CFTR: Domains, Structure, and Function

Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) (Collins, 1992). Over 500 naturally occurring mutations have been identified in CF gene which are located in all of the domains of the protein (Kerem et al., 1990; Mercier et al., 1993; Ghanem et al., 1994; Fanen et al., 1992; Ferec et al., 1992; Cutting et al., 1990). Early studies by several investigators characterized CFTR as a chloride channel (Anderson et al.; 1991b,c; Bear et al., 1991). The complex secondary structure of the protein suggested that CFTR might possess other functions in addition to being a chloride channel. Studies have established that the CFTR functions not only as a chloride channel but is indeed a regulator of sodium channels (Stutts et al., 1995), outwardly rectifying chloride channels (ORCC) (Gray et al., 1989; Garber et al., 1992; Egan et al., 1992; Hwang et al., 1989; Schwiebert et al., 1995) and also the transport of ATP (Schwiebert et al., 1995; Reisin et al., 1994). This mini-review deals with the studies which elucidate the functions of the various domains of CFTR, namely the transmembrane domains, TMD1 and TMD2, the two cytoplasmic nucleotide binding domains, NBD1 and NBD2, and the regulatory, R, domain.     

Immune plexins and semaphorins: old proteins,new immune functions

Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012), epithelial (Miao et al., 1999; Fujii et al., 2002), and immune systems (Takamatsu and Kumanogoh, 2012) as well as diverse cell processes including angiogenesis (Serini et al., 2009; Sakurai et al., 2012), embryogenesis (Perala et al., 2012), and cancer (Potiron et al., 2009; Micucci et al., 2010). Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin domain (Hota and Buck, 2012). The plexins and semaphorins are divided into four and eight subfamilies respectively based on their structural homology. Semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intracellular tails. Plexins contain the semaphorin domain and long intracellular tails (Hota and Buck, 2012). The majority of plexin and semaphorin research has focused on the nervous system, particularly the developing nervous system, where these proteins are found to mediate many common neuronal cell processes including cell movement, cytoskeletal rearrangement, and signal transduction (Choi et al., 2008; Takamatsu et al., 2010). Their roles in the immune system are the focus of this review.     

贵州遵义松林黑沙坡早寒武世牛蹄塘生物群中镇巴虫的发现

贵州遵义松林中南村黑沙坡下寒武统牛蹄塘生物群下部层位产有大型三叶虫,计有2属3种,1未定种：Zhenbaspis subconica S. G Zhang in Lu et al. , 1974, Z. longa Zhou in Lee et al. , 1975 ; Zhenbaspis sp. , Runnania similis Lee in Yin et Lee, , 1978, 确认 Zhenbaspis (Zhenxiongaspis) Lin et Yin in Yin et Lee, 1978,为 Zhenbastn‘sChang et Chu in Lu et al. ,1974的同义名。探讨Zhenbaspis的古地理分布及演化趋势。论文还描述与Zhenbaspis,Runnania共生的Tsunyidiscus及Mianxiandiscus,其中Mianxiandiscus产于下生物群即牛蹄塘组近底部,再次证实牛蹄塘下生物群的时代早于澄江生物群。     

Flow cytometric analysis of European flat oyster, Ostrea edulis, haemocytes using a monoclonal antibody specific for granulocytes

