Investigation of the terminal P4 domain in a series of D-phenylglycinamide-based factor Xa inhibitors

Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats.     

Investigation of factor Xa inhibitors containing non-amidine S1 elements

Several non-amidino S1 derivatives of the 1,2-diaminobenzene-based scaffold (4) were synthesized and evaluated for their ability to bind to the active site and inhibit the human protease factor Xa. A subset of these compounds were also evaluated for their anticoagulant effects in human plasma as measured by prothrombin time (PT).     

Large Hawk‐Cuckoo Hierococcyx sparverioides parasitism on the Chinese Babax Babax lanceolatus may be an evolutionarily recent host–parasite system

We documented brood parasitism by the poorly studied Large Hawk‐Cuckoo on a previously unknown host species, the Chinese Babax. Furthermore, we describe a new egg colour for the Large Hawk‐Cuckoo. The parasitism rate of Chinese Babax nests over 4 years was 6.9% (11 of 159 nests), with significant temporal variation. The Large Hawk‐Cuckoo laid immaculate white eggs that appeared non‐mimetic to the blue Babax eggs, an impression that was confirmed by avian visual modelling. Nevertheless, most Cuckoo eggs were accepted by the host, suggesting that this host–parasite system may be evolutionarily recent.     

Seasonal Pulses of Marburg Virus Circulation in Juvenile Rousettus aegyptiacus Bats Coincide with Periods of Increased Risk of Human Infection

Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ∼2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (∼six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.     

Parnassia palustris: a genetically diverse species in Scandinavia

Patterns of variation at nine enzyme loci were examined in 528 plants representing diploid and tetraploid populations of Parnassia palustris s. l. in Europe to assess genetic variation patterns and migration history. Half of the plants showed a unique multilocus phenotype and 75% of all phenotypes occurred only in Scandinavia. Diploid populations showed similar levels of genetic diversity as other widespread outbreeding species with animal-mediated pollination and F -statistics indicated excessive heterozygosity and low rates of gene flow among them. In spite of dramatic population histories caused by the ice ages, diploid populations have maintained the same genetic diversity in Scandinavia as in central and southern Europe. Northern populations have apparently been established through the gradual advance of genetically variable populations and patterns of variation at individual loci indicate different migration routes, from the south-south-west and the east-north-east, respectively. The data strongly support a repeated autoploid origin of the tetraploid cytotype which has been much more successful than the diploid progenitors in colonizing new land since the last ice age. High genetic diversity in Scandinavia has apparently been obtained by a combination of immigration of plants from different source areas and recurrent formation of autotetraploids from diploid progenitors.  © 2003 The Linnean Society of London, Botanical Journal of the Linnean Society , 2003, 142 , 347−372.     

State-Dependent Mate-Assessment and Mate-Selection Behavior in Female Threespine Sticklebacks (Gasterosteus aculeatus, Gasterosteiformes: Gasterosteidae)

Most investigations of mate-choice have focused on the outcomes of mate-choice (i.e. which mates are chosen), and thus we generally know very little about how mates are chosen (i.e. how mates are found, assessed, and selected). Mate-choice by females has been shown to be dependent on the state of the female, with females being less selective when limited by time or energy. This result could be caused by changes in female mate-assessment or mate-selection behavior. We examined whether manipulations of time and energy affected the mate-choice behavior of female threespine stickleback ( Gasterosteus aculeatus ). We found that female mate-choice behavior, when not divided into stages, was affected by both of the manipulations. This matches previous findings. When we divided female courtship behavior into six stages, we found that the two manipulations affected different portions of the mate-choice process. The holding-time manipulation changed female behavior at the beginning and end of the mate-choice process and the swimming manipulation changed female behavior only at the end of the mate-choice process. Neither of the manipulations significantly affected female behavior in the middle portion of the mate-choice process. Thus, the mate-choice process appears to be composed of multiple state-dependent decisions. We discuss how a better mechanistic understanding of how female state affects female mate-choice behavior can produce testable predictions and provide a basis for investigating the evolution of mating systems.