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The study identifies two families, each with three siblings affected with retinitis pigmentosa (RP) and sharing large overlapping homozygous regions harboring the IMPG2 gene on chromosome 3. Results show the IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, suggesting that mutations in a structural component of the interphotoreceptor matrix can cause autosomal-recessive RP.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.anbehav.2009.06.036 Byline: Michelle den Hollander, Darryl T. Gwynne Abstract: Despite widespread evidence for the benefits of polyandry, there are costs associated with each mating for females, and for many species, it is unknown whether the costs of extra matings outweigh the benefits. In the seed beetle Callosobruchus maculatus (Coleoptera: Chrysomelidae: Bruchinae), costs might come from male harassment during mating attempts or from injuries that females sustain during copulation. Benefits of mating might come from nutrients or water transferred in the ejaculate. If mating is costly overall, male presence (sexual harassment) and multiple mating in C. maculatus is expected to reduce female fitness. Females were housed with differing numbers of males (1-4) and differing opportunities for copulation. When females were both harassed by and could remate with more than one male, they had lower lifetime reproductive rates and reduced life span relative to monandrous females. These results indicate that when females are continually exposed to multiple males, the direct benefits of multiple mating do not compensate for the costs. Author Affiliation: Department of Ecology and Evolutionary Biology, University of Toronto Article History: Received 2 December 2008; Revised 22 January 2009; Accepted 8 June 2009 Article Note: (miscellaneous) MS. number: A08-00768R

A genome-wide homozygosity mapping study is conducted to identify genes that cause cone dystrophy (CD) and achromatopsia (ACHM), which are constituents of early-onset cone photoreceptor disorders in humans. Results reveal that mutations in the PDE6C gene cause the diseases associated with early-onset photoreceptor disorders.

[Display omitted] CC chemokine receptor 2 and CCL2 are highly involved in cancer growth and metastasis, and immune escape. Raised sodium ion concentrations in solid tumours have also been correlated to metastasis and immune modulation. Sodium ions can modulate class A G protein-coupled receptors through the sodium ion binding site characterized by a highly conserved aspartic acid residue (D2.50), also present in CCR2. Hence, we further explored this binding site in CCR2 by radioligand binding studies and mutagenesis. Modulation of three distinctly binding radioligands by sodium ions and amiloride derivates was investigated. Sodium ions were observed to be relatively weak modulators of antagonist binding, but substantially increased 125I-CCL2 dissociation from CCR2. 6-Substituted Hexamethylene Amiloride (HMA) modulated all tested radioligands. Induced-fit docking of HMA in the presumed sodium ion binding site of CCR2 confirmed its binding site. Finally, investigation of (cancer-associated) mutations in the sodium ion binding site showed a markedly decreased expression compared to wild type. Only two mutants, G123A3.35 and G127K3.39, were able to be bound by [3H]INCB3344 and [3H]CCR2-RA-[ R ]. Thus, mutagenesis showed that the sodium ion binding site residues, which are distinct from other class A GPCRs and related to chemokine receptor evolution, are crucial for receptor integrity. Moreover, the tested mutations appeared to have no effect on modulation observed by HMA or a minor effect on sodium chloride modulation on the tested radioligands. All in all, these results invite further exploration of the CCR2 sodium ion binding site in (cancer) biology, and potentially as a third druggable binding site. [ABSTRACT FROM AUTHOR]

• HFNC is a potential feasible rescue respiratory treatment strategy for frail elderly COVID-19 patients. • Using HFNC in fragile COVID-19 patients in the wards results in a survival rate of 25%. • For fragile COVID-19 ICU and frail HFNC patients in the wards mortality is comparable. Invasive mechanical ventilation is the treatment of choice in COVID-19 patients when hypoxemia persists, despite maximum conventional oxygen administration. Some frail patients with severe hypoxemic respiratory failure are deemed not eligible for invasive mechanical ventilation. To investigate whether High-flow nasal cannula (HFNC) in the wards could serve as a rescue therapy in these frail patients. This retrospective cohort study included frail COVID-19 patients admitted to the hospital between March 9th and May 1st 2020. HFNC therapy was started in the wards. The primary endpoint was the survival rate at hospital discharge. Thirty-two patients with a median age of 79.0 years (74.5–83.0) and a Clinical Frailty Score of 4 out of 9 (3–6) were included. Only 6% reported HFNC tolerability issues. The overall survival rate was 25% at hospital discharge. This study suggests that, when preferred, HFNC in the wards could be a potential rescue therapy for respiratory failure in vulnerable COVID-19 patients. [ABSTRACT FROM AUTHOR]

Because European maximum guidance values of mycotoxins are only available for feed, mycotoxin exposure in animals is mainly monitored by feed analysis. However, proper sample collection is needed to ensure reliable results because of uneven distributions and disproportional spread of mycotoxins in feed which can hamper the evaluation of mycotoxin exposure in animals. A cross-sectional study was performed on 40 randomly selected broiler farms in Belgium. During a farm visit at the animal's age of 28 d, a pooled feed sample at the beginning and the end of the feed line was collected. Feed samples were analyzed by a validated multimycotoxin LC-MS/MS method. Moreover, serum samples were collected from 10 randomly selected chickens per farm. Serum concentrations of mycotoxins and major in vivo phase I metabolites were analyzed quantitatively, whereas the presence of phase II metabolites was determined in a qualitative approach by an UPLC-HRMS method. Deoxynivalenol (DON) was the most frequently occurring mycotoxin, being present in 74% of the feed samples, with an average concentration of 270 ± 171 μg/kg and a maximum concentration of 751 μg/kg in positive samples. Also the acetylated forms 3- and 15-acetyldeoxynivalenol (3 and 15ADON) were present in half of the samples, however, at lower concentrations (8 ± 3 μg 3ADON and 10 ± 7 μg 15ADON/kg). Only in 17.5% of the farms, DON was detected in serum samples at a mean serum concentration and standard deviation (SD) of 11 ± 19 ng/mL. The maximum serum concentration of 49 ng DON/mL was detected in broilers which were fed a diet that was contaminated with 191 μg DON/kg, whereas the maximum concentration of DON in feed was 751 μg/kg. Besides, 3 and 15ADON were only detected in 10% of the serum samples (max. 1.3 ng/mL). Sulfate conjugates of DON were only detected in a few serum samples. Qualitative screening for phase II metabolites of other mycotoxins showed similar results. Overall, correlations between feed and serum concentrations of all mycotoxins were lacking (R2 = 0.18 for DON). [ABSTRACT FROM AUTHOR]

Purpose Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design Pooled analysis of cross-sectional data. Participants Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures AMD features and stage; lipid measurements. Results HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14–1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91–0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10–1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10–7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10–6 and P = 1.6 × 10–4). Conclusions Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered. [ABSTRACT FROM AUTHOR]