Pedagogies against dispossession: Principles for a transformative eco/demopedagogy as a vehicle for social and environmental justice

Se analiza el contenido pedagógico de las luchas que las comunidades Zapatistas y las comunidades purépechas en México llevan a cabo contra del despojo y por la defensa de los territorios y el entorno ecológico. Se plantea que tales luchas de resistencia de los pueblos indígenas, en la medida que se orientan a la defensa del territorio y toda forma de vida que habita sobre éste, producen saberes y prácticas pedagógicas sobre los cuáles es posible construir, en los países del norte del mundo, una pedagogía transformativa que busque la protección de la vida a partir de formas de democracia densa y contra-hegemónica. El artículo discute una serie de principios que pueden orientar la práctica de una pedagogía crítica de corte ambientalista, democrática y emancipatoria, que aquí denominaremos eco/demopedagogía transformativa. Este artículo construye sobre los postulados teóricos de la pedagogía de la liberación latinoamericana y la pedagogía crítica norteamericana. Su base metodológica es la investigación documental y la observación etnográfica directa en las comunidades indígenas mencionadasThis paper discusses the pedagogical implications of the struggles that the Zapatistas in Chiapas and the Purépecha communities in Mexico have been carrying out against dispossession and for the defense of the territories and the ecological environment. Such struggles, insofar as they focus on the defense of territories and all forms of life that dwell on it produce forms of pedagogical praxis from which we can learn and build, in the Global North, a form of transformative pedagogy aimed at stimulating the conscientization about and protection of all forms of life based on counter-hegemonic and transformative forms of democracy. The article discusses a set of principles that are meant to guide the development and practice of an environmental/ecological, democratic and emancipatory critical pedagogy, which we have labelled herein transformative eco/demopedagogy. This article builds upon the theoretical tradition developed by the Latin American liberation pedagogy and the North American critical pedagogy. Documentary research and direct ethnographic observation in the aforementioned indigenous communities constitute, likewise, the methodological basis of this articl

Late-onset thymidine kinase 2 deficiency: a review of 18 cases

BACKGROUND: TK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the 'myopathic form' of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity. METHODS: We describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12. RESULTS: The mean age of onset was 31 years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients. CONCLUSIONS: The late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency.Instituto de Salud Carlos III PI16-01843 PI16/00579 CP09/00011Subdirección General de Evaluación y Fomento de la Investigación Sanitaria PI16-01843 PI16/00579 CP09/00011 PI 15/00431 PMP15/0002

Neuromuscular disease classification system

Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic pattern

Late-onset thymidine kinase 2 deficiency: a review of 18 cases

Mitochondrial myopathy; Multiple deletions; TK2 deficiencyMiopatia mitocondrial; Delecions múltiples; Deficiència de TK2Miopatía mitocondrial; Deleciones múltiples; Deficiencia de TK2BACKGROUND: TK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the 'myopathic form' of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity. METHODS: We describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12. RESULTS: The mean age of onset was 31 years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients. CONCLUSIONS: The late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency

Optical diagnosis in still images of colorectal polyps: comparison between expert endoscopists and PolyDeep, a Computer-Aided Diagnosis system

