Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality

Human mesenchymal stem/stromal cells (hMSC) are increasingly used in advanced cellular therapies. The clinical use of hMSCs demands sequential cell expansions. As it is well established that membrane glycerophospholipids (GPL) provide precursors for signaling lipids that modulate cellular functions, we studied the effect of the donor''s age and cell doublings on the GPL profile of human bone marrow MSC (hBMSC). The hBMSCs, which were harvested from five young and five old adults, showed clear compositional changes during expansion seen at the level of lipid classes, lipid species, and acyl chains. The ratio of phosphatidylinositol to phosphatidylserine increased toward the late-passage samples. Furthermore, 20:4n-6-containing species of phosphatidylcholine and phosphatidylethanolamine accumulated while the species containing monounsaturated fatty acids (FA) decreased during passaging. Additionally, in the total FA pool of the cells, 20:4n-6 increased, which happened at the expense of n-3 polyunsaturated FAs, especially 22:6n-3. The GPL and FA correlated with the decreased immunosuppressive capacity of hBMSCs during expansion. Our observations were further supported by alterations in the gene expression levels of several enzymes involved in lipid metabolism and immunomodulation. The results show that extensive expansion of hBMSCs harmfully modulates membrane GPLs, affecting lipid signaling and eventually impairing functionality.     

Revision of the western Palaearctic Mesoleptus (Hymenoptera: Ichneumonidae)

The western Palaearctic species of the genus Mesoleptus Gravenhorst 1829 are redescribed and keys are given for their identification. Also a key for the identification of the three stilpnine genera (Atractodes, Mesoleptus, and Stilpnus) is given and the biology of the genus is discussed shortly. The following species are described as new: Mesoleptus hispanicus n. sp., M. sawoniewiczi n. sp. and M. tunisiensis n. sp. The male of Mesoleptus tobiasi Jonaitis is described for the first time. New combinations is M. incessor (Haliday). New synonyms number 143 and 34 lectotypes are chosen.     

Modified Lipoprotein-Derived Lipid Particles Accumulate in Human Stenotic Aortic Valves

In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proportion of the phospholipids were found to contain arachidonic acid, the common precursor of a number of proinflammatory lipid mediators. Next, we isolated and characterized extracellular lipid particles from human stenotic and non-stenotic control valves, and compared them to plasma lipoproteins from the same subjects. The extracellular valvular lipid particles were isolated from 15 stenotic and 14 non-stenotic aortic valves. Significantly more apoB-100-containing lipid particles were found in the stenotic than in the non-stenotic valves. The majority of the lipid particles isolated from the non-stenotic valves had sizes (23±6.2 nm in diameter) similar to those of plasma low density lipoprotein (LDL) (22±1.5 nm), while the lipid particles from stenotic valves were not of uniform size, their sizes ranging from 18 to more than 500 nm. The lipid particles showed signs of oxidative modifications, and when compared to isolated plasma LDL particles, the lipid particles isolated from the stenotic valves had a higher sphingomyelin/phosphatidylcholine –ratio, and also higher contents of lysophosphatidylcholine and unesterified cholesterol. The findings of the present study reveal, for the first time, that in stenotic human aortic valves, infiltrated plasma lipoproteins have undergone oxidative and lipolytic modifications, and become fused and aggregated. The generated large lipid particles may contribute to the pathogenesis of human aortic stenosis.     

Pyrophosphate-Fueled Na+ and H+ Transport in Prokaryotes

SUMMARY

In its early history, life appeared to depend on pyrophosphate rather than ATP as the source of energy. Ancient membrane pyrophosphatases that couple pyrophosphate hydrolysis to active H⁺ transport across biological membranes (H⁺-pyrophosphatases) have long been known in prokaryotes, plants, and protists. Recent studies have identified two evolutionarily related and widespread prokaryotic relics that can pump Na⁺ (Na⁺-pyrophosphatase) or both Na⁺ and H⁺ (Na⁺,H⁺-pyrophosphatase). Both these transporters require Na⁺ for pyrophosphate hydrolysis and are further activated by K⁺. The determination of the three-dimensional structures of H⁺- and Na⁺-pyrophosphatases has been another recent breakthrough in the studies of these cation pumps. Structural and functional studies have highlighted the major determinants of the cation specificities of membrane pyrophosphatases and their potential use in constructing transgenic stress-resistant organisms.     

