Comparing to its sister-family (Rhinolophidae), Hipposideridae was less studied by cytogenetic approaches. Only a few high-resolution G-banded karyotypes have been reported so far, and most of the conclusions on the...Comparing to its sister-family (Rhinolophidae), Hipposideridae was less studied by cytogenetic approaches. Only a few high-resolution G-banded karyotypes have been reported so far, and most of the conclusions on the karyotypic evolution in Hipposideridae were based on conventional Giemsa-staining. In this study, we applied comparative chromosome painting, a method of choice for genome-wide comparison at the molecular level, and G- and C-banding to establish comparative map between five hipposiderid species from China, using a whole set of chromosome-specific painting probes from one of them (Aselliscus stoliczkanus). G-band and C-band comparisons between homologous segments defined by chromosome painting revealed that Robertsonian translocations, paracentric inversions and heterochromatin addition could be the main mechanism of chromosome evolution in Hipposideridae. Comparative analysis of the conserved chromosomal segments among five hipposiderid species and outgroup species suggests that bi-armed chromosomes should be included into the ancestral karyotype of Hipposideridae, which was previously believed to be exclusively composed of acrocentric chromosomes.展开更多
Lung cancer is a leading cause of cancer death worldwide. Some lung cancer patients correlate with a gas of radon besides smoking. To search for common chromosomal aberrations in lung cancer cell lines established fro...Lung cancer is a leading cause of cancer death worldwide. Some lung cancer patients correlate with a gas of radon besides smoking. To search for common chromosomal aberrations in lung cancer cell lines established from patients induced by different factors, a combined approach of chromosome sorting, forward and reverse chromosome painting was used to characterize karyotypes of two lung adenocarcinoma cell lines: A549 and GLC-82 with the latter line derived from a patient who has suffered long-term exposure to environmental radon gas pollution. The chromosome painting results revealed that complex chromosomal rearrangements occurred in these two lung adenocarcinoma cell lines. Thirteen and twenty-four abnormal chromosomes were identified An A549 and GLC-82 cell lines, respectively. Almost half of abnormal chromosomes in these two cell lines were formed by non-reciprocal translocations, the others were derived from deletions and duplication/or amplification in some chromosomal regions. Furthermore, two apparently common breakpoints, HSA8q24 and 12q14 were found in these two lung cancer cell lines.展开更多
Approximately one fifth of the world's plants are at risk of extinction.Of these,a significant number exist as populations of few individuals,with limited distribution ranges and under enormous pressure due to hab...Approximately one fifth of the world's plants are at risk of extinction.Of these,a significant number exist as populations of few individuals,with limited distribution ranges and under enormous pressure due to habitat destruction.In China,these most-at-risk species are described as 'plant species with extremely small populations'(PSESP).Implementing conservation action for such listed species is urgent.Storing seeds is one of the main means of ex situ conservation for flowering plants.Spore storage could provide a simple and economical method for fern ex situ conservation.Seed and spore germination in nature is a critical step in species regeneration and thus in situ conservation.But what is known about the seed and spore biology(storage and germination) of at-risk species? We have used China's PSESP(the first group listing) as a case study to understand the gaps in knowledge on propagule biology of threatened plant species.We found that whilst germination information is available for 28 species(23%of PSESP),storage characteristics are only known for 8%of PSESP(10 species).Moreover,we estimate that 60%of the listed species may require cryopreservation for long-term storage.We conclude that comparative biology studies are urgently needed on the world's most threatened taxa so that conservation action can progress beyond species listing.展开更多
The aim of this review is to give a comprehensive and concise overview of coronary embryology and normal coronary anatomy, describe common variants of normal and summarize typical patterns of anomalous coronary artery...The aim of this review is to give a comprehensive and concise overview of coronary embryology and normal coronary anatomy, describe common variants of normal and summarize typical patterns of anomalous coronary artery anatomy. Extensive iconography supports the text, with particular attention to images obtained in vivo using non-invasive imaging. We have divided this article into three groups, according to their frequency in the general population: Normal, normal variant and anomaly. Although congenital coronary artery anomalies are relatively uncommon, they are the second most common cause of sudden cardiac death among young athletes and therefore warrant detailed review. Based on the functional relevance of each abnormality, coronary artery anomalies can be classified as anomalies with obligatory ischemia, without ischemia or with exceptional ischemia. The clinical symptoms may include chest pain, dyspnea, palpitations, syncope, cardiomyopathy, arrhythmia, myocardial infarction and sudden cardiac death. Moreover, it is important to also identify variants and anomalies without clinical relevance in their own right as complications during surgery or angioplasty can occur.展开更多
Most defective and unwanted cells die by apoptosis, cells without damaging the surrounding tissue. Once a an exquisitely controlled genetic programme for removing such cell has committed to apoptosis, the process is r...Most defective and unwanted cells die by apoptosis, cells without damaging the surrounding tissue. Once a an exquisitely controlled genetic programme for removing such cell has committed to apoptosis, the process is remarkably efficient, and is completed within a few minutes of initiation. This point of no retum for an apoptotic cell is commonly held to be the point at which the outer mitochondrial membrane is permeabilised, a process regulated by the Bcl-2 family of proteins. How these proteins regulate this decision point is central to diseases such as cancer where apoptotic control is lost. In this review, we will discuss apoptotic signalling and how a cell makes the irreversible decision to die. We will focus on one set of survival signals, those derived by cell adhesion to the extracellular matrix (ECM), and use these to highlight the complexities of apoptotic signalling. In particular, we will illustrate how multiple signalling pathways converge to determine critical cell fate decisions.展开更多
