Origin of Irreversibility of Cell Cycle Start in Budding Yeast

In budding yeast, the commitment to entry into a new cell division cycle is made irreversible by positive feedback-driven expression of the G1 cyclins Cln1,2

Consistency and discrepancy in the atmospheric response to Arctic sea-ice loss across climate models

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordThe decline of Arctic sea ice is an integral part of anthropogenic climate change. Sea-ice loss is already having a significant impact on Arctic communities and ecosystems. Its role as a cause of climate changes outside of the Arctic has also attracted much scientific interest. Evidence is mounting that Arctic sea-ice loss can affect weather and climate throughout the Northern Hemisphere. The remote impacts of Arctic sea-ice loss can only be properly represented using models that simulate interactions among the ocean, sea ice, land and atmosphere. A synthesis of six such experiments with different models shows consistent hemispheric-wide atmospheric warming, strongest in the mid-to-high-latitude lower troposphere; an intensification of the wintertime Aleutian Low and, in most cases, the Siberian High; a weakening of the Icelandic Low; and a reduction in strength and southward shift of the mid-latitude westerly winds in winter. The atmospheric circulation response seems to be sensitive to the magnitude and geographic pattern of sea-ice loss and, in some cases, to the background climate state. However, it is unclear whether current-generation climate models respond too weakly to sea-ice change. We advocate for coordinated experiments that use different models and observational constraints to quantify the climate response to Arctic sea-ice loss.J.A.S. and R.B. were funded by the Natural Environment Research Council (NE/P006760/1). C.D. acknowledges the National Science Foundation (NSF), which sponsors the National Center for Atmospheric Research. D.M.S. was supported by the Met Office Hadley Centre Climate Programme (GA01101) and the APPLICATE project, which is funded by the European Union’s Horizon 2020 programme. X.Z. was supported by the NSF (ARC#1023592). P.J.K. and K.E.M. were supported by the Canadian Sea Ice and Snow Evolution Network, which is funded by the Natural Science and Engineering Research Council of Canada. T.O. was funded by Environment and Climate Change Canada (GCXE17S038). L.S. was supported by the National Oceanic and Atmospheric Administration’s Climate Program Office

Population stratification may bias analysis of PGC-1α as a modifier of age at Huntington disease motor onset

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive and behavioral disturbances, caused by the expansion of a CAG trinucleotide repeat in the HD gene. The CAG allele size is the major determinant of age at onset (AO) of motor symptoms, although the remaining variance in AO is highly heritable. The rs7665116 SNP in PPARGC1A, encoding the mitochondrial regulator PGC-1α, has been reported to be a significant modifier of AO in three European HD cohorts, perhaps due to affected cases from Italy. We attempted to replicate these findings in a large collection of (1,727) HD patient DNA samples of European origin. In the entire cohort, rs7665116 showed a significant effect in the dominant model (p value = 0.008) and the additive model (p value = 0.009). However, when examined by origin, cases of Southern European origin had an increased rs7665116 minor allele frequency (MAF), consistent with this being an ancestry-tagging SNP. The Southern European cases, despite similar mean CAG allele size, had a significantly older mean AO (p < 0.001), suggesting population-dependent phenotype stratification. When the generalized estimating equations models were adjusted for ancestry, the effect of the rs7665116 genotype on AO decreased dramatically. Our results do not support rs7665116 as a modifier of AO of motor symptoms, as we found evidence for a dramatic effect of phenotypic (AO) and genotypic (MAF) stratification among European cohorts that was not considered in previously reported association studies. A significantly older AO in Southern Europe may reflect population differences in genetic or environmental factors that warrant further investigation

Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington’s disease motor onset

Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. It is caused by the expansion of the HTT CAG repeat, which is the major determinant of age at onset (AO) of motor symptoms. Aberrant function of N-methyl-D-aspartate receptors and/or overexposure to dopamine has been suggested to cause significant neurotoxicity, contributing to HD pathogenesis. We used genetic association analysis in 1,628 HD patients to evaluate candidate polymorphisms in N-methyl-D-aspartate receptor subtype genes (GRIN2A rs4998386 and rs2650427, and GRIN2B rs1806201) and functional polymorphisms in genes in the dopamine pathway (DAT1 3′ UTR 40-bp variable number tandem repeat (VNTR), DRD4 exon 3 48-bp VNTR, DRD2 rs1800497, and COMT rs4608) as potential modifiers of the disease process. None of the seven polymorphisms tested was found to be associated with significant modification of motor AO, either in a dominant or additive model, after adjusting for ancestry. The results of this candidate-genetic study therefore do not provide strong evidence to support a modulatory role for these variations within glutamatergic and dopaminergic genes in the AO of HD motor manifestations

Respective impacts of Arctic sea ice decline and increasing greenhouse gases concentration on Sahel precipitation

The impact of climate change on Sahel precipitation is uncertain and has to be widely documented. Recently, it has been shown that Arctic sea ice loss leverages the global warming effects worldwide, suggesting a potential impact of Arctic sea ice decline on tropical regions. However, defining the specific roles of increasing greenhouse gases (GHG) concentration and declining Arctic sea ice extent on Sahel climate is not straightforward since the former impacts the latter. We avoid this dependency by analysing idealized experiments performed with the CNRM-CM5 coupled model. Results show that the increase in GHG concentration explains most of the Sahel precipitation change. We found that the impact due to Arctic sea ice loss depends on the level of atmospheric GHG concentration. When the GHG concentration is relatively low (values representative of 1980s), then the impact is moderate over the Sahel. However, when the concentration in GHG is levelled up, then Arctic sea ice loss leads to increased Sahel precipitation. In this particular case the ocean-land meridional gradient of temperature strengthens, allowing a more intense monsoon circulation. We linked the non-linearity of Arctic sea ice decline impact with differences in temperature and sea level pressure changes over the North Atlantic Ocean. We argue that the impact of the Arctic sea ice loss will become more relevant with time, in the context of climate change

What’s in a price? the American raw cotton market in Liverpool and the Anglo-American war

This article argues that an embryonic futures market was present in Liverpool during the Anglo-American war. The analysis of a previously unseen dataset of printed Prices Currents has facilitated not only a price series of raw cotton prices, but an in-depth analysis of the ‘construction’ of those raw cotton prices. By positing a definition of.an embryonic futures market and then analysing each of the features of a such a market in turn, this study demonstrates the existence of an embryonic futures market in early nineteenth-century Liverpool

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

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

Deagrarianisation and forest revegetation in a biodiversity hotspot on the Wild Coast, South Africa

Deagraianisation is a worldwide phenomenon with widespread social, ecological and economic effects yet with little consensus on the local or higher level causes. There have been contested views on the causes and consequences of deagrarianisation on South Africa’s Wild Coast, which is an international biodiversity hotspot. Using GIS, household interviews and ecological sampling, we compared the perspectives of current and former cultivators as to why some have abandoned farming, whilst also tracking the uses and woody plant cover and composition of fields abandoned at different periods. The GIS analysis showed that field abandonment had been ongoing over several decades, with a decline from 12.5 % field cover in 1961 to 2.7 % in 2009. The area of forests and woodlands almost doubled in the corresponding period. There was a distinct peak in field abandonment during the time of political transition at the national level in the early 1990s. This political change led to a decrease in government support for livestock farming, which in turn resulted in reduced animal draught power at the household and community level, and hence reduced cropping. The study showed it is largely the wealthier households that have remained in arable agriculture and that the poorer households have abandoned farming. The abandoned fields show a distinct trend of increasing woody biomass and species richness with length of time since abandonment, with approximately three woody plant species added per decade. Most local respondents dislike the increases in forest and woodland extent and density because of anxiety about wild animals causing harm to crops and even humans, and the loss of an agricultural identity to livelihoods and the landscape