Author Correction: mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis.

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mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis.

mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.

Distinguishing the effects of selection from demographic history in the genetic variation of two sister passerines based on mitochondrial-nuclear comparison.

Determining the mechanisms responsible for the distribution of genetic diversity in natural populations has occupied a central role in molecular evolution. Our study was motivated by the unprecedented observation that a widespread Eurasian flycatcher, Ficedula albicilla, exhibited no variation at the mitochondrial DNA (mtDNA) ND2 gene in 75 individuals sampled over a 5000-km distance. In contrast, its sister species, F. parva, had low but considerably higher levels of mtDNA variation. We assessed whether natural selection or demographic factors could explain the absence of mtDNA variation in F. albicilla. Eighteen nuclear genes were sequenced to estimate the two species' phylogeographic histories, and for comparison to the mtDNA data. Multilocus coalescence analyses suggested that F. albicilla experienced a population expansion perhaps following a population bottleneck. Simulations based on this demographic history, however, did not replicate the extremely low level of mtDNA variation. Historical range changes based on ecological niche models also failed to explain the observed mtDNA patterns. Neutrality tests (DHEW and ML-HKA) suggested a non-neutral pattern in the mtDNA of F. albicilla. We found a transmembrane-skewed distribution of nonsynonymous substitutions between the two species, three of which caused functional change; the results implied that positive selection could have targeted mtDNA. Several lines of evidence support selection rather than demographic history as the main force influencing the patterns of mtDNA variation. Despite the influence of natural selection, many of the phylogeographic inferences derived from mtDNA were robust, including species limits and a high level of gene flow among populations within species.

Detection and identification of occult HBV in blood donors in Taiwan using a commercial, multiplex, multi-dye nucleic acid amplification technology screening test.

BACKGROUND: The ability of a new generation commercial, multiplex, multi-dye test from Roche, the cobas TaqScreen MPX test, version 2.0, to detect and identify occult HBV infections was evaluated using routine donor samples from Kaohsiung Blood Bank, Taiwan. STUDY DESIGN AND METHODS: A total of 5973 samples were tested by nucleic acid amplification technology (NAT); 5898 in pools of six, 66 in pools of less than six and nine samples individually. NAT-reactive samples were retested with alternative NAT tests, and follow-up samples from the donors were tested individually by NAT and for all the HBV serological markers. RESULTS: Eight NAT-only-reactive donors were identified, and follow-up samples were obtained from six of the donors. The results indicated that all eight donors had an occult HBV infection with viral loads <12 IU/ml. CONCLUSION: The cobas(®) TaqScreen MPX test, version 2.0, has an advantage over the current Roche blood screening test, the cobas TaqScreen MPX test, for screening donations in countries with a high prevalence of occult HBV infections since the uncertainty associated with identifying samples with very low viremia is removed by the ability of the test to identify the viral target in samples that are reactive with the cobas TaqScreen MPX test, version 2.0.

The origin of photovoltaic responses in BiFeO3 multiferroic ceramics.

Multiferroic BiFeO(3) (BFO) ceramics with electrodes of indium tin oxide (ITO) and Au thin films exhibit significant photovoltaic effects under near-ultraviolet illumination (λ = 405 nm) and show strong dependences on light wavelength, illumination intensity, and sample thickness. The correlation between photovoltaic responses and illumination intensity can be attributed to photo-excited and thermally generated charge carriers in the interface depletion region between BFO ceramic and ITO thin film. A theoretical model is developed to describe the open-circuit photovoltage and short-circuit photocurrent density as a function of illumination intensity. This model can be applied to the photovoltaic effects in p-n junction type BFO thin films and other systems. The BFO ceramic exhibits stronger photovoltaic responses than the ferroelectric Pb(1-x)La(x)(Zr(y)Ti(1-y))(1-x/4)O(3) (PLZT) ceramics under near-ultraviolet illumination. Comparisons are made with other systems and models for the photovoltaic effect.

Functional characterisation of a complex mutation in the α(1,4)galactosyltransferase gene in Taiwanese individuals with p phenotype.

BACKGROUND AND OBJECTIVE: Individuals with p phenotype lack P1, P(k) and P antigens on red blood cells, presumably as a result of deficiency in the enzyme α(1,4)galactosyltransferase (A4GALT). The aim of this study was to explore the molecular background of a Taiwanese family with p phenotype. MATERIALS AND METHODS: Blood samples from two p siblings and seven family members were investigated. The coding region of the A4GALT gene was analysed by polymerase chain reaction and direct sequencing. The wild- and mutant-complementary DNAs (cDNAs) of A4GALT were cloned into an expression vector and transfected to Chinese hamster ovary (CHO) cells. P(k) expression on the transfected cells was analysed by flow cytometry and the activities of A4GALT were measured by high-performance liquid chromatography. RESULTS: The two individuals with p phenotype were homozygous for the complex mutation, which was caused by a combined deletion and insertion between nt 418 and 428. No expression of P(k) and no enzyme activity were observed in cells transfected with the mutant construct. CONCLUSION: The first case of p phenotype in Taiwan was caused by a non-functional allele resulting from a homozygous complex mutation of A4GALT gene.

