West Midlands, United Kingdom

University College Birmingham

www.ucb.ac.uk
West Midlands, United Kingdom

University College Birmingham, is a university in Birmingham, England. It was awarded full University status in 2012 along with Newman University. The university is located in central Birmingham and offers both vocational and academic education at both undergraduate and postgraduate level. The university specialises in the areas of hospitality and the culinary arts, hairdressing and beauty, tourism, business enterprise, marketing, business management, accounting, finance, events management, sports management, sports medicine, sports therapy and Early Years education. Wikipedia.

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Laing R.W.,University College Birmingham
Current Opinion in Organ Transplantation | Year: 2017

PURPOSE OF REVIEW: Normothermic machine perfusion of the liver (NMP-L) is a novel technology recently introduced into the practice of liver transplantation. This review recapitulates benefits of normothermic perfusion over conventional static cold storage and summarizes recent publications in this area. RECENT FINDINGS: The first clinical trials have demonstrated both safety and feasibility of NMP-L. They have shown that machine perfusion can entirely replace cold storage or be commenced following a period of cold ischaemia. The technology currently allows transplant teams to extend the period of organ preservation for up to 24?h. Results from the first randomized control trial comparing NMP-L with static cold storage will be available soon. One major advantage of NMP-L technology over other parallel technologies is the potential to assess liver function during NMP-L. Several case series have suggested parameters usable for liver viability testing during NMP-L including bile production and clearance of lactic acidosis. NMP-L allows viability testing of high-risk livers. It has shown the potential to increase utilization of donor organs and improve transplant procedure logistics. SUMMARY: NMP-L is likely to become an important technology that will improve organ preservation as well as have the potential to improve utilization of extended criteria donor livers. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Reynolds J.J.,University College Birmingham
Nature Genetics | Year: 2017

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Ponomaryov T.,University College Birmingham
Circulation Research | Year: 2017

RATIONALE:: Deep vein thrombosis (DVT) and its complication pulmonary embolism have high morbidity reducing quality of life and leading to death. Cellular mechanisms of DVT initiation remain poorly understood. OBJECTIVE:: We sought to determine the role of mast cells (MCs) in DVT initiation and validate MCs as a potential target for DVT prevention. METHODS AND RESULTS:: In a mouse model, DVT was induced by partial ligation (stenosis) of the inferior vena cava (IVC). We demonstrated that two strains of mice deficient for MCs were completely protected from DVT. Adoptive transfer of in vitro differentiated MCs restored thrombosis. Mast cells were present in the venous wall, and the number of granule-containing MCs decreased with thrombosis. Pharmacological depletion of MCs granules or prevention of MC degranulation also reduced DVT. Basal plasma levels of von Willebrand factor and recruitment of platelets to the IVC wall after DVT induction were reduced in MC-deficient mice. Stenosis application increased plasma levels of soluble P-selectin in wild-type but not in MC-deficient mice. Mast cell releasate elevated ICAM-1 expression on HUVEC in vitro. Topical application of compound 48-80, an MC secretagogue, or histamine, a Weibel-Palade body secretagogue from MCs, potentiated DVT in wild-type mice, and histamine restored thrombosis in MC-deficient animals. CONCLUSIONS:: Mast cells exacerbate DVT likely through endothelial activation and Weibel-Palade body release, which is, at least in part, mediated by histamine. As MCs do not directly contribute to normal hemostasis, they can be considered potential targets for prevention of DVT in humans. © 2017 American Heart Association, Inc.


Haussmann I.U.,Coventry University | Bodi Z.,University of Nottingham | Sanchez-Moran E.,University College Birmingham | Mongan N.P.,University of Nottingham | And 3 more authors.
Nature | Year: 2016

N6-methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) and is decoded by YTH domain proteins. The mammalian mRNA m6A methylosome is a complex of nuclear proteins that includes METTL3 (methyltransferase-like 3), METTL14, WTAP (Wilms tumour 1-associated protein) and KIAA1429. Drosophila has corresponding homologues named Ime4 and KAR4 (Inducer of meiosis 4 and Karyogamy protein 4), and Female-lethal (2)d (Fl(2)d) and Virilizer (Vir). In Drosophila, fl(2)d and vir are required for sex-dependent regulation of alternative splicing of the sex determination factor Sex lethal (Sxl). However, the functions of m6A in introns in the regulation of alternative splicing remain uncertain. Here we show that m6A is absent in the mRNA of Drosophila lacking Ime4. In contrast to mouse and plant knockout models, Drosophila Ime4-null mutants remain viable, though flightless, and show a sex bias towards maleness. This is because m6A is required for female-specific alternative splicing of Sxl, which determines female physiognomy, but also translationally represses male-specific lethal 2 (msl-2) to prevent dosage compensation in females. We further show that the m6A reader protein YT521-B decodes m6A in the sex-specifically spliced intron of Sxl, as its absence phenocopies Ime4 mutants. Loss of m6A also affects alternative splicing of additional genes, predominantly in the 5' untranslated region, and has global effects on the expression of metabolic genes. The requirement of m6A and its reader YT521-B for female-specific Sxl alternative splicing reveals that this hitherto enigmatic mRNA modification constitutes an ancient and specific mechanism to adjust levels of gene expression.


