Physiology. Cold current in thermoreceptive neurons

We sense the temperature of our skin and surroundings using specific thermoreceptors, which are sensitive to cold and warmth, but little is known about how these receptors transduce temperature into electrical activity. We have discovered an inward ionic current that is activated by moderate cooling in a small number of rat sensory neurons. This current has features that are found in intact cold receptors, including sensitization by menthol, adaptation upon sustained cooling, and modulation by calcium, and is likely to be important in cold sensing.     

Pixel switching of epitaxial Pd/YHx/CaF2 switchable mirrors

Exposure of rare-earth films to hydrogen can induce a metal-insulator transition, accompanied by pronounced optical changes. This 'switchable mirror' effect has received considerable attention from theoretical, experimental and technological points of view. Most systems use polycrystalline films, but the synthesis of yttrium-based epitaxial switchable mirrors has also been reported. The latter form an extended self-organized ridge network during initial hydrogen loading, which results in the creation of micrometre-sized triangular domains. Here we observe homogeneous and essentially independent optical switching of individual domains in epitaxial switchable mirrors during hydrogen absorption. The optical switching is accompanied by topographical changes as the domains sequentially expand and contract; the ridges block lateral hydrogen diffusion and serve as a microscopic lubricant for the domain oscillations. We observe the correlated changes in topology and optical properties using in situ atomic force and optical microscopy. Single-domain phase switching is not observed in polycrystalline films, which are optically homogeneous. The ability to generate a tunable, dense pattern of switchable pixels is of technological relevance for solid-state displays based on switchable mirrors.     

大叶白麻叶化学成分的研究

从大叶白麻[poacynumhendersonii(Hookf)woodson]叶中分得2个木脂素类化舍物,经理化常数测定和光谱分析,分别鉴定为(-)-丁香脂素[(-)-Syringaresino1]和( )-松脂素-4-O-β-D-葡萄糖甙[( )-Pinoresionol-4-0-β-D-glucopyranoside].     

Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA

The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism. Correspondingly, loss of function of PTEN, a negative regulator of PI3K, or activating mutations in AKT1, AKT2 or AKT3 have been found in distinct disorders featuring overgrowth or hypoglycemia. We performed exome sequencing of DNA from unaffected and affected cells from an individual with an unclassified syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified the cancer-associated mutation encoding p.His1047Leu in PIK3CA, the gene that encodes the p110α catalytic subunit of PI3K, only in affected cells. Sequencing of PIK3CA in ten additional individuals with overlapping syndromes identified either the p.His1047Leu alteration or a second cancer-associated alteration, p.His1047Arg, in nine cases. Affected dermal fibroblasts showed enhanced basal and epidermal growth factor (EGF)-stimulated phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) generation and concomitant activation of downstream signaling relative to their unaffected counterparts. Our findings characterize a distinct overgrowth syndrome, biochemically demonstrate activation of PI3K signaling and thereby identify a rational therapeutic target.     

Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer

PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN) in seven families affected with Fanconi anemia and cancer in early childhood, demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer.     

PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene

PALB2 interacts with BRCA2, and biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia. We identified monoallelic truncating PALB2 mutations in 10/923 individuals with familial breast cancer compared with 0/1,084 controls (P = 0.0004) and show that such mutations confer a 2.3-fold higher risk of breast cancer (95% confidence interval (c.i.) = 1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition.     

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and found heterozygous and mosaic mutations in PORCN in other affected females and males, respectively. PORCN encodes the human homolog of Drosophila melanogaster porcupine, an endoplasmic reticulum protein involved in secretion of Wnt proteins.