Climate change has already triggered species distribution shifts in many parts of the world. Increasing impacts are expected for the future, yet few studies have aimed for a general understanding of ...the regional basis for species vulnerability. We projected late 21st century distributions for 1,350 European plants species under seven climate change scenarios. Application of the International Union for Conservation of Nature and Natural Resources Red List criteria to our projections shows that many European plant species could become severely threatened. More than half of the species we studied could be vulnerable or threatened by 2080. Expected species loss and turnover per pixel proved to be highly variable across scenarios (27-42% and 45-63% respectively, averaged over Europe) and across regions (2.5-86% and 17-86%, averaged over scenarios). Modeled species loss and turnover were found to depend strongly on the degree of change in just two climate variables describing temperature and moisture conditions. Despite the coarse scale of the analysis, species from mountains could be seen to be disproportionably sensitive to climate change (≈60% species loss). The boreal region was projected to lose few species, although gaining many others from immigration. The greatest changes are expected in the transition between the Mediterranean and Euro-Siberian regions. We found that risks of extinction for European plants may be large, even in moderate scenarios of climate change and despite inter-model variability.
Aims/hypothesis
Sirtuin 1 (SIRT1) has emerged as a key metabolic regulator of glucose homeostasis and insulin secretion. Enhanced SIRT1 activity has been shown to be protective against diabetes, ...although the mechanisms remain largely unknown. The aim of this study was to determine how SIRT1 regulates insulin secretion in the pancreatic beta cell.
Methods
Pancreatic beta cell-specific
Sirt1
deletion was induced by tamoxifen injection in 9-week-old
Pdx1CreER
:
floxSirt1
mice (
Sirt1
BKO). Controls were injected with vehicle. Mice were assessed metabolically via glucose challenge, insulin tolerance tests and physical variables. In parallel,
Sirt1
short interfering RNA-treated MIN6 cells (SIRT1KD) and isolated
Sirt1
BKO islets were used to investigate the effect of SIRT1 inactivation on insulin secretion and gene expression.
Results
OGTTs showed impaired glucose disposal in
Sirt1
BKO mice due to insufficient insulin secretion. Isolated
Sirt1
BKO islets and SIRT1KD MIN6 cells also exhibited impaired glucose-stimulated insulin secretion. Subsequent analyses revealed impaired α-ketoisocaproic acid-induced insulin secretion and attenuated glucose-induced Ca
2+
influx, but normal insulin granule exocytosis in
Sirt1
BKO beta cells. Microarray studies revealed a large cluster of mitochondria-related genes, the expression of which was dysregulated in SIRT1KD MIN6 cells. Upon further analysis, we demonstrated an explicit defect in mitochondrial function: the inability to couple nutrient metabolism to mitochondrial membrane hyperpolarisation and reduced oxygen consumption rates.
Conclusions/interpretation
Taken together, these findings indicate that in beta cells the deacetylase SIRT1 regulates the expression of specific mitochondria-related genes that control metabolic coupling, and that a decrease in beta cell
Sirt1
expression impairs glucose sensing and insulin secretion.
Summary Background Growth faltering remains common in children in sub-Saharan Africa and is associated with substantial morbidity and mortality. Due to a very slow decline in the prevalence of ...stunting, the total number of children with stunting continues to rise in sub-Saharan Africa. Identification of effective interventions remains a challenge. Methods We analysed the effect of 36 years of intensive health interventions on growth in infants and young children from three rural Gambian villages. Routine growth data from birth to age 2 years were available for 3659 children between 1976 and 2012. Z scores for weight-for-age, length-for-age, weight-for-length, mid-upper-arm circumference, and head circumference were calculated using the WHO 2006 growth standards. Seasonal patterns of mean Z scores were obtained by Fourier regression. We additionally defined growth faltering as fall in Z score between 3 months and 21 months of age. Findings We noted secular improvements in all postnatal growth parameters (except weight-for-length), accompanied by declines over time in seasonal variability. The proportion of children with underweight or stunting at 2 years of age halved during four decades of the study period, from 38·7% (95% CI 33·5–44·0) for underweight and 57·1% (51·9–62·4) for stunting. However, despite unprecedented levels of intervention, postnatal growth faltering persisted, leading to poor nutritional status at 24 months (length-for-age Z score −1·36, 95% CI −1·44 to −1·27, weight-for-age Z score −1·20, −1·28 to −1·11, and head circumference Z score −0·51, −0·59 to −0·43). The prevalence of stunting and underweight remained unacceptably high (30·0%, 95% CI 27·0–33·0, for stunting and 22·1%, 19·4 to 24·8, for underweight). Interpretation A combination of nutrition-sensitive and nutrition-specific interventions has achieved a halving of undernutrition rates, but despite these intensive interventions substantial growth faltering remains. We need to understand the missing contributors to growth faltering to guide development of new interventions. Funding UK Medical Research Council, UK Department for International Development.
As the severe acute respiratory syndrome coronavirus-2 pandemic has proceeded, ventilation has been recognized increasingly as an important tool in infection control. Many hospitals in Ireland and ...the UK do not have mechanical ventilation and depend on natural ventilation. The effectiveness of natural ventilation varies with atmospheric conditions and building design. In a challenge test of a legacy design ward, this study showed that portable air filtration significantly increased the clearance of pollutant aerosols of respirable size compared with natural ventilation, and reduced spatial variation in particle persistence. A combination of natural ventilation and portable air filtration is significantly more effective for particle clearance than either intervention alone.
