Linkage studies with chromosome 17 DNA markers in 45 neurofibromatosis 1 families

A locus for von Recklinghausen neurofibromatosis (NF1) has recently been mapped near the chromosome 17 centromere. We have extended these linkage studies by genotyping 45 NF1 families with three DNA probes known to be linked to the chromosome 17 centromeric region. Of 34 families informative for NF1 and at least one of the three probes, 28 families show no recombinants with the disease gene. These data provide additional support for genetic homogeneity of NF1 and for a primary NF1 locus linked to the chromosome 17 centromere. Among the informative families were 7 families with apparent new NF1 mutations. Our data suggest that these mutations are probably at the chromosome 17 NF1 locus.     

Atmin modulates Pkhd1 expression and may mediate Autosomal Recessive Polycystic Kidney Disease (ARPKD) through altered non-canonical Wnt/Planar Cell Polarity (PCP) signalling

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a genetic disorder with an incidence of ~1:20,000 that manifests in a wide range of renal and liver disease severity in human patients and can lead to perinatal mortality. ARPKD is caused by mutations in PKHD1, which encodes the large membrane protein, Fibrocystin, required for normal branching morphogenesis of the ureteric bud during embryonic renal development. The variation in ARPKD phenotype suggests that in addition to PKHD1 mutations, other genes may play a role, acting as modifiers of disease severity. One such pathway involves non-canonical Wnt/Planar Cell Polarity (PCP) signalling that has been associated with other cystic kidney diseases, but has not been investigated in ARPKD. Analysis of the Atmin^Gpg6 mouse showed kidney, liver and lung abnormalities, suggesting it as a novel mouse tool for the study of ARPKD. Further, modulation of Atmin affected Pkhd1 mRNA levels, altered non-canonical Wnt/PCP signalling and impacted cellular proliferation and adhesion, although Atmin does not bind directly to the C-terminus of Fibrocystin. Differences in ATMIN and VANGL2 expression were observed between normal human paediatric kidneys and age-matched ARPKD kidneys. Significant increases in ATMIN, WNT5A, VANGL2 and SCRIBBLE were seen in human ARPKD versus normal kidneys; no substantial differences were seen in DAAM2 or NPHP2. A striking increase in E-cadherin was also detected in ARPKD kidneys. This work indicates a novel role for non-canonical Wnt/PCP signalling in ARPKD and suggests ATMIN as a modulator of PKHD1.     

Movements of beluga whales (Delphinapterus leucas) in Bristol Bay,Alaska

We describe the annual distribution of beluga whales (Delphinapterus leucas) in Bristol Bay, Alaska, using data from 31 satellite‐linked transmitters during 2002–2011. Bristol Bay has one of the largest and best studied Pacific salmon (Oncorhynchus spp.) fisheries in the world, allowing us to link the seasonal distribution of belugas to that of salmon. During salmon migrations, beluga movements were restricted to river entrances. Belugas generally did not relocate to different river entrances or change bays during peak salmon periods. However, the location of belugas was not related to the number of salmon passing counting towers, suggesting that belugas were either selecting locations that were good for catching salmon or there were simply more salmon than belugas needed to supply their nutritional needs. The distribution of belugas expanded after salmon runs ended, and was greatest in winter when belugas ranged beyond the inner bays, traveling as far west as Cape Constantine. Belugas continued to frequent the inner bays in winter whenever sea ice conditions allowed, e.g., when winds moved sea ice offshore; however, they were never located south of the southern ice edge in open water or outside of Bristol Bay.     

Replication and fine mapping of asthma-associated loci in individuals of African ancestry

Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.     

Nicotinic Receptor-Mediated Release of Noradrenaline in the Human Neuroblastoma SH-SY5Y

Abstract: Dimethylphenylpiperazinium iodide (a nicotinic agonist) evokes noradrenaline release from human neuroblastoma SH-SY5Y cells that have been pretreated with 12- O -tetradecanoylphorbol 13-acetate for 8 min. This effect of dimethylphenylpiperazinium iodide was inhibited by 1 μ M mecamylamine but not by 1 μ M atropine, which suggests that SH-SY5Y cells express nicotinic receptors coupled to the release of noradrenaline. Dimethylphenylpiperazinium iodide-evoked release was enhanced by 5 μ M Bay K 8644 (an L-type calcium agonist) and inhibited by 1 μ M nifedipine. Dimethylphenylpiperazinium iodide depolarised SH-SY5Y cells and enhanced the level of intracellular calcium in cells loaded with fura 2. The effects of dimethylphenylpiperazinium iodide on noradrenaline release, depolarisation, and intracellular calcium levels were all inhibited by 1 μ M desmethylimipramine. The results of this study show that nicotinic receptors in SH-SY5Y cells stimulate noradrenaline release by activation of L-type calcium channels.     

Defective ion regulation in a class of membrane-excitation mutants in Paramecium

The “paranoiac” mutants of Paramecium aurelia show prolonged backward swimming in solutions containing Na⁺, unlike wild-type paramecia, which jerk back and forth in Na⁺ solutions. The paranoiac mutants in Na⁺ solutions also show large losses of cellular K⁺ and large influxes of Na⁺. Three different paranoiac mutants all show similar defects in ion regulation but to different degrees. Wild-type Paramecium, in contrast, shows no Na⁺-dependent loss of cellular K⁺ and a much smaller Na⁺ influx. In K⁺-containing solutions, there is no difference between wild-type and paranoiac paramecia with respect to their cellular K⁺ content.The Na⁺ influx, the K⁺ loss, and the duration of backward swimming are all proportional to the extracellular Na⁺ concentration. Electrophysiologically, the backward swimming of the paranoiac mutants corresponds to a prolonged depolarization of the membrane potential, while the backward jerks of wild-type Paramecium correspond to a series of transient depolarizations. We propose that the large Na⁺ influxes and the large K⁺ effluxes in paranoiacs occur during the periods of backward swimming, while the membrane is depolarized.     

Composition of cellulin,the unique chitin-glucan granules of the fungus,Apodachlya sp.

Cellulin granules, the polysaccharide inclusions found uniquely in oomycetous fungi of the order Leptomitales, were isolated from Apodachlya sp. The granules were prepared free of cell wall and cytoplasmic contaminants. Biochemical analyses and X-ray diffraction studies demonstrated that the granules were composed of 60% chitin and 39% glucan consisting of β-1,3-and β-1,6-linked glucose units. A protein content of only 0.1% was attributed to an insignificant amount of cytoplasmic contamination. Isolated granules and those in situ showed no apparent differences in their microscopic form.     

Zur Physiologie der Pollenkeimung bei Corylus avellana: Pollen- und Narbensaugkräfte. Quellungserscheinungen der Kolloide des Pollens

Ohne ZusammenfassungHerrn Dr. A. Frey-Wyssling, Zürich, bin ich für die kritische Durchsicht des Manuskriptes, Herrn Dr. E. Funk, St. Gallen, für Hilfe bei der Volumenberechnung des Protoplasten, Herrn Dr. E. Müller, Schaffhausen, für Beschaffung von Glaskammern, Herrn Dr. 0. Widmer, St. Gallen, für die Herstellung von Zuckerlösungen, Herrn Dr. E. Wieser, St. Gallen, für die mikrophotographischen Aufnahmen und Herrn Prof. Dr, M. Wildi, St. Gallen, für die Durchsicht der englischen Zusammenfassung zu großem Dank verpflichtet.     

Influence of Polymer Aggregation and Liquid Immiscibility on Morphology Tuning by Varying Composition in PffBT4T‐2DT/Nonfullerene Organic Solar Cells

The temperature‐dependent aggregation behavior of PffBT4T polymers used in organic solar cells plays a critical role in the formation of a favorable morphology in fullerene‐based devices. However, there is little investigation into the impact of donor/acceptor ratio on morphology tuning, especially for nonfullerene acceptors (NFAs). Herein, the influence of composition on morphology is reported for blends of PffBT4T‐2DT with two NFAs, O‐IDTBR and O‐IDFBR. The monotectic phase behavior inferred from differential scanning calorimetry provides qualitative insight into the interplay between solid–liquid and liquid–liquid demixing. Transient absorption spectroscopy suggests that geminate recombination dominates charge decay and that the decay rate is insensitive to composition, corroborated by negligible changes in open‐circuit voltage. Exciton lifetimes are also insensitive to composition, which is attributed to the signal being dominated by acceptor excitons which are formed and decay in domains of similar size and purity irrespective of composition. A hierarchical morphology is observed, where the composition dependence of size scales and scattering intensity from resonant soft X‐ray scattering (R‐SoXS) is dominated by variations in volume fractions of polymer/polymer‐rich domains. Results suggest an optimal morphology where polymer crystallite size and connectivity are balanced, ensuring a high probability of hole extraction via such domains.