Serine Racemase Regulated by Binding to Stargazin and PSD-95: POTENTIAL N-METHYL-d-ASPARTATE-α-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID (NMDA-AMPA) GLUTAMATE NEUROTRANSMISSION CROSS-TALK*

d-Serine, an endogenous co-agonist for the glycine site of the synaptic NMDA glutamate receptor, regulates synaptic plasticity and is implicated in schizophrenia. Serine racemase (SR) is the enzyme that converts l-serine to d-serine. In this study, we demonstrate that SR interacts with the synaptic proteins, postsynaptic density protein 95 (PSD-95) and stargazin, forming a ternary complex. SR binds to the PDZ3 domain of PSD-95 through the PDZ domain ligand at its C terminus. SR also binds to the C terminus of stargazin, which facilitates the cell membrane localization of SR and inhibits its activity. AMPA receptor activation internalizes SR and disrupts its interaction with stargazin, therefore derepressing SR activity, leading to more d-serine production and potentially facilitating NMDA receptor activation. These interactions regulate the enzymatic activity as well as the intracellular localization of SR, potentially coupling the activities of NMDA and AMPA receptors. This shuttling of a neurotransmitter synthesizing enzyme between two receptors appears to be a novel mode of synaptic regulation.     

Caffeine-induced Ca2+ oscillations in type I horizontal cell of carp retina: A mathematical model

Oscillations in intracellular free Ca²⁺ concentration ([Ca²⁺]_i) have been observed in a variety of cell types. In the present study, we constructed a mathematical model to simulate the caffeine-induced [Ca²⁺]_i oscillations based on experimental data obtained from isolated type I horizontal cell of carp retina. The results of model analysis confirm the notion that the caffeine-induced [Ca²⁺]_i oscillations involve a number of cytoplasmic and endoplasmic Ca²⁺ processes that interact with each other. Using this model, we evaluated the importance of store-operated channel (SOC) in caffeine-induced [Ca²⁺]_i oscillations. The model suggests that store-operated Ca²⁺ entry (SOCE) is elicited upon depletion of the endoplasmic reticulum (ER). When the SOC conductance is set to 0, caffeine-induced [Ca²⁺]_i oscillations are abolished, which agrees with the experimental observation that [Ca²⁺]_i oscillations were abolished when SOC was blocked pharmacologically, verifying that SOC is necessary for sustained [Ca²⁺]_i oscillations.     

Hidden Population Structure and Cross-species Transmission of Whipworms (Trichuris sp.) in Humans and Non-human Primates in Uganda

Background

Whipworms (Trichuris sp.) are a globally distributed genus of parasitic helminths that infect a diversity of mammalian hosts. Molecular methods have successfully resolved porcine whipworm, Trichuris suis, from primate whipworm, T. trichiura. However, it remains unclear whether T. trichiura is a multi-host parasite capable of infecting a wide taxonomic breadth of primate hosts or a complex of host specific parasites that infect one or two closely related hosts.

Methods and Findings

We examined the phylogenetic structure of whipworms in a multi-species community of non-human primates and humans in Western Uganda, using both traditional microscopy and molecular methods. A newly developed nested polymerase chain reaction (PCR) method applied to non-invasively collected fecal samples detected Trichuris with 100% sensitivity and 97% specificity relative to microscopy. Infection rates varied significantly among host species, from 13.3% in chimpanzees (Pan troglodytes) to 88.9% in olive baboons (Papio anubis). Phylogenetic analyses based on nucleotide sequences of the Trichuris internal transcribed spacer regions 1 and 2 of ribosomal DNA revealed three co-circulating Trichuris groups. Notably, one group was detected only in humans, while another infected all screened host species, indicating that whipworms from this group are transmitted among wild primates and humans.

Conclusions and Significance

Our results suggest that the host range of Trichuris varies by taxonomic group, with some groups showing host specificity, and others showing host generality. In particular, one Trichuris taxon should be considered a multi-host pathogen that is capable of infecting wild primates and humans. This challenges past assumptions about the host specificity of this and similar helminth parasites and raises concerns about animal and human health.     

Impact of human papilloma virus infection on the response of head and neck cancers to anti-epidermal growth factor receptor antibody therapy

Infection with human papillomaviruses (HPVs) characterizes a distinct subset of head and neck squamous cell cancers (HNSCCs). HPV-positive HNSCC preferentially affect the oropharynx and tonsils. Localized HPV-positive HNSCCs have a favorable prognosis and treatment outcome. However, the impact of HPV in advanced or metastatic HNSCC remains to be defined. In particular, it is unclear whether HPV modulates the response to cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), which is a mainstay of treatment of advanced HNSCC. To this end, we have examined the sensitivity of HPV-positive and -negative HNSCC models to cetuximab and cytotoxic drugs in vitro and in vivo. In addition, we have stably expressed the HPV oncogenes E6 and E7 in cetuximab-sensitive cancer cell lines to specifically investigate their role in the antibody response. The endogenous HPV status or the expression of HPV oncogenes had no significant impact on cetuximab-mediated suppression of EGFR signaling and proliferation in vitro. Cetuximab effectively inhibited the growth of E6- and E7-expressing tumors grafted in NOD/SCID mice. In support, formalin-fixed, paraffin-embedded tumor samples from cetuximab-treated patients with recurrent or metastatic HNSCC were probed for p16^INK4a expression, an established biomarker of HPV infection. Response rates (45.5% versus 45.5%) and median progression-free survival (97 versus 92 days) following cetuximab-based therapy were similar in patients with p16^INK4A-positive and p16^INK4A-negative tumors. In conclusion, HPV oncogenes do not modulate the anti-EGFR antibody response in HSNCC. Cetuximab treatment should be administered independently of HPV status.     

一株耐锌真菌CTB430-1分离鉴定及其富集特性

从某锌尾砂坝土壤中筛选分离、纯化得到一株对锌具有较强抗性的菌株,命名为CTB430-1.对菌株进行形态观察、生理生化试验,采用ITS基因序列分析并构建系统发育树,鉴定该菌为黄曲霉（Aspergillus flavus）.研究其对Zn（Ⅱ）抗性和富集特性.结果表明：Zn（Ⅱ）对该菌株的最低抑菌浓度为800 mg/L;菌株对Zn（Ⅱ）的富集量在250 mg/L时达到最大,为40.37 mg/g;采用扫描和透射电镜观察富集前后菌丝体表面形态和内部结构变化,表明Zn（Ⅱ）毒害作用可能导致生长中菌丝表面结构破坏,CTB430-1富集Zn（Ⅱ）由表面吸附和胞内富集两部分组成.     

Bracoviruses recruit host integrases for their integration into caterpillar’s genome

Some DNA viruses infect host animals usually by integrating their DNAs into the host genome. However, the mechanisms for integration remain largely unknown. Here, we find that Cotesia vestalis bracovirus (CvBV), a polydnavirus of the parasitic wasp C. vestalis (Haliday), integrates its DNA circles into host Plutella xylostella (L.) genome by two distinct strategies, conservatively and randomly, through high-throughput sequencing analysis. We confirmed that the conservatively integrating circles contain an essential “8+5” nucleotides motif which is required for integration. Then we find CvBV circles are integrated into the caterpillar’s genome in three temporal patterns, the early, mid and late stage-integration. We further identify that three CvBV-encoded integrases are responsible for some, but not all of the virus circle integrations, indeed they mainly participate in the processes of early stage-integration. Strikingly, we find two P. xylostella retroviral integrases (PxIN1 and PxIN2) are highly induced upon wasp parasitism, and PxIN1 is crucial for integration of some other early-integrated CvBV circles, such as CvBV_04, CvBV_12 and CvBV_24, while PxIN2 is important for integration of a late-integrated CvBV circle, CvBV_21. Our data uncover a novel mechanism in which CvBV integrates into the infected host genome, not only by utilizing its own integrases, but also by recruiting host enzymes. These findings will strongly deepen our understanding of how bracoviruses regulate and integrate into their hosts.     

不同生长光强下8种红树植物幼苗叶片的光响应特征

为探讨红树植物光适应的生理生态策略,对6种真红树植物[无瓣海桑(Sonneratia apetala)、秋茄(Kandelia candel)、木榄(Bruguiera gymnorrhiza)、桐花树(Aegiceras corniculatum)、老鼠簕(Acanthus ilicifolius)、卤蕨(Acrostichum aureum)]和2种半红树植物[银叶树(Heritiera littoralis)、黄槿(Hibiscus tiliaceus)]的1 a生幼苗在不同生长光强(自然光强的100%、45%、30%、10%)下的光合光响应特征进行了研究。结果表明,不同生长光强对红树植物光响应特征的影响因物种而异,遮荫显著提高了秋茄和木榄的最大净光合速率(Pmax),而对其他红树植物的Pmax没有显著影响;秋茄在45%光强下具有较高的Pmax,木榄的Pmax则在45%和30%光强下显著高于其他2个处理。随着生长光强的下降,秋茄幼苗叶片的光饱和点显著上升,木榄、老鼠簕和卤蕨的光补偿点呈下降趋势,木榄和卤蕨的表观量子效率升高的同时暗呼吸速率下降。木榄、老鼠簕和卤蕨具有较强的耐荫性,...     

昆明动物园笼养倭蜂猴的能量代谢

食物是动物适应性生存的基础,能量平衡对动物生存、繁殖和进化起着至关重要的作用 (McNab,1988).     

土壤微生物多样性影响因素及研究方法的现状与展望

土壤微生物是土壤生态系统的重要组成部分, 在土壤有机物质分解和养分释放、能量转移等生物地化循环中起着重要作用。随着人们对生物多样性重要性认识的不断深入及研究方法的不断改进, 土壤微生物多样性, 尤其是功能多样性的研究工作逐渐受到生态学家的重视。本文从土壤微生物多样性的影响因素以及研究方法等方面阐述了目前国内外土壤微生物多样性的研究现状, 并对其未来研究方向进行了展望。