SPL7013 Gel (VivaGel?) Retains Potent HIV-1 and HSV-2 Inhibitory Activity following Vaginal Administration in Humans

SPL7013 Gel (VivaGel^®) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with ≥5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup™ pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p≤0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), p = 0.9]; HSV-2 [94% (91,97), p = 0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus.

Trial Registration

The study is registered at ClinicalTrials.gov under identifier: {"type":"clinical-trial","attrs":{"text":"NCT00740584","term_id":"NCT00740584"}}NCT00740584     

New Silurian cooksonias from dolostones of north-eastern North America

New specimens of Cooksonia and Hostinella are described from the Bertie Group of Ontario and New York State, which is dated by faunas as latest Silurian (Přídolí). The rare plant fossils are unusual in that they are preserved in fine-grained, slightly argillaceous dolostones ('waterlime') rather than clastic rocks. At least two species of Cooksonia are present, one with ± globular sporangial morphology close to C. hemisphaerica Lang. Those with ellipsoidal/discoidal sporangia are compared with C. pertoni Lang, C .  paranensis Gerrienne et al . and C. bohemica Schweitzer, the latter represented by a single specimen from the Přídolí of the Czech Republic. However, the paucity of specimens, which prevents assessment of taphonomic influences on shape, combined with the absence of any anatomical features and the gross morphological simplicity of the fossils, precludes specific assignment. Specimens of Hostinella include one in which apices and a lateral basal structure resembling a root are preserved. It is concluded that the Laurentian assemblage of Ontario and New York State is less diverse and disparate than coeval assemblages, which are also preserved in marine rocks. Its preservation in limestones may have been facilitated by the hypersalinity inferred from various sedimentary features, which would restrict the activity of many decomposers.  © 2004 The Linnean Society of London, Botanical Journal of the Linnean Society , 2004, 146 , 399–413.     

The South American catfish genus Auchenipterus Valenciennes, 1840 (Ostariophysi: Siluriformes: Auchenipteridae): monophyly and relationships, with a revisionary study

The Neotropical catfishes of the genus Auchenipterus Valenciennes (1840) are reviewed. The genus is hypothesized to be a monophyletic assemblage on the basis of the shared presence of grooves in the ventral surface of the head that accommodate adducted mental barbels. A possible second synapomorphy, the presence of papillae on the dorsal and medial surface of the ossified maxillary barbel of mature males, is tentatively advanced pending discovery of adult males of three species. Contrary to previous hypotheses which considered Auchenipterus to consist of a maximum of five species, we recognize 11 species, including two previously undescribed forms, A. britskii and A. menezesi: Auchenipterus is broadly distributed through the Rio Orinoco, Rio Amazonas, and Rio de La Plata basins, and the coastal drainages of the Guianas, with one species in the Rio Pindare-Mirim and Rio Parnaiba basins of northeastern Brazil. Auchenipterus nuchalis, previously thought to be broadly distributed across the range of the genus, is found to rather have a restricted distribution in the eastern portions of the Amazon basin, the lower portions of the Rio Tocantins, and lower courses of some rivers in Suriname and French Guiana. Citations of A. nuchalis from elsewhere in the range of the genus are of other species. Euanemus Müller & Troschel (1842) and Ceratocheilus Miranda Ribeiro (1918) are considered synonyms of Auchenipterus. Euanemus colymbetes Müller & Troschel (1842) is considered a synonym of Auchenipterus (fen/ata Valenciennes (1840), and A. paysanduanus Devincenzi (1933) is placed into the synonymy of A. nigripinnis Boulenger (1895). A neotype is designated for Hypopthalmus nuchalis Spix & Agassiz (1829). Lectotypes are designated for Euanemus colymbetes and Auchenipterus nigripinnis.     

