Detection of Q-matrix misspecification using two criteria for validation of cognitive structures under the Least Squares Distance Model

Cognitive Diagnostic Models (CDMs) aim to provide information about the degree to which individuals have mastered specific attributes that underlie the success of these individuals on test items. The Q-matrix is a key element in the application of CDMs, because contains links item-attributes representing the cognitive structure proposed for solve the test. Using a simulation study we investigated the performance of two model-fit statistics (MAD and LSD) to detect misspecifications in the Q-matrix within the least squares distance modeling framework. The manipulated test design factors included the number of respondents (300, 500, 1000), attributes (1, 2, 3, 4), and type of model (conjunctive vs disjunctive). We investigated MAD and LSD behavior under correct Q-matrix specification, with Qmisspecifications and in a real data application. The results shows that the two model-fit indexes were sensitive to Q-misspecifications, consequently, cut points were proposed to use in applied context.Detección de errores de especificación en la matriz Q utilizando dos criterios de validación de estructuras cognitivas con el Modelo de las Distancias Mínimo Cuadráticas (LSDM). Los Modelos de Diagnóstico Cognitivo (MDC) tienen por objeto proporcionar información sobre el grado en que los individuos dominan atributos específicos para resolver correctamente los items de un test. La matriz Q es un elemento clave en la aplicación de los MDC porque contiene vínculos entre items y atributos que representan la estructura cognitiva propuesta para resolver la prueba. Por medio de un estudio de simulación, se determinó el rendimiento de dos estadísticos de ajuste (MAD y LSD) para detectar errores de especificación en la matriz Q dentro del marco del modelo de la distancia mínimo cuadrática. Los factores manipulados en el diseño del test incluyen: número de encuestados (300, 500, 1000), número de atributos (1, 2, 3, 4), y el tipo de modelo (conjuntivo vs. disyuntivo). Se investigó el comportamiento de los valores MAD y LSD bajo una correcta especificación de Q, con errores de especificación en Q y en una aplicación de datos reales. Los resultados muestran que los dos índices son sensibles a los errores de especificación de Q, por este motivo se proponen puntos de corte para usar en aplicaciones del modelo

TSQ fluorochrome incubation increase autometallographic zinc detection in primary cell cultures of astrocytes

In this work, we have analyzed the combination of direct (TSQ) and indirect (AMG) zinc detection methods in order to increase the sensitivity to a better study of the zinc uptake. For that purpose, rat primary cell cultured astrocytes were used. Intracellular Zn levels were visualized by using the TSQ zinc fluorochrome, either in normal conditions or after supplementary addition of 50 µM ZnSO4 to the culture. Fluorescence was recorded with an Olympus microscope BX50WI, equipped with a Hamamatsu ORCA digital camera controlled with the Aquacosmos software. Monolayers were fixed and ionic zinc precipitated by sodium sulphide or sodium selenite. Autometallographic zinc detection was the last step to detect zinc in cell cultures. Zincosome formation were visualized meanwhile the zinc fluorochrome TSQ in light microscopy, with or without adding zinc to cell monolayers. Additionally, we tested the better zinc precipitation and fixative method in order to preserve zinc ions and make them suitable for AMG development, selecting 0.1% sodium sulphide and 4% PFA. TSQ incubation demonstrated that are crucial for AMG zinc detection in both, prior and after the cell fixation. We found the setting parameters by which the zinc ion content of zincosomes can be maintained and visualized in optimal conditions and circumstances, either for optical and electron microscopy zinc detection studies

Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming

During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition impairs both mitochondrial fragmentation and generation of iPS cell colonies. Drp1 phosphorylation depends on Erk activation in early reprogramming, which occurs, at least in part, due to downregulation of the MAP kinase phosphatase Dusp6. Taken together, our data indicate that mitochondrial fission controlled by an Erk-Drp1 axis constitutes an early and necessary step in the reprogramming process to pluripotency

