In search of the visual pigment template

Absorbance spectra were recorded by microspectrophotometry from 39 different rod and cone types representing amphibians, reptiles, and fishes, with A1- or A2-based visual pigments and [lambda]max ranging from 357 to 620 nm. The purpose was to investigate accuracy limits of putative universal templates for visual pigment absorbance spectra, and if possible to amend the templates to overcome the limitations. It was found that (1) the absorbance spectrum of frog rhodopsin extract very precisely parallels that of rod outer segments from the same individual, with only a slight hypsochromic shift in [lambda]max, hence templates based on extracts are valid for absorbance in situ; (2) a template based on the bovine rhodopsin extract data of Partridge and De Grip (1991) describes the absorbance of amphibian rod outer segments excellently, contrary to recent electrophysiological results; (3) the [lambda]max/[lambda] invariance of spectral shape fails for A1 pigments with small [lambda]max and for A2 pigments with large [lambda]max, but the deviations are systematic and can be readily incorporated into, for example, the Lamb (1995) template. We thus propose modified templates for the main “[alpha]-band” of A1 and A2 pigments and show that these describe both absorbance and spectral sensitivities of photoreceptors over the whole range of [lambda]max. Subtraction of the [alpha]-band from the full absorbance spectrum leaves a “[beta]-band” described by a [lambda]max-dependent Gaussian. We conclude that the idea of universal templates (one for A1- and one for A2-based visual pigments) remains valid and useful at the present level of accuracy of data on photoreceptor absorbance and sensitivity. The sum of our expressions for the [alpha]- and [beta]-band gives a good description for visual pigment spectra with [lambda]max > 350 nm

Translation to practice: a randomised controlled study of an evidenced based booklet targeted at breast care nurses in the United Kingdom

BACKGROUND: In the United Kingdom (UK), it was documented that a problem of knowledge transfer existed within the speciality of breast-cancer care, thus depriving patients of receiving optimal care. Despite increasingly robust research evidence indicating recommendation of whole body exercise for people affected by breast cancer, commensurate changes to practice were not noted amongst breast-care nurses (BCNs). AIM: To evaluate the effect of a targeted booklet, Exercise and Breast Cancer: A Booklet for Breast-Care Nurses, on changes in knowledge, reported practice, and attitudes of BCNs in the UK. METHOD: A prospective, experimental approach was used for designing a pre- and post-test randomised controlled study. Comparisons of knowledge, reported practice, and attitudes based on responses to a questionnaire were made at two time-points in two groups of BCNs (control and experimental). The unit of randomisation and analysis was hospital clusters of BCNs. The sample comprised 92 nurses from 62 hospitals. Analysis consisted of descriptive statistics and clustered regression techniques: clustered logistic regression for knowledge items, clustered linear regression for knowledge scores, ologit for attitude and reported practice items, and clustered multiple regression for paired and multiple variable analysis. RESULTS: A statistically significant increase in knowledge and changes in reported practice and attitudes were found. Robust variables affecting knowledge acquisition were: promotion of health, promotion of exercise, and understanding how exercise can reduce cancer-related fatigue. DISCUSSION: The study has shown that evidence-based printed material, such as an information booklet, can be used as an effective research dissemination method when developed for needs, values, and context of a target audience. CONCLUSIONS: This practical approach to research dissemination could be replicated and applied to other groups of nurses.</p

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Pesticide effects on nitrogen cycle related microbial functions and community composition

The extensive application of pesticides in agriculture raises concerns about their potential negative impact on soil microorganisms, being the key drivers of nutrient cycling. Most studies have investigated the effect of a single pesticide on a nutrient cycling in single soil type. We, for the first time, investigated the effect of 20 commercial pesticides with different mode of actions, applied at their recommended dose and five times their recommended dose, on nitrogen (N) microbial cycling in three different agricultural soils from southern Australian. Functional effects were determined by measuring soil enzymatic activities of β-1,4-N-acetyliglucosaminidase (NAG) and L-leucine aminopeptidase (LAP), potential nitrification (PN), and the abundance of functional genes involved in N cycling (amoA and nifH). Effects on nitrifiers diversity were determined with amplicon sequencing. Overall, the pesticides effect on N microbial cycling was dose-independent and soil specific. The fungicides flutriafol and azoxystrobin, the herbicide chlorsulfuron and the insecticide fipronil induced a significant reduction in PN and β-1,4-N-acetylglucosaminidase activity (P < 0.05) (NAG) in the alkaline loam soil with low organic carbon content i.e. a soil with properties which typically favors pesticide bioavailability and therefore potential toxicity. For the nitrifier community, the greatest pesticide effects were on the most dominant Nitrososphaeraceae (ammonia-oxidizing archaea; AOA) whose abundance increased significantly compared to the less dominant AOA and other nitrifiers. The inhibiting effects were more evident in the soil samples treated with fungicides. By testing multiple pesticides in a single study, our findings provide crucial information that can be used for pesticide hazard assessment. © 2021 Elsevier B.V

Enhanced cardiac phosphoinositide 3-kinase (p110α) using gene therapy attenuates cardiac remodeling in type 2 diabetic mice

Diabetic cardiomyopathy is a distinct form of heart disease that represents a major cause of death and disability in diabetic patients, particularly the more prevalent type-2 diabetic population. In the current study, we investigated administration of recombinant adeno-associated viral vectors carrying a constitutively-active PI3K(p110α) construct (rAAV6-caPI3K) at a clinically-relevant time point attenuates diabetic cardiomyopathy in a pre-clinical type-2 diabetes (T2D) model. T2D was induced by a combination of high-fat diet and low-dose streptozotocin, and confirmed by increased body weight, hyperglycemia, and impaired glucose tolerance. After 18 weeks of untreated diabetes, impaired left ventricular (LV) systolic dysfunction was evident, as confirmed by echocardiography. A single tail vein injection of rAAV6-caPI3K gene therapy was then administered. Mice were followed for an additional 8 weeks before end-point. Administration of cardiac targeted rAAV6-caPI3K attenuates diabetes-induced cardiac remodeling by limiting cardiac fibrosis and cardiomyocyte hypertrophy. The diabetes-induced LV systolic dysfunction was reversed with rAAV6-caPI3K as demonstrated by improved fractional shortening and velocity of circumferential fiber shortening. This cardioprotection occurred in combination with reduced LV ROS levels and an associated decrease in markers of endoplasmic reticulum stress. Together, the findings demonstrate that cardiac-selective increases in PI3K(p110α), via rAAV6-caPI3K, attenuates diabetic cardiomyopathy in a mouse model of T2D.Darnel Prakoso, Miles J. De Blasio, Mitchel Tate, Helen Kiriazis, Daniel G. Donner, Hongwei Qian ... et al

Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart

AIMS : The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, β-N-acetylglucosamine (O-GlcNAc), is increased in pre-clinical models of diabetes, implicating protein O-GlcNAc modification in diabetes-induced heart failure. Our aim was to specifically examine cardiac manipulation of the two regulatory enzymes of this process on the cardiac phenotype, in the presence and absence of diabetes, utilising cardiac-targeted recombinant-adeno-associated viral-vector-6 (rAAV6)-mediated gene delivery. METHODS AND RESULTS : In human myocardium, total protein O-GlcNAc modification was elevated in diabetic relative to non-diabetic patients, and correlated with left ventricular (LV) dysfunction. The impact of rAAV6-delivered O-GlcNAc transferase (rAAV6-OGT, facilitating protein O-GlcNAcylation), O-GlcNAcase (rAAV6-OGA, facilitating de-O-GlcNAcylation), and empty vector (null) were determined in non-diabetic and diabetic mice. In non-diabetic mice, rAAV6-OGT was sufficient to impair LV diastolic function and induce maladaptive cardiac remodelling, including cardiac fibrosis and increased Myh-7 and Nppa pro-hypertrophic gene expression, recapitulating characteristics of diabetic cardiomyopathy. In contrast, rAAV6-OGA (but not rAAV6-OGT) rescued LV diastolic function and adverse cardiac remodelling in diabetic mice. Molecular insights implicated impaired cardiac PI3K(p110α)-Akt signalling as a potential contributing mechanism to the detrimental consequences of rAAV6-OGT in vivo. In contrast, rAAV6-OGA preserved PI3K(p110α)-Akt signalling in diabetic mouse myocardium in vivo and prevented high glucose-induced impairments in mitochondrial respiration in human cardiomyocytes in vitro. CONCLUSION: Maladaptive protein O-GlcNAc modification is evident in human diabetic myocardium, and is a critical regulator of the diabetic heart phenotype. Selective targeting of cardiac protein O-GlcNAcylation to restore physiological O-GlcNAc balance may represent a novel therapeutic approach for diabetes-induced heart failure.Darnel Prakoso, Shiang Y Lim, Jeffrey R Erickson, Rachel S Wallace, Jarmon G Lees, Mitchel Tate ... et al