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Physical activity, health-related quality of life and depression during pregnancy

This study examines physical activity patterns among women, from pre-pregnancy to the second trimester of pregnancy, and the relationship between physical activity status based on physical activity guidelines and health-related quality of life (HRQoL) and depression over pregnancy. 56 healthy pregnant women self reported physical activity, HRQoL and depression at 10-15 and 19-24 weeks of pregnancy and physical activity before pregnancy. Whereas vigorous leisure physical activity decreased after conception, moderate leisure physical activity and work related physical activity remained stable over time. The prevalence of recommended physical activity was 39.3% and 12.5% in the 1st and 2nd trimesters of pregnancy respectively, and 14.3% pre-pregnancy. From the 1st to the 2nd pregnancy trimester, most physical HRQoL dimensions scores decreased and only mental component increased, independently of physical activity status. No changes in mean depression scores were observed. These data suggest that physical activity patterns change with pregnancy and that physical and mental components are differentially affected by pregnancy course, independently of physical activity status.

Evaluación del efecto del láser y magnetoterapia en miopatía experimental valorando biomarcadores de estrés oxidativo, histomorfometría y actividad enzimática mitocondrial. Evaluation of the effect of laser and magnetic therapy in experimental myopathy assessing oxidative stress biomarkers, histomorphometry and mitochondrial enzyme activity

El láser de baja y media energía y la magnetoterapia son utilizados en desórdenes osteomioarticulares por sus efectos analgésico, antiinflamatorio y trófico, entre los más destacados. Sin embargo, son insuficientes las investigaciones sobre su mecanismo de acción y antecedentes científicos que avalen sus efectos. Es por ello, que la determinación de acontecimientos celulares y moleculares que ocurren durante la interacción de estos tipos de energía con el sistema muscular, sería relevante para el conocimiento y optimización de tales terapias en las ciencias biomédicas. En las miopatías inflamatorias idiopáticas, se encuentra afectada la estructura, morfología y bioquímica del tejido muscular. La energía que éste requiere para el normal funcionamiento es generada en la mitocondria. Esta organela también es la responsable de la generación de especies oxidantes provocando estrés oxidativo y el inicio de los procesos de apoptosis. Por lo antes dicho, consideramos que la determinación de los biomarcadores inflamatorios asociados a estrés oxidativo, realizando el análisis histomorfométrico ultraestructural y valorando la actividad de los complejos enzimáticos mitocondriales, permitiría una evaluación de la acción terapéutica del láser y la magnetoterapia en un modelo experimental de miopatía. Para ello se propone evaluar el efecto de la magnetoterapia y del láser de baja energía (He-Ne y As.Ga) en miopatía experimental determinando indicadores inflamatorios asociados a estrés oxidativo, análisis histomorfométrico y valoración de la actividad enzimática mitocondrial. Específicamente: -Determinar indicadores inflamatorios y de estrés oxidativo: Oxido Nítrico, Grupos carbonilos, L-citrulina, Fibrinógeno, Superóxido dismutasa, Glutation peroxidasa y Catalasa por espectrofotometría. -Identificar los cambios anatomopatológicos del músculo esquelético por microscopía óptica (MO): cuantificación del infiltrado inflamatorio; MO de alta resolución (MOAR) y por microscopía electrónica: histomorfometría de la ultraestructura miofibrilar y mitocondrial. -Valorar las actividades enzimáticas de la citrato sintasa y de los complejos: I (NADH-ubiquinona reductasa), II (succinato-ubiquinona-reductasa) III (ubiquinona-citocromo c-reductasa) y IV (citocromo c-oxidasa); en mitocondrias de tejido muscular por espectrofotometría. -Evaluar la actividad apoptótica en las fibras musculares de los diferentes grupos por ténica de T.U.N.E.L. Las mediciones mitocondriales (por ME) y de infiltrado inflamatorio (por MO) se realizarán en un total de 5 fotos de aumentos similares en forma aleatoria por grupo estudiado (n=10). Los cambios estructurales observados se analizarán en el programa Axiovision 4.8, para cuantificar el área total ocupada, número total y grado de alteración de las mitocondrias y el porcentaje de infiltrado inflamatorio determinando el grado de inflamación. Los resultados de los datos cuantitativos se analizarán aplicando ANAVA (test de Fisher para comparaciones múltiples); y para los datos categóricos se utilizará Chi cuadrado (test de Pearson), estableciéndose un nivel de significación de p < 0.05 para todos los casos. Importancia del Proyecto: La salud y el bienestar del hombre son los logros perseguidos por las ciencias de la salud. La obtención de terapias curativas o paliativas con un mínimo de efectos colaterales para el enfermo se incluye en estos logros. Por esto y todo lo anteriormente expuesto es que consideramos de gran importancia poder esclarecer desde las ciencias básicas los efectos celulares y moleculares en modelos experimentales la acción de la terapia con láser y magnetoterapia para una aplicación clínica con base científica en todas las áreas de las Ciencias Médicas. In the idiopathic inflammatory myopathies, is affected the structure, morphology and biochemistry of muscle tissue. The mitochondria is responsible for the generation of oxidizing species leading to oxidative stress and the beginning of the process of apoptosis. As said before, we consider the determination of inflammatory biomarkers related to oxidative stress, by ultrastructural morphometric analysis and assessing the activity of mitochondrial enzyme complexes, permit an evaluation of the therapeutic action of laser and magnetic therapy in an experimental model myopathy. We propose to evaluate the effect of the treatment identifying indicators in experimental inflammatory myopathy associated with oxidative stress, histomorphometric analysis and assessment of mitochondrial enzyme activity. Specifically -determining: Nitric oxide, carbonyl groups, L-citrulline, fibrinogen, superoxide dismutase, glutathione peroxidase and catalase by spectrophotometry. -Identify the pathological changes in skeletal muscle by optical microscopy (OM): quantification of the inflammatory infiltrate, OM high resolution (MOAR) and electron microscopy, histomorphometry of myofibrillar and mitochondrial ultrastructure. -Evaluate the enzymatic activity of citrate synthase and complexes: I, II, III and IV in mitochondria muscle tissue by spectrophotometry. -Evaluate apoptotic activity in muscle fibers by TUNEL technique of Mitochondrial measurements and inflammatory infiltration (by OM) was performed in a total of 5 photos of similar increases in random by the study group (n = 10). The structural changes observed are discussed in the program Axiovision 4.8, to quantify number, degree of alteration of mitochondria and the percentage of inflammatory infiltrate determining the degree of inflammation. The results of the quantitative data were analyzed using ANOVA (Fisher test), and categorical data with Chi-square (Pearson test), establishing a significance level of p <0.05.

Dinámica poblacional de Streptococcus mutans en niños de edad escolar de la provincia de Córdoba. Population dynamics of Streptococcus mutans in school age children in the province of Córdoba

La caries dental es una enfermedad infecciosa, crónica y trasmisible, que se caracteriza por la desmineralización de los tejidos duros del diente, producida por la acción de los ácidos resultantes de la actividad metabólica del biofilm desarrollado sobre los dientes. Si bien, la etiología de la caries sería polimicrobiana, los estreptococos del grupo mutans son señalados como los principales protagonistas en el inicio de la lesión cariosa. En la pared celular se destacan proteínas que participan en procesos de adhesión, agregación y co-agregación, además de polisacáridos que muestran distintas especificidades antigénicas, lo que permite distinguir cuatro serotipos: c, e, f y k. Es escasa la información de las características antigénicas de las cepas circulantes de estreptococos del grupo mutans y se desