759 research outputs found

    Journalism 'fixers', hyper-precarity and the violence of the entrepreneurial self

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    Syed I Ashraf, Sean Phelan, "Journalism ‘fixers’, hyper-precarity and the violence of the entrepreneurial self" First Published in "Journalism" January 24, 2022 https://doi.org/10.1177/14648849211065306,Publishe

    Neural stem cell transcriptional networks highlight genes essential for nervous system development

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    Neural stem cells must strike a balance between self-renewal and multipotency, and differentiation. Identification of the transcriptional networks regulating stem cell division is an essential step in understanding how this balance is achieved. We have shown that the homeodomain transcription factor, Prospero, acts to repress self-renewal and promote differentiation. Among its targets are three neural stem cell transcription factors, Asense, Deadpan and Snail, of which Asense and Deadpan are repressed by Prospero. Here, we identify the targets of these three factors throughout the genome. We find a large overlap in their target genes, and indeed with the targets of Prospero, with 245 genomic loci bound by all factors. Many of the genes have been implicated in vertebrate stem cell self-renewal, suggesting that this core set of genes is crucial in the switch between self-renewal and differentiation. We also show that multiply bound loci are enriched for genes previously linked to nervous system phenotypes, thereby providing a shortcut to identifying genes important for nervous system development

    Flexural behaviour of hybrid steel-GFRP reinforced concrete continuous T-beams

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    YesThis paper presents test results of six full scale reinforced concrete continuous T beams. One beam was reinforced with glass fibre reinforced polymer (GFRP) bars while the other five beams were reinforced with a different combination of GFRP and steel bars. The ratio of GFRP to steel reinforcement at both mid-span and middle-support sections was the main parameter investigated. The results showed that adding steel reinforcement to GFRP reinforced concrete T-beams improves the flexural stiffness, ductility and serviceability in terms of crack width and deflection control. However, the moment redistribution at failure was limited because of the early yielding of steel reinforcement at a beam section that does not reach its moment capacity and could still carry more loads due to the presence of FRP reinforcement. The experimental results were compared with the ultimate moment prediction of ACI 440.2R-17, and with the existing theoretical equations for deflection prediction. It was found that the ACI 440.2R-17 reasonably estimated the moment capacity of both mid-span and middle support sections. Conversely, the available theoretical deflection models underestimated the deflection of hybrid reinforced concrete T-beams at all load stages

    The genomes of two key bumblebee species with primitive eusocial organization

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    Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

    The role of mutations in core protein of hepatitis B virus in liver fibrosis

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    The core protein of hepatitis B virus encompasses B- and T-cell immunodominant epitopes and subdivided into two domains: the N-terminal and the functional C-terminal consisted phosphorylation sites. Mutations of the core gene may change the conformation of the core protein or cause alteration of important epitopes in the host immune response. In this study twenty nine men (mean age 40 ± 9 years old) with chronic hepatitis B were recruited for direct sequencing of the core gene. Serum ALT and HBV DNA level were measured at the time of liver biopsy. The effects of core protein mutations on patients' characteristics and subsequently mutations in B cell, T helper and cytotoxic T lymphocyte (CTL) epitopes and also C-terminal domain of core protein on the activity of liver disease was evaluated. Liver fibrosis was significantly increased in patients with core protein mutation (1.0 ± 0.8 vs 1.9 ± 1.4 for mean stage of fibrosis P = 0.05). Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both). Patients with mutation in C-terminal domain had higher serum ALT (62 ± 17 vs 36 ± 12 IU/l, p = 0.02). Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features. Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein

    Is salinity the main ecologic factor that shapes the distribution of two endemic Mediterranean plant species of the genus Gypsophila?

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s11104-014-2218-2Aims Responses to salt stress of two Gypsophila species that share territory, but with different ecological optima and distribution ranges, were analysed. G. struthium is a regionally dominant Iberian endemic gypsophyte, whereas G. tomentosa is a narrow endemic reported as halophyte. Theworking hypothesis is that salt tolerance shapes the presence of these species in their specific habitats. Methods Taking a multidisciplinary approach, we assessed the soil characteristics and vegetation structure at the sampling site, seed germination and seedling development, growth and flowering, synthesis of proline and cation accumulation under artificial conditions of increasing salt stress and effect of PEG on germination and seedling development. Results Soil salinity was low at the all sampling points where the two species grow, but moisture was higher in the area of G. tomentosa. Differences were found in the species salt and drought tolerance. The different parameters tested did not show a clear pattern indicating the main role of salt tolerance in plant distribution. Conclusions G. tomentosa cannot be considered a true halophyte as previously reported because it is unable to complete its life cycle under salinity. The presence of G. tomentosa in habitats bordering salt marshes is a strategy to avoid plant competition and extreme water stressSoriano, P.; Moruno Manchón, JF.; Boscaiu Neagu, MT.; Vicente Meana, Ó.; Hurtado, A.; Llinares Palacios, JV.; Estrelles, E. (2014). Is salinity the main ecologic factor that shapes the distribution of two endemic Mediterranean plant species of the genus Gypsophila?. Plant and Soil. 384(1-2):363-379. doi:10.1007/s11104-014-2218-2S3633793841-2Alonso MA (1996) Flora y vegetación del Valle de Villena (Alicante). 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    Best practice approach for redo-surgeries after sleeve gastrectomy, an expert's modified Delphi consensus

