Miracle-dz/UniFAR-FTUs huggingface dataset:
Heat‐induced shift in coral microbiome reveals several members of the Rhodobacteraceae family as indicator species for thermal stress in Porites lutea

The coral holobiont is a complex ecosystem consisting of coral animals and a highly diverse consortium of associated microorganisms including algae, fungi, and bacteria. Several studies have highlighted the importance of coral‐associated bacteria and their potential roles in promoting the host fitness and survival. Recently, dynamics of coral‐associated microbiomes have been demonstrated to be linked to patterns of coral heat tolerance. Here, we examined the effect of elevated seawater temperature on the structure and diversity of bacterial populations associated with Porites lutea, using full‐length 16S rRNA sequences obtained from Pacific Biosciences circular consensus sequencing. We observed a significant increase in alpha diversity indices and a distinct shift in microbiome composition during thermal stress. There was a marked decline in the apparent relative abundance of Gammaproteobacteria family Endozoicomonadaceae after P. lutea had been exposed to elevated seawater temperature. Concomitantly, the bacterial community structure shifted toward the predominance of Alphaproteobacteria family Rhodobacteraceae. Interestingly, we did not observe an increase in relative abundance of Vibrio‐related sequences in our heat‐stressed samples even though the appearance of Vibrio spp. has often been detected in parallel with the increase in the relative abundance of Rhodobacteraceae during thermal bleaching in other coral species. The ability of full‐length 16S rRNA sequences in resolving taxonomic uncertainty of associated bacteria at a species level enabled us to identify 24 robust indicator bacterial species for thermally stressed corals. It is worth noting that the majority of those indicator species were members of the family Rhodobacteraceae. The comparison of bacterial community structure and diversity between corals in ambient water temperature and thermally stressed corals may provide a better understanding on how bacteria symbionts contribute to the resilience of their coral hosts to ocean warming.
Effects of antihypertensives, lipid-modifying drugs, glycaemic control drugs and sodium bicarbonate on the progression of stages 3 and 4 chronic kidney disease in adults: a systematic review and meta-analysis

Objective To evaluate the effects of drug interventions that may modify the progression of chronic kidney disease (CKD) in adults with CKD stages 3 and 4. Design Systematic review and meta-analysis. Methods Searching MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, International Clinical Trials Registry Platform, Health Technology Assessment, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index and Clinical Trials Register, from March 1999 to July 2018, we identified randomised controlled trials (RCTs) of drugs for hypertension, lipid modification, glycaemic control and sodium bicarbonate, compared with placebo, no drug or a drug from another class, in ≥40 adults with CKD stages 3 and/or 4, with at least 2 years of follow-up and reporting renal function (primary outcome), proteinuria, adverse events, maintenance dialysis, transplantation, cardiovascular events, cardiovascular mortality or all-cause mortality. Two reviewers independently screened citations and extracted data. For continuous outcomes, we used the ratio of means (ROM) at the end of the trial in random-effects meta-analyses. We assessed methodological quality with the Cochrane Risk of Bias Tool and confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results We included 35 RCTs and over 51 000 patients. Data were limited, and heterogeneity varied. Final renal function (estimated glomerular filtration rate) was 6% higher in those taking glycaemic control drugs (ROM 1.06, 95% CI 1.02 to 1.10, I2=0%, low GRADE confidence) and 4% higher in those taking lipid-modifying drugs (ROM 1.04, 95% CI 1.00 to 1.08, I2=88%, very low GRADE confidence). For RCTs of antihypertensive drugs, there were no significant differences in renal function. Treatment with lipid-modifying drugs led to a 36% reduction in cardiovascular disease and 26% reduction in all-cause mortality. Conclusions Glycaemic control and lipid-modifying drugs may slow the progression of CKD, but we found no pooled evidence of benefit nor harm from antihypertensive drugs. However, given the data limitations, further research is needed to confirm these findings. PROSPERO registration number CRD42015017501.
The effects of supercritical carbon dioxide extraction and cold-pressed hexane extraction on the chemical composition and feeding value of rapeseed meal for broiler chickens

