Clinical and laboratory aspects of a trichinellosis outbreak in Izmir, Turkey

Epidemiological, clinical and laboratory data were collected during an outbreak of trichinellosis, which occurred in Izmir, Turkey, between January and March 2004. The source of the infection was raw meatballs made with a mixture of uncooked beef and pork. Of 474 persons who were admitted at the Ataturk Training and Research Hospital during this period with a history of raw meatball consumption, the diagnosis of trichinellosis was confirmed for 154 (32.5%, 87 males and 67 females; mean age 31 years, range 6-67 years). Among persons with a confirmed diagnosis, 79% had myalgia, 77% weakness and malaise, 63% arthralgia, 40% jaw pain, 68% fever, 63% periorbital and/or facial oedema, 49% oedema at the trunk and limb, 42% abdominal pain, 40% nausea and vomiting, 28% diarrhoea, 23% subconjunctival haemorrhage, 25% macular or petechial rash, 4% subungual haemorrhage, 15% cardiac complaints and 0.2% neurological complaints. Nine patients (5.8%) were hospitalised due to severe myalgia (n = 2), high fever (n = 3), neurological manifestations (n = 1), thrombophlebitis (n = 2) and palmar erythema (n = 1). Eosinophilia was present in 88% of the confirmed cases at the admission. Elevated levels of serum creatine phosphokinase, lactic dehydrogenase and aspartate aminotransferase were detected in 72%, 70% and 16% of the confirmed cases, respectively. The seroconversion occurred in most of the infected people between the 4th and 6th weeks after the infection. All of the confirmed cases were treated with mebendazole. People with severe symptoms were treated also with prednisolone (60 mg/day for three days) and those with a moderately severe clinical pattern received a non-steroid anti-inflammatory drug (naproxen sodium, 550 mg/day). All confirmed cases recovered without any clinical sequela.     

Whole genome sequencing of Turkish genomes reveals functional private alleles and impact of genetic interactions with Europe,Asia and Africa

Background

Turkey is a crossroads of major population movements throughout history and has been a hotspot of cultural interactions. Several studies have investigated the complex population history of Turkey through a limited set of genetic markers. However, to date, there have been no studies to assess the genetic variation at the whole genome level using whole genome sequencing. Here, we present whole genome sequences of 16 Turkish individuals resequenced at high coverage (32 × -48×).

Results

We show that the genetic variation of the contemporary Turkish population clusters with South European populations, as expected, but also shows signatures of relatively recent contribution from ancestral East Asian populations. In addition, we document a significant enrichment of non-synonymous private alleles, consistent with recent observations in European populations. A number of variants associated with skin color and total cholesterol levels show frequency differentiation between the Turkish populations and European populations. Furthermore, we have analyzed the 17q21.31 inversion polymorphism region (MAPT locus) and found increased allele frequency of 31.25% for H1/H2 inversion polymorphism when compared to European populations that show about 25% of allele frequency.

Conclusion

This study provides the first map of common genetic variation from 16 western Asian individuals and thus helps fill an important geographical gap in analyzing natural human variation and human migration. Our data will help develop population-specific experimental designs for studies investigating disease associations and demographic history in Turkey.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-963) contains supplementary material, which is available to authorized users.     

The role of unequal crossover in alpha-satellite DNA evolution: a computational analysis.

Human DNA consists of a large number of tandem repeat sequences. Such sequences are usually called satellites, with the primary example being the centromeric alpha-satellite DNA. The basic repeat unit of the alpha-satellite DNA is a 171 bp monomer. Arbitrary monomer pairs usually have considerable sequence divergence (20-40%). However, with the exception of peripheral alpha-satellite DNA, monomers can be grouped into blocks of k-monomers (4 < or = k < or = 20) between which the divergence rate is much smaller (e.g., 5%). Perhaps the simplest and best understood mechanism for tandem repeat array evolution is unequal crossover. Although it is possible that alpha-satellite sequences developed as a result of subsequent unequal crossovers only, no formal computational framework seems to have been developed to verify this possibility. In this paper, we develop such a framework and report on experiments which imply that pericentromeric alpha-satellite segments (which are devoid of higher order structure) are evolutionarily distinct from the higher order repeat segments. It is likely that the higher order repeats developed independently in distinct regions of the genome and were carried into their current locations through an unknown mechanism of transposition.     

