Chloride (Cl
) has traditionally been considered a micronutrient largely excluded by plants due to its ubiquity and abundance in nature, its antagonism with nitrate (NO
), and its toxicity when ...accumulated at high concentrations. In recent years, there has been a paradigm shift in this regard since Cl
has gone from being considered a harmful ion, accidentally absorbed through NO
transporters, to being considered a beneficial macronutrient whose transport is finely regulated by plants. As a beneficial macronutrient, Cl
determines increased fresh and dry biomass, greater leaf expansion, increased elongation of leaf and root cells, improved water relations, higher mesophyll diffusion to CO
, and better water- and nitrogen-use efficiency. While optimal growth of plants requires the synchronic supply of both Cl
and NO
molecules, the NO
/Cl
plant selectivity varies between species and varieties, and in the same plant it can be modified by environmental cues such as water deficit or salinity. Recently, new genes encoding transporters mediating Cl
influx (
and
), Cl
efflux (
and
), and Cl
compartmentalization (
,
,
and
) have been identified and characterized. These transporters have proven to be highly relevant for nutrition, long-distance transport and compartmentalization of Cl
, as well as for cell turgor regulation and stress tolerance in plants.
The wear behavior of two plasma-sprayed zirconia–yttria coatings was studied at high temperatures. Agglomerated and sintered, as well as fused and crushed zirconia–yttria feedstock powders were used ...to manufacture bimodal and monomodal coatings by atmospheric plasma spraying onto an INCONEL 718 substrate previously coated with a NiCrAlY bond coat. The structure of the coatings was analyzed by SEM on their cross section and surface. The samples were subjected to wear conditions by sliding contact through a ball-on-disk test up to 1000 °C, using an alumina ball 6 mm in diameter as the counterbody, on which a load of 5 N was applied. The samples were rotated during 20000 cycles, reaching a speed of 0.10 m·s
−1
at the contact area with the counterbody. The porosity, phase, and mechanical properties were determined before and after wear tests. The results indicate that at 25 °C, both coatings have enough mechanical resistance to withstand the tribological conditions they were exposed to. Therefore, low wear rates were produced by ductile deformation. The tribological conditions became more aggressive as the thermal stresses increased with the test temperature, producing cracking, and detaching particles in the coatings tested at 500 and 750 °C. Consequently, high wear rates related to brittle deformation were obtained. However, the transformation of the amorphous phase to the
t
′-zirconia phase, produced at 1000 °C, increased the hardness of both coatings and, consequently, their wear resistance; thus, the predominant mechanism of damage was ductile deformation, with wear rates similar to those obtained when the coatings were tested at 25 °C.
Tumor-infiltrating lymphocytes (TIL) in the residual disease (RD) of triple-negative breast cancers (TNBC) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into ...tumor cell-autonomous molecular pathways affecting these features are lacking.
We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1-targeted immunotherapy in mouse models of breast cancer.
Presence of TILs in the RD was significantly associated with improved prognosis. Genetic or transcriptomic alterations in Ras-MAPK signaling were significantly correlated with lower TILs. MEK inhibition upregulated cell surface MHC expression and PD-L1 in TNBC cells both in vivo and in vitro. Moreover, combined MEK and PD-L1/PD-1 inhibition enhanced antitumor immune responses in mouse models of breast cancer.
These data suggest the possibility that Ras-MAPK pathway activation promotes immune-evasion in TNBC, and support clinical trials combining MEK- and PD-L1-targeted therapies. Furthermore, Ras/MAPK activation and MHC expression may be predictive biomarkers of response to immune checkpoint inhibitors.
For most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and ...pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases.
In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses.
Of the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcγRIIIa. Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent.
This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.
Aim: The objective of this systematic review and meta‐analysis was to assess the effect of pramlintide on glycemic control, weight and incidence of nausea and hypoglycaemia in patients with type 2 ...diabetes mellitus (T2DM) and in obese patients without diabetes (OBP).
Methods: Eight randomized, clinical trials were identified from multiple databases. Qualitative assessments and quantitative analyses were performed.
Results: In four T2DM studies (N = 930,duration of studies 16–52weeks,120–150mcg/dose BID–TID), all patients received insulin therapy. In four obesity studies (N = 686,duration of studies 6–24weeks,120–360mcg/dose BID–TID), equivalent volumes of placebo were administered before major meals. Pramlintide significantly reduced haemoglobin A1c (HbA1c) (−0.33% 95% CI −0.51, −0.14, p = 0.004) and weight (−2.57 kg, 95% CI −3.44, −1.70, p < 0.00001) versus the control group. More patients in the control group reported hypoglycaemia of any severity versus the pramlintide group (risk ratio 0.84 95% CI 0.69, 10.3, p = 0.09). In OBP, pramlintide caused a reduction in weight (−2.27 kg 95% CI −2.88, −1.66, p < 0.00001). When event data from both populations were combined, patients randomized to pramlintide were 1.8 times more likely to report nausea of any severity versus control (p = 0.0005).
