Size of Cell-Surface Kv2.1 Domains is Governed by Growth Fluctuations

AbstractThe Kv2.1 voltage-gated potassium channel forms stable clusters on the surface of different mammalian cells. Even though these cell-surface structures have been observed for almost a decade, little is known about the mechanism by which cells maintain them. We measure the distribution of domain sizes to study the kinetics of their growth. Using a Fokker-Planck formalism, we find no evidence for a feedback mechanism present to maintain specific domain radii. Instead, the size of Kv2.1 clusters is consistent with a model where domain size is established by fluctuations in the trafficking machinery. These results are further validated using likelihood and Akaike weights to select the best model for the kinetics of domain growth consistent with our experimental data

Lees and Moonshine: Remembering Richard III, 1485-1635

Published version of article deposited in accordance with Sherpa Romeo guidelines. © University of Chicago Press, 2010publication-status: AcceptedNot long after Shakespeare’s birth (1564) the last witnesses to the reign of Richard III (1483-85) would have reached the end of their lives. Richard III (c. 1592) occupies a distinctive historical moment in relation to its subject – a period after the extinction of living memory, but still within the horizon of communicative memory, the period in which stories and recollections may be transmitted across multiple generations. This essay explores how memories and “postmemories” of Richard’s reign were preserved, transmitted and transformed over the course of the sixteenth century and into the seventeenth. Whilst reflecting the powerful influence of emerging contexts including the Reformation and, ultimately, Shakespeare’s play, these memories remained distinct from and sometimes at odds with textual history. They survived because they offered their bearers a resource for interpreting and resisting the predicaments of the present, from the problem of tyranny to the legacies of the Reformation

Selfie-Objectification:Self-Objectification and Positive Feedback (“Likes”) are Associated with Frequency of Posting Sexually Objectifying Self-Images on Social Media

The present study is the first to examine the extent to which young adult women post objectifying self-images on social media, and whether the frequency of posting such content can be predicted by self-objectification and positive feedback (likes). Eighty-six young adult women from the UK (Age M = 19.88; SD = 1.34, Range = 18-24) completed self-report measures of self-objectification and social media use. The 20 most recent images they had posted on their personal Instagram accounts were downloaded (Image N = 1720) and content analysed for self-objectifying content. The analysis found that 29.77% of participants’ Instagram images were objectified, though there were individual differences. Higher frequency of posting objectified self-images was associated with trait self-objectification and receiving more likes on this type of self-image, relative to non-objectified self-images. The implications of the novel findings for objectification theory are discussed within

Volcanic controls on the microbial habitability of Mars‐analogue hydrothermal environments

Due to their potential to support chemolithotrophic life, relic hydrothermal systems on Mars are a key target for astrobiological exploration. We analysed water and sediments at six geothermal pools from the rhyolitic Kerlingarfjöll and basaltic Kverkfjöll volcanoes in Iceland, to investigate the localised controls on the habitability of these systems in terms of microbial community function. Our results show that host lithology plays a minor role in pool geochemistry and authigenic mineralogy, with the system geochemistry primarily controlled by deep volcanic processes. We find that by dictating pool water pH and redox conditions, deep volcanic processes are the primary control on microbial community structure and function, with water input from the proximal glacier acting as a secondary control by regulating pool temperatures. Kerlingarfjöll pools have reduced, circum-neutral CO2-rich waters with authigenic calcite-, pyrite- and kaolinite-bearing sediments. The dominant metabolisms inferred from community profiles obtained by 16S rRNA gene sequencing are methanogenesis, respiration of sulphate and sulphur (S0) oxidation. In contrast, Kverkfjöll pools have oxidised, acidic (pH 42- and high argillic alteration, resulting in Al-phyllosilicate-rich sediments. The prevailing metabolisms here are iron oxidation, sulphur oxidation and nitrification. Where analogous ice-fed hydrothermal systems existed on early Mars, similar volcanic processes would likely have controlled localised metabolic potential and thus habitability. Moreover, such systems offer several habitability advantages, including a localised source of metabolic redox pairs for chemolithotrophic microorganisms and accessible trace metals. Similar pools could have provided transient environments for life on Mars; when paired with surface or near-surface ice, these habitability niches could have persisted into the Amazonian. Additionally, they offer a confined site for biosignature formation and deposition that lends itself well to in situ robotic exploration

Optimal nitrogen application rates for three intensively-managed hardwood tree species in the southeastern USA

Forest production can be limited by nutrient and water availability, and tree species are expected to respond differently to fertilization and irrigation. Despite these common expectations, multi-species comparisons are rare, especially ones implementing a range of fertilization rates crossed with irrigation. This study compares the response of three forest hardwood species to numerous nitrogen (N) fertilization levels and water availability using a novel non-replicated technique. A range of N levels was included to determine how N affected the growth response curve, and statistical procedures for comparing these non-linear response functions are presented. We used growth and yield data to calculate the Land Expectation Value (LEV) for these intensive management treatments, and to determine the optimal growing conditions (accounting for tree productivity and grower expenses). To accomplish these objectives, we used a series of cottonwood, sycamore, and sweetgum plots that received a range of N fertilization with or without irrigation. Regression is an economical approach to define treatment responses in large-scale experiments, and we recommend >3 treatment levels so the response of any single plot does not disproportionally influence the line. The non-replicated plots showed a strong positive N response below 150 kg N ha -1 yr -1, beyond which little response was observed. However, different amounts of fertilization were required for the greatest biomass accumulation rate in each tree species. Cottonwood and sycamore growth was optimized with less than 150 kg N ha -1 yr -1 while sweetgum growth was optimized with less than 100 kg N ha -1 yr -1. Results from this experiment should be representative of many of the nutrient-poor soils in the Coastal Plain in the southeastern USA. The LEVs were not positive for any treatment x genotype combination tested when using irrigation or liquid fertilizer, but our analysis showed that several non-irrigated treatments in sycamore and sweetgum did result in positive LEVs when fertilized with granular urea

Above- and below-ground biomass accumulation, production, and distribution of sweetgum and loblolly pine grown with irrigation and fertilization.

Abstract: Increased forest productivity has been obtained by improving resource availability through water and nutrient amendments. However, more stress-tolerant species that have robust site requirements do not respond consistently to irrigation. An important factor contributing to robust site requirements may be the distribution of biomass belowground, yet available information is limited. We examined the accumulation and distribution of above- and below-ground biomass in sweetgum (Liqrridambar sfyrac$lua L.) and loblolly pine (Pinus taeda L.) stands receiving irrigation and fertilization. Mean annual aboveground production after 4 years ranged from 2.4 to 5.1 ~g.ha-'.year' for sweetgum and from 5.0 to 6.9 ~g.ha-l.year-l for pine. Sweetgum responded positively to irrigation and fertilization with an additive response to irrigation + fertilization. Pine only responded to fertilization. Sweetgum root mass fraction (RME)in creased with fertilization at 2 years and decreased with fertilization at 4 years. There were no detectable treatment differences in loblolly pine RMF. Development explained from 67% to 98% of variation in shoot versus root allometry for ephemeral and perennial tissues, fertilization explained no more than 5% of the variation in for either species, and irrigation did not explain any. We conclude that shifts in allocation from roots to shoots do not explain nutrient-induced growth stimulations

Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

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