12 research outputs found
The Challenges to Improving Public Services and Judicial Operations: A unique balance between pursuing justice and public service in Indonesia
Get PDFThis chapter explores judicial perspectives on sentencing minor drug offenders in Indonesia. As a basis for the framework for this study, a concept of Goffman on dramaturgy was used to explain the dramaturgical competence of the panel judges in their attempts to show accountability to their audiences (i.e., the sphere of politics, the public, and religion). Conceptualisation of this study stems from this author former self-identity as a judge but also from the author biography since the author more familiar with the practical pressure and challenges of lower court judges. This chapter contributes to knowledge by considering that the judicial awareness of the issues surrounding justice and public acceptance led to the situation where they were attempting to present a unique balance between pursuing justice and public service
Prevalence of Brucella in Raw Milk: An Example from Turkey
Get PDFWOS: 000439047000015PubMed ID: 29984724Aim: Brucellosis is a highly contagious zoonotic infection affecting livestock and human beings. This study aimed to investigate the prevalence of Brucella in raw milk collected from a provincial center and central villages in the Central Anatolian region. Materials and Methods: This cross-sectional study was completed between March and September of 2016. The sample size for research was calculated as 263 milk samples with the Epi Info 2000 program. Samples were tested with the milk ring test, Rose Bengal test, and standard Brucella tube agglutination test. Suspicious samples according to these tests were seeded on medium for observation. Results: In this study, 202 cow's milk samples collected from 14 central villages were researched for the presence of Brucella abortus, a Brucella species bacterium. According to the medium seeding results, 35 of 202 raw cow's milk samples ( 17.32%) were identified as suspicious. Conclusion: The research investigated the prevalence of Brucella in milk samples collected from bovine farms used for consumption and production of raw milk products. The most significant infection route in our region is considered to be consumption of milk and milk products such as raw milk and fresh cheese. Especially in rural areas, households consuming their own produced milk are common. In regions with family-style milk and milk product production and consumption, interventional studies with the aim of improving knowledge, attitudes, and behavior related to zoonotic diseases should not be neglected
Sick building symptoms among hospital workers associated with indoor air quality and personal factors
Get PDFThis study assesses the interior air quality and infective factors in a hospital in Turkey to provide data about air quality to protect hospital workers. This study measured indoor air quality in eight different locations in a hospital, including particulate matter (PM2.5 and PM1), carbon dioxide, carbon monoxide, temperature, humidity and microbiological matter. The highest PM2.5 and PM1 concentrations were in emergency service, and the highest CO2 was measured in the paediatric clinic. The poor interior air quality results are the most important cross-sectional data. For all participants, the prevalence of eye, upper respiratory tract, lower respiratory tract, skin and non-specific sick building syndrome symptoms were 23.0%, 40.7%, 22.5%, 36.3% and 63.7%, respectively. When sick building syndrome symptoms and environmental factors were investigated, skin symptoms increased 1.82 times in areas with stagnant air flow (p = 0.046; OR = 1.823; 95% CI: 1.010–3.290). Non-specific symptoms increased 2.17 times in locations with dry indoor air (p = 0.039; OR = 2.176; 95% CI: 1.041–4.549). Hospital workers are exposed to conditions that may increase the risk of a variety of sick building syndrome symptoms. Although the air quality measurements were not above the recommended limits in the hospital, long-term exposures should be considered for those experiencing sick building syndrome-related symptoms. © The Author(s) 2019
Crimean-Congo Hemorrhagic Fever Virus Infection in Domestic Ruminants in Van Province, a Non-endemic Region in Turkey
No full textBackground: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease of humans that is most widespread in Africa, Asia, the Middle East and Southeast Europe. The disease has continued to be a health problem in Turkey and other endemic countries in recent years. CCHF virus does not cause clinical disease in animal hosts but develops an antibody response and a transient viraemia. The aim of this study is to evaluate the status of CCHF infection serologically and virologically in livestock in the Van region, a non-endemic area in Turkey. Methods: A total of 491 whole blood and 491 serum specimens were collected from cattle, sheep and goats in different locations of Van province in Turkey from May 2020 to October 2021. To determine the CCHFV-specific antibody, all sera from animals were tested with a double-Ag ELISA-Ab kit. An RT-PCR assay was performed on total leucocyte samples for the virological study to detect the presence of European lineage-1 CCHFV nucleic acids and viraemic animals. Result: The prevalence of CCHFV-specific antibodies in animals was found to be 36.4%. The seroprevalence values detected were 11.6%, 64.45% and 81.63% in cattle, sheep and goats, respectively. In the RT-PCR assay, 1.22% (6/491) of the tested animals were found to be viraemic at the time of sampling
Serum CXCL-13 levels are associated with active neurological involvement in patients with systemic lupus erythematosus
