CD86+ or HLA-G+ can be transferred via trogocytosis from myeloma cells to T cells and are associated with poor prognosis

The transfer of membrane proteins between cells during contact, known as trogocytosis, can create novel cells with a unique phenotype and altered function. We demonstrate that trogocytosis is more common in multiple myeloma (MM) than chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia; that T cells are more probable to be recipients than B or natural killer cells; that trogocytosis occurs independently of either the T-cell receptor or HLA compatibility; and that after trogocytosis, T cells with acquired antigens can become novel regulators of T-cell proliferation. We screened 168 patients with MM and found that CD86 and human leukocyte antigen G (HLA-G) were antigens commonly acquired by T cells from malignant plasma cells. CD3(+)CD86(acq+) and CD3(+) HLA-G(acq+) cells were more prevalent in bone marrow than peripheral blood samples. The presence of either CD86 or HLA-G on malignant plasma cells was associated with a poor prognosis. CD38(++) side population cells expressed HLA-G, suggesting that these putative myeloma stem cells could generate immune tolerance. HLA-G(+) T cells had a regulatory potency similar to natural Tregs, thus providing another novel mechanism for MM to avoid effective immune surveillance.     

Functional analysis of HIV type 1 Nef gene variants from adolescent and adult survivors of perinatal infection

Throughout the world, infants and children with HIV-1 infection are increasingly surviving into adolescence and adulthood. As HIV Nef is an important determinant of the pathogenic potential of the virus, we examined nef alleles in a cohort of extreme long-term survivors of HIV infection (average age of 16.6 years) to determine if Nef defects might have contributed to patient survival. HIV nef gene sequences were amplified for phylogenetic analysis from 15 adolescents and adults infected by mother-to-child transmission (n=10) or by blood transfusion (n=5). Functional analysis was performed by inserting patient-derived nef sequences into an HIV-derived vector that permits simultaneous evaluation of the impact of the Nef protein on MHC-I and CD4 cell surface expression. We found evidence of extensive nef gene diversity, including changes in known functional domains involved in the downregulation of cell surface MHC-I and CD4. Only 3 of 15 individuals (20%) had nef alleles with a loss of the ability to downregulate either CD4 or MHC-I. Survival into adulthood with HIV infection acquired in infancy is not uniformly linked to loss of function in nef. The Nef protein remains a potential target for immunization or pharmacologic intervention.     

Male Breast Cancer: A Population-Based Comparison with Female Breast Cancer in Hong Kong,Southern China: 1997–2006

Background

Male breast cancer (MBC) is uncommon. As a result, there is limited availability of studies and reviews and even fewer reports from Asia. This is the largest population-based study to compare Chinese MBC patients with female patients during a 10-year period in Hong Kong, Southern China.

Methods

A retrospective review of medical records of 132 male and 8,118 female breast cancer patients between year 1997 and 2006 in Hong Kong was performed. Each MBC patient was matched with three female breast cancer patients for further analysis. Different characteristics, overall, breast-cancer specific, and disease-free survivals (DFS) were compared.

Results

Mean age at diagnosis of male and female patients was 64.5 and 52.7 years respectively. Male patients showed lower histological grade, overall stage, smaller tumor size, and more positive sensitivity in hormone receptors. They were more likely to die of causes other than breast cancer. Matched analysis found that the 5-year overall survival (OS), breast-cancer–specific mortality, and DFS for male and female patients were 78.7, 90.5, 90.5, and 77.9, 86.4, and 81.4 % respectively. Male patients had poorer OS at early overall stage but better breast-cancer—specific mortality rates at any age (p < 0.01). Male patients had a significant risk of dying due to any cause in the presence of distant relapse and had less risk of dying when tumor was ER-positive and HER2-positive.

Conclusions

Chinese male breast cancer patients tend to have poorer OS but better breast-cancer—specific survival compared with their female counterparts.     

