The main goal of this paper is to study the effect of wet/dry season and the depth on several parameters of the forest soil. This work has shown that the concentration of Al3+ increases and that the ...concentration of exchangeable cations (Ca2+, Mg2+) and pHs (distilled water and CaCl2) decreases with the increase in depth and that these results are correlated. The concentrations of exchangeable cations (Al3+, Ca2+, Mg2+) and organic matter (OM) are affected by dry/wet season. Rain increases the solubility of organic carbon, thus decreasing OM and releasing exchangeable cations (Al3+, Ca2+, Mg2+). P (available) shows an increase in its concentration with an increase in depth. The low concentration of P (available) in the soil samples could be due to the low pH of the soils. The value of pHpzc is influenced by exchangeable cations (Al3+, Ca2+, Mg2+), and the pHs (CaCl2 and distilled water) are higher than pHpzc. This means that the net charge of these soils is negative. CEC and CECpotential decrease with the increase in depth in most soil samples. For mostly of the samples, the season (wet/dry) does not affect CEC, CECpotential, K+, or Na+.
O principal objetivo deste trabalho é estudar o efeito da estação chuva/seca e a profundidade sobre diversos parâmetros do solo de floresta. Este trabalho mostrou que a concentração de Al3+ aumenta e ...que a concentração de cátions trocáveis (Ca2+, Mg2+) e pH (água destilada e CaCl2) diminuem com o aumento na profundidade e estes resultados são interdependentes. As concentrações de cátions trocáveis (Al3+, Ca2+, Mg2+) e matéria orgânica (MO) são afetadas pela estação seca/chuva. Chuva aumenta a solubilidade de carbono orgânico, portanto diminui MO e libera cátions trocáveis (Al3+, Ca2+, Mg2+). P (trocável) mostra um aumento na sua concentração com um aumento na profundidade. A pequena concentração de P (trocável) nas amostras de solo pode ser devido ao baixo pH dos solos. O valor de pHpzc é influenciado pelos cátions trocáveis (Al3+, Ca2+, Mg2+), e os pHs (CaCl2 e água destilada) são maiores do que pHpzc. Isto significa que a carga destes solos é negativa. CTC e CTCpotencial diminuem com o aumento da profundidade para a maioria das amostras de solos. A estação (seco/chuva) não afeta CTC, CTCpotencial, K+, ou Na+, para a maioria das amostras.
In an exploratory analysis, we investigated the association between programmed death ligand 1 (PD-L1), tumor mutational burden (TMB), T-cell-inflamed gene expression profile (TcellinfGEP), and ...stromal signature with outcomes of pembrolizumab in urothelial carcinoma (UC).
Patients with advanced UC received first-line pembrolizumab 200 mg every 3 weeks in the single-arm phase II KEYNOTE-052 trial (NCT02335424) and salvage pembrolizumab 200 mg every 3 weeks or chemotherapy (paclitaxel/docetaxel/vinflunine) in the randomized phase III KEYNOTE-045 trial (NCT02256436). The association of each biomarker (continuous variable) with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was evaluated using logistic regression (ORR) and Cox PH (PFS, OS), adjusted for ECOG PS; nominal P values were calculated without multiplicity adjustment (one-sided, pembrolizumab; two-sided, chemotherapy). Significance was prespecified at α = 0.05.
In KEYNOTE-052, PD-L1, TMB, and TcellinfGEP were significantly associated with improved outcomes; stromal signature was significantly associated with worse outcomes. In KEYNOTE-045, although findings for TMB and TcellinfGEP with pembrolizumab were consistent with those of KEYNOTE-052, PD-L1 was not significantly associated with improved outcomes, nor was stromal signature associated with worse outcomes with pembrolizumab; chemotherapy was not associated with outcomes in a consistent manner for any of the biomarkers. Hazard ratio (HR) estimates at prespecified cutoffs showed an advantage for pembrolizumab versus chemotherapy regardless of PD-L1 or TMB, with a trend toward lower HRs in the combined positive score ≥10 and the TMB ≥175 mutation/exome subgroup. For TcellinfGEP, PFS and OS HRs were lower in the TcellinfGEP-nonlow subgroup regardless of treatment.
Multiple biomarkers characterizing the tumor microenvironment may help predict response to pembrolizumab monotherapy in UC, and potential clinical utility of these biomarkers may be context-dependent.
The serotonin 2A (5-HT
2A
) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat ...strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putative genetic rat model of schizophrenia-related features. The RHA-I strain shows increased 5-HT
2A
and decreased mGlu2 receptor binding levels in prefrontal cortex (PFC). Here, we looked for differences in gene expression and transcriptional regulation of these receptors. The striatum (STR) was included in the analysis. 5-HT
2A
, 5-HT
1A
, and mGlu2 mRNA and
3
Hketanserin binding levels were measured in brain homogenates. As expected, 5-HT
2A
binding was significantly increased in PFC in the RHA-I rats, while no difference in binding was observed in STR. Surprisingly, 5-HT
2A
gene expression was unchanged in PFC but significantly decreased in STR. mGlu2 receptor gene expression was significantly decreased in both PFC and STR. No differences were observed for the 5-HT
1A
receptor. Chromatin immunoprecipitation assay revealed increased trimethylation of histone 3 at lysine 27 (H3K27me3) at the promoter region of the
HTR2A
gene in the STR. We further looked at the Akt/GSK3 signaling pathway, a downstream point of convergence of the serotonin and glutamate system, and found increased phosphorylation levels of GSK3β at tyrosine 216 and increased β-catenin levels in the PFC of the RHA-I rats. These results reveal region-specific regulation of the 5-HT
2A
receptor in the RHA-I rats probably due to absence of mGlu2 receptor that may result in differential regulation of downstream pathways.
Among the 'most wanted' targets in cancer therapy is the oncogene MYC, which coordinates key transcriptional programs in tumor development and maintenance. It has, however, long been considered ...undruggable. OMO-103 is a MYC inhibitor consisting of a 91-amino acid miniprotein. Here we present results from a phase 1 study of OMO-103 in advanced solid tumors, established to examine safety and tolerability as primary outcomes and pharmacokinetics, recommended phase 2 dose and preliminary signs of activity as secondary ones. A classical 3 + 3 design was used for dose escalation of weekly intravenous, single-agent OMO-103 administration in 21-day cycles, encompassing six dose levels (DLs). A total of 22 patients were enrolled, with treatment maintained until disease progression. The most common adverse events were grade 1 infusion-related reactions, occurring in ten patients. One dose-limiting toxicity occurred at DL5. Pharmacokinetics showed nonlinearity, with tissue saturation signs at DL5 and a terminal half-life in serum of 40 h. Of the 19 patients evaluable for response, 12 reached the predefined 9-week time point for assessment of drug antitumor activity, eight of those showing stable disease by computed tomography. One patient defined as stable disease by response evaluation criteria in solid tumors showed a 49% reduction in total tumor volume at best response. Transcriptomic analysis supported target engagement in tumor biopsies. In addition, we identified soluble factors that are potential pharmacodynamic and predictive response markers. Based on all these data, the recommended phase 2 dose was determined as DL5 (6.48 mg kg
).ClinicalTrials.gov identifier: NCT04808362 .
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