There are large knowledge gaps regarding how to control stem cells growth and differentiation.The limitations of currently available technologies,such as growth factors and/or gene therapies has led to the search of a...There are large knowledge gaps regarding how to control stem cells growth and differentiation.The limitations of currently available technologies,such as growth factors and/or gene therapies has led to the search of alternatives.We explore here how a cell’s epigenome influences determination of cell type,and potential applications in tissue engineering.A prevalent epigenetic modification is the acetylation of DNA core histone proteins.Acetylation levels heavily influence gene transcription.Histone deacetylase (HDAC) enzymes can remove these acetyl groups,leading to the formation of a condensed and more transcriptionally silenced chromatin.Histone deacetylase inhibitors (HDACis) can inhibit these enzymes,resulting in the increased acetylation of histones,thereby affecting gene expression.There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering,potentially providing novel tools to control stem cell fate.This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone,cardiac,neural tissues),including the history,current status and future perspectives of using HDACis for stem cell research and tissue engineering,with particular attention paid to how different HDAC isoforms may be integral to this field.展开更多
Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the ma...Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the major sites of interaction between a cell and its extracellular matrix(ECM)microenvironment,thus outside mechanical signals can be sensed at focal adhesions through transmembrane receptor integrins.In particular,it has been shown that matrix elasticity can control the cell fate<sup>[4]</sup>by modulating the interactions between ECM proteins and their receptor integrins<sup>[5,6]</sup>.For example,different rigidity of polyacrylamide(PA)gels can lead to different density of ECM ancho-展开更多
Response to vernalization and photoperiod are the main determinants controlling the time to flowering in temperate cereals. While the individual genes that determine a plant's response to these environmental signa...Response to vernalization and photoperiod are the main determinants controlling the time to flowering in temperate cereals. While the individual genes that determine a plant's response to these environmental signals are well characterized, the combinatorial effect on flowering time of allelic variants for multiple genes remains unresolved. This study investigated the genetic control of flowering-time in a biparental population of spring barley, derived from a wide cross between a late-flowering European and an early-flowering North-American cultivar. While the major flowering time genes are not segregating in the Beka ×Logan cross, large variation in flowering was observed. We identified five QTL, with both parents found to contribute early alleles. The catalog of QTL discovered aligns with several candidate genes affecting flowering time in barley. The combination of particular alleles at HvCEN, HvELF3 and HvFT1 in Logan are responsible for the earliness of this cultivar. Interestingly, earliness for flowering could be further enhanced, with Beka found to contribute three early alleles, including a QTL colocating with a HvFD-like gene, suggesting that there are diverse aspects of the flowering-time pathway that have been manipulated in these two cultivars. Epistatic interactions between flowering-time QTL or candidate genes were observed in field data and confirmed under controlled conditions. The results of this study link photoperiod-dependent flowering-time genes with earliness per se genes into a single model, thus providing a unique framework that can be used by geneticists and breeders to optimize flowering time in barley.展开更多
The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis ...The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6 st p.R279 Q. We show that human GP130 p.R281 Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice Il6 st p.R279 Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11 RA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.展开更多
AIM:To report on the utilization of eye care services and its associated factors among those with unilateral visual impairment(VI)in a rural South Indian population.METHODS:A population based cross-sectional study...AIM:To report on the utilization of eye care services and its associated factors among those with unilateral visual impairment(VI)in a rural South Indian population.METHODS:A population based cross-sectional study was conducted in three districts(Adilabad,Mahbubnagar and West Godavari)in the state of Andhra Pradesh,India.A detailed interview and a comprehensive eye examination were conducted. Those with unilateral VI were asked questions about noticing any change in vision and on utilization of eye care services. The most important reason reported by the participant for not utilizing the services was used for the analysis. Multiple logistic regression models were used to examine the association between noticing a change in vision and socio-demographic variables such as age,gender,education and area of residence,severity and causes of VI.RESULTS:Among the 4456 participants aged ≥16y who were administered the questionnaire,53.2% were women,and 54.7% had no education. Of the 489(11%; 95% CI:10.1-11.9)people with unilateral VI,399(81.6%)participants reported noticing a change in their vision over the last five years but only 136(34.1%)participants had soughteye care consultation. Those who had any education(OR:1.9; 95% CI:1.1-3.2),had blindness(OR:2.7; 95% CI:1.4-5.2),and cataract(OR:2.1; 95% CI:1.0-4.3)as a cause of unilateral VI were more like to seek eye care consultations. The most commonly reported reasons for not seeking eye care services were "do not have money for eye checkup" in 30.7% of the participants followed by "do not have a serious problem"(30.0%).CONCLUSION:A large proportion of rural population though noticed a change in their vision did not seek eye care due to financial and person-related reasons. Eye care service providers need to address these barriers to enhance the uptake of eye care services among those with unilateral VI.展开更多
