Familial breast cancer represents a minor percentage of all human breast cancers. Mutations in two high susceptibility genes
BRCA1
and
BRCA2
explain around 25 % of familial breast cancers, while ...other high, moderate and low susceptibility genes explain up to 20 % more of breast cancer families. Thus, it is important to decipher the genetic architecture of families that show no mutations to improve genetic counselling. The comprehensive description of familial breast cancer using different techniques and platforms has shown to be very valuable for better patient diagnosis, tumour surveillance, and ultimately patient treatment. This review focuses on the complex landscape of pathological, protein, genetic and genomic features associated with
BRCA1
-,
BRCA2
-, and
non
-
BRCA1/BRCA2
-related cancers described up to date. Special emphasis deserves the coexistence of distinct molecular breast cancer subtypes, the development of tumour classifiers to predict
BRCA1/2
mutations, and the last insights from recent whole genome sequencing studies and miRNA profiling.
The photolysis of five frequent emerging contaminants (Benzotriazole, Chlorophene, N,N-diethyl-m-toluamide or DEET, Methylindole, and Nortriptyline HCl) was investigated in ultrapure water under ...monochromatic ultraviolet radiation at 254 nm and by a combination of UV and hydrogen peroxide. The results revealed that the photolysis rates followed first-order kinetics, with rate constant values depending on the nature of the specific compound, the pH, and the presence or absence of the scavenger tert-butanol. Quantum yields were also determined and values in the range of 53.8 × 10−3 − 9.4 × 10−3 mol E−1 for Benzotriazole, 525 × 10−3 − 469 × 10−3 mol E−1 for Chlorophene, 2.8 × 10−3 − 0.9 × 10−3 mol E−1 for DEET, 108 × 10−3 − 165 × 10−3 mol E−1 for Methylindole, and 13.8 × 10−3 − 15.0 × 10−3 mol E−1 for Nortriptyline were obtained. The study also found that the UV/H2O2 process enhanced the oxidation rate in comparison to direct photolysis. High-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) technique was applied to the concentrations evaluation and further identification of the parent compounds and their by-products, which allowed the proposal of the degradation pathways for each compound. Finally, in order to assess the aquatic toxicity in the photodegradation of these compounds, the Vibrio fischeri acute toxicity test was used, and the results indicated an initial increase of this parameter in all cases, followed by a decrease in the specific case of Benzotriazole, DEET, Methylindole, and Chlorophene.
► Photolysis of five emerging contaminants (EC) was investigated. ► First-order rate constants and quantum yields were determined for each EC. ► The combined UV/H2O2 process provided a significant increase in the reaction rates. ► Intermediates were identified and the degradation pathways were proposed. ► Toxicity measurements showed an initial increase, followed by a decrease.
•The removal of 5 neonicotinoids by UV irradiation, UV/H2O2 and UV/PS was investigated.•The quantum yields for the UV photolysis of neonicotinoids at 254 nm were determined.•The degradation rate of ...neonicotinoids followed pseudo-first order kinetics.•Indirect photolysis was important only for neonicotinoids with low quantum yield.•Natural organic matter and radical scavengers inhibited the removal of neonicotinoids.
Neonicotinoids are a new class of insecticides whose potential side-effects on the human health and the environment have not yet been well investigated. Recently, the EU approved the Decision 2015/495 establishing a watch list of substances for Union-wide monitoring in the field of water policy, which includes five neonicotinoids: thiamethoxam (TMX), imidacloprid (ICP), clothianidin (CTD), thiacloprid (TCP) and acetamiprid (AMP). The photodegradation of neonicotinoids by monochromatic UV irradiation (254 nm) has been investigated. The photolysis rate followed pseudo-first order kinetics, with rate constant values depending on the nature of the specific compound, pH, and the presence or absence of radical scavengers. A method based on atrazine actinometry provided the following quantum yields at pH = 7: (77 ± 3) × 10−3, (43 ± 2) × 10−3, (48 ± 1) × 10−3, (17 ± 2) × 10−3 and (5 ± 2) × 10−3 mol E−1 for TMX, CTD, ICP, TCP and AMP, respectively. The effects of the presence of bicarbonate, nitrate, nitrite and chloride ions on the simultaneous photodegradation of nicotinoids were not very significant, and only the removal of AMP, the least photosensitive neonicotinoid, was negatively affected. However, the photodegradation of neonicotinoids was clearly inhibited by the addition of humic acids. The results obtained in experiments performed in the presence of hydrogen peroxide or persulfate indicated that while direct UV photolysis was the main degradation pathway for TMX and even for CTD, ICP and TCP, the contribution of indirect photolysis (radical pathway) was important in the case of pollutants with low values of quantum yield such as AMP. Although the presence of natural organic and inorganic matter in real water matrices decreased the degradation rate of the selected neonicotinoids, UV photolysis and the AOPs UV/H2O2 and UV/PS processes constitute efficient technologies for the removal of these pollutants from contaminated waters.