Background PolyDeep is a computer-aided detection and classification (CADe/x) system trained to detect and classify polyps. During colonoscopy, CADe/x systems help endoscopists to predict the histology of colonic lesions. Objective To compare the diagnostic performance of PolyDeep and expert endoscopists for the optical diagnosis of colorectal polyps on still images. Methods PolyDeep Image Classification (PIC) is an in vitro diagnostic test study. The PIC database contains NBI images of 491 colorectal polyps with histological diagnosis. We evaluated the diagnostic performance of PolyDeep and four expert endoscopists for neoplasia (adenoma, sessile serrated lesion, traditional serrated adenoma) and adenoma characterization and compared them with the McNemar test. Receiver operating characteristic curves were constructed to assess the overall discriminatory ability, comparing the area under the curve of endoscopists and PolyDeep with the chi- square homogeneity areas test. Results The diagnostic performance of the endoscopists and PolyDeep in the characterization of neoplasia is similar in terms of sensitivity (PolyDeep: 89.05%; E1: 91.23%, p=0.5; E2: 96.11%, p<0.001; E3: 86.65%, p=0.3; E4: 91.26% p=0.3) and specificity (PolyDeep: 35.53%; E1: 33.80%, p=0.8; E2: 34.72%, p=1; E3: 39.24%, p=0.8; E4: 46.84%, p=0.2). The overall discriminative ability also showed no statistically significant differences (PolyDeep: 0.623; E1: 0.625, p=0.8; E2: 0.654, p=0.2; E3: 0.629, p=0.9; E4: 0.690, p=0.09). In the optical diagnosis of adenomatous polyps, we found that PolyDeep had a significantly higher sensitivity and a significantly lower specificity. The overall discriminative ability of adenomatous lesions by expert endoscopists is significantly higher than PolyDeep (PolyDeep: 0.582; E1: 0.685, p < 0.001; E2: 0.677, p < 0.0001; E3: 0.658, p < 0.01; E4: 0.694, p < 0.0001). Conclusion PolyDeep and endoscopists have similar diagnostic performance in the optical diagnosis of neoplastic lesions. However, endoscopists have a better global discriminatory ability than PolyDeep in the optical diagnosis of adenomatous polyps.Instituto de Salud Carlos III | Ref. PI21/01771Instituto de Salud Carlos III | Ref. CD22/00087Instituto de Salud Carlos III | Ref. INT22/00009Instituto de Salud Carlos III | Ref. FI22/00203Unión Europea NextGenerationEU/PRTRAgencia Estatal de Investigación | Ref. DPI2017-87494-RAgencia Estatal de Investigación | Ref. PDC2021-121644-I00Xunta de Galicia | Ref. ED431G 2019/06Xunta de Galicia | Ref. ED431C 2022/03-GRCXunta de Galicia | Ref. ED481B-2023-00

Patterns of Spiny Lobster (Panulirus argus) Postlarval Recruitment in the Carribbean: A CRTR Project

As part of the Coral Reef Targeted Research (CRTR) Program, a partnership between the Global Environment Facility and the World Bank, our research team examined the recruitment patterns of Caribbean spiny lobster (Panulirus argus) postlarvae among regions in the Caribbean, with a particular focus on Mesoamerica. Our goal was to collect comparable information on postlarval supply among regions and to provide data to test predictions of connectivity generated from a coupled biophysical oceanographic model of lobster larval dispersal. Here we present the results of the postlarval recruitment monitoring program. We monitored the catch of postlarvae on Witham-style collectors at sites in the Caribbean from March 2006 to May 2009, although the duration and frequency of sampling varied among locations. Recruitment varied considerably among months and locations. It peaked in the Western Caribbean in the fall (Oct - Dec), whereas in Florida, Puerto Rico, and Venezuela peaks were in spring (Feb - April) with a smaller peak in the fall. Sites generally fell into two groups with respect to monthly variability in recruitment: low variability sites (e.g., Honduras, southern Mexico, Venezuela) and high variability sites (e.g., Florida, San Andres Islands, Puerto Rico, northern Mexico). Recruitment magnitude varied locally, but generally increased (lowest to highest) from Puerto Rico, San Andres Islands, Honduras, Mexico, Venezuela, to Florida. Recruitment trends mirrored fishery catch in some locations, implying a recruit-to-stock linkage. Recruitment was significantly correlated among several sites, suggesting similarity in their larval sources and oceanographic regimes

Altered myogenesis and premature senescence underlie human TRIM32-related myopathy

TRIM32 is a E3 ubiquitin -ligase containing RING, B-box, coiled-coil and six C-terminal NHL domains. Mutations involving NHL and coiled-coil domains result in a pure myopathy (LGMD2H/STM) while the only described mutation in the B-box domain is associated with a multisystemic disorder without myopathy (Bardet-Biedl syndrome type11), suggesting that these domains are involved in distinct processes. Knock-out (T32KO) and knockin mice carrying the c.1465G > A (p.D489N) involving the NHL domain (T32KI) show alterations in muscle regrowth after atrophy and satellite cells senescence. Here, we present phenotypical description and functional characterization of mutations in the RING, coiled-coil and NHL domains of TRIM32 causing a muscle dystrophy. Reduced levels of TRIM32 protein was observed in all patient muscle studied, regardless of the type of mutation (missense, single amino acid deletion, and frameshift) or the mutated domain. The affected patients presented with variable phenotypes but predominantly proximal weakness. Two patients had symptoms of both muscular dystrophy and Bardet-Biedl syndrome. The muscle magnetic resonance imaging (MRI) pattern is highly variable among patients and families. Primary myoblast culture from these patients demonstrated common findings consistent with reduced proliferation and differentiation, diminished satellite cell pool, accelerated senescence of muscle, and signs of autophagy activation.Health Institute Carlos III PI16-01843 JR15/00042FEDER PI16-01843 JR15/00042Fundación Progreso y Salud, Junta de Andalucía PI-0085-2016Australian National Health and Medical Research Council (NHMRC) APP1122952 APP111751

