Allelic Variation within the Emv-15 Locus Defines Genomic Sequences Closely Linked to the agouti Locus on Mouse Chromosome 2

Gene(s) at the agouti locus act within the microenvironment of the hair follicle to switch pigment synthesis in the melanocyte between eumelanin (black or brown pigment) and phaeomelanin (yellow pigment). Many phenotypic variants of this locus have been described. The mechanism(s) of gene action causing such variation in coat-color phenotype is not known. The close linkage of an endogenous ecotropic murine leukemia provirus, Emv-15, to the lethal yellow mutation of the agouti locus provides a means to molecularly access genes at or near the agouti locus. We have identified and used a unique mouse sequence flanking the Emv-15 provirus to define three alleles of the Emv-15 locus. We found a correlation between the presence of specific Emv-15 alleles and the origins of specific agouti locus mutations, confirming close linkage. However, we found some exceptions which suggest that the Emv-15 locus is closely linked to, but genetically separable from, the agouti locus.     

Genomic Organization and Mutation Analysis ofp73in Oligodendrogliomas with Chromosome 1 p-Arm Deletions

p73, a protein having substantial structural and functional similarity to p53, has recently been identified and demonstrated to be a potential tumor suppressor. Its location on human chromosome 1p36.33 implicates p73 as a candidate for neuroblastoma. Like neuroblastoma, oligodendrogliomas also show a high frequency of deletions in chromosome 1p36.3. To determine whetherp73is a potential tumor suppressor gene involved in the development of oligodendrogliomas, we performed mutation analysis ofp73in oligodendrogliomas with chromosome 1 p-arm deletions. We first determined the genomic organization and the intron–exon boundary sequences of thep73gene by long PCR, vectorette PCR, and Southern hybridization. This gene spans about 65 kb with a large first intron. Primer pairs for the amplification of each of the 13 p73 encoding exons were designed in corresponding introns. The amplicons were then analyzed using the denaturing high-performance liquid chromatography system for mutations in thep73gene. Twenty oligodendroglioma samples with 1p36.3 deletions were screened, but no mutations were detected except for several polymorphisms. It is thus clear thatp73is not a candidate gene for oligodendroglioma despite its location in the frequently deleted 1p36.3 region.     

Effects of ovariectomy of the dogfish Scyliorhinus canicula L. on circulating levels of androgen and oestradiol and on pituitary gonadotrophin content

Levels of androgens and oestradiol in dogfish, Scyliorhinus canicula , plasma, measured by radioimmunoassay, decrease markedly after ovariectomy (OVX). The magnitude and latency of these responses varies according to length of captivity preceding the operation and the time of year at which ovariectomy is performed. Androgens are cleared more rapidly than oestradiol from plasma following OVX, and levels of both steroids are reduced after laparotomy (LAP) in November but not in March. An extract of ventral lobes of the dogfish pituitary induces a significant increase in the circulating androgen levels in LAP fish but not in OVX fish, indicating that the ovary is the major site of androgen production in response to stimulation by dogfish gonadotrophin. Intramuscular injections of oestradiol benzoate (2.5 mg per fish) into LAP fish produce a significant reduction in the gonadotrophin content of the pituitary ventral lobe, measured in the quail testicular cell bioassay, when compared to LAP and unoperated controls. However, no significant changes in the gonadotrophin content of the ventral lobe were seen five days after OVX in June.     

Regional co-ordinator for haemophilia in domiciliary practice.

The North-east Thames Region has appointed a nursing sister to co-ordinate the organisation of care for haemophiliacs in the region. As a result of the appointment, facilities for home treatment have expanded rapidly. Several associate centres providing care to haemophiliacs have been set up around the region in addition to the four main haemophilia centres, which are all in the south-west corner of the region. As well as providing support and supervision of patients on home treatment, the co-ordinator helps to place haemophiliac children in suitable schools, maintains the regional register of haemophiliacs, and has a more general role in ensuring that services are available where they are needed throughout the region.     

Catchment areas in general practice and their relation to size and quality of practice and deprivation: a descriptive study in one London borough.