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    Background: Sleeve gastrectomy (SG) is the most common metabolic and bariatric surgical (MBS) procedure worldwide. Despite the desired effect of SG on weight loss and remission of obesity-associated medical problems, there are some concerns regarding the need to do revisional/conversional surgeries after SG. This study aims to make an algorithmic clinical approach based on an expert-modified Delphi consensus regarding redo-surgeries after SG, to give bariatric and metabolic surgeons a guideline that might help for the best clinical decision. Methods: Forty-six recognized bariatric and metabolic surgeons from 25 different countries participated in this Delphi consensus study in two rounds to develop a consensus on redo-surgeries after SG. An agreement/disagreement ≥ 70.0% on statements was considered to indicate a consensus. Results: Consensus was reached for 62 of 72 statements and experts did not achieve consensus on 10 statements after two rounds of online voting. Most of the experts believed that multi-disciplinary team evaluation should be done in all redo-procedures after SG and there should be at least 12 months of medical and supportive management before performing redo-surgeries after SG for insufficient weight loss, weight regain, and gastroesophageal reflux disease (GERD). Also, experts agreed that in case of symptomatic GERD in the presence of adequate weight loss, medical treatment for at least 1 to 2 years is an acceptable option and agreed that Roux-en Y gastric bypass is an appropriate option in this situation. There was disagreement consensus on efficacy of omentopexy in rotation and efficacy of fundoplication in the presence of a dilated fundus and GERD. Conclusion: Redo-surgeries after SG is still an important issue among bariatric and metabolic surgeons. The proper time and procedure selection for redo-surgery need careful considerations. Although multi-disciplinary team evaluation plays a key role to evaluate best options in these situations, an algorithmic clinical approach based on the expert's consensus as a guideline can help for the best clinical decision-making.info:eu-repo/semantics/publishedVersio

    Analysis of Mitochondrial DNA Sequences in Childhood Encephalomyopathies Reveals New Disease-Associated Variants

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    BACKGROUND: Mitochondrial encephalomyopathies are a heterogeneous group of clinical disorders generally caused due to mutations in either mitochondrial DNA (mtDNA) or nuclear genes encoding oxidative phosphorylation (OXPHOS). We analyzed the mtDNA sequences from a group of 23 pediatric patients with clinical and morphological features of mitochondrial encephalopathies and tried to establish a relationship of identified variants with the disease. METHODOLOGY/PRINCIPLE FINDINGS: Complete mitochondrial genomes were amplified by PCR and sequenced by automated DNA sequencing. Sequencing data was analyzed by SeqScape software and also confirmed by BLASTn program. Nucleotide sequences were compared with the revised Cambridge reference sequence (CRS) and sequences present in mitochondrial databases. The data obtained shows that a number of known and novel mtDNA variants were associated with the disease. Most of the non-synonymous variants were heteroplasmic (A4136G, A9194G and T11916A) suggesting their possibility of being pathogenic in nature. Some of the missense variants although homoplasmic were showing changes in highly conserved amino acids (T3394C, T3866C, and G9804A) and were previously identified with diseased conditions. Similarly, two other variants found in tRNA genes (G5783A and C8309T) could alter the secondary structure of Cys-tRNA and Lys-tRNA. Most of the variants occurred in single cases; however, a few occurred in more than one case (e.g. G5783A and A10149T). CONCLUSIONS AND SIGNIFICANCE: The mtDNA variants identified in this study could be the possible cause of mitochondrial encephalomyopathies with childhood onset in the patient group. Our study further strengthens the pathogenic score of known variants previously reported as provisionally pathogenic in mitochondrial diseases. The novel variants found in the present study can be potential candidates for further investigations to establish the relationship between their incidence and role in expressing the disease phenotype. This study will be useful in genetic diagnosis and counseling of mitochondrial diseases in India as well as worldwide

    Induction of Apoptosis Coupled to Endoplasmic Reticulum Stress in Human Prostate Cancer Cells by n-butylidenephthalide

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    BACKGROUND: N-butylidenephthalide (BP) exhibits antitumor effect in a variety of cancer cell lines. The objective of this study was to obtain additional insights into the mechanisms involved in BP induced cell death in human prostate cancer cells. METHODS/PRINCIPAL FINDINGS: Two human prostate cancer cell lines, PC-3 and LNCaP, were treated with BP, and subsequently evaluated for their viability and cell cycle profiles. BP caused cell cycle arrest and cell death in both cell lines. The G0/G1 phase arrest was correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. To determine the mechanisms of BP-induced growth arrest and cell death in prostate cancer cell lines, we performed a microarray study to identify alterations in gene expression induced by BP in the LNCaP cells. Several BP-induced genes, including the GADD153/CHOP, an endoplasmic reticulum stress (ER stress)-regulated gene, were identified. BP-induced ER stress was evidenced by increased expression of the downstream molecules GRP78/BiP, IRE1-α and GADD153/CHOP in both cell lines. Blockage of IRE1-α or GADD153/CHOP expression by siRNA significantly reduced BP-induced cell death in LNCaP cells. Furthermore, blockage of JNK1/2 signaling by JNK siRNA resulted in decreased expression of IRE1-α and GADD153/CHOP genes, implicating that BP-induced ER stress may be elicited via JNK1/2 signaling in prostate cancer cells. BP also suppressed LNCaP xenograft tumor growth in NOD-SCID mice. It caused 68% reduction in tumor volume after 18 days of treatment. CONCLUSIONS: Our results suggest that BP can cause G0/G1 phase arrest in prostate cancer cells and its cytotoxicity is mediated by ER stress induction. Thus, BP may serve as an anticancer agent by inducing ER stress in prostate cancer
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