Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges

Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular and genetic diversity. Diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC) are the major histological types. GC may be sporadic or hereditary; sporadic GC is related to environmental and genetic low-risk factors and hereditary GC is caused by inherited high-risk mutations, so far identified only for the diffuse histotype. DGC phenotypic heterogeneity challenges the current understanding of molecular mechanisms underlying carcinogenesis. The definition of a DGC-specific mutational profile remains controversial, possibly reflecting the heterogeneity of DGC-related histological subtypes [signet-ring cell carcinoma (SRCC) and poorly cohesive carcinoma not otherwise specified (PCC-NOS)]. Indeed, DGC and DGC-related subtypes may present specific mutational profiles underlying the particularly aggressive behaviour and dismal prognosis of DGC vs IGC and PCC-NOS vs SRCC. In this systematic review, we revised the histological presentations, molecular classifications and approved therapies for gastric cancer, with a focus on DGC. We then analysed results from the most relevant studies, reporting mutational analysis data specifying mutational frequencies, and their relationship with DGC and IGC histological types, and with specific DGC subtypes (SRCC and PCC-NOS). We aimed at identifying histology-associated mutational profiles with an emphasis in DGC and its subtypes (DGC vs IGC; sporadic vs hereditary DGC; and SRCC vs PCC-NOS). We further used these mutational profiles to identify the most commonly affected molecular pathways and biological functions, and explored the clinical trials directed specifically to patients with DGC. This systematic analysis is expected to expose a DGC-specific molecular profile and shed light into potential targets for therapeutic intervention, which are currently missing.The authors acknowledge the support of the National Infrastructure ‘GenomePT’ – National Laboratory for Genome Sequencing and Analysis (POCI-01-0145-FEDER-022184). J.G-P acknowledges the support of Faculty of Medicine from University of Porto, specifically by the Doctoral Programme in Biomedicine and the Solve-RD Project (H2020-SC1-2017-Single-Stage-RTD) for his PhD fellowship. R.B-M. acknowledges the support of Institute of Biomedical Sciences Abel Salazar from University of Porto, specifically by the Doctoral Programme BiotechHealth and the FCT – Fundação para a Ciência e a Tecnologia for her PhD fellowship (ref. SFRH/BD/145132/2019). This research and its authors were funded by FEDER – Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project ‘Institute for Research and Innovation in Health Sciences’ (POCI-01-0145-FEDER-007274). This work was also financed by the projects NORTE-01-0145-FEDER-000003 (DOCnet) and NORTE-01-0145-FEDER-000029 (CANCER) – supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) – project POCI-01-0145-FEDER-016390 (CancelStem) and PTDC/BTM-TEC/30164/2017 (3DChroMe), funded by ERDF, POCI and FCT

Estudo palinostratigráfico do setor Malhadinha, região NE Alvares, concelho de Mértola, Faixa Piritosa Ibérica

Cartografia geológica realizada pelo Laboratório Nacional de Energia e Geologia (LNEG) acompanhada por estudos palinostratigráficos na região de Malhadinha, NE de Alvares, localizada no setor WNW da Faixa Piritosa Ibérica (FPI), concelho de Mértola, possibilitaram o conhecimento de detalhe da estratigrafia local. Apresentam-se as idades obtidas por palinologia para as formações Barranco do Homem e Filito-Quartzítica, ambas de idade do Famenniano superior, e Freixial, de idade do Viseano superior, correlacionando-se os dados obtidos com a geologia regional da FPI. Os dados obtidos confirmam o predomínio de estruturas alóctones no setor norte da Faixa Piritosa, entre Alvares e a fronteira espanhola.Geological mapping performed by the National Laboratory of Energy and Geology (LNEG) and palynostratigraphic studies carried out in Malhadinha region, NE of Alvares village, located in the northern sector of the Iberian Pyrite Belt (IPB), WNW of Mértola, allowed to obtain a detailed knowledge of the local stratigraphy. Age data obtained by palynology to the Barranco do Homem (upper Famennian age), Phyllite-Quartzite (upper Famennian age), and Freixial (Visean age), formations are presented and discussed according to the IPB regional geological setting. The age data confirm the predominance of alloctonous tectonic structures in the studied region, in line with previous structural interpretations for the North Sector of the Portuguese part of the Iberian Pyrite Belt.(undefined

Characterization of the second- and third-order nonlinear optical susceptibilities of monolayer MoS2_2 using multiphoton microscopy

We report second- and third-harmonic generation in monolayer MoS$_\mathrm{2}$ as a tool for imaging and accurately characterizing the material's nonlinear optical properties under 1560 nm excitation. Using a surface nonlinear optics treatment, we derive expressions relating experimental measurements to second- and third-order nonlinear sheet susceptibility magnitudes, obtaining values of $|\chi_s^{(2)}|=2.0\times10^{-20}$ m$^2$ V$^{-1}$ and for the first time for monolayer MoS$_\mathrm{2}$, $|\chi_s^{(3)}|=1.7\times10^{-28}$ m$^3$ V$^{-2}$. These sheet susceptibilities correspond to effective bulk nonlinear susceptibility values of $|\chi_{b}^{(2)}|=2.9\times10^{-11}$ m V$^{-1}$ and $|\chi_{b}^{(3)}|=2.4\times10^{-19}$ m$^2$ V$^{-2}$, accounting for the sheet thickness. Experimental comparisons between MoS$_\mathrm{2}$ and graphene are also performed, demonstrating $\sim$3.4 times stronger third-order sheet nonlinearity in monolayer MoS$_\mathrm{2}$, highlighting the material's potential for nonlinear photonics in the telecommunications C band.Comment: Accepted by 2D Materials, 28th Oct 201

Aqueous humor erythropoietin levels in open-angle glaucoma patients with and without TTR V30M familial amyloid polyneuropathy

Purpose: Glaucoma is the leading cause of irreversible blindness in familial amyloidotic polyneuropathy (FAP) patients. Erythropoietin (EPO) is a cytokine that has been shown to play a role in neuroprotection and is endogenously produced in the eye. EPO levels in the aqueous humor are increased in eyes with glaucoma. In this study, we evaluated the EPO concentration in the aqueous humor of FAP and non-FAP patients, with and without glaucoma. Methods: Undiluted aqueous humor samples were obtained from 42 eyes that underwent glaucoma surgery, phacoemulsification, or vitrectomy. EPO concentration in the aqueous humor and blood were measured using the Immulite 2000 Xpi using an automatic analyzer (Siemens Healthcare Diagnostics). Results: The mean EPO concentration in the aqueous humor of non-FAP glaucoma eyes group 2 (75.73±13.25 mU/ml) was significantly higher than non-FAP cataract eyes (17.22±5.33 mU/ml; p<0.001), FAP glaucoma eyes (18.82±10.16 mU/ml; p<0.001), and FAP nonglaucoma eyes (20.62±6.22 mU/ml; p<0.001). There was no statistically significant difference between FAP nonglaucoma eyes versus non-FAP cataract eyes (p = 0.23) and FAP glaucoma eyes versus FAP nonglaucoma eyes (p = 0.29). In the glaucoma groups, there was no correlation between the aqueous humor EPO concentration and the ocular pressure (p = 0.95) and mean deviation (p = 0.41). There was no correlation between the EPO serum concentration and EPO aqueous humor concentration in our patients (p = 0.77). Conclusions: Unlike other glaucomatous patients, FAP patients with glaucoma do not show increased and potentially neuroprotective endocular EPO production in the aqueous humor and may need more aggressive glaucoma management

Caracterização fenológia da pereira limeira cultivada no Vale do São Francisco,

Sendo assim o presente trabalho foi desenvolvido tendo como o objetivo de caracterizar os estágios fenológicos da variedade de pereira Limeira, no Vale do São Francisco, em Petrolina, PE

Quebra de dormência de macieira (Malus domestica) Eva cultivada no Vale do São Francisco.

O objetivo deste estudo foi avaliar o efeito de doses de cianamida hidrogenada (CH), nitrato 23 de cálcio (NC) e nitrato de potássio (NK) na quebra da dormência de macieiras, cultivar Eva no Vale do São Francisco, em Petrolina-PE

Cianamida hidrogenada na quebra de dormência de cultivares de macieiras (Malus domestica) no Semiárido brasileiro.

O objetivo deste estudo foi avaliar o efeito da cianamida hidrogenada, na quebra da dormência de macieiras das variedades, Daiane, Gala e Princesa, no Submédio Vale do São Francisco em Petrolina-PE

Cianamida hidrogenada, nitrato de potássio e Ubyfol para a quebra de dormência da pereira cv. Princesinha cultivada no Vale do São Francisco.

O objetivo deste estudo foi avaliar o efeito da cianamida hidrogenada (CH), nitrato de cálcio e Ubyfol®, na quebra da dormência da pereira cv. Princesinha no Vale do São Francisco em Petrolina-PE

Caracterização fenológia da pereira Princesinha cultivada no Vale do São Francisco.

O presente trabalho objetivou caracterizar os estádios fenológicos e a frutificação efetiva da pereira cv. Princesinha, cultivada sob clima Semiárido tropical, em Petrolina, PE