News Article | November 22, 2016
Site: www.theguardian.com

UK universities are helping lead the world on environmental research – but when it comes to their own back yard they appear to be falling behind. Only a quarter are on track to meet their carbon reduction targets by 2020. Teams leading environmental initiatives are being cut and sustainability strategies have not been renewed, according to the results of the 2016 People & Planet University League, published on Tuesday (see below). Lack of government support for public sector sustainability is blamed for the stalling of energy-saving schemes. It is the fourth year that the league – ranking institutions by environmental and ethical performance – has recorded fewer universities on course to meet their legally binding target of reducing emissions by 43% from 2005 levels by 2020. But not all have abandoned their green goals, with “first class” status being awarded to 30 of the 150 universities. This year Nottingham Trent University, which tops the table, opened the Pavilion, its first carbon negative building. Brighton University, in second place, has made sustainability one of its four core values. The University of Warwick – the biggest mover, up from 129 last year to 34th – is launching a unique BASc cross-disciplinary degree in global sustainable development. Nottingham Trent’s high score reflects its commitment to engage staff and students, and its aim to include sustainability in all its courses, while the University of Brighton has managed to reduce its carbon footprint despite expanding in size and opening its buildings for longer hours. “Sustainability is a core value in our university,” says Prof Debra Humphris, Brighton’s vice-chancellor. “With students and staff we aim to embed sustainable practices; we all need to play our part.” A spokesman for the University of Warwick said its improved showing could be partly due to the different way statistics for the league have been collected this year. “They may have picked up more of the things we are doing this year, such as the bike hire scheme, the £5,000 fund to support student projects, and our staff and student green champions initiative,” he said. The 2016 league table, based on information in the public domain, scores institutions on such factors as the commitment of senior management, the employment of dedicated sustainability staff, divesting from investment in the fossil fuel industry and meeting public sector carbon reduction commitments. It also considers employment factors, such as paying staff the living wage, joining Electronics Watch to improve workers’ rights in that industry and investing in projects that do not exploit or pollute communities. Before 2010 and the election of the coalition and the Conservative governments, there was a flurry of carbon reduction initiatives linked to higher education funding, says People & Planet, a student campaigning network. “Sustainability drivers such as the capital investment framework (which made tranches of funding contingent on plans to reduce carbon emissions), the higher education green academy and the student green fund have all been removed. Today, it says, “the landscape looks bereft of any significant support or incentive for sustainable development in universities in England.” “We can now see the concerning impact of the current government’s short-termism with regard to energy and climate policy,” says Hannah Smith, co-director for campaigns and research. “Environmental sustainability has been removed from the government’s annual grant letter setting out higher education funding, leaving the Higher Education Funding Council [Hefce] without the resources it had in the past to support sustainable practice.” Wealth and academic prestige appear to be uncorrelated to progress on sustainability and ethical employment and procurement. The University of Oxford comes 46th and Cambridge 57th. Grant Anderson, Nottingham Trent’s environmental manager, says that in the past, external pressures were useful in engaging senior management in the sustainability drive. “These now don’t exist. However, it hasn’t impeded us. We continue to expand from an initial focus on carbon, waste, transport etc to a more holistic approach, understanding the sustainability opportunities of our core business of education and research. “We made it a formal requirement six months ago that all of our courses incorporate at least one of the 17 UN sustainable development goals. We don’t specify what they include, that is up to the academics, but we think it will give our students an edge in their careers to have considered some of the environmental challenges they will face in their lifetimes. For example, chemistry students are exploring their role in finding solutions to feeding the world in a sustainable way and primary education students learn practical gardening skills at the university’s food share allotments that they will be able to share with their future pupils.” Government policy is likely to continue to have an impact, however – but a less positive one. Abigail Dombey, Brighton’s environmental manager, says the university has recently installed 893 solar panels, which will save £40,000 a year in energy bills and reduce its carbon footprint by more than 100 tonnes a year. “But the feed-in tariffs – the financial incentives for generating electricity from renewable sources – have been slashed by the government so there is much less incentive to invest in renewable energy.” She fears some universities could also face higher taxes under the business rates revaluation from next April through the government’s proposal to increase the rateable value of solar panels. As charities, most universities are exempt from at least 80% of business rates but some pay 20% and all pay rates on buildings used commercially. The bottom 10 in the green league are mostly small, specialist institutions that are less likely to have the resources to employ staff to oversee environmental issues. However, the small specialist Royal Agricultural University, at 16th in the league, shows that a lot can be achieved on a smaller scale. St Mary’s University in Twickenham, London, with 4,400 students, came in the bottom 10 after researchers found it had no environmental policy or strategy, no publicly available carbon management plan, ethical investment policy or evidence of dedicated sustainability staff. In response, a spokesman said the findings were “not reflective of St Mary’s approach to sustainability” and that “the university has extensive environmental policies including strategies for carbon management, biodiversity and sustainable catering”. Hefce says its capital investment framework remains in force and requires universities and colleges to “demonstrate that their capital investment plans are aligned with the goal of managing environmental impact and that they have an acceptable carbon management plan in place”. It adds: “The HE sector has developed its expertise significantly over the last decade or so and they are the real experts in what the sector needs to do to drive sustainability plans forward.” Top 20 1 Nottingham Trent University 2 University of Brighton 3 Manchester Metropolitan University 4 Cardiff Metropolitan University 5 University of Worcester 6 Aston University 7 City, University of London 8 = Newcastle University 8 = University of Gloucestershire 10 Swansea University 11 University of Bedfordshire 12 Plymouth University 13 De Montfort University 14 London School of Economics 15 Keele University 16= University of Exeter 16= Royal Agricultural University 18 University of Greenwich 19 University of Bradford 20 Bournemouth University Bottom 10 141 Heythrop College, University of London 142 Writtle University College 143 University of St Mark & St John 144 St Mary’s University, Twickenham 145 Royal Northern College of Music 146 University College Birmingham 147 Stranmillis University College 148 University of Bolton 149 Royal Veterinary College 150 Trinity Laban Conservatoire of Music and Dance • For the full league table go to peopleand planet.org/university-league/table • This article was amended on 22 November 2016 to correct the rankings for four universities in the top 20, and to put Bournemouth University at No 20 rather than Coventry University. The article was also amended to correct a reference to the Royal Agricultural College; it has been the Royal Agricultural University since 2013.