Small genome of the fungus Escovopsis weberi,a specialized disease agent of ant agriculture

Many microorganisms with specialized lifestyles have reduced genomes. This is best understood in beneficial bacterial symbioses, where partner fidelity facilitates loss of genes necessary for living independently. Specialized microbial pathogens may also exhibit gene loss relative to generalists. Here, we demonstrate that Escovopsis weberi, a fungal parasite of the crops of fungus-growing ants, has a reduced genome in terms of both size and gene content relative to closely related but less specialized fungi. Although primary metabolism genes have been retained, the E. weberi genome is depleted in carbohydrate active enzymes, which is consistent with reliance on a host with these functions. E. weberi has also lost genes considered necessary for sexual reproduction. Contrasting these losses, the genome encodes unique secondary metabolite biosynthesis clusters, some of which include genes that exhibit up-regulated expression during host attack. Thus, the specialized nature of the interaction between Escovopsis and ant agriculture is reflected in the parasite’s genome.The highly evolved agricultural lifestyle of leaf-cutting ants has attracted particular attention because these ants cultivate a symbiotic fungus that serves as their major food source. These ants cut leaves, preprocess them into small pieces, and feed them to the cultivated fungus (1). The capacity of the cultivated fungus to break down plant material gives ant agriculturalists access to the vast nutrient stores locked within neotropical plants (Fig. 1A) (2–5). The symbiosis between fungus-growing ants and their cultivated fungi has persisted for at least 50 million years (6).Open in a separate windowFig. 1.Escovopsis weberi, a specialized mycoparasite of the fungus-growing ant symbiosis, has a small genome compared with other Pezizomycotina fungi. (A) Both fungus-growing ants and the mycoparasite E. weberi use the ants’ cultivated fungi as their primary food source. The ability of the cultivated fungi to efficiently break down plant material gives both consumers access to the biomass of neotropical plants. (B) Size and protein-coding gene content of genomes of diverse fungi in the Pezizomycotina. Bayesian phylogeny estimated using partial amino acid alignments of three genes (Rpb1, Rpb2, ef1-α). All posterior probabilities are greater than 0.95. Phylogeny is rooted with Sacchormyces cervesiae (not shown). (C) Relationship between genome size and gene content. A list of genomes included in this panel is in SI Appendix, Table S1.Like human agriculture, ant agriculture is hampered by disease. The ants’ fungal crops are attacked and consumed by fungal parasites of the genus Escovopsis (Ascomycota, Pezizomycotina: anamorphic Hypocreales) (Fig. 1A) (7), which have evolved in association with the ants and their cultivated fungi (8). Escovopsis infection can have detrimental impacts on garden health and, consequently, on the survival of ant colonies (9, 10). Such mycoparasitism, the phenomenon whereby one fungus is parasitic on another fungus, is rare. It is most well-known for species from the genus Trichoderma, some of which are used as biocontrol agents for fungal diseases and others of which attack human-cultivated fungi (11–13). In contrast to Trichoderma species, however, Escovopsis species grow poorly in their hosts’ absence (SI Appendix, Figs. S1 and S2).Escovopsis species have never been isolated outside of fungus-growing ant colonies, and different strains of Escovopsis are capable of attacking the fungi grown by different fungus-growing ant species (8, 14, 15). The long-term, specialized evolutionary history of the association between Escovopsis and their hosts provides a unique venue to explore the consequences of host specialization on pathogen genome evolution. Here, we assemble and annotate the genome of a strain of Escovopsis weberi. Consistent with expectations under an evolutionary transition toward using a narrow host range, and similar to many other specialized, host-associated microbes (16, 17), E. weberi exhibits gene loss. Contrasting other fungal pathogens, the large genomes of which are expanded with genetic elements that influence host adaptation (18), the genome size of Escovopsis is small compared with those of its closest sequenced relatives.     

Regenerative Cell and Tissue-based Therapies for Pulmonary Arterial Hypertension

Within the span of 2 decades, cell-based regenerative therapies for pulmonary arterial hypertension have progressed from bench-side hypotheses to clinical realities. Promising preclinical investigations that examined the therapeutic potential of endothelial progenitor cell and mesenchymal stem cell populations have demonstrated the safety and efficacy of these cell types and provided the foundation for first-in-man clinical trials. Moreover, these studies have improved our understanding of the therapeutic mechanisms by which stem/progenitor cells exert their regenerative functions. Ultimately, these discoveries have led to new applications for stem and progenitor cells including the autologous cell reseeding of decellularized or synthetic lung scaffolds. In this review, an overview of established and emerging cell and tissue regenerative therapies for pulmonary lung diseases are presented, along with discussion of recent advancements in the emerging field of repopulating decellularized or bioengineered lung scaffolds with stem/progenitor cells for allogeneic transplant.