Animal modelling for inherited central vision loss.

Disease-causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale-up of new therapies. Examples of innovative approaches will be presented such as lentiviral-based transgenesis in pigs and adeno-associated virus (AAV)-gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans.

Welfare loss with municipal amalgamations and the willingness-to-pay for the municipality name

Functional advantages and drawbacks are commonly mentioned to rationally justify or condemn municipality amalgamations. However, many consolidation projects are resisted by local governments or citizens on the grounds that amalgamation would dampen local identity. A municipality's name change is probably the most visible sign of the loss of community bond experienced by citizens at amalgamation time. This article aims to put a value on this loss by measuring citizen willingness to pay for their city name. This methodological approach innovates upon the literature on municipal amalgamation and place branding by exploiting the versatility of the so-called contingent valuation method (CVM). CVM confronts respondents, in a survey setting, with a hypothetical market in which a characteristic of interest is exchanged. Here the characteristic is the possibility to retain one's city name for an amalgamated jurisdiction. The article presents the estimates provided by a survey conducted in four Swiss cities.

Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes

Genome duplications increase genetic diversity and may facilitate the evolution of gene subfunctions. Little attention, however, has focused on the evolutionary impact of lineage-specific gene loss. Here, we show that identifying lineage-specific gene loss after genome duplication is important for understanding the evolution of gene subfunctions in surviving paralogs and for improving functional connectivity among human and model organism genomes. We examine the general principles of gene loss following duplication, coupled with expression analysis of the retinaldehyde dehydrogenase Aldh1a gene family during retinoic acid signaling in eye development as a case study. Humans have three ALDH1A genes, but teleosts have just one or two. We used comparative genomics and conserved syntenies to identify loss of ohnologs (paralogs derived from genome duplication) and to clarify uncertain phylogenies. Analysis showed that Aldh1a1 and Aldh1a2 form a clade that is sister to Aldh1a3-related genes. Genome comparisons showed secondarily loss of aldh1a1 in teleosts, revealing that Aldh1a1 is not a tetrapod innovation and that aldh1a3 was recently lost in medaka, making it the first known vertebrate with a single aldh1a gene. Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival. We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications. Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

Job loss among immigrant and native workers: evidence from Spain's economic downturn

The profound crisis that has affected the Spanish economy since mid - 2008 has been characterized by significant job losses and a marked rise in the country´s unemployment rate. However, unemployment has had a differential impact on different population groups. Compared to native, immigrant workers have experienced higher rates of job loss. Against this backdrop, this paper examines the differences between immigrants and natives (distinguished by gender) in terms of their probability of suffering job loss in the downturn of late 2008 and 2009. Our results indicate that the higher rate of job loss among female immigrant workers can be fully explained by their lower endowment of human capital. By contrast, human capital endowment and over-representation in certain occupations, sectors and regions in which the crisis had greatest impact do not appear to be the only reason for the penalty suffered by immigrant males in terms of their chances of losing their job in the downturn.

The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases.

UNLABELLED: Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivityin vitro Recently, we reported that inactivation of a single HA-activating protease gene,Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection ofTmprss2knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion ofTmprss4alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast,Tmprss2(-/-)Tmprss4(-/-)double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virusin vivo IMPORTANCE: Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously thatTmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes,Tmprss2andTmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection. Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza virusesin vivo.

Population connectivity buffers genetic diversity loss in a seabird

Background Ancient DNA has revolutionized conservation genetic studies as it allows monitoring of the genetic variability of species through time and predicting the impact of ecosystems" threats on future population dynamics and viability. Meanwhile, the consequences of anthropogenic activities and climate change to island faunas, particularly seabirds, remain largely unknown. In this study, we examined temporal changes in the genetic diversity of a threatened seabird, the Cory"s shearwater (Calonectris borealis). Findings We analysed the mitochondrial DNA control region of ancient bone samples from the late-Holocene retrieved from the Canary archipelago (NE Atlantic) together with modern DNA sequences representative of the entire breeding range of the species. Our results show high levels of ancient genetic diversity in the Canaries comparable to that of the extant population. The temporal haplotype network further revealed rare but recurrent long-distance dispersal between ocean basins. The Bayesian demographic analyses reveal both regional and local population size expansion events, and this is in spite of the demographic decline experienced by the species over the last millennia. Conclusions Our findings suggest that population connectivity of the species has acted as a buffer of genetic losses and illustrate the use of ancient DNA to uncover such cryptic genetic events.

Features extraction based on the Discrete Hartley Transform for closed contour

In this paper the authors propose a new closed contour descriptor that could be seen as a Feature Extractor of closed contours based on the Discrete Hartley Transform (DHT), its main characteristic is that uses only half of the coefficients required by Elliptical Fourier Descriptors (EFD) to obtain a contour approximation with similar error measure. The proposed closed contour descriptor provides an excellent capability of information compression useful for a great number of AI applications. Moreover it can provide scale, position and rotation invariance, and last but not least it has the advantage that both the parameterization and the reconstructed shape from the compressed set can be computed very efficiently by the fast Discrete Hartley Transform (DHT) algorithm. This Feature Extractor could be useful when the application claims for reversible features and when the user needs and easy measure of the quality for a given level of compression, scalable from low to very high quality.

