The tunica adventitia of human arteries and veins as a source of mesenchymal stem cells

We previously demonstrated that human pericytes, which encircle capillaries and microvessels, give rise in culture to genuine mesenchymal stem cells (MSCs). This raised the question as to whether all MSC are derived from pericytes. Pericytes and other cells defined on differential expression of CD34, CD31, and CD146 were sorted from the stromal vascular fraction of human white adipose tissue. Besides pericytes, CD34+ CD31- CD146- CD45- cells, which reside in the outmost layer of blood vessels, the tunica adventitia, natively expressed MSC markers and gave rise in culture to clonogenic multipotent progenitors identical to standard bone marrow-derived MSC. Despite common MSC features and developmental properties, adventitial cells and pericytes retain distinct phenotypes and genotypes through culture. However, in the presence of growth factors involved in vascular remodeling, adventitial cells acquire a pericytes-like phenotype. In conclusion, we demonstrate the co-existence of 2 separate perivascular MSC progenitors: pericytes in capillaries and microvessels and adventitial cells around larger vessels

Mental health in the pandemic: a repeated cross-sectional mixed-method study protocol to investigate the mental health impacts of the coronavirus pandemic in the UK.

Funder: MQ: Transforming Mental Health; Grant(s): MQBF/3INTRODUCTION: The WHO declared a global pandemic on 11 March 2020. Since then, the world has been firmly in the grip of the COVID-19. To date, more than 211 730 035 million confirmed cases and more than 4 430 697 million people have died. While controlling the virus and implementing vaccines are the main priorities, the population mental health impacts of the pandemic are expected to be longer term and are less obvious than the physical health ones. Lockdown restrictions, physical distancing, social isolation, as well as the loss of a loved one, working in a frontline capacity and loss of economic security may have negative effects on and increase the mental health challenges in populations around the world. There is a major demand for long-term research examining the mental health experiences and needs of people in order to design adequate policies and interventions for sustained action to respond to individual and population mental health needs both during and after the pandemic. METHODS AND ANALYSIS: This repeated cross-sectional mixed-method study conducts regular self-administered representative surveys, and targeted focus groups and semi-structured interviews with adults in the UK, as well as validation of gathered evidence through citizens' juries for contextualisation (for the UK as a whole and for its four devolved nations) to ensure that emerging mental health problems are identified early on and are properly understood, and that appropriate policies and interventions are developed and implemented across the UK and within devolved contexts. STATA and NVIVO will be used to carry out quantitative and qualitative analysis, respectively. ETHICS AND DISSEMINATION: Ethics approval for this study has been granted by the Cambridge Psychology Research Ethics Committee of the University of Cambridge, UK (PRE 2020.050) and by the Health and Life Sciences Research Ethics Committee of De Montfort University, UK (REF 422991). While unlikely, participants completing the self-administered surveys or participating in the virtual focus groups, semi-structured interviews and citizens' juries might experience distress triggered by questions or conversations. However, appropriate mitigating measures have been adopted and signposting to services and helplines will be available at all times. Furthermore, a dedicated member of staff will also be at hand to debrief following participation in the research and personalised thank-you notes will be sent to everyone taking part in the qualitative research.Study findings will be disseminated in scientific journals, at research conferences, local research symposia and seminars. Evidence-based open access briefings, articles and reports will be available on our study website for everyone to access. Rapid policy briefings targeting issues emerging from the data will also be disseminated to inform policy and practice. These briefings will position the findings within UK public policy and devolved nations policy and socioeconomic contexts in order to develop specific, timely policy recommendations. Additional dissemination will be done through traditional and social media. Our data will be contextualised in view of existing policies, and changes over time as-and-when policies change

Heterologous expression of cytotoxic sesquiterpenoids from the medicinal mushroom Lignosus rhinocerotis in yeast

Background: Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system. Results: Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C 15 H 26 O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, ß-elemene, ß-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and a-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1 H and 13 C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and a-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC 50 value of 3.5 ± 0.58 µg/ml while a-cadinol is less active (IC 50 = 18.0 ± 3.27 µg/ml). Conclusions: This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushrooms

Resequencing and comparative genomics of stagonospora nodorum: Sectional gene absence and effector discovery

Stagonospora nodorum is an important wheat (Triticum aestivum) pathogen in many parts of the world, causing major yield losses. It was the first species in the large fungal Dothideomycete class to be genome sequenced. The reference genome sequence (SN15) has been instrumental in the discovery of genes encoding necrotrophic effectors that induce disease symptoms in specific host genotypes. Here we present the genome sequence of two further S. nodorum strains (Sn4 and Sn79) that differ in their effector repertoire from the reference. Sn79 is avirulent on wheat and produces no apparent effectors when infiltrated onto many cultivars and mapping population parents. Sn4 is pathogenic on wheat and has virulences not found in SN15. The new strains, sequenced with short-read Illumina chemistry, are compared with SN15 by a combination of mapping and de novo assembly approaches.Each of the genomes contains a large number of strain-specific genes, many of which have no meaningful similarity to any known gene. Large contiguous sections of the reference genome are absent in the two newly sequenced strains. We refer to these differences as “sectional gene absences.” The presence of genes in pathogenic strains and absence in Sn79 is added to computationally predicted properties of known proteins to produce a list of likely effector candidates. Transposon insertion was observed in the mitochondrial genomes of virulent strains where the avirulent strain retained the likely ancestral sequence. The study suggests that short-read enabled comparative genomics is an effective way to both identify new S. nodorum effector candidates and to illuminate evolutionary processes in this species

Heterologous expression of cytotoxic sesquiterpenoids from the medicinal mushroom Lignosus rhinocerotis in yeast

Background: Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system. Results: Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C15H26O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, β-elemene, β-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and α-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1H and 13C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and α-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC50 value of 3.5 ± 0.58 μg/ml while α-cadinol is less active (IC50 = 18.0 ± 3.27 μg/ml). Conclusions: This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushroomsH-YYY is supported by an Australian Awards Endeavour Research Fellowship. MJM-G received an Australian Awards Endeavour Scholarship and a Mexican CONACYT scholarship. YH-C is supported by an Australian Research Council Future Fellowship (FT160100233). This work was partially supported by Funda‑ mental Research Grant Scheme (FRGS): FP029-2014A from Ministry of Science, Technology and Innovation, Malaysia, and Postgraduate Research Grant (PPP): PG144/2014B from University of Malaya

Cepstral peak prominence: a comprehensive analysis

An analytical study of cepstral peak prominence (CPP) is presented, intended to provide an insight into its meaning and relation with voice perturbation parameters. To carry out this analysis, a parametric approach is adopted in which voice production is modelled using the traditional source-filter model and the first cepstral peak is assumed to have Gaussian shape. It is concluded that the meaning of CPP is very similar to that of the first rahmonic and some insights are provided on its dependence with fundamental frequency and vocal tract resonances. It is further shown that CPP integrates measures of voice waveform and periodicity perturbations, be them either amplitude, frequency or noise

Stress, sex, and motivated behaviors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137361/1/jnr23815.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137361/2/jnr23815_am.pd

Identification of cardiac organ damage in arterial hypertension: insights by echocardiography for a comprehensive assessment

: Arterial hypertension, a widespread disease, whose prevalence increases with age, represents a major risk factor for cardiovascular events, causing damage in several organs, including the heart. In this context, echocardiography has a clear and pivotal role, being able to assess cardiac morphology and detect haemodynamic changes induced by this disease. 2018 European Society of Cardiology/European Society of Hypertension guidelines on AH identified main echo parameters such as left ventricular mass, relative wall thickness and left atrial volume, for detecting cardiac organ damage. The present review highlights the advantage of additional echocardiographic parameters such as diastolic measurement and both thoracic and abdominal aortic dimensions. An overlook on aortic valve should also be suggested to detect aortic regurgitation and stenosis, both frequent complications in hypertensive patients. In this kind of comprehensive assessment, the combination of standard and advanced echocardiography (speckle tracking echocardiography and, with a lesser extent, three-dimensional echocardiography) could be considered to improve the diagnostic accuracy, stratify prognosis and address management in arterial hypertension

Senescence and aging – causes, consequences, and therapeutic avenues

Aging is the major risk factor for cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. Although we are far from understanding the biological basis of aging, research suggests that targeting the aging process itself could ameliorate many age-related pathologies. Senescence is a cellular response characterized by a stable growth arrest and other phenotypic alterations that include a proinflammatory secretome. Senescence plays roles in normal development, maintains tissue homeostasis, and limits tumor progression. However, senescence has also been implicated as a major cause of age-related disease. In this regard, recent experimental evidence has shown that the genetic or pharmacological ablation of senescent cells extends life span and improves health span. Here, we review the cellular and molecular links between cellular senescence and aging and discuss the novel therapeutic avenues that this connection opens