Association between mean platelet volume levels and inflammation in SLE patients presented with arthritis

Background: Systemic lupus erythematosus (SLE) may be characterized by periods of remissions and chronic or acute relapses. The complexity of clinical presentation of the SLE patients leads to incorrect evaluation of disease activity. Mean platelet volume (MPV) has been studied as a simple inflammatory marker in several diseases. There is no study in the literature about MPV levels in adult SLE patients with arthritis.Objectives: We aimed to investigate the MPV levels in the SLE population with arthritis during and between activations.Methods: The study consisted of 44 SLE patients with arthritis in activation period (Group 1), the same 44 SLE patients with arthritis in remission period (Group 2) and 44 healthy controls (Group 3). Erythrocyte sedimentation rate (ESR), creactive protein (CRP), white blood cell count, platelet count, and mean platelet volume (MPV) levels were retrospectively recorded from patient files.Results: The mean ages of the SLE subjects were 42 ± 16 years, while the mean ages of controls was 41 ± 17 years. MPV was significantly lower in Group 1(7.66±0.89fL) than in Group 2 (8.61±1.06 fL) and Group 3(8.62±1.11fL) (p<0.0001). The differences between groups reached statistical significance.Conclusions: We suggest that MPV levels decrease in patients with arthritis of SLE activation when compared to the same patients in remission and healthy controls.Key words: Systemic lupus erythematosus, Arthritis, Mean platelet volum

Case report – ancient schwannoma of the scrotum

BACKGROUND: Scrotal schwannoma is a rare neoplasm and poses a diagnostic challenge to urologists. This article describes a rare case of ancient scrotal schwannoma and reviews the current modality of investigation and treatment of this tumour. CASE REPORT: A 28 year old man presented with a 3-month history of an asymptomatic scrotal swelling. Ultrasonography and computer topography revealed an intra-scrotal and extra-testicular mass without local invasion. Surgical excision was undertaken and histology was an ancient schwannoma of the scrotum. CONCLUSION: Schwannoma is a benign encapsulating neoplasm with an overall low incidence, occurring mostly in the head and neck region and seldom in the scrotum. Histology shows two distinctive patterns, Antoni type A and B areas. Variations of schwannoma such as cellular, ancient, glandular and epithelioid are observed based on the appearances. Ancient schwannoma exhibits pleomorphism without mitosis as the result of cellular degeneration, which can lead to an erroneous diagnosis of malignancy. Imaging modalities are non-specific for schwannomas, but can define tumour size, site and extension. The mainstay treatment is complete excision, although local recurrence may occur in large and incompletely excised lesions. Malignant change is exceedingly rare

A Persistence Detector for Metabolic Network Rewiring in an Animal

Biological systems must possess mechanisms that prevent inappropriate responses to spurious environmental inputs. Caenorhabditis elegans has two breakdown pathways for the short-chain fatty acid propionate: a canonical, vitamin B12-dependent pathway and a propionate shunt that is used when vitamin B12 levels are low. The shunt pathway is kept off when there is sufficient flux through the canonical pathway, likely to avoid generating shunt-specific toxic intermediates. Here, we discovered a transcriptional regulatory circuit that activates shunt gene expression upon propionate buildup. Nuclear hormone receptor 10 (NHR-10) and NHR-68 function together as a persistence detector in a type 1, coherent feed-forward loop with an AND-logic gate to delay shunt activation upon propionate accumulation and to avoid spurious shunt activation in response to a non-sustained pulse of propionate. Together, our findings identify a persistence detector in an animal, which transcriptionally rewires propionate metabolism to maintain homeostasis

Keynote Lecture – The Interplay of Multiple Hazards and Urban Development: The context of Istanbul

