Miracle-dz/UniFAR-FTUs huggingface dataset:
The Immunity Gap Challenge: Protection against a Recent Florida Clade 2 Equine Influenza Strain

Vaccination is one of the most effective tools for limiting the impact of equine influenza (EI). The humoral immunity established following a primary vaccination course can decrease significantly between the second (V2) and third immunisations (V3), leaving some horses insufficiently protected for several weeks. This so-called “immunity gap” poses a challenge to all EI vaccines. During this period, the EI infection of vaccinated animals may be followed by marked clinical signs and virus shedding. However, several EI vaccines have been shown to stimulate equine influenza virus (EIV)-specific cell-mediated immunity, which is likely to play a role in protection against EIV infection and/or mitigate the clinical and virological signs of EI. Reducing the interval between V2 and V3 has been shown to be counterproductive to longer-term immunity. Further research is needed to define and address the “immunity gap” in horses. This study aimed to measure the level of protection induced by a whole inactivated, ISCOMatrix adjuvanted, EI and tetanus vaccine (Equilis Prequenza-Te) when challenged during the immunity gap (i.e., immediately before the recommended boost immunisation, more than 5 months after V2) using infection with a recent heterologous Florida Clade 2 (FC2) equine influenza virus (EIV) strain. This vaccine was tested in a Welsh mountain pony model. A group of seven ponies was vaccinated twice, 4 weeks apart. The protective antibody response was measured and ponies were challenged, along with 5 unvaccinated control ponies, by experimental infection with the FC2 A/eq/Northamptonshire/1/13 EIV strain, 158 days (around 5.2 months) after V2 and their clinical signs and virus shedding were monitored. EI serology was measured by single radial haemolysis (SRH) and haemagglutination inhibition (HI). Clinical signs and virus shedding (measured by qRT-PCR and hen’s egg titration) were compared with controls. All vaccinates had detectable, low SRH antibody titres and most had detectable, low HI titres. Significant clinical and virological protection was observed in vaccinates (p < 0.05), supporting the good performance of this vaccine against a recent EIV strain. In this study, the impact of the immunity gap in ponies was limited after primary vaccination with this whole inactivated, ISCOMatrix adjuvanted EI and tetanus vaccine (Equilis Prequenza-Te) when infected several months after V2 with a recent FC2 strain, which is representative of EIV circulating in the EU.
Interorganelle Communication: Peroxisomal MALATE DEHYDROGENASE2 Connects Lipid Catabolism to Photosynthesis through Redox Coupling in Chlamydomonas[OPEN]

Knockout of the peroxisomal MALATE DEHYDROGENASE2 drastically alters photosynthesis and the metabolism of fatty acids and starch upon nitrogen deprivation and high light exposure in the green microalga Chlamydomonas reinhardtii. Plants and algae must tightly coordinate photosynthetic electron transport and metabolic activities given that they often face fluctuating light and nutrient conditions. The exchange of metabolites and signaling molecules between organelles is thought to be central to this regulation but evidence for this is still fragmentary. Here, we show that knocking out the peroxisome-located MALATE DEHYDROGENASE2 (MDH2) of Chlamydomonas reinhardtii results in dramatic alterations not only in peroxisomal fatty acid breakdown but also in chloroplast starch metabolism and photosynthesis. mdh2 mutants accumulated 50% more storage lipid and 2-fold more starch than the wild type during nitrogen deprivation. In parallel, mdh2 showed increased photosystem II yield and photosynthetic CO2 fixation. Metabolite analyses revealed a >60% reduction in malate, together with increased levels of NADPH and H2O2 in mdh2. Similar phenotypes were found upon high light exposure. Furthermore, based on the lack of starch accumulation in a knockout mutant of the H2O2-producing peroxisomal ACYL-COA OXIDASE2 and on the effects of H2O2 supplementation, we propose that peroxisome-derived H2O2 acts as a regulator of chloroplast metabolism. We conclude that peroxisomal MDH2 helps photoautotrophs cope with nitrogen scarcity and high light by transmitting the redox state of the peroxisome to the chloroplast by means of malate shuttle- and H2O2-based redox signaling.
Exploiting the Thiobarbituric Acid Scaffold for Antibacterial Activity

