Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes

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江西吉安灰头麦鸡的繁殖生态研究

灰头麦鸡Vanellus cinereus在江西吉安地区是夏候鸟.2010 ～2011年对当地灰头麦鸡的繁殖生态进行了调查研究.结果表明,当地灰头麦鸡最早2月20日迁入,最晚9月17日迁离,居留时间约为7个月;3月初开始产卵,平均窝卵数3.8枚(n=14),平均卵大小48.0 mm×34.5 mm,平均卵重28.8 g(n =38);产满窝卵后即开始孵卵,孵卵由雌雄鸟共同承担;孵卵期为28 ～31 d;孵化率为90.15％.     

Therapeutic and pharmacokinetic characterizations of an anti-amyloidogenic bis-styrylbenzene derivative for Alzheimer’s disease treatment

Alzheimer’s disease drug discovery regarding exploration into the molecules and processes has focused on the intrinsic causes of the brain disorder correlated with the accumulation of amyloid-β. An anti-amyloidogenic bis-styrylbenzene derivative, KMS80013, showed excellent oral bioavailability (F = 46.2%), facilitated brain penetration (26%, iv) in mouse and target specific in vivo efficacy in acute AD mouse model attenuating the cognitive deficiency in Y-maze test. Acute toxicity (LD₅₀ >2000 mg/kg) and hERG channel inhibition (14% at 10 μM) results indicated safety of KMS80013.     

An Excitatory Neural Assembly Encodes Short-Term Memory in the Prefrontal Cortex

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Proteomic analysis of castor bean tick Ixodes ricinus: a focus on chemosensory organs

In arthropods, the large majority of studies on olfaction have been focused on insects, where most of the proteins involved have been identified. In particular, chemosensing in insects relies on two families of membrane receptors, olfactory/gustatory receptors (ORs/GRs) and ionotropic receptors (IRs), and two classes of soluble proteins, odorant-binding proteins (OBPs) and chemosensory proteins (CSPs). In other arthropods, such as ticks and mites, only IRs have been identified, while genes encoding for OBPs and CSPs are absent. A third class of soluble proteins, called Niemann-Pick C2 (NPC2) has been suggested as potential carrier for semiochemicals both in insects and other arthropods.Here we report the results of a proteomic analysis on olfactory organs (Haller's organ and palps) and control tissues of the tick Ixodes ricinus, and of immunostaining experiments targeting NPC2s. Adopting different extraction and proteomic approaches, we identified a large number of proteins, and highlighted those differentially expressed. None of the 13 NPC2s known for this species was found. On the other hand, using immunocytochemistry, we detected reaction against one NPC2 in the Haller's organ and palp sensilla. We hypothesized that the low concentration of such proteins in the tick's tissues could possibly explain the discrepant results. In ligand-binding assays the corresponding recombinant NPC2 showed good affinity to the fluorescent probe N-phenylnaphthylamine and to few organic compounds, supporting a putative role of NPC2s as odorant carriers.     

Thyreophoran vertebrae from the Callovian (Middle Jurassic) of the Vaches Noires cliffs (Normandy,France), with remarks on the dinosaur assemblage from the Vaches Noires

Two associated incomplete thyreophoran dorsal vertebrae from the Callovian Marnes de Dives Formation of the Vaches Noires cliffs, on the Normandy coast, are referred to an indeterminate stegosaur that appears to be different from Lexovisaurus, previously reported from the Callovian of western France. These vertebrae are the first evidence of thyreophorans from the Vaches Noires and complement the dinosaur assemblage from this locality, which hitherto consisted of several theropod taxa and an indeterminate sauropod. The dinosaur record from the Vaches Noires is heavily dominated by theropods and this imbalance is difficult to explain. A possible explanation may be that the dinosaur sample from the Vaches Noires is too small to be statistically significant and representative of the original faunal assemblage from which it is derived.     

不同海拔梯度高寒草地地下生物量与环境因子的关系

以新疆天山南坡的巴音布鲁克高寒草地为对象, 研究了不同海拔梯度高寒草地地下生物量的变化及其与环境因子的关系.结果表明: 随着海拔的升高, 高寒草原、高寒草原化草甸和高寒草甸的地下生物量逐渐增大, 二者呈极显著正相关( P<0.01 ).地下生物量从表层至底层逐渐递减,呈“T”形分布.高寒草原、高寒草原化草甸和高寒草甸0～10 cm土层的地下生物量分别占总地下生物量的68.1%、84.1%和86.7%.地下生物量与大气温度呈极显著负相关, 与相对湿度和土壤含水量呈极显著正相关(P<0.01 ), 而与有机质、速效氮和pH等无显著相关.     

Conodont biostratigraphy of Tournaisian shallow-water carbonates in central Guangxi,South China

The conodont faunas of Tournaisian shallow-water carbonates from central Guangxi are described mainly for biostratigraphic purposes. A complete series of samples was collected from the Long’an and Du’an formations in the Long’an section. These formations are characterized by lime-mudstone, skeletal and peloidal wackestone, packstone and grainstone with typical shallow-water biota. Overall, these samples produced 809 identifiable Pl elements, belonging to 50 species in 11 genera, of which one species and one subspecies are new. The fauna enables the establishment of seven biozones (in ascending order): Polygnathus spicatus, Siphonodella homosimplex, S. sinensis, S. dasaibaensis, Polygnathus communis carina Acme, Gnathodus cuneiformis, and P. communis porcatus zones. Based on these new collections from central Guangxi and on data from the literature, a conflated Tournaisian conodont zonation is proposed for shallow-water successions in South China. Most of the conodont zones correlate well with their counterparts recognized in Western Europe, which may be of greater significance in stratigraphic correlation than previously thought.     

Anilinotriazoles as potent gamma secretase modulators

The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile.     

Genetic factors in individual radiation sensitivity

Cancer risk and radiation sensitivity are often associated with alterations in DNA repair, cell cycle, or apoptotic pathways. Interindividual variability in mutagen or radiation sensitivity and in cancer susceptibility may also be traced back to polymorphisms of genes affecting e.g. DNA repair capacity. We studied possible associations between 70 polymorphisms of 12 DNA repair genes with basal and initial DNA damage and with repair thereof. We investigated DNA damage induced by ionizing radiation in lymphocytes isolated from 177 young lung cancer patients and 169 cancer-free controls. We also sought replication of our findings in an independent sample of 175 families (in total 798 individuals). DNA damage was assessed by the Olive tail moment (OTM) of the comet assay. DNA repair capacity (DRC) was determined for 10, 30 and, 60 min of repair.Genes involved in the single-strand-repair pathway (SSR; like XRCC1 and MSH2) as well as genes involved in the double-strand-repair pathway (DSR; like RAD50, XRCC4, MRE11 and ATM) were found to be associated with DNA damage. The most significant association was observed for marker rs3213334 (p = 0.005) of XRCC1 with basal DNA damage (B), in both cases and controls. A clear additive effect on the logarithm of OTM was identified for the marker rs1001581 of the same LD-block (p = 0.039): B_CC = −1.06 (95%-CI: −1.16 to −0.96), B_CT = −1.02 (95%-CI: −1.11 to −0.93) and B_TT = −0.85 (95%-CI: −1.01 to −0.68). In both cases and controls, we observed significantly higher DNA basal damage (p = 0.007) for carriers of the genotype AA of marker rs2237060 of RAD50 (involved in DSR). However, this could not be replicated in the sample of families (p = 0.781). An alteration to DRC after 30 min of repair with respect to cases was observed as borderline significant for marker rs611646 of ATM (involved in DSR; p = 0.055), but was the most significant finding in the sample of families (p = 0.009).Our data indicate that gene variation impacts measurably on DNA damage and repair, suggesting at least a partial contribution to radiation sensitivity and lung cancer susceptibility.