Tomorrow’s Cities is the UK Research and Innovation (UKRI) Global Challenges Research Fund (GCRF) Urban Disaster Risk Hub – an interdisciplinary research hub with the aim to catalyse a transition from crisis management to multi-hazard risk-informed and inclusive planning in four cities in low-and-middle income countries. Istanbul in Turkey is one of the four cities investigated. It is one of the largest urban agglomerations in Europe where more than 15 million people reside in more than 1 million buildings. Considering that the population was 4.75 million in 1980, Istanbul’s urban sprawl was inevitable. Due to an imbalance between the population growth and housing supply, Istanbul’s urbanization was shaped by illegal construction processes producing the gecekondus in almost every part of the city (Gencer and Mentese, 2016). Unplanned urban expansion was so rapid that the urban master plan of 1980, which set the limits and strategies for urban development, became completely invalid by 1989 (Tapan, 1998). This situation led to the development of a new urban master plan in 1994 that included geoscientific analysis, and which highlighted the possibility of losses due to an earthquake on the segments of the North Anatolian Fault in the Marmara Sea. Uncontrolled and unplanned development continued in Istanbul until 1999 when two major earthquakes hit the region causing at least 18.000 deaths and $16 billion economic loss. These events changed the authorities’ perspective to earthquake risk and its mitigation. As a result, the 1998 earthquake resistant design code (published one year before the 1999 earthquakes) was widely embraced and implemented. Furthermore, several urban transformation projects have taken place in the last 20 years for reducing disaster risk. These have had varied success, with research to date showing that areas selected for urban transformation were often chosen on the basis of land value rather than hazard risk, and that a pro-poor approach is missing. Despite these efforts, Istanbul’s earthquake risk remains high. Furthermore, recent urban development plans are seeing the city expand into undeveloped lands to the west, increasing exposure to new hazards, namely flash flooding and landslides. The combined impact of these hazards is not evenly distributed, and the associated risks are heightened by poor infrastructural resilience and social vulnerabilities. Therefore, it is crucial to integrate different types of hazards and risks into the urban development context for future scenarios, so that a physically and socio-economically safer development that prioritizes the wellbeing of local communities can be facilitated. This presentation summarises the research conducted in Istanbul over the first 18 months of the Tomorrow’s Cities Project by a consortium of Turkish and UK researchers. This research spans the better characterisation of earthquake and landslide hazards, development of analysis methods for predicting the response of case study buildings to multiple hazards and a Bayesian network based approach for assessing road infrastructure resilience under multiple hazard scenarios. Furthermore, plans for building a Resilient Urban Development Decision Support Environment (RUD-DSE) for communicating the relevance of this research on future urban planning is described

Efficient cleavage of aryl ether C–O linkages by Rh–Ni and Ru–Ni nanoscale catalysts operating in water

Bimetallic Ru–Ni and Rh–Ni nanocatalysts coated with a phase transfer agent efficiently cleave aryl ether C–O linkages in water in the presence of hydrogen. For dimeric substrates with weaker C–O linkages, i.e. α-O-4 and β-O-4 bonds, low loadings of the precious metal (Rh or Ru) in the nanocatalysts quantitatively afford monomers, whereas for the stronger 4-O-5 linkage higher amounts of the precious metal are required to achieve complete conversion. Under the optimized, relatively mild operating conditions, the C–O bonds in a range of substituted ether compounds are efficiently cleaved, and mechanistic insights into the reaction pathways are provided. This work paves the way to sustainable approaches for the hydrogenolysis of C–O bonds

High-Energy Molecular-Frame Photoelectron Angular Distributions: A Molecular Bond-Length Ruler

We present an experimental and theoretical study of core-level ionization of small hetero- and homo-nuclear molecules employing circularly polarized light and address molecular-frame photoelectron angular distributions in the light's polarization plane (CP-MFPADs). We find that the main forward-scattering peaks of CP-MFPADs are slightly tilted with respect to the molecular axis. We show that this tilt angle can be directly connected to the molecular bond length by a simple, universal formula. The extraction of the bond length becomes more accurate as the photoelectron energy is increased. We apply the derived formula to several examples of CP-MFPADs of C 1s and O 1s photoelectrons of CO, which have been measured experimentally or obtained by means of ab initio modeling. The photoelectron kinetic energies range from 70 to 1000~eV and the extracted bond lengths agree well with the known bond length of the CO molecule in its ground state. In addition, we discuss the influence of the back-scattering contribution that is superimposed over the analyzed forward-scattering peak in case of homo-nuclear diatomic molecules as N$_2$