Arenavirus Coinfections Are Common in Snakes with Boid Inclusion Body Disease

Recently, novel arenaviruses were found in snakes with boid inclusion body disease (BIBD); these form the new genus Reptarenavirus within the family Arenaviridae. We used next-generation sequencing and de novo sequence assembly to investigate reptarenavirus isolates from our previous study. Four of the six isolates and all of the samples from snakes with BIBD contained at least two reptarenavirus species. The viruses sequenced comprise four novel reptarenavirus species and a representative of a new arenavirus genus.     

Preoperative Axillary Staging with 3.0-T Breast MRI: Clinical Value of Diffusion Imaging and Apparent Diffusion Coefficient

The axillary staging in newly diagnosed breast cancer is under major evolution. The aims of this study were to define the diagnostic performance of 3.0-T diffusion-weighted imaging (DWI) in the detection of axillary metastases in newly diagnosed breast cancer, to assess apparent diffusion coefficients (ADCs) for histopathologically confirmed metastatic lymph nodes in a clinical setting. Altogether 52 consecutive breast cancer patients underwent magnetic resonance imaging and DWI in addition to axillary ultrasound. ADCs of axillary lymph nodes were analysed by two breast radiologists and ultrasound-guided core biopsies were taken. In a separate reading by one radiologist two types of region of interests were used for a smaller group of patients. Altogether 56 axillae (121 lymph nodes) were included in the statistical analysis. Metastatic axillae (51.8%) had significantly lower ADCs (p<0.001). Mean ADCs were 0.663–0.676 x 10^-3 mm²/s for the histologically confirmed metastatic LNs and 1.100–1.225 x 10^-3 mm²/s for the benign. The sensitivity, specificity, and accuracy of DWI were 72.4%, 79.6%, and 75.9%, respectively with threshold ADC 0.812 x 10^-3 mm²/s. Region of interest with information on the minimum value increased the diagnostic performance (area under the curve 0.794 vs. 0.619). Even though ADCs are significantly associated with histopathologically confirmed axillary metastases the diagnostic performance of axillary DWI remains moderate and ultrasound-guided core biopsies or sentinel lymph node biopsies cannot be omitted.     

Characterization of a New Epidemic Necrotic Pyoderma in Fur Animals and Its Association with Arcanobacterium phocae Infection

A new type of pyoderma was detected in Finnish fur animals in 2007. The disease continues to spread within and between farms, with severe and potentially fatal symptoms. It compromises animal welfare and causes considerable economic losses to farmers. A case-control study was performed in 2010–2011 to describe the entity and to identify the causative agent. Altogether 99 fur animals were necropsied followed by pathological and microbiological examination. The data indicated that the disease clinically manifests in mink (Neovison vison) by necrotic dermatitis of the feet and facial skin. In finnraccoons (Nyctereutes procyonoides), it causes painful abscesses in the paws. Foxes (Vulpes lagopus) are affected by severe conjunctivitis and the infection rapidly spreads to the eyelids and facial skin. A common finding at necropsy was necrotic pyoderma. Microbiological analysis revealed the presence of a number of potential causative agents, including a novel Streptococcus sp. The common finding from all diseased animals of all species was Arcanobacterium phocae. This bacterium has previously been isolated from marine mammals with skin lesions but this is the first report of A. phocae isolated in fur animals with pyoderma. The results obtained from this study implicate A. phocae as a potential causative pathogen of fur animal epidemic necrotic pyoderma (FENP) and support observations that the epidemic may have originated in a species -shift of the causative agent from marine mammals. The variable disease pattern and the presence of other infectious agents (in particular the novel Streptococcus sp.) suggest a multifactorial etiology for FENP, and further studies are needed to determine the environmental, immunological and infectious factors contributing to the disease.     

Two 17beta-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7.

Two 17β-hydroxysteroid dehydrogenases (17HSDs), type 1 and type 7, are enzymes of estradiol biosynthesis, in addition to which rodent type 1 enzymes are also able to catalyze androgens. Both of the 17HSDs are abundantly expressed in ovaries, the type 1 enzyme in granulosa cells and type 7 in luteinized cells. The expression of 17HSD7, which has also been described as a prolactin receptor-associated protein (PRAP), is particularly up-regulated in corpus luteum during the second half of rodent pregnancy. A moderate or slight signal for mouse 17HSD7/PRAP mRNA has also been demonstrated in samples of placenta and mammary gland, for example. Human, but not rodent, 17HSD1 is expressed in placenta, breast epithelium and endometrium in addition to ovaries. A cell-specific enhancer, silencer and promoter in the hHSD17B1 gene participate in the regulation of type 1 enzyme expression. The enhancer consists of several subunits, including a retinoic acid response element, the silencer has a binding motif for GATA factors, and the proximal promoter contains adjacent and competing AP-2 and Sp binding sites.