Both environmental and genetic factors contribute to the development of diabetes mellitus and although monogenic disorders are rare,they offer unique insights into the fundamental biology underlying the disease.Mutati...Both environmental and genetic factors contribute to the development of diabetes mellitus and although monogenic disorders are rare,they offer unique insights into the fundamental biology underlying the disease.Mutations of the insulin gene or genes involved in the response to protein misfolding cause early onset diabetes.These have revealed an important role for endoplasmic reticulum stress in β-cell survival.This form of cellular stress occurs when secretory proteins fail to fold efficiently.Of all the professional secretory cells we possess,β-cells are the most sensitive to endoplasmic reticulum stress because of the large fluctuations in protein synthesis they face daily.Studies of endoplasmic reticulum stress signaling therefore offer the potential to identify new drug targets to treat diabetes.展开更多
Identifying genetic variants that contribute to phenotypic variation is expected to provide insights into the etiology of complex traits. Here we show how combining genetic mapping in an outbred population of rats wit...Identifying genetic variants that contribute to phenotypic variation is expected to provide insights into the etiology of complex traits. Here we show how combining genetic mapping in an outbred population of rats with sequence data from the progenitors of the population made it possible to identify causal variants and genes for a large number of phenotypes. We identified 355 genomic loci contributing to 122 measures relevant to six models of disease, including fear-related behaviors and experimental autoimmune encephalomyelitis. At 35 of those loci we identified the responsible gene, and in some cases, the responsible variant.展开更多
Viticulture,like other fields of agriculture,is currently facing important challenges that will be addressed only through sustained,dedicated and coordinated research.Although the methods used in biology have evolved ...Viticulture,like other fields of agriculture,is currently facing important challenges that will be addressed only through sustained,dedicated and coordinated research.Although the methods used in biology have evolved tremendously in recent years and now involve the routine production of large data sets of varied nature,in many domains of study,including grapevine research,there is a need to improve the findability,accessibility,interoperability and reusability(FAIR-ness)of these data.Considering the heterogeneous nature of the data produced,the transnational nature of the scientific community and the experience gained elsewhere,we have formed an open working group,in the framework of the International Grapevine Genome Program(www.vitaceae.org),to construct a coordinated federation of information systems holding grapevine data distributed around the world,providing an integrated set of interfaces supporting advanced data modeling,rich semantic integration and the next generation of data mining tools.To achieve this goal,it will be critical to develop,implement and adopt appropriate standards for data annotation and formatting.The development of this system,the GrapeIS,linking genotypes to phenotypes,and scientific research to agronomical and oeneological data,should provide new insights into grape biology,and allow the development of new varieties to meet the challenges of biotic and abiotic stress,environmental change,and consumer demand.展开更多
Media convergence is a media change led by technological innovation.Applying media convergence technology to the study of clustering in Chinese medicine can significantly exploit the advantages of media fusion.Obtaini...Media convergence is a media change led by technological innovation.Applying media convergence technology to the study of clustering in Chinese medicine can significantly exploit the advantages of media fusion.Obtaining consistent and complementary information among multiple modalities through media convergence can provide technical support for clustering.This article presents an approach based on Media Convergence and Graph convolution Encoder Clustering(MCGEC)for traditonal Chinese medicine(TCM)clinical data.It feeds modal information and graph structure from media information into a multi-modal graph convolution encoder to obtain the media feature representation learnt from multiple modalities.MCGEC captures latent information from various modalities by fusion and optimises the feature representations and network architecture with learnt clustering labels.The experiment is conducted on real-world multimodal TCM clinical data,including information like images and text.MCGEC has improved clustering results compared to the generic single-modal clustering methods and the current more advanced multi-modal clustering methods.MCGEC applied to TCM clinical datasets can achieve better results.Integrating multimedia features into clustering algorithms offers significant benefits compared to single-modal clustering approaches that simply concatenate features from different modalities.It provides practical technical support for multi-modal clustering in the TCM field incorporating multimedia features.展开更多
