Assessing Dispersal Patterns of Fish Propagules from an Effective Mediterranean Marine Protected Area

Successfully enforced marine protected areas (MPAs) have been widely demonstrated to allow, within their boundaries, the recovery of exploited species and beyond their boundaries, the spillover of juvenile and adult fish. Little evidence is available about the so-called ‘recruitment subsidy’, the augmented production of propagules (i.e. eggs and larvae) due to the increased abundance of large-sized spawners hosted within effective MPAs. Once emitted, propagules can be locally retained and/or exported elsewhere. Patterns of propagule retention and/or export from MPAs have been little investigated, especially in the Mediterranean. This study investigated the potential for propagule production and retention/export from a Mediterranean MPA (Torre Guaceto, SW Adriatic Sea) using the white sea bream, Diplodus sargus sargus, as a model species. A multidisciplinary approach was used combining 1) spatial distribution patterns of individuals (post-settlers and adults) assessed through visual census within Torre Guaceto MPA and in northern and southern unprotected areas, 2) Lagrangian simulations of dispersal based on an oceanographic model of the region and data on early life-history traits of the species (spawning date, pelagic larval duration) and 3) a preliminary genetic study using microsatellite loci. Results show that the MPA hosts higher densities of larger-sized spawners than outside areas, potentially guaranteeing higher propagule production. Model simulations and field observation suggest that larval retention within and long-distance dispersal across MPA boundaries allow the replenishment of the MPA and of exploited populations up to 100 km down-current (southward) from the MPA. This pattern partially agrees with the high genetic homogeneity found in the entire study area (no differences in genetic composition and diversity indices), suggesting a high gene flow. By contributing to a better understanding of propagule dispersal patterns, these findings provide crucial information for the design of MPAs and MPA networks effective to replenish fish stocks and enhance fisheries in unprotected areas.     

Characterization of neutralizing antibody responses elicited by clade A envelope immunogens derived from early transmitted viruses

The vast majority of studies with candidate immunogens based on the human immunodeficiency virus envelope (Env) have been conducted with Env proteins derived from clade B viruses isolated during chronic infection. Whether non-clade B Env protein immunogens will elicit antibodies with epitope specificities that are similar to those of antibodies elicited by clade B Envs and whether the antibodies elicited by Envs derived from early transmitted viruses will be similar to those elicited by Envs derived from viruses isolated during chronic infection are currently unknown. Here we performed immunizations with four clade A Envs, cloned directly from the peripheral blood of infected individuals during acute infection, which differed in lengths and extents of glycosylation. The antibody responses elicited by these four Envs were compared to each other and to those elicited by a well-characterized clade B Env immunogen derived from the SF162 virus, which was isolated during chronic infection. Only one clade A Env, the one with the fewer glycosylation sites, elicited homologous neutralizing antibodies (NAbs); these did not target the V1, V2, or V3 regions. In contrast, all four clade A Envs elicited anti-V3 NAbs against "easy-to-neutralize" clade B and clade A isolates, irrespective of the variable region length and extent of glycosylation of the Env used as an immunogen. These anti-V3 NAbs did not access their epitopes on homologous and heterologous clade A, or B, neutralization-resistant viruses. The length and extent of glycosylation of the variable regions on the clade A Env immunogens tested did not affect the breadth of the elicited NAbs. Our data also indicate that the development of cross-reactive NAbs against clade A viruses faces similar hurdles to the development of cross-reactive anti-clade B NAbs.     

How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor: lessons from interleukin-15 (IL-15)/IL-15 receptor alpha

While it is well appreciated that receptors for secreted cytokines transmit ligand-induced signals, little is known about additional roles for cytokine receptor components in the control of ligand transport and secretion. Here, we show that interleukin-15 (IL-15) translocation into the endoplasmic reticulum occurs independently of the presence of IL-15 receptor α (IL-15Rα). Subsequently, however, IL-15 is transported through the Golgi apparatus only in association with IL-15Rα and then is secreted. This intracellular IL-15/IL-15Rα complex already is formed in the endoplasmic reticulum and, thus, enables the further trafficking of complexed IL-15 through the secretory pathway. Just transfecting IL-15Rα in cells, which transcribe but normally do not secrete IL-15, suffices to induce IL-15 secretion. Thus, we provide the first evidence of how a cytokine is chaperoned through the secretory pathway by complexing with its own high-affinity receptor and show that IL-15/IL-15Rα offers an excellent model system for the further exploration of this novel mechanism for the control of cytokine secretion.     

蒜香藤叶挥发油的化学成分

蒜香藤（Pseudocalymma alliaceum Sandw．）又名紫铃藤,为紫葳科（Bignoniaceae）常绿藤状灌木,原产于南美洲的圭亚那和巴西。蒜香藤花、叶在搓揉之后,有浓浓的大蒜香味,其叶深绿富有光泽,花形大而优美,中国许多地方已引种栽培,一般作为篱笆、围墙美化或凉亭、棚架装饰之用。蒜香藤具有浓郁的蒜香,甚至可作为蒜的替代物用于烹饪。但有关其叶挥发性成分研究尚未见报道。本文利用气相色谱-质谱联用技术（GC—MS）分析了西双版纳植物园引种栽培的蒜香藤叶挥发油的化学成分,以期为合理开发和利用蒜香藤植物资源提供科学依据。     