Her onginþ seo boc: On the loss and retention of grammatical gender in Early Middle English

Tutkielma käsittelee kieliopillisen suvun säilymistä myöhäisessä muinaisenglannissa (Late Old English) ja varhaiskeskienglannissa (Early Middle English). Tutkielman tavoitteena on päätellä, kuinka kieliopillinen suku säilyy kolmessa muinaisenglannin/varhaiskeskienglannin aikakautta edustavassa tekstissä. Lähdeaineisto on valittu edustamaan aikaa (1150-1225), jolloin kieliopillisen suvun on sanottu kadonneen englannin kielestä. Lähdeaineisto myös edustaa kahta eri tekstilajia, ja tarjoaa siten aineistoa niiden väliseen vertailuun. Aineistosta on analysoitu nominien päätteitä, demonstratiivipronomineja sekä anaforisia persoonapronomineja, joissa substantiivien kieliopillinen suku näkyy. Osa anaforisista viittauksista on selitettävissä personifikaatiolla, jolloin elottomiin objekteihin tai käsitteisiin on liitetty inhimillistäviä piirteitä. Tutkimuksen perusteella kieliopillinen suku säilyy vielä joissakin muodoissa 1200- luvulle saakka. Merkittävää on aineistossa esiintyvä runsas vaihtelu ja pyhimyselämänkertojen ja lääketieteellisen tekstin väliset erot.

Loss of intestinal epithelial barrier function in Salmonella Enteritidis infection

Intestinal infection with Salmonella enterica serotype Enteritidis, a food-borne infection spread to humans especially through contaminated eggs and egg-products as well as undercooked contaminated fresh meat, is the most common cause of intestinal inflammation in the European Union. Enteritis caused by Salmonella Enteritidis is characterized by fever, diarrhoea and abdominal pain. The disruption of the intestinal epithelial barrier function contributes to diarrhoea and is responsible for the perpetuation of the inflammatory process. In this sense, oxidative stress and the proinflammatory cytokines TNF-α, IFN-γ and IL-1β are described to induce the disorganization of the tight junctions (TJ), the most apical epithelial intercellular junctions and responsible for the paracellular permeability. The interest of this chapter relies not only in the investigation dealing with the mechanisms of TJ regulation but also in the contribution to the development of new tools for the prevention of epithelial barrier disruption in enteritis caused by Salmonella Enteritidis.

Green tea catechin inhibits fatty acid synthase without stimulating carnitine Palmitoyltransferase-1 or inducing weight loss in experimental animals

Background: The enzyme fatty acid synthase (FASN) is highly expressed in many human carcinomas and its inhibition is cytotoxic to human cancer cells. The use of FASN inhibitors has been limited until now by anorexia and weight loss, which is associated with the stimulation of fatty acid oxidation. Materials and Methods: The in vitro effect of (-)-epigallocatechin-3-gallate (EGCG) on fatty acid metabolism enzymes, on apoptosis and on cell signalling was evaluated. In vivo, the effect of EGCG on animal body weight was addressed. Results: EGCG inhibited FASN activity, induced apoptosis and caused a marked decrease of human epidermal growth factor receptor 2 (HER2), phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular (signal)-regulated kinase (ERK) 1/2 proteins, in breast cancer cells. EGCG did not induce a stimulatory effect on CPT-1 activity in vitro (84% of control), or on animal body weight in vivo (99% of control). Conclusion: EGCG is a FASN inhibitor with anticancer activity which does not exhibit cross-activation of fatty acid oxidation and does not induce weight loss, suggesting its potential use as an anticancer drug.

Invasive species and habitat degradation in Iberian streams: an analysis of their role in freshwater fish diversity loss

Mediterranean endemic freshwater fish are among the most threatened biota in the world. Distinguishing the role of different extinction drivers and their potential interactions is crucial for achieving conservation goals. While some authors argue that invasive species are a main driver of native species declines, others see their proliferation as a co-occurring process to biodiversity loss driven by habitat degradation. It is difficult to discern between the two potential causes given that few invaded ecosystems are free from habitat degradation, and that both factors may interact in different ways. Here we analyze the relative importance of habitat degradation and invasive species in the decline of native fish assemblages in the Guadiana River basin (southwestern Iberian Peninsula) using an information theoretic approach to evaluate interaction pathways between invasive species and habitat degradation (structural equation modeling, SEM). We also tested the possible changes in the functional relationships between invasive and native species, measured as the per capita effect of invasive species, using ANCOVA. We found that the abundance of invasive species was the best single predictor of natives’ decline and had the highest Akaike weight among the set of predictor variables examined. Habitat degradation neither played an active role nor influenced the per capita effect of invasive species on natives. Our analyses indicated that downstream reaches and areas close to reservoirs had the most invaded fish assemblages, independently of their habitat degradation status. The proliferation of invasive species poses a strong threat to the persistence of native assemblages in highly fluctuating environments. Therefore, conservation efforts to reduce native freshwater fish diversity loss in Mediterranean rivers should focus on mitigating the effect of invasive species and preventing future invasions