•The removal of 5 emerging contaminants (ECs) by UV/PS was investigated.•Rate constants of ECs with sulfate radicals were determined by competition kinetics.•The degradation rate of ECs followed ...pseudo-first order kinetics.•The maximum degradation rate was achieved at near neutral pH.•Natural organic matter and radical scavengers inhibited the removal of ECs.
The degradation of five selected emerging contaminants (ECs) including 1H-benzotriazole (BZ), N,N-diethyl-m-toluamide or DEET (DT), chlorophene (CP), 3-methylindole (ML), and nortriptyline hydrochloride (NH) in aqueous solutions by UV-activated persulfate (UV/PS) has been investigated. Selected ECs were not effectively degraded by direct UV photolysis or dark PS. However, their photodegradation efficiency significantly increased with addition of PS due to the generation of SO4− and HO. Second order rate constants for the reaction between SO4− and each EC were determined by competition kinetics, being the values at pH 7 2.0 × 1010, 1.2 × 1010, 1.8 × 109, 1.1 × 109 and 9.5 × 108 M−1 s−1 for NH, ML, CP, BZ and DT, respectively. While the dose of PS exerted a positive influence on the degradation of ECs, the highest degradation rate was observed at near neutral pH. With respect to the influence of background water matrix constituents, bicarbonate showed an inhibition effect on the removal of DT, BZ and NH and promoted the degradation of CP and especially of ML, which can be explained by their high reaction rate with carbonate radicals. The presence of humic acids inhibited the degradation of selected ECs, probably due to light screening and radical scavenging. Both radical species SO4− and HO exert an important role on the oxidation of the ECs investigated by the UV/PS system, being the contribution of SO4− predominant for those compounds that present high reactivity with this radical. Although the presence of inorganic and organic matter in real water matrices decreased the degradation rate of selected ECs, UV/PS process is an efficient option for their removal from contaminated waters.
In recent years, high-throughput next-generation sequencing technology has allowed a rapid increase in diagnostic capacity and precision through different bioinformatics processing algorithms, tools, ...and pipelines. The identification, annotation, and classification of sequence variants within different target regions are now considered a gold standard in clinical genetic diagnosis. However, this procedure lacks the ability to link regulatory events such as differential splicing to diseases. RNA-seq is necessary in clinical routine in order to interpret and detect among others splicing events and splicing variants, as it would increase the diagnostic rate by up to 10–35%. The transcriptome has a very dynamic nature, varying according to tissue type, cellular conditions, and environmental factors that may affect regulatory events such as splicing and the expression of genes or their isoforms. RNA-seq offers a robust technical analysis of this complexity, but it requires a profound knowledge of computational/statistical tools that may need to be adjusted depending on the disease under study. In this article we will cover RNA-seq analyses best practices applied to clinical routine, bioinformatics procedures, and present challenges of this approach.
Apparent rate constants for the reactions of four selected pharmaceutical compounds (metoprolol, naproxen, amoxicillin, and phenacetin) with chlorine in ultra-pure (UP) water were determined as a ...function of the pH. It was found that amoxicillin (in the whole pH range 3–12), and naproxen (in the low pH range 2–4) presented high reaction rates, while naproxen (in the pH range 5–9), and phenacetin and metoprolol (in the pH range 2.5–12 for phenacetin, and 3–10 for metoprolol) followed intermediate and slow reaction rates. A mechanism is proposed for the chlorination reaction, which allowed the evaluation of the intrinsic rate constants for the elementary reactions of the ionized and un-ionized species of each selected pharmaceutical with chlorine. An excellent agreement is obtained between experimental and calculated rate constants by this mechanism.
The elimination of these substances in several waters (a groundwater, a surface water from a public reservoir, and two effluents from municipal wastewater treatment plants) was also investigated at neutral pH. The efficiency of the chlorination process with respect to the pharmaceuticals elimination and the formation THMs was also established. It is generally observed that the increasing presence of organic and inorganic matter in the water matrices demand more oxidant agent (chlorine), and therefore, less chlorine is available for the oxidation of these compounds. Finally, half-life times and oxidant exposures (CT) required for the removal of 99% of the four pharmaceuticals are also evaluated. These parameters are useful for the establishment of safety chlorine doses in oxidation or disinfection stages of pharmaceuticals in treatment plants.
High pressure X-ray diffraction, Raman scattering, and electrical measurements, together with theoretical calculations, which include the analysis of the topological electron density and electronic ...localization function, evidence the presence of an isostructural phase transition around 2 GPa, a Fermi resonance around 3.5 GPa, and a pressure-induced decomposition of SnSb2Te4 into the high-pressure phases of its parent binary compounds (α-Sb2Te3 and SnTe) above 7 GPa. The internal polyhedral compressibility, the behavior of the Raman-active modes, the electrical behavior, and the nature of its different bonds under compression have been discussed and compared with their parent binary compounds and with related ternary materials. In this context, the Raman spectrum of SnSb2Te4 exhibits vibrational modes that are associated but forbidden in rocksalt-type SnTe; thus showing a novel way to experimentally observe the forbidden vibrational modes of some compounds. Here, some of the bonds are identified with metavalent bonding, which were already observed in their parent binary compounds. The behavior of SnSb2Te4 is framed within the extended orbital radii map of BA2Te4 compounds, so our results pave the way to understand the pressure behavior and stability ranges of other “natural van der Waals” compounds with similar stoichiometry.
Background
Type I gastric neuroendocrine tumors (gNETs) arise from hypergastrinemia in patients with autoimmune chronic atrophic gastritis. According to the classical model, the gastric H+/K+ ATPase ...was the causative autoantigen recognized by CD4+ T cells in chronic autoimmune scenario that secretes IL-17 and correlates with parietal cell (PC) atrophy, which drives to gastric achlorhydria and increases the risk for gastric neoplasms. However, the mechanism by which the inflammatory response correlates with PC atrophy is not clearly defined.
Methods
Recently, we found that the ATP4A
p.R703C
mutation impaired PC function and gastric acidification, which drove familial gNET. Our group constructed a knock-in mouse model for the
ATP4A
mutation, which has served us to better understand the relation between impaired capability to export protons across the plasma membrane of PCs and tumor progression.
Results
The ATP4A
p.R703C
mutation drives gastric achlorhydria, but also deregulates the acid–base balance within PCs, affecting mitochondrial biogenesis. Mitochondrial malfunction activates ROS signaling, which triggers caspase-3-mediated apoptosis of parietal cells. In addition, when gastric euchlorhydria was restored, mitochondrial function is recovered. Infection by
H. pylori
promotes destabilization of the mitochondria of the PCs by a mechanism similar to that described for APT4A
p.R703C
carriers.
Conclusions
A genetic origin that drives mitochondria alteration would initiate the gastric chronic inflammation instead of the classical IL-17 secretion-mediated mechanism explanation. Gastric euchlorhydria restoration is suggested to be indicated for mitochondrial recover. Our results open a new window to understand gastric neoplasms formation but also the inflammatory mechanisms and autoimmune disorders conducted by genetic origin that composes a premalignant scenario.
Four UF membranes (denoted GH, GK, PT and PW with MWCO of 1000, 2000, 5000 and 20,000
Da, respectively) and four NF membranes (denoted DL, CK, DK and HL, with an approximate MWCO of 150–300
Da in all ...cases) were used for the filtration of an effluent generated in a municipal wastewater plant after a secondary treatment. The influence of the most important operating variables (nature and MWCO of the membranes, transmembrane pressure, tangential velocity, and temperature) on the permeate flux was widely discussed, and the resistances to the permeate flux were determined following the resistances in series model. Rejection coefficients for parameters that measure the global pollutant content of the effluent (chemical oxygen demand, total organic carbon, absorbance at 254
nm, turbidity, total nitrogen and total phosphorus) were also evaluated, and the results revealed that both UF and NF are feasible options for the treatment of this effluent, yielding a permeate stream that can be reused in several applications. Finally, 28 pharmaceutical compounds were initially detected in this effluent, and their respective rejection coefficients were determined, with eliminations higher than 75% in the case of NF with the HL membrane. Therefore, it is concluded that NF is an excellent option for the removal of toxic pharmaceuticals in municipal wastewaters.
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