甘薯愈伤组织中的淀粉酶

从甘薯愈伤组织和块根可溶性提取物中淀粉酶的非变性凝胶电泳和活性染色发现 ,愈伤组织和块根的淀粉酶完全不同。前者有 4种不同大小的淀粉酶 (2种α 淀粉酶和 2种 β 淀粉酶 ) ,而后者只有一种 (β 淀粉酶 ) ;其次 ,块根 β 淀粉酶对EDTA和 β 巯基乙醇都不敏感 ,而愈伤组织的淀粉酶对EDTA和 β 巯基乙醇都敏感。这些结果表明甘薯愈伤组织中不仅淀粉酶同工酶的数量多 ,而且包括α和 β两种类型。     

Iron autoxidation and free radical generation: effects of buffers, ligands, and chelators.

The pH of the solution along with chelation and consequently coordination of iron regulate its reactivity. In this study we confirmed that, in general, the rate of Fe(II) autoxidation increases as the pH of the solution is increased, but chelators that provide oxygen ligands for the iron can override the affect of pH. Additionally, the stoichiometry of the Fe(II) autoxidation reaction varied from 2:1 to 4:1, dependent upon the rate of Fe(II) autoxidation, which is dependent upon the chelator. No partially reduced oxygen species were detected during the autoxidation of Fe(II) by ESR using DMPO as the spin trap. However, upon the addition of ethanol to the assay, the DMPO:hydroxyethyl radical adduct was detected. Additionally, the hydroxylation of terephthalic acid by various iron-chelator complexes during the autoxidation of Fe(II) was assessed by fluorometric techniques. The oxidant formed during the autoxidation of EDTA:Fe(II) was shown to have different reactivity than the hydroxyl radical, suggesting that some type of hypervalent iron complex was formed. Ferrous iron was shown to be able to directly reduce some quinones without the reduction of oxygen. In conclusion, this study demonstrates the complexity of iron chemistry, especially the chelation of iron and its subsequent reactivity.     

牛尾草中一新的对映-贝壳杉烷型二萜

从牛尾草[Isodon ternifolius(D.Don)Kudo]的地上部分分离得到一个新的对映－贝壳杉烷型二萜,命名为牛尾草素H（1）,通过波谱方法鉴定了它的结构。此外,还分离得到5个已知的对映－贝壳杉烷型二萜化合物：香茶菜醛（2）,长管香茶菜素A,E和G（3－5）,开展香茶菜素E（6）,以及木樨草素（7）,芹菜素（8）,α－香树脂醇（9）,乌索酸（10）和2α－羟基乌索酸（11）。     

鸡脚参中一个新木脂素

从鸡脚参[Orthosiphon wulfenioides (Diels)Hand.-Marzz.]根中提取分离了一个新的木脂素,命名为鸡脚参木脂素。其结构由NMR、MS等波谱分析确定。初步活性实验显示该化合物不具备抗真菌和抗肿瘤活性。     

细叶香茶菜中两个新的对映—贝壳杉烷二萜化合物

从云南中甸产细叶香茶菜 (Isodontenuifolia (W .W .Smith)Kudo)的地上部分分离得到 6个化合物 ,它们的结构通过波谱方法得到鉴定。其中化合物 1和 2为新的对映_贝壳杉烷二萜化合物 ,即细叶香茶菜甲素 (3β ,6α ,15 β_trihydroxy_1α ,7β_diacetoxy_11β ,16 β_epoxy_ent_kaurane) (1)和细叶香茶菜乙素 (1α,6α ,11β_trihydroxy_3β,7β_diacetoxy_ent_kaur_16_en_15_one) (2 )。     

The KRAS-regulated kinome identifies WEE1 and ERK coinhibition as a potential therapeutic strategy in KRAS-mutant pancreatic cancer

Oncogenic KRAS drives cancer growth by activating diverse signaling networks, not all of which have been fully delineated. We set out to establish a system-wide profile of the KRAS-regulated kinase signaling network (kinome) in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). We knocked down KRAS expression in a panel of six cell lines and then applied multiplexed inhibitor bead/MS to monitor changes in kinase activity and/or expression. We hypothesized that depletion of KRAS would result in downregulation of kinases required for KRAS-mediated transformation and in upregulation of other kinases that could potentially compensate for the deleterious consequences of the loss of KRAS. We identified 15 upregulated and 13 downregulated kinases in common across the panel of cell lines. In agreement with our hypothesis, all 15 of the upregulated kinases have established roles as cancer drivers (e.g., SRC, TGF-β1, ILK), and pharmacological inhibition of one of these upregulated kinases, DDR1, suppressed PDAC growth. Interestingly, 11 of the 13 downregulated kinases have established driver roles in cell cycle progression, particularly in mitosis (e.g., WEE1, Aurora A, PLK1). Consistent with a crucial role for the downregulated kinases in promoting KRAS-driven proliferation, we found that pharmacological inhibition of WEE1 also suppressed PDAC growth. The unexpected paradoxical activation of ERK upon WEE1 inhibition led us to inhibit both WEE1 and ERK concurrently, which caused further potent growth suppression and enhanced apoptotic death compared with WEE1 inhibition alone. We conclude that system-wide delineation of the KRAS-regulated kinome can identify potential therapeutic targets for KRAS-mutant pancreatic cancer.