Biodynamic Studies of Hamster Flank Organ Growth: Hormonal Influences

The biodynamic response of flank organs of male and female hamsters to androgenic stimulation has been studied by autoradiographic and electron microscopic techniques, as well as by routine histology and gross observation. Intraperitoneal administration of 2.5mg of testosterone on alternate days resulted in bilateral increase in palpable bulk, and pigmentation of flank organs of females, males, and castrated males. Topical application of testosterone, dihydrotestosterone (DHT), methyltestosterone, or androstenedione to one flank organ of females resulted in unilateral stimulation of sebaceous gland growth and pigmentation. Androsterone, epiandrosterone, and progesterone did not cause flank organ growth or increased pigmentation when applied topically. Histologic changes in flank organs of castrated males following testosterone administration are described. Auto0radiographic studies indicate a decrease in the labeling index of flank organ sebaceous gland cells within 20 hours after castration and a subsequent significant increase in the labeling index within 10 hours after a single intraperitoneal administration of 2.5mg of testosterone. Pigmentation of flank organs is due to the presence of dendritic cells in the dermis which contain dense structures resembling stage IV melanosomes

Mechanism of Ad5 Vaccine Immunity and Toxicity: Fiber Shaft Targeting of Dendritic Cells

Recombinant adenoviral (rAd) vectors elicit potent cellular and humoral immune responses and show promise as vaccines for HIV-1, Ebola virus, tuberculosis, malaria, and other infections. These vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. At the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after systemic high-dose recombinant adenovirus serotype 5 (rAd5) vector administration in a human gene therapy trial. The mechanism responsible for these effects is poorly understood. Here, we define the mechanism by which Ad5 targets immune cells that stimulate adaptive immunity. rAd5 tropism for dendritic cells (DCs) was independent of the coxsackievirus and adenovirus receptor (CAR), its primary receptor or the secondary integrin RGD receptor, and was mediated instead by a heparin-sensitive receptor recognized by a distinct segment of the Ad5 fiber, the shaft. rAd vectors with CAR and RGD mutations did not infect a variety of epithelial and fibroblast cell types but retained their ability to transfect several DC types and stimulated adaptive immune responses in mice. Notably, the pyrogenic response to the administration of rAd5 also localized to the shaft region, suggesting that this interaction elicits both protective immunity and vector-induced fevers. The ability of replication-defective rAd5 viruses to elicit potent immune responses is mediated by a heparin-sensitive receptor that interacts with the Ad5 fiber shaft. Mutant CAR and RGD rAd vectors target several DC and mononuclear subsets and induce both adaptive immunity and toxicity. Understanding of these interactions facilitates the development of vectors that target DCs through alternative receptors that can improve safety while retaining the immunogenicity of rAd vaccines

Corneal Refractive Surgery in Patients with History of Optic Neuritis

Purpose The purpose of this study was to evaluate the risk of recurrence of optic neuritis after corneal refractive surgery in patients with a history of optic neuritis and to examine the safety and efficacy of the procedure in this population. Methods This was a retrospective chart review of patients with a history of optic neuritis who underwent laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) at a single tertiary center from June 1996 to December 2014. Fifteen eyes of 14 patients were included in this study. Visual acuity before and after the surgery was recorded. Patients were followed-up for over five years postoperatively for the recurrence of optic neuritis. Results The average LogMAR best corrected visual acuity (BCVA) preoperatively was 0.12 ± 0.19 (–0.10 to 0.60) and postoperatively was 0.06 ± 0.10 (–0.10 to 0.30). No eyes lost lines of BCVA. The average LogMAR uncorrected distance visual acuity (UDVA) after surgery was 0.12 ± 0.13 (0.00 to 0.48). Twenty-eight percent of patients reached a UDVA of 20/20 or better after refractive surgery. Optic neuritis recurred in 3/15 (20%) eyes and 3/14 patients (21%). Conclusion While corneal refractive procedures appear safe in patients with a history of optic neuritis, our data suggest that their efficacy may be reduced

Corneal Refractive Surgery in Patients with History of Optic Neuritis

Purpose: The purpose of this study was to evaluate the risk of recurrence of optic neuritis after corneal refractive surgery in patients with a history of optic neuritis and to examine the safety and efficacy of the procedure in this population. Methods: This was a retrospective chart review of patients with a history of optic neuritis who underwent laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) at a single tertiary center from June 1996 to December 2014. Fifteen eyes of 14 patients were included in this study. Visual acuity before and after the surgery was recorded. Patients were followed-up for over five years postoperatively for the recurrence of optic neuritis. Results: The average LogMAR best corrected visual acuity (BCVA) preoperatively was 0.12 ± 0.19 (–0.10 to 0.60) and postoperatively was 0.06 ± 0.10 (–0.10 to 0.30). No eyes lost lines of BCVA. The average LogMAR uncorrected distance visual acuity (UDVA) after surgery was 0.12 ± 0.13 (0.00 to 0.48). Twenty-eight percent of patients reached a UDVA of 20/20 or better after refractive surgery. Optic neuritis recurred in 3/15 (20%) eyes and 3/14 patients (21%). Conclusion: While corneal refractive procedures appear safe in patients with a history of optic neuritis, our data suggest that their efficacy may be reduced

Astigmatic correction with implantation of a light adjustable vs monofocal lens: a single site analysis of a randomized controlled trial

AIM To evaluate the light adjustable lens (LAL) vs a standard monofocal lens in achieving target astigmatic refraction and improving postoperative uncorrected distance visual acuity (UDVA). METHODS This randomized controlled clinical trial included 40 patients with pre-existing astigmatism and visually significant cataract. Twenty-eight patients received the LAL and 12 control patients received a monofocal intraocular lens (IOL) after cataract extraction at a single institution. The patients with the LAL underwent adjustment by ultraviolet (UV) light postoperatively plus subsequent lock-in procedures and all patients returned to clinic for follow up of study parameters at 6, 9, and 12mo. Manifest refraction, distance visual acuity, and adverse events were recorded at each visit. RESULTS The mean cylinder before adjustment in eyes with the LAL was -0.89±0.58 D (-2.00 to 0.00 D) and -0.34±0.34 D (-1.25 to 0.00 D) after lock-in (P=1.68x10−8). The mean cylinder in patients with the monofocal lens was -1.00±0.32 D (-1.50 to -0.50 D) at 17-21d postoperatively, which was statistically different from the LAL cylinder post lock-in (P=1.43x10−6). UDVA in the LAL group was 20/20 or better in 79% of patients post lock-in with good stability over 12mo compared with 33% of the control patients with UDVA of 20/20 or better. CONCLUSION These results demonstrate that the LAL is more effective in achieving target refractions and improving postoperative UDVA in patients with pre-existing corneal astigmatism than a standard monofocal lens

Multi-Messenger Astronomy with Extremely Large Telescopes

The field of time-domain astrophysics has entered the era of Multi-messenger Astronomy (MMA). One key science goal for the next decade (and beyond) will be to characterize gravitational wave (GW) and neutrino sources using the next generation of Extremely Large Telescopes (ELTs). These studies will have a broad impact across astrophysics, informing our knowledge of the production and enrichment history of the heaviest chemical elements, constrain the dense matter equation of state, provide independent constraints on cosmology, increase our understanding of particle acceleration in shocks and jets, and study the lives of black holes in the universe. Future GW detectors will greatly improve their sensitivity during the coming decade, as will near-infrared telescopes capable of independently finding kilonovae from neutron star mergers. However, the electromagnetic counterparts to high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus demand ELT capabilities for characterization. ELTs will be important and necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve

JINGLE, a JCMT legacy survey of dust and gas for galaxy evolution studies: II. SCUBA-2 850 μm data reduction and dust flux density catalogues

We present the SCUBA-2 850μm component of JINGLE, the new JCMT large survey for dust and gas in nearby galaxies, which with 193 galaxies is the largest targeted survey of nearby galaxies at 850 μm. We provide details of our SCUBA-2 data reduction pipeline, optimized for slightly extended sources, and including a calibration model adjusted to match conventions used in other far-infrared (FIR) data. We measure total integrated fluxes for the entire JINGLE sample in 10 infrared/submillimetre bands, including all WISE, Herschel-PACS, Herschel-SPIRE, and SCUBA-2 850 μm maps, statistically accounting for the contamination by CO(J = 3-2) in the 850 μm band. Of our initial sample of 193 galaxies, 191 are detected at 250 μm with a ≥5σ significance. In the SCUBA-2 850 μm band we detect 126 galaxies with ≥3σ significance. The distribution of the JINGLE galaxies in FIR/sub-millimetre colour-colour plots reveals that the sample is not well fit by single modified-blackbody models that assume a single dust-emissivity index (β). Instead, our new 850 μm data suggest either that a large fraction of our objects require β < 1.5, or that a model allowing for an excess of sub-mm emission (e.g. a broken dust emissivity law, or a very cold dust component ≲10 K) is required. We provide relations to convert FIR colours to dust temperature and β for JINGLE-like galaxies. For JINGLE the FIR colours correlate more strongly with star-formation rate surface-density rather than the stellar surface-density, suggesting heating of dust is greater due to younger rather than older stellar-populations, consistent with the low proportion of early-type galaxies in the sample

Structural basis of trehalose recognition by the mycobacterial LpqY-SugABC transporter

The Mycobacterium tuberculosis (Mtb) LpqY-SugABC ATP-binding cassette transporter is a recycling system that imports trehalose released during remodelling of the Mtb cell-envelope. As this process is essential for the virulence of the Mtb pathogen it may represent an important target for tuberculosis drug and diagnostic development, but the transporter specificity and molecular determinants of substrate recognition are unknown. To address this, we have determined the structural and biochemical basis of how mycobacteria transport trehalose using a combination of crystallography, STD NMR, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays and the synthesis of trehalose analogues. This analysis pinpoints key residues of the LpqY substrate binding lipoprotein that dictate substrate-specific recognition and has revealed which disaccharide modifications are tolerated. These findings provide critical insights into how the essential Mtb LpqY-SugABC transporter reuses trehalose and modified analogues, and specifies a framework that can be exploited for the design of new anti-tubercular agents and/or diagnostic tools

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The origin and speciation of orchids

SummaryOrchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis.We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants.The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica.These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation