Ferroptosis is an iron-dependent form of non-apoptotic cell death, but its molecular mechanism remains largely unknown. Here, we demonstrate that heat shock protein beta-1 (HSPB1) is a negative ...regulator of ferroptotic cancer cell death. Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in cancer cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis. Protein kinase C-mediated HSPB1 phosphorylation confers protection against ferroptosis by reducing iron-mediated production of lipid reactive oxygen species. Moreover, inhibition of the HSF1-HSPB1 pathway and HSPB1 phosphorylation increases the anticancer activity of erastin in human xenograft mouse tumor models. Our findings reveal an essential role for HSPB1 in iron metabolism with important effects on ferroptosis-mediated cancer therapy.
Global biogeography of coral recruitment Price, N. N.; Muko, S.; Legendre, L. ...
Marine ecology. Progress series (Halstenbek),
07/2019, Letnik:
621
Journal Article
Recenzirano
Odprti dostop
Despite widespread climate-driven reductions of coral cover on tropical reefs, little attention has been paid to the possibility that changes in the geographic distribution of coral recruitment could ...facilitate beneficial responses to the changing climate through latitudinal range shifts. To address this possibility, we compiled a global database of normalized densities of coral recruits on settlement tiles (corals m−2) deployed from 1974 to 2012, and used the data therein to test for latitudinal range shifts in the distribution of coral recruits. In total, 92 studies provided 1253 records of coral recruitment, with 77% originating from settlement tiles immersed for 3–24 mo, herein defined as long-immersion tiles (LITs); the limited temporal and geographic coverage of data from short-immersion tiles (SITs; deployed for <3 mo) made them less suitable for the present purpose. The results from LITs show declines in coral recruitment, on a global scale (i.e. 82% from 1974 to 2012) and throughout the tropics (85% reduction at <20° latitude), and in creases in the sub-tropics (78% increase at >20° latitude). These trends indicate that a global decline in coral recruitment has occurred since 1974, and the persistent reduction in the densities of recruits in equatorial latitudes, coupled with increased densities in sub-tropical latitudes, suggests that coral recruitment may be shifting poleward.
NK cells are central to anti-tumor immunity and recently showed efficacy for treating hematologic malignancies. However, their dysfunction in the hostile tumor microenvironment remains a pivotal ...barrier for cancer immunotherapies against solid tumors. Using cancer patient samples and proteomics, we found that human NK cell dysfunction in the tumor microenvironment is due to suppression of glucose metabolism via lipid peroxidation-associated oxidative stress. Activation of the Nrf2 antioxidant pathway restored NK cell metabolism and function and resulted in greater anti-tumor activity in vivo. Strikingly, expanded NK cells reprogrammed with complete metabolic substrate flexibility not only sustained metabolic fitness but paradoxically augmented their tumor killing in the tumor microenvironment and in response to nutrient deprivation. Our results uncover that metabolic flexibility enables a cytotoxic immune cell to exploit the metabolic hostility of tumors for their advantage, addressing a critical hurdle for cancer immunotherapy.
We report the identification and genome characterization of a novel bocavirus, feline bocavirus (FBoV), and novel bocaviruses closely related to canine bocavirus (CBoV) strain Con-161 in stray cats ...and dogs in Hong Kong, respectively. FBoV was detected by PCR in 7.2, 0.3, 1.6, 2.0 and 0.8% of faecal, nasal, urine, kidney and blood samples, respectively, from 364 cats, while CBoV was detected in 4.6, 5.1, 6.3 and 0.3% of faecal, nasal, urine and blood samples, respectively, from 351 dogs. Three FBoV genomes sequenced revealed the presence of three ORFs characteristic of bocaviruses. Phylogenetic analysis showed that FBoVs were related only distantly to other bocaviruses, forming a distinct cluster within the genus, with ≤ 5.7% nucleotide identities to the genome of minute virus of canines. The four CBoV genomes sequenced shared 87.4-89.2% nucleotide identities with that of CBoV strain Con-161. In addition to the three bocavirus ORFs, they encoded an additional ORF, ORF4, immediately downstream of the ORF for non-structural protein 1 (NS1), which was not found in other bocaviruses including CBoV strain Con-161. They also possessed a putative second exon encoding the C-terminal region of NS1 and conserved RNA-splicing signals, previously described in human bocaviruses. Partial VP1/VP2 sequence analysis of 23 FBoV and 25 CBoV strains demonstrated inter-host genetic diversity, with two potential genetic groups of FBoV and a novel CBoV group, CBoV-HK, distinct from the three groups, CBoV-A to -C, found in the USA. Although the pathogenicity of FBoV and CBoV remains to be determined, their presence in different host tissues suggested wide tissue tropism.