Flow analysis by using solenoid valves for As(III) determination in natural waters by an on-line separation and pre-concentration system coupled to a tungsten coil atomizer

A flow system coupled to a tungsten coil atomizer in an atomic absorption spectrometer (TCA-AAS) was developed for As(III) determination in waters, by extraction with sodium diethyldithiocarbamate (NaDDTC) as complexing agent, and by sorption of the As(III)-DDTC complex in a micro-column filled with 5 mg C18 reversed phase (10 µL dry sorbent), followed by elution with ethanol. A complete pre-concentration/elution cycle took 208 s, with 30 s sample load time (1.7 mL) and 4 s elution time (71 µL). The interface and software for the synchronous control of two peristaltic pumps (RUN/ STOP), an autosampler arm, seven solenoid valves, one injection valve, the electrothermal atomizer and the spectrometer Read function were constructed. The system was characterized and validated by analytical recovery studies performed both in synthetic solutions and in natural waters. Using a 30 s pre-concentration period, the working curve was linear between 0.25 and 6.0 µg L-1 (r = 0.9976), the retention efficiency was 94±1% (6.0 µg L-1), and the pre-concentration coefficient was 28.9. The characteristic mass was 58 pg, the mean repeatability (expressed as the variation coefficient) was 3.4% (n=5), the detection limit was 0.058 µg L-1 (4.1 pg in 71 µL of eluate injected into the coil), and the mean analytical recovery in natural waters was 92.6 ± 9.5 % (n=15). The procedure is simple, economic, less prone to sample loss and contamination and the useful lifetime of the micro-column was between 200-300 pre-concentration cycles.

Effects of Weight Loss on Adipose Tissue, Liver and Heart Metabolism in Humans

Obesity has become the leading cause of many chronic diseases, such as type 2 diabetes and cardiovascular diseases. The prevalence of obesity is high in developed countries and it is also a major cause of the use of health services. Ectopic fat accumulation in organs may lead to metabolic disturbances, such as insulin resistance.Weight loss with very-low-energy diet is known to be safe and efficient. Weight loss improves whole body insulin sensitivity, but its effects on tissue and organ level in vivo are not well known. The aims of the studies were to investigate possible changes of weight loss in glucose and fatty acid uptake and perfusion and fat distribution at tissue and organ level using positron emission tomography and magnetic resonance imaging and spectroscopy in 34 healthy obese subjects. The results showed that whole-body insulin sensitivity increased after weight loss with very-low-energy diet and this is associated with improved skeletal muscle insulin-stimulated glucose uptake, but not with adipose tissue, liver or heart glucose uptake. Liver insulin resistance decreased after weight loss. Liver and heart free fatty acid uptakes decreased concomitantly with liver and heart triglyceride content. Adipose tissue and myocardial perfusion decreased. In conclusion, enhanced skeletal muscle glucose uptake leads to increase in whole-body insulin sensitivity when glucose uptake is preserved in other organs studied. These findings suggest that lipid accumulation found in the liver and the heart in obese subjects without co-morbidies is in part reversible by reduced free fatty acid uptake after weight loss. Reduced lipid accumulation in organs may improve metabolic disturbances, e.g. decrease liver insulin resistance. Keywords: Obesity, weight loss, very-low-energy diet, adipose tissue metabolism, liver metabolism, heart metabolism, positron emission tomography

Combined application of continuous wavelet transform-zero crossing technique in the simultaneous spectrophotometric determination of perindopril and indapamid in tablets

Signal processing methods based on the combined use of the continuous wavelet transform (CWT) and zero-crossing technique were applied to the simultaneous spectrophotometric determination of perindopril (PER) and indapamide (IND) in tablets. These signal processing methods do not require any priory separation step. Initially, various wavelet families were tested to identify the optimum signal processing giving the best recovery results. From this procedure, the Haar and Biorthogonal1.5 continuous wavelet transform (HAAR-CWT and BIOR1.5-CWT, respectively) were found suitable for the analysis of the related compounds. After transformation of the absorbance vectors by using HAAR-CWT and BIOR1.5-CWT, the CWT-coefficients were drawn as a graph versus wavelength and then the HAAR-CWT and BIOR1.5-CWT spectra were obtained. Calibration graphs for PER and IND were obtained by measuring the CWT amplitudes at 231.1 and 291.0 nm in the HAAR-CWT spectra and at 228.5 and 246.8 nm in BIOR1.5-CWT spectra, respectively. In order to compare the performance of HAAR-CWT and BIOR1.5-CWT approaches, derivative spectrophotometric (DS) method and HPLC as comparison methods, were applied to the PER-IND samples. In this DS method, first derivative absorbance values at 221.6 for PER and 282.7 nm for IND were used to obtain the calibration graphs. The validation of the CWT and DS signal processing methods was carried out by using the recovery study and standard addition technique. In the following step, these methods were successfully applied to the commercial tablets containing PER and IND compounds and good accuracy and precision were reported for the experimental results obtained by all proposed signal processing methods.