Conclusions: Pramlintide was associated with a small reduction in HbA1c, and a modest reduction in weight in patients with T2DM or OBP. There was increased incidence of nausea but not hypoglycaemia at any time during therapy. Studies about the long‐term effect of pramlintide on diabetes‐ and cardiovascular‐related complications and cost‐effectiveness analyses are needed.
Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, ...we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.
Molecular information is crucial for species identification when facing challenging morphology‐based specimen identifications. The use of DNA barcodes partially solves this problem, but in some cases ...when PCR is not an option (i.e., primers are not available, problems in reaction standardization), amplification‐free approaches could be an optimal alternative. Recent advances in DNA sequencing, like the MinION device from Oxford Nanopore Technologies (ONT), allow to obtain genomic data with low laboratory and technical requirements, and at a relatively low cost. In this study, we explore ONT sequencing for molecular species identification from a total DNA sample obtained from a neotropical rodent and we also test the technology for complete mitochondrial genome reconstruction via genome skimming. We were able to obtain “de novo” the complete mitogenome of a specimen from the genus Melanomys (Cricetidae: Sigmodontinae) with average depth coverage of 78X using ONT‐only data and by combining multiple assembly routines. Our pipeline for an automated species identification was able to identify the sample using unassembled sequence data (raw) in a reasonable computing time, which was substantially reduced when a priori information related to the organism identity was known. Our findings suggest ONT sequencing as a suitable candidate to solve species identification problems in metazoan nonmodel organisms and generate complete mtDNA datasets.
The findings of this study suggest ONT sequencing as a suitable candidate to solve species identification problems in metazoan nonmodel organisms and generate complete mtDNA datasets.
Two ZrO2-Al2O3 atmospheric plasma coatings were applied to a pressed and sintered aluminosilicate refractory brick, which were compared to an electro-melted alumina-zirconia-silica (AZS) refractory ...typically used in the glass industry for its high temperature wear resistance. The samples were subjected to sliding contact using a ball-on-disk test at 25, 500, 750, and 1000 °C and then, physical, crystallographic, and mechanical characterizations were performed before and after the wear tests in order to monitor the wear behavior. Both ZrO2-Al2O3 coatings exhibited better wear performance than the electro-melted AZS refractory at all temperatures evaluated, owing to their high hardness and fracture toughness, which were mainly related to the increase of α-Al2O3 and t-ZrO2 phases from γ-Al2O3 and the crystallization of amorphous phases respectively. In the same way, both coatings also showed the same wear mechanisms at all temperatures evaluated. At 25 °C, wear by ductile deformation was identified, while at 500 and 750 °C, wear by brittle deformation was produced, and at 1000 °C, the transition of wear from brittle to ductile deformation was evident. For the electro-melted AZS refractory, until 750 °C, wear by brittle deformation was developed, while at 1000 °C, wear by both, brittle and ductile deformation was detected.
•The wear resistance at 1000 °C of two different ZrO2-Al2O3 coatings was evaluated.•The quantity of α-Al2O3 and t-ZrO2 increased at 1000 °C in both coatings.•Both ZrO2-Al2O3 coatings showed similar wear resistance at 1000 °C.•Both coatings showed better wear resistance at 1000 °C than the reference refractory.•Both coatings can protect the refractory used as substrate at 1000 °C.
•Grape seed, chestnut and tea extract reduced lipid oxidation.•Natural antioxidants permits obtain more attractive products for the consumers.•By-products could be used in meat industry as natural ...antioxidants.
The effect of the addition of natural antioxidants (tea, chestnut and grape seed extracts) on physico-chemical and oxidative stability of refrigerated stored pig pâtés was studied. This effect was compared with that showed by the synthetic antioxidant BHT. Pâté samples were analysed at 0, 4, 8 and 24weeks of refrigerated storage (4°C).
Colour parameters were affected by storage period and antioxidant extract. Samples with CHE and GRA extracts showed lower total colour difference between 0 and 24weeks. The amount of TBARS gradually increased during refrigerated storage with the exception of pâtés that have CHE extract in composition. At the sampling end point, the lower TBARS values were obtained in samples with TEA and GRA extracts. Finally, the evolution of volatile compounds during storage showed an increase in the lipid-derived volatile values after refrigerated storage, since samples with TEA and GRA extract showed the lowest values.
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