17 research outputs found
Urban forest fragmentation impoverishes native mammalian biodiversity in the tropics
Urban expansion has caused major deforestation and forest fragmentation in the tropics. The impacts of habitat fragmentation on biodiversity are understudied in urban forest patches, especially in the tropics and little is known on the conservation value of the patches for maintaining mammalian biodiversity. In this study, camera trapping was used to determine the species composition and species richness of medium‐ and large‐sized mammals in three urban forest patches and a contiguous forest in Peninsular Malaysia. We identified the key vegetation attributes that predicted mammal species richness and occurrence of herbivores and omnivores in urban forest patches. A total number of 19 mammal species from 120 sampling points were recorded. Contiguous forest had the highest number of species compared to the urban forest patches. Sunda Pangolin and Asian Tapir were the only conservation priority species recorded in the urban forest patches and contiguous forest, respectively. Top predators such as Malayan Tiger and Melanistic Leopard were completely absent from the forest patches as well as the contiguous forest. This was reflected by the abundance of wild boars. We found that mammal species richness increased with the number of trees with DBH less than 5 cm, trees with DBH more than 50 cm, and dead standing trees. In the future, the remaining mammal species in the urban forest patches are expected to be locally extinct as connecting the urban forest patches may be infeasible due to land scarcity. Hence, to maintain the ecological integrity of urban forest patches, we recommend that stakeholders take intervention measures such as reintroduction of selected species and restocking of wild populations in the urban forest patches to regenerate the forest ecosystems
Habitat occupancy patterns and activity rate of native mammals in tropical fragmented peat swamp reserves in Peninsular Malaysia
Intensive land use plays a major role in tropical peat swamp deforestation in Southeast Asia. In Peninsular Malaysia, the North Selangor Peat Swamp Forest (NSPSF) is the second largest remaining peatland ecosystem. Although the NSPSF is recognized as a biodiversity hotspot area in the region, this peat swamp forest is rapidly shrinking because of the expansion of commercial oil palm agriculture. More than 87% of the NSPSF has been designated as reserves, but in reality, this is not comparable to protected area status. The NSPSF is under constant threats from forest conversions, forest fires, and road constructions. Faunal biodiversity loss is likely to occur in the NSPSF unless immediate action is taken by stakeholders. To determine the habitat occupancy and activity rate of native mammals, we conducted camera-trap survey at 45 sites located within the NSPSF. From a total survey effort of 2565 trap nights in an area of 778 km2, 16 mammal species were recorded. Our data provide vital information on the occupancy of high conservation value species in the NSPSF. However, we did not record Sumatran rhinoceros (Dicerorhinus sumatrensis) and Malayan tiger (Panthera tigris), nor did we find any indirect evidence such as footprints, indicating that these species are extirpated from this region. We found that mammal activity rate responded differently to in situ habitat quality and landscape factors according to feeding guild. Government stakeholders should focus on prohibiting further forest conversion and prioritize the upgrading NSPSF’s conservation status from reserve to protected area
Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ
Abstract Introduction Basal-like and luminal breast cancers have distinct stromal–epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal–epithelial interactions evolve in benign and pre-invasive lesions. Methods To study epithelial–stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ). We used gene expression microarrays to identify pathways induced by coculture in premalignant cells (MCF10DCIS) compared with normal and benign cells (MCF10A and MCF10AT1). Relevant pathways were then evaluated in vivo for associations with basal-like subtype and were targeted in vitro to evaluate effects on morphogenesis. Results Our results show that premalignant MCF10DCIS cells express characteristic gene expression patterns of invasive basal-like microenvironments. Furthermore, while hepatocyte growth factor (HGF) secretion is upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured with either atypical (MCF10AT1) or premalignant (MCF10DCIS) cells, only MCF10DCIS cells upregulated the HGF receptor MET. In three-dimensional cultures, upregulation of HGF/MET in MCF10DCIS cells induced morphological changes suggestive of invasive potential, and these changes were reversed by antibody-based blocking of HGF signaling. These results are relevant to in vivo progression because high expression of a novel MCF10DCIS-derived HGF signature was correlated with the basal-like subtype, with approximately 86% of basal-like cancers highly expressing the HGF signature, and because high expression of HGF signature was associated with poor survival. Conclusions Coordinated and complementary changes in HGF/MET expression occur in epithelium and stroma during progression of pre-invasive basal-like lesions. These results suggest that targeting stroma-derived HGF signaling in early carcinogenesis may block progression of basal-like precursor lesions
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute
neurological illness with high mortality among children occur annually in Muzaffarpur, the country’s largest litchi
cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness.
Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory
investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were
children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or
altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals
for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood,
cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious
pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or
methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic
derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness
were expressed as matched odds ratios and odds ratios (unmatched analyses).
Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral
hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration
of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched
odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness
onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis
on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal).
Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in
48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens
had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi
arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged
from 44·9 μg/g to 220·0 μg/g.
Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both
hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising
litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected
illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations,
underscoring the importance of using systematic methods in other unexplained illness outbreaks
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Habitat fragmentation and logging affect the occurrence of lesser mouse-deer in tropical forest reserves
Due to rapid urbanization, logging, and agricultural expansion, forest fragmentation is negatively affecting native wildlife populations throughout the tropics. This study examined the effects of landscape and habitat characteristics on the lesser mouse-deer, Tragulus kanchil, populations in Peninsular Malaysia. We conducted camera-trap survey at 315 sampling points located within 8 forest reserves. An assessment of site-level and landscape variables was conducted at each sampling point. Our study provides critical ecological information for managing and conserving understudied populations of T. kanchil. We found that the detection of T. kanchil was attributed to forest fragmentation in which forest patches had four times greater detection of T. kanchil than continuous forest. The detection of T. kanchil was nearly three times higher in peat swamp forest compared to lowland dipterocarp forests. Surprisingly, the detection of T. kanchil was higher in logged forests (logging ceased at least 30 years ago) than unlogged forests. The detection of T. kanchil increased with the presence of trees, particularly those with DBH of 5 cm to 45 cm, canopy cover, number of saplings and palms, number of dead fallen trees, and distance from nearest roads. However, detection decreased with a greater number of trees with DBH greater than 45 cm and higher elevations, and greater detections where creeping bamboo was abundant. We recommend that conservation stakeholders take the necessary steps (e.g., eradicating poaching, habitat degradation, and further deforestation) to support the conservation of mouse-deer species and its natural habitats
La renonciation aux droits fondamentaux. La libre disposition de soi et le règne de l'échange
Legal and illegal logging is prevalent throughout the tropics, impacting on natural habitat and wildlife. This study aimed to investigate the sensitivity of forest mammals to selective logging in the lowland dipterocarp forests of South-West Peninsular Malaysia and identify the underlying factors that determine species occurrence. A total of 120 camera trap locations were deployed within selectively logged and unlogged forests. We found that unlogged forest had greater wildlife occurrences compared to selectively logged forests, including two endangered mammal species not found in logged forest. Forest vegetation structure characteristics such as the abundance of lianas, large trees, saplings, palms, bamboo and seedlings were associated with mammal species richness. Mammal species richness increased with number of forest trees, particularly those with a DBH of >45 cm, but this was limited to high altitude forest. Worryingly, we did not detect any large mammalian apex predators such as leopards or tigers in either unlogged or selectively logged forests. The absence of these animals may be the result of poaching, habitat degradation or other pressures; these mammals are expected to be present in intact forests in Peninsular Malaysia. Restoring logged forests and preserving the remaining unlogged lowland dipterocarp forests are critically important to safeguard mammalian biodiversity in the region. Besides that, we recommend that conventional logging practices are replaced with reduced impact logging methods.</p
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Summary: Background: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. Methods: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). Findings: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. Interpretation: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. Funding: US Centers for Disease Control and Prevention
Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study
Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12–1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13–1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25–1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08–1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15–1·32], p<0·0001; and for ORMDL3 (β 1·19 [1·12–1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15–1·44], p<0·0001). Interpretation: Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12–21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus.6 month embargo; published: 01 May 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]