BKV Agnoprotein Interacts with α-Soluble N-Ethylmaleimide-Sensitive Fusion Attachment Protein, and Negatively Influences Transport of VSVG-EGFP

Background: The human polyomavirus BK (BKV) infects humans worldwide and establishes a persistent infection in the kidney. The BK virus genome encodes three regulatory proteins, large and small tumor-antigen and the agnoprotein, as well as the capsid proteins VP1 to VP3. Agnoprotein is conserved among BKV, JC virus (JCV) and SV40, and agnoprotein-deficient mutants reveal reduced viral propagation. Studies with JCV and SV40 indicate that their agnoproteins may be involved in transcription, replication and/or nuclear and cellular release of the virus. However, the exact function(s) of agnoprotein of BK virus remains elusive. Principal Findings: As a strategy of exploring the functions of BKV agnoprotein, we decided to look for cellular interaction partners for the viral protein. Several partners were identified by yeast two-hybrid assay, among them a-SNAP which is involved in disassembly of vesicles during secretion. BKV agnoprotein and a-SNAP were found to partially co-localize in cells, and a complex consisting of agnoprotein and a-SNAP could be co-immunoprecipitated from cells ectopically expressing the proteins as well as from BKV-transfected cells. The N-terminal part of the agnoprotein was sufficient for the interaction with a-SNAP. Finally, we could show that BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter suggesting that agnoprotein may modulate exocytosis. Conclusions: We have identified the first cellular interaction partner for BKV agnoprotein. The most N-terminal part of BKV agnoprotein is involved in the interaction with a-SNAP. Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter

JC Virus T-Antigen Regulates Glucose Metabolic Pathways in Brain Tumor Cells

Recent studies have reported the detection of the human neurotropic virus, JCV, in a significant population of brain tumors, including medulloblastomas. Accordingly, expression of the JCV early protein, T-antigen, which has transforming activity in cell culture and in transgenic mice, results in the development of a broad range of tumors of neural crest and glial origin. Evidently, the association of T-antigen with a range of tumor-suppressor proteins, including p53 and pRb, and signaling molecules, such as β-catenin and IRS-1, plays a role in the oncogenic function of JCV T-antigen. We demonstrate that T-antigen expression is suppressed by glucose deprivation in medulloblastoma cells and in glioblastoma xenografts that both endogenously express T-antigen. Mechanistic studies indicate that glucose deprivation-mediated suppression of T-antigen is partly influenced by 5′-activated AMP kinase (AMPK), an important sensor of the AMP/ATP ratio in cells. In addition, glucose deprivation-induced cell cycle arrest in the G1 phase is blocked with AMPK inhibition, which also prevents T-antigen downregulation. Furthermore, T-antigen prevents G1 arrest and sustains cells in the G2 phase during glucose deprivation. On a functional level, T-antigen downregulation is partially dependent on reactive oxygen species (ROS) production during glucose deprivation, and T-antigen prevents ROS induction, loss of ATP production, and cytotoxicity induced by glucose deprivation. Additionally, we have found that T-antigen is downregulated by the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), and the pentose phosphate inhibitors, 6-aminonicotinamide and oxythiamine, and that T-antigen modulates expression of the glycolytic enzyme, hexokinase 2 (HK2), and the pentose phosphate enzyme, transaldolase-1 (TALDO1), indicating a potential link between T-antigen and metabolic regulation. These studies point to the possible involvement of JCV T-antigen in medulloblastoma proliferation and the metabolic phenotype and may enhance our understanding of the role of viral proteins in glycolytic tumor metabolism, thus providing useful targets for the treatment of virus-induced tumors