Multiband optical variability of 3C 279 on diverse time-scales

We have monitored the flat spectrum radio quasar, 3C 279, in the optical B, V, R, and I passbands from 2018 February to 2018 July for 24 nights, with a total of 716 frames, to study flux, colour, and spectral variability on diverse time-scales. 3C 279 was observed using seven different telescopes: two in India, two in Argentina, two in Bulgaria, and one in Turkey to understand the nature of the source in optical regime. The source was found to be active during the whole monitoring period and displayed significant flux variations in B, V, R, and I passbands. Variability amplitudes on intraday basis varied from 5.20 to 17.9 per cent. A close inspection of variability patterns during our observation cycle reveals simultaneity among optical emissions from all passbands. During the complete monitoring period, progressive increase in the amplitude of variability with frequency was detected for our target. The amplitudes of variability in B, V, R, and I passbands have been estimated to be 177 per cent, 172 per cent, 171 per cent, and 158 per cent, respectively. Using the structure function technique, we found intraday time-scales ranging from ∼23 min to about 115 min. We also studied colour–magnitude relationship and found indications of mild bluer-when-brighter trend on shorter time-scales. Spectral indices ranged from 2.3 to 3.0 with no clear trend on long-term basis. We have also generated spectral energy distributions for 3C 279 in optical B, V, R, and I passbands for 17 nights. Finally, possible emission mechanisms causing variability in blazars are discussed briefly.Fil: Agarwal, Aditi. Indian Institute of Astrophysics; IndiaFil: Cellone, Sergio Aldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; ArgentinaFil: Andruchow, Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Mammana, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; ArgentinaFil: Singh, Mridweeka. Aryabhatta Research Institute of Observational Sciences; IndiaFil: Anupama, G. C.. Indian Institute of Astrophysics; IndiaFil: Mihov, B.. Bulgarian Academy of Sciences; BulgariaFil: Raj, Ashish. Indian Institute of Astrophysics; IndiaFil: Slavcheva Mihova, L.. Bulgarian Academy of Sciences; BulgariaFil: Özdönmez, Aykut. Tübİtak National Observatory; TurquíaFil: Ege, Ergün. Istanbul University; Turquí

U6 snRNA m6A modification is required for accurate and efficient splicing of C. elegans and human pre-mRNAs

pre-mRNA splicing is a critical feature of eukaryotic gene expression. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs and associated proteins. Spliceosomal snRNAs carry multiple RNA modifications with the potential to affect different stages of pre-mRNA splicing. Here, we show that the conserved U6 snRNA m6A methyltransferase METT-10 is required for accurate and efficient cis- and trans-splicing of C. elegans pre-mRNAs. The absence of METT-10 in C. elegans and METTL16 in humans primarily leads to alternative splicing at 5′ splice sites with an adenosine at +4 position. In addition, METT-10 is required for splicing of weak 3′ cis- and trans-splice sites. We identified a significant overlap between METT-10 and the conserved splicing factor SNRNP27K in regulating 5′ splice sites with +4A. Finally, we show that editing endogenous 5′ splice site +4A positions to +4U restores splicing to wild-type positions in a mett-10 mutant background, supporting a direct role for U6 snRNA m6A modification in 5′ splice site recognition. We conclude that the U6 snRNA m6A modification is important for accurate and efficient pre-mRNA splicing.</p

U6 snRNA m6A modification is required for accurate and efficient splicing of C. elegans and human pre-mRNAs

pre-mRNA splicing is a critical feature of eukaryotic gene expression. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs and associated proteins. Spliceosomal snRNAs carry multiple RNA modifications with the potential to affect different stages of pre-mRNA splicing. Here, we show that the conserved U6 snRNA m6A methyltransferase METT-10 is required for accurate and efficient cis- and trans-splicing of C. elegans pre-mRNAs. The absence of METT-10 in C. elegans and METTL16 in humans primarily leads to alternative splicing at 5′ splice sites with an adenosine at +4 position. In addition, METT-10 is required for splicing of weak 3′ cis- and trans-splice sites. We identified a significant overlap between METT-10 and the conserved splicing factor SNRNP27K in regulating 5′ splice sites with +4A. Finally, we show that editing endogenous 5′ splice site +4A positions to +4U restores splicing to wild-type positions in a mett-10 mutant background, supporting a direct role for U6 snRNA m6A modification in 5′ splice site recognition. We conclude that the U6 snRNA m6A modification is important for accurate and efficient pre-mRNA splicing.</p

The E6 Oncoprotein from HPV16 Enhances the Canonical Wnt/?-Catenin Pathway in Skin Epidermis In Vivo

