The cargo protein MAP17 (PDZK1IP1) regulates the cancer stem cell pool activating the Notch pathway by abducting NUMB

Purpose: Cancer stem cells (CSC) are self-renewing tumor cells, with the ability to generate diverse differentiated tumor cell subpopulations. They differ from normal stem cells in the deregulation of the mechanisms that normally control stem cell physiology. CSCs are the origin of metastasis and highly resistant to therapy. Therefore, the understanding of the CSC origin and deregulated pathways is important for tumor control. Experimental Design: We have included experiments in vitro, in cell lines and tumors of different origins. We have used patient-derived xenografts (PDX) and public transcriptomic databases of human tumors. Results: MAP17 (PDZKIP1), a small cargo protein overexpressed in tumors, interacts with NUMB through the PDZ-binding domain activating the Notch pathway, leading to an increase in stem cell factors and cancer-initiating–like cells. Identical behavior was mimicked by inhibiting NUMB. Conversely, MAP17 downregulation in a tumor cell line constitutively expressing this gene led to Notch pathway inactivation and a marked reduction of stemness. In PDX models, MAP17 levels directly correlated with tumorsphere formation capability. Finally, in human colon, breast, or lung there is a strong correlation of MAP17 expression with a signature of Notch and stem cell genes. Conclusions: MAP17 overexpression activates Notch pathway by sequestering NUMB. High levels of MAP17 correlated with tumorsphere formation and Notch and Stem gene transcription. Its direct modification causes direct alteration of tumorsphere number and Notch and Stem pathway transcription. This defines a new mechanism of Notch pathway activation and Stem cell pool increase that may be active in a large percentage of tumors.Ministerio de Economía y Competitividad PI15/00045, CTS-1848Junta de Andalucía PI-00-96-2014, PI-0306-201

Meta-analysis: associated factors for the adoption and disclosure of CSR practices in the banking sector

This document seeks to identify the associated factors that lead banking institutions to adopt and disclose CSR practices, considering that previous studies show contradictory results. Therefore, is important to integrate the findings from previous research, given the importance of CSR practices for the financial performance and the level of risk of organizations. The study employed the random effect meta-analysis technique, the data analysis was carried out with papers published between 2005 and 2021 and integrates the results of research that has analyzed a total of 6208 observations in 40 countries. The results of the research show a significant positive association between, legitimacy of existence and reputation as associated factors for developing CSR practices, whereas the regulation, the inclusion of foreign board members, and stakeholder relationships have an insignificant positive association as an associated factor with the development of CSR practices. Corporate governance factors have a significant positive relationship with the presence of women on the board and the size of the board. In addition, the board’s independence and the duality of the CEO have an insignificant negative association. This paper provides evidence of the need for research in CSR practices in the banking sector, especially in Latin America where the literature is almost non-existent. In addition, it also shows the need for research on corporate governance factors, especially on how the presence of women on the board influences the development of CSR practices, considering the scarce existing literature that analyses these factors

Hepatopancreatic ganglioneuroma in a young dog: a case report

The clinical, pathological and immunohistochemical features of a hepatobiliary and pancreatic ganglioneuroma in a seven-month-old dog are described. The dog presented progressive weight loss, anorexia and abdominal pain. At laparoscopic examination numerous whitish nodules ranging from 0.5 to 1 cm in diameter were found in the peripancreatic tissues, the bile duct system and perihepatic tissues. Due to poor prognosis the dog was euthanized and necropsy was conducted. Tumour nodules were not noted in the other examined abdominal organs. Microscopically, the nodules were composed of large, well differentiated neurons embedded in an abundant stroma of nerve fibres and connective fibrous tissue. Through immunohistochemistry analysis, neurons were found to express neurofilaments and did not express S-100 protein. The histopathological and immunohistochemical features were consistent with a diagnosis of ganglioneuroma. This case is atypical as the majority of reported canine ganglioneuromas involve the gastrointestinal tract. The early age of the dog is also considered to be atypical for this tumou

The Effectiveness and Recommendation of Motor Imagery Techniques for Rehabilitation after Anterior Cruciate Ligament Reconstruction: A Systematic Review

Motor imagery (MI) reported positive effects in some musculoskeletal rehabilitation processes. The main objective of this study was to analyze the effectiveness of MI interventions after anterior cruciate ligament (ACL) reconstruction. A systematic review was conducted from November 2018 to December 2019 in PubMed, Scopus, Web of Science, The Cochrane Library, and Physiotherapy Evidence Database (PEDro). The methodological quality, degree of recommendation, and levels of evidence were analyzed. A total of six studies were included. Selected studies showed unequal results (positive and negative) regarding pain, anxiety, fear of re-injury, function, and activities of daily living. Regarding the range of motion, anthropometric measurements, and quality of life, the results were not conclusive. Muscle activation, strength, knee laxity, time to remove external support, and neurobiological factors showed some favorable results. Nevertheless, the results were based on a limited number of studies, small sample sizes, and a moderate-weak degree of recommendation. In conclusion, our review showed a broader view of the current evidence, including a qualitative assessment to implement MI after ACL surgery. There was no clear evidence that MI added to physiotherapy was an effective intervention after ACL surgery, although some studies showed positive results in clinical outcomes. More adequately-powered long-term randomized controlled trials are necessary

Circulating miRNAs as predictive biomarkers of type 2 diabetes mellitus development in coronary heart disease patients fromt he CORDIOPREV study

Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers, and they may be a more sensitive way to predict development of the disease than the currently used tools. Our aim was to identify whether circulating miRNAs, added to clinical and biochemical markers, yielded better potential for predicting type 2 diabetes. The study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at baseline by qRT-PCR, and other strong biomarkers to predict diabetes were determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342) than HbA1c alone (AUC = 0.6950). The miRNA and HbA1cbased model did not improve when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI = 2.61–48.65). Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of type 2 diabetes in clinical practice

Detection of indigenous organic matter in rocks from the interpretation of carbon molecular forms in the laser-induced plasma.

Oil shale, a sedimentary rock containing organic matter and a variety of inorganic minerals including carbonates and kerogens, serves as a significant source of organic material on Earth [1]. Kerogen, the most abundant form of organic matter, differs in chemical composition based on the microorganisms that contributed to its formation [2]. Laser-induced breakdown spectroscopy (LIBS) is a powerful analytical technique used on the Mars rover, allowing elemental characterization of Martian rocks, soils, and sediments. This study presents the first-ever detection of natural organic matter in oil shale using LIBS under simulated Martian conditions. Through an analysis of emitting species including CN and C2, LIBS successfully identifies the presence of organic compounds in this sedimentary rock. The ability to detect and characterize natural organic matter in oil shale, known for its potential to suggest the existence of ancient life, holds significant relevance in astrobiology. Furthermore, this information contributes to the identification of biosignatures and aids in the development of planetary exploration strategies. Oil shale samples were analyzed using LIBS under simulated Martian conditions after being crushed, pressed into pellets, and subjected to pyrolysis to remove organic matter. The analysis revealed significant changes in the infrared spectra, confirming the absence of aliphatic hydrocarbons after pyrolysis [3]. The LIBS results demonstrated the presence of molecular species associated with hydrocarbons, such as CN and C2, through distinct spectral emissions. The absence of these emissions in the pyrolyzed sample further supported the detection of organic matter originating from kerogen.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Detection of kerogens in sedimentary rocks by LIBS. Implications for the search for biosignatures on Mars.

Congreso Internacional dedicado a la aplicaciones de LIBSOil shale is a sedimentary rock that naturally contains organic matter. In its chemical composition presents a wide range of inorganic minerals including carbonates, silicates, etc. and kerogens – a mixture of fossil hydrocarbons. Kerogen is insoluble in normal organic solvents, being the most abundant source of organic matter on Earth [1,2]. Chemical composition of a particular kerogen differs as a function of the source microrganisms that participated to the sediment and may be classified into three categories [3]. Type I kerogen, produced by algae or eventually bacteria and is the less abundant; type II, derived from other aquatic organisms (phytoplankton and zooplankton); the most common on Earth is type III, generated from organic plant matter. To the best of our knowledge, this work demonstrates for the first time the detection of natural organic matter in different rock of oil shales with a total organic carbon content between (2.78 % and 15.06 %) using LIBS under Martian conditions. A linear correlation was found between the net CN intensity and the concentration of total organic material of the samples under CO2 and Martian atmosphere. The fact that natural organic matter can be detected and characterized by LIBS in this kind of sedimentary rock – known for suggesting the existence ancient life - through its emitting species such as CN or C2 is of great relevance in astrobiology. Results presented here, may provide essential understanding on the search for biosignatures on Mars and for the development of planetary exploration strategies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Induced Systemic Resistance (ISR) and Fe Deficiency Responses in Dicot Plants

Plants develop responses to abiotic stresses, like Fe deficiency. Similarly, plants also develop responses to cope with biotic stresses provoked by biological agents, like pathogens and insects. Some of these responses are limited to the infested damaged organ, but other responses systemically spread far from the infested organ and affect the whole plant. These latter responses include the Systemic Acquired Resistance (SAR) and the Induced Systemic Resistance (ISR). SAR is induced by pathogens and insects while ISR is mediated by beneficial microbes living in the rhizosphere, like bacteria and fungi. These root-associated mutualistic microbes, besides impacting on plant nutrition and growth, can further boost plant defenses, rendering the entire plant more resistant to pathogens and pests. In the last years, it has been found that ISReliciting microbes can induce both physiological and morphological responses to Fe deficiency in dicot plants. These results suggest that the regulation of both ISR and Fe deficiency responses overlap, at least partially. Indeed, several hormones and signaling molecules, like ethylene (ET), auxin, and nitric oxide (NO), and the transcription factor MYB72, emerged as key regulators of both processes. This convergence between ISR and Fe deficiency responses opens the way to the use of ISR-eliciting microbes as Fe biofertilizers as well as biopesticides. This review summarizes the progress in the understanding of the molecular overlap in the regulation of ISR and Fe deficiency responses in dicot plants. Root-associated mutualistic microbes, rhizobacteria and rhizofungi species, known for their ability to induce morphological and/or physiological responses to Fe deficiency in dicot plant species are also reviewed herei

Ethylene and phloem signals are involved in the regulation of responses to Fe and P deficiencies in roots of strategy I plants

Iron (Fe) and phosphorus (P) are two essential mineral nutrients whose acquisition by plants presents important environmental and economic implications. Both elements are abundant in most soils but scarcely available to plants. To prevent Fe or P deficiency dicot plants initiate morphological and physiological responses in their roots aimed to specifically acquire these elements. The existence of common signals in Fe and P deficiency pathways suggests the signaling factors must act in conjunction with distinct nutrient-specific signals in order to confer tolerance to each deficiency. Previous works have shown the existence of cross talk between responses to Fe and P deficiency, but details of the associated signaling pathways remain unclear. Herein, the impact of foliar application of either P or Fe on P and Fe responses was studied in P- or Fe-deficient plants of Arabidopsis thaliana, including mutants exhibiting altered Fe or P homeostasis. Ferric reductase and acid phosphatase activities in roots were determined as well as the expression of genes related to P and Fe acquisition. The results obtained showed that Fe deficiency induces the expression of P acquisition genes and phosphatase activity, whereas P deficiency induces the expression of Fe acquisition genes and ferric reductase activity, although only transitorily. Importantly, these responses were reversed upon foliar application of either Fe or P on nutrient-starved plants. Taken together, the results reveal interactions between P- and Fe-related phloem signals originating in the shoots that likely interact with hormones in the roots to initiate adaptive mechanisms to tolerate deficiency of each nutrient