Background: Persons living with severe mental illness (SMI) which includes schizophrenia, bipolar affective disorder and recurrent major depressive disorder are predisposed to risky sexual behavior (RSB). There is a p...Background: Persons living with severe mental illness (SMI) which includes schizophrenia, bipolar affective disorder and recurrent major depressive disorder are predisposed to risky sexual behavior (RSB). There is a paucity of data on this problem in sub-Saharan Africa and where research has been undertaken, only a limited range of risk factors have been considered and most of it was undertaken before antiretroviral therapy was universally available, hence the need for this study. The objective of this study was to determine the prevalence and factors associated with risky sexual behavior among individuals with SMI attending care in central and south western Uganda. Methods: A cross sectional study was conducted among 393 persons with SMI attending two psychiatric out-patient facilities in Uganda. Psychiatric disorder was confirmed using MINI International Neuropsychiatric Interview version 7.2. RSB was defined as engaging in at least one of four risky sexual behaviours that have been associated with HIV infection in the Ugandan psychosocial environment in the last three months using an 8 item RSB questionnaire used for assessment of RSB. Prevalence of RSB and associated correlates were determined using multiple logistic regression. Results: The Prevalence of RSB in last 3 months’ periods was 24.2% (95% CI: 20.2% - 28.7%). The factors that were independently significantly associated with RSB were: trauma related (history of childhood trauma, past and current sexual abuse, past and current physical abuse) current psychosocial challenges (mental health stigma) and psychiatric illness factors (history of a past manic episode, current psychotic episode, severity of depressive symptoms and severity of manic symptoms). Conclusions: One quarter of clinic attending respondents with severe mental illness in Uganda practice risky sexual behaviour. Factors associated with risky sexual behaviour fall under the domains of past and present trauma, current psychosocial challenges and psychiatric illness factors. This calls for a multi-sectoral approach that includes community awareness about the nature of SMI and the rights of persons with SMI and measures to improve Psychiatric symptom management.展开更多
Background: Persisting neurological and cognitive impairments are common after cerebralmalaria. Although risk factors for gross deficits on discharge have been described, few studies have examined those associated wit...Background: Persisting neurological and cognitive impairments are common after cerebralmalaria. Although risk factors for gross deficits on discharge have been described, few studies have examined those associated with persistent impairments. Methods: The risk factors for impairments following cerebral malaria were determined by examining hospital records of 143 children aged 6-9 years, previously admitted with cerebral malaria, who were assessed at least 20 months after discharge to detect motor, speech and language, and other cognitive (memory, attention, and non-verbal functioning) impairments. Results: The median age on admission was 30 months (IQR 19-42) and the median time from discharge to assessment was 64 months (IQR 40-78). Thirty four children (23.8% ) were defin-ed as having impairments: 14 (9.8% ) in motor, 16 (11.2% ) in speech and language, and 20 (14.0% ) in other cognitive functions. Previous seizures (OR 5.6, 95% CI 2.0 to 16.0), deep coma on admission (OR 28.8, 95% CI 3.0 to 280), focal neurological signs observed during admission (OR 4.6, 95% CI 1.1 to 19.6), and neurological deficits on discharge (OR 4.5, 95% CI 1.4 to 13.8) were independently associated with persisting impairments. In addition, multiple seizures were associated with motor impairment, age < 3 years, severe malnutrition, features of intracranial hypertension, and hypoglycaemia with language impairments, while prolonged coma, severe malnutrition, and hypoglycaemia were associated with impairments in other cognitive functions. Conclusions: Risk factors for persisting neurological and cognitive impairments following cerebral malaria include multiple seizures, deep/prolonged coma, hypoglycaemia, and clinical features of intracranial hypertension. Although there are overlaps in impaired functions and risk factors, the differences in risk factors for specific functions may suggest separate mechanisms for neuronal damage. These factors could form the basis of future preventive strategies for persisting impairments.展开更多
The spined loach Cobitis taenia, is listed as a protected species under Appendix 3 of the Bern Convention and Annex II of the European Council Directive (92/43/EEC) on the conservation of natural habitats and of wild ...The spined loach Cobitis taenia, is listed as a protected species under Appendix 3 of the Bern Convention and Annex II of the European Council Directive (92/43/EEC) on the conservation of natural habitats and of wild fauna and flora. It is desirable therefore to understand the genetic diversity within European populations. In a molecular genetic analysis of the cytochrome b gene in Cobitis taenia from three sites in the upper reaches of the River Trent catchment, a novel high frequency variant was identified which has not been previously reported in any European or Non-European population.展开更多
基金supported by grants from the National Natural Science Foundation of China(30770293)the Ministry of Science and Technology of China(2005DKA21502)
文摘Comparing to its sister-family (Rhinolophidae), Hipposideridae was less studied by cytogenetic approaches. Only a few high-resolution G-banded karyotypes have been reported so far, and most of the conclusions on the karyotypic evolution in Hipposideridae were based on conventional Giemsa-staining. In this study, we applied comparative chromosome painting, a method of choice for genome-wide comparison at the molecular level, and G- and C-banding to establish comparative map between five hipposiderid species from China, using a whole set of chromosome-specific painting probes from one of them (Aselliscus stoliczkanus). G-band and C-band comparisons between homologous segments defined by chromosome painting revealed that Robertsonian translocations, paracentric inversions and heterochromatin addition could be the main mechanism of chromosome evolution in Hipposideridae. Comparative analysis of the conserved chromosomal segments among five hipposiderid species and outgroup species suggests that bi-armed chromosomes should be included into the ancestral karyotype of Hipposideridae, which was previously believed to be exclusively composed of acrocentric chromosomes.
