Interferon- γ receptor-1 gene promoter polymorphisms and susceptibility for brucellosis in Makkah region

Background: Genetic polymorphisms that affect the production levels of certain cytokines and/or their receptors may determine the risk, severity or protection in some infectious diseases like brucellosis.Objectives: The aim of this study was to investigate the association of certain known Interferon-γ Receptor-1 (IFN-γ R1) gene promoter polymorphisms and the susceptibility to infection with Brucellosis in Saudi population.Methods: A cases-control association study was conducted in 69 individuals with human brucellosis and 94 healthy individuals. Genotyping of IFN-γ R1 – 56 C>T and IFN-γ R1 – 611 A>G polymorphism in both patients and healthy controls was done by PCR- restriction enzyme length polymorphisms (PCR-RFLP) and PCR- confronting two primer pairs (PCR-CTPP) methods and were assessed for potential associations with susceptibility for human brucellosis and their mode of penetrance.Results: Interestingly, we have designed a PCR-CTPP system to be used for genotyping of    IFN-γ R1 – 611 A > G polymorphism. The PCR-CTPP is an accurate method for genotyping of SNPs. Moreover, it is time-saving, inexpensive and easy to perform.Conclusion: Both tested polymorphisms, IFN-γ R1 – 56 C>T and IFN-γ R1 -611 A>G polymorphism had no role in genetic susceptibility to human brucellosis in the study population. The PCR-CTPP can be used for genotyping IFN-γ R1 – 611 A > G polymorphism and other types of mutation.Keywords: Brucellosis; susceptibility; IFN-γ R1 gene promoter polymorphisms

Comparison of data recovery techniques on master file table between Aho-Corasick and logical data recovery based on efficiency

Data recovery is one of the tools used to obtain digital forensics from various storage media that rely entirely on the file system used to organize files in these media. In this paper, two of the latest techniques of file recovery from file system (new technology file system (NTFS)) logical data recovery, Aho-Corasick data recovery were studied, examined and a practical comparison was made between these two techniques according to the speed and accuracy factors using three global datasets. It was noted that all previous studies in this field completely ignored the time criterion despite the importance of this standard. On the other hand, algorithms developed with other algorithms were not compared. The proposed comparison of this paper aims to detect the weaknesses and strength of both algorithms to develop a new algorithm that is more accurate and faster than both algorithms. The paper concluded that the logical algorithm was superior to the Aho-Corasick algorithm according to the speed criterion, whereas the algorithms gave the same results according to the accuracy criterion. The paper leads to a set of suggestions for future research aimed at achieving a highly efficient and high-speed data recovery algorithm such as the file-carving algorithm

Interferon- \u3b3 receptor-1 gene promoter polymorphisms and susceptibility for brucellosis in Makkah region

Background: Genetic polymorphisms that affect the production levels of certain cytokines and/or their receptors may determine the risk, severity or protection in some infectious diseases like brucellosis. Objectives: The aim of this study was to investigate the association of certain known Interferon-\u3b3 Receptor-1 (IFN-\u3b3 R1) gene promoter polymorphisms and the susceptibility to infection with Brucellosis in Saudi population. Methods: A cases-control association study was conducted in 69 individuals with human brucellosis and 94 healthy individuals. Genotyping of IFN-\u3b3 R1 \u2013 56 C>T and IFN-\u3b3 R1 \u2013 611 A>G polymorphism in both patients and healthy controls was done by PCR- restriction enzyme length polymorphisms (PCR-RFLP) and PCR- confronting two primer pairs (PCR-CTPP) methods and were assessed for potential associations with susceptibility for human brucellosis and their mode of penetrance. Results: Interestingly, we have designed a PCR-CTPP system to be used for genotyping of IFN-\u3b3 R1 \u2013 611 A > G polymorphism. The PCR-CTPP is an accurate method for genotyping of SNPs. Moreover, it is time-saving, inexpensive and easy to perform. Conclusion: Both tested polymorphisms, IFN-\u3b3 R1 \u2013 56 C>T and IFN-\u3b3 R1 -611 A>G polymorphism had no role in genetic susceptibility to human brucellosis in the study population. The PCR-CTPP can be used for genotyping IFN-\u3b3 R1 \u2013 611 A > G polymorphism and other types of mutation

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

Trial design: Computer guided normal-low versus normal-high potassium control in critically ill patients: Rationale of the GRIP-COMPASS study

Background: Potassium depletion is common in hospitalized patients and can cause serious complications such as cardiac arrhythmias. In the intensive care unit (ICU) the majority of patients require potassium suppletion. However, there are no data regarding the optimal control target in critically ill patients. After open-heart surgery, patients have a strongly increased risk of atrial fibrillation or atrial flutter (AFF). In a novel trial design, we examined if in these patients different potassium control-targets within the normal range may have different effects on the incidence of AFF. Methods/Design: The "computer-driven Glucose and potassium Regulation program in Intensive care Patients with COMparison of PotASSium targets within normokalemic range (GRIP-COMPASS) trial" is a single-center prospective trial in which a total of 1200 patients are assigned to either a potassium control-target of 4.0 mmol/L or 4.5 mmol/L in consecutive alternating blocks of 50 patients each. Potassium levels are regulated by the computer-assisted potassium suppletion algorithm called GRIP-II (Glucose and potassium regulation for Intensive care Patients). Primary endpoint is the in-hospital incidence of AFF after cardiac surgery. Secondary endpoints are: in-hospital AFF in medical patients or patients after non-cardiac surgery, actually achieved potassium levels and their variation, electrolyte and glucose levels, potassium and insulin requirements, cumulative fluid balance, (ICU) length of stay, ICU mortality, hospital mortality and 90-day mortality. Discussion: The GRIP-COMPASS trial is the first controlled clinical trial to date that compares potassium targets. Other novel methodological elements of the study are that it is performed in ICU patients where both targets are within the normal range and that a computer-assisted potassium suppletion algorithm is used

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically-modified animal models, together with biochemical and pharmacological approaches, we provide a high resolution expression map and a detailed functional characterization of A2AR-CB1R heteromers in the dorsal striatum. Specifically, our data unveil that the A2AR-CB1R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington’s disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases

Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer

BACKGROUND: Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and −4 are highly expressed, but PAR-3 shows low expression and unclear functions. METHODS: Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGFβ monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. RESULTS: We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and −4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGFβ in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. CONCLUSIONS: Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2203-7) contains supplementary material, which is available to authorized users