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Geographic and environmental variation in the animal microbiota can be directly linked to the evolution and wild fitness of their hosts but often appears to be disordered. Here, we sought to better understand patterns that underlie wild variation in the microbiota composition of Drosophila melanogaster . First, environmental temperature predicted geographic variation in fly microbial communities better than latitude did. The microbiota also differed between wild flies and their diets, supporting previous conclusions that the fly microbiota is not merely a reflection of diet. Flies feeding on different diets varied significantly in their microbiota composition, and flies sampled from individual apples were exceptionally depauperate for the Lactic Acid Bacteria (LAB), a major bacterial group in wild and laboratory flies. However, flies bore significantly more LAB when sampled from other fruits or compost piles. Follow-up analyses revealed that LAB abundance in the flies uniquely responds to fruit decomposition, whereas other microbiota members better indicate temporal seasonal progression. Finally, we show that diet-dependent variation in the fly microbiota is associated with phenotypic differentiation of fly lines collected in a single orchard. These last findings link covariation between the flies' dietary history, microbiota composition, and genetic variation across relatively small (single-orchard) landscapes, reinforcing the critical role that environment-dependent variation in microbiota composition can play in local adaptation and genomic differentiation of a model animal host., Significance Statement: The microbial communities of animals influence their hosts' evolution and wild fitness, but it is hard to predict and explain how the microbiota varies in wild animals. Here, we describe that the microbiota composition of wild Drosophila melanogaster can be ordered by temperature, humidity, geographic distance, diet decomposition, and diet type. We show how these determinants of microbiota variation can help explain lactic acid bacteria (LAB) abundance in the flies, including the rarity of LAB in some previous studies. Finally, we show that wild fly phenotypes segregate with the flies' diet and microbiota composition, illuminating links between the microbiota and host evolution. Together, these findings help explain how variation in microbiota compositions can shape an animal's life history.

Purpose: Age-related cataract is the leading cause of blindness worldwide. Variants in the EPHA2 gene increase the disease risk, and its knockout in mice causes cataract. We investigated whether age, sex, and genetic background, risk factors for age-related cataract, and Epha2 genotype influence Epha2-related cataract development in mice., Methods: Cataract development was monitored in Epha2+/+, Epha2+/-, and Epha2-/- mice (Epha2Gt(KST085)Byg) on C57BL/6J and FVB:C57BL/6J (50:50) backgrounds. Cellular architecture of lenses, endoplasmic reticulum (ER) stress, and redox state were determined using histological, molecular, and analytical techniques., Results: Epha2-/- and Epha2+/- mice on C57BL/6J background developed severe cortical cataracts by 18 and 38 weeks of age, respectively, compared to development of similar cataract significantly later in Epha2-/- mice and no cataract in Epha2+/- mice in this strain on FVB background, which was previously reported. On FVB:C57BL/6J background, Epha2-/- mice developed severe cortical cataract by 38 weeks and Epha2+/- mice exhibited mild cortical cataract up to 64 weeks of age. Progression of cataract in Epha2-/- and Epha2+/- female mice on C57BL/6J and mixed background, respectively, was slower than in matched male mice. N-cadherin and β-catenin immunolabeling showed disorganized lens fiber cells and disruption of lens architecture in Epha2-/- and Epha2+/- lenses, coinciding with development of severe cataracts. EPHA2 immunolabeling showed intracellular accumulation of the mutant EPHA2-β-galactosidase fusion protein that induced a cytoprotective ER stress response and in Epha2+/- lenses was also accompanied by glutathione redox imbalance., Conclusions: Both, Epha2-/- and Epha2+/- mice develop age-related cortical cataract; age as a function of Epha2 genotype, sex, and genetic background influence Epha2-related cataractogenesis in mice.

Tiopronin is an FDA-approved thiol drug currently used to treat cystinuria and rheumatoid arthritis. However, due to its antioxidant properties, it may be beneficial in a variety of other conditions. One primary obstacle to its wider application is its limited bioavailability, which necessitates administration of high systemic doses to achieve localized therapeutic effects. Incorporation of a drug delivery vehicle can solve this dilemma by providing a means of controlled, targeted release. Functionalized nanodiamond is a promising theranostic platform that has demonstrated great potential for biomedical applications, including drug delivery. Design of nanodiamond theranostic platforms requires comprehensive understanding of drug-platform interactions, and the necessary physical chemical investigations have only been realized for a limited number of compounds. Towards the long-term goal of developing a nanodiamond-tiopronin treatment paradigm, this study aims to shed light on the effects of nanodiamond surface chemistry on adsorption and release of tiopronin. Specifically, adsorption isotherms were measured and fit to Langmuir and Freundlich models for carboxylated, hydroxylated, and aminated nanodiamonds, and release was monitored in solutions at pH 4.0, 5.8, 7.3, and 8.1. Our results indicate that aminated nanodiamonds exhibit the highest loading capacity while hydroxylated nanodiamonds are the most effective for sustained release. Therefore, a high degree of flexibility may be afforded by the use of nanodiamonds with different surface chemistries optimized for specific applications.

Aim: To evaluate the efficacy of a technical modification to reduce the incidence of traumatic cataract induced by Descemet stripping automated endothelial keratoplasty (DSAEK) performed in phakic eyes., Methods: A retrospective cohort study. The records of all patients with a clear crystalline lens and endothelial failure that underwent modified DSAEK at our insitution were reviewed. In this modification, in order to avoid inadvertent touch of the insertion forceps against the exposed crystalline lens while passing across the anterior chamber, the incision sites were shifted from the standard 9 and 3 o'clock positions, superiorly to the 10 and 2 o'clock position respectively. Formation of typically traumatic, anterior subcapsular cataract in these patients was compared to that observed in a cohort including all the patients with a clear crystalline lens and endothelial failure that underwent conventional DSAEK at our institution., Results: The study group included 49 eyes following modified DSAEK and the control group included 35 eyes following DSAEK with conventional incision sites. Anterior subcapsular cataract occurring 4mo or less postoperatively was identified in 2 of 49 (4%) eyes in the study group and 7 of 35 (20%) eyes in the control group. The rates of traumatic cataract were significantly higher in the control group in comparison to the study group ( P =0.03, RR=4.9, 95%CI 1.08-22.1)., Conclusion: Traumatic cataract formation following phakic DSAEK may be avoided with a simple modification to the position of the incision sites.

Descemet's membrane detachments (DMD) are relatively common after cataract surgery and most do not require any treatment. However, if large DMD are not treated appropriately, significant visual morbidity can ensue. We aim to develop a guideline for the management of DMD post cataract surgery based on a retrospective review of all cases encountered at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia over a 4-year period from 2010 to 2014. We suggest conservative management if the visual axis is not involved; however, after 3mo surgical intervention may be warranted to prevent corneal sequelae. In cases where the visual axis is involved we suggest early intervention with air tamponade. The main risk factor for irreversible corneal oedema and subsequent endothelial transplant appears to be direct endothelial trauma rather than the DMD itself.

We present a case of a central Descemet's membrane detachment (DMD) induced by an Ophthalmic Viscosurgical Device during phacoemulsification surgery that resolved spontaneously, leaving a best spectacle corrected visual acuity of 20/20. The detachment was monitored with serial anterior segment optical coherence tomography images. Most cases of central DMD reported in the literature have been managed surgically to facilitate rapid visual recovery and minimize the risk of scarring. Our case adds to the literature in providing an alternative management strategy where surgical intervention may not be possible.

Objective: To report the outcome of mushroom keratoplasty for the treatment of full thickness corneal disease in pediatric patients with healthy endothelium., Methods: A retrospective analysis of pediatric patients who underwent mushroom keratoplasty. The medical records of pediatric patients suffering from full thickness corneal stromal disease with normal endothelium who underwent mushroom keratoplasty at our Institution were included. A two-piece donor graft consisting of a large anterior stromal lamella (9.0 mm in diameter and ±250 μm in thickness) and a small posterior lamella (5-6.5 mm in diameter) including deep stroma and endothelium, prepared with the aid of a microkeratome had been transplanted in all cases. Ophthalmic examination including slit lamp examination, best corrected visual acuity, and corneal topography was performed preoperatively and at each postoperative visit on all patients. The endothelial cells were assessed by specular microscopy in these patients., Results: Six eyes of six patients (five males and one female) were included. The mean age was 9.3 years (range 5-15 years). Average follow-up was 17.8 months (range 9-48 months). There were no early or late complications recorded. All corneas were clear at the last follow up visit. Preoperative best corrected visual acuity (BCVA) was worse than 20/70 in all six eyes. Postoperatively, four eyes achieved BCVA of 20/40 or better. Endothelial cell loss (n eyes = 3 averaged 24% (range 19-31%). The mean endothelial cell loss was 24% (range 19-31%) among these patients., Conclusions: Microkeratome assisted mushroom keratoplasty is a viable surgical option for pediatric eyes with full thickness corneal stromal disease and healthy endothelium. Mushroom keratoplasty combines the refractive advantage of a large penetrating keratoplasty with the survival advantage of a small penetrating keratoplasty. Furthermore, mushroom keratoplasty exhibits the mechanical advantage of a shaped keratoplasty.

We determined that the variability in the oxygen cost and thus the caloric expenditure of cycling at a given work rate (i.e., cycling economy) observed among highly endurance-trained cyclists (N = 19; mean +/- SE; VO2max, 4.9 +/- 0.1 l.min-1; body weight, 71 +/- 1 kg) is related to differences in their % Type I muscle fibers. The percentage of Type I and II muscle fibers was determined from biopsies of the vastus lateralis muscle that were histochemically stained for ATPase activity. When cycling a Monark ergometer at 80 RPM at work rates eliciting 52 +/- 1, 61 +/- 1, and 71 +/- 1% VO2max, efficiency was determined from the caloric expenditure responses (VO2 and RER using open circuit spirometry) to steady-state exercise. Gross efficiency (GE) was calculated as the ratio of work accomplished.min-1 to caloric expenditure.min-1, whereas delta efficiency (DE) was calculated as the slope of this relationship between approximately 50 and 70% VO2max. The % Type I fibers ranged from 32 to 76%, and DE when cycling ranged from 18.3 to 25.6% in these subjects. The % Type I fibers was positively correlated with both DE (r = 0.85; P less than 0.001; N = 19) and GE (r = 0.75; P less than 0.001; N = 19) during cycling. Additionally, % Type I fibers was positively correlated with GE (r = 0.74; P less than 0.001; N = 13) measured during the novel task of two-legged knee extension; performed at a velocity of 177 +/- 6 degrees.s-1 and intensity of 50 and 70% of peak VO2 for that activity.(ABSTRACT TRUNCATED AT 250 WORDS)