ABSTRACT The chemical characteristics of rapeseed meal (RSM) produced from two cultivars of UK-grown rapeseed, by both supercritical carbon dioxide extraction (ScCO2) and cold-pressed hexane extraction (CpHe) were examined. Their nutritional value, with and without protease, was then assessed in a broiler digestibility trial. Basal feed was substituted with one of four RSM batches (200 g/kg) following adjustments for dry matter (DM) and ether extract (EE) content. Half of each diet was supplemented with a mono-component protease derived from Bacillus subtilis (Axtra®PRO, Danisco Animal Nutrition, Malborough, UK) giving a total of eight test diets. Two control diets, with and without protease were also fed. At 13 d age male Ross 308 broilers were randomly allocated to seven replicate pens (five birds per pen) and assigned to one of 10 diets. Total excreta were collected from 17 to 21 d age and feed intake was recorded. Pre-caecal protein digestibility (pcPd) was determined using TiO2 as an indigestible marker. Colourimetrically CpHe RSM was substantially darker than ScCO2 counterparts. The influence of oil recovery method (ORM) was also evident in DM, EE, ash free neutral detergent fibre (aNDFom), neutral detergent insoluble crude protein (NDICP) and glucosinolate content (GLS). The content of DM, EE and GLS was higher in ScCO2 RSM whereas aNDFom and NDICP levels were greater in CpHe RSM. Protein solubility in KOH was greater in ScCO2 RSM whilst levels of NDICP were lower. Collectively these results suggest that less heat damage was incurred to the RSM during ScCO2 extraction. There was no significant main effect of cultivar nor were any significant interactions observed between treatment factors. Rapeseed meal ScCO2 produced greater metabolisable energy, pcPd, nitrogen retention and energy metabolisability (p < 0.05). Protease supplementation increased pcPd (p < 0.05) irrespective of ORM and cultivar. The key implications of these findings are that by adopting oil recovery methods that minimise the exposure of RSM to thermal treatments and by adding a compatible protease there is scope to increase the nutritional value of RSM for broilers and increase its utilisation in modern poultry production.
Antiproliferative Effect of Gaillardin from Inula oculus-christi in Human Leukemic Cells

Abstract Gaillardin (GLN) is a sesquiterpene lactone isolated from the chloroform extract of Inula oculus-christi L. This natural compound has shown cytotoxicity in various cancerous cell line. However, its effect on leukemic cells is ambiguous. Due to the neurotoxicity of vincristine (VCR) in acute lymphoblastic leukemia (ALL), we aimed to examine the cytotoxic effects of GLN alone and in combination with vincristine on induction of apoptosis, and cell cycle progression in ALL cell lines (NALM-6 and MOLT-4). Our results displayed that GLN could induce cytotoxic effects in MOLT-4 and NALM-6 with IC50 values of 7.3 and 6.1 μM, respectively. In this study, we demonstrated that GLN induces cytotoxicity through G0/G1 phase arrest followed by apoptosis in a dose-dependent manner. Fortunately, this natural compound did not show significant cytotoxic effects on normal cells. This study demonstrated that GLN was capable to extend chemotherapeutic sensitivity in ALL cells by reducing VCR concentration without constraining its effectiveness. Therefore, it might act as a promising anticancer agent for the treatment of leukemia.
Delivery of antisense oligonucleotide using polyethylenimine-based lipid nanoparticle modified with cell penetrating peptide

Abstract Efficient and stable delivery system of antisense oligonucleotide (ASO) is important and urgently needed. Here, an ASO delivery system, Lp-PPRP, which contains a cationic polymer based on PEI (branched, 25 kDa), named PEI-PC and a palmitic acid modified R8 (R8-PA) was prepared to deliver a kind of ASO, LOR-2501. The characteristics of the nanoparticles and the cellular uptake of LOR-2501 in HeLa cells and A549 cells were studied. Lp-PPRP showed suitable particle size and zeta potential to combine with LOR-2501; the particle size and zeta potential of Lp-PPRP/LOR were 276.87 ± 5.63 nm and 18.03 ± 0.25 mV. In vitro experiments suggested that Lp-PPRP had lower cytotoxic and higher transfection efficiency for delivering LOR-2501 compared with PEI. The addition of PEI-PC and R8-PA contributed to enhance the transfection efficiency of the nanoparticles. In HeLa cells and A549 cells, Lp-PPRP could transport LOR-2501 and down-regulate the level of R1 protein efficiently, and the R1 down regulations were 64.56% and 66.34%, respectively. Results suggested potential utility of Lp-PPRP in the development of ASO in tumor therapy.
Lateral orbitofrontal gray matter abnormalities in subjects with problematic smartphone use

