Sequence analysis of a microsatellite and its flanking regions in intraspecific hybrids of grapevine (Vitis vinifera L.)

Microsatellite (MS) VVMD21 (BOWERS et al. 1999) was taken as a model to explore the molecular basis of polymorphism in a panel of 6 grapevine accessions (Vitis vinifera L.), consisting of Sangiovese and Cabernet Sauvignon and 4 F1 plants derived from crossing both varieties. The 12 alleles of both parents and the progeny were cloned and sequenced. The microsatellite repeat (AG)n>6 was found in each sequence, together with a poly-T rich region that showed irregularity. Furthermore, single nucleotide deletion or exchange (point mutations) were found in the microsatellite flanking regions

The role of cooperation amongst cities, universities, research bodies and civil society organizations on urban food policies in Africa as innovative actions in the cadre of the Milan urban food policy pact

Within the framework of the international debate focusing on experiences emerging from cities in the global North, this paper aims to explore urban food policies under the lens of a global South perspective, paying particular attention to African cities and taking into account the common elements they present -compared with other urban contexts and territories- but also the specificities and uniqueness of them with respect to the process of urbanization and the linkages existing amongst cities and food. Urban food policies are powerful institutional actions, able to build more sustainable food systems of contemporary cities. These innovative policies are designed with a systemic and cross-sectoral approach, capable of acting at the intersection of different issues and fields such as water, waste, planning, health, transport, education, environment, trade, but also food and nutrition security, self-sufficiency and food sovereignty. We will describe an overview of initiatives developed in African cities, in view of the values stemming from the New Urban Agenda and the recommended actions by the recent Milan Urban Food Policy Pact, as an inspiring and propelling opportunity for new forms of territorial partnerships which could promote new types of cooperation amongst cities, universities, research bodies and civil society organizations from global North and South. Our research follows also the broader Italian development agenda. Under this light we will describe the mobilization of a number of institutional actors towards enhancing collaboration with the African context, drawing a geography of priorities, places and initiatives that are being activated in this field. The paper will identify a series of cross-cutting issues (such as land tenure, climate change, urban agriculture, rural-urban migration, waste management) to create a set of interpretative geographies, comparing cases across different African perspectives (for instance, environmental and socio-cultural) to identify common grounds and regional features

Intrinsic and Extrinsic Modulators of the Epithelial to Mesenchymal Transition: Driving the Fate of Tumor Microenvironment

The epithelial to mesenchymal transition (EMT) is an evolutionarily conserved process. In cancer, EMT can activate biochemical changes in tumor cells that enable the destruction of the cellular polarity, leading to the acquisition of invasive capabilities. EMT regulation can be triggered by intrinsic and extrinsic signaling, allowing the tumor to adapt to the microenvironment demand in the different stages of tumor progression. In concomitance, tumor cells undergoing EMT actively interact with the surrounding tumor microenvironment (TME) constituted by cell components and extracellular matrix as well as cell secretome elements. As a result, the TME is in turn modulated by the EMT process toward an aggressive behavior. The current review presents the intrinsic and extrinsic modulators of EMT and their relationship with the TME, focusing on the non-cell-derived components, such as secreted metabolites, extracellular matrix, as well as extracellular vesicles. Moreover, we explore how these modulators can be suitable targets for anticancer therapy and personalized medicine

Reassessment of the NF1 Variants of Unknown Significance Found During the 20-Year Activity of a Genetics Diagnostic Laboratory

The finding of variants of uncertain significance (VUS) in the activity of a diagnostic genetic laboratory is a common issue, which is however provisional and needs to be periodically re-evaluated, due to the continuous advancements in our knowledge of the genetic diseases. Neurofibromatosis type 1, caused by the occurrence of heterozygous pathogenic NF1 variants, is a good model for studying the evolution of VUS, due to the widespread use of genetic testing for the disease, the constant enrichment of the international databases with NF1 variants and the full adult penetrance of the disease, which makes genotyping the parents a crucial step in the diagnostic workflow. The present study retrospectively reviewed and reinterpreted the genetic test results of NF1 in a diagnostic genetic laboratory in the period from January 1, 2000 to December 31, 2020. All the VUS were reinterpreted using the 2015 consensus standards and guidelines for the interpretation. Out of 589 NF1 genetic tests which were performed in the period, a total of 85 VUS were found and reinterpreted in 72 cases (84.7%): 21 (29.2%) were reclassified as benign/likely benign, whereas 51 (70.8%) were recoded as pathogenic/likely pathogenic with a significant trend distribution (Chi square test for trend p=0.005). Synonymous VUS have mainly been reclassified as class 1 and 2 (7/8, 87.5%), whereas missense variants have been attributed to class 4 and 5 in 38 out of the 58 cases (65.5%). These findings underline an improvement in the classification of variants over time, suggesting that a reinterpretation of the genetic tests should be routinely performed to support the physicians in the clinical diagnosis of genetic diseases

Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status

KRAS and BRAF genotyping of synchronous colorectal carcinomas.

Abstract. v‑Ki‑ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genotyping is required prior to anti‑epidermal growth factor receptor monoclonal antibody therapy administered in cases of metastatic colorectal carcinoma (CRC). Thus, KRAS mutation screening is required for patient management. The present study reported the experience of KRAS/v‑raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational screening on synchronous CRC pairs from 26 patients, which were defined as index lesions (ILs) and concurrent lesions (CLs) on the basis of tumor grade and dimension and their respective lymph node and distant metastases. Overall, KRAS mutations were present in 38.4% of patients, whereas BRAF mutations were present at a frequency of 11.5%. The genotyping of paired synchronous carcinomas indicated that 11 patients (42.3%) exhibited discordant KRAS mutational statuses in terms of the presence of a mutation in only one lesion of the pair or of two different mutations harbored by each lesion. BRAF mutations were present in the synchronous tumors of two cases, whereas in two other cases, only the IL or CL harbored mutant BRAF. Overall, the mutational statuses of distant and lymph node metastases confirm the genetic heterogeneity of synchronous primary tumors. These results highlighted the fact that adequate sampling and comprehensive testing, when feasible, is likely to optimize the decision‑making process for treatment approaches, even in the relatively rare event of multiple synchronous lesions