The importance of haemocytes in mollusc defence mechanisms can be inferred from their functions. They participate in pathogen elimination by phagocytosis (Cheng, 1981; Fisher, 1986). Hydrolytic enzymes and cytotoxic molecules produced by haemocytes contribute to the destruction of pathogenic organisms (Cheng, 1983; Leippe & Renwrantz, 1988; Charlet et al., 1996; Hubert et al., 1996; Roch et al., 1996). Haemocytes may also be involved in immunity modulation by the production of cytokines and neuropeptides (Hughes et al., 1990; Stefano et al., 1991; Ottaviani et al., 1996). As a result, the literature dealing with bivalve haemocyte studies has increased during the last two decades. Most of these publications use microscopy for morphological analysis (Seiler & Morse, 1988; Auffret, 1989; Hine & Wesney, 1994; Giamberini et al., 1996; Carballal et al., 1997; Lopez et al., 1997; Nakayama et al., 1997), and functional analysis (e.g. phagocytosis) (Hinsch & Hunte, 1990; Tripp, 1992; Mourton et al., 1992; Fryer & Bayne, 1996; Mortensen & Glette, 1996). Flow cytometry represents a rapid technique applicable to both morphological and functional studies of cells in suspension. While the measurements based on autofluorescence provide information on cell morphology, the analyses with fluorescent markers including labelled antibodies, offer data on phenotyping and cell functions. As a result, its application has greatly contributed to the investigation of immunocyte functions and differentiation in vertebrates (Stewart et al., 1986; Rothe & Valet, 1988; Ashmore et al., 1989; Koumans-van Diepen et al., 1994; Rombout et al., 1996; Caruso et al., 1997). Some authors studied oyster haemocyte populations by flow cytometry based on cellular autofluorescence (Friedl et al., 1988; Fisher & Ford, 1988; Ford et al., 1994). However, no analysis using specific monoclonal antibodies has been reported to date. In this study, a protocol for studying European flat oyster, Ostrea edulis, haemocytes by flow cytometry using a monoclonal antibody specific for granulocytes and an indirect immunofluorescence technique have been developed. European flat oysters, Ostrea edulis, 7-9 cm in shell length were obtained from shellfish farms in Marenne Oléron bay (Charente Maritime, France) on the French Atlantic coast. All individuals were purchased just before each experiment and processed without any previous treatment.     

For catch bonds, it all hinges on the interdomain region

Tensile mechanical force was long assumed to increase the detachment rates of biological adhesive bonds (Bell, 1978). However, in the last few years, several receptor-ligand pairs were shown to form "catch bonds," whose lifetimes are enhanced by moderate amounts of force. These include the bacterial adhesive protein FimH binding to its ligand mannose (Thomas et al., 2002; Thomas et al., 2006), blood cell adhesion proteins P- and L-selectin binding to sialyl Lewis X (sLe(X))-containing ligands (Marshall et al., 2003; Evans et al., 2004; Sarangapani et al., 2004), and the myosin-actin motor protein interaction (Guo and Guilford, 2006). The structural mechanism behind this counterintuitive force-enhanced catch bond behavior is of great interest.     

泥河湾盆地上新世生物地层序列与环境

总结了泥河湾盆地晚上新世生物地层,讨论了12个剖面含哺乳动物化石层位的相互关系,以稻地老窝沟剖面的地层顺序为基础排列出约3.7～2.6Ma时段内的9个代表性的生物地层单位。哺乳动物以Paenelimnoecus chinensis、Lunanosorex cf.L.lii、Trischizolagus、Pliopentalagus nihewanicus、Ungaromys、Mimomys sp.、Chardina truncatus、Mesosiphneus praetingi、M, paratingi、Plio- siphneus lyratus、Pseudomeriones complicidens、Castor anderssoni、Huaxiamys downsi、Chardinomys yusheensis、C.nihowanicus、Hipparion houfenense和Gazella blacki组合为特征。动物群在时代上与榆社麻则沟动物组合、静乐红土动物群、灵台雷家河剖面V带及任家沟静乐红粘土动物组合、宁县水磨沟动物组合、游河动物群及沂南棋盘山洞穴动物组合相当。动物群所反映的是温带草原为主、间有树林和干草原的稀树草原环境。     