Function changing mutations in glucocorticoid receptor evolution correlate with their relevance to mode coupling

Nonlinear effects in protein dynamics are expected to play role in function, particularly of allosteric nature, by facilitating energy transfer between vibrational modes. A recently proposed method focusing on the non‐Gaussian shape of the configurational population near equilibrium projects this information onto real space in order to identify the aminoacids relevant to function. We here apply this method to three ancestral proteins in glucocorticoid receptor (GR) family and show that the mutations that restrict functional activity during GR evolution correlate significantly with locations that are highlighted by the nonlinear contribution to the near‐native configurational distribution. Our findings demonstrate that the analysis of nonlinear effects in protein dynamics can be harnessed into a predictive tool for functional site determination. Proteins 2016; 84:655–665. © 2016 Wiley Periodicals, Inc.     

Increase in rat intestinal permeability to endotoxin during hyperthermia

Victims of heat stroke exhibit several clinical features which are also encountered in endotoxaemia. In order to investigate these similarities hyperthermic rats were used to explore the possibility that high body temperature results in increased permeability of intestinal wall to endotoxin. 125I endotoxin was introduced into intestinal segments taken from non-heat exposed rats. The segments were then incubated at 37 degrees C or 45 degrees C. Intestinal segments from heat stressed rats were similarly prepared and incubated at 37 degrees C. Leakage of endotoxin from segments taken from heat stressed rats was three times greater than from those from non-heat stressed rats, as were the segments from non-heat stressed rats which were incubated at 45 degrees C. These results indicate that the intestinal membrane is damaged by heat and that an increase in outward leakage of microbial endotoxins from the gut then occurs. This might contribute to the pathophysiological picture of heatstroke.     

Comparison of the immunosuppressive properties of milk growth factor and transforming growth factors beta 1 and beta 2

The effects of the newly isolated bovine milk growth factor (MGF) which shows N-terminal homology to transforming growth factor beta 2 were compared with the effects of porcine transforming growth factor beta 1 and beta 2 (pTGF-beta 1 and -beta 2) on human T lymphocyte activation. Freshly isolated human PBMC were stimulated with either PHA, anti-CD3 + phorbol-12,13-dibutyrate (PDBu), or with a combination of ionomycin + PDBu. MGF, pTGF-beta 1, and pTGF-beta 2 decreased mitogen-induced [3H]thymidine incorporation by 30 to 75% in a dose-dependent manner. The maximum degree of inhibition was obtained at 1 ng/ml (40 pM) and could not be increased by increasing the concentration of teh transforming growth factor 10-fold. Stimulation of fresh T cells with the recall Ag tetanus toxoid was also inhibited (85%) by MGF at pM concentrations as was the proliferation of a human T cell clone specific for purified protein derivative. The effects of MGF and pTGF-beta 1 on anti-CD3-mediated increase of intracellular Ca2+ (Cai2+) was investigated by using the Fura-2 method. Neither MGF nor pTGF-beta 1 inhibited this increase in Cai2+ induced by a mitogenic concentration of anti-CD3 antibody. In order to determine whether TGF-beta preferentially inhibited the CD4+ or CD8+ subpopulation of human T cells, a limiting dilution analysis system, which allows every T cell to proliferate, was used. pTGF-beta 1 at a concentration of 5 ng/ml decreased the frequency of proliferating T cell precursors of both the CD4+ and CD8+ subsets to a similar extent. Furthermore, MGF, pTGF-beta 1, and pTGF-beta 2 also decreased IL-2 mediated [3H]thymidine incorporation into human PBL Con A blasts and the IL-4-mediated [3H]thymidine incorporation of purified T lymphocytes costimulated with PDBu by 70%. In conclusion, bovine MGF exerts suppressive effects on human T cells stimulated with Ag, mitogens, or interleukins, and the degree of T cell suppression is similar (or identical) to those of pTGF-beta 1 or -beta 2.     

