Quantifying the Impact of Gene Flow on Phenotype-Environment Mismatch: A Demonstration with the Scarlet Monkeyflower Mimulus cardinalis

Geographic range margins offer testing grounds for limits to adaptation. If range limits are concordant with niche limits, range expansions require the evolution of new phenotypes that can maintain populations beyond current range margins. However, many species\u27 range margins appear static over time, suggesting limits on the ability of marginal populations to evolve appropriate phenotypes. A potential explanation is the swamping gene flow hypothesis, which posits that asymmetrical gene flow from large, well-adapted central populations prevents marginal populations from locally adapting. We present an empirical framework for combining gene flow, environment, and fitness-related phenotypes to infer the potential for maladaptation, and we demonstrate its application using the scarlet monkeyflower Mimulus cardinalis. We grew individuals sampled from populations on a latitudinal transect under varied temperatures and determined the phenotypic deviation (PD), the mismatch between phenotype and local environment. We inferred gene flow among populations and predicted that populations receiving the most temperature- or latitude-weighted immigration would show the greatest PD and that these populations were likely marginal. We found asymmetrical gene flow from central to marginal populations. Populations with more latitude-weighted immigration had significantly greater PD but were not necessarily marginal. Gene flow may limit local adaptation in this species, but swamping gene flow is unlikely to explain its northern range limit

Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker

THE HUNDRED BILLION DOLLAR BONUS: Global Energy Efficiency Lessons from India

At a time when India and other nations are grappling with myriad energy-related challenges, including unstable, costly power sources and growing greenhouse gas emissions, energy efficiency offers an alternative at a fraction of the cost of other new sources of energy. A consortium of leading Indian regulators, nongovernmental organizations, and international experts has recognized this opportunity and is working to develop effective policies that will bring significant domestic benefits to India while accelerating the global transition to energy efficiency

Stereoselective Total Synthesis of (−)‐Thallusin for Bioactivity Profiling

Chemical mediators are key compounds for controlling symbiotic interactions in the environment. Here, we disclose a fully stereoselective total synthesis of the algae differentiation factor (−)‐thallusin that utilizes sophisticated 6‐ endo ‐cyclization chemistry and effective late‐stage sp 2 –sp 2 ‐couplings using non‐toxic reagents. An EC 50 of 4.8 pM was determined by quantitative phenotype profiling in the green seaweed Ulva mutabilis (Chlorophyte), underscoring this potent mediator‘s enormous, pan‐species bioactivity produced by symbiotic bacteria. SAR investigations indicate that (−)‐thallusin triggers at least two different pathways in Ulva that may be separated by chemical editing of the mediator compound structure

Magnetic Resonance Imaging in Clinical Trials of Diabetic Kidney Disease

Chronic kidney disease (CKD) associated with diabetes mellitus (DM) (known as diabetic kidney disease, DKD) is a serious and growing healthcare problem worldwide. In DM patients, DKD is generally diagnosed based on the presence of albuminuria and a reduced glomerular filtration rate. Diagnosis rarely includes an invasive kidney biopsy, although DKD has some characteristic histological features, and kidney fibrosis and nephron loss cause disease progression that eventually ends in kidney failure. Alternative sensitive and reliable non-invasive biomarkers are needed for DKD (and CKD in general) to improve timely diagnosis and aid disease monitoring without the need for a kidney biopsy. Such biomarkers may also serve as endpoints in clinical trials of new treatments. Non-invasive magnetic resonance imaging (MRI), particularly multiparametric MRI, may achieve these goals. In this article, we review emerging data on MRI techniques and their scientific, clinical, and economic value in DKD/CKD for diagnosis, assessment of disease pathogenesis and progression, and as potential biomarkers for clinical trial use that may also increase our understanding of the efficacy and mode(s) of action of potential DKD therapeutic interventions. We also consider how multi-site MRI studies are conducted and the challenges that should be addressed to increase wider application of MRI in DKD

A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase

l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase. Cathepsin B (CTSB), which is produced constitutively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and Erwinia chrysanthemi. Asparaginyl endopeptidase (AEP), which is overexpressed predominantly in high-risk subsets of ALL, specifically degraded ASNase. AEP thereby destroys ASNase activity and may also potentiate antigen processing, leading to allergic reactions. Using AEP-mediated cleavage sequences, we modeled the effects of the protease on ASNase and created a number of recombinant ASNase products. The N24 residue on the flexible active loop was identified as the primary AEP cleavage site. Sole modification at this site rendered ASNase resistant to AEP cleavage and suggested a key role for the flexible active loop in determining ASNase activity. We therefore propose what we believe to be a novel mechanism of drug resistance to ASNase. Our results may help to identify alternative therapeutic strategies with the potential of further improving outcome in childhood ALL

