Endometrial response to IVF hormonal manipulation: Comparative analysis of menopausal, down regulated and natural cycles

BACKGROUND: Uterine luminal epithelial cell response to different hormonal strategies was examined to determine commonality when an endometrium attains a receptive, stimulated, morphological profile that may lead to successful implantation. METHODS: Endometrial biopsies from 3 cohorts of patients were compared. The tissue samples taken from these patients were categorized into 8 different groups according to their baseline and the hormone regime used. RESULTS: Pre-treatment natural cycle tissue was variable in appearance. Downregulation with a GnRH analogue tissue appeared menopausal in character. HRT after downregulation resulted in tissue uniformity. HRT in menopause resulted in a 'lush' epithelial surface. HST in the natural cycle improved the morphology with significant difference in secretion between the two regimes examined. CONCLUSIONS: Down regulation plus HRT standardized surface appearance but tissue response is significantly different from the natural cycle, natural cycle plus HRT or menopause plus HRT. HRT in menopause reinstates tissue to a state similar to a natural cycle but significantly different from a natural cycle plus HST. HST with a natural cycle is similar to tissue from the natural cycle but significant differences reflect the influence of the particular hormones present (at any point) within the cycle

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

Content and quality of websites supporting self-management of chronic breathlessness in advanced illness: A systematic review

Chronic breathlessness is a common, burdensome and distressing symptom in many advanced chronic illnesses. Self-management strategies are essential to optimise treatment, daily functioning and emotional coping. People with chronic illness commonly search the internet for advice on self-management. A review was undertaken in June 2015 to describe the content and quality of online advice on breathlessness self-management, to highlight under-served areas and to identify any unsafe content. Google was searched from Sydney, Australia, using the five most common search terms for breathlessness identified by Google Trends. We also hand-searched the websites of national associations. Websites were included if they were freely available in English and provided practical advice on self-management. Website quality was assessed using the American Medical Association Benchmarks. Readability was assessed using the Flesch-Kincaid grades, with grade 8 considered the maximum acceptable for enabling access. Ninety-one web pages from 44 websites met the inclusion criteria, including 14 national association websites not returned by Google searches. Most websites were generated in the USA (n=28, 64%) and focused on breathing techniques (n=38, 86%) and chronic obstructive pulmonary disease (n=27, 61%). No websites were found to offer unsafe advice. Adherence to quality benchmarks ranged from 9% for disclosure to 77% for currency. Fifteen (54%) of 28 written websites required grade ≈ 3/49 reading level. Future development should focus on advice and tools to support goal setting, problem solving and monitoring of breathlessness. National associations are encouraged to improve website visibility and comply with standards for quality and readability

Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development

The role of the chemokine receptor CXCR4 in infection with feline immunodeficiency virus

Infection with feline immunodeficiency virus (FIV) leads to the development of a disease state similar to AIDS in man. Recent studies have identified the chemokine receptor CXCR4 as the major receptor for cell culture-adapted strains of FIV, suggesting that FIV and human immunodeficiency virus (HIV) share a common mechanism of infection involving an interaction between the virus and a member of the seven transmembrane domain superfamily of molecules. This article reviews the evidence for the involvement of chemokine receptors in FIV infection and contrasts these findings with similar studies on the primate lentiviruses HIV and SIV (simian immunodeficiency virus)

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

The clonal root system of balsam poplar in upland sites of Quebec and Alberta

Balsam poplar seeds are short-lived and require moist seedbeds soon after they are released to germinate. In addition to sexual reproduction, balsam poplar stands can regenerate clonally by root suckering. The origin of stands will in turn affect their genetic structure and root system architecture, which are poorly understood for upland forest stands. Three stands were hydraulically excavated in Quebec (moist) and Alberta (dry) to determine the origin of trees and to characterize root systems with respect to presence of parental roots and root grafts connections. Clones were identified using single-nucleotide polymorphism (SNPs), and all stems, roots and root grafts were aged using dendrochronology techniques. All 82 excavated trees were of sucker origin, and four of the six stands contained a single clone. Parental root connections were found between 22% and 25% of excavated trees, and 53% and 48% of trees were linked with a root graft between the same or different clones, in Alberta and Quebec, respectively. Mean distance between trees connected by parental root was significantly lower than the distance between unconnected trees (0.47 ± 0.25 m vs. 3.14 ± 0.15 m and 1.55 ± 0.27 m vs. 4.25 ± 0.13 m) in Alberta and in Quebec, respectively. The excavations also revealed many dead stumps with live roots, maintained through root connections with live trees. This research highlights that balsam poplar growing in upland stands is a clonal species that can maintain relatively high genotypic diversity, with frequent root connections between trees at maturity. Maintaining an extensive root system through root connections increases the chances of a clone surviving when the above ground tree is dead and may also enhance the resilience of balsam poplar stands after disturbance

Role of Symbiotic Auxotrophy in the Rhizobium-Legume Symbioses

Symbiotic auxotrophy occurs in both determinate pea and indeterminate bean nodules demonstrating its importance for bacteroid formation and nodule function in legumes with different developmental programmes. However, only small quantities of branched chain amino acids are needed and symbiotic auxotrophy did not occur in the Sinorhizobium meliloti-alfalfa symbiosis under the conditions measured. The contrasting symbiotic phenotypes of aap bra mutants inoculated on different legumes probably reflects altered timing of amino acid availability, development of symbiotic auxotrophy and nodule developmental programmes

Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

<b>BACKGROUND:</b> The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.<p></p> <b>RESULTS:</b> Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.<p></p> <b>CONCLUSIONS:</b> Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

Influenza virus infections in cats

In the past, cats were considered resistant to influenza. Today, we know that they are susceptible to some influenza A viruses (IAVs) originating in other species. Usually, the outcome is only subclinical infection or a mild fever. However, outbreaks of feline disease caused by canine H3N2 IAV with fever, tachypnoea, sneezing, coughing, dyspnoea and lethargy are occasionally noted in shelters. In one such outbreak, the morbidity rate was 100% and the mortality rate was 40%. Recently, avian H7N2 IAV infection occurred in cats in some shelters in the USA, inducing mostly mild respiratory disease. Furthermore, cats are susceptible to experimental infection with the human H3N2 IAV that caused the pandemic in 1968. Several studies indicated that cats worldwide could be infected by H1N1 IAV during the subsequent human pandemic in 2009. In one shelter, severe cases with fatalities were noted. Finally, the highly pathogenic avian H5N1 IAV can induce a severe, fatal disease in cats, and can spread via cat-to-cat contact. In this review, the Advisory Board on Cat Diseases (ABCD), a scientifically independent board of experts in feline medicine from 11 European countries, summarises current data regarding the aetiology, epidemiology, pathogenesis, clinical picture, diagnostics, and control of feline IAV infections, as well as the zoonotic risks