Identifying autism loci and genes by tracing recent shared ancestry

To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of "homozygosity mapping" in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations.     

Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.     

Effect of tilmicosin on chemotactic, phagocytic, and bactericidal activities of bovine and porcine alveolar macrophages

OBJECTIVE: To evaluate chemotactic, phagocytic, and bactericidal activities of bovine and porcine alveolar macrophages (AM) exposed to tilmicosin. ANIMALS: 12 healthy calves and 12 healthy pigs. PROCEDURES: Lungs were obtained immediately after euthanasia; AM were collected by means of bronchoalveolar lavage and density gradient centrifugation. Chemotactic activity was evaluated by exposing AM to lipopolysaccharide or macrophage inhibitory peptide during incubation with tilmicosin. Phagocytic activity was evaluated by incubating AM with tilmicosin for 24 hours and then with tilmicosin-resistant Salmonella serotype Typhimurium. Bactericidal activity was evaluated by incubating AM with tilmicosin (0, 10, or 20 microg/ml for bovine AM; 0 or 10 microg/ml or 10 microg/ml but washed free of tilmicosin for porcine AM) and then with Mannheimia haemolytica (bovine AM) or with Actinobacillus pleuropneumoniae or Pasteurella multocida (porcine AM). RESULTS: Tilmicosin had no significant effects on chemotactic or phagocytic activities of bovine or porcine AM. The time-course of bactericidal activity was best described by polynomial equations. Time to cessation of bacterial growth and area under the time versus bacterial number curve were significantly affected by incubation of AM with tilmicosin. CONCLUSIONS AND CLINICAL RELEVANCE: Results show that bactericidal activity of bovine and porcine AM was enhanced by tilmicosin, but not in proportion to the reported ability of AM to concentrate tilmicosin intracellularly. With or without exposure to tilmicosin, the time-course of bactericidal activity of bovine AM against M haemolytica and of porcine AM against A pleuropneumoniae or P multocida was too complex to be reduced to a simple linear equation.     

Assessing common bottlenose dolphin (Tursiops truncatus) population structure in Mississippi Sound and coastal waters of the north central Gulf of Mexico

1. Population structure of highly mobile marine organisms can be complex and difficult to study, but it is important to understand how populations partition themselves within their environment for accurate assessment of both natural and anthropogenic impacts and successful management. The 2010 Deepwater Horizon oil spill negatively impacted common bottlenose dolphins (Tursiops truncatus) within Mississippi Sound and the surrounding north central Gulf of Mexico (GOMx); however, little was known about their underlying population structure in these waters. Thus, it was unclear how many demographically independent populations were affected by the spill.
2. Common bottlenose dolphin samples were collected throughout inshore waters of Mississippi Sound and coastal waters of the north-central GOMx. Mitochondrial DNA control region sequence data and 19 nuclear microsatellite loci were analysed to determine how many populations are present and characterize their range throughout these waters.
3. Bayesian clustering and migration analyses identified two genetically distinct and demographically independent populations: one predominantly inhabiting Mississippi Sound and adjacent coastal waters, and a second population extending generally from offshore of Mobile Bay, Alabama, east along the Florida Panhandle. Neither of these populations align with the currently delineated management stocks previously used to estimate impacts from the oil spill on common bottlenose dolphins in this portion of the GOMx.
4. These results suggest that revisions may be necessary so that management stocks accurately represent the demographically independent populations present in these waters. Furthermore, better comprehension of underlying population structure will enhance impact assessments on common bottlenose dolphins and provide more appropriate baseline data to support future restoration and conservation objectives.

     

A Mycobacterium leprae-specific human T cell epitope cross-reactive with an HLA-DR2 peptide

Mycobacterium leprae induces T cell reactivity and protective immunity in the majority of exposed individuals, but the minority that develop leprosy exhibit various types of immunopathology. Thus, the definition of epitopes on M. leprae antigens that are recognized by T cells from different individuals might result in the development of an effective vaccine against leprosy. A sequence from the 65-kD protein of this organism was recognized by two HLA-DR2-restricted, M. leprae-specific helper T cell clones that were derived from a tuberculoid leprosy patient. Synthetic peptides were used to define this epitope as Leu-Gln-Ala-Ala-Pro-Ala-Leu-Asp-Lys-Leu. A similar peptide that was derived from the third hypervariable region of the HLA-DR2 chain, Glu-Gln-Ala-Arg-Ala-Ala-Val-Asp-Thr-Tyr, also activated the same clones. The unexpected cross-reactivity of this M. leprae-specific DR2-restricted T cell epitope with a DR2 peptide may have to be considered in the design of subunit vaccines against leprosy.     

A high-resolution paleoclimate record spanning the past 25,000 years in southern East Africa

High-resolution profiles of the mass accumulation rate of biogenic silica and other geochemical proxies in two piston cores from northern Lake Malawi provide a climate signal for this part of tropical Africa spanning the past 25,000 years. The biogenic silica mass accumulation rate was low during the relatively dry late Pleistocene, when the river flux of silica to the lake was suppressed. Millennial-scale fluctuations, due to upwelling intensity, in the late Pleistocene climate of the Lake Malawi basin appear to have been closely linked to the Northern Hemisphere climate until 11 thousand years ago. Relatively cold conditions in the Northern Hemisphere coincided with more frequent north winds over the Malawi basin, perhaps resulting from a more southward migration of the Intertropical Convergence Zone.     

Investigations into the thiamine and riboflavin content of malt and the effects of malting and roasting on their final content

A simple and effective method for the analysis of thiamine (B₁) and riboflavin (B₂) vitamers, in unmalted and malted grains, by high performance liquid chromatography (HPLC) has been developed. This method makes use of trichloroacetic acid (TCA) as an extraction medium to effectively clean up the sample and analyze the vitamer content with high accuracy (R² > 0.9992; %RSD < 5%). This method was employed in the routine analysis of a wide range of malted and unmalted grains, and it was found that lighter colored malts contain higher concentrations (2–5 times higher) of thiamine and riboflavin vitamers compared to darker colored malts. The malting process has no effect on the overall riboflavin content; however, both steeping and kilning processes cause increases in thiamine vitamer content. Roasting profiles show that thiamine and riboflavin vitamer concentrations are significantly effected when the temperature reaches 120 °C, which explains why roasted products have lower vitamer content than paler malts.     

ACC合成酶和ACC氧化酶基因家族在番茄乙烯过表达突变体Epinastics果实中的差别表达(英文)

利用 Ｎｏｒｔｈｅｒｎ 杂交和核酸保护分析（ＲＰＡ）检测了番茄ＡＣＣ 合成酶（ＡＣＳ）和 ＡＣＣ氧化酶（ＡＣＯ）基因家族在番茄突变体Ｅｐｉｎａｓｔｉｃｓ （Ｅｐｉ）果实中的表达特性,同时测定了Ｅｐｉ果实自动催化乙烯合成系统的特性⒚ＥＰＩ等位基因的突变诱导了ＬＥＡＣＳ２ 和ＬＥＡＣＯ１ 两个基因的过表达,这是Ｅｐｉ果实的乙烯过表达的主要成因⒚ＥＰＩ突变同时显著抑制了ＬＥＡＣＳ４ 和 ＬＥＡＣＯ３ 的表达强度⒚这些结果初步鉴别了这两个基因家族在番茄果实上表达的各个成员的转录调节途径⒚同时表明,番茄单基因乙烯反应突变体是研究ＡＣＳ和ＡＣＯ基因家族各成员转录调节特性的一种有用工具⒚