Osp/Claudin-11 Forms a Complex with a Novel Member of the Tetraspanin Super Family and β1 Integrin and Regulates Proliferation and Migration of Oligodendrocytes

Oligodendrocyte-specific protein (OSP)/claudin-11 is a major component of central nervous system myelin and forms tight junctions (TJs) within myelin sheaths. TJs are essential for forming a paracellular barrier and have been implicated in the regulation of growth and differentiation via signal transduction pathways. We have identified an OSP/claudin-11–associated protein (OAP)1, using a yeast two-hybrid screen. OAP-1 is a novel member of the tetraspanin superfamily, and it is widely expressed in several cell types, including oligodendrocytes. OAP-1, OSP/claudin-11, and β1 integrin form a complex as indicated by coimmunoprecipitation and confocal immunocytochemistry. Overexpression of OSP/claudin-11 or OAP-1 induced proliferation in an oligodendrocyte cell line. Anti–OAP-1, anti–OSP/claudin-11, and anti–β1 integrin antibodies inhibited migration of primary oligodendrocytes, and migration was impaired in OSP/claudin-11–deficient primary oligodendrocytes. These data suggest a role for OSP/claudin-11, OAP-1, and β1 integrin complex in regulating proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair

Business Educator Issue Two September 2022: Research and Scholarship: Building Sustainable Futures.

Co-editors’ Introduction Welcome to Business Educator Issue 2 (2021-2022). This Working Paper series is for scholars, researchers, early career researchers, members of the PhD community and students whose research and scholarship are located within Management Learning and Business Education. The purpose of this Working Paper series is to provide a peer-reviewed publication to support the development of high-quality outputs from research in the areas of: - Management Learning including leadership and management development approaches; coaching; professional development; reflexivity; creativity and innovation in management learning; developing resilient and agile managers; internationalisation of management learning across cultures. - Business Education including business pedagogies; creative approaches to learning and teaching; online and hybrid approaches; digital business education; the student experience; student as partners; collaborative approaches to business education; inclusive business education practices; work-based learning, experiential learning; internationalisation of business education. We are delighted that this second issue reflects the breadth of the experience within the research community in the Faculty of Business, Law, and Tourism and beyond by including working papers from early career researchers, colleagues from University of Sunderland in London and established internationally recognised researchers. Following the Call for Papers in October 2021, this issue contains three working papers and starts with a timely topic for all on ‘Securing the future of work: an analysis on skill gaps between Business Education and industry needs in the UK’ by Dr Giuseppe Cantafio (Senior Lecturer (Academic Development APP and TEF University of Sunderland in London) and Awajioyem Miracle Ikoawaji (MSc International Business Management, University of Sunderland in London). This paper considers and reflects upon emerging technologies, disruptions and rapid evolution faced in the business environment. They present the case for new managers entering the market to acquire the skills needed to thrive and grow in a fastchanging environment. This is followed by a paper from established researchers on ‘An exploration of the impact of TNE programmes on graduate employability using stakeholder approach’ by Professor Monika Foster (Head of School of Business and Management, University of Sunderland), Dr Yuan Zhai (Lecturer in Business, University of Teesside) and Dr Derek Watson (Associate Professor, University of Sunderland). This paper focuses on TNE student graduateness and career progression. They provide insights and outline informed guidance on the design and delivery of TNE programmes to further enrich graduate employability. This is followed by a paper by an early career researcher on ‘A conceptual study on the application of qualitative methods to the study of international master foundation students’ online engagement during the pandemic lockdown’ by Iris Ren. This paper presents an emerging conceptualisation of the experience of the impact of Covid-19 on teaching practice for a teacher whose cultural differences have presented unique opportunities and challenges for developing their praxis and teaching of international postgraduate students

Myelolipoma of the Pelvis: A Case Report and Review of Literature

Myelolipomas are uncommon, benign tumors which typically occur in the adrenal glands and consist of mature adipose tissue and benign hematopoietic components. Myelolipomas can occur outside of the adrenal glands, but the presacral region, retroperitoneum, pelvis, and mediastinum are unusual locations for these tumors. It is important to recognize this entity in these locations since they can attain massive sizes leading to pressure symptoms and need to be differentiated from the malignant tumors like liposarcomas. We present a myelolipoma case in the presacral region. Our case illustrates the clinical approach of these tumors in such unusual locations