Synthesis and acid ionization constants of cyclic cystine peptides

Cyclic peptide disulfides of the general formula were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-_n-Cys(Trt)-OBu^t] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK¹= 2.35–2.84) and to terminal amino group (pK₂= 5.61–6.93); pK₁, values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK₂, values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO——-NH⁺₃-) formation.     

Detection of New H5N1 High Pathogenicity Avian Influenza Viruses in Winter 2021–2022 in the Far East,Which Are Genetically Close to Those in Europe

Many high pathogenicity avian influenza (HPAI) cases in wild birds due to H5N1 HPAI virus (HPAIV) infection were reported in northern Japan in the winter of 2021–2022. To investigate the epidemiology of HPAIVs brought to Japan from surrounding areas, a genetic analysis of H5 HPAIVs isolated in northern Japan was performed, and the pathogenicity of the HPAIV in chickens was assessed by experimental infection. Based on the genetic analysis of the hemagglutinin gene, pathogenic viruses detected in northern Japan as well as one in Sakhalin, the eastern part of Russia, were classified into the same subgroup as viruses prevalent in Europe in the same season but distinct from those circulating in Asia in winter 2020–2021. High identities of all eight segment sequences of A/crow/Hokkaido/0103B065/2022 (H5N1) (Crow/Hok), the representative isolates in northern Japan in 2022, to European isolates in the same season could also certify the unlikeliness of causing gene reassortment between H5 HPAIVs and viruses locally circulating in Asia. According to intranasal challenge results in six-week-old chickens, 50% of the chicken-lethal dose of Crow/Hok was calculated as 10^4.5 times of the 50% egg-infectious dose. These results demonstrated that the currently prevalent H5 HPAIVs could spread widely from certain origins throughout the Eurasian continent, including Europe and the Far East, and implied a possibility that contagious viruses are gathered in lakes in the northern territory via bird migration. Active monitoring of wild birds at the global level is essential to estimate the geographical source and spread dynamics of HPAIVs.     

Counseling Fathers (2010) by C.Z. Oren and D.C. Oren

No abstract available for this article.     

Genetic variants of the Crimean-Congo hemorrhagic fever virus circulating in endemic areas of Southern Tajikistan in 2009

Five-hundred-and-six Hyalomma anatolicum ticks were collected and studied in two Crimean-Congo hemorrhagic fever (CCHF) endemic regions of Tajikistan. Antigen and RNA of the CCHF virus were detected in 3.4% of tick pools from the Rudaki district using ELISA and RT-PCR tests. As for the Tursunzade district, viral antigen was identified in 9.0% of the samples and viral RNA was identified in 8.1% of the samples. Multiple alignment of the obtained nucleotide sequences of a region of the S-segment of the genome of the CCHF virus 287 nucleotides in length (996–1282) and the multiple alignment of the deduced amino-acid sequences of the samples carried out to compare with CCHF virus strains from the GenBank database, as well as their phylogenetic analysis, enabled us to conclude that the Asia 1 and Asia 2 genotypes of the CCHF virus are circulating in Tajikistan. It is important to note that the genotype Asia 1 virus was detected in Tajikistan for the first time.     

A GCH1 haplotype confers sex‐specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21–5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry. Am. J. Hematol. 89:187–193, 2014. © 2013 Wiley Periodicals, Inc.     

Characterization of diet-dependent metabolic serotypes: primary validation of male and female serotypes in independent cohorts of rats

Our research seeks to identify serum profiles, or serotypes, that reflect substantial changes in food intake in both male and female rats. This report validates previously defined subsets of redox-active low-molecular-weight metabolites using independent cohorts of ad libitum consumption (AL) and energy or dietary restricted (DR) 6-mo-old male and female rats. In the male study, both hierarchical cluster analysis (HCA) and principal component analysis (PCA) distinguished the dietary groups of origin in the second male cohort with >85% accuracy using 56 analytically and biologically valid metabolites. Further analysis revealed that 29 metabolites (nine previously unidentified metabolites + 20 chosen from the 56 metabolites) enabled HCA to distinguish dietary groups at 100% efficacy. In the female study, the 63 previously identified serum metabolites were sufficiently robust to enable classification of the dietary intake of two female cohorts (cohorts 2 and 3) that were independent of the cohort on which these markers were initially identified (cohort 1). Classification accuracy was 94 and 100% using HCA and PCA, respectively, in the female cohort 2. HCA and PCA revealed that the 63-metabolite profile distinguished AL and DR samples at 91 and 100% accuracy in the female cohort 3, establishing the 63-metabolite dataset as our baseline profile. These studies used independent cohorts to validate and potentially improve upon previously defined metabolic serotype in male and female rats and set the stage for pattern recognition-based approaches to establish metabolome-based categorical separations.