Background and aims Smartphone use is becoming commonplace and exerting adequate control over smartphone use has become an important mental health issue. Little is known about the neurobiology underlying problematic smartphone use. We hypothesized that structural abnormalities in the fronto-cingulate brain region could be implicated in problematic smartphone use, similar to that has been reported for Internet gaming disorder and Internet addiction. This study investigated fronto-cingulate gray matter abnormalities in problematic smartphone users, particularly those who spend time on social networking platforms. Methods The study included 39 problematic smartphone users with excessive use of social networking platforms via smartphone and 49 normal control male and female smartphone users. We conducted voxel-based morphometric analysis with diffeomorphic anatomical registration using an exponentiated Lie algebra algorithm. Region of interest analysis was performed on the fronto-cingulate region to identify whether gray matter volume (GMV) differed between the two groups. Results Problematic smartphone users had significantly smaller GMV in the right lateral orbitofrontal cortex (OFC) than healthy controls, and there were significant negative correlations between GMV in the right lateral OFC and the Smartphone Addiction Proneness Scale (SAPS) score, including the SAPS tolerance subscale. Conclusions These results suggest that lateral orbitofrontal gray matter abnormalities are implicated in problematic smartphone use, especially in social networking platform overuse. Small GMV in the lateral OFC was correlated with an increasing tendency to be immersed in smartphone use. Our results suggest that orbitofrontal gray matter abnormalities affect regulatory control over previously reinforced behaviors and may underlie problematic smartphone use.
Quantifying the impact of small molecule ligands on G-quadruplex stability against Bloom helicase

Abstract G-quadruplex (GQ) stabilizing small molecule (SM) ligands have been used to stabilize human telomeric GQ (hGQ) to inhibit telomerase activity, or non-telomeric GQs to manipulate gene expression at transcription or translation level. GQs are known to inhibit DNA replication unless destabilized by helicases, such as Bloom helicase (BLM). Even though the impact of SM ligands on thermal stability of GQs is commonly used to characterize their efficacy, how these ligands influence helicase-mediated GQ unfolding is not well understood. Three prominent SM ligands (an oxazole telomestatin derivative, pyridostatin, and PhenDC3), which thermally stabilize hGQ at different levels, were utilized in this study. How these ligands influence BLM-mediated hGQ unfolding was investigated using two independent single-molecule approaches. While the frequency of dynamic hGQ unfolding events was used as the metric in the first approach, the second approach was based on quantifying the cumulative unfolding activity as a function of time. All three SM ligands inhibited BLM activity at similar levels, 2–3 fold, in both approaches. Our observations suggest that the impact of SM ligands on GQ thermal stability is not an ideal predictor for their inhibition of helicase-mediated unfolding, which is physiologically more relevant.
Resilience and quality of life (QoL) of head and neck cancer and brain tumour survivors in Pakistan: an analytical cross-sectional study protocol

Background Cancer is a devastating disease and has detrimental effects on the quality of life (QoL) of cancer survivors and interferes with their treatment compliance. The aim of the study is to assess resilience and QoL among cancer survivors and to evaluate the important factors affecting their resilience and QoL, with respect to the Pakistani cultural context. Method and analysis A cross-sectional study will be conducted at a tertiary care hospital in Karachi, Pakistan. A minimum sample size of 250 head and neck cancers and 250 brain tumour survivors with 10% inflation for non-response rate will be required. The SD of QoL and resilience will range from 16.5 to 40.8 for head and neck cancer, and 12.7 to 34.1 for brain tumour, at 5% level of significance, with 2.5 precision. QoL will be assessed by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-H&N35 and EORTC QLQ-BN20 and resilience will be evaluated by Wagnild and Young’s 14-item scale. Mean±SD will be reported for resilience and QoL scores. Unadjusted and adjusted β-coefficients, with 95% CI, will be reported by using multiple linear regression analysis. Correlation analysis will also be performed using Pearson or Spearman rank correlation coefficients. A p value of <0.05 will be considered significant. Ethics and dissemination Ethical approval has been obtained from the Aga Khan University Pakistan’s Ethical Review Committee. Written informed consent will be taken from the participants by trained research assistants. A trained psychologist will provide on-spot counselling to the participants and those identified with severe depression will be referred to a psychiatrist. The study materials will be kept under lock and key and the electronic data base will be password protected and will only be accessed by the research team. The study findings will be disseminated through publications conferences and workshops and research briefs. Trial registration number Clinicaltrials.gov registry (NCT03466762).
Butyrate‐producing gut bacteria and viral infections in kidney transplant recipients: A pilot study

The gut microbiome is being associated increasingly with development of infections besides Clostridium difficile infection. A recent study found an association between butyrate‐producing gut (BPG) bacteria and less frequent development of lower respiratory viral infections in allogeneic hematopoietic stem cell transplant recipients (Haak et al, Blood 131(26): 2978, 2018). In this investigation, we examine the relationship between the abundance of BPG bacteria and the development of viral infections in a cohort of kidney transplant recipients.
Passive rewilding may (also) restore phylogenetically rich and functionally resilient forest plant communities.