No full textBackground: Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse systemic manifestations, including neuropsychiatric involvement (NPSLE), which can vary in severity and prognosis. Diagnosing NPSLE remains challenging, necessitating reliable diagnostic markers. CXCL13, a B-cell chemokine implicated in SLE, has garnered attention for its potential role in NPSLE. Purpose: This study aimed to assess serum CXCL-13 levels in NPSLE patients compared to SLE patients without neuropsychiatric symptoms and healthy controls. Research Design: All study groups were studied CXCL-13 levels from blood samples. Study Sample: One hundred twenty-five participants were categorized into four groups: SLE patients with active NPSLE (n = 6), SLE patients with inactive NPSLE (n = 26), SLE patients without NPSLE (n = 71), and healthy controls (n = 22). Data Collection and Analyses: Serum samples were collected at the time of enrollment and CXCL-13 levels were analysed by Enzyme Linked ImmunoSorbent Assay (ELISA) method. Results: Results indicated significantly elevated CXCL-13 levels in active NPSLE patients compared to other SLE patient groups and healthy controls (p < 0.001 for all). Patients with SLE, including those with inactive NPSLE or no history of NPSLE, had statistically significantly higher serum CXCL-13 levels compared to the control group (p < 0.001). Additionally, serum CXCL-13 levels positively correlated with disease activity assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Conclusion: This study underscores the association between serum CXCL-13 levels and neuropsychiatric involvement in SLE, as well as their correlation with disease activity. Moreover, previous research suggesting a link between CXCL-13 levels and clinical activity in SLE further supports its potential as a diagnostic marker for NPSLE. Nevertheless, further investigations are warranted to validate the utility of CXCL-13 as a diagnostic tool for NPSLE and its role in disease management. © The Author(s) 2025
Computational approaches for investigating protein-ligand interactions - towards an in-depth understanding of the dengue virus methyltransferase
Get PDFInteractions between proteins and their ligands play crucial roles in many
biological processes, such as metabolism, signaling, transport, regulation or
molecular recognition. Understanding the molecular basis of protein-ligand
interactions is thus of great interest, not only for modeling complex biological
systems but also for applications in drug discovery. However, structural details
for most of these interactions have not been characterized experimentally.
Therefore, computational methods have become increasingly important for
investigating biological systems at an atomistic level.
This work aims at a better understanding of the molecular basis of disease
related viral methyltransferases, their interactions with small molecules and
the catalytic mechanism, which may on the long perspective help to develop a
treatment against neglected tropical diseases. Furthermore, we aim to advance
the current methods for the computational prediction of a protein's molecular
function and its biological role in the cell. In addition, we aim to complement
currently available computational strategies for estimating protein ligand
interaction energies.
Dengue fever is a rapidly emerging, still neglected tropical disease which
causes significant mortality and morbidity in humans. For the discovery of novel
classes of compounds inhibiting dengue virus methyltransferase, a combination of
structure-based virtual screening and enzymatic inhibition assays is employed.
From the shortlist of 263 candidates selected by virtual screening, ten
compounds are found to specifically inhibit the target enzyme with IC50
values in the low uM range. Promising compounds are selected for further
experimental characterization and the inhibitory activity of the two most active
compounds is confirmed.
For obtaining a better understanding of the molecular basis of the target
enzyme's function, molecular dynamics simulations and mixed quantum
mechanics/molecular mechanics calculations are employed to investigate the
mechanisms of the enzymatically catalyzed reaction at an atomistic level. Based
on a structural model of the target protein in complex with its RNA substrate,
the impact of mutations on ligand binding, geometric arrangements and reaction
energy barriers are evaluated computationally. In addition, for a detailed
characterization of the underlying chemical reactions, ab initio electronic
structure calculations are performed on model systems approximating the
biological structure.
The reliable prediction of ligand binding sites is crucial for characterizing
proteins with unknown function. Therefore, the use of computational predictions
of protein function and ligand binding sites for proteins without experimental
structures are assessed in a blind and objective way. Limitations in the current
prediction methods are analyzed and suggestions for a more reliable evaluation
are given. Following those suggestions, an extended and fully automated
assessment is implemented in the Continuous Automated Model EvaluatiOn (CAMEO)
framework.
Computational identification of protein-ligand interactions can greatly
facilitate the drug discovery process. Thus, we establish a straightforward,
rapid scoring function that aims to identify the best poses out of an ensemble
of pre-docked poses, by quantifying the degree of burial and the electrostatic
interactions of the ligand in a binding site. The scoring function is evaluated
on a set of high quality protein-ligand complex structures, where the results
show promisingly high retrieval rates for selecting the best poses from a pool
of decoy poses.