Thiobarbituric acid (TBA) has been considered a privileged structure for developing antimicrobial agents. Diversity was obtained at positions N and at C5 through acylation, Schiff base formation, Knoevenagel condensation, and thioamide and enamine formation. The present work describes the synthesis of small libraries based on the TBA moiety and above‐mentioned reactions. Preliminary antimicrobial activity screening of the prepared compounds against selected bacteria (both Gram‐positive and ‐negative) showed the best results for the Boc‐Phe‐TBA derivative. These results could be useful for designing and building libraries based on other amino acids with distinct protecting groups.
A Current Overview of the Biological and Cellular Effects of Nanosilver

Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges from 1 to 100 nanometers in diameter. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism on which it is tested, are all large determining factors on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signalling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress—as well as the effects of nanosilver on the responses to such stresses—are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum (ER) function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis—as well as other pathway alterations—are examined in this review.
SLEep among diabetic patients and their GlycaEmic control (SLEDGE): A pilot observational study

Recent cohort studies have proven the association between sleep deprivation and adverse glycemic control (GC). The aim of this study was to assess the prevalence of excessive daytime sleepiness (EDS), a subjective measure of sleep deprivation, among type 2 diabetic mellitus (T2DM) patients and its association with GC.
Investigation of mother-to-child transmission of HIV in pregnancy and among HIV-exposed infants accessing care at a PMTCT clinic in southwest Nigeria

ABSTRACT Background: Over 90% of infant acquired immunodeficiency syndrome (AIDS) cases have been through mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Consequent to this, prevention of mother-to-child transmission (PMTCT) programs have instituted as dual purposes for prevention of HIV transmission from mother to child and enrollment of infected pregnant women and their families into antiretroviral treatment (ART) program. However, there are still some breakthrough infections and challenges. Therefore, this study was designed to assess risk of HIV transmission among HIV-exposed infants on follow-up at a PMTCT clinic in an antiretroviral (ARV) referral health facility in southwest Nigeria. Methods: A cohort of 60 purposively recruited consenting pregnant women referred to PMTCT HIV clinic in Ibadan, southwest Nigeria were enrolled and followed up for 1 year (2015–2016). A well-structured epidemiological questionnaire was used to capture all relevant information. Data were then analyzed by SPSS version 21 (St. Louis, MO, USA), while bivariate and multivariate analyses were used to identify associations. Results: A total of 44 mothers and their infants were available for the analysis with an attrition rate of 26.7%. The mean age of mothers at enrollment to follow-up was 32.9 years (SD = 4.2 years). Two (4.5%, 95% CI: 7.2–12.3%) of the infants were HIV positive by DNA PCR test. There was no linear relationship between age of the mothers with CD4 count or viral load both before and after delivery but there was a significant positive relationship with year on ARV (r = 0.318, 95% CI: 0.024–0.562). Infants of rural dwelling mothers were at 3.39 (adjusted odds ratio (AOR) = 3.39, 95% CI: 1.32, 2.29) times higher risk of vertical HIV transmission compared to those of urban dwelling mothers. Infants delivered at home had 2.61(AOR = 2.61, 95% CI: 1.59, 7.91) times higher risk of MTCT compared to those delivered at health institution. Mixed feeding was also another important predictor in which the risk of MTCT was about two (AOR = 2.21, 95% CI: 0.68, 9.97) times higher compared to exclusive breastfeeding. Conclusions: There was a high risk of MTCT of HIV among exposed infants on follow-up at the PMTCT clinic of Adeoyo Maternity Teaching referral hospital. Our findings will assist health policy makers in providing important information capable of enhancing assurance HIV control in such population and in raising the standard of PMTCT program in Nigeria.
Golimumab induction and maintenance for moderate to severe ulcerative colitis: results from GO-COLITIS (Golimumab: a Phase 4, UK, open label, single arm study on its utilization and impact in ulcerative Colitis)

Objective GO-COLITIS aimed to measure the effectiveness of subcutaneous golimumab in tumour necrosis factor-α antagonist–naive patients with moderate to severe ulcerative colitis (UC) despite conventional treatment. Design GO-COLITIS was an open label, single arm, phase 4 study with a pragmatic design which reflected UK clinical practice. Adult patients were eligible if diagnosed with UC ≥3 months, partial Mayo score (PMS) 4–9. Patients received subcutaneous golimumab induction (200 mg initially and 100 mg at week 2) followed at week 6 by 50 mg or 100 mg (depending on weight) every 4 weeks until week 54 with a 12-week follow-up. Efficacy was measured by PMS at baseline, week 6, 30, 54 and 66. Health-related quality of life (HRQoL; Inflammatory Bowel Disease Questionnaire (IBDQ) and EuroQol Group 5 Dimensions Health Questionnaire (EQ-5D)) was assessed at baseline, week 6 and week 54. All safety adverse events (AEs) were recorded. Results 207 patients were enrolled and 205 received golimumab (full analysis set (FAS)205). At week 6, 68.8% (95% CI 62.0% to 75.1%) and 38.5% (95% CI 31.8% to 45.6%) of patients were in response and remission, respectively, using PMS. At the end of the induction phase, 140/141 patients in clinical response continued into the maintenance phase (Maintenance FAS). Sustained clinical response through week 54 was achieved in 51/205 (24.9%) of the FAS205 population and 51/140 (36.4%) of the Maintenance FAS population. Statistically significant improvements from baseline to week 6 were observed for the IBDQ total score and for each IBDQ domain score (bowel symptoms, emotional function, systemic symptoms and social function), as well as the EQ-5D index score and associated visual analogue scale score (p<0.0001). Improvement of HRQoL was sustained through week 54. Serious AEs leading to treatment discontinuation occurred in 8.8% of patients. Conclusion In this study measuring patient-reported outcomes in patients with moderate to severe UC, golimumab induced and maintained response as measured by PMS and significantly improved quality of life measures. Trial registration number NCT02092285; 2013-004583-56.
GABA immunostaining in the central complex of dicondylian insects

The central complex is a group of midline‐crossing neuropils in the insect brain involved in head direction coding, sky compass navigation, and spatial visual memory. To compare the neuroarchitecture and neurochemistry of the central complex in insects that differ in locomotion, ways of orientation, time of activity (diurnal, nocturnal), and evolutionary history, we studied the distribution of γ‐aminobutyric acid (GABA) immunostaining in the central complex of 29 species, ranging from Zygentoma to Diptera. In all species, the lower division of the central body was densely innervated by GABA‐immunoreactive tangential neurons. These neurons had additional arborizations in the bulb, a distinct region of synaptic complexes in the lateral complex, and somata in a cell cluster mediodorsally to the antennal lobe. Differences in the appearance of GABA immunostaining in the lower division of the central body corresponded to differences in neuropil architecture, such as transformation of the lower division into a toroid in certain Diptera and Heteroptera. In nearly all species two additional systems of tangential neuron of the upper division of the central body were GABA‐immunoreactive. One of these systems diffusely invaded a superior layer, while the second system showed fan‐like projections in an inferior layer. Sparse immunostaining in the protocerebral bridge was detected in cockroaches, a cricket, and two hemipteran species. The data show that three systems of GABA‐immunoreactive tangential neurons of the central body are highly conserved and suggest that the layered organization of the upper division of the central body is, likewise, largely maintained from basal to advanced species.
Molecular bloodmeal analyses reveal that Trypanosoma cruzi‐infected, native triatomine bugs often feed on humans in houses in central Brazil

The identification of bloodmeal sources in triatomine bugs (Hemiptera: Reduviidae) is important in understanding vector–host associations and in measuring the risk for Chagas' disease transmission. The bloodmeal sources of triatomines infected with Trypanosoma cruzi (Trypanosomatida: Trypanosomatidae) caught in houses in central Brazil (Goiás State and the Federal District) were investigated during 2012–2014. Mitochondrial cytochrome b amplicons were used to identify bloodmeals through high‐resolution melting and DNA sequencing. Most bugs were found to have fed on either humans (45.7%) or chickens (43.1%). Human blood was detected in Triatoma sordida (n = 22/50 bugs), Triatoma pseudomaculata (n = 7/11 bugs), Panstrongylus megistus (n = 10/24 bugs), Panstrongylus geniculatus (n = 1/3 bugs) and Rhodnius neglectus (n = 18/28 bugs) (all: Hemiptera: Reduviidae). Sequencing identified Necromys (Rodentia: Cricetidae) mouse blood in P. geniculatus and Tropidurus (Squamata: Tropiduridae) lizard blood in T. pseudomaculata and T. sordida. These findings reveal new vector–host associations. The present results suggest frequent contact between humans and T. cruzi‐infected triatomines in central Brazil and indicate that Chagas' disease transmission by native vectors is an ongoing threat.
Expression of the Vaccinia Virus Antiapoptotic F1 Protein Is Blocked by Protein Kinase R in the Absence of the Viral E3 Protein

Previous studies have shown that E3-deficient vaccinia virus triggers apoptosis of infected cells. Our study demonstrates that this proapoptotic phenotype stems, at least in part, from the failure of the mutant virus to produce adequate quantities of the viral F1 protein, which acts at the mitochondria to directly block apoptosis. Our data establish a regulatory link between the vaccinia virus proteins that suppress the innate response to double-stranded RNA and those that block the intrinsic apoptotic pathway. ABSTRACT Poxviruses encode many proteins with the ability to regulate cellular signaling pathways. One such protein is the vaccinia virus innate immunity modulator E3. Multiple functions have been ascribed to E3, including modulating the cellular response to double-stranded RNA, inhibiting the NF-κB and IRF3 pathways, and dampening apoptosis. Apoptosis serves as a powerful defense against damaged and unwanted cells and is an effective defense against viral infection; many viruses therefore encode proteins that prevent or delay apoptosis. Here, we present data indicating that E3 does not directly inhibit the intrinsic apoptotic pathway; instead, it suppresses apoptosis indirectly by stimulating expression of the viral F1 apoptotic inhibitor. Our data demonstrate that E3 promotes F1 expression by blocking activation of the double-stranded RNA-activated protein kinase R (PKR). F1 mRNA is present in cells infected with E3-null virus, but the protein product does not detectably accumulate, suggesting a block at the translational level. We also show that two 3′ coterminal transcripts span the F1 open reading frame (ORF), a situation previously described for the vaccinia virus mRNAs encoding the J3 and J4 proteins. One of these is a conventional monocistronic transcript of the F1L gene, while the other arises by read-through transcription from the upstream F2L gene and does not give rise to appreciable levels of F1 protein. IMPORTANCE Previous studies have shown that E3-deficient vaccinia virus triggers apoptosis of infected cells. Our study demonstrates that this proapoptotic phenotype stems, at least in part, from the failure of the mutant virus to produce adequate quantities of the viral F1 protein, which acts at the mitochondria to directly block apoptosis. Our data establish a regulatory link between the vaccinia virus proteins that suppress the innate response to double-stranded RNA and those that block the intrinsic apoptotic pathway.
ABO blood type and risk of hepatocellular carcinoma: a meta-analysis

ABSTRACT Background: ABO blood type is an invariant factor. There is a link between ABO blood type and some malignancies, such as gastric, pancreatic, and skin cancer. The role of ABO blood type in the pathogenesis of hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to explore the relationship between ABO blood type and risk of HCC. Methods: Literature search was conducted among the PubMed, EMBASE, and Cochrane Library databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: Seven papers were included. They included 92,847 healthy subjects, 5,463 patients with hepatitis, 294 cirrhotic patients, and 3,322 HCC patients. The proportion of blood type O was significantly lower in HCC patients than healthy subjects (OR = 0.76, 95%CI = 0.66–0.87, P < 0.0001) without any significant heterogeneity (P = 0.55, I2 = 0%). The proportions of blood types A, B, and AB were not significantly different between HCC patients and healthy subjects. The proportion of ABO blood type was not significantly different between patients with HCC and those with hepatitis or cirrhosis. Conclusion: HCC patients might have a lower proportion of blood type O than healthy subjects. Among the patients with chronic liver diseases, ABO blood type might not be associated with the risk of HCC.
Topological analyses of functional connectomics: A crucial role of global signal removal, brain parcellation, and null models

Recently, functional connectome studies based on resting‐state functional magnetic resonance imaging (R‐fMRI) and graph theory have greatly advanced our understanding of the topological principles of healthy and diseased brains. However, how different strategies for R‐fMRI data preprocessing and for connectome analyses jointly affect topological characterization and contrastive research of brain networks remains to be elucidated. Here, we used two R‐fMRI data sets, a healthy young adult data set and an Alzheimer's disease (AD) patient data set, and up to 42 analysis strategies to comprehensively investigate the joint influence of three key factors (global signal regression, regional parcellation schemes, and null network models) on the topological analysis and contrastive research of whole‐brain functional networks. At the global level, we first found that these three factors affected not only the quantitative values but also the individual variability profile in small‐world related metrics and modularity, wherein global signal regression exhibited the predominant influence. Moreover, strategies without global signal regression and with topological randomization null model enhanced the sensitivity of the detection of differences between AD and control groups in small‐worldness and modularity. At the nodal level, strategies of global signal regression dominantly influenced the spatial distribution of both hubs and between‐group differences in terms of nodal degree centrality. Together, we highlight the remarkable joint influence of global signal regression, regional parcellation schemes and null network models on functional connectome analyses in both health and diseases, which may provide guidance for the choice of analysis strategies in future functional network studies.
A Reverse Genetics System for Zika Virus Based on a Simple Molecular Cloning Strategy

The Zika virus (ZIKV) has recently attracted major research interest as infection was unexpectedly associated with neurological manifestations in developing foetuses and with Guillain-Barré syndrome in infected adults. Understanding the underlying molecular mechanisms requires reverse genetic systems, which allow manipulation of infectious cDNA clones at will. In the case of flaviviruses, to which ZIKV belongs, several reports have indicated that the construction of full-length cDNA clones is difficult due to toxicity during plasmid amplification in Escherichia coli. Toxicity of flaviviral cDNAs has been linked to the activity of cryptic prokaryotic promoters within the region encoding the structural proteins leading to spurious transcription and expression of toxic viral proteins. Here, we employ an approach based on in silico prediction and mutational silencing of putative promoters to generate full-length cDNA clones of the historical MR766 strain and the contemporary French Polynesian strain H/PF/2013 of ZIKV. While for both strains construction of full-length cDNA clones has failed in the past, we show that our approach generates cDNA clones that are stable on single bacterial plasmids and give rise to infectious viruses with properties similar to those generated by other more complex assembly strategies. Further, we generate luciferase and fluorescent reporter viruses as well as sub-genomic replicons that are fully functional and suitable for various research and drug screening applications. Taken together, this study confirms that in silico prediction and silencing of cryptic prokaryotic promoters is an efficient strategy to generate full-length cDNA clones of flaviviruses and reports novel tools that will facilitate research on ZIKV biology and development of antiviral strategies.