Apolipoprotein A1 Baltimore (Arg10→Leu), a new ApoA1 variant

Summary A new apolipoprotein A1 (APOA1) gene variant has been identified in a family ascertained through a proband undergoing coronary angiography. The variant, ApoA1 Baltimore, was due to a mutation at codon 34 of the third exon of the APOA1 gene (CGA to CTA) that resulted in an arginine-to-leucine substitution at the tenth amino acid of the mature ApoA1 and a change in charge of -1. The mutation abolishes a TaqI restriction site and it is easily detectable after polymerase chain reaction amplification of genomic DNA. The proband was heterozygous for the mutation. Eight other members of the pedigree had the same ApoA1 variant. Cosegregation of the variant with hypoalphalipoproteinemia could not be demonstrated and the association of this mutation with hypoalphalipoproteinemia was confined to three affected members of the nuclear family. No effect of the mutant on any lipoprotein phenotype could be established.     

Modelling the presence of anchovy Engraulis encrasicolus in the Aegean Sea during early summer, based on satellite environmental data

Acoustic and satellite environmental data as well as bathymetry data were used to model the presence of anchovy, Engraulis encrasicolus during early summer in the northern Aegean Sea (Eastern Mediterranean). Generalized Additive Models (GAMs) were used for modelling and subsequently applied in a predictive mode to identify those areas in the Greek Seas and the entire Mediterranean basin that could support species’ presence. Model results were evaluated with the estimation of Receiver Operating Characteristic (ROC)-plots as well as qualitatively, based on (a) acoustic data from concurrent studies in certain areas of the northern Aegean Sea that were not included in the estimation of the GAM model and (b) historical acoustic data from the central Aegean and Ionian Seas. Mapping the estimated environmental conditions in the Mediterranean basin indicated areas that generally agree with the known distribution grounds of anchovy, such as the straits of Sicily and coastal waters of Tunisia, areas in the Tyrrhenian Sea, the Adriatic Sea, the Gulf of Lions and the Catalan Sea. Guest editor: V. D. Valavanis Essential Fish Habitat Mapping in the Mediterranean     

Gene therapy for achromatopsia

The present review summarizes the current status of achromatopsia (ACHM) gene therapy‐related research activities and provides an outlook for their clinical application. ACHM is an inherited eye disease characterized by a congenital absence of cone photoreceptor function. As a consequence, ACHM is associated with strongly impaired daylight vision, photophobia, nystagmus and a lack of color discrimination. Currently, six genes have been linked to ACHM. Up to 80% of the patients carry mutations in the genes CNGA3 and CNGB3 encoding the two subunits of the cone cyclic nucleotide‐gated channel. Various animal models of the disease have been established and their characterization has helped to increase our understanding of the pathophysiology associated with ACHM. With the advent of adeno‐associated virus vectors as valuable gene delivery tools for retinal photoreceptors, a number of promising gene supplementation therapy programs have been initiated. In recent years, huge progress has been made towards bringing a curative treatment for ACHM into clinics. The first clinical trials are ongoing or will be launched soon and are expected to contribute important data on the safety and efficacy of ACHM gene supplementation therapy.     

Citric acid production by Yarrowia lipolytica cultivated on olive-mill wastewater-based media

Yarrowia lipolytica ACA-DC 50109 cultivated on olive-mill wastewater (O.M.W.)-based media, enriched with commercial-industrial glucose, presented an efficient cell growth. Parameters of growth were unaffected by the presence of O.M.Ws in the growth medium. In diluted O.M.Ws enriched with high glucose amounts (initial sugar concentration, 65 g l(-1)), a notable quantity of total citric acid was produced (28.9 g l(-1)). O.M.W.-based media had a noteworthy stimulating effect on the production of citric acid, since both final citric acid concentration and conversion yield of citric acid produced per unit of sugar consumed were higher when compared with the respective parameters obtained from trials without added O.M.W. Adaptation of the strain in O.M.W.-based media favoured the biosynthesis of cellular unsaturated fatty acids (principally of oleic and palmitoleic acids). Additionally, a non-negligible decrease of the phenolic compounds in the growth medium [up to 15% (wt/wt)], a slight decrease of the phyto-toxicity, and a remarkable decolourisation of the O.M.W. were observed. All these results suggest the potentiality of O.M.Ws utilisation in the fermentation process of citric acid production.     

Neuropeptide Y Activates Protein Kinase C in Hamster Suprachiasmatic Nuclei Brain Slices

The mammalian circadian clock in the suprachiasmatic nuclei (SCN) can be phase-shifted by neuropeptide Y applied in the subjective day. Previous studies suggested that neuropeptide Y might act through a protein kinase C (PKC)-dependent mechanism. We directly measured PKC activity in suprachiasmatic nuclei brain slices following application of neuropeptide Y. PKC activity increased 5 min after neuropeptide Y application, with a return to baseline levels 15 min after application. An initial small decrease in PKC activity 1 min after neuropeptide Y application was also observed after control applications of artificial cerebrospinal fluid. Our results support the hypothesis that phase shifts induced by neuropeptide Y involve activation of PKC.     

Chromosome 21 and down syndrome: from genomics to pathophysiology

The sequence of chromosome 21 was a turning point for the understanding of Down syndrome. Comparative genomics is beginning to identify the functional components of the chromosome and that in turn will set the stage for the functional characterization of the sequences. Animal models combined with genome-wide analytical methods have proved indispensable for unravelling the mysteries of gene dosage imbalance.     

Linearization and purification of BAC DNA for the development of transgenic mice

Bacterial artificial chromosome (BAC) vectors are increasingly used for generation of transgenic mice due to the relatively large size and the stability of their inserts compared to YACs. We have compared methods for purification and linearization of BACs, and describe an optimised protocol for preparation of high quality linear BAC DNA based on terminase digestion, electroelution of linearized DNA together with simple preliminary multiplex PCR screening to detect transgenic mice. Linearized BAC DNA purified this way was successfully used for the development of transgenic mice containing 2–4 copies of the transgene.     

Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors

In some Palestinian communities, the prevalence of inherited prelingual deafness is among the highest in the world. As an initial step towards understanding the genetic causes of hearing loss in the Palestinian population, 48 independently ascertained probands with non-syndromic hearing loss were evaluated for mutations in the connexin 26 gene. Of the 48 deaf probands, 11 (23%) were homozygous or compound heterozygous for mutations in GJB2. Five different mutations were identified: ivs1(+1) G-->A, 35delG, 167delT, T229C, 235delC. Nine deaf probands were homozygous and only two compound heterozygous. Among 400 hearing Palestinian controls, one carrier was observed (for 167delT). We show that GJB2 ivs1(+1) G-->A disrupts splicing, yielding no detectable message. Linkage disequilibrium analysis suggests, in the Palestinian and Israeli populations, a common origin of the 35delG mutation, which is worldwide, and of 167delT, which appears specific to Israeli Ashkenazi and Palestinian populations. A high prevalence of deafness, high frequency of homozygosity rather than compound heterozygosity among deaf, and low mutation carrier frequency together reflect the high levels of consanguinity of many extended Palestinian families. Some of the 25 families with multiple cases of inherited prelingual deafness and wildtype GJB2 sequences may represent as-yet-unknown genes for inherited hearing loss.