Influence of environment on speech-sound discrimination: findings from a longitudinal study

Event-related potentials (ERPs) from 134 children were obtained at 3 and 8 years of age and recorded to a series of consonant-vowel speech syllables and their nonspeech analogues. The HOME inventory was administered to these same children at 3 and 8 years of age and the sample was divided into 2 groups (low vs. high) based on their HOME scores. Discriminant functions analyses using ERP responses to speech and non-speech analogues successfully classified HOME scores obtained at 3 and 8 years of age and discriminated between children who received low vs. high levels of stimulation for language and reading.     

The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection

To elucidate an outline of the mechanism of eukaryotic translation initiation, 48S complex formation was analyzed on defined mRNAs in reactions reconstituted in vitro from fully purified translation components. We found that a ribosomal 40S subunit, eukaryotic initiation factor (eIF) 3, and the eIF2 ternary complex form a 43S complex that can bind to the 5'-end of an unstructured 5'-untranslated region (5'-UTR) and in the presence of eIF1 scan along it and locate the initiation codon without a requirement for adenosine triphosphate (ATP) or factors (eIF4A, eIF4B, eIF4F) associated with ATP hydrolysis. Scanning on unstructured 5'-UTRs was enhanced by ATP, eIFs 4A and 4B, and the central domain of the eIF4G subunit of eIF4F. Their omission increased the dependence of scanning on eIFs 1 and 1A. Ribosomal movement on 5'-UTRs containing even weak secondary structures required ATP and RNA helicases. eIF4F was essential for scanning, and eIFs 4A and 4B were insufficient to promote this process in the absence of eIF4F. We report that in addition to its function in scanning, eIF1 also plays a principal role in initiation codon selection. In the absence of eIF1, 43S complexes could no longer discriminate between cognate and noncognate initiation codons or sense the nucleotide context of initiation codons and were able to assemble 48S complexes on 5'-proximal AUG triplets located only 1, 2, and 4 nt from the 5'-end of mRNA.     

BRCA1 and BRCA2 mutations in Russian familial breast cancer

We have screened index cases from 25 Russian breast/ovarian cancer families for germ‐line mutations in all coding exons of the BRCA1 and BRCA2 genes, using multiplex heteroduplex analysis. In addition we tested 22 patients with breast cancer diagnosed before age 40 without family history and 6 patients with bilateral breast cancer. The frequency of families with germline mutations in BRCA was 16% (4/25). One BRCA1 mutation, 5382insC, was found in three families. The results of present study, and those of a separate study of 19 breast‐ovarian cancer families, suggest that BRCA1 5382insC is a founder mutation in the Russian population. Three BRCA2 mutations were found in patients with breast cancer without family history: two in young patients and one in patients with bilateral breast cancer. Four novel BRCA2 mutations were identified: three frameshift (695insT, 1528del4, 9318del4) and one nonsense (S1099X). © 2002 Wiley‐Liss, Inc.     

Oxygen uptake-heart rate relationship in élite wheelchair racers

The American College of Sports Medicine (ACSM) recommends that, as a general rule for health purposes, individuals should exercise at 40%–85% of their maximal oxygen uptakes. Moreover, it has been suggested that 55%–90% of the maximal heart rate may be used as an alternative estimate of these percentage maximal oxygen uptake values. The present study examined the relationship between percentage peak heart rate (% HR_peak) and percentage peak oxygen uptake (% ) during steady-state incremental intensity wheelchair propulsion of 16 élite, male wheelchair racers (WR). Oxygen uptake was determined during each submaximal exercise stage and heart rate (HR) was continuously monitored. The was subsequently determined using a separate protocol. Linear regression equations of % HR_peak versus % for each participant included % HR_peak values corresponding to 40%, 60%, 80% and 85% . The linear regression equation, derived as the group mean of the slope and intercept terms determined for each individual, was: . The group mean of the individual correlation coefficients for the relationship was 0.99. The values of % HR_peak for each of the % values below 85% were significantly greater (P<0.01) than those suggested by the ACSM. This suggests that the ACSM guidelines below 85% , based on % HR_peak, may underestimate the relative exercise intensity (i.e. % ) in the WR population. However, in élite level WR, % HR_peak can be recommended as an alternative estimate of % at wheelchair propulsion intensities of 85% or more. Electronic Publication     

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children

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Conventional methods versus 16S ribosomal DNA sequencing for identification of nontuberculous mycobacteria: cost analysis

The clinical profile of nontuberculous mycobacteria (NTM) has been raised by the human immunodeficiency virus and AIDS pandemic. Different laboratory techniques, often molecular based, are available to facilitate the rapid and accurate identification of NTM. The expense of these advanced techniques has been questioned. At the National Reference Center for Mycobacteriology and the Health Sciences Center, University of Manitoba, in Winnipeg, Canada, we performed a direct cost analysis of laboratory techniques for commercial DNA probe-negative (Gen-Probe, Inc., San Diego, Calif.), difficult-to-identify NTM. We compared the costs associated with conventional phenotypic methodology (biochemical testing, pigment production, growth, and colony characteristics) and genotypic methodology (16S ribosomal DNA [rDNA] sequence-based identification). We revealed a higher cost per sample with conventional methods, and this cost varied with organism characteristics: $80.93 for slowly growing, biochemically active NTM; $173.23 for slowly growing, biochemically inert NTM; and $129.40 for rapidly growing NTM. The cost per sample using 16S rDNA sequencing was $47.91 irrespective of organism characteristics, less than one-third of the expense associated with phenotypic identification of biochemically inert, slow growers. Starting with a pure culture, the turnaround time to species identification is 1 to 2 days for 16S rDNA sequencing compared to 2 to 6 weeks for biochemical testing. The accuracy of results comparing both methodologies is briefly discussed. 16S rDNA sequencing provides a cost-effective alternative in the identification of clinically relevant forms of probe-negative NTM. This concept is not only useful in mycobacteriology but also is highly applicable in other areas of clinical microbiology.     

Leishmania major modulates chemokine and chemokine receptor expression by dendritic cells and affects their migratory capacity

Dendritic cells (DC) both produce and respond to chemokines. We examined the profiles of chemokines and chemokine receptors expressed by DC and their chemotactic response after interaction with Leishmania major. Expression of the chemokine receptors CCR2 and CCR5 by DC and their responsiveness to the respective ligands, CCL2 and CCL3, were downregulated, while the level of CCR7 and the DC response to its ligand CCL21 were enhanced. These parasite-induced alterations were observed with DC from L. major-resistant and -susceptible mice. In contrast, expression of the chemokine CXCL10 was elicited only in DC from L. major-resistant mice.     

Increased interleukin 4 (IL-4) receptor expression and IL-4-induced decrease in IL-12 production by Langerhans cells infected with Leishmania major

Langerhans cells (LC) take up Leishmania major and are critical for the induction of the parasite-specific T-cell response. Their functional activities are regulated by cytokines. We analyzed whether infection of LC with L. major modulates the expression of their cytokine receptors. The expression of the interleukin 4 (IL-4) receptor was increased on infected LC from susceptible mice but not on those from resistant mice. Moreover, IL-4 treatment strongly decreased the lipopolysaccharide-induced IL-12 response of infected LC from susceptible mice. This modulation of IL-4 receptor expression and IL-12 production by infection of LC with Leishmania may contribute to the development of Th2 cells and to susceptibility to infection.