Groundwater reservoirs constitute important freshwater resources. However, these ecosystems are highly vulnerable to contamination and have to rely on the resident microbiota to attenuate the impact ...of this contamination. Nitrate is one of the main contaminants found in groundwater, and denitrification is the main process that removes the compound. In this study, the response to nutrient load on indigenous microbial communities in groundwater from a low impacted aquifer in Uruguay was evaluated. Denitrification rates were measured in groundwater samples from three different sites with nitrate, acetate and pyrite amendments. Results showed that denitrification is feasible under in situ nitrate and electron donor concentrations, although the lack of readily available organic energy source would limit the attenuation of higher nitrate concentrations. DNA-stable isotope probing, combined with amplicon sequencing of 16S rRNA, nirS and nirK genes, was used to identify the active denitrifiers. Members of the phylum Betaproteobacteria were the dominant denitrifiers in two of three sites, with different families being observed; members of the genus Vogesella (Neisseriaceae) were key denitrifiers at one site, while the genera Dechloromonas (Rhodocyclaceae) and Comamonas (Comamonadaceae) were the main denitrifiers detected at the other sites.
A quarter of patients with essential thrombocythemia or primary myelofibrosis carry a driver mutation of CALR, the calreticulin gene. A 52-bp deletion (type 1) and a 5-bp insertion (type 2 mutation) ...are the most frequent variants. These indels might differentially impair the calcium binding activity of mutant calreticulin. We studied the relationship between mutation subtype and biological/clinical features of the disease. Thirty-two different types of CALR variants were identified in 311 patients. Based on their predicted effect on calreticulin C-terminal, mutations were classified as: (i) type 1-like (65%); (ii) type 2-like (32%); and (iii) other types (3%). Corresponding CALR mutants had significantly different estimated isoelectric points. Patients with type 1 mutation, but not those with type 2, showed abnormal cytosolic calcium signals in cultured megakaryocytes. Type 1-like mutations were mainly associated with a myelofibrosis phenotype and a significantly higher risk of myelofibrotic transformation in essential thrombocythemia. Type 2-like CALR mutations were preferentially associated with an essential thrombocythemia phenotype, low risk of thrombosis despite very-high platelet counts and indolent clinical course. Thus, mutation subtype contributes to determining clinical phenotype and outcomes in CALR-mutant myeloproliferative neoplasms. CALR variants that markedly impair the calcium binding activity of mutant calreticulin are mainly associated with a myelofibrosis phenotype.
Noise is the price to pay when trying to clone or amplify arbitrary quantum states. However, the quantum noise associated with linear phase-insensitive amplifiers can be avoided by relaxing the ...requirement of a deterministic operation. Here we present the experimental realization of a novel concept of a probabilistic noiseless linear amplifier that is able to amplify coherent states at the highest levels of effective gain and final state fidelity ever reached. Based on a sequence of photon addition and subtraction, this high-fidelity amplification scheme is likely to become an essential tool for applications of quantum communication and metrology.
Biliary lithiasis is common worldwide, affecting almost 20% of the general population, though few experience symptoms. The frequency of choledocholithiasis in patients with symptomatic cholelithiasis ...is estimated to be 10–33%, depending on patients' age. Unlike gallbladder lithiasis, the medical and surgical treatment of common bile duct stones is uncertain, having changed over the last few years. The prior gold standard treatment for cholelithiasis and choledocholithiasis was open cholecystectomy with bile duct clearance, choledochotomy, and/or surgical sphincterotomy. In the last 10–15 years, new treatment approaches to the complex pathology of choledocholithiasis have emerged with the advent of endoscopic retrograde cholangiopancreatography (ERCP), laparoscopic surgery, and advanced diagnostic procedures. Although ERCP followed by laparoscopic cholecystectomy is the preferred mode of management, a single-step strategy (laparo-endoscopic rendezvous) has gained acceptance due to lesser morbidity and a lower risk of iatrogenic damage. Given the above, a tailored approach relying on careful evaluation of the disease is necessary in order to minimize complication risks and overall costs. Yet, the debate remains open, with no consensus on the superiority of laparo-endoscopic rendezvous to more conventional approaches.
Cholesterol (Cho) is an essential lipophilic molecule in cells; however, both its decrease and its increase may favor the development of neurological diseases such as Alzheimer's disease (AD). ...Although copper (Cu) is an essential trace metal for cells, the increased plasma concentration of its free form has been linked with AD development and severity. AD affects aged people, but its prevalence and severity are higher in women than in men. We have previously shown that Cu promotes Cho de novo synthesis in immature neurons as well as increased Cho in membrane rafts and Aβ levels in culture medium, but there are no results yet regarding sex differences in the effects of sublethal Cu exposure on Cho de novo synthesis.