The contribution of the Wnt signaling pathway to human papilloma virus (HPV)-induced carcinogenesis is poorly understood. In high-grade dysplastic lesions that are caused by high-risk HPVs (HR-HPV), ?-catenin is often located in the cell nucleus, which suggests that Wnt pathway may be involved in the development of HPV-related carcinomas. Most of the oncogenic potential of HR-HPVs resides on the PDZ-binding domain of E6 protein. We hypothesized that the PDZ-binding domain of the HPV16-E6 oncoprotein induces the nuclear accumulation of ?-catenin due to its capacity to degrade PDZ-containing cellular targets. To test this hypothesis, we evaluated the staining pattern of ?-catenin in the skin epidermis of transgenic mice expressing the full-length E6 oncoprotein (K14E6 mice) and measured LacZ gene expression in K14E6 mice that were crossed with a strain expressing LacZ that was knocked into the Axin2 locus (Axin2+/LacZ mice). Here, we show that the E6 oncoprotein enhances the nuclear accumulation of ?-catenin, the accumulation of cellular ?-catenin–responsive genes, and the expression of LacZ. None of these effects were observed when a truncated E6 oncoprotein that lacks the PDZ-binding domain was expressed alone (K14E6?PDZ mice) or in combination with Axin2+/LacZ. Conversely, cotransfection with either E6 or E6?PDZ similarly enhanced canonical Wnt signaling in short-term in vitro assays that used a luciferase Wnt/?-catenin/TCF-dependent promoter. We propose that the activation of canonical Wnt signaling could be induced by the HPV16-E6 oncoprotein; however, the participation of the E6 PDZ-binding domain seems to be important in in vivo models only. Mol Cancer Res; 10(2); 250–8. ©2011 AACR

Standard survey methods for estimating colony losses and explanatory risk factors in Apis mellifera

This chapter addresses survey methodology and questionnaire design for the collection of data pertaining to estimation of honey bee colony loss rates and identification of risk factors for colony loss. Sources of error in surveys are described. Advantages and disadvantages of different random and non-random sampling strategies and different modes of data collection are presented to enable the researcher to make an informed choice. We discuss survey and questionnaire methodology in some detail, for the purpose of raising awareness of issues to be considered during the survey design stage in order to minimise error and bias in the results. Aspects of survey design are illustrated using surveys in Scotland. Part of a standardized questionnaire is given as a further example, developed by the COLOSS working group for Monitoring and Diagnosis. Approaches to data analysis are described, focussing on estimation of loss rates. Dutch monitoring data from 2012 were used for an example of a statistical analysis with the public domain R software. We demonstrate the estimation of the overall proportion of losses and corresponding confidence interval using a quasi-binomial model to account for extra-binomial variation. We also illustrate generalized linear model fitting when incorporating a single risk factor, and derivation of relevant confidence intervals

Case report: First case of neuromelioidosis in Europe: CNS infection caused by Burkholderia pseudomallei

Neuromelioidosis is a rare CNS infection caused by Burkholderia pseudomallei and is characterized by high morbidity and mortality. Our report presents the diagnostic and therapeutic approach of the first case of neuromelioidosis confirmed in Europe. A 47-year-old man with a medical history of recurrent otitis with otorrhea and fever after tympanoplasty and radical cavity revision operation on the left ear was admitted with headache, decreased level of consciousness, dysarthria, left-sided hemiparesis, and urinary incontinence. After extensive investigations including MRI, microbiological, serological, and CSF analyses, and, ultimately, brain biopsy, a diagnosis of neuromelioidosis was established. Despite antibiotic treatment, the patient showed no clinical improvement and remained in a severely compromised neurological state under mandatory mechanical ventilation. Neuromelioidosis can pose a diagnostic challenge requiring an extensive diagnostic evaluation because of its uncommon clinical and radiological presentations

Case Report: Sublingual Microcirculatory Alterations in a Covid-19 Patient With Subcutaneous Emphysema, Venous Thrombosis, and Pneumomediastinum

The Corona virus disease 2019 (Covid-19) has brought a wide range of challenges in intensive care medicine. Understanding of the pathophysiology of Covid-19 relies on interpreting of its impact on the vascular, particularly microcirculatory system. Herein we report on the first use of the latest generation hand-held vital microscope to evaluate the sublingual microcirculation in a Covid-19 patient with subcutaneous emphysema, venous thrombosis and pneumomediastinum. Remarkably, microcirculatory parameters of the patient were increased during the exacerbation period, which is not a usual finding in critically ill patients mostly presenting with a loss of hemodynamic coherence. In contrast, recovery from the disease led to a subsequent amelioration of these parameters. This report clearly shows the importance of microcirculatory monitoring for evaluating the course and the adequacy of therapy in Covid-19 patients