Host preferences in a phonotactic parasitoid of field crickets: the relative importance of host song characters

Abstract.  1. Predators, including insect parasitoids, often eavesdrop on prey signals, and as a result, predation can have important effects on the evolution of prey signalling behaviour.
2. The phonotactic parasitoid fly, Ormia ochracea , uses the calling songs of male field crickets to locate their field crickets hosts. In the western USA, this fly parasitises the variable field cricket, Gryllus lineaticeps . Previous work with one fly population suggested that female flies, like female field crickets, preferentially orient to male songs with higher chirp rates and longer chirp durations, although a limited range of male song types was used in this previous study. The current study, with a different fly population, used field-based, two-speaker choice tests to examine: (1) the effect of male chirp rate and chirp duration on fly attraction, using a natural range of song types; and (2) the relative importance of these song types in host selection by the flies.
3. Three lines of evidence suggested that chirp rate is more important than chirp duration in host selection. (a) The flies consistently preferred higher chirp rates but only sometimes preferred longer chirp durations. (b) The flies consistently preferred higher chirp rate/shorter chirp duration songs to lower chirp rate/longer chirp duration songs. (c) Preferences for longer chirp durations could be eliminated by increasing the amplitude of the less attractive song type, while preferences for higher chirp rates could only sometimes be eliminated by increasing the amplitude of the less attractive song type.
4. Fly predation may favour lower chirp rates and shorter chirp durations in G. lineaticeps , and may have resulted in stronger selection on chirp rate than on chirp duration.     

Estrogen regulation of trefoil factor 1 expression by estrogen receptor alpha and Sp proteins

Estrogen-responsive genes in human breast cancer cells often have an estrogen response element (ERE) positioned next to an Sp1 binding site. In chromatin immunoprecipitation (ChIP) assays, we investigated the binding of estrogen receptor alpha (ER), Sp1, and Sp3 to the episomal and native estrogen-responsive trefoil factor 1 (TFF1; formerly pS2) promoter in MCF-7 breast cancer cells. Mutation of the Sp site upstream of the ERE reduced estrogen responsiveness and prevented binding of Sp1 and Sp3, but not ER to the episomal promoter. In the absence of estradiol (E2), Sp1, Sp3, histone deacetylase 1 (HDAC), and HDAC2, and low levels of acetylated H3 and H4 are associated with the native promoter, with the histones being engaged in dynamic reversible acetylation. Following E2 addition, levels of ER and acetylated H3 and H4 bound to the native promoter increases. There is clearance of Sp1, but not of Sp3, from the promoter while HDAC1 and HDAC2 remain bound. These data are consistent with a model in which Sp1 or Sp3 aid in recruitment of HDACs and histone acetyltransferases (HATs) to mediate dynamic acetylation of histones associated with the TFF1 promoter, which is in a state of readiness to respond to events occurring following the addition of estrogen.     

Activity following arousal in winter in North American vespertilionid bats

• 1 Many bat species hibernate to conserve energy during winter and like all hibernators they commonly arouse. During these arousals, some bats may undertake activities away from the hibernation site. Systematic ecological studies of the frequency and purpose of winter activity in temperate zone bats of North America are rare and much of the literature involves observations of single individuals or unmarked populations.
• 2 We review the available literature on winter activity among North American vespertilionid bats to highlight the paucity of data on this subject and to stimulate future research. Due to the lack of repeated, systematic studies on most North American species, the conclusions drawn are general or pertain only to parts of the geographical range of any species.
• 3 We suggest that winter activity is ubiquitous among temperate zone bats, but the degree and purpose of activity varies greatly between and within species. In general, cave‐dwelling bats tend to be relatively inactive compared with tree and foliage roosting bats during winter.
• 4 Cave‐dwelling and tree cavity‐dwelling species do not appear to feed, but they do drink and occasionally copulate during the hibernation period. Species that hibernate in foliage or leaf litter are the most active species during winter and may feed and drink throughout winter, although they probably do not copulate because of their solitary nature.
• 5 We encourage researchers to conduct studies on all aspects of winter activity for North American vespertilionids across wide latitudinal and altitudinal gradients. We suggest studies in the near future be focused on estimating the energetic costs and benefits of winter activity through determination of the frequency and intensity of winter feeding activity and more thorough examinations of movements within and among caves. Studies on common, wide‐ranging species have the potential to illuminate large‐scale patterns and differences and should be favoured over studies on rarer species.

     

Compression or tension? The stress distribution in the proximal femur

Background  

Questions regarding the distribution of stress in the proximal human femur have never been adequately resolved. Traditionally, by considering the femur in isolation, it has been believed that the effect of body weight on the projecting neck and head places the superior aspect of the neck in tension. A minority view has proposed that this region is in compression because of muscular forces pulling the femur into the pelvis. Little has been done to study stress distributions in the proximal femur. We hypothesise that under physiological loading the majority of the proximal femur is in compression and that the internal trabecular structure functions as an arch, transferring compressive stresses to the femoral shaft.