We examined the potential sex-specific impact of sublethal Cu concentrations on de novo Cho synthesis in primary cultures of male and female astrocytes. We also explored whether this had any correlation with variations in Cho and APP levels within neuronal membrane rafts.
Flow cytometry analysis demonstrated that Cu treatment leads to a greater increase in ROS levels in female astrocytes than in males. Furthermore, through RT-PCR analysis, we observed an upregulation of SREBP-2 and HMGCR. Consistently, we observed an increase in de novo Cho synthesis. Finally, western blot analysis indicated that the levels of ABCA1 increase after Cu treatment, accompanied by a higher release of radiolabeled Cho and an elevation in Cho and APP levels in neuronal membrane rafts. Importantly, all these results were significantly more pronounced in female astrocytes than in males.
Our findings confirm that Cu stimulates Cho synthesis in astrocytes, both in a ROS-dependent and -independent manner. Moreover, female astrocytes displayed elevated levels of HMGCR, and de novo Cho synthesis compared to males following TBH and Cu treatments. This corresponds with higher levels of Cho released into the culture medium and a more significant Cho and APP rise within neuronal rafts. We consider that the increased risk of AD in females partly arises from sex-specific responses to metals and/or exogenous substances, impacting key enzyme regulation in various biochemical pathways, including HMGCR.
Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA ...mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells. We exploited the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1), and its physiological tropism toward cell nucleus. TNBC cell lines over-expressing TfR-1 were successfully recognized by H-Ferritin, displaying a fast internalization into the cells. HOla induced remarkable cytotoxic effect in cancer cells, exhibiting 1000-fold higher anticancer activity compared to free olaparib (Ola). Accordingly, HOla treatment enhanced PARP-1 cleavage, DNA double strand breaks and Ola delivery into the nuclear compartment. Our findings suggest that H-Ferritin nanoformulation strongly enhances cytotoxic efficacy of Ola as a stand-alone therapy in both BRCA-mutated and wild type TNBC cells, by promoting targeted nuclear delivery.
We present the experimental realization of a scheme, based on single-photon interference, for implementing superpositions of distinct quantum operations. Its application to a thermal light field (a ...well-categorized classical entity) illustrates quantum superposition from a new standpoint and provides a direct and quantitative verification of the bosonic commutation relation between creation and annihilation operators. By shifting the focus towards operator superpositions, this result opens interesting alternative perspectives for manipulating quantum states.
Abstract
As COVID-19 outbreak enters its second phase of lockdown ease, healthcare plans involve elective surgery re-establishment to provide essential life-saving care. Patients are increasingly ...requesting information about their facility's readiness for safely performing surgery. This information should be open and transparent including patient's education with objective data regarding the state of the pandemic in the country and the control measures undertaken by the facility.
Neuroinflammation comprises a feature of many neurological disorders that is accompanied by the activation of glial cells and the release of pro‐inflammatory cytokines and chemokines. Such activation ...is a normal response oriented to protect neural tissue and it is mainly regulated by microglia and astroglia. However, excessive and chronic activation of glia may lead to neurotoxicity and may be harmful for neural tissue. The ovarian hormone oestradiol exerts protective actions in the central nervous system that, at least in part, are mediated by a reduction of reactive gliosis. Several selective oestrogen receptor modulators may also exert neuroprotective effects by controlling glial inflammatory responses. Thus, tamoxifen and raloxifene decrease the inflammatory response caused by lipopolysaccharide, a bacterial endotoxin, in mouse and rat microglia cells in vitro. Tamoxifen and raloxifene are also able to reduce microglia activation in the brain of male and female rats in vivo after the peripheral administration of lipopolysaccharide. In addition, tamoxifen decreases the microglia inflammatory response induced by irradiation. Furthermore, treatment with tamoxifen and raloxifene resulted in a significant reduction of the number of reactive astrocytes in the hippocampus of young, middle‐aged and older female rats after a stab wound injury. Tamoxifen, raloxifene and the new selective oestrogen receptor modulators ospemifene and bazedoxifene decrease the expression and release of interleukine‐6 and interferon‐γ inducible protein‐10 in cultured astrocytes exposed to lipopolysaccharide. Ospemifene and bazedoxifene exert anti‐inflammatory effects in astrocytes by a mechanism involving classical oestrogen receptors and the inhibition of nuclear factor‐kappa B p65 transactivation. These data suggest that oestrogenic compounds are candidates to counteract brain inflammation under neurodegenerative conditions by targeting the production and release of pro‐inflammatory molecules by glial cells.
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