Roles of Tet2 in meiosis,fertility and reproductive aging

Dear Editor, Ten-eleven translocation(Tet)enzymes play important roles in DNA demethylation involved in various biological pro-cesses including stem cell pluripotency and differentiation,and tumorigenesis(Dawlaty et al.,2013;Wu and Zhang,2017).Tet2 deficiency or mutation leads to severe hematopoietic defects or myeloid malignancies in mice(Delhommeau et al.,2009;Ko et al.,2010;Moran-Crusio et al.,2011).Restoration of TET2 blocks aberrant self-re-newal and leukemia progression in patients possessing TET2 mutations(Cimmino et al.,2017).DNA methylation-based biomarkers,or"epigenetic clocks",link developmental and maintenance processes to biological aging(Horvath and Raj,2018).Interestingly,age-associated TET2 mutations have been found to drive myeloid dysfunction,cancer and cardiovascular disease(review(Ferrone et al.,2020)).Nevertheless,there has been lack of direct evidence demonstrating that Tet2 mutations or deficiency can actually accelerate aging.     

ChAnge, Stress, Sustainability and Aquatic ecosystem Resilience In North African wetland lakes during the 20th century: an introduction to integrated biodiversity studies within the CASSARINA Project

The CASSARINA Project is a co-ordinated joint study of recent environmental change in North African wetland lakes. Nine primary sites were selected for detailed study comprising three sites in each of Morocco, Tunisia and Egypt. Multi-disciplinary studies were undertaken by scientists from each of these countries working in co-operation with colleagues in the UK and Norway. The detailed results are presented in a consecutive suite of papers that describe both modern ecosystem attributes and the recent environmental histories of each site. This paper presents an overview of the aims, structure and initial results of the project.Modern site attributes measured were water quality and phytoplankton (Fathi et al., 2001), zooplankton (Ramdani et al., 2001b), fish (Kraïem et al., 2001) and littoral vegetation (Ramdani et al., 2001a). Baseline water quality data showed that one site (Megene Chitane) was acid with low salinity but the others had high alkalinities with varying degrees of brackishness. All the sites tended to be eutrophic and the phytoplankton was mainly dominated by green or blue-green algae. Where fish were present, growth rates were high with marginally highest rates in the Egyptian Delta lakes (Kraïem et al., 2001). Marginal vegetation surveys showed that emergent macrophytes were still extensive only in the Delta lakes (Ramdani et al., 2001a) where they form important refuges and restrict water pollution. In 1998, one Moroccan wetland lake (Merja Bokka) was drained completely for cultivation.Site specific environmental change records for the 20th century period were obtained using palaeolimnological techniques. Sediment core chronologies (Appleby et al., 2001) were based mainly on radio-isotopes (²¹⁰Pb and ¹³⁷Cs). Sedimentary remains of aquatic biota, diatoms, zooplankton, higher plants and benthic animals (Flower et al., 2001; Ramdani et al., 2001c; Birks et al., 2001a) and pollen (Peglar et al., 2001) were investigated (Birks et al., 2001b). Major differences in past species abundances were found and were interpreted in terms relevant to biodiversity and water quality/availability change. Metals and pesticide residues in sediment cores indicated that lake contamination was generally lower than in some European sites but some DDE profiles showed a close correspondence with known usage histories (Peters et al., 2001).Hydrological changes affecting water quality and availability mainly arose from land-use intensification during the 20th century and are shown to be the main driver of biodiversity disturbance at all nine CASSARINA sites. Summarizing floristic and faunistic changes using species richness values indicated that freshening of the Delta lakes during this century generally increased aquatic diversity. Species richness also increased during the final drainage of Bokka but tended to decline in acid Chitane. Modern sampling showed that phytoplankton and epiphytic diatom diversity was higher in the Delta lakes but this was not so for zooplankton. Each biological group reacted differently to environmental disturbance and this lack of concordance makes overall diversity changes difficult to predict.     

New Phytologist 140 (1998), 363–383

In the November 1998 issue of New Phytologist , we published the Tansley review 'Gibberellins: regulating genes and germination' by Sian Ritchie and Simon Gilroy ( New Phytol. (1998) 140 , 363–383). Since its publication, it has come to our attention that text associated with Fig. 4 was omitted during production. The correct figure is reprinted here in full.
We apologise to the author and to our readers for this mistake.
Figure 4. Promoter sequences of various genes expressed in the cereal aleurone and shown to be regulated by GA. The position of each sequence is indicated relative to the start codon. Regions identified as being involved in regulation of the genes are highlighted, as are similar regions in other genes. Sites at which protein has been shown to bind are also indicated. ( a ) Barley Amy 32b (Sutcliff et al ., 1993; Whittier et al ., 1987); wheat Amy 2/54 (Huttley et al ., 1992; Rushton et al ., 1992; Rushton et al ., 1995); barley Amy 46 (Khursheed & Rogers, 1988); barley Amy 2/p155 (Knox et al ., 1987); barley aleurain (Whittier et al ., 1987); barley β-glucanase II (Wolf, 1992); wheat cathepsin B-like (Cejudo et al ., 1992); rice ubiquitin-conjugating enzyme (Chen et al ., 1995). ( b ). Wheat Amy 1/18 (Rushton et al ., 1992); barley Amy pHV 19 (Jacobsen & Close, 1991; Gubler & Jacobsen, 1992)/ Amy 1 / 6-4 (Khursheed & Rogers, 1988; Rogers, Lanahan & Rogers 1994); rice OSamy-a / Amy 3c (Ou-Lee et al ., 1988; Sutcliff et al ., 1991; Yu et al ., 1992; Goldman et al ., 1994); rice Amy 3B (Sutcliffe et al ., 1991); rice OSamy-c (Kim et al ., 1992; Kim & Wu, 1992; Tanida et al ., 1994); rice Amy 1A (Huang et al ., 1990; Itoh et al ., 1995).
Figure 4 ( b ). For legend see facing page.     

Epigenetic Variations in Plant Hybrids and Their Potential Roles in Heterosis

Heterosis,one of the most important biological phenomena,refers to the phenotypic superiority of a hybrid over its genetically diverse parents with respect to many traits such as biomass,growth rate and yield.Despite its successful application in breeding and agronomic production of many crop and animal varieties,the molecular basis of heterosis remains elusive.The classic genetic explanations for heterosis centered on three hypotheses:dominance (Davenport,1908;Bruce,1910;Keeble and Pellew,1910;Jones,1917),overdominance (East,1908;Shull,1908) and epistasis (Powers,1944;Yu et al.,1997).However,these hypotheses are largely conceptual and not connected to molecular principles,and are therefore insufficient to explain the molecular basis of heterosis (Birchler et al.,2003).Recently,many studies have explored the molecular mechanism of heterosis in plants at a genome-wide level.These studies suggest that global differential gene expression between hybrids and parental lines potentially contributes to heterosis in plants (e.g.,Swanson-Wagner et al.,2006;Zhang et al.,2008;Wei et al.,2009;Song et al.,2010).Research suggests that genetic components,including cis-acting elements and trans-acting factors,are critical regulators of differential gene expression in hybrids (Hochholdinger and Hoecker,2007;Springer and Stupar,2007;Zhang et al.,2008).However,other research indicates that epigenetic components,the regulators of chromatin states and genome activity,also have the potential to impact heterosis (e.g.,Ha et al.,2009;He et al.,2010;Groszmann et al.,2011;Barber et al.,2012;Chodavarapu et al.,2012;Greaves et al.,2012a;Shen et al.,2012).     

Sinoatrial node pacemaker cells:cardiomyocyte-or neuron-like cells?

