The phenotype and genotype of rheumatoid arthritis in the Democratic Republic of Congo

Introduction

Little is known about rheumatoid arthritis in the black, particularly in Congolese, populations. Our objective was to describe the phenotype and genotype of rheumatoid arthritis (RA) in Congolese.

Methods

All consecutive rheumatoid arthritis (RA) patients attending Kinshasa University Hospital in a three-year time period were included. Demographics, clinical features and tobacco consumption were noted. Disease Activity Score (DAS)-28 based on the erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire (HAQ), anti-citrullinated peptide antibodies (CCP) antibodies and rheumatoid factor (RF) were determined. Radiographs were scored according to Sharp-van der Heijde. On a subset of patients and controls HLA-DRB1 typing was performed.

Results

A total of 114 females and 14 males aged 51.2 ± 14.9 were included. Mean duration of symptoms was four years. Moderate tobacco consumption was reported in a minority of patients. DAS-28 at first visit was >5.1 and HAQ ≥0.5 in all patients. X-rays showed joint erosions and/or joint space narrowing, mostly of a moderate grade in 55.8% of patients. Anti-CCP and/or RF were present in 48.6% of patients with available data (n = 72) and in 3.0% of controls (n = 67). Radiographic changes and nodules were more frequent in RF or anti-CCP positive patients. One copy of the shared epitope was found in 13 patients (35.1%) and 3 controls (12.5%). Two copies were found in one patient (2.7%) and in one control (4.2%).

Conclusion

Congolese patients with RA consult long after disease onset. Despite this delay, the majority presents without major damage and is RF, anti-CCP and SE negative. We put forward the hypothesis that besides different environmental factors there is probably also a particular genetic risk profile in Congolese patients, different from the HLA-DRB1 shared epitope.     

A novel harmony search-K means hybrid algorithm for clustering gene expression data

Recent progress in bioinformatics research has led to the accumulation of huge quantities of biological data at various data sources. The DNA microarray technology makes it possible to simultaneously analyze large number of genes across different samples. Clustering of microarray data can reveal the hidden gene expression patterns from large quantities of expression data that in turn offers tremendous possibilities in functional genomics, comparative genomics, disease diagnosis and drug development. The k- ¬means clustering algorithm is widely used for many practical applications. But the original k-¬means algorithm has several drawbacks. It is computationally expensive and generates locally optimal solutions based on the random choice of the initial centroids. Several methods have been proposed in the literature for improving the performance of the k-¬means algorithm. A meta-heuristic optimization algorithm named harmony search helps find out near-global optimal solutions by searching the entire solution space. Low clustering accuracy of the existing algorithms limits their use in many crucial applications of life sciences. In this paper we propose a novel Harmony Search-K means Hybrid (HSKH) algorithm for clustering the gene expression data. Experimental results show that the proposed algorithm produces clusters with better accuracy in comparison with the existing algorithms.     

Habitat preferences of Maculinea arion and its Myrmica host ants: implications for habitat management in Italian Alps

Projections of climate-change scenarios indicate that many Maculinea arion populations will disappear from Europe over the next 50 years. Extinctions will be particularly concentrated around the southern limits of the species?? range, such as the Italian peninsula, except mountain populations, mainly in the Alps. M. arion is a social parasite of Myrmica ants and its survival depends on the presence and abundance of two resources, i.e. (1) a specific larval foodplant and (2) a suitable Myrmica host ant. We collected data on Thymus plants distribution, Myrmica ants abundance, turf height around Myrmica nests, distance between nests and the closest thyme plant (Thymus pulegioides), and vegetation structure at 14 patches of a M. arion fragmented population occurring in the Western Italian Alps (Val Ferret: Aosta). We found that patches with the highest abundance of M. arion had significantly higher foodplant abundance. Among 407 nests belonging to nine Myrmica species, we found M. arion larvae in one Myrmica lonae and in two Myrmica sulcinodis nests. The distribution of M. sulcinodis nests showed the best spatial overlap with Thymus plants. M. sulcinodis was also significantly more abundant on pastures showing high M. arion density, and therefore offered higher adoption probabilities to develop butterfly larvae. On M. arion habitat patches, the mean turf height around Myrmica nests varied from 10.5 to 22.3 cm and best matched the habitat requirements of T. pulegioides. Thus, we suggest that extensive grazing is needed to maintain the two most important resources for M. arion. Moreover, patches where M. arion was abundant included more numerous plant species characteristic of these mountain pastures, as well as higher plant diversity (Shannon index). As a consequence, M. arion represents an umbrella species and a good indicator for the conservation status of mountain grasslands.     

Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17-74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS.     

A computational approach to characterization of bovine sperm chromatin alterations

We describe here a computational morphology-based approach to the investigation of possible causes of chromatin alterations in sperm. A comprehensive set of state-of-the-art and geometric measures are computationally extracted from toluidine blue stained images and analyzed to infer the possible processes leading to normal and abnormal chromatin formation while seeking a possible taxonomy of chromatin alterations and their influence on sperm head morphology. Using this methodology, we have identified higher chromatin fragility at some specific points of the sperm head. Despite the lack of correlation between morphologies of sperm head and chromatin structure, four main morphological types of chromatin alterations in bull spermatozoa have been identified and their possible causes discussed.     

Trifluoromethyl ketone inhibitors of fatty acid amide hydrolase: a probe of structural and conformational features contributing to inhibition

The examination of a series of trifluoromethyl ketone inhibitors of Fatty Acid Amide Hydrolase (FAAH, oleamide hydrolase, anandamide amidohydrolase) is detailed in efforts that define structural and conformational properties that contribute to enzyme inhibition and substrate binding. The results imply an extended bound conformation, highlight a role for the presence, position, and stereochemistry of a delta cis double bond, and suggest little apparent role for C11-C18/C22 of the fatty acid amide substrates.     

Complex mate searching in the satin bowerbird Ptilonorhynchus violaceus

Mate-choice studies typically focus on male traits affecting female mating decisions, but few studies seek to identify the behavioral rules females use when searching for mates. Current models suggest that females may either directly compare a set of males ("pooled comparison") or compare each male to an internal standard ("sequential-search rule") when judging the suitability of potential mates. Models also differ in other specific aspects, such as the predicted number of sampling bouts initiated and the tendency of females to return to males after previous visits. We monitored 63 female satin bowerbirds, Ptilonorhynchus violaceus, during mate sampling to reconstruct their search patterns. We found that females typically sampled several males and returned to the most attractive male for mating: a behavior consistent with the pooled-comparison tactic. Females, however, varied in the number of males sampled; some visited only one male before mating. We found that this variation can be explained by differences among females in the number of mates, the date mate searching is initiated, and long-term experience with males. Further, females were observed to initiate two distinct sampling bouts, with the rejection of most of their potential mates occurring before the start of the second sampling bout. This suggests that the choices of potential mates are narrowed prior to the second sampling bout and that the later visits may function to reconsider preliminary decisions made during the first sampling bout or to resolve decisions concerning the remaining potential mates. Our results indicate that mate searching is a complex process in which females use multiple sampling bouts to find suitable mates and in which several different factors influence their search behavior.     

Mitochondrial DNA alteration in obstructive sleep apnea

Background

Obstructive Sleep Apnea (OSAS) is a disease associated with the increase of cardiovascular risk and it is characterized by repeated episodes of Intermittent Hypoxia (IH) which inducing oxidative stress and systemic inflammation. Mitochondria are cell organelles involved in the respiratory that have their own DNA (MtDNA). The aim of this study was to investigate if the increase of oxidative stress in OSAS patients can induce also MtDNA alterations.

Methods

46 OSAS patients (age 59.27 ± 11.38; BMI 30.84 ± 3.64; AHI 36.63 ± 24.18) were compared with 36 control subjects (age 54.42 ± 6.63; BMI 29.06 ± 4.7; AHI 3.8 ± 1.10). In blood cells Content of MtDNA and nuclear DNA (nDNA) was measured in OSAS patients by Real Time PCR. The ratio between MtDNA/nDNA was then calculated. Presence of oxidative stress was evaluated by levels of Reactive Oxygen Metabolites (ROMs), measured by diacron reactive oxygen metabolite test (d-ROM test).

Results

MtDNA/nDNA was higher in patients with OSAS than in the control group (150.94 ± 49.14 vs 128.96 ± 45.8; p = 0.04), the levels of ROMs were also higher in OSAS subjects (329.71 ± 70.17 vs 226 ± 36.76; p = 0.04) and they were positively correlated with MtDNA/nDNA (R = 0.5, p < 0.01).

Conclusions

In OSAS patients there is a Mitochondrial DNA damage induced by the increase of oxidative stress. Intermittent hypoxia seems to be the main mechanism which leads to this process.