基金supported partly by grants from the Ministry of Science and Technology of China(2005DKA21502)the Joint Foundation of Science and Technology Bureau of Yunnan Province and Kunming Medical University(2007C0024R)
文摘Lung cancer is a leading cause of cancer death worldwide. Some lung cancer patients correlate with a gas of radon besides smoking. To search for common chromosomal aberrations in lung cancer cell lines established from patients induced by different factors, a combined approach of chromosome sorting, forward and reverse chromosome painting was used to characterize karyotypes of two lung adenocarcinoma cell lines: A549 and GLC-82 with the latter line derived from a patient who has suffered long-term exposure to environmental radon gas pollution. The chromosome painting results revealed that complex chromosomal rearrangements occurred in these two lung adenocarcinoma cell lines. Thirteen and twenty-four abnormal chromosomes were identified An A549 and GLC-82 cell lines, respectively. Almost half of abnormal chromosomes in these two cell lines were formed by non-reciprocal translocations, the others were derived from deletions and duplication/or amplification in some chromosomal regions. Furthermore, two apparently common breakpoints, HSA8q24 and 12q14 were found in these two lung cancer cell lines.
基金Funding (No. U1302262) to W.B. Sun from the NSFC-Yunnan joint fund on key projects is gratefully acknowledgedThe Royal Botanic Gardens, Kew receives grant-in-aid from Defra+1 种基金This joint work was undertaken under the Memorandum of Agreement (2014e24) on Plant and Fungal Science between the Chinese Academy of Sciences and the Trustees of the Royal Botanic Gardens, KewHWP thanks Darwin Initiative Project 21-003 on cycads for funding
文摘Approximately one fifth of the world's plants are at risk of extinction.Of these,a significant number exist as populations of few individuals,with limited distribution ranges and under enormous pressure due to habitat destruction.In China,these most-at-risk species are described as 'plant species with extremely small populations'(PSESP).Implementing conservation action for such listed species is urgent.Storing seeds is one of the main means of ex situ conservation for flowering plants.Spore storage could provide a simple and economical method for fern ex situ conservation.Seed and spore germination in nature is a critical step in species regeneration and thus in situ conservation.But what is known about the seed and spore biology(storage and germination) of at-risk species? We have used China's PSESP(the first group listing) as a case study to understand the gaps in knowledge on propagule biology of threatened plant species.We found that whilst germination information is available for 28 species(23%of PSESP),storage characteristics are only known for 8%of PSESP(10 species).Moreover,we estimate that 60%of the listed species may require cryopreservation for long-term storage.We conclude that comparative biology studies are urgently needed on the world's most threatened taxa so that conservation action can progress beyond species listing.
基金financial support from the Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King's College London and King’s College Hospital NHS Foundation TrustThe Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC under grant number WT 088641/Z/09/Z+2 种基金King’s College London and UCL Comprehensive Cancer Imaging CentreFunded by the CRUK and EPSRC in association with the MRC and Do H (England)Funded by the British Heart Foundation award RE/08/003
文摘The aim of this review is to give a comprehensive and concise overview of coronary embryology and normal coronary anatomy, describe common variants of normal and summarize typical patterns of anomalous coronary artery anatomy. Extensive iconography supports the text, with particular attention to images obtained in vivo using non-invasive imaging. We have divided this article into three groups, according to their frequency in the general population: Normal, normal variant and anomaly. Although congenital coronary artery anomalies are relatively uncommon, they are the second most common cause of sudden cardiac death among young athletes and therefore warrant detailed review. Based on the functional relevance of each abnormality, coronary artery anomalies can be classified as anomalies with obligatory ischemia, without ischemia or with exceptional ischemia. The clinical symptoms may include chest pain, dyspnea, palpitations, syncope, cardiomyopathy, arrhythmia, myocardial infarction and sudden cardiac death. Moreover, it is important to also identify variants and anomalies without clinical relevance in their own right as complications during surgery or angioplasty can occur.