The sinoatrial node(SAN)is the headquarter of heartbeat throughout our lifetime(Lakatta et al.,2010;Cingolani et al.,2018;Peters et al.,2020).Every beat of the heart is triggered by a bioelectric pulse spontaneously released by SAN pacemaker cells(SANPCs)(Yaniv et al.,2014;Yavari et al.,2017).In adult human heart,the SAN is a crescent-shaped structure of 1-2 cm long and 0.5 cm wide,which is located at the junction of the superior vena cava and the right atrium and lies along the sulcus terminalis(John et al.,2016).However,the nature of SANPCs remains incompletely known.In general,SANPCs have long been considered as specialized cardiomyocytes(Van Eif et al.,2018;Linscheid et al.,2019;Galang et al.,2020;).However,SANPCs do not have myofibril and T-tube,thus not sharing the contractility property of cardiomyocytes(Satoh,2003;Protze et al.,2017).Interestingly,SANPCs share some electrophysiolog-ical characteristics with neurons:excitability and conductiv-ity.In addition,SANPCs have their intrinsic autonomic rhythm,while neurons also possess the intrinsic ability to generate spontaneous electrical impulses(Lisman et al.,2018).Whether SANPCs are neuron-like cells that reside in the heart remains enigmatic in the field.     

Small bending,big curvature

<正>The classical "Cholodny-Went theory" predicted that directional stimuli trigger the redistribution of auxin, which governs the differential growth of plant organs through potent effects on cell expansion, thereby establishing an"auxin-then-growth" paradigm; this theory has been validated for both gravitropism and phototropism in plants(reviewed in Muthert et al., 2020).     

陕西洛南下寒武统辛集组疑难管状化石桶螺(Cupitheca)

本文对采自陕西洛南上湾剖面下寒武统辛集组疑难管状化石Cupitheca进行了研究,系统厘定和描述了两个种,分别为Cupitheca holocyclata和Cupitheca costellata,并对Cupithecidae科进行了重新修订。本文所描述标本的壳体多为次生磷酸盐化保存,壳体表面纹饰保存较好;C.holocyclata管体表面为横向纹饰,C.costellata管体表面为纵向纹饰。C.holocyclata全球广布,如南澳大利亚、南极乔治王岛、格陵兰东北部、加拿大纽芬兰等地皆有报道,产出于下寒武统中上部地层,具有一定的洲际地层对比意义。本文为C.holocyclata在中国首次发现。C.costellata仅发现于华北,即本文所研究的洛南辛集组及其同期地层安徽淮南与霍邱的雨台山组。     

浙江天台盆地晚白垩世恐龙蛋新类型(英文)

浙江天台盆地上白垩统赖家组和赤城山组是我国最重要的恐龙蛋化石产出地层之一。近年来,我们对天台盆地陆相红层中的恐龙蛋化石层位进行了详细厘定,对恐龙蛋类型进行了系统描述,并对前人报道的一些属种进行了分类订正。研究显示,天台恐龙蛋化石群基本上可分为7蛋科、12蛋属和15蛋种,代表了我国晚白垩世早期的恐龙蛋化石组合。本文简要报道了主要产自天台盆地赤城山组的双塘似蜂窝蛋(新蛋属、新修订种)、木鱼山半蜂窝蛋(新蛋属、新蛋种)、国清寺副蜂窝蛋(新修订种)、天台棱柱形蛋(新修订种)和张头槽马赛克蛋(新蛋属、新修订种)等3新蛋属、5新蛋种和修订种的主要鉴定特征,并建立一新蛋科——似蜂窝蛋科。     

