dry Mixed-Conifer Forest

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    Structural conditions in southwestern “frequent-fire” forests, or forests that have a history of frequent, low-severity fire, have changed considerably since Euro-American settlement (ca. late 1800's); these changes are primarily due to excessive livestock grazing, extractive logging, road construction, and organized fire suppression. As a result of these land-use changes, forest densities in many locations have increased, contributing to increases in fire size and severity and alterations to ecosystem function. A recognition of these impacts has prompted interest in forest restoration treatments across broad swaths of the landscape. Forest restoration attempts to mimic the natural range of variability - or the structure and function inherent to intact natural ecosystems - but many aspects of these ecosystems are poorly understood. In combination with studies of the natural disturbance regime, reference conditions and studies of the natural range of variability also provide an ecological basis for silvicultural treatments. Spatial pattern, or the horizontal distribution of trees, is an important component of the natural range of variability and influences a wide array of ecological processes. With this study, we reconstructed historical structure (density and spatial pattern) and species composition for four dry mixed-conifer stands on the Mogollon Rim, Arizona, USA. We reconstructed conditions from the year 1879, the time of the widespread cessation of fire in the area. We found that these forests showed evidence of increased tree density between 1879 and 2014 with major increases in density in the smaller size classes. During this time period, the number of live trees ha-1 increased from an average of 129.5 to 744.3, basal area increased from 10.1 to 41.9 m2 ha-1, and mean canopy cover increased from 14.8 to 54.7 percent. Our results also showed shifts in species composition to a higher relative proportion of Abies concolor, and Pseudotsuga menziesii, and a lower relative proportion of Pinus ponderosa and Quercus gambelii. Mean group size, or the average number of trees in explicit tree groups, also increased as tree canopy cover became more continuous. Finally, we investigated the roles of different species groups within fine-scale spatial pattern. Species groups showed distinctly different patterns, suggesting that the patterns of individual species are an important consideration during the implementation of silvicultural treatments that are meant to mimic natural patterns and processes. Mechanical treatments and thinning operations in dry mixed-conifer forests on the Mogollon Rim should target an aggregated spatial structure of leave trees with a range of group sizes within a given site. Treatments based on the natural range of variability are likely to increase resistance and resilience of these ecosystems in the face of uncertain future conditions

    Associations between police harassment and distrust in and reduced access to healthcare among Black sexual minority men: A longitudinal analysis of HPTN 061

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    Objective: Evaluate associations between racialized and homophobia-based police harassment (RHBPH) and healthcare distrust and utilization among Black Sexual Minority Men (BSMM). Methods: We utilized data from a longitudinal cohort study from HIV Prevention Trials Network (HPTN) 061 with baseline, six and 12 month follow-up assessments. Using multivariable analysis, we evaluated associations between RHBPH and healthcare distrust and utilization reported at the 6 and 12 month visits. Results: Of 1553 BSMM present at baseline, 1160 were available at six-month follow-up. In multivariable analysis, increasing frequency of RHBPH was associated with increasing levels of distrust in healthcare providers (aOR 1.31, 95% CI: 1.00, 1.74) and missing 50% or more of healthcare visits at six-month follow-up (aOR 1.93, 95% CI: 1.09, 3.43). Conclusions: Recent experiences of RHBPH are associated with reduced trust in and access to healthcare among BSMM, with more frequent RHBPH associated with greater vulnerability.</p

    Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

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    Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management

    The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation

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    Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes. The neuropeptide receptor Nmur1 was preferentially expressed by ILC2s at steady state and after IL-25 stimulation. Neuromedin U (NMU), the ligand of NMUR1, activated ILC2s in vitro, and in vivo co-administration of NMU with IL-25 strongly amplified allergic inflammation. Loss of NMU-NMUR1 signalling reduced ILC2 frequency and effector function, and altered transcriptional programs following allergen challenge in vivo. Thus, NMUR1 signalling promotes inflammatory ILC2 responses, highlighting the importance of neuro-immune crosstalk in allergic inflammation at mucosal surfaces

    Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq

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    Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME).We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation. As tumor grade increases, we find enhanced proliferation of malignant cells, larger pools of undifferentiated glioma cells, and an increase in macrophage over microglia expression programs in TME. Our work provides a unifying model for IDH-mutant gliomas and a general framework for dissecting the differences among human tumor subclasses.National Cancer Institute (U.S.) (Grant P30-CA14051

    Children must be protected from the tobacco industry's marketing tactics.

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    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability
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