ATP-dependent peptide release from mitochondria of reticulocytes

ATP-dependent release of TCA-precipitable peptides from mitochondria-containing stroma (MCS) is described. The process is independent of ubiquitin, but is sensitive to hemin and to heat treatment. Neither chloramphenicol nor EGTA inhibit. 50% of the activity is dependent on charged tRNA. The peptides released from MCS possess a molecular mass of about 1–5 kDa and are degraded to TCA-soluble compounds by a cytosolic protease system (fraction II) without ubiquitin.     

Implicit Value Updating Explains Transitive Inference Performance: The Betasort Model

Transitive inference (the ability to infer that B > D given that B > C and C > D) is a widespread characteristic of serial learning, observed in dozens of species. Despite these robust behavioral effects, reinforcement learning models reliant on reward prediction error or associative strength routinely fail to perform these inferences. We propose an algorithm called betasort, inspired by cognitive processes, which performs transitive inference at low computational cost. This is accomplished by (1) representing stimulus positions along a unit span using beta distributions, (2) treating positive and negative feedback asymmetrically, and (3) updating the position of every stimulus during every trial, whether that stimulus was visible or not. Performance was compared for rhesus macaques, humans, and the betasort algorithm, as well as Q-learning, an established reward-prediction error (RPE) model. Of these, only Q-learning failed to respond above chance during critical test trials. Betasort’s success (when compared to RPE models) and its computational efficiency (when compared to full Markov decision process implementations) suggests that the study of reinforcement learning in organisms will be best served by a feature-driven approach to comparing formal models.     

Toll-like receptor (TLR) 2-9 agonists-induced cytokines and chemokines: I. Comparison with T cell receptor-induced responses

The cells of innate and adaptive immunity, although activated by different ligands, engage in cross talk to ensure a successful immune outcome. To better understand this interaction, we examined the demographic picture of individual TLR (TLRs 2-9) -driven profiles of eleven cytokines (IFN-alpha/beta, IFN-gamma, IL-12p40/IL-12p70, IL-4, 1L-13, TNF-alpha, IL-1beta, IL-2, IL-10) and four chemokines (MCP-1, MIP1beta, IL-8, and RANTES), and compared them with direct T-cell receptor triggered responses in an assay platform using human PBMCs. We find that T-cell activation by a combination of anti-CD3/anti-CD28/PHA induced a dominant IL-2, IL-13, and Type-II interferon (IFN-gamma) response without major IL-12 and little Type-I interferon (IFN-alphabeta) release. In contrast, TLR7 and TLR9 agonists induced high levels of Type-I interferons. The highest IFN-gamma levels were displayed by TLR8 and TLR7/8 agonists, which also induced the highest levels of pro-inflammatory cytokines IL-12, TNF-alpha, and IL-1beta. Amongst endosomal TLRs, TLR7 displayed a unique profile producing weak IL-12, IFN-gamma, TNF-alpha, IL-1beta, and IL-8. TLR7 and TLR9 resembled each other in their cytokine profile but differed in MIP-1beta and MCP1 chemokine profiles. Gram positive (TLR2, TLR2/6) and gram negative (TLR4) pathogen-derived TLR agonists displayed significant similarities in profile, but not in potency. TLR5 and TLR2/6 agonists paralleled TLR2 and TLR4 in generating pro-inflammatory chemokines MCP-1, MIP-1beta, RANTES, and IL-8 but yielded weak TNF-alpha and IL-1 responses. Taken together, the data show that diverse TLR agonists, despite their operation through common pathways induce distinct cytokine/chemokine profiles that in turn have little or no overlap with TCR-mediated response.