Febre Q en remugants domèstics i salvatges del Pirineu

La Febre Q és una malaltia que pot arribar a ser molt greu en persones, causada per la infecció de Coxiella burnetii. El seu principal reservori són vaques, cabres i ovelles, però també s'hi troba a remugants salvatges. Jorge Ramón López Olvera, del Servei d'Ecopatologia de Fauna Salvatge, explica l'estudi que han dut a terme per determinar la presència del bacteri a la fauna del Pirineu català.La Fiebre Q es una enfermedad que puede llegar a ser muy grave en personas, causada por la infección de Coxiella burnetii. Su principal reservorio son vacas, cabras y ovejas, pero también se encuentra en rumiantes salvajes. Jorge Ramón López Olvera, del Servicio de Ecopatología de Fauna Salvaje, explica el estudio que han llevado a cabo para determinar la presencia de la bacteria en la fauna del Pirineo catalán.Q Fever is a disease that can be severe for humans. It is caused by Coxiella burnetii infection and cattle, goats and sheep are considered its main reservoir, but it and can also be found in wild ruminants. Jorge Ramón López Olvera, from the Servicio de Ecopatología de Fauna Salvaje, brings us to the study carried out to determine the presence of this bacteria in animals from the Catalan Pyrenees

c‑MYC Triggers Lipid Remodelling During Early Somatic Cell Reprogramming to Pluripotency

Metabolic rewiring and mitochondrial dynamics remodelling are hallmarks of cell reprogramming, but the roles of the reprogramming factors in these changes are not fully understood. Here we show that c-MYC induces biosynthesis of fatty acids and increases the rate of pentose phosphate pathway. Time-course profiling of fatty acids and complex lipids during cell reprogramming using lipidomics revealed a profound remodelling of the lipid content, as well as the saturation and length of their acyl chains, in a c-MYC-dependent manner. Pluripotent cells displayed abundant cardiolipins and scarce phosphatidylcholines, with a prevalence of monounsaturated acyl chains. Cells undergoing cell reprogramming showed an increase in mitochondrial membrane potential that paralleled that of mitochondrial-specific cardiolipins. We conclude that c-MYC controls the rewiring of somatic cell metabolism early in cell reprogramming by orchestrating cell proliferation, synthesis of macromolecular components and lipid remodelling, all necessary processes for a successful phenotypic transition to pluripotency

Serological survey of Coxiella burnetii at the wildlife-livestock interface in the Eastern Pyrenees, Spain

Coxiella burnetii is a zoonotic bacterium that infects a wide range of animal species and causes the disease Q fever. Both wild and domestic ruminants may be relevant in the epidemiology of C. burnetii infection. In order to investigate the significance of the ruminant host community in the alpine and subalpine ecosystems of the Eastern Pyrenees, Northeastern Spain, in the epidemiology of Q fever, a serological survey was performed on samples from 599 wild and 353 sympatric domestic ruminants. Specific antibodies against C. burnetii were detected with a commercial enzyme-linked immunosorbent assay (ELISA). Domestic sheep showed the highest prevalence (12.7 %, CI 95 % 8.6-16.9), followed by European mouflon (Ovis orientalis musimon) with a 6.8 % prevalence (CI 95 % 1.6-12.1), red deer (Cervus elaphus) with 2.4 % (CI 95 % 0-5.6), and cattle with a prevalence of 1.1 % (CI 95 % 0-3.2). No positive domestic goats, fallow deer (Dama dama), roe deer (Capreolus capreolus) and Southern chamois (Rupicapra pyrenaica) were detected. Sheep flock prevalence was 75 % (nine of the 12 sheep flocks sampled were positive, within-flock prevalence ranging from 11.1 to 25.0 %), whereas cattle herd prevalence was 11.1 % (one out of the nine cattle herds sampled was positive, within-herd prevalence of 10.0 %. Both domestic and wild ruminants from the alpine and subalpine ecosystems of the Eastern Pyrenees were exposed to C. burnetii. The higher seroprevalence in sheep and its relative abundance suggest that this species may have a major contribution to the ecology of C. burnetii. Conversely, wild ruminants do not seem to represent a relevant host community for C. burnetii maintenance in the Eastern Pyrenees

Generation of a disease-specific iPS cell line derived from a patient with Charcot-Marie-Tooth type 2K lacking functional GDAP1 gene

Human CMT2-FiPS4F1 cell line was generated from fibroblasts of a patient with Charcot-Marie-Tooth disease harbouring the following mutations in the GDAP1 gene in heterozygosis: p.Q163X/p.T288NfsX3. This patient did not present mutations in the PM22, MPZ or GJB genes. Human reprogramming factors OCT3/4, KLF4, SOX2 and C-MYC were delivered using a non-integrative methodology that involves the use of Sendai virus

Reappraising the use of forearm rings for bat species

Altres ajuts: acords transformatius de la UABLong-term mark-recapture studies are essential for bat conservation. Over the last decades, millions of bats across Europe and America have been marked with forearm rings for this purpose. Although it is considered a cost-effective method compared to Passive Integrated Transponders (PIT) tags, direct injuries from using forearm rings have been reported since their very first use. Yet, their impact on bats' welfare has not been systematically evaluated and remains a highly controversial issue among the scientific community and policymakers. Here we assess the impact of forearm rings and PIT tags on the health of different bat species. We reviewed 12 years of the existing recapture data of free-ranging bats from NE Spain and evaluated the impact of both marking tools in a captive colony of Carollia perspicillata, by assessing the development of skin lesions and levels of cortisol metabolites in guano (CG) after marking. We report that 55.1 % (435/790) of the recaptured free-ranging bats with forearm rings presented skin lesions. All banded C. perspicillata (n = 22, 100 %) developed skin lesions, whereas none of the PIT-tagged (n = 21) presented lesions. Levels of CG were significantly higher after marking with forearm rings only for one group. Banded C. perspicillata exhibited discomfort-associated behaviours due to forearm rings. Under the "precautionary principle", we recommend the ban of forearm rings for all bat species until species-specific studies under controlled conditions are performed and approved by a legally constituted ethics committee. Consideration of other long-term marking tools is mandatory to align with global bat conservation strategies

Searching free zinc at the ultrastructural level in cultured astrocytes

Zinc is an element that is necessary for many physiological functions in the body but may play an important role in diseases affecting most systems in the body if its balance is altered by environmental, toxicological or idiosyncrasy of subjects. We have centred our investigation in central nervous system, using cultured astrocytes since they are involved in clearance of zinc exocytated to the extracellular medium during synaptic transmission. In previous works we have used a zinc fluorochrome, i.e., the TSQ (6-Methoxy-(8-p-toluenesulfonamido)quinoline) to in vivo zinc uptake in cultured astrocytes and its accumulation in organelles named zincosomes. However, the precise location of these zinc-enriched structures (zincosomes) at the ultrastructural level is a very hard task. In a previous attempt at the electron microscopy level, only topographical approximation by combining light and electron microscopy allowed us to identify selected zincosomes previously marked with TSQ. Now, our objective is to adapt zinc autometallography (Timm’s method) to TSQ labelled cultured astrocytes. For the electron microscopic detection of zincosomes, the first important step is to achieve a good zinc precipitation during or previous to glutaraldehyde fixation. Surprisingly, neither ditizone nor selenite were successful as zinc precipitating agents; only sodium sulphide gave us good results. We also found that while glutaraldehyde is the best option for animal experimentation, paraformaldehyde prefixation gave us best results. Paraformaldehyde prefixation allowed both ultrastructure preservation as well as zinc-precipitated-detection with Timm autometallography in semithin sections. These semithin sections were included again and zincosomes become clearly visible in ultrathin sections

Ethanol impairs extracellular zinc intake in cultured astrocytes

Zinc (Zn) deficiency is present in many physiological and health problems. Among circumstances involved in Zn deficiency, ethanol consumption appears as a prominent cause. In the CNS substantial amounts of Zn appear accumulated in synaptic vesicles of a particular class of neurons: the Zn enriched neurons very abundant in the telencephalon and cerebral cortex. This is the so called synaptic Zn which is simultaneously released with the neurotransmitter thus exerting a neuromodulator role during synaptic transmission. Neighbour astrocytic processes have to capture the excess of both extracellular Zn and neurotransmitter in order to maintain efficient synaptic transmission between neurons. In this work we analyze the effect of exposure to 30 mM ethanol for 7 days in the ability of cultured rat astrocytes to capture and manage extracellular Zn. Intracellular Zn levels were visualized by using the TSQ Zn fluorochrome, either in normal culture conditions or after supplementary addition of 50 μM ZnSO4 to the culture. Fluorescence was recorded with an Olympus microscope BX50WI, equipped with a Hamamatsu ORCA digital camera controlled with the Aquacosmos software. Basal Zn levels in cultured astrocytes was greatly and significantly lower in ethanol treated cells (about 30% of control cultures). These differences were consistently maintained after addition of extracellular Zn to cell monolayers, resulting in a lower ability to uptake or retain Zn. The Zn was uptaked by the endocytic pathway, as demonstrated by the marker FM1-43 and was mainly confined to bright organelles that were more abundant in control cells. In conclusion, ethanol impairs astrocyte Zn management resulting in a lower capacity for extracellular Zn intake in resting conditions and after extracellular addition. It has been proposed that an efficient method to palliate Zn deficiency it could be a dietary supplement. Nevertheless, this study suggests that a dietary Zn supplementation may not be enough for recovery of cellular normal function in alcoholic cultured astrocytes