Impairment of ubiquitin-proteasome system by E334K cMyBPC modifies channel proteins, leading to electrophysiological dysfunction

Cardiac arrhythmogenesis is regulated by channel proteins whose protein levels are in turn regulated by the ubiquitin-proteasome system (UPS). We have previously reported on UPS impairment induced by E334K cardiac myosin-binding protein C (cMyBPC), which causes hypertrophic cardiomyopathy (HCM) accompanied by arrhythmia. We hypothesized that UPS impairment induced by E334K cMyBPC causes accumulation of cardiac channel proteins, leading to electrophysiological dysfunction. Wild-type or E334K cMyBPC was overexpressed in HL-1 cells and primary cultured neonatal rat cardiac myocytes. The expression of E334K cMyBPC suppressed cellular proteasome activities. The protein levels of K_v1.5, Na_v1.5, Hcn4, Ca_v3.2, Ca_v1.2, Serca, RyR2, and Ncx1 were significantly higher in cells expressing E334K cMyBPC than in wild type. They further increased in cells pretreated with MG132 and had longer protein decays. The channel proteins retained the correct localization. Cells expressing E334K cMyBPC exhibited higher Ca²⁺ transients and longer action potential durations (APDs), accompanied by afterdepolarizations and higher apoptosis. Those augments of APD and Ca²⁺ transients were recapitulated by a simulation model. Although a Ca²⁺ antagonist, azelnidipine, neither protected E334K cMyBPC from degradation nor affected E334K cMyBPC incorporation into the sarcomere, it normalized the APD and Ca²⁺ transients and partially reversed the levels of those proteins regulating apoptosis, thereby attenuating apoptosis. In conclusion, UPS impairment caused by E334K cMyBPC may modify the levels of channel proteins, leading to electrophysiological dysfunction. Therefore, UPS impairment due to a mutant cMyBPC may partly contribute to the observed clinical arrhythmias in HCM patients.     

长木蜂的形态和生物学观察

长木蜂Xylocopa tranquebarorum(Swederus)属于多访花性昆虫。本文报道了长木蜂的形态特征、生活史及幼虫和成虫的行为等生物学特性。该蜂在南京地区1年发生1代,以成虫在巢室内越冬。翌年的3月下旬成虫开始外出活动,主要是筑巢、采集粉蜜、酿贮蜂粮和产卵。6月中旬至7月下旬新一代成虫羽化,新羽化的成虫群集在蜜源植物青桐树上补充营养,并在青桐的附近空中婚飞、交配。室内观察长木蜂的卵期9～11d,平均(9.97±0.76)d;幼虫期19～22d,平均(20.30±1.18)d,预蛹期8～9d,平均(8.53±0.51)d,蛹期19～21d,平均(19.67±0.66)d。雌雄比为2.17∶1。雌蜂酿制蜂粮的盛期在5月上旬,采集蜂粮的最佳时期在5月上中旬。该蜂的卵产在块状的蜂粮上,卵长10.06～13.34mm,腊肠形或香蕉形,略弯曲,两端钝圆,头部略窄与尾部,尾部最宽,重(0.0438±0.0122)g。     

普通齿蛉幼虫的呼吸系统及呼吸行为

研究了普通齿蛉Neoneuromus ignobilis Navás幼虫的呼吸系统及其呼吸行为。结果表明:普通齿蛉幼虫为全气门式(10对气门)呼吸系统,前中胸、中后胸之间、腹部8节各有1对气门,腹部8节各有气管鳃1对,前6对细短,管状,有较短绒毛,后2对气管鳃较粗长,呈羽毛状。腹部1～7节各有1对毛簇,第8腹节无毛簇。侧纵干气管较粗,4束,自前胸前缘部分成左右2组,每组两根侧纵干气管,向胸腹部延伸,二级气管分别伸达各个气门和毛簇,腹部每节由毛簇处的二级气管分支而来的三级气管相连或延伸至消化道等处。气管鳃中无气管。有毛簇呼吸、气门呼吸和体壁呼吸3种呼吸方式,在水中以毛簇呼吸为主,在陆上进行气门呼吸和体壁呼吸。     

番石榴实蝇寄主选择性试验

番石榴实蝇Bactrocera correcta(Bezzi)是一种为害多种水果的害虫,近年来在云南的元江暴发成灾。本试验选择番石榴实蝇的常见寄主:梨、芒果、苹果、桃、橙及芒果的不同品种进行室内试验,比较番石榴实蝇雌虫产卵对寄主的选择性及不同寄主对番石榴实蝇生长发育的影响。结果显示,番石榴实蝇雌虫对5种供试水果的寄生选择性大小依次为桃>梨>芒果>橙>苹果;番石榴实蝇对芒果不同品种的寄生选择性为三年芒>台农行1号>虎豹牙>胭脂芒>鹰嘴芒;番石榴实蝇在不同寄主上的蛀果期(卵及幼虫的历期)具有极显著的差异,以寄生桃和芒果的最短;从梨和苹果上饲养出的蛹最轻,且极显著低于其它寄主上饲养出来的蛹重;苹果上寄生的番石榴实蝇蛹重与蛀果期呈显著的正相关,而寄生梨的番石榴实蝇蛹重与蛀果期呈极显著的负相关。结果表明,番石榴实蝇雌虫产卵对不同寄主或同一寄主不同品种有明显的选择性,且该选择行为与其后代的生长发育有关。     

