Extracellular vesicle signalling in atherosclerosis

Atherosclerosis is a major cardiovascular disease and in 2016, the World Health Organisation (WHO) estimated 17.5 million global deaths, corresponding to 31% of all global deaths, were driven by inflammation and deposition of lipids into the arterial wall. This leads to the development of plaques which narrow the vessel lumen, particularly in the coronary and carotid arteries. Atherosclerotic plaques can become unstable and rupture, leading to myocardial infarction or stroke. Extracellular vesicles (EVs) are a heterogeneous population of vesicles secreted from cells with a wide range of biological functions. EVs participate in cell-cell communication and signalling via transport of cargo including enzymes, DNA, RNA and microRNA in both physiological and patholophysiological settings. EVs are present in atherosclerotic plaques and have been implicated in cellular signalling processes in atherosclerosis development, including immune responses, inflammation, cell proliferation and migration, cell death and vascular remodeling during progression of the disease. In this review, we summarise the current knowledge regarding EV signalling in atherosclerosis progression and the potential of utilising EV signatures as biomarkers of disease

Regulation of the subcellular distribution of key cellular RNA-processing factors during permissive human cytomegalovirus infection

Alternative splicing and polyadenylation of human cytomegalovirus (HCMV) immediate-early (IE) pre-mRNAs are temporally regulated and rely on cellular RNA-processing factors. This study examined the location and abundance of essential RNA-processing factors, which affect alternative processing of UL37 IE pre-mRNAs, during HCMV infection. Serine/threonine protein kinase 1 (SRPK1) phosphorylates serine/arginine-rich proteins, necessary for pre-spliceosome commitment. It was found that HCMV infection progressively increased the abundance of cytoplasmic SRPK1, which is regulated by subcellular partitioning. The essential polyadenylation factor CstF-64 was similarly increased in abundance, albeit in the nucleus, proximal to and within viral replication compartments (VRCs). In contrast, the location of polypyrimidine tract-binding protein (PTB), known to adversely affect splicing of HCMV major IE RNAs, was temporally regulated during infection. PTB co-localized with CstF-64 in the nucleus at IE times. By early times, PTB was detected in punctate cytoplasmic sites of some infected cells. At late times, PTB relocalized to the nucleus, where it was notably excluded from HCMV VRCs. Moreover, HCMV infection induced the formation of nucleolar stress structures, fibrillarin-containing caps, in close proximity to its VRCs. PTB exclusion from HCMV VRCs required HCMV DNA synthesis and/or late gene expression, whereas the regulation of SRPK1 subcellular distribution did not. Taken together, these results indicated that HCMV increasingly regulates the subcellular distribution and abundance of essential RNA-processing factors, thereby altering their ability to affect the processing of viral pre-mRNAs. These results further suggest that HCMV infection selectively induces sorting of nucleolar and nucleoplasmic components

Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis

B-Chronic Lymphocytic Leukemia (CLL) is an incurable disease predominantly characterized by apoptosis resistance. We have previously described a VEGF signaling pathway that generates apoptosis resistance in CLL B cells. We found induction of significantly more apoptosis in CLL B cells by co-culture with an anti-VEGF antibody. To increase the efficacy of these agents in CLL therapy we have focused on the use of gold nanoparticles (GNP). Gold nanoparticles were chosen based on their biocompatibility, very high surface area, ease of characterization and surface functionalization. We attached VEGF antibody (AbVF) to the gold nanoparticles and determined their ability to kill CLL B cells. Gold nanoparticles and their nanoconjugates were characterized using UV-Visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). All the patient samples studied (N = 7) responded to the gold-AbVF treatment with a dose dependent apoptosis of CLL B cells. The induction of apoptosis with gold-AbVF was significantly higher than the CLL cells exposed to only AbVF or GNP. The gold-AbVF treated cells showed significant down regulation of anti-apoptotic proteins and exhibited PARP cleavage. Gold-AbVF treated and GNP treated cells showed internalization of the nanoparticles in early and late endosomes and in multivesicular bodies. Non-coated gold nanoparticles alone were able to induce some levels of apoptosis in CLL B cells. This paper opens up new opportunities in the treatment of CLL-B using gold nanoparticles and integrates nanoscience with therapy in CLL. In future, potential opportunities exist to harness the optoelectronic properties of gold nanoparticles in the treatment of CLL