The hallmarks of Alzheimer’s disease (AD) are the aggregates of amyloid-β (Aβ) peptides and tau protein. Autophagy is a major cellular pathway leading to the removal of aggregated proteins. We have ...reported recently that autophagy was responsible for amyloid precursor protein cleaved C-terminal fragment (APP-CTF) degradation and amyloid β clearance in an Atg5-dependent manner. Here we aimed to elucidate the molecular mechanism by which autophagy mediates the degradation of APP-CTF and the clearance of amyloid β. Through affinity purification followed by mass spectrum analysis, we identified adaptor protein (AP) 2 together with phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) as binding proteins of microtubule-associated protein 1 light chain 3 (LC3). Further analysis showed that AP2 regulated the cellular levels of APP-CTF. Knockdown of AP2 reduced autophagy-mediated APP-CTF degradation. Immunoprecipitation and live imaging analysis demonstrated that AP2 and PICALM cross-link LC3 with APP-CTF. These data suggest that the AP-2/PICALM complex functions as an autophagic cargo receptor for the recognition and shipment of APP-CTF from the endocytic pathway to the LC3-marked autophagic degradation pathway. This molecular mechanism linking AP2/PICALM and AD is consistent with genetic evidence indicating a role for PICALM as a risk factor for AD.
Organic Rankine Cycle (ORC) could be used to recover low-grade waste heat. When a vehicle is running, the engine exhaust gas states have a wide range of variance. Defining the operational conditions ...of the ORC that achieve the maximum utilization of waste heat is important. In this paper the performance of different working fluids operating in specific regions was analyzed using a thermodynamic model built in Matlab together with REFPROP. Nine different pure organic working fluids were selected according to their physical and chemical properties. The results were compared in the regions when net power outputs were fixed at 10
kW. Safety levels and environmental impacts were also evaluated. The outcomes indicate that R11, R141b, R113 and R123 manifest slightly higher thermodynamic performances than the others; however, R245fa and R245ca are the most environment-friendly working fluids for engine waste heat-recovery applications. The optimal control principle of ORC under the transient process is discussed based on the analytical results.
► R11, R141b, R113 and R123 manifest the best thermodynamic performances. ► R245fa and R245ca are the most environment-friendly working fluids for the engine waste heat-recovery application. ► The condensing temperature has more important effect than the evaporating pressure to the performance of ORC. ► The optimal control principle of ORC under the transient process was defined according to the calculation results for the vehicle engine waste heat-recovery application. ► ORC thermodynamic model was built in Matlab together with REFPROP.
Masses of single-walled carbon nanotubes (SWNTs) with a large mean diameter of about 1.85 nanometers, synthesized by a semicontinuous hydrogen arc discharge method, were employed for hydrogen ...adsorption experiments in their as-prepared and pretreated states. A hydrogen storage capacity of 4.2 weight percent, or a hydrogen to carbon atom ratio of 0.52, was achieved reproducibly at room temperature under a modestly high pressure (about 10 megapascal) for a SWNT sample of about 500 milligram weight that was soaked in hydrochloric acid and then heat-treated in vacuum. Moreover, 78.3 percent of the adsorbed hydrogen (3.3 weight percent) could be released under ambient pressure at room temperature, while the release of the residual stored hydrogen (0.9 weight percent) required some heating of the sample. Because the SWNTs can be easily produced and show reproducible and modestly high hydrogen uptake at room temperature, they show promise as an effective hydrogen storage material.
EUS-guided hepaticoenterostomy (EUS-HE) usually is reserved for palliation of malignant biliary obstruction after failed endoscopic retrograde cholangiography (ERC) or inaccessible biliary tree in ...surgically altered anatomy (SAA). We describe the outcome of EUS-HE and antegrade therapy for benign biliary disease in patients with SAA.
Retrospective review of 20 consecutive patients with surgically altered anatomy and benign biliary obstruction who underwent EUS-HE performed by 1 endoscopist at a tertiary-care center over a 3-year period.
During the study period, 37 patients underwent EUS-HE; 24 for benign disease. Of these, 20 patients had SAA and were analyzed (15 women, mean age, 62 years). SAA consisted of 9 Roux-en-Y gastric bypasses, 6 Roux-en-Y hepaticojejunostomy, 2 Billroth II procedures, and 3 Whipple procedures. Indications for ERC were common bile duct stones (n = 8), benign postoperative strictures (n = 7), chronic pancreatitis (n = 3), inflammatory stricture (n = 1), and treatment of a bile leak (n = 1). Five patients had previously failed balloon enteroscopy-assisted ERCs. The approach was transgastric in 15 and transjejunal in 5. In all cases, a branch of the left hepatic duct with a mean diameter of 7.8 mm was accessed. Median stent length was 80 mm, with diameters of 8 or 10 mm. Antegrade, definitive endoscopic therapy via the HE was performed in 18 patients, with an average of 2.7 procedures performed for resolution of stones and/or downstream strictures. HE stents were removed in 17 patients after a mean of 91 days without adverse events. Three patients experienced mild adverse events (1 with postprocedural pancreatitis after placement of a 10F transpapillary stent, 1 with postprocedural abdominal pain, and 1 with postprocedural cholangitis) requiring hospitalization for fewer than 3 nights; no severe adverse events occurred. The average postprocedural hospital stay was 1.3 days. No deaths occurred during follow-up.
EUS-HE is safe and effective in the management of benign biliary obstruction in patients with surgically altered anatomy. It creates a portal to allow definitive, antegrade therapy and is a viable alternative to other endoscopic methods in this patient population.
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