文摘Most defective and unwanted cells die by apoptosis, cells without damaging the surrounding tissue. Once a an exquisitely controlled genetic programme for removing such cell has committed to apoptosis, the process is remarkably efficient, and is completed within a few minutes of initiation. This point of no retum for an apoptotic cell is commonly held to be the point at which the outer mitochondrial membrane is permeabilised, a process regulated by the Bcl-2 family of proteins. How these proteins regulate this decision point is central to diseases such as cancer where apoptotic control is lost. In this review, we will discuss apoptotic signalling and how a cell makes the irreversible decision to die. We will focus on one set of survival signals, those derived by cell adhesion to the extracellular matrix (ECM), and use these to highlight the complexities of apoptotic signalling. In particular, we will illustrate how multiple signalling pathways converge to determine critical cell fate decisions.
基金funded by the EPSRC Centre for Doctoral Training in Tissue Engineering and Regenerative Medicine–Innovation in Medical and Biological Engineeringpartially sponsored by the EU [FP7/ 2007-2013] for ‘SkelGEN’ consortium (n° 318553) and the British Council
文摘There are large knowledge gaps regarding how to control stem cells growth and differentiation.The limitations of currently available technologies,such as growth factors and/or gene therapies has led to the search of alternatives.We explore here how a cell’s epigenome influences determination of cell type,and potential applications in tissue engineering.A prevalent epigenetic modification is the acetylation of DNA core histone proteins.Acetylation levels heavily influence gene transcription.Histone deacetylase (HDAC) enzymes can remove these acetyl groups,leading to the formation of a condensed and more transcriptionally silenced chromatin.Histone deacetylase inhibitors (HDACis) can inhibit these enzymes,resulting in the increased acetylation of histones,thereby affecting gene expression.There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering,potentially providing novel tools to control stem cell fate.This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone,cardiac,neural tissues),including the history,current status and future perspectives of using HDACis for stem cell research and tissue engineering,with particular attention paid to how different HDAC isoforms may be integral to this field.
基金supported in part by NIH HL098472NSF CBET0846429
文摘Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the major sites of interaction between a cell and its extracellular matrix(ECM)microenvironment,thus outside mechanical signals can be sensed at focal adhesions through transmembrane receptor integrins.In particular,it has been shown that matrix elasticity can control the cell fate<sup>[4]</sup>by modulating the interactions between ECM proteins and their receptor integrins<sup>[5,6]</sup>.For example,different rigidity of polyacrylamide(PA)gels can lead to different density of ECM ancho-
基金supported by the Spanish Ministry of Economy and Competitiveness(grant numbers AGL2010-21929 and AGL2013-48756-R)the Spanish Ministry of Economy and Competitiveness,the Agencia Estatal de Investigación,and the European Regional Development Fund(grant number AGL2016–80967-R)Government of Aragon(Research Group A08_20R)。
文摘Response to vernalization and photoperiod are the main determinants controlling the time to flowering in temperate cereals. While the individual genes that determine a plant's response to these environmental signals are well characterized, the combinatorial effect on flowering time of allelic variants for multiple genes remains unresolved. This study investigated the genetic control of flowering-time in a biparental population of spring barley, derived from a wide cross between a late-flowering European and an early-flowering North-American cultivar. While the major flowering time genes are not segregating in the Beka ×Logan cross, large variation in flowering was observed. We identified five QTL, with both parents found to contribute early alleles. The catalog of QTL discovered aligns with several candidate genes affecting flowering time in barley. The combination of particular alleles at HvCEN, HvELF3 and HvFT1 in Logan are responsible for the earliness of this cultivar. Interestingly, earliness for flowering could be further enhanced, with Beka found to contribute three early alleles, including a QTL colocating with a HvFD-like gene, suggesting that there are diverse aspects of the flowering-time pathway that have been manipulated in these two cultivars. Epistatic interactions between flowering-time QTL or candidate genes were observed in field data and confirmed under controlled conditions. The results of this study link photoperiod-dependent flowering-time genes with earliness per se genes into a single model, thus providing a unique framework that can be used by geneticists and breeders to optimize flowering time in barley.
基金supported by funding from the Medical Research Council (MRC) through the WIMM Strategic Alliance (G0902418 and MC_UU_12025) and to E. Y.J. (G9900061),the Department of Health, UK, Quality, Improvement, Development and Initiative Scheme (QIDIS) (AOMW)the Wellcome Trust (Project Grant 093329 to AOMW and SRFT+8 种基金Investigator Award 102731 to AOMWgrant 090532/Z/09/Z supporting the Wellcome Trust Centre for Human Genetics)supported by the Crohn’s & Colitis Foundation of America (CCFA)the Leona M. and Harry B. Helmsley Charitable Trustfunded by the NIHR Oxford Biomedical Research Centresupported by the Deutsche Forschungsgemeinschaft (SCHW1730/1-1)supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn (grant number SFB841 to F.K., D.S.-A., and S.R.-J.SFB877 to S.R.-J.)the Cluster of Excellence “Inflammation at Interfaces” to S.R.-J.