OBJECTIVE: To relate the sizes of general practice catchment areas in one London borough to list size, deprivation payments, medical staffing, and locally and nationally recognised measures of quality. DESIGN: Study of general practice catchment area maps. SETTING: London borough of Lambeth. SUBJECTS: 60 out of the 71 general practices in Lambeth. MAIN OUTCOME MEASURES: Practice catchment area size with corrections for numbers of doctors and patients. RESULTS: Catchment area size varied greatly between practices, showing an almost 150-fold difference between the largest and smallest practices. This size differential was even more marked when the size of the catchment area was corrected for the number of general practitioners in the practice, where a 300-fold difference was found. Substantial differences existed between practices in each of the four locally assigned quality bands. The weakest practices had catchment areas three times as large as those of the strongest practices. When corrected for medical staffing, the difference was eight times as great. A calculated measure of patient dispersion showed that the practice population of the strongest practices was four times as densely clustered as that of the weakest practices, whose patients were more widely geographically dispersed. CONCLUSIONS: Large variations exist in the size of catchment areas of inner city practices even when corrected for numbers of doctors and patients. These differences are associated with variations in quality of care.     

Phenotypic profiling of mGlu7 knockout mice reveals new implications for neurodevelopmental disorders

Neurodevelopmental disorders are characterized by deficits in communication, cognition, attention, social behavior and/or motor control. Previous studies have pointed to the involvement of genes that regulate synaptic structure and function in the pathogenesis of these disorders. One such gene, GRM7, encodes the metabotropic glutamate receptor 7 (mGlu₇), a G protein‐coupled receptor that regulates presynaptic neurotransmitter release. Mutations and polymorphisms in GRM7 have been associated with neurodevelopmental disorders in clinical populations; however, limited preclinical studies have evaluated mGlu₇ in the context of this specific disease class. Here, we show that the absence of mGlu₇ in mice is sufficient to alter phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep. Moreover, Grm7 knockout mice exhibit an attenuated response to amphetamine. These findings provide rationale for further investigation of mGlu₇ as a potential therapeutic target for neurodevelopmental disorders such as idiopathic autism, attention deficit hyperactivity disorder and Rett syndrome.     

Evolutionary temperature compensation of carbon fixation in marine phytoplankton

The efficiency of carbon sequestration by the biological pump could decline in the coming decades because respiration tends to increase more with temperature than photosynthesis. Despite these differences in the short‐term temperature sensitivities of photosynthesis and respiration, it remains unknown whether the long‐term impacts of global warming on metabolic rates of phytoplankton can be modulated by evolutionary adaptation. We found that respiration was consistently more temperature dependent than photosynthesis across 18 diverse marine phytoplankton, resulting in universal declines in the rate of carbon fixation with short‐term increases in temperature. Long‐term experimental evolution under high temperature reversed the short‐term stimulation of metabolic rates, resulting in increased rates of carbon fixation. Our findings suggest that thermal adaptation may therefore have an ameliorating impact on the efficiency of phytoplankton as primary mediators of the biological carbon pump.     

Slr4, a newly identified S-layer protein from marine Gammaproteobacteria,is a major biofilm matrix component

S-layers are paracrystalline proteinaceous lattices that surround prokaryotic cells, forming a critical interface between the cells and their extracellular environment. Here, we report the discovery of a novel S-layer protein present in the Gram-negative marine organism, Pseudoalteromonas tunicata D2. An uncharacterized protein (EAR28894) was identified as the most abundant protein in planktonic cultures and biofilms. Bioinformatic methods predicted a beta-helical structure for EAR28894 similar to the Caulobacter S-layer protein, RsaA, despite sharing less than 20% sequence identity. Transmission electron microscopy revealed that purified EAR28894 protein assembled into paracrystalline sheets with a unique square lattice symmetry and a unit cell spacing of ~9.1 nm. An S-layer was found surrounding the outer membrane in wild-type cells and completely removed from cells in an EAR28894 deletion mutant. S-layer material also appeared to be “shed” from wild-type cells and was highly abundant in the extracellular matrix where it is associated with outer membrane vesicles and other matrix components. EAR28894 and its homologs form a new family of S-layer proteins that are widely distributed in Gammaproteobacteria including species of Pseudoalteromonas and Vibrio, and found exclusively in marine metagenomes. We propose the name Slr4 for this novel protein family.