Passive rewilding is increasingly seen as a promising tool to counterbalance biodiversity losses and recover native forest ecosystems. One key question, crucial to understanding assembly processes and conservation issues underlying land-use change, is the extent to which functional and phylogenetic diversity may recover in spontaneous recent woodlands. Here, we compared understorey plant communities of recent woodlands (which result from afforestation on agricultural lands during the 20th century) with those of ancient forests (uninterrupted for several centuries) in a hotspot of farmland abandonment in western Europe. We combined taxonomic, functional, and phylogenetic diversity metrics to detect potential differences in community composition, structure (richness, divergence), conservation importance (functional originality and specialisation, evolutionary distinctiveness) and resilience (functional redundancy, response diversity). The recent and ancient forests harbored clearly distinct compositions, especially regarding the taxonomic and phylogenetic facets. Recent woodlands had higher taxonomic functional and phylogenetic richness and a higher evolutionary distinctiveness, whereas functional divergence and phylogenetic divergence were higher in ancient forests. On another hand, we did not find any significant differences in functional specialisation, originality, redundancy, or response diversity between recent and ancient forests. Our study constitutes one of the first empirical pieces of evidence that recent woodlands may spontaneously regain plant communities phylogenetically rich and functionally resilient, at least as much as those of ancient relict forests. As passive rewilding is the cheapest restoration method, we suggest that it should be a very useful tool to restore and conserve native forest biodiversity and functions, especially when forest areas are restricted and fragmented.
MiR-16a regulates milk fat metabolism by targeting large tumor suppressor kinase 1 (LATS1) in bovine mammary epithelial cells.

Milk contains a number of beneficial fatty acids including short and medium chain, and unsaturated conjugated and non-conjugated fatty acids. In this study, microRNA sequencing of mammary tissue collected in early-, peak-, mid- and late-lactation periods was performed to determine the miRNA expression profiles. miR-16a was one of the differentially-expressed miRNA and was selected for in-depth functional studies pertaining to fatty acid metabolism. The mimic of miR-16a impaired fat metabolism (triacylglycerol and cholesterol) while knock down of miR-16a promoted fat metabolism in vitro in bovine mammary epithelial cells (BMECs). In addition, in vitro work with BMECs also revealed that miR-16a had a negative effect on the cellular concentration of cis 9-C18:1, total C18:1, C20:1 and C22:1 and long-chain polyunsaturated fatty acids. Therefore, these data suggesting a negative effect on fatty acid metabolism extend the discovery of the key role of miR-16a in mediating adipocyte differentiation. Through a combination of bioinformatics analysis, target gene 3 'UTR luciferase reporter assays and Western blotting, we identified large tumor suppressor kinase 1 (LATS1) as a target of miR-16a. Transfection of siRNA-LATS1 into BMECs led to increases in triacylglycerol, cholesterol and cellular fatty acid concentrations suggesting a positive role of LATS1 in mammary cell fatty acid metabolism. In summary, data suggest that miR-16a regulates biological processes associated with intracellular triacylglycerol, cholesterol, and unsaturated fatty acid synthesis through LATS1. These data provide a theoretical and experimental framework for further clarifying the regulation of lipid metabolism in mammary cells of dairy cows.
Structural or dispositional? An experimental investigation of the experience of winning in social casino games (and impulsivity) on subsequent gambling behaviors

Background and aims In the present research, we experimentally investigated whether the experience of winning (i.e., inflated payout rates) in a social casino game influenced social casino gamers’ subsequent decision to gamble for money. Furthermore, we assessed whether facets of dispositional impulsivity – negative and positive urgency in particular – also influenced participants’ subsequent gambling. Methods Social casino gamers who were also current gamblers (N = 318) were asked to play a social casino game to assess their perceptions of the game in exchange for $3. Unbeknownst to them, players were randomly assigned to one of three experimental conditions: winning (n = 110), break-even (n = 103), or losing (n = 105). After playing, participants were offered a chance to gamble their $3 renumeration in an online roulette game. Results A total of 280 participants (88.1%) elected to gamble, but no between-condition variation in the decision to gamble emerged. Furthermore, there were no differences in gambling on the online roulette between condition. However, higher levels of both negative and positive urgency increased the likelihood of gambling. Finally, impulsivity did not moderate the relationship between experience of winning and decision to gamble. Conclusion The results suggest that dispositional factors, including impulsive urgency, are implicated in the choice to gamble for social casino gamers following play.
Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes

ABSTRACT Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification ‘Compulsive Sexual Behavior Disorder’ is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD – cg18222192 (MIR708)(p < 10E-05,pFDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, pFDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.