Pneumocystis murina MSG gene family and the structure of the locus associated with its transcription

Analysis of the Pneumocystis murina MSG gene family and expression-site locus showed that, as in Pneumocystis carinii, P. murina MSG genes are arranged in head-to-tail tandem arrays located on multiple chromosomes, and that a variety of MSG genes can reside at the unique P. murina expression site. Located between the P. murina expression site and attached MSG gene is a block of 132 basepairs that is also present at the beginning of MSG genes that are not at the expression site. The center of this sequence block resembles the 28 basepair CRJE of P. carinii, but the block of conserved sequence in P. murina is nearly five times longer than in P. carinii, and much shorter than in P. wakefieldiae. These data indicate that the P. murina expression-site locus has a distinct structure.     

Post-natal imprinting: evidence from marsupials

Genomic imprinting has been identified in therian (eutherian and marsupial) mammals but not in prototherian (monotreme) mammals. Imprinting has an important role in optimising pre-natal nutrition and growth, and most imprinted genes are expressed and imprinted in the placenta and developing fetus. In marsupials, however, the placental attachment is short-lived, and most growth and development occurs post-natally, supported by a changing milk composition tailor-made for each stage of development. Therefore there is a much greater demand on marsupial females during post-natal lactation than during pre-natal placentation, so there may be greater selection for genomic imprinting in the mammary gland than in the short-lived placenta. Recent studies in the tammar wallaby confirm the presence of genomic imprinting in nutrient-regulatory genes in the adult mammary gland. This suggests that imprinting may influence infant post-natal growth via the mammary gland as it does pre-natally via the placenta. Similarly, an increasing number of imprinted genes have been implicated in regulating feeding and nurturing behaviour in both the adult and the developing neonate/offspring in mice. Together these studies provide evidence that genomic imprinting is critical for regulating growth and subsequently the survival of offspring not only pre-natally but also post-natally.     

2013 年全球新药研发报告——第一部分:新药及生物制品（Ⅲ）

该年度报告涉及2013 年最新上市的56 种新药及生物制品,包括20 种新孤儿药和10 种全新药物,以及获得美国FDA“新突破药物”称号的前3 名药物。此外,该年度报告还讨论了30 种重要的延伸性新药（新适应证、新剂型和现有药物的新复方）,以及19 种年内首次获批但在该报告结束时尚未上市的新药。     

2013 年全球新药研发报告——第一部分:新药及生物制品（Ⅱ）

该年度报告涉及2013 年最新上市的56 种新药及生物制品,包括20 种新孤儿药和10 种全新药物,以及获得美国FDA“新突破药物”称号的前3 名药物。此外,该年度报告还讨论了30 种重要的延伸性新药（新适应证、新剂型和现有药物的新复方）,以及19 种年内首次获批但在该报告结束时尚未上市的新药。     

The biology of Placostylus ambagiosus (Pulmonata: Bulimulidae) in New Zealand: Part 2. Population changes,growth, mortality and life expectancy

The large land snail Placostylus ambagiosus (Pulmonata: Bulimulidae) was studied in northernmost New Zealand from 1988 to 2004. At Cape Maria van Diemen (CMvD), more juveniles than adults were found, although estimates showed adults as the most abundant. A cohort, hatched after rodent control commenced in 1990, began maturing in 1995, but 89% died by 1997 (partly through competition with garden snails, Cornu aspersum), before numbers partially recovered by 2003. At Surville Cliffs, adults were estimated to be more abundant than juveniles but few juveniles were observed. Numbers under 12 food plants fluctuated between 425 and 657. Many snails dispersed after horses (Equus caballus) partially defoliated their food plants but returned once these recovered. A translocated population increased after rodent control commenced in 1999, but declined when rodent control ceased in 2002. Another translocated population declined when rodents were present and never recovered even after rodent control commenced in 2002. Snails took 2.8–11.7 years to mature from half-grown juveniles depending on location. Estimated adult life expectancies were 5.2 years at CMvD and 10.0 years at Surville Cliffs. Small juvenile snails experienced the highest mortality, and snails that moved between food plants experienced increased mortality. These results are discussed in relation to conservation management.     

Saved from extinction? Establishment and dispersal of Mercury Islands tusked weta,Motuweta isolata,following translocation onto mammal-free islands

The Mercury Islands tusked weta, Motuweta isolata (Orthoptera: Anostostomatidae), survived only on 13 ha Ahu or Middle Island, a mammal-free island in the Mercury Group, New Zealand. Between 2000 and 2009, 567 individuals were translocated in nine releases to six nearby islands from which mammals had been removed. These translocations occurred to reduce the chance of accidental extinction of the Middle Island population of only a few hundred adults and to contribute to the restoration of the other islands. All translocated insects originated from the captive-bred progeny of one male and two females collected from Middle Island between 1998 and 2001. Their establishment on Double and Red Mercury Islands, after their releases in 2000 and 2001 respectively, was confirmed by searching plots, and by using footprint tracking tunnels on Red Mercury Island between 2008 and 2012. Tracking tunnels provided better data and proved more cost effective than searching plots for detecting large tusked weta. Tracking tunnels demonstrated that the population on Red Mercury expanded outwards from the release sites by 50–100 m each year between 2009 and 2012. These weta are now estimated to be present over more than half the Island. Tusked weta have also survived on Stanley, Korapuki and Ohinau Islands after releases in 2007, but they remain within 100 m of the release sites. No confirmed progeny of the weta released on Cuvier Island in 2008 and 2011 were detected. No tusked weta were detected on Middle Island using tracking tunnels on eight occasions between 2009 and 2012, suggesting this species is likely to be locally extinct. Despite possible failure on one island, these translocations have resulted in a significant conservation success outcome.     

A cell-based computational modeling approach for developing site-directed molecular probes

Modeling the local absorption and retention patterns of membrane-permeant small molecules in a cellular context could facilitate development of site-directed chemical agents for bioimaging or therapeutic applications. Here, we present an integrative approach to this problem, combining in silico computational models, in vitro cell based assays and in vivo biodistribution studies. To target small molecule probes to the epithelial cells of the upper airways, a multiscale computational model of the lung was first used as a screening tool, in silico. Following virtual screening, cell monolayers differentiated on microfabricated pore arrays and multilayer cultures of primary human bronchial epithelial cells differentiated in an air-liquid interface were used to test the local absorption and intracellular retention patterns of selected probes, in vitro. Lastly, experiments involving visualization of bioimaging probe distribution in the lungs after local and systemic administration were used to test the relevance of computational models and cell-based assays, in vivo. The results of in vivo experiments were consistent with the results of in silico simulations, indicating that mitochondrial accumulation of membrane permeant, hydrophilic cations can be used to maximize local exposure and retention, specifically in the upper airways after intratracheal administration.