Unsaturated 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholines (unsaturated platelet-activating factor): aggregation of human platelets after incubation with indomethacin, creatinephosphate/creatinephosphokinase, xylocain and hirudine, and serotonin release after incubation with indomethacin

Unsaturated platelet-activating factor (PAF) aggregates thrombocytes of healthy female volunteers and releases within 1 min up to 30.95% of the platelet serotonin. Indomethacin does not inhibit the aggregation but reduces the release of serotonin induced by unsaturated PAF in citrated platelet-rich plasma (PRP). Creatinephosphate combined with creatinephosphokinase (CP/CPK) inhibits the second phase, whereas xylocain inhibits the first and second phase of aggregation induced by unsaturated PAF. Hirudine shows no influence on the aggregation induced by unsaturated PAF.     

High-throughput screening of the yeast kinome: identification of human serine/threonine protein kinases that phosphorylate the hepatitis C virus NS5A protein

The hepatitis C virus NS5A protein plays a critical role in virus replication, conferring interferon resistance to the virus through perturbation of multiple intracellular signaling pathways. Since NS5A is a phosphoprotein, it is of considerable interest to understand the role of phosphorylation in NS5A function. In this report, we investigated the phosphorylation of NS5A by taking advantage of 119 glutathione S-transferase-tagged protein kinases purified from Saccharomyces cerevisiae to perform a global screening of yeast kinases capable of phosphorylating NS5A in vitro. A database BLAST search was subsequently performed by using the sequences of the yeast kinases that phosphorylated NS5A in order to identify human kinases with the highest sequence homologies. Subsequent in vitro kinase assays and phosphopeptide mapping studies confirmed that several of the homologous human protein kinases were capable of phosphorylating NS5A. In vivo phosphopeptide mapping revealed phosphopeptides common to those generated in vitro by AKT, p70S6K, MEK1, and MKK6, suggesting that these kinases may phosphorylate NS5A in mammalian cells. Significantly, rapamycin, an inhibitor commonly used to investigate the mTOR/p70S6K pathway, reduced the in vivo phosphorylation of specific NS5A phosphopeptides, strongly suggesting that p70S6 kinase and potentially related members of this group phosphorylate NS5A inside the cell. Curiously, certain of these kinases also play a major role in mRNA translation and antiapoptotic pathways, some of which are already known to be regulated by NS5A. The findings presented here demonstrate the use of high-throughput screening of the yeast kinome to facilitate the major task of identifying human NS5A protein kinases for further characterization of phosphorylation events in vivo. Our results suggest that this novel approach may be generally applicable to the screening of other protein biochemical activities by mechanistic class.     

粘虫(Pseudaletia separata(Walker))生殖系统的解剖

本文内容是研究粘虫(Pseudaletia separata(Walker)生殖系统的形态构造。全文分为雄性内部生殖器、雄性外部生殖器、雌性内部生殖器及雌性外部生殖器四部分。 粘虫的雄性内生殖器中, 有睾丸一对, 左右并列, 呈扁椭圆形, 外被紫红色睾丸膜; 输精管一对, 基部膨大成二对贮精囊; 射精管分成复射精管及单射精管两部分。雄性外生殖器的构造极为复杂, 第9腹节的背、腹板分别形成马鞍状的背兜及基腹弧; 第10腹节仅有其附肢特化成钩形突、颚形突和背兜侧突等; 抱握器占雄性外生殖器中的大部分, 其顶上角具长约1毫米的端刺一枚, 此为本种特征之一, 可以此与近似种区别; 阳茎由基部球状的阳茎囊和端部柄状的阳茎端组成, 内具内阳茎及角状器:雄性外生殖器中有关器官的肌肉来源亦作了叙述。 精液是以贮存于精球的方式授入雌体, 精球分为精球体、精球柄及系带三部分。 雌性内生殖器中, 卵巢为多滋式, 一对, 各由四个卵巢管组成, 两组卵巢管再与一对侧输卵管相连, 后者通入中输卵管中, 中输卵管后端连有外生殖腔, 其外方的开口是为产卵孔; 受精囊为长形梨状物, 分成主囊及副囊两部分, 两者在顶部愈合, 并由此发出受精管与外生殖腔相通, 在主囊顶端有受精囊腺; 附腺一对, 与附腺囊相连, 后者通入附腺主囊, 并由此开口入外生殖腔。雌性外生殖器是由交配囊和产卵器组成, 前者复可分成囊导管、囊体及囊颈三部分, 其外方的开口为交配囊孔, 有导精管从囊颈连于外生殖腔; 产卵器由第8、9腹节组成, 非呈特殊构造。     

Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver

Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats.     

Re-evaluation of Sinocastor (Rodentia: Castoridae) with implications on the origin of modern beavers

The extant beaver, Castor, has played an important role shaping landscapes and ecosystems in Eurasia and North America, yet the origins and early evolution of this lineage remain poorly understood. Here we use a geometric morphometric approach to help re-evaluate the phylogenetic affinities of a fossil skull from the Late Miocene of China. This specimen was originally considered Sinocastor, and later transferred to Castor. The aim of this study was to determine whether this form is an early member of Castor, or if it represents a lineage outside of Castor. The specimen was compared to 38 specimens of modern Castor (both C. canadensis and C. fiber) as well as fossil specimens of C. fiber (Pleistocene), C. californicus (Pliocene) and the early castorids Steneofiber eseri (early Miocene). The results show that the specimen falls outside the Castor morphospace and that compared to Castor, Sinocastor possesses a: 1) narrower post-orbital constriction, 2) anteroposteriorly shortened basioccipital depression, 3) shortened incisive foramen, 4) more posteriorly located palatine foramen, 5) longer rostrum, and 6) longer braincase. Also the specimen shows a much shallower basiocciptal depression than what is seen in living Castor, as well as prominently rooted molars. We conclude that Sinocastor is a valid genus. Given the prevalence of apparently primitive traits, Sinocastor might be a near relative of the lineage that gave rise to Castor, implying a possible Asiatic origin for Castor.     

Algorithmic approaches to aid species' delimitation in multidimensional morphospace

Background  

The species is a fundamental unit of biological pattern and process, but its delimitation has proven a ready source of argument and disagreement. Here, we discuss four key steps that utilize statistical thresholds to describe the morphological variability within a sample and hence assess whether there is evidence for one or multiple species. Once the initial set of biologically relevant traits on comparable individuals has been identified, there is no need for the investigator to hypothesise how specimens might be divided among groups, nor the traits on which groups might be separated.     

Tricyclic antidepressants, quinacrine and a novel, synthetic chimera thereof clear prions by destabilizing detergent-resistant membrane compartments

Prion diseases are invariably fatal, neurodegenerative diseases transmitted by an infectious agent, PrPSc, a pathogenic, conformational isoform of the normal prion protein (PrPC). Heterocyclic compounds such as acridine derivatives like quinacrine abolish prion infectivity in a cell culture model of prion disease. Here, we report that these compounds execute their antiprion activity by redistributing cholesterol from the plasma membrane to intracellular compartments, thereby destabilizing membrane domains. Our findings are supported by the fact that structurally unrelated compounds with known cholesterol-redistributing effects - U18666A, amiodarone, and progesterone - also possessed high antiprion potency. We show that tricyclic antidepressants (e.g. desipramine), another class of heterocyclic compounds, displayed structure-dependent antiprion effects and enhanced the antiprion effects of quinacrine, allowing lower doses of both drugs to be used in combination. Treatment of ScN2a cells with quinacrine or desipramine induced different ultrastructural and morphological changes in endosomal compartments. We synthesized a novel drug from quinacrine and desipramine, termed quinpramine, that led to a fivefold increase in antiprion activity compared to quinacrine with an EC50 of 85 nm. Furthermore, simvastatin, an inhibitor of cholesterol biosynthesis, acted synergistically with both heterocyclic compounds to clear PrPSc. Our data suggest that a cocktail of drugs targeting the lipid metabolism that controls PrP conversion may be the most efficient in treating Creutzfeldt-Jakob disease.