The Iowa Homemaker vol.25, no.2

Keeping Up With Today, Jeanne O’Connor, page 2 Veishea Blueprints the Future, Charla Muschott, page 3 This is Merrill Palmer, Marjorie Osenbrug, page 4 Home Economists on the Air, Charlene Stettler, page 5 Vicky Faces a Busy Summer, Josephine Ahern, page 6 Alum Directs Army Kitchen in Wales, Lt. Mary E. Scoltock, page 8 Women Devise Costume Jewelry, Madeline Morrison, page 9 Chile Outgrows Food Traditions, Ruth Gaessler, Carlos Krassa, page 10 Summer School or Summer Positions, Victoria McKibben, page 11 What’s New in Home Economics, Doris Adams, page 12 Restaurants Introduce Apprentice Course, Betsy Nichols, page 14 Teach Toymaking, Marjorie Moodie, page 17 Booklet Discusses Teaching Career, Marian Hoppe, page 19 Frances Madigan, ’44, Traveling Journalist, Joan Visser, page 21 Ever Eaten Eggshells?, Lois Gramlich, page 23 Faculty and Students Revise Curriculum, Jeanne O’Connor, page 2

The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis

Evidence exists for an immunomodulatory effect of endocrine therapy in hormone receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study was to define the prognostic and predictive value of tumor immune markers and the tumor immune profile in HR+ve BC, treated with different endocrine treatment regimens. 2,596 Dutch TEAM patients were treated with 5 years of adjuvant hormonal treatment, randomly assigned to different regimens: 5 years of exemestane or sequential treatment (2.5 years of tamoxifen–2.5 years of exemestane). Immunohistochemistry was performed for HLA class I, HLA-E, HLA-G, and FoxP3. Tumor immune subtypes (IS) (low, intermediate & high immune susceptible) were determined by the effect size of mono-immune markers on relapse rate. Patients on sequential treatment with high level of tumor-infiltrating FoxP3+ cells had significant (p = 0.019, HR 0.729, 95 % CI 0.560–0.949) better OS. Significant interaction for endocrine treatment and FoxP3+ presence was seen (OS p < 0.001). Tumor IS were only of prognostic value for the sequentially endocrine-treated patients (RFP: p = 0.035, HR intermediate IS 1.420, 95 % CI 0.878–2.297; HR low IS 1.657, 95 % CI 1.131–2.428; BCSS: p = 0.002, HR intermediate IS 2.486, 95 % CI 1.375–4.495; HR low IS 2.422, 95 % CI 1.439–4.076; and OS: p = 0.005, HR intermediate IS 1.509, 95 % CI 0.950–2.395; HR low IS 1.848, 95 % CI 1.277–2.675). Tregs and the tumor IS presented in this study harbor prognostic value for sequentially endocrine-treated HR+ve postmenopausal BC patients, but not for solely exemestane-treated patients. Therefore, these markers could be used as a clinical risk stratification tool to guide adjuvant treatment in this BC population

Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies

African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling

Distribuição geográfica de pequenos mamíferos não voadores nas bacias dos rios Araguaia e Paraná, região centro-sul do Brasil

We collected small mammals in two hydrographic basins in central Brazil, namely the Paraná and Araguaia basins, with the aim of examining the composition of forest dwelling small mammal species and to compare their geographic distributions. Fourteen sites were sampled, eight in the Paraná basin and six in the Araguaia basin. A total of 20 species of small mammals was registered (8 marsupials and 12 rodents), 16 of them in live traps (5,253 trap-nights) and eight in pitfalls (224 trap-nights), adding to a total of 161 captures of 139 individuals. The Paraná basin showed 16 species (trap-nights: 3,115 and 104 respectively) and the Araguaia basin 11 species (trap-nights: 2,138 and 120 respectively), being both richness similar when the rarefaction method was applied. Seven (35%) out of the 20 species recorded occurred in both basins. The marsupial Didelphis albiventris Lund, 1840 was the most abundant species. The marsupials species recorded were D. albiventris, Caluromys philander (Linnaeus, 1758), Cryptonanus cf. agricolai Voss, Lunde & Jansa, 2005, Gracilinanus agilis (Burmeister, 1854), G. microtarsus (Wagner, 1842), Lutreolina crassicaudata (Desmarest, 1804), Marmosa murina (Linnaeus, 1758), and Philander opossum (Linnaeus, 1758). The rodent species recorded were Akodon gr. cursor, Calomys tener (Winge, 1887), Nectomys rattus (Pelzen, 1883), N. squamipes (Brants, 1827), Oecomys bicolor (Tomes, 1860), Oryzomys maracajuensis Langguth & Bonvicino, 2002, Oryzomys cf. marinhus, O. megacephalus (Fischer, 1814), Oligoryzomys fornesi (Massoia, 1973), Oligoryzomys sp., Proechimys longicaudatus (Rengger, 1830) and P. roberti (Thomas, 1901). The range extension of some species is discussed, in addition to biogeographic considerations. The Caiapós Mountains may have been a geographic barrier for some small mammal species in the face of the retraction and expansion of forests in the past