文摘The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6 st p.R279 Q. We show that human GP130 p.R281 Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice Il6 st p.R279 Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11 RA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.
基金Supported by Hyderabad Eye Research Foundation,India and Christoffel-Blindenmission(CBM),Bensheim,Germany
文摘AIM:To report on the utilization of eye care services and its associated factors among those with unilateral visual impairment(VI)in a rural South Indian population.METHODS:A population based cross-sectional study was conducted in three districts(Adilabad,Mahbubnagar and West Godavari)in the state of Andhra Pradesh,India.A detailed interview and a comprehensive eye examination were conducted. Those with unilateral VI were asked questions about noticing any change in vision and on utilization of eye care services. The most important reason reported by the participant for not utilizing the services was used for the analysis. Multiple logistic regression models were used to examine the association between noticing a change in vision and socio-demographic variables such as age,gender,education and area of residence,severity and causes of VI.RESULTS:Among the 4456 participants aged ≥16y who were administered the questionnaire,53.2% were women,and 54.7% had no education. Of the 489(11%; 95% CI:10.1-11.9)people with unilateral VI,399(81.6%)participants reported noticing a change in their vision over the last five years but only 136(34.1%)participants had soughteye care consultation. Those who had any education(OR:1.9; 95% CI:1.1-3.2),had blindness(OR:2.7; 95% CI:1.4-5.2),and cataract(OR:2.1; 95% CI:1.0-4.3)as a cause of unilateral VI were more like to seek eye care consultations. The most commonly reported reasons for not seeking eye care services were "do not have money for eye checkup" in 30.7% of the participants followed by "do not have a serious problem"(30.0%).CONCLUSION:A large proportion of rural population though noticed a change in their vision did not seek eye care due to financial and person-related reasons. Eye care service providers need to address these barriers to enhance the uptake of eye care services among those with unilateral VI.
基金Supported by a PhD studentship form Diabetes UK (for Thomas SE)
文摘Both environmental and genetic factors contribute to the development of diabetes mellitus and although monogenic disorders are rare,they offer unique insights into the fundamental biology underlying the disease.Mutations of the insulin gene or genes involved in the response to protein misfolding cause early onset diabetes.These have revealed an important role for endoplasmic reticulum stress in β-cell survival.This form of cellular stress occurs when secretory proteins fail to fold efficiently.Of all the professional secretory cells we possess,β-cells are the most sensitive to endoplasmic reticulum stress because of the large fluctuations in protein synthesis they face daily.Studies of endoplasmic reticulum stress signaling therefore offer the potential to identify new drug targets to treat diabetes.
文摘Identifying genetic variants that contribute to phenotypic variation is expected to provide insights into the etiology of complex traits. Here we show how combining genetic mapping in an outbred population of rats with sequence data from the progenitors of the population made it possible to identify causal variants and genes for a large number of phenotypes. We identified 355 genomic loci contributing to 122 measures relevant to six models of disease, including fear-related behaviors and experimental autoimmune encephalomyelitis. At 35 of those loci we identified the responsible gene, and in some cases, the responsible variant.
基金The foundations and the first draft of this paper were set up during a workshop organized in Bordeaux,France in February 2015 with the financial support of the Gallo Wine Company,INRA and of the Institut des Sciences de la Vigne et du Vin.
文摘Viticulture,like other fields of agriculture,is currently facing important challenges that will be addressed only through sustained,dedicated and coordinated research.Although the methods used in biology have evolved tremendously in recent years and now involve the routine production of large data sets of varied nature,in many domains of study,including grapevine research,there is a need to improve the findability,accessibility,interoperability and reusability(FAIR-ness)of these data.Considering the heterogeneous nature of the data produced,the transnational nature of the scientific community and the experience gained elsewhere,we have formed an open working group,in the framework of the International Grapevine Genome Program(www.vitaceae.org),to construct a coordinated federation of information systems holding grapevine data distributed around the world,providing an integrated set of interfaces supporting advanced data modeling,rich semantic integration and the next generation of data mining tools.To achieve this goal,it will be critical to develop,implement and adopt appropriate standards for data annotation and formatting.The development of this system,the GrapeIS,linking genotypes to phenotypes,and scientific research to agronomical and oeneological data,should provide new insights into grape biology,and allow the development of new varieties to meet the challenges of biotic and abiotic stress,environmental change,and consumer demand.