A-kinase anchoring protein-Lbc promotes pro-fibrotic signaling in cardiac fibroblasts

In response to stress or injury the heart undergoes an adverse remodeling process associated with cardiomyocyte hypertrophy and fibrosis. Transformation of cardiac fibroblasts to myofibroblasts is a crucial event initiating the fibrotic process. Cardiac myofibroblasts invade the myocardium and secrete excess amounts of extracellular matrix proteins, which cause myocardial stiffening, cardiac dysfunctions and progression to heart failure. While several studies indicate that the small GTPase RhoA can promote profibrotic responses, the exchange factors that modulate its activity in cardiac fibroblasts are yet to be identified. In the present study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor (GEF) activity, is critical for activating RhoA and transducing profibrotic signals downstream of type I angiotensin II receptors (AT₁Rs) in cardiac fibroblasts. In particular, our results indicate that suppression of AKAP-Lbc expression by infecting adult rat ventricular fibroblasts with lentiviruses encoding AKAP-Lbc specific short hairpin (sh) RNAs strongly reduces the ability of angiotensin II to promote RhoA activation, differentiation of cardiac fibroblasts to myofibroblasts, collagen deposition as well as myofibroblast migration. Interestingly, AT₁Rs promote AKAP-Lbc activation via a pathway that requires the α subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as a key Rho-guanine nucleotide exchange factor modulating profibrotic responses in cardiac fibroblasts.     

低分子肝素对早发型重度子痫前期治疗对母婴结局的影响分析

目的:探讨低分子肝素对早发型重度子痫前期治疗情况,并分析治疗对母婴结局的影响。方法:选择我院2012年1月~12月收治的早发型重度子痫前期患者120例,随机分为观察组和对照组,每组60例。对照组给予常规治疗,观察组在对照组治疗基础上加用低分子肝素。比较两组血压、24 h尿量、尿蛋白定量、尿酸、血常规、凝血功能及孕周延长时间、围产儿结局和产妇并发症。结果:两组患者临床指标无差异(P0.05),治疗后两组血压、24 h尿量、尿蛋白定量均显著改善,观察组红细胞压积、纤维蛋白原降低明显高于对照组,而观察组患者的产妇并发症和围产儿不良结局发生率均低于对照组,且产妇孕周延长时间明显多于对照组,差异有统计学意义(P0.05)。两组患者的血小板、凝血酶原时间等治疗前后均无明显变化(P0.05)。结论:低分子肝素对早发型重度子痫前期的治疗能有效抑制高凝状态,改善肾功能,延长孕周时间,可有效减少患者并发症的发生,改善母婴预后,值得临床推广应用。     

Hypothermia Modulates Cytokine Responses After Neonatal Rat Hypoxic-Ischemic Injury and Reduces Brain Damage

While hypothermia (HT) is the standard-of-care for neonates with hypoxic ischemic injury (HII), the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18) or normothermia (NT, 35℃; n = 15). Outcomes included magnetic resonance imaging (MRI), neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII). Lesion volumes (24 hr) were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19). Lesion volumes rebounded at 72 hr (48 hr post-HT) with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β) at all time points (p < .05); monocyte chemoattractant protein-1 (MCP-1) trended toward being decreased in HT pups (p = .09). The stem cell signaling molecule, stromal cell-derived factor-1 (SDF-1) was not altered by HT. Our data demonstrate that HT reduces total and penumbral lesion volumes (at 24 and 48 hr), potentially by decreasing IL-1β without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72 hr post-HII when IL-1β levels remained low suggests that after rewarming, mechanisms unrelated to IL-1β expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury.     

Kymachrysa,a new genus of Nearctic Green Lacewings (Neuroptera,Chrysopidae, Chrysopini)

Two North American species of green lacewings have undergone a number of changes in their generic assignments and are currently classified as incertae sedis. Here we demonstrate that adults (both sexes) and larvae of these species share a set of features that distinguishes them from currently described genera. Thus, to promote nomenclatural stability in Chrysopidae, we describe Kymachrysa, a gen. n. that contains the two species – Kymachrysa intacta (Navás), comb. n. and Kymachrysa placita (Banks), comb. n.. Also, we present modifications for the current generic-level key, illustrations, as well as biological information for identifying the genus and its known species.