Finally, a novel human-computer interface device is described which facilitates
the interaction with the computational representation of complex biological
systems by employing natural and intuitive movements
The application of the fragment-based screening approach to RmlA protein and PA1645 structure
No full textP. aerguinosa is a serious human bacterial pathogen. This thesis describes attempts to use
structural biology to identify new starting points for drugs against P. aerguinosa .A number of
fragment-based screening techniques were used in order to identify potential inhibitors to P.
aerguinosa RmlA protein, the first enzyme in the L-Rhamnose pathway. A 500 “Rule of 3”
Fragment Library (Maybridge) was investigated. The first approach was the application of
Differential Scanning Fluorimetry (DSF) approach to detect ligands that bind and stabilize
RmlA protein. The stabilisation of RmlA was determined by thermal unfolding in the presence
of each of the 500 compounds. 21 of those compounds were found to increase the protein
stability. The library was then screened by NMR spectroscopy for binding to RmlA. Two
techniques were evaluated STD and WaterLOGSY. 106 compounds gave positive results in
both NMR experiments. These hits were then tested by a simple STD competition binding with
dTTP, a natural RmlA substrate, in order to identify those binding at the active or allosteric
site. 21 out of the 106 compounds were observed to compete with dTTP. The results were
compared to the results of the DSF screening. Compounds that tested positive in the dTTP
competition binding STD experiment and in the DSF screening were tested for their ability to
inhibit RmlA in a biological assay. A coupled enzyme assay was used to monitor RmlA
activity. Only one compound, 3-pyridin-3-ylaniline, showed significant inhibition of the
enzyme activity.
The PA1645 protein from P. aerguinosa has been identified as essential. The protein was
overexpressed, purified and crystallised. Data were collected at Diamond on beamline IO3 and
phases were determined by S-SAD at a wavelength of 1.6Å. Final coordinates have been
deposited in the protein data bank under entry code 2XU8. The structure has 3 molecules in the asymmetric unit. There is some ambiguity as to the validity of the proposed trimeric
arrangement, with results from solution and crystal disagreeing.
Fragment-based screening approach has been applied to RmlA protein, using the DSF
technique, a number of ligand-based NMR experiments and a coupled enzyme biological
assay. 3-pyridin-3-ylaniline was the only compound that showed significant inhibition of the
enzyme activity. The structure of PA1645 from P. aerguinosa has been solved. This work will
help to design new drugs to combat multi-drug resistant P. aerguinosa and MTB
Genetic Susceptibility to Clozapine-Induced Agranulocytosis/Neutropenia Across Ethnicities: Results From a New Cohort of Turkish and Other Caucasian Participants, and Meta-Analysis
No full textClozapine (CLZ) is considered the most effective antipsychotic, but its use is associated with neutropenia (CIN) and agranulocytosis (CIA). Although the exact etiology of these hazardous side effects is unknown, 4 genetic polymorphisms have been implicated by genomewide association studies (GWAS), mostly performed in North-Western Europeans. These polymorphisms are rs113332494 (HLA-DQB1), rs41549217 (HLA-B), and rs1546308/rs149104283 (SLCO1B3/7), several of which were not directly genotyped but imputed. To test whether these 4 single-nucleotide polymorphisms (SNPs) are associated with CIN/CIA in a Turkish population and in a more extensive group of Caucasians, we directly genotyped these polymorphisms using Taqman and Sanger sequencing and performed logistic regression. We divided our participants (234 CLZ-using participants of whom 31 CIN/CIA cases) into (1) North-Western European, (2) Turkish, (3) Caucasian (=1 + 2); and (4) a total group (Caucasian + other ethnicities). Rs113332494 (HLA-DQB1) was significantly associated with CIN/CIA in the total group (P = 3.5 10-8), in the Caucasian group (P = 9.3 10-6) and in the Turkish group (P = 2.8 10-5). Rs41549217 (HLA-B) was nominally significant in the Caucasian group (P = .018). In meta-analysis of our results and the previously reported genome-wide results, 3 SNPs were significantly associated with CIN/CIA in participants with Caucasian ancestry: rs113332494 (P = 2.05 10-8), rs41549217 (P = 7.19 10-9), and rs149104283 (P = 5.54 10-9), with the result for rs1546308 (SCLO1B3/SCLO1B7) being significantly heterogeneous across studies. Our results hint at ethnicity-dependent and clinically relevant effects of genetic polymorphisms on the risk to develop CIN/CIA. Pharmacogenetic testing can complement clinical decision making and thus empower appropriate CLZ prescribing, but ancestry should be taken into account when performing such testing for CLZ. The Author(s) 2020
