23 research outputs found
Paired opposing leukocyte receptors recognizing rapidly evolving ligands are subject to homogenization of their ligand binding domains
Some leukocyte receptors come in groups of two or more where the partners share ligand(s) but transmit opposite signals. Some of the ligands, such as MHC class I, are fast evolving, raising the problem of how paired opposing receptors manage to change in step with respect to ligand binding properties and at the same time conserve opposite signaling functions. An example is the KLRC (NKG2) family, where opposing variants have been conserved in both rodents and primates. Phylogenetic analyses of the KLRC receptors within and between the two orders show that the opposing partners have been subject to post-speciation gene homogenization restricted mainly to the parts of the genes that encode the ligand binding domains. Concerted evolution similarly restricted is demonstrated also for the KLRI, KLRB (NKR-P1), KLRA (Ly49), and PIR receptor families. We propose the term merohomogenization for this phenomenon and discuss its significance for the evolution of immune receptors
Emergency surgical intervention by mobile surgical team in the NICU
Purpose:
Our objective was to compare observed and expected genotype proportions from newborn screening
surveys of structural hemoglobin variants.
Methods:
We conducted a systematic review of newborn screening surveys of hemoglobins S and C in Africa and the
Middle-East. We compared observed frequencies to those expected assuming Hardy-Weinberg equilibrium
(HWE). Significant deviations were identified by an exact test. The fixation index FIS was calculated to assess
excess homozygosity. We compared newborn estimates corrected and uncorrected for HWE deviations
using demographic data.
Results:
Sixty samples reported genotype counts for hemoglobin variants in Africa and the Middle-East. Observed
and expected counts matched in 27%. The observed number of sickle-cell anemia (SCA) individuals was
higher than expected in 42 samples, reaching significance (p<0.05) in 24. High FIS were common across the
study regions. The estimated total number of newborns with SCA, corrected based on FIS, were 33,261
annual births instead of 24,958 for the 38 samples across sub-Saharan Africa and 1,109 annual births instead
of 578 for 12 samples from the Middle East.
Conclusion:
Differences between observed and expected genotype frequencies are common in surveys of hemoglobin
variants in the study regions. Further research is required to identify and quantify factors responsible for
such deviations. Estimates based on HWE might substantially underestimate the annual number of SCA
affected newborns (up to one third in sub-Saharan Africa and one half in the Middle East)
Incidence of sickle cell disease in an unselected cohort of neonates born in Berlin, Germany
Discrepant results from sampling different lumens of multilumen catheters: the case for sampling all lumens
Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers
Guidance Statement for the Management of Febrile Neutropenia in Pediatric Patients Receiving Cancer-Directed Therapy in Central America and the Caribbean
Transgenic Sickle Cell Disease Mice Have High Mortality and Dysregulated Immune Responses After Vaccination
Background Children with sickle cell disease (SCD) are susceptible to recurrent infections, which are often life threatening and necessitate frequent vaccinations. Given the altered baseline immunity and proinflammatory state associated with SCD, we sought to determine the relative safety and efficacy of vaccination in transgenic SCD mice. Methods Eight week-old SCD mice were vaccinated with ovalbumin (OVA) and aluminum hydroxide weekly for three weeks by the intraperitoneal (IP) or intramuscular (IM) route. One week after the third vaccination, serum cytokines/chemokines, immunoglobulins, and bronchoalveolar lavage (BAL) fluid cytokines were measured. Results Only SCD mice were prone to mortality associated with vaccination as 40% of the animals died after the IP vaccinations and 50% died after the IM vaccinations. Serum IgG2b and IgM were significantly lower in SCD than C57Bl/6 mice after vaccination, but OVA-specific IgE was significantly higher. Serum interleukin 1 alpha (IL-1α), IL-2, IL-5, macrophage inflammatory protein 1 alpha (MIP-1α), and granulocyte macrophage-colony stimulating factor (GM-CSF) were significantly lower in SCD mice than C57Bl/6 mice after vaccination, whereas BAL fluid IL-1β and IL-6 were elevated. Conclusions Mice with SCD appear to have a dysregulated immune response to vaccination. Thus, the relative safety and immunogenicity of vaccination should be studied in greater detail in the context of SCD