Vaginal microbiome-hormonal contraceptive interactions associate with the mucosal proteome and HIV acquisition

Alterations to the mucosal environment of the female genital tract, such as genital inflammation, have been associated with increased HIV acquisition in women. As the microbiome and hormonal contraceptives can affect vaginal mucosal immunity, we hypothesized these components may interact in the context of HIV susceptibility. Using previously published microbiome data from 685 women in the CAPRISA-004 trial, we compared relative risk of HIV acquisition in this cohort who were using injectable depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), and combined oral contraceptives (COC). In women who were Lactobacillus-dominant, HIV acquisition was 3-fold higher in women using DMPA relative to women using NET-EN or COC (OR: 3.27; 95% CI: 1.24–11.24, P = 0.0305). This was not observed in non-Lactobacillus-dominant women (OR: 0.95, 95% CI: 0.44–2.15, P = 0.895) (interaction P = 0.0686). Higher serum MPA levels associated with increased molecular pathways of inflammation in the vaginal mucosal fluid of Lactobacillus-dominant women, but no differences were seen in non-Lactobacillus dominant women. This study provides data suggesting an interaction between the microbiome, hormonal contraceptives, and HIV susceptibility.     

Migration of Gasterophilus intestinalis larvae (Diptera: Gasterophilidae) in the equine oral cavity

Cogley T. P., Anderson J. R. and Cooley L. J. 1982. Migration of Gasterophilus intestinalis larvae (Diptera: Gasterophilidae) in the equine oral cavity. International Journal for Parasitology12: 473–480. Larvae of G. intestinalis pursued a specific migratory pathway within the equine oral cavity en route to the stomach. The larval migration included the following sequence: burrowing in the tongue mucosa, invasion of the interdental spaces, transitory attachment at the root of the tongue and movement to the stomach. The molt from first to second instar did not occur in the tongue, as commonly believed, but between the interdental spaces. Ninety five percent of the larvae invading the interdental spaces were associated with gingiva of the upper molars. SEM analysis revealed further details of the oral migration: (1) air holes excavated in the epithelium which connect with deeper burrows; (2) an intimate association between air holes and posterior spiracles of larvae; (3) precise impressions of larvae in tissue immediately surrounding the most recently formed burrows; and (4) initial larval entry into the tongue through the use of natural disruptions or healing lesions. Factors influencing the development of the oral migration are discussed.     

Neoadjuvant Sequential Docetaxel Followed by High‐Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial

To report the results of the DECT trial, a phase II study of locally advanced or operable HER2‐positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA‐IIIB HER2‐positive BC, 18–75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m² intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3‐weekly cycles of epirubicin 120 mg/m² and cyclophosphamide, 600 mg/m², plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8–78). Four‐year recurrence‐free survival was 74.7% (95%CI, 58.2–91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541–2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.     

Estimating parameters of speciation models based on refined summaries of the joint site-frequency spectrum

Understanding the processes and conditions under which populations diverge to give rise to distinct species is a central question in evolutionary biology. Since recently diverged populations have high levels of shared polymorphisms, it is challenging to distinguish between recent divergence with no (or very low) inter-population gene flow and older splitting events with subsequent gene flow. Recently published methods to infer speciation parameters under the isolation-migration framework are based on summarizing polymorphism data at multiple loci in two species using the joint site-frequency spectrum (JSFS). We have developed two improvements of these methods based on a more extensive use of the JSFS classes of polymorphisms for species with high intra-locus recombination rates. First, using a likelihood based method, we demonstrate that taking into account low-frequency polymorphisms shared between species significantly improves the joint estimation of the divergence time and gene flow between species. Second, we introduce a local linear regression algorithm that considerably reduces the computational time and allows for the estimation of unequal rates of gene flow between species. We also investigate which summary statistics from the JSFS allow the greatest estimation accuracy for divergence time and migration rates for low (around 10) and high (around 100) numbers of loci. Focusing on cases with low numbers of loci and high intra-locus recombination rates we show that our methods for the estimation of divergence time and migration rates are more precise than existing approaches.     

The polyketide cyclase RemF from Streptomyces resistomycificus contains an unusual octahedral zinc binding site

RemF is a polyketide cyclase involved in the biosynthesis of the aromatic pentacyclic metabolite resistomycin in Streptomyces resistomycificus. The enzyme is a member of a structurally hitherto uncharacterized class of polyketide cyclases. The crystal structure of RemF was determined by SAD and refined to 1.2 Å resolution. The enzyme subunit shows a β-sandwich structure with a topology characteristic for the cupin fold. RemF contains a metal binding site located at the bottom of the predominantly hydrophobic active site cavity. A zinc ion is coordinated to four histidine side chains, and two water molecules in octahedral ligand sphere geometry, highly unusual for zinc binding sites in proteins.     

Malacofauna Cuaternaria del litoral norte de Santa Cruz (Patagonia, Argentina)

The molluscan content from three “marine terraces” (TM) preserved along 250 km of the Santa Cruz province provided 49 molluscan taxa (33 Gastropoda and 16 Bivalvia) and the first Quaternary records for Ataxocerithium pullum, Crepidula protea, C. aculeata, Adelomelon ferrusacii, Brachidontes rodriguezi, Aequipecten tehuelchus, Ostrea tehuelcha, and Solen tehuelchus. The mollusca assemblages suggest typical marine nearshore conditions similar to the adjacent modern littoral (Southwestern Atlantic), with mostly hard substrates, shallow and cold waters. The TMVI (+ 5-15 m a.s.l., ca. 8-1.2 ka A.P.) is mainly characterized by dominance of Brachidontes spp., Nacella spp. and Mytilus edulis, associated with Siphonaria lessoni. No evidence has been found for the TMVI of clear biotic responses or strong palaeobiogeographic effects during the time span of the Climatic Optimum (“Hypsithermal”, mid-Holocene) which has been documented for other coastal areas northward in Argentina, down to ca. 44-45° S. Scarce differences distinguish the TMV (+ 15-30 m a.s.l., ca. 108-137 ka A.P., MIS5?) and TMIV (+ 20-30 m a.s.l., ca. 242 ka A.P.) regarding the Holocene and the modern littoral. Within the TMV, Clausinella, Eurhomalea, Solen tehuelchus and Brachidontes cf. darwinianus (typically in warmer waters) are exclusive; in the TMIV, Trophon, Buccinanops, Brachidontes and Pectinidae are characteristic. Predominance of Trophon spp. (typically in cold Magallanic waters) in modern samples vs. scarcity or absence in the TM suggest slightly lower modern SST. Several taxonomic similitudes with the Pacific Sudamerican coast (e.g., Fissurella,Nacella, Tegula, Crepidula, Trochita, and Acanthina) could respond to cold currents helping cold-water immigrants to join southern Southamerican Atlantic after the opening of the Drake Passage.     

Adventitious rooting is enhanced by methyl jasmonate in tobacco thin cell layers

Adventitious roots (ARs) are induced by auxins. Jasmonic acid (JA) and methyl jasmonate (MeJA) are also plant growth regulators with many effects on development, but their role on ARs needs investigation. To this aim, we analyzed AR formation in tobacco thin cell layers (TCLs) cultured with 0.01–10 μM MeJA, either under root-inductive conditions, i.e., on medium containing 10 μM indole-3-butyric acid (IBA) and 0.1 μM kinetin, or without hormones. The explants were excised from the cultivars Samsun, Xanthii and Petite Havana, and from genotypes with altered AR-forming ability in response to auxin, namely the non-rooting rac mutant and the over-rooting Agrobacterium rhizogenes rolB transgenic line. Results show that NtRNR1 (G1/S) and Ntcyc29 (G2/M) gene activity, cell proliferation and meristemoid formation were stimulated in hormone-cultured TCLs by submicromolar MeJA concentrations. The meristemoids developed either into ARs and xylogenic nodules, or into xylogenic nodules only (rac TCLs). MeJA-induced meristemoid over-production characterized rolB TCLs. No rooting or xylogenesis occurred under hormone-free conditions, independently of MeJA and genotype. Endogenous JA progressively (days 1–4) increased in hormone-cultured TCLs in the absence of MeJA. JA levels were enhanced by 0.1 μM MeJA, on both days 1 and 4. Endogenous IBA was the only auxin detected, both in the free form and as IBA-glucose. Free IBA increased up to day 2, remaining constant thereafter (day 4). Its level was enhanced by 0.1 μM MeJA only on day 1, while IBA conjugation was not affected by MeJA. Taken together, these results show that an interplay between jasmonates and auxins regulates AR formation and xylogenesis in tobacco TCLs.     

Upper extremity biomechanics in computer tasks differ by gender

ObjectivesThis laboratory study examined gender differences in upper extremity postures, applied forces, and muscle activity when a computer workstation was adjusted to individual anthropometry according to current guidelines.MethodsFifteen men and 15 women completed five standardized computer tasks: touch-typing, completing a form, editing text, sorting and resizing graphical objects and navigating intranet pages. Subjects worked at a height-adjustable workstation with the keyboard on top of the work surface and the mouse to the right. Subjects repeated the text editing task with the mouse in two other locations: a “high” mouse position, which simulated using a keyboard drawer with the mouse on the primary work surface, and “center” mouse position with the mouse between the keyboard and the body, centered with the body’s center line. Surface electromyography measured muscle activity; electrogoniometric and magnetic motion analysis system measured wrist, forearm and upper arm postures; load-cells measured typing forces; and a force-sensing mouse measured applied forces.ResultsRelative forces applied to the keyboard, normalized muscle activity of two forearm muscles, range of motion for the wrist and shoulder joints and external rotation of the shoulder were higher for women (p < 0.05). When subjects were dichotomized instead by anthropometry (either large/small shoulder width or arm length), the differences in forces, muscle activity of the shoulder and wrist posture and shoulder posture became more pronounced with smaller subjects having higher values. Postural differences between the genders increased in the high mouse position and decreased in the center mouse location.ConclusionsWhen a workstation is adjusted per current guidelines differences in upper extremity force, muscle activity and postural factors still exist between genders. However, these were often stronger when subjects were grouped by anthropometry suggesting that perhaps the computer input devices themselves should be scaled to be more in proportion with the anthropometry and strength of the user.