Microbial starch-binding domains are superior to granule-bound starch synthase I for anchoring luciferase to potato starch granules

Microbial starch-binding domains (SBD) and granule-bound starch synthase I (GBSSI) are proteins which are accumulated in potato starch granules. The efficiency of SBD and GBSSI for targeting active luciferase reporter proteins to granules during starch biosynthesis was compared. GBSSI or SBD sequences were fused to the N- or C-terminus of the luciferase (LUC) gene, via an artificial Pro-Thr encoding linker sequence. The genes were introduced into an amylose-free (amf) potato mutant. It appeared that SBD was superior to GBSSI as a targeting sequence, mainly because the luciferase retained higher activity in the SBD-containing fusion proteins than in the GBSSI-containing ones.     

Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1

Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.     

Identification of SLC39A4, a gene involved in acrodermatitis enteropathica

We have characterized the human gene SLC39A4, which encodes a protein with features characteristic of a ZIP zinc transporter. The chromosomal location and expression of SLC39A4, together with mutational analysis of eight families affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally involved in the pathogenesis of this condition.     

Mutations in KERA, encoding keratocan, cause cornea plana

Specialized collagens and small leucine-rich proteoglycans (SLRPs) interact to produce the transparent corneal structure. In cornea plana, the forward convex curvature is flattened, leading to a decrease in refraction. A more severe, recessively inherited form (CNA2; MIM 217300) and a milder, dominantly inherited form (CNA1; MIM 121400) exist. CNA2 is a rare disorder with a worldwide distribution, but a high prevalence in the Finnish population. The gene mutated in CNA2 was assigned by linkage analysis to 12q (refs 4, 5), where there is a cluster of several SLRP genes. We cloned two additional SLRP genes highly expressed in cornea: KERA (encoding keratocan) in 12q and OGN (encoding osteoglycin) in 9q. Here we report mutations in KERA in 47 CNA2 patients: 46 Finnish patients are homozygous for a founder missense mutation, leading to the substitution of a highly conserved amino acid; and one American patient is homozygous for a mutation leading to a premature stop codon that truncates the KERA protein. Our data establish that mutations in KERA cause CNA2. CNA1 patients had no mutations in these proteoglycan genes.     

Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187.

Dominantly inherited familial amyloidosis, Finnish type (FAF) is caused by the accumulation of a 71-amino acid amyloidogenic fragment of mutant gelsolin (GSN). FAF is common in Finland but is very rare elsewhere. In Finland and in two American families, the mutation is a G654A transition leading to an Asp to Asn substitution at residue 187. We found the same mutation in a Dutch family but a Danish FAF family had a G654T mutation, predicting Asp to Tyr at residue 187. We also found the G654T transversion in a Czech family. Using GSN polymorphisms, different haplotypes were found in the Danish and Czech families. We conclude that substitution of the uncharged Asn or Tyr for the acidic Asp at residue 187 creates a conformation that may be preferentially amyloidogenic for GSN.     

On the Contribution of Wu Wen-Tsün to Algebraic Topology

The aim of this article is to present the contribution of Wu Wen-Tsün to Algebraic Topology and more precisely to the theory of characteristic classes. Several papers provide complete and welldocumented biography and academic career of Wu Wen-Tsün, in particular, Hudecek, 2014; O'Connor and Robertson, 2006; Wen-Tsün Wu's Academic Career, 2006; Selected works of Wen-Tsun Wu, 2008.The author does not repeat the details provided in these papers concerning the Wu Wen-Tsün's bibliography, we will just mention people involved in the Wu Wen-Tsün's period in France.In addition to Wu Wen-Tsün's papers, the Dieudonné's book(Dieudonné, 1960) provides an excellent presentation of main results of Wu Wen-Tsün in Algebraic and Differential Topology. The author will use and abuse of this book(and refer to) when suitable.In the introduction, the author recalls mainly historical facts concerning the contribution of Wu Wen-Tsün to Algebraic Topology. The second section shows speci?cally the contribution of Wu WenTsün to the Stiefel-Whitney classes and introduces the third section, dealing with the(real) Wu classes.The author provides de?nition, properties as well as further developments and generalizations of the Wu classes. The fourth and ?fth sections are devoted to recent applications: In Cobordism theory and in Mathematical Physics. The author notices that Wu classes have been used as well in other domains,in particular surgery theory(Madsen and Milgram, 1979). The last section concerns the complex Wu classes and shows that the more recent Mather classes coincide with the previously de?ned complex Wu classes, that is a result from Zhou(1994)(see also Liu, 1996).This article is devoted to the contribution of Wu Wen-Tsün to the theory of Characteristic Classes,which coincides with his "French period"(1947–1951). However, speaking of Algebraic Topology, it is worthwhile to mention the important contribution of Wu Wen-Tsün to the Theory of realization of complexes or manifolds in Euclidean spaces and of embedding classes. That coincides with his return to China(1956–1965).     

Photonics: tuning holes in photonic-crystal nanocavities

One challenge in photonics is strongly to confine light in small volumes in order to increase light-matter interaction. Akahane et al. propose a new concept for increasing the lifetime of this interaction, based on tailoring of the Fourier spectrum of cavity modes, which they believe is demonstrated by the surprising enhancement (roughly tenfold) of the quality factor Q of the cavity as a result of fine-tuning the mirror-hole geometry in a photonic-crystal nanocavity. Here we question the validity of their concept and argue that the improvement in Q is due to an increase in the impedance wave matching at the cavity edges and to a slow-wave effect. This alternative interpretation opens the way to new cavity designs.