Mapping of human X-linked hypophosphataemic rickets by multilocus linkage analysis

Summary Eleven families with X-linked dominant hypophosphataemic rickets (HPDR) have been typed for a series of X chromosome markers. Linkage with probe 99.6 (DXS41) was demonstrated with a peak lod score of 4.82 at 10% recombination. Multilocus linkage analysis showed that HPDR maps distal to 99.6; this probe has previously been located at Xp22.31-p21.3 by in situ hybridisation. In the mouse hypophosphataemia (Hyp) maps to the distal part of the X chromosome; our location in man is consistent with a scheme which relates the mouse and human X chromosomes by two rearrangements. No marker has yet been found which shows no recombination with HPDR.     

Poliovirus type 3: molecular cloning of the genome and nucleotide sequence of the region encoding the protease and polymerase proteins.

Overlapping cDNA clones representing the entire genome of poliovirus type 3 have been prepared in E. coli by two separate methods. Cloning of RNA . cDNA hybrids produced a more comprehensive set of clones with generally larger cDNA inserts than cloning of double - stranded cDNA. A restriction map of the entire genome and the nucleotide sequence of 2003 bases from the 3' terminus, comprising the region encoding the protease and polymerase proteins, are presented.     

Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non- Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.      

Sequences of junction fragments in the deletion-prone region of the dystrophin gene

The Duchenne muscular dystrophy locus is remarkable in that it shows a high mutation rate and the majority of mutations found are deletions. These deletions are generated as meiotic as well as mitotic events and occur preferentially in the central region of the gene. Nothing is known so far about the mechanisms involved. This paper reports the first sequencing of deletion junctions in the dystrophin gene. The data from a study of two patients with deletions in the central region of dystrophin show the breakpoints to lie in regions of introns in which stretches of dA-dT are seen. The relationship between these observations and possible mechanisms for the mutations is discussed.     

Schistosoma mansoni: the effect of regional lymphadenectomy on the level of protection induced in mice by radiation-attenuated cercariae

The lymph nodes which drain the sites of percutaneous vaccination with optimally irradiated cercariae of Schistosoma mansoni were surgically excised in studies to determine their role in the induction of protective immunity. Lymphadenectomy of the axillary and inguinal nodes which drain the abdominal exposure site, or of the cervical node which drains the aural site of exposure, five days prior to vaccination reduced the levels of resistance by two-thirds. Excision of these nodes on Days 5, 10, 15, or 20 postvaccination also significantly reduced the levels of immunity induced, though ablation was less effective at later times. Removal of lymph nodes not draining the site of vaccination had no effect on the induction of resistance. We interpret the results as indicating that successful vaccination of mice against S. mansoni requires the presentation of antigen to lymphocytes in local lymph nodes draining the vaccination site, rather than distant lymphoid organs such as the spleen.     

Long-term change in an unmanaged population of wych elm subjected to Dutch elm disease

1 Changes in a population of Ulmus glabra in Lady Park Wood (UK), a mixed deciduous native woodland, were studied by means of permanent transects. All individuals reaching 1.3 m height were recorded at irregular intervals from 1945 to 1993.
2 Dutch elm disease struck this population in about 1972. Most of the canopy and subcanopy stems were killed, but a few, slow-growing, subcanopy individuals survived unscathed.
3 Subsequent seedling regeneration and growth of sprouts from rootstocks of infected trees was substantial and vigorous. Twenty-three years after the outbreak of disease the number of elm individuals had increased by about 40%. Disease has, however, continued to afflict vigorous, exposed individuals.
4 The large-scale distribution of elm has been unaffected, but the small-scale pattern has changed due to the concentration of seedling regeneration in gaps.
5 The elm population appears to be differentiating into (i) a large high-turnover subpopulation of fast-growing, but repeatedly diseased maiden individuals and sprouts, and (ii) a small, low-turnover subpopulation of slow-growing individuals rooted in suboptimally dry, secluded sites.     

Helminth Infection and Commensal Microbiota Drive Early IL-10 Production in the Skin by CD4+ T Cells That Are Functionally Suppressive

The skin provides an important first line of defence and immunological barrier to invasive pathogens, but immune responses must also be regulated to maintain barrier function and ensure tolerance of skin surface commensal organisms. In schistosomiasis-endemic regions, populations can experience repeated percutaneous exposure to schistosome larvae, however little is known about how repeated exposure to pathogens affects immune regulation in the skin. Here, using a murine model of repeated infection with Schistosoma mansoni larvae, we show that the skin infection site becomes rich in regulatory IL-10, whilst in its absence, inflammation, neutrophil recruitment, and local lymphocyte proliferation is increased. Whilst CD4⁺ T cells are the primary cellular source of regulatory IL-10, they expressed none of the markers conventionally associated with T regulatory (T_reg) cells (i.e. FoxP3, Helios, Nrp1, CD223, or CD49b). Nevertheless, these IL-10⁺ CD4⁺ T cells in the skin from repeatedly infected mice are functionally suppressive as they reduced proliferation of responsive CD4⁺ T cells from the skin draining lymph node. Moreover, the skin of infected Rag^-/- mice had impaired IL-10 production and increased neutrophil recruitment. Finally, we show that the mechanism behind IL-10 production by CD4⁺ T cells in the skin is due to a combination of an initial (day 1) response specific to skin commensal bacteria, and then over the following days schistosome-specific CD4⁺ T cell responses, which together contribute towards limiting inflammation and tissue damage following schistosome infection. We propose CD4⁺ T cells in the skin that do not express markers of conventional T regulatory cell populations have a significant role in immune regulation after repeated pathogen exposure and speculate that these cells may also help to maintain skin barrier function in the context of repeated percutaneous insult by other skin pathogens.