Daley A.,University College Birmingham
Cochrane database of systematic reviews (Online) | Year: 2011

Evidence suggests that many perimenopausal and early postmenopausal women will experience menopause symptoms, hot flushes being the most common. Symptoms caused by fluctuating levels of oestrogen may be alleviated by HRT but there has been a marked global decline in its use due to concerns about the risks and benefits of HRT; consequently many women are now seeking alternatives. As large numbers of women are choosing not to take HRT, it is increasingly important to identify evidence based lifestyle modification interventions that have potential to reduce vasomotor menopausal symptoms. To examine the effectiveness of any type of exercise intervention in the management of vasomotor menopausal symptoms (hot flushes and night sweats) in perimenopausal and postmenopausal women. Searches of the following electronic bibliographic databases were performed to identify randomised controlled trials (RCTs): Cochrane Menstrual Disorders and Subfertility Group Specialised trials register; Cochrane Library (CENTRAL) (Wiley Internet interface), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Science Citation Index and Social Science Citation Index (Web of Science), CINAHL (Ovid) and SPORT Discus. Searches included dates up until 16-24 March 2010. RCTs in which any type of exercise intervention were compared no treatment/control or other treatments in the management of menopausal vasomotor symptoms in symptomatic perimenopausal/postmenopausal women. Six studies were deemed eligible for inclusion. Three authors independently extracted data from eligible studies. Three meta-analyses according to comparator the group were performed. In the comparison of exercise versus no treatment/control (three studies), the non-significant effect size Standardised Mean Difference (SMD) for vasomotor symptoms was -0.14 (95% CI: -0.54 to 0.26); SMD was -0.04, -0.25, -0.38. For the analysis of exercise versus HRT (three studies), the non-significant SMD was 0.49 (95% CI: -0.27 to 1.26); SMD across studies was 0.13, 0.19 and 1.52, with all studies favouring HRT. In the comparison of exercise versus yoga (two studies), the non-significant SMD was -0.09 (95%CI:-0.64 to 0.45); SMD was -0.37 and 0.19. All comparisons were based on small samples. One small study reported data that could not be included in the meta-analysis; in this study hot flush scores were significantly lower in the exercise plus soy milk group (83%) than soy milk only group (72%). The existing studies provided insufficient evidence to determine the effectiveness of exercise as a treatment for vasomotor menopausal symptoms, or whether exercise is more effective than HRT or yoga.


