Similar hypotensive responses to resistance exercise with and without blood flow restriction

Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances.     

Comparison of Plastic Packaging Waste Management Options: Feedstock Recycling versus Energy Recovery in Germany

Plastics recycling, especially as prescribed by the German Ordinance on Packaging Waste (Verpackungsverordnung), is a conspicuous example of closing material loops on a large scale. In Germany, an industry‐financed system (Duales System Deutschland) was established in 1991 to collect and recycle packaging waste from households. To cope with mixed plastics, various “feedstock‐recycling” processes were developed. We discuss the environmental benefits and the cost‐benefit ratio of the system relative to municipal solid waste (MSW) incineration, based on previously published life‐cycle assessment (LCA) studies. Included is a first‐time investigation of energy recovery in all German incinerators, the optimization opportunities, the impact on energy production and substitution processes, an estimation of the costs, and a cost‐benefit assessment. In an LCA, the total environmental impact of MSW incineration is mainly determined by the energy recovery ratio, which was found on average to reach 39% in current German incineration plants. Due to low revenues from additional energy generation, it is not cost‐effective to optimize the plants energetically. Energy from plastic incineration substitutes for a specific mixture of electric base‐load power, district heating, and process steam generation. Any additional energy from waste incineration will replace, in the long term, mainly natural gas, rather than coal. Incineration of plastic is compared with feedstock recycling methods in different scenarios. In all scenarios, the incineration of plastic leads to an increase of CO2 emissions compared to landfill, whereas feedstock recycling reduces CO2 emissions and saves energy resources. The costs of waste incineration are assumed to decrease by about 30% in the medium term. Today, the calculated costs of CO2 reduction in feedstock recycling are very high, but are ex‐pected to decline in the near future. Relative to incineration, the costs for conserving energy via feedstock recycling are 50% higher, but this gap will close in the near future if automatic sorting and processing are implemented in Germany.     

CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma

Cancer stem cells (CSCs) have been implicated in the initiation and maintenance of tumour growth as well as metastasis. Recent reports link stemness to epithelial–mesenchymal transition (EMT) in cancer. However, there is still little knowledge about the molecular markers of those events. In silico analysis of RNA profiles of 36 pancreatic ductal adenocarcinomas (PDAC) reveals an association of the expression of CD95 with EMT and stemness that was validated in CSCs isolated from PDAC surgical specimens. CD95 expression was also higher in metastatic pancreatic cells than in primary PDAC. Pharmacological inhibition of CD95 activity reduced PDAC growth and metastasis in CSC-derived xenografts and in a murine syngeneic model. On the mechanistic level, Sck was identified as a novel molecule indispensable for CD95''s induction of cell cycle progression. This study uncovers CD95 as a marker of EMT and stemness in PDAC. It also addresses the molecular mechanism by which CD95 drives tumour growth and opens tantalizing therapeutic possibilities in PDAC.Recent analysis of the cellular heterogeneity within the tumour mass revealed the existence of cells that share characteristics with stem cells of the tissue of origin.¹ These cells are responsible for the tumour''s resistance to current therapies and therefore provide new perspectives in cancer treatment. Cancer stem cells (CSCs) or tumour-initiating cells (TICs) are characterized by their self-renewal and differentiation capacity, which are assessed by their ability to generate a heterogeneous tumour in immunocompromised mice in serial transplantations.² In pancreatic cancer, those properties were initially shown by cells expressing CD24, CD44 and ESA (epithelial surface antigen).³Pancreatic cancer is the fourth leading cause of cancer-related death in the United States of America.⁴ The highly malignant phenotype of pancreatic ductal adenocarcinoma (PDAC) results from aggressive invasion and early metastatic potential. Epithelial–mesenchymal transition (EMT) is considered to be the first step of metastatic spread. During this process, the tumour cells master the ability to detach from their neighbours and gain motile and invasive properties enabling them to spread via blood or lymph vessels.⁵ As cells undergo EMT, they lose their epithelial features including sheet-like architecture, polarity and E-cadherin expression and gradually gain motility and expression of mesenchymal markers such as N-cadherin, fibronectin and vimentin. Recent studies have uncovered a link between the EMT and the acquisition of stem cell characteristics.^{6, 7} Most growth factors such as TGF-β, HGF, EGF, IGF and FGF are known to trigger EMT.⁸ Interestingly, there is growing evidence that the so-called ‘death receptor'' CD95 (Fas/Apo-1) behaves like a growth factor receptor in cancer cells.^{9, 10, 11}CD95 was first discovered as the initiator of programmed cell death by forming death-inducing signalling complex (DISC, including Fas-associated death domain, FADD and caspase-8/10) upon stimulation with CD95 ligand (CD95L).¹² However, mitogen-activated protein kinases (MAPKs), leading to p38, JNK or extracellular signal-regulated kinase (ERK) 1/2 activation, were also reported to be driven by CD95.^{13, 14} In glioblastoma multiforme (GBM), CD95-induced migration depends on the formation of the so-called phosphatidyl-inositol 3-kinase (PI3K) activation complex (PAC),^{11, 12} consisting of the Src family kinase (SFK), Yes and p85, the regulatory subunit of PI3K. PAC components, however, differ between cell types, encompassing also other SFKs or the Syk tyrosine kinase.^{15, 16}Here, we show that the expression of CD95 increases in primary PDACs as compared with non-tumour-bearing pancreas and is higher in metastatic pancreatic cells than in primary PDAC. In CSCs isolated from primary PDAC surgical specimens, the expression of CD95 positively correlates with EMT markers. We also identified Sck as the molecular link between CD95 and activation of the PI3K and MAPK pathways. Neutralization of the CD95L reduces PDAC growth and metastasis. The present study defines CD95 and its downstream signalling pathway components as new targets for PDAC therapy.     

Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress

Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1−/− intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology.     

Bat Airway Epithelial Cells: A Novel Tool for the Study of Zoonotic Viruses

Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, Carollia perspicillata (Seba''s short-tailed bat) and Eidolon helvum (Straw-colored fruit bat), were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.