十种海洋寡毛类纤毛虫:形态学及分类学修订

利用活体观察和蛋白银染色技术对近年来采自青岛、大亚湾、湛江沿岸水体的10个海洋寡毛类纤毛虫种:侧扁急游虫Strombidium apolatum Wilbert & Song,2005、具头急游虫Strombidium capitatum (Leegaard,1995) Kahl,1932、广东急游虫Strombidium guangdongense Liu,et al.,2016、拟卡氏急游虫Strombidiumparacalkinsi (Lei,et al.,1999) Agatha,2004、拟楔尾急游虫Strombidium parastylifer Song,et al.,2009、铃木急游虫Strombidium suzukii Song,et al.,2009、束腰旋游虫Spirostrombidium cinctum (Kahl,1932) Petz,et al.,1995、杨科夫平游虫Parallelostrombidium jankowski (Song,et al.,2009) Song,et al.,2018、卡尔平游虫Parallelostrombidium kahli (Song,et al.,2009) Song,et al.,2018、最小拟盗虫Strombidinopsis minima (Gruber,1884) Song & Bradbury,1998的形态学开展了比较研究,补充和厘定了有关形态特征、纤毛图式以及性状变异等分类学新信息。     

An integrated rapid nucleic acid detection assay based on recombinant polymerase amplification for SARS-CoV-2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes the outbreak of coronavirus disease 2019 (COVID-19) (Li et al., 2020a). Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19 (Wu et al., 2020a; Zhu et al., 2020). Currently, a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection (Corman et al., 2020; Hussein et al., 2020; Ruhan et al., 2020; Veyer et al., 2020). Conventional qPCR involves virus inactivation, nucleic acid extraction, and qPCR amplification procedures. Therefore, the process is complicated, which usually takes longer than 2 h, and requires biosafety laboratories and professional staff. Thus, qPCR is not suitable for use in field or medical units. To reduce the operation steps, automatic integrated qPCR detection systems that combine nucleic acid extraction and qPCR amplification in a sealed cartridge were developed to detect viruses in clinical samples (Li et al., 2020b). However, the detection time is still longer than 1 h. Therefore, rapid nucleic acid detection systems are needed to further improve the detection efficiency.     

Is oral microbiome of children able to maintain resistance and functional stability in response to short-term interference of ingesta?

Dear Editor, A series of studies had focused on the ecological stability of human microbiome (Lozupone et al.,2012;Faith et al.,2013;Moya and Ferrer,2016).Despite the continuous perturbation and the highly personalized composition within the human microbiome (Human Microbiome Project,2012),healthy adults stably maintain their microbial communities in terms of space and time (Faith et al.,2013;Moya and Ferrer,2016;Oh et al.,2016).This stability is proved to be critical for the well-being of human body (Lozupone et al.,2012).On the contrary,major shifts in microbial community composition are often related to diseases (Lynch and Pedersen,2016).     

Mighty Piwis defend the germline against genome intruders

Piwis are a germline-specific subclass of the Argonaute family of RNA interference (RNAi) effector proteins that are associated with a recently discovered group of small RNAs (piRNAs). Recent studies in Drosophila and zebrafish directly implicate Piwi proteins in piRNA biogenesis to maintain transposon silencing in the germline genome (Brennecke et al., 2007; Gunawardane et al., 2007; Houwing et al., 2007). This function may be conserved in mice as loss of Miwi2, a mouse Piwi homolog, leads to germline stem cell and meiotic defects correlated with increased transposon activity (Carmell et al., 2007).     

Vestibular input to brain monoamine neurons--a review

Yates et al. reported that serotonergic RN neurons are associated with vestibulo-sympathetic responses and may control BP changes during body repositioning (Yates et al., 1992; 1993). Pompeiano et al. demonstrated that LC-NA neurons participate in the postural control and modify the vestibulo-spinal reflex (Pompeiano et al., 1990; 1991a; 2001). Nishiike et al. (1996a) examined the effects of caloric vestibular stimulation on the neuronal activity of LC-NA neurons in rats. The predominant effect of CA with both hot- and cold-water on the electrical activity of LC neurons is inhibitory and persists for several minutes. GABAA receptors located on the postsynaptic membrane of LC neurons are responsible for these inhibitory responses. The VLM may inhibit LC neuronal activity in response to the CA via GABAA receptors (Nishiike et al., 1997). It is suggested that LC-NA inhibition is involved in the development of motion sickness (Nishiike et al., 2001).