Congenital cutaneous mucinosis with spontaneous regression: an atypical cutaneous mucinosis of infancy?

The nomenclature and classification of cutaneous mucinosis is quite complex. An updated classification of idiopathic cutaneous mucinosis (lichen myxoedematosus), included three clinicopathological subsets: a generalized papular and sclerodermoid form, a localized papular form, and an atypical or intermediate form. Cutaneous mucinosis occurring in infancy is very rare. We report a 7-month-old boy with a history of multiple opalescent papules over his fingers and toes since birth. The lesions spontaneously regressed and became indiscernible after 5 years of clinical follow-up. The condition was similar to cutaneous mucinosis of infancy but was also unique because of its spontaneous regression and acral location.

Transplant of cultured autologous pure melanocytes after laser-abrasion for the treatment of segmental vitiligo.

Segmental vitiligo is a special type of vitiligo with unilateral distribution of lesions and has a stable course. Clinically, many patients with segmental vitiligo have unsatisfactory responses to topical corticosteroid or UV phototherapy. We have developed a technique for the isolation of melanocytes from a small specimen of normally pigmented skin obtained via a suction blister. The melanocytes can be proliferated in culture and then replanted onto laser-abrased vitiliginous areas. We used this procedure to treat 25 patients with segmental vitiligo that were refractory to medical therapy. The repigmented portion of the total treated area amounted to 95-100% in 21 patients and 65 to 94% in 4 patients. The response rate to treatment was 100% in this study. No scarring or other side-effects developed. The results of this study demonstrate that this method is a valuable tool for the treatment of patients with segmental vitiligo.

Growth hormone gene polymorphisms and growth performance traits in Duroc, Landrace and Tao-Yuan pigs.

This study investigated the restriction fragment length polymorphism (RFLP) of the porcine growth hormone (pGH) gene in Duroc, Landrace, and Tao-Yuan pigs and its effects on growth performance and levels of plasma growth hormone in peripheral circulation. Genomic DNA extracted from 81 Tao-Yuan, 60 Landrace and 48 Duroc pigs were subjected to Southern blot hybridization with a pGH cDNA probe. Polymorphism was detected with the restriction enzymes TaqI and DraI. A comparison of these three breeds showed significant differences in allelic frequencies. Blood samples for radioimmunoassay (RIA) of GH were collected biweekly during the experimental period from pigs 12 to 40 weeks of age. Tao-Yuan pigs showed a mean plasma GH level (2.51 +/- 1.23 ng/mL) that was much lower than that of the Landrace (3.80 +/- 1.52 ng/mL) and Duroc (4.20 +/- 1.03 ng/mL) pigs (P < 0.05). Moreover, the Tao-Yuan pigs also showed poorer growth performance than the Landrace and the Duroc pigs both in the daily weight gain (0.37 +/- 0.06 vs. 0.67 +/- 0.05 and 0.70 +/- 0.05 kg/day, P < 0.01) and feed efficiency (3.12 +/- 0.28 vs. 2.60 +/- 0.14 and 2.52 +/- 0.12, P < 0.05). These results suggest that the growth performance trait in these pigs is highly correlated with their growth hormone genotype.

Gender determination in single bovine blastomeres by polymerase chain reaction amplification of sex-specific polymorphic fragments in the amelogenin gene.

A sensitive technique for the sexing of bovine embryos was developed using polymerase chain reaction (PCR) amplification of the bovine amelogenin (bAML) gene on the X- and Y-chromosomes of Holstein dairy cattle. Cloning and DNA sequencing showed a 45.1% homology between the fifth intron of the bAML-X and bAML-Y gene with multiple deletions. A pair of sex-specific primers was designed to allow amplification of a single fragment of 467-bp from the X-chromosome of female cattle and two fragments of 467-bp and 341-bp from the X- and Y-chromosomes of male cattle. The primers were successfully applied to bovine sexing from single blastomeres isolated from day-6 to day-7 cow embryos by direct cell lysis and PCR. Our protocol of embryo sexing should be applicable to the diagnosis of defective genes in vitro in human embryos and in other domestic or recreational animals.