Complete mitochondrial genome of six Cheilinusundulatus (Napoleon Wrasse): an endangeredmarine fish species from Sabah, Malaysia

We report here the complete mitochondrial (mt) genomes of six individuals of Cheilinus undulatus (Napoleon Wrasse), an endangered marine fish species. The six mt DNA sequences had an average size of 17,000 kb and encoded 22 tRNA, two sRNA, 13 highly conserved protein coding genes and a control region. The polymorphic variation (control region) in these six individuals suggests their potential use as a specific marker for phylogeographic conservation. Moreover, the sequence polymorphism within the control region (D-loop) suggests that this locus can be applied for phylogenetic studies

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Mitochondrial Genome analysis and genetic charaterization of endangered Humphead Wrasse, Cheilinus Undula Tus (Ruppell, 1835) from Sabah, Malaysia

Mitochondrial (mt) Deoxyribonucleic acid (DNA) loci have been employed in various marine taxa, including reef fishes with the objective of resolving phylogeny, assigning parentage and delineating haplotypes. In this study, complete mtDNA genome was sequenced and the D-Loop locus was applied to estimate the population status of the Humphead Wrasse (HHW) Chetllnus undulatus. The Humphead Wrasse (HHW) is a long-lived reef-associated fish and the largest member of wrasses (family Labridae). However, it is endangered throughout its natural distributional range, primarily due to being a target in the Live Reef Fish for Food Trade. Specimens tissue were collected from three localities in Sabah, i.e. Kota Kinabalu, Sandakan and Semporna. The objectives of this study are 1) to sequence the mtDNA of the HHW, and 2) to identify population structure using D-LOOP of the HHW. The result of the sequencing data assemblies yielded six mitochondrial genomes and deposited into the National Center for Biotechnology Information (NCBI) with the accession number MH675879, MH675880, MH688049, MH688050, MH688051, MH688052. The result from AMOVA and overall Fst (-0.02914) showed that all three population absent from population structuring despite geographical distinct. The AMOVA showed a variation (100%) arise within the population instead among population. The neutrality test from Tajima' D (Kota Kinabalu: -1.825 and Sandakan: -1.009), and more sensitive Fu's Fs Statistic (Kota Kinabalu: -3.9844 and Sandakan-1.149), and mismatch distribution showed unimodal graph pattern suggested as C undulatus undergoes recent population expansion. Haplotype frequency analysis produce a total 25 haplotypes whereas unique 11 haplotype is detected from three local population. High haplotypic diversity encountered in the Kota Kinabalu (0.682), Sandakan (0.902) and Sempona (1.000) and low nucleotide diversity in Kota Kinabalu (0.003), Sandakan (0.004), and Semporna (0.002), and starburst pattern of common haplotypes median joining network support C undulatus population expansion. The first genetic characterization data from mtDNA and all three populations structure analysis of C undulatus from Sabah study provide a new insight for conservation attention

Improving the membrane performance in tangential flow filtration by reducing its clogging using automatic controller system

The discharge sago effluents produceharmful effect to the environment. Hence, the treatment of the sago effluent under microfiltration (MF) process is necessary to reduce the impact to the biodiversity. The treatment for sago effluent can be done by using Tangential Filtration Flow system (TFF). However, clogging is the drawback factor. The main agenda for this project is to minimise the clogging and, therefore, increase the life-span of the membrane by using automated controller system. Besides, reduction in maintenance cost of the complete system for the treatment of the sago effluent is achieved. The effectiveness of this process is evaluated by the trans-membrane pressure (TMP) and permeate flux rate(L/h/m2)

Highly Aligned Centrifugal Spun Polyacrylonitrile Nanofibers Collected and Processed with Automated Tracks

Abstract A parallel automated track collector is integrated with a rationally designed centrifugal spinning head to collect aligned polyacrylonitrile (PAN) nanofibers. Centrifugal spinning is an extremely promising nanofiber fabrication technology due to high production rates. However, continuous oriented fiber collection and processing presents challenges. Engineering solutions to these two challenges are explored in this study. A 3D‐printed head design, optimized through a computational fluid dynamics simulation approach, is utilized to limit unwanted air currents that disturb deposited nanofibers. An automated track collecting device has pulled deposited nanofibers away from the collecting area. This results in a continuous supply of individual aligned nanofibers as opposed to the densely packed nanofiber mesh ring that is deposited on conventional static post collectors. The automated track collector allows for simple integration of the postdraw processing step that is critical to polymer fiber manufacturing for enhancing macromolecular orientation and mechanical properties. Postdrawing has enhanced the mechanical properties of centrifugal spun PAN nanofibers, which have different crystalline properties compared with conventional PAN microfiber. These technological developments address key limitations of centrifugal spinning that can facilitate high production rate commercial fabrication of highly aligned, high‐performance polymer nanofibers

Activation of Stimulator of IFN Genes (STING) Causes Proteinuria and Contributes to Glomerular Diseases

The signaling molecule stimulator of IFN genes (STING) was identified as a crucial regulator of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-STING pathway, and this signaling pathway regulates inflammation and energy homeostasis under conditions of obesity, kidney fibrosis, and AKI. However, the role of STING in causing CKD, including diabetic kidney disease (DKD) and Alport syndrome, is unknown. To investigate whether STING activation contributes to the development and progression of glomerular diseases such as DKD and Alport syndrome, immortalized human and murine podocytes were differentiated for 14 days and treated with a STING-specific agonist. We used diabetic mice, mice with experimental Alport syndrome, mice, and STING knockout mice to assess the role of the STING signaling pathway in kidney failure. , murine and human podocytes express all of the components of the cGAS-STING pathway. , activation of STING renders mice susceptible to albuminuria and podocyte loss. STING is activated at baseline in mice with experimental DKD and Alport syndrome. STING activation occurs in the glomerular but not the tubulointerstitial compartment in association with autophagic podocyte death in Alport syndrome mice and with apoptotic podocyte death in DKD mouse models. Genetic or pharmacologic inhibition of STING protects from progression of kidney disease in mice with DKD and Alport syndrome and increases lifespan in Alport syndrome mice. The activation of the STING pathway acts as a mediator of disease progression in DKD and Alport syndrome. Targeting STING may offer a therapeutic option to treat glomerular diseases of metabolic and nonmetabolic origin or prevent their development, progression, or both