Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency: Medical and Immunological Implications

The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most

MEASLES MORTALITY AND MALNUTRITION IN RWANDA

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Reconstructing the environmental conditions around the Silurian Ireviken Event using the carbon isotope composition of bulk and palynomorph organic matter

The carbon isotope composition (δ13C) of bulk organic matter and two palynomorph groups (scolecodonts and chitinozoans) from the Llandovery-Wenlock strata of Gotland (E Sweden) are compared to gain knowledge about carbon cycling in the Silurian (sub)tropical shelf environment. The δ13C values of the palynomorphs are mostly lower than the δ13C values of the bulk organic matter, and the δ13C values of the benthic scolecodonts are lower than those of the planktonic chitinozoans. While the difference between bulk and palynomorph δ13C may be in part a function of trophic state, the lower values of the scolecodonts relative to those of chitinozoans, which are assumed to live in the well-mixed water column, might imply an infaunal mode of life for the polychaetes that carried the scolecodonts. Lower δ13C for the scolecodonts in the middle of the section may represent variations in primary marine productivity (supported by acritarch abundance data), oxidation of organic matter in the bottom waters, or genera effects. In general, however, trends between the three data sets are parallel, indicating similarities in the low frequency, environmentally forced controls. The δ13C data show a decreasing trend from the base of the section, up to a horizon well below the base of the Upper Visby Formation. At this level, and therefore probably several 10 kyr before the δ13C increase in the carbonates, the δ13C organic values increase by ~1‰. This perhaps is an expression of a changed composition of the bulk organic matter associated with the extinction events prior to the Llandovery-Wenlock boundary

Vagrant benthos (Annelida; Polychaeta) associated with Upper Ordovician carbonate mud-mounds of subsurface Gotland, Sweden.

Micropalaeontological investigations of Upper Ordovician carbonate mud-mounds and enclosing strata of subsurface Gotland, Sweden, demonstrate that jaw-bearing polychaetes formed the most diverse faunal element associated with these build-ups. Although not present within the mound cores (intra-mound facies), scolecodonts, or polychaete jaws, occur abundantly immediately below and particularly above the mounds; the supra-mound facies also has the most diverse fossil assemblages. By contrast to the scolecodont distribution, the most diverse conodont faunas were recorded in the intra-mound facies. This reinforces the fact that scolecodont and conodont abundance and diversity numbers are commonly inverse to one another, suggesting that these metazoans occupied different niches and responded differently to taphonomical processes. The polychaete assemblage has no less than 27 species belonging to 12 genera, of which Oenonites, Mochtyella and Pistoprion are the most abundant. The assemblage has a characteristic Baltic signature and is similar in taxonomic composition to coeval ones from other areas of the Baltoscandian palaeobasin, such as that of present-day Estonia. A principal component analysis clusters the Gotland assemblage most closely to those recorded from shallow to transitional shelf environments of Estonia, indicatino that the mud-mounds were formed in such environments

Palynology, microfacies and biostratigraphy across the Daleje Event (Lower Devonian, lower to upper Emsian): new insights from the offshore facies of the Prague Basin, Czech Republic

The Zlíchovian/Dalejan boundary interval (Emsian, Lower Devonian) of the Pekárek Mill section was studied employing biostratigraphy (dacryoconarid tentaculites, conodonts) and palynology (chitinozoans, prasinophytes, scolecodonts) and microfacies analysis in order to shed more light on the timing and characteristics of the Daleje Event. The results of our study stress the great importance of the base of the Nowakia elegans Zone for the substage level division of the Emsian. Onset of the Daleje transgression is linked with higher terrigenous input, and coinciding changes in the chitinozoan assemblages were recorded at this level. The transgression at the base of the N. elegans Zone preceded the main transgression taking place in the N. cancellata Zone; it can be correlated with the Upper Zlíchov Event. For the first time, Emsian chitinozoans and a jawed polychaete fauna are described in detail from the Prague Basin and can be correlated with other northern Gondwanan regions. The family-level composition of scolecodont assemblage confirms the dominance of paulinitids in the peri-Gondwanan realm.Fil: Tonarová, Petr. Czech Geological Survey; República ChecaFil: Vodráková, Stanislava. Czech Geological Survey; República ChecaFil: Ferrová, Lenka. Czech Geological Survey; República ChecaFil: de la Puente, Graciela Susana. Universidad Nacional del Comahue. Facultad de Ingeniería. Departamento de Geología y Petróleo; ArgentinaFil: Hints, Olle. Institute Of Geology, Tallinn University Of Technology; EstoniaFil: Frýda, Jiří. Czech Geological Survey; República ChecaFil: Kubajko, Michal. Czech Geological Survey; República Chec

Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought