Analysis of the temporary evolution of the Romanian migration flows abroad, on migration routes

This article analyses the international migration of the Romanians based on their direction, within the extent of 1990-2008. The tendencies are being examined depending on the region of origin and of destination of the migrants and also depending on the residential environment of migrants. The study details the labour circular migration, divided on the fourth main courses. The authors try to conduct a literature review on the subject, emphasising the conclusions of different studies conducted for the considered period.International migration, migration routes, migration flows, circular migration, permanent migration, Romanians migration

Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors

Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to identify clinically suitable drug vulnerabilities. Targeting PCSK9 expression with siRNA or PCSK9 specific inhibitor (PF-06446846) impaired OC cell survival. In addition, overexpression of PCSK9 induced robust AKT phosphorylation along with increased expression of ERK1/2 and MEK1/2, suggesting a pro-survival role of PCSK9 in OC cells. Moreover, our drug testing revealed marked differences in cytotoxic responses to drugs targeting metabolic pathways of high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC) PDCs. Our results show that targeting PCSK9 expression could impair OC cell survival, which warrants further investigation to address the dependency of this cancer on lipogenesis and omental metastasis. Moreover, the differences in metabolic gene expression and drug responses of OC PDCs indicate the existence of a metabolic heterogeneity within OC subtypes, which should be further explored for therapeutic improvements

Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors

Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to identify clinically suitable drug vulnerabilities. Targeting PCSK9 expression with siRNA or PCSK9 specific inhibitor (PF-06446846) impaired OC cell survival. In addition, overexpression of PCSK9 induced robust AKT phosphorylation along with increased expression of ERK1/2 and MEK1/2, suggesting a pro-survival role of PCSK9 in OC cells. Moreover, our drug testing revealed marked differences in cytotoxic responses to drugs targeting metabolic pathways of high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC) PDCs. Our results show that targeting PCSK9 expression could impair OC cell survival, which warrants further investigation to address the dependency of this cancer on lipogenesis and omental metastasis. Moreover, the differences in metabolic gene expression and drug responses of OC PDCs indicate the existence of a metabolic heterogeneity within OC subtypes, which should be further explored for therapeutic improvements

Contributions to the optimization of the eco-conditionality system in direct payments for romanian farmers in the period 2021-2027

The paper proposes to conduct a study on the optimal use of the CAP's "eco-conditionality" instrument in the context of the revision of the normative framework and procedures regarding the schemes and support measures for farmers in the period 2015-2020 and the conditions applicable to them. Were also considered the significance of applying this instrument as well as the issues that may arise from their non-application/improper application. In terms of eligibility requirements, declared surface, payment rights, and surface control sanctions, the results of the verification of surface payment requests for the years 2015 to 2021 reveal that a total of 7,800,417 payment requests (applicants) were made for a declared area of 9,684,116 ha (annual average), with a total payment request value of approximately €6,018,442.1 thousand. After the farmers' declared territories were verified, SAPS sanctions (unpaid amount) in the amount of €372,122.8 thousand were put into effect. The primary role of agriculture, which accords this industry a particular standing in EU regulations, is that of a supplier of agri-food goods for the general public's use. All strategies for developing, supporting, and funding the CAP are built on this role. We put forth the following suggestions in relation to the optimization of the cross-compliance mechanism within direct payments for farmers. To lessen the obligations for small agricultural holdings where the risk is lower, the eco-conditionality requirements must be designed in a way that takes into consideration the size of the agricultural holding. Farmers and their control bodies must be able to understand the mandatory requirements for farmers and their control elements. It is advisable to eliminate GAEC standards and SMR requirements that are difficult to audit and cannot be quantified. In any scenario, the quantity and nature of cross-compliance requirements must be altered. Mandatory standards for farmers and the aspects of their control must be pertinent and simple for farmers and control organizations to comprehend. It is advisable to eliminate GAEC standards and SMR requirements that are difficult to audit and cannot be quantified. In any scenario, the quantity and nature of cross-compliance requirements must be altered. Inspection quotas should be lowered if particular control bodies have risk analysis systems that adhere to Community legal requirements and information on the extent of compliance. Additionally, risk analysis models can be built for locations vulnerable to cross-compliance in order to decrease the control sample

New insights into the molecular mechanisms of ROR1, ROR2, and PTK7 signaling from the proteomics and pharmacological modulation of ROR1 interactome

ROR1, ROR2, and PTK7 are Wnt ligand-binding members of the receptor tyrosine kinase family. Despite their lack of catalytic activity, these receptors regulate skeletal, cardiorespiratory, and neurological development during embryonic and fetal stages. However, their overexpression in adult tissue is strongly connected to tumor development and metastasis, suggesting a strong pharmacological potential for these molecules. Wnt5a ligand can activate these receptors, but lead to divergent signaling and functional outcomes through mechanisms that remain largely unknown. Here, we developed a cellular model by stably expressing ROR1, ROR2, and PTK7 in BaF3 cells that allowed us to readily investigate side-by-side their signaling capability and functional outcome. We applied proteomic profiling to BaF3 clones and identified distinctive roles for ROR1, ROR2, and PTK7 pseudokinases in modulating the expression of proteins involved in cytoskeleton dynamics, apoptotic, and metabolic signaling. Functionally, we show that ROR1 expression enhances cell survival and Wnt-mediated cell proliferation, while ROR2 and PTK7 expression is linked to cell migration. We also demonstrate that the distal C-terminal regions of ROR1 and ROR2 are required for receptors stability and downstream signaling. To probe the pharmacological modulation of ROR1 oncogenic signaling, we used affinity purification coupled to mass spectrometry (AP-MS) and proximity-dependent biotin identification (BioID) to map its interactome before and after binding of GZD824, a small molecule inhibitor previously shown to bind to the ROR1 pseudokinase domain. Our findings bring new insight into the molecular mechanisms of ROR1, ROR2, and PTK7, and highlight the therapeutic potential of targeting ROR1 with small molecule inhibitors binding to its vestigial ATP-binding site.Peer reviewe

Evaluation of the implementation of eco-conditionality rules on support schemes and measures for farmers in the period 2018-2021

The present work starts from a real truth, namely that agriculture is an important factor of social stability with an essential role in maintaining the ecological balance. The main purpose of the paper is to evaluate the implementation of the ecoconditionality rules on support schemes and measures for farmers in the period 2018-2021 and to optimize the crosscompliance system in the direct payments for farmers in Romania by finding the best model for the implementation of the cross-compliance (ecoconditionalitate) rules in the period 2021-2027 that corresponds to the specific objectives of the PAC and the economic interests of the farmers. The main objectives of the CAP are: increasing agricultural productivity, guaranteeing a fair standard of living for the rural population, stabilizing agricultural product markets and guaranteeing of food security for the population and farmers income. To accomplish this goal, the work aimed at the following study objectives: Assess the implementation of the rules on cross compliance schemes and measures to support farmers in 2018- 2020, by analyzing the results for monitoring compliance and cross compliance penalties; Development of a simplified model for implementation of cross compliance rules applicable to schemes and support measures for farmers in the period 2018-2020, based on a set of standards/requirements relevant and an effective administration and control for each area subject to cross compliance. To achieve this goal, the work aims to develop a simplified model for the implementation of the cross-compliance rules applicable to support schemes and measures for farmers in the period 2015-2020, based on a set of relevant standards / requirements and an efficient administration and control system for each domain subjected to cross-compliance

DFT calculations and electrochemical studies on azulene ligands for heavy metal ions detection using chemically modified electrodes

A computational study on three related derivatives of 5-[(azulen-1-yl)methylene]-2-thioxoimidazolidin-4-one was conducted using density functional theory by calculating a series of molecular descriptors and properties of their optimized geometries (electrostatic and local ionization potentials, molecular frontier orbitals, etc.). Thermodynamic properties (zero-point energy, enthalpy, constant volume heat capacity, entropy and Gibbs energy) for these derivatives have been calculated and related to ligands electrochemical behavior. Reduction and oxidation potentials have been correlated to their calculated energy levels for LUMO and HOMO orbitals. Chemically modified electrodes based on these derivatives have been tested in view of heavy metal ions recognition, and their detection limits have been correlated to the calculated values of electron affinity

STRN-ALK rearranged pediatric malignant peritoneal mesothelioma - Functional testing of 527 cancer drugs in patient-derived cancer cells

Genetic rearrangements involving the anaplastic lymphoma kinase (ALK) gene create oncogenic drivers for several cancers, including malignant peritoneal mesothelioma (MPeM). Here, we report genomic and functional precision oncology profiling on a rare case of a 5-year old patient diagnosed with wide-spread and aggressive MPeM, driven by STRN-ALK rearrangement. We established genomically representative patient-derived cancer cells (PDCs) from the tumor sample and performed high-throughput drug sensitivity testing with 527 oncology compounds to identify potent inhibitors. As expected, the PDCs were overall sensitive to the ALK inhibitors, although the eight different inhibitors tested had variable efficacy. We also discovered other effective inhibitors, such as MEK/ERK inhibitors and those targeting pathways downstream of ALK as well as Bcl-xl inhibitors. In contrast, most cytotoxic drugs were not very effective. ALK inhibitors synergized with MEK and PI3K/mTOR inhibitors, highlighting potential combinatorial strategies to enhance drug efficacy and tackle drug resistance. Based on genomic data and associated functional validation, the patient was treated with the ALK inhibitor crizotinib in combination with conventional chemotherapy (cisplatin and gemcitabine). A complete disease remission was reached, lasting now for over 3 years. Our results illustrate a rare pediatric cancer case, and highlight the potential of functional precision oncology to discover pathogenetic drivers, validate dependency on driver signals, compare different inhibitors against each other and potentially enhance targeted treatments by drug combinations. Such real-time implementation of functional precision oncology could pave the way towards safer and more effective personalized cancer therapies for individual pediatric cancer patients with rare tumors.Peer reviewe