Biallelic variants in ADAMTS15 cause a novel form of distal arthrogryposis

Purpose We aimed to identify the underlying genetic cause for a novel form of distal arthrogryposis. Methods Rare variant family-based genomics, exome sequencing, and disease-specific panel sequencing were used to detect ADAMTS15 variants in affected individuals. Adamts15 expression was analyzed at the single-cell level during murine embryogenesis. Expression patterns were characterized using in situ hybridization and RNAscope. Results We identified homozygous rare variant alleles of ADAMTS15 in 5 affected individuals from 4 unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. Radiographic investigations showed physiological interphalangeal joint morphology. Additional features included knee, Achilles tendon, and toe contractures, spinal stiffness, scoliosis, and orthodontic abnormalities. Analysis of mouse whole-embryo single-cell sequencing data revealed a tightly regulated Adamts15 expression in the limb mesenchyme between embryonic stages E11.5 and E15.0. A perimuscular and peritendinous expression was evident in in situ hybridization in the developing mouse limb. In accordance, RNAscope analysis detected a significant coexpression with Osr1, but not with markers for skeletal muscle or joint formation. Conclusion In aggregate, our findings provide evidence that rare biallelic recessive trait variants in ADAMTS15 cause a novel autosomal recessive connective tissue disorder, resulting in a distal arthrogryposis syndrome

Intrauterine growth restriction and placental angiogenesis

Background: Vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (b-FGF), and endothelial nitric oxide synthase (eNOS) are factors that take part in placental angiogenesis. They are highly expressed during embryonic and fetal development, especially in the first trimester. In this study, we aimed to investigate the role of placental angiogenesis in the development of intrauterine growth restriction (IUGR) by comparing the levels of expression of VEGF-A, b-FGF, and eNOS in normal-term pregnancy and IUGR placentas.Methods: The expression of VEGF-A, b-FGF, and eNOS was studied using the avidin-biotin-peroxidase method in placental tissues diagnosed as normal (n = 55) and IUGR (n = 55). Results were evaluated in a semi-quantitative manner.Results: The expression of all the markers was significantly higher (p < 0.001) in cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, vascular smooth muscle cells, chorionic villous stromal cells, and villous vascular endothelial cells of the IUGR placentas when compared with those collected from normal-term pregnancies.Conclusion: Increased expression of VEGF-A, b-FGF, and eNOS may be the result of inadequate uteroplacental perfusion, supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR. © 2010 Barut et al; licensee BioMed Central Ltd

Co-circulation of West Nile virus and distinct insect-specific flaviviruses in Turkey

Background: Active vector surveillance provides an efficient tool for monitoring the presence or spread of emerging or re-emerging vector-borne viruses. This study was undertaken to investigate the circulation of flaviviruses. Mosquitoes were collected from 58 locations in 10 provinces across the Aegean, Thrace and Mediterranean Anatolian regions of Turkey in 2014 and 2015. Following morphological identification, mosquitoes were pooled and screened by nested and real-time PCR assays. Detected viruses were further characterised by sequencing. Positive pools were inoculated onto cell lines for virus isolation. Next generation sequencing was employed for genomic characterisation of the isolates. Results: A total of 12,711 mosquito specimens representing 15 species were screened in 594 pools. Eleven pools (2%) were reactive in the virus screening assays. Sequencing revealed West Nile virus (WNV) in one Culex pipiens (s.l.) pool from Thrace. WNV sequence corresponded to lineage one clade 1a but clustered distinctly from the Turkish prototype isolate. In 10 pools, insect-specific flaviviruses were characterised as Culex theileri flavivirus in 5 pools of Culex theileri and one pool of Cx. pipiens (s.l.), Ochlerotatus caspius flavivirus in two pools of Aedes (Ochlerotatus) caspius, Flavivirus AV-2011 in one pool of Culiseta annulata, and an undetermined flavivirus in one pool of Uranotaenia unguiculata from the Aegean and Thrace regions. DNA forms or integration of the detected insect-specific flaviviruses were not observed. A virus strain, tentatively named as “Ochlerotatus caspius flavivirus Turkey”, was isolated from an Ae. caspius pool in C6/36 cells. The viral genome comprised 10,370 nucleotides with a putative polyprotein of 3,385 amino acids that follows the canonical flavivirus polyprotein organisation. Sequence comparisons and phylogenetic analyses revealed the close relationship of this strain with Ochlerotatus caspius flavivirus from Portugal and Hanko virus from Finland. Several conserved structural and amino acid motifs were identified. Conclusions: We identified WNV and several distinct insect-specific flaviviruses during an extensive biosurveillance study of mosquitoes in various regions of Turkey in 2014 and 2015. Ongoing circulation of WNV is revealed, with an unprecedented genetic diversity. A probable replicating form of an insect flavivirus identified only in DNA form was detected