To assess the effectiveness of strategies incorporating training and support of traditional birth attendants on the outcomes of perinatal, neonatal, and maternal death in developing countries. Systematic review with meta-analysis. Medline, Embase, the Allied and Complementary Medicine database, British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, BioMed Central, PsycINFO, Latin American and Caribbean Health Sciences Literature database, African Index Medicus, Web of Science, Reproductive Health Library, and Science Citation Index (from inception to April 2011), without language restrictions. Search terms were "birth attend*", "traditional midwife", "lay birth attendant", "dais", and "comadronas". Review methods We selected randomised and non-randomised controlled studies with outcomes of perinatal, neonatal, and maternal mortality. Two independent reviewers undertook data extraction. We pooled relative risks separately for the randomised and non-randomised controlled studies, using a random effects model. We identified six cluster randomised controlled trials (n=138 549) and seven non-randomised controlled studies (n=72 225) that investigated strategies incorporating training and support of traditional birth attendants. All six randomised controlled trials found a reduction in adverse perinatal outcomes; our meta-analysis showed significant reductions in perinatal death (relative risk 0.76, 95% confidence interval 0.64 to 0.88, P<0.001; number needed to treat 35, 24 to 70) and neonatal death (0.79, 0.69 to 0.88, P<0.001; 98, 66 to 170). Meta-analysis of the non-randomised studies also showed a significant reduction in perinatal mortality (0.70, 0.57 to 0.84, p<0.001; 48, 32 to 96) and neonatal mortality (0.61, 0.48 to 0.75, P<0.001; 96, 65 to 168). Six studies reported on maternal mortality and our meta-analysis showed a non-significant reduction (three randomised trials, relative risk 0.79, 0.53 to 1.05, P=0.12; three non-randomised studies, 0.80, 0.44 to 1.15, P=0.26). Perinatal and neonatal deaths are significantly reduced with strategies incorporating training and support of traditional birth attendants.


RAR-related orphan receptor-γt (ROR-γt) directs differentiation of proinflammatory T helper 17 (TH17) cells and is a potential therapeutic target in chronic autoimmune and inflammatory diseases. However, ROR-γt–dependent group 3 innate lymphoid cells ILC3s provide essential immunity and tissue protection in the intestine, suggesting that targeting ROR-γt could also result in impaired host defense after infection or enhanced tissue damage. Here, we demonstrate that transient chemical inhibition of ROR-γt in mice selectively reduces cytokine production from TH17 but not ILCs in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. Temporal deletion of Rorc (encoding ROR-γt) in mature ILCs also did not impair cytokine response in the steady state or during infection. Finally, pharmacologic inhibition of ROR-γt provided therapeutic benefit in mouse models of intestinal inflammation and reduced the frequency of TH17 cells but not ILCs isolated from primary intestinal samples of individuals with inflammatory bowel disease (IBD). Collectively, these results reveal differential requirements for ROR-γt in the maintenance of TH17 cell and ILC3 responses and suggest that transient inhibition of ROR-γt is a safe and effective therapeutic approach during intestinal inflammation. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Although the inhibitory effects of therapeutic glucocorticoids (GCs) on dendritic cells (DCs) are well established, the roles of endogenous GCs in DC homeostasis are less clear. A critical element regulating endogenous GC concentrations involves local conversion of inactive substrates to active 11-hydroxyglucocorticoids, a reduction reaction catalyzed within the endoplasmic reticulum by an enzyme complex containing 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and hexose-6-phosphate dehydrogenase (H6PDH). In this study, we found that this GC amplification pathway operates both constitutively and maximally in steady state murine DC populations and is unaffected by additional inflammatory stimuli. Under physiologic conditions, 11βHSD1-H6PDH increases the sensitivity of plasmacytoid DCs (pDCs) to GC-induced apoptosis and restricts the survival of this population through a cell-intrinsic mechanism. Upon CpG activation, the effects of enzyme activity are overridden, with pDCs becoming resistant to GCs and fully competent to release type I interferon. CD8α(+) DCs are also highly proficient in amplifying GC levels, leading to impaired maturation following toll-like receptor-mediated signaling. Indeed, pharmacologic inhibition of 11βHSD1 synergized with CpG to enhance specific T-cell responses following vaccination targeted to CD8α(+) DCs. In conclusion, amplification of endogenous GCs is a critical cell-autonomous mechanism for regulating the survival and functions of DCs in vivo.


Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (≈3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1–5 and 6–10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ≈50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (≈9 months; 139±3 versus 126±3 mm Hg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease. © 2014 American Heart Association, Inc

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