Effects of Modeled Microgravity on Expression Profiles of Micro RNA in Human Lymphoblastoid Cells

Among space radiation and other environmental factors, microgravity or an altered gravity is undoubtedly the most significant stress experienced by living organisms during flight. In comparison to the static 1g, microgravity has been shown to alter global gene expression patterns and protein levels in cultured cells or animals. Micro RNA (miRNA) has recently emerged as an important regulator of gene expression, possibly regulating as many as one-third of all human genes. miRNA represents a class of single-stranded noncoding regulatory RNA molecules (~ 22 nt) that control gene expressions by inhibiting the translation of mRNA to proteins. However, very little is known on the effect of altered gravity on miRNA expression. We hypothesized that the miRNA expression profile will be altered in zero gravity resulting in regulation of the gene expression and functional changes of the cells. To test this hypothesis, we cultured TK6 human lymphoblastoid cells in Synthecon s Rotary cell culture system (bioreactors) for 72 h either in the rotating (10 rpm) to model the microgravity in space or in the static condition. The cell viability was determined before and after culturing the cells in the bioreactor using both trypan blue and guava via count. Expressions of a panel of 352 human miRNA were analyzed using the miRNA PCRarray. Out of 352 miRNAs, expressions of 75 were significantly altered by a change of greater than 1.5 folds and seven miRNAs were altered by a fold change greater than 2 under the rotating culture condition. Among these seven, miR-545 and miR-517a were down regulated by 2 folds, whereas miR-150, miR-302a, miR-139-3p, miR-515-3p and miR-564 were up regulated by 2 to 8 folds. To confirm whether this altered miRNA expression correlates with gene expression and functional changes of the cells, we performed DNA Illumina Microarray Analysis and validated the related genes using q-RT PCR

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID “Meet the Experts” 2015 Workshop Summary

The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chainnull (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting

Interprocedural slicing of multithreaded programs with applications to Java

Slicing is a well-known program reduction technique where for a given program P and a variable of interest v at some statement P in the program, a program slice contains those set of statements belonging to P that affect v. This article presents two algorithms for interprocedural slicing of concurrent programs--a context-insensitive algorithm and a context-sensitive algorithm. The context-insensitive algorithm is efficient and correct (it includes every statement that may affect the slicing criterion) but is imprecise since it may include certain extra statements that are unnecessary. Precise slicing has been shown to be undecidable for concurrent programs. However, the context-sensitive algorithm computes correct and reasonably precise slices, but has a worst-case exponential-time complexity. Our context-sensitive algorithm computes a closure of dependencies while ensuring that statements sliced in each thread belong to a realizable path in that thread.A realizable path in a thread with procedure calls is one that reflects the fact that when a procedure finishes, execution returns to the site of the most recently executed call in that thread. One of the novelties of this article is a practical solution to determine whether a given set of statements in a thread may belong to a realizable path. This solution is precise even in the presence of recursion and long call chains in the flow graph.The slicing algorithms are applicable to concurrent programs with shared memory, interleaving semantics, explicit wait/notify synchronization and monitors. We first give a solution for a simple model of concurrency and later show how to extend the solution to the Java concurrency model. We have implemented the algorithms for Java bytecode and give experimental results.© AC

Pointer analysis of multithreaded Java programs

This paper presents a context-sensitive and path-sensitive, intra-thread and inter-thread solution to combined pointer analysis, escape analysis and data dependence analysis of multithreaded Java programs which uses a sparse representation. We build and maintain a complete Static Single Assignment (SSA) form even for fields variables. We show how to compute inter-thread dependencies for multithreaded programs with structured fork-join constructs, open-ended threads, recursively generated threads, monitors, and wait-notify synchronization. We have implemented our algorithm in a slicer for Java programs. Our experimental results show that a sparse representation improves the analysis time and strong updates on field variables improves the precision.© AC

Dental manifestations in Ehlers Danlos syndrome (EDS) - Report of a case

Ehlers Danlos Syndrome (EDS) is an unusual disease entity afflicting many body systems. It is a hereditary disorder of the connective tissue. Dental manifestations are described. Attention is drawn to the role of the dentist in diagnosing a generalized disorder

Cervical lymphnode metastasis in oral squamous cell carcinoma: Correlation of manual palpation, ultrasonographic, and histopathological findings

Introduction: The staging of cervical lymphadenopathy is an important consideration in the management of oral cancer as it determines the patients' prognosis. Ultrasound is used to image the cervical lymph nodes for staging because it is noninvasive and there is no radiation exposure to the patient. Aim: To investigate the applicability and diagnostic relevance of sonography in staging cervical lymphnode metastases. Materials and Methods: Cervical lymphnodes of the patients were subjected to manual palpation and ultrasound evaluation for its size, number, shape, borders, internal echoes, echogenic hilus, and central necrosis. The manual palpation findings and ultrasound features of the lymphnodes were compared with the histological features for malignant and nonmalignant nodes. Results: When short axis of node is more than 10 mm, 86% were metastatic, nodes with irregular borders were metastatic in 84%, in the absence of the echogenic hilus, 93% were metastatic, 81% were metastatic with heterogeneous nodes, and nodes with central necrosis showed 90% metastasis. Conclusion: By using ultrasound no single parameter showed high sensitivity, specificity, and accuracy

Osteopetrosis: Report of a rare case

Osteopetrosis is a rare genetic disorder that causes generalized sclerosis of bone due to a defect in bone resorption and remodeling. Osteomyelitis is well documented as a complication of osteopetrosis. This disease can be severe and difficult to treat in the osteopetrotic patient. Prevalence is about 0.005% in general population. There are relatively few cases reported of osteopetrosis and its actual cause is not known. Dental abnormalities that present radiographically are delayed eruption and missing teeth. The overall clinical and radiographic findings of this patient were sufficient to arrive at the diagnosis of osteopetrosis

OxLDL/HDL ratio and its correlation to myeloperoxidase activity in ACS patients

Background: Oxidative stress in ACS patients results in oxidation of lipoproteins. Resultant oxLDL (oxidized Low Density Lipoprotein) is a marker for lipid peroxidation. OxLDL/HDL ratio can be used as predictor of oxidative stress and inflammation in atherosclerotic cardiovascular diseases. Myeloperoxidase (MPO), oxidative stress related enzyme, increases in inflammatory conditions. Aim and Objectives: To evaluate oxLDL/HDL ratio in ACS patients. Correlation analysis of oxLDL/HDL ratio to oxidative stress markers, MPO and Malondialdehyde (MDA) were also attempted. Materials and Method: 60 ACS patients from Hospital’s Cardiac Care Unit and 60 controls from Hospital’s Health Checkup were selected. Results: oxLDL and oxLDL/HDL ratio were significantly higher in ACS patients. Significant increase was observed in Myeloperoxidase, MDA, Total cholesterol, Low Density Lipoprotein and Triglycerides in ACS patients. Significant positive correlation was observed between oxLDL/HDL and MPO and also between oxLDL/HDL and MDA. Conclusion: Increase in MPO, oxLDL and oxLDL/HDL ratio in ACS is indicative of the significance of MPO in oxidative damage to lipoproteins in cardiovascular disease (CVD) and in incidence of acute events in CVD. We suggest that oxLDL/HDL ratio and MPO can be used as predictive markers to monitor the precipitation of acute events in CVD