Aims/hypothesis
Using a novel directed differentiation protocol, we recently generated up to 25% insulin-producing cells from human embryonic stem cells (hESCs) (insulin
+
cells). At this juncture, ...it was important to functionally and molecularly characterise these hESC-derived insulin
+
cells and identify key differences and similarities between them and primary beta cells.
Methods
We used a new reporter hESC line with green fluorescent protein (GFP) cDNA targeted to the
INS
locus by homologous recombination (
INS
GFP/w
) and an untargeted hESC line (HES2).
INS
GFP/w
allowed efficient identification and purification of GFP-producing (INS:GFP
+
) cells. Insulin
+
cells were examined for key features of adult beta cells using microarray, quantitative PCR, secretion assays, imaging and electrophysiology.
Results
Immunofluorescent staining showed complete co-localisation of insulin with GFP; however, cells were often multihormonal, many with granules containing insulin and glucagon. Electrophysiological recordings revealed variable K
ATP
and voltage-gated Ca
2+
channel activity, and reduced glucose-induced cytosolic Ca
2+
uptake. This translated into defective glucose-stimulated insulin secretion but, intriguingly, appropriate glucagon responses. Gene profiling revealed differences in global gene expression between INS:GFP
+
cells and adult human islets; however, INS:GFP
+
cells had remarkably similar expression of endocrine-lineage transcription factors and genes involved in glucose sensing and exocytosis.
Conclusions/interpretation
INS:GFP
+
cells can be purified from differentiated hESCs, providing a superior source of insulin-producing cells. Genomic analyses revealed that INS:GFP
+
cells collectively resemble immature endocrine cells. However, insulin
+
cells were heterogeneous, a fact that translated into important functional differences within this population. The information gained from this study may now be used to generate new iterations of functioning beta cells that can be purified for transplant.
The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: ...the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.
Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is increasingly recognized for its potential in the discovery of novel biomarkers directly from tissue sections. ...However, there are no MALDI IMS studies as yet on the adipose tissue, a lipid-enriched tissue that plays a pivotal role in the development of obesity-associated disorders. Herein, we aimed at developing an optimized method for analyzing adipose tissue lipid composition under both physiological and pathological conditions by MALDI IMS. Our studies showed an exacerbated lipid delocalization from adipose tissue sections when conventional strategies were applied. However, our optimized method using conductive-tape sampling and 2,5-dihydroxybenzoic acid (DHB) as a matrix, preserved the anatomical organization and minimized lipid diffusion from sample sections. This method enabled the identification of a total of 625 down-regulated and 328 up-regulated m/z values in the adipose tissue from a rat model of extreme obesity as compared to lean animals. Combination of MALDI IMS and liquid chromatography (LC)-MS/MS data identified 44 differentially expressed lipid species between lean and obese animals, including phospholipids and sphingomyelins. Among the lipids identified, SM(d18:0_18:2), PE(P-16:0_20:0), and PC(O-16:0_16:1) showed a differential spatial distribution in the adipose tissue of lean vs. obese animals. In sum, our method provides a valuable new tool for research on adipose tissue that may pave the way for the identification of novel biomarkers of obesity and metabolic disease.
Display omitted
•Conventional matrix deposition induced lipid diffusion in adipose tissue sections.•Conductive-tape sampling and DHB reduced adipose tissue lipid delocalization.•MALDI IMS revealed 625 down- and 328 up-regulated m/z values linked to obesity.•MALDI IMS revealed obesity-related differences in adipose tissue lipid distribution.
Several medical procedures involving the respiratory tract are considered as ‘aerosol-generating procedures’. Aerosols from these procedures may be inhaled by bystanders, and there are consequent ...concerns regarding the transmission of infection or, specific to nebulized therapy, secondary drug exposure.
To assess the efficacy of a proprietary high-efficiency-particulate-air-filtering extractor tent on reducing the aerosol dispersal of nebulized bronchodilator drugs.
The study was conducted in an unoccupied outpatient room at St. James's Hospital, Dublin, Ireland. A novel real-time, fluorescent particle counter, the Wideband Integrated Bioaerosol Sensor (WIBS), monitored room air continuously for 3 h. Baseline airborne particle count and count during nebulization of bronchodilator drug solutions were recorded.
Nebulization within the tent prevented any increase over background level. Nebulization directly into room air resulted in mean fluorescent particle counts of 4.75 x 105/m3 and 4.21 x 105/m3 for Ventolin and Ipramol, respectively, representing more than 400-fold increases over mean background level. More than 99.3% of drug particles were <2 μm in diameter and therefore small enough to enter the lower respiratory tract.
The extractor tent was completely effective for the prevention of airborne spread of drug particles of respirable size from nebulized therapy. This suggests that extractor tents of this type would be efficacious for the prevention of airborne infection from aerosol-generating procedures during the COVID-19 pandemic.
Summary
The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus ...400 IU of vitamin D
3
daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.
Introduction
This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality.
Methods
WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS).
Results
Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio HR for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38–1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44–0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive.
Conclusion
Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.
This study analysed the effectiveness of plasma treatment on airborne bacteria and surface counts during a 14-day intervention within a four-bedded bay in an adult respiratory ward at Cork University ...Hospital, Ireland. One-hundred-litre air samples were collected twice daily every weekday for 4 weeks, with settle plates and surface swabs. The plasma treatment did not have an effect on airborne bacteria and fungi that was detectable by culture. However, the possibility that culture-based sampling may be insufficiently sensitive to detect an effect, or that the duration of the study was insufficient for plasma treatment to affect a complex environment, cannot be excluded.
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