Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway

Lethal congenital contractural syndrome type 2 (LCCS2) is an autosomal recessive neurogenic form of arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. We previously mapped LCCS2 to 6.4 Mb on chromosome 12q13 and have now narrowed the locus to 4.6 Mb. We show that the disease is caused by aberrant splicing of ERBB3, which leads to a predicted truncated protein. ERBB3 (Her3), an activator of the phosphatidylinositol-3-kinase/Akt pathway--regulating cell survival and vesicle trafficking--is essential for the generation of precursors of Schwann cells that normally accompany peripheral axons of motor neurons. Gain-of-function mutations in members of the epidermal growth-factor tyrosine kinase-receptor family have been associated with predilection to cancer. This is the first report of a human phenotype resulting from loss of function of a member of this group.     

Distinct and combined roles of the MAP kinases of Cochliobolus heterostrophus in virulence and stress responses

Pathogenicity mitogen-activated protein kinases (MAPKs), related to yeast FUS3/KSS1, are essential for virulence in fungi, including Cochliobolus heterostrophus, a necrotrophic pathogen causing Southern corn leaf blight. We compared the phenotypes of mutants in three MAPK genes: HOG1, MPS1, and CHK1. The chk1 and mps1 mutants show autolytic appearance, light pigmentation, and dramatic reduction in virulence and conidiation. Similarity of mps1 and chk1 mutants is reflected by coregulation by these two MAPKs of several genes. Unlike chk1, mps1 mutants are female-fertile and form normal-looking appressoria. HOG1 mediates resistance to hyperosmotic and, to a lesser extent, oxidative stress, and is required for stress upregulation of glycerol-3-phosphate phosphatase, transaldolase, and a monosaccharide transporter. Hog1, but not Mps1 or Chk1, was rapidly phosphorylated in response to increased osmolarity. The hog1 mutants have smaller appressoria and cause decreased disease symptoms on maize leaves. Surprisingly, loss of MPS1 in a wild-type or hog1 background improved resistance to some stresses. All three MAPKs contribute to the regulation of central developmental functions under normal and stress conditions, and full virulence cannot be achieved without appropriate input from all three pathways.     

Do phytoliths play an antiherbivory role in southwest Asian Asteraceae species and to what extent?

Phytoliths (silica bodies) occur in Poaceae species in large numbers and have been shown to have antiherbivory roles. However, phytoliths occur also in many other taxa in much smaller numbers, which raises the question of the extent of both their potential and actual antiherbivory role in these taxa. In order to address the question of their potential antiherbivory role, we sampled 20 wild-growing southwest Asian species of the family Asteraceae, species of which have a much lower phytolith concentrations than Poaceae taxa. We studied the potential positive effect of grazing on phytolith formation and the possible tendency of plants to have higher concentrations of such defence structures in their reproductive organs. We sampled plants from populations of 12 non-spiny and eight spiny species growing in un-grazed and grazed plots in seven sites along a large rainfall gradient (80–900 mm mean annual) in Israel, a region known for its long and intensive grazing history. The study included 21 pairs of un-grazed and grazed plants from 16 of these 20 species. In addition, ten populations of eight species were sampled in order to examine whether phytolith concentrations in the reproductive organs are higher than in vegetative organs. We did not find consistently higher phytolith concentrations in grazed plants compared to un-grazed plants of the same species and habitat (15 species), and in 12 out of 21 pairs of un-grazed and grazed plants (from 15 species) we even found higher phytolith concentrations in un-grazed plants, a phenomenon which was more common in the more arid sites. Phytolith concentrations in inflorescences are commonly (6 out of the 8 species) lower than in the rest of the shoot. We conclude that the antiherbivory potential of phytoliths in the southwest Asian Asteraceae as a group is much smaller than in the Poaceae.     

Cytokinetic abscission is an acute G1 event

Animal cell division ends with the cutting of the microtubule and membrane intercellular bridge connecting the 2 daughter cells. This process, known as cytokinetic abscission (abscission), is widely regarded as the last step of cytokinesis, i.e., the last step of the cell cycle. Major breakthroughs have been recently achieved, illuminating mechanistic aspects of abscission; however, the timing of abscission with respect to the mammalian cell cycle remains unclear. In this study, we carefully measured the onset and progression of abscission in dividing cells expressing a G1 reporter. We conclude that abscission commences long after cells enter the G1 phase. Affiliating abscission with G1 is beyond semantics since it essentially postulates that the last step of the cell cycle is regulated in, and probably by, the following cycle.     

Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy

The essential micronutrient selenium is found in proteins as selenocysteine (Sec), the only genetically encoded amino acid whose biosynthesis occurs on its cognate tRNA in humans. In the final step of selenocysteine formation, the essential enzyme SepSecS catalyzes the conversion of Sep-tRNA to Sec-tRNA. We demonstrate that SepSecS mutations cause autosomal-recessive progressive cerebellocerebral atrophy (PCCA) in Jews of Iraqi and Moroccan ancestry. Both founder mutations, common in these two populations, disrupt the sole route to the biosynthesis of the 21st amino acid, Sec, and thus to the generation of selenoproteins in humans.     

The Relationship between the Golden Spiny Mouse Circadian System and Its Diurnal Activity: An Experimental Field Enclosures and Laboratory Study

Examples of animals that switch activity times between nocturnality and diurnality in nature are relatively infrequent. Furthermore, the mechanism for switching activity time is not clear: does a complete inversion of the circadian system occur in conjunction with activity pattern? Are there switching centers downstream from the internal clock that interpret the clock differently? Or does the switch reflect a masking effect? Answering these key questions may shed light on the mechanisms regulating activity patterns and their evolution. The golden spiny mouse (Acomys russatus) can switch between nocturnal and diurnal activity. This study investigated the relationship between its internal circadian clock and its diurnal activity pattern observed in the field. The goal is to understand the mechanisms underlying species rhythm shifts in order to gain insight into the evolution of activity patterns. All golden spiny mice had opposite activity patterns in the field than those under controlled continuous dark conditions in the laboratory. Activity and body temperature patterns in the field were diurnal, while in the laboratory all individuals immediately showed a free‐running rhythm starting with a nocturnal pattern. No phase transients were found toward the preferred nocturnal activity pattern, as would be expected in the case of true entrainment. Moreover, the fact that the free‐running activity patterns began from the individuals' subjective night suggests that golden spiny mice are nocturnal and that their diurnality in their natural habitat in the field results from a change that is downstream to the internal clock or reflects a masking effect.     

High myopia caused by a mutation in LEPREL1, encoding prolyl 3-hydroxylase 2

Autosomal-recessive high-grade axial myopia was diagnosed in Bedouin Israeli consanguineous kindred. Some affected individuals also had variable expressivity of early-onset cataracts, peripheral vitreo-retinal degeneration, and secondary sight loss due to severe retinal detachments. Through genome-wide linkage analysis, the disease-associated gene was mapped to ～1.7 Mb on chromosome 3q28 (the maximum LOD score was 11.5 at θ = 0 for marker D3S1314). Sequencing of the entire coding regions and intron-exon boundaries of the six genes within the defined locus identified a single mutation (c.1523G>T) in exon 10 of LEPREL1, encoding prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The mutation affects a glycine that is conserved within P3H isozymes. Analysis of wild-type and p.Gly508Val (c.1523G>T) mutant recombinant P3H2 polypeptides expressed in insect cells showed that the mutation led to complete inactivation of P3H2.