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991.
992.
Aim We consider three hypotheses – MacArthur and Wilson’s island biogeography theory (IBT), Lack’s habitat diversity idea and the ‘target effect’– that explain the pattern of decreased species richness on small and distant islands. Location We evaluate these hypotheses using a detailed dataset on the occurrence and abundance of terrestrial birds on nine islands off the coast of Britain and the Republic of Ireland. Methods  Unlike previous studies, we compile data on species that visit the islands, rather than just those that breed on them. We divided the species into five mutually exclusive categories based upon their migratory status and where they regularly breed: British residents, summer visitors to Britain, winter visitors to Britain, and vagrants from Europe or beyond Europe. For each species group on each island we calculated the average number of species visiting each year. We then regressed the average number of species against island area and distance to the mainland (all variables were log‐transformed). We also compared the average number of species visiting each island with the average number of species breeding on each island. Results  Average number of visiting British residents decreased significantly with increasing island distance, but showed no relationship with island area. There was no significant relationship between island area or island distance and average number of summer or winter visitors. European and non‐European vagrants likewise showed no relationship between numbers of species visiting and island distance. However, the relationship between island area and number of visiting species was significant for both these categories; as island area increases so too does the number of visiting species. Main conclusions  As predicted by IBT, there were fewer visiting species on more distant islands. There were substantially more visitors to each island than breeding species, supporting Lack’s argument that lower bird richness is not a result of varying immigration rates (as predicted by IBT) but rather a result of some other island property, e.g. fewer resources. Birds make a decision to either leave an island or stay and breed. The target effect was also clearly demonstrated by the increase in European and non‐European breeders with increasing island size.  相似文献   
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BackgroundIn the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physiciansConclusionsAcceptability of antiretroviral generics in this French population was mostly dictated by the patient’s and physician’s knowledge and use of generics overall. It should be improved with an efficient information of both patients and physicians.  相似文献   
996.
Establishment and maintenance of the correct epigenetic code is essential for a plethora of physiological pathways and disturbed epigenetic patterns can provoke severe consequences, e.g. tumour formation. In recent years, epigenetic drugs altering the epigenome of tumours actively have been developed for anti-cancer therapies. However, such drugs could potentially also affect other physiological pathways and systems in which intact epigenetic patterns are essential. Amongst those, male fertility is one of the most prominent. Consequently, we addressed possible direct effects of two epigenetic drugs, decitabine and vorinostat, on both, the male germ line and fertility. In addition, we checked for putative transgenerational epigenetic effects on the germ line of subsequent generations (F1–F3). Parental adult male C57Bl/6 mice were treated with either decitabine or vorinostat and analysed as well as three subsequent untreated generations derived from these males. Treatment directly affected several reproductive parameters as testis (decitabine & vorinostat) and epididymis weight, size of accessory sex glands (vorinostat), the height of the seminiferous epithelium and sperm concentration and morphology (decitabine). Furthermore, after decitabine administration, DNA methylation of a number of loci was altered in sperm. However, when analysing fertility of treated mice (fertilisation, litter size and sex ratio), no major effect of the selected epigenetic drugs on male fertility was detected. In subsequent generations (F1–F3 generations) only subtle changes on reproductive organs, sperm parameters and DNA methylation but no overall effect on fertility was observed. Consequently, in mice, decitabine and vorinostat neither affected male fertility per se nor caused marked transgenerational effects. We therefore suggest that both drugs do not induce major adverse effects—in terms of male fertility and transgenerational epigenetic inheritance—when used in anti-cancer-therapies.  相似文献   
997.
Proteolytic processing of amyloid-β precursor protein (APP) by beta-site APP cleaving enzyme 1 (BACE1) is the initial step in the production of amyloid beta (Aβ), which accumulates in senile plaques in Alzheimer’s disease (AD). Essential for this cleavage is the transport and sorting of both proteins through endosomal/Golgi compartments. Golgi-localized γ-ear-containing ARF-binding (GGA) proteins have striking cargo-sorting functions in these pathways. Recently, GGA1 and GGA3 were shown to interact with BACE1, to be expressed in neurons, and to be decreased in AD brain, whereas little is known about GGA2. Since GGA1 impacts Aβ generation by confining APP to the Golgi and perinuclear compartments, we tested whether all GGAs modulate BACE1 and APP transport and processing. We observed decreased levels of secreted APP alpha (sAPPα), sAPPβ, and Aβ upon GGA overexpression, which could be reverted by knockdown. GGA-BACE1 co-immunoprecipitation was impaired upon GGA-GAE but not VHS domain deletion. Autoinhibition of the GGA1-VHS domain was irrelevant for BACE1 interaction. Our data suggest that all three GGAs affect APP processing via the GGA-GAE domain.  相似文献   
998.
Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to one's genetic and environmental makeups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott–Aldrich syndrome in two genetic backgrounds and carbon sources. We found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment, or a combination thereof. Specifically, the compensatory mutation rate and type, the molecular rescue mechanism, the genetic target, and the associated fitness cost varied across contexts. The course of compensatory evolution is therefore highly contingent on the initial conditions in which the deleterious mutation occurs. In addition, these results reveal biologically favored therapeutic targets for the Wiskott–Aldrich syndrome, including the target of an unrelated clinically approved drug. Our results experimentally illustrate the importance of epistasis and environmental evolutionary constraints that shape the adaptive landscape and evolutionary rate of molecular networks.  相似文献   
999.
The CRISPR (clustered, regularly, interspaced, short, palindromic repeats)–Cas (CRISPR-associated genes) systems of archaea and bacteria provide adaptive immunity against viruses and other selfish elements and are believed to curtail horizontal gene transfer (HGT). Limiting acquisition of new genetic material could be one of the sources of the fitness cost of CRISPR–Cas maintenance and one of the causes of the patchy distribution of CRISPR–Cas among bacteria, and across environments. We sought to test the hypothesis that the activity of CRISPR–Cas in microbes is negatively correlated with the extent of recent HGT. Using three independent measures of HGT, we found no significant dependence between the length of CRISPR arrays, which reflects the activity of the immune system, and the estimated number of recent HGT events. In contrast, we observed a significant negative dependence between the estimated extent of HGT and growth temperature of microbes, which could be explained by the lower genetic diversity in hotter environments. We hypothesize that the relevant events in the evolution of resistance to mobile elements and proclivity for HGT, to which CRISPR–Cas systems seem to substantially contribute, occur on the population scale rather than on the timescale of species evolution.  相似文献   
1000.

Introduction

According to some studies, ascorbic acid possesses antiviral properties. These studies were mainly focused on the common cold, with very few focusing on other viral infections.

Case presentation

We report the case of a 54-year-old Caucasian woman with chronic arthralgia due to persistent parvovirus B19 viremia. High doses of ascorbic acid treatment were initiated due to the failure of conventional analgesic therapy. Clinical benefit was observed with a simultaneous loss of biological parvovirus B19 viremia.

Conclusions

This observation shows a potential benefit of the use of ascorbic acid against parvovirus B19 infections, even if this case is not sufficient to draw any definite conclusions.  相似文献   
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