基金China Academy of Chinese Medical Sciences,Grant/Award Number:CI2021A00512。
文摘Media convergence is a media change led by technological innovation.Applying media convergence technology to the study of clustering in Chinese medicine can significantly exploit the advantages of media fusion.Obtaining consistent and complementary information among multiple modalities through media convergence can provide technical support for clustering.This article presents an approach based on Media Convergence and Graph convolution Encoder Clustering(MCGEC)for traditonal Chinese medicine(TCM)clinical data.It feeds modal information and graph structure from media information into a multi-modal graph convolution encoder to obtain the media feature representation learnt from multiple modalities.MCGEC captures latent information from various modalities by fusion and optimises the feature representations and network architecture with learnt clustering labels.The experiment is conducted on real-world multimodal TCM clinical data,including information like images and text.MCGEC has improved clustering results compared to the generic single-modal clustering methods and the current more advanced multi-modal clustering methods.MCGEC applied to TCM clinical datasets can achieve better results.Integrating multimedia features into clustering algorithms offers significant benefits compared to single-modal clustering approaches that simply concatenate features from different modalities.It provides practical technical support for multi-modal clustering in the TCM field incorporating multimedia features.
文摘Background: Persons living with severe mental illness (SMI) which includes schizophrenia, bipolar affective disorder and recurrent major depressive disorder are predisposed to risky sexual behavior (RSB). There is a paucity of data on this problem in sub-Saharan Africa and where research has been undertaken, only a limited range of risk factors have been considered and most of it was undertaken before antiretroviral therapy was universally available, hence the need for this study. The objective of this study was to determine the prevalence and factors associated with risky sexual behavior among individuals with SMI attending care in central and south western Uganda. Methods: A cross sectional study was conducted among 393 persons with SMI attending two psychiatric out-patient facilities in Uganda. Psychiatric disorder was confirmed using MINI International Neuropsychiatric Interview version 7.2. RSB was defined as engaging in at least one of four risky sexual behaviours that have been associated with HIV infection in the Ugandan psychosocial environment in the last three months using an 8 item RSB questionnaire used for assessment of RSB. Prevalence of RSB and associated correlates were determined using multiple logistic regression. Results: The Prevalence of RSB in last 3 months’ periods was 24.2% (95% CI: 20.2% - 28.7%). The factors that were independently significantly associated with RSB were: trauma related (history of childhood trauma, past and current sexual abuse, past and current physical abuse) current psychosocial challenges (mental health stigma) and psychiatric illness factors (history of a past manic episode, current psychotic episode, severity of depressive symptoms and severity of manic symptoms). Conclusions: One quarter of clinic attending respondents with severe mental illness in Uganda practice risky sexual behaviour. Factors associated with risky sexual behaviour fall under the domains of past and present trauma, current psychosocial challenges and psychiatric illness factors. This calls for a multi-sectoral approach that includes community awareness about the nature of SMI and the rights of persons with SMI and measures to improve Psychiatric symptom management.
文摘Background: Persisting neurological and cognitive impairments are common after cerebralmalaria. Although risk factors for gross deficits on discharge have been described, few studies have examined those associated with persistent impairments. Methods: The risk factors for impairments following cerebral malaria were determined by examining hospital records of 143 children aged 6-9 years, previously admitted with cerebral malaria, who were assessed at least 20 months after discharge to detect motor, speech and language, and other cognitive (memory, attention, and non-verbal functioning) impairments. Results: The median age on admission was 30 months (IQR 19-42) and the median time from discharge to assessment was 64 months (IQR 40-78). Thirty four children (23.8% ) were defin-ed as having impairments: 14 (9.8% ) in motor, 16 (11.2% ) in speech and language, and 20 (14.0% ) in other cognitive functions. Previous seizures (OR 5.6, 95% CI 2.0 to 16.0), deep coma on admission (OR 28.8, 95% CI 3.0 to 280), focal neurological signs observed during admission (OR 4.6, 95% CI 1.1 to 19.6), and neurological deficits on discharge (OR 4.5, 95% CI 1.4 to 13.8) were independently associated with persisting impairments. In addition, multiple seizures were associated with motor impairment, age < 3 years, severe malnutrition, features of intracranial hypertension, and hypoglycaemia with language impairments, while prolonged coma, severe malnutrition, and hypoglycaemia were associated with impairments in other cognitive functions. Conclusions: Risk factors for persisting neurological and cognitive impairments following cerebral malaria include multiple seizures, deep/prolonged coma, hypoglycaemia, and clinical features of intracranial hypertension. Although there are overlaps in impaired functions and risk factors, the differences in risk factors for specific functions may suggest separate mechanisms for neuronal damage. These factors could form the basis of future preventive strategies for persisting impairments.
文摘The spined loach Cobitis taenia, is listed as a protected species under Appendix 3 of the Bern Convention and Annex II of the European Council Directive (92/43/EEC) on the conservation of natural habitats and of wild fauna and flora. It is desirable therefore to understand the genetic diversity within European populations. In a molecular genetic analysis of the cytochrome b gene in Cobitis taenia from three sites in the upper reaches of the River Trent catchment, a novel high frequency variant was identified which has not been previously reported in any European or Non-European population.