Altered myogenesis and premature senescence underlie human TRIM32-related myopathy

TRIM32 is a E3 ubiquitin -ligase containing RING, B-box, coiled-coil and six C-terminal NHL domains. Mutations involving NHL and coiled-coil domains result in a pure myopathy (LGMD2H/STM) while the only described mutation in the B-box domain is associated with a multisystemic disorder without myopathy (Bardet-Biedl syndrome type11), suggesting that these domains are involved in distinct processes. Knock-out (T32KO) and knockin mice carrying the c.1465G > A (p.D489N) involving the NHL domain (T32KI) show alterations in muscle regrowth after atrophy and satellite cells senescence. Here, we present phenotypical description and functional characterization of mutations in the RING, coiled-coil and NHL domains of TRIM32 causing a muscle dystrophy. Reduced levels of TRIM32 protein was observed in all patient muscle studied, regardless of the type of mutation (missense, single amino acid deletion, and frameshift) or the mutated domain. The affected patients presented with variable phenotypes but predominantly proximal weakness. Two patients had symptoms of both muscular dystrophy and Bardet-Biedl syndrome. The muscle magnetic resonance imaging (MRI) pattern is highly variable among patients and families. Primary myoblast culture from these patients demonstrated common findings consistent with reduced proliferation and differentiation, diminished satellite cell pool, accelerated senescence of muscle, and signs of autophagy activation.Health Institute Carlos III PI16-01843 JR15/00042FEDER PI16-01843 JR15/00042Fundación Progreso y Salud, Junta de Andalucía PI-0085-2016Australian National Health and Medical Research Council (NHMRC) APP1122952 APP111751

TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice

Trabajo de investigación doctoral de Wael Hegazy Hassan Moustafa bajo la dirección de Juan Carlos Vázquez ChagoyánThe efforts for the development and testing of vaccines against Trypanosoma cruzi infection have increased during the past years. We have designed a TcVac series of vaccines composed of T. cruzi derived, GPI-anchored membrane antigens. The TcVac vaccines have been shown to elicit humoral and cellular mediated immune responses and provide significant (but not complete) control of experimental infection in mice and dogs. Herein, we aimed to test two immunization protocols for the delivery of DNA-prime/ DNA-boost vaccine (TcVac1) composed of TcG2 and TcG4 antigens in a BALB/c mouse model. Mice were immunized with TcVac1 through intradermal/electroporation (IDE) or intramuscular (IM) routes, challenged with T. cruzi, and evaluated during acute phase of infection. The humoral immune response was evaluated through the assessment of anti-TcG2 and anti-TcG4 IgG subtypes by using an ELISA. Cellular immune response was assessed through a lymphocyte proliferation assay. Finally, clinical and morphopathological aspects were evaluated for all experimental animals. Our results demonstrated that when comparing TcVac1 IDE delivery vs IM delivery, the former induced significantly higher level of antigen-specific antibody response (IgG2a + IgG2b > IgG1) and lymphocyte proliferation, which expanded in response to challenge infection. Histological evaluation after challenge infection showed infiltration of inflammatory cells (macrophages and lymphocytes) in the heart and skeletal tissue of all infected mice. However, the largest increase in inflammatory infiltrate was observed in TcVac1_IDE/Tc mice when compared with TcVac1_IM/Tc or non-vaccinated/infected mice. The extent of tissue inflammatory infiltrate was directly associated with the control of tissue amastigote nests in vaccinated/ infected (vs. non-vaccinated/infected) mice. Our results suggest that IDE delivery improves the protective efficacy of TcVac1 vaccine against T. cruzi infection in mice when compared with IM delivery of the vaccine.Universidad Autónoma de Estado de México (proyecto No. 3326/2012C), Consejo Nacional de Ciencia y Tecnología (Proyecto No. 156701) . Beca CONACyT a M.Sc. Wael Hegazy Hassan Moustafa (Beca numero No. 518232/291117)

Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets

Ullrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered