Myotubular Myopathy in a Girl with a Deletion at Xq27-q28 and Unbalanced X Inactivation Assigns the MTMI Gene to a 600-kb Region

A young girl with a clinically moderate form of myotubular myopathy was found to carry a cytogenetically detectable deletion in Xq27-q28. The deletion had occurred de novo on the paternal X chromosome. It encompasses the fragile X (FRAXA) and Hunter syndrome (IDS) loci, and the DXS304 and DXS455 markers, in Xq27.3 and proximal Xq28. Other loci from the proximal half of Xq28 (DXS49, DXS256, DXS258, DXS305, and DXS497) were found intact. As the X-linked myotubular myopathy locus (MTM1) was previously mapped to Xq28 by linkage analysis, the present observation suggested that MTM1 is included in the deletion. However, a significant clinical phenotype is unexpected in a female MTM1 carrier. Analysis of inactive X-specific methylation at the androgen receptor gene showed that the deleted X chromosome was active in ~80% of leukocytes. Such unbalanced inactivation may account for the moderate MTM1 phenotype and for the mental retardation that later developed in the patient. This observation is discussed in relation to the hypothesis that a locus modulating X inactivation may lie in the region. Comparison of this deletion with that carried by a male patient with a severe Hunter syndrome phenotype but no myotubular myopathy, in light of recent linkage data on recombinant MTM1 families, led to a considerable refinement of the position of the MTM1 locus, to a region of ~600 kb, between DXS304 and DXS497.     

Presence ofAspergillus Mich. ex Fr. in several different biotopes in Córdoba (Spain)

The medical, veterinary and saprophytic importance ofAspergillus has been acknowledged by many authors. This paper reports on the occurrence ofAspergillus species in the air and dust of Córdoba (Spain). Four studied were done: first, on the air of three rooms and the outside area of 14 homes over 2 years; second, outdoor air in the west of the central district, with three samples daily over 1 year; third, the air inside and outside four of the largest silos and commercial grain warehouses in the province, over 1 year: and fourth, the dust of 12 primary schools in Córdoba city, for two consecutive school years. For air-sampling, volumetric and gravimetric methods were used, both with a culture medium and with 20-min exposure. For dust-sampling, a customised vacuum cleaner was used; samples collected were inoculated onto Petri dishes containing culture medium. A total of 38Aspergillus species were identified (we also detected four ascosporic states). A comparison of the results obtained at each of the sampling sites was made and an analysis of variance revealed quantitatively significant differences between sampling times.     

Airborne pollen concentrations,solid particle content in the air and allergy symptoms in Córdoba (Spain)

During 1991 and 1992, hourly measurements were taken of solid particulates (size, 22–25 μm).Olea and grass pollen and spores. The results were then compared with symptoms recorded in patients consulting the Allergy Unit during the period of highest pollen concentrations (April–June). The spore-trap slides were studied by spectrophotometry in order to analyse the total solid particulates content in the air as a possible synergic agent of the pollen. This allowed the volume of material present in the air to be determined and expressed as a percentage of total optical density (OD). Allergy symptom data were obtained from the study of subjective clinical records completed by patients, who were required to note down the severity of a selected series of symptoms every 4 h using a scale from 0–3. The results showed a clear link during the season between hourly peaks and pollen concentrations, and the different patterns of response associated with the dominant pollen types. An attempt has been made to determine whether a relationship exists between the increment of the optical density and the symptomatic response. The positive relationship encountered seems to indicate that a synergic agent takes an active part in the effects produced by pollen in the patients.     

Use of stable isotopes in studies on the metabolism of amphetamine (1)

Microsomal coincubation of 1,1,1-²H₃-amphetamine and unlabelled N-hydroxyamphetamine yielded ²H-incorporation into recovered N-hydroxyamphetamine. The mole fraction of ²H in recovered phenylacetone was always close to but less than one, indicating that N-hydroxyamphetamine is not a necessary intermediate in the formation of phenylacetone. However, coincubation of ²H-labelled hydroxylamine with unlabelled 2-nitro-1-phenylpropane indicated an incorporation of ²H into both recovered nitro compound and phenylacetone. Some phenylacetone is thus formed from the nitro metabolite. Similar experiments showed phenylacetone oxime not to be a necessary intermediate in the conversion of hydroxylamine to the nitro compound. Incubation of phenyl-labelled (²H) phenylacetone gave 5 deuterium-labelled metabolites, including $\text{small}$ quantities of labelled benzoic acid, indicating that it is a true though minor metabolite.     

Vertical variation in urticaceae airborne pollen concentration

The pollen contents at different heights (1.5 and 15 m) of species of the Urticaceae family have been studied by sampling with Hirst type volumetric samplers. In order to achieve this, the two pollen types belonging to this family have been treated separately,Urtica urens-Parietaria sp. on the one hand andUrtica membranacea on the other, the latter having a smaller pollen grain. The results show that meteorological factors are bound to influence the behaviour of both these types of pollen in relation to height. With damp weather the pollen contents vary very slightly at different heights while when the weather is dry and calm, differences in pollen content at different heights become more significant. Nevertheless, when the atmosphere is stratified, the behaviour of each pollen type is different. The results show that, for most of the months considered, there is a higher pollen content ofU. membranacea at upper heights, whileU. urens-Parietaria sp. has higher levels of pollen content at a lower height. High temperatures, absence of rain and calm weather conditions favour the presence of convective phenomena which in turn create a favourable atmosphere for the vertical transportation of the small pollen grains ofU. membranacea, which are better represented in the samplers placed at 15 m.     

Synthesis of a bicyclic BPTI mimetic containing 4-thioproline replacing Cys38

Summary The synthesis of a backbone bicyclic nonapeptide that mimics the binding site of bovine pancreatic trypsin inhibitor (BPTI) is described. The BPTI mimetic, which containscis-thioproline replacing Cys³⁸ of the protein, inhibits trypsin with a K _i of 76 μM.     

Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion in RPE65

The RPE65 gene encodes a 65-kDa microsomal protein expressed exclusively in retinal pigment epithelium (RPE). Mutations in the human RPE65 gene have recently been identified in patients with autosomal recessive, severe, childhood-onset retinal dystrophy. Here we report the characterization of a 2.4-kb canine Rpe65 cDNA. The longest open reading frame predicts a 533-amino-acid protein with a calculated molecular mass of about 61 kDa prior to protein modification. Sequence comparison shows that RPE65 is highly conserved throughout mammalian evolution. We have identified a homozygous 4-bp deletion (485delAAGA) in putative exon 5 of the canine Rpe65 gene in affected animals of a highly inbred kinship of Swedish briard/briard-beagle dogs, in which an autosomal recessive, early-onset, and progressive retinal dystrophy segregates. The deletion results in a frameshift and leads to a premature stop codon after inclusion of 52 canine RPE65-unrelated amino acids from residue 153 onward. More than two-thirds of the wildtype polypeptide chain will be missing, and the mutant protein is most likely nonfunctional (null allele). Clinical features of the canine disease are quite similar to those described in human. Therefore this form of canine retinal dystrophy provides an attractive animal model of the corresponding human disorder with immediate significance for various therapeutic approaches, including RPE transplantation.     

The effect of water availability on fuel deposition of two staging Sylvia warblers

In order to succeed in crossing extensive ecological barriers, migratory birds usually deposit fuel en route. High rates of fuel deposition may enable birds to shorten their total migration time and are therefore advantageous for time‐minimizing migrants. Several studies have suggested that water provision may increase food utilization in non‐migratory birds. The goal of this study was to test the influence of water availability on the fuel deposition of en route migratory passerines. We studied fuel deposition of blackcaps Sylvia atricapilla and lesser whitethroats S. curruca staging in a plantation of Mount Atlas gum‐tree Pistacia atlantica in the northern Negev desert, Israel, during the autumns of 2000 and 2002. We manipulated water availability at the site and measured the effect of water supplementation on fuel deposition of birds of both species. We found that when water was available, blackcaps had higher fuel loads and higher fuel deposition rates than during control trials. However, water availability had no effect on fuel deposition of lesser whitethroats. Species‐specific differences in adaptations to arid conditions, reflected in the species’ winter habitat preferences, may be responsible for the between‐species dissimilarity in responding to water provision. We suggest that water availability may have strong ecological and evolutionary consequences for birds migrating through arid environments, by its possible effect on bird behavior and physiology.     

Protein phosphorylation patterns during in vitro maturation of the goat oocyte

Protein phosphorylation patterns were studied by radiolabelling goat cumulus oocyte complexes with [³²P]orthophosphate for various periods of time. The radiolabelled denuded oocytes were assessed for nuclear status and were used individually for gel electrophoresis. This study demonstrated that specific changes in protein phosphorylations were programmed during goat oocyte maturation. One of the most prominent changes was a general increase in the phosphorylation rate at germinal vesicle breakdown (GVBD). From 8 hr of culture, dominant phosphoprotein bands with apparent molecular weights of 27, 31, 40, and 50 kD were observed; they remained at this level until the metaphase II stage. In the molecular weight range of 65–80 kD, the protein phosphorylation pattern exhibited characteristic differences, with a complex series of phosphoproteins appearing and disappearing, during maturation. Addition of 6-dimethylaminopurine (6-DMAP) at the onset of culture blocked the maturation process after GVBD and induced a dramatic condensation of chromatin. When added at different times after GVBD, 6-DMAP invariably induced chromosome condensation. This inhibition was partly reversible; i.e., after removal of the drug, oocytes were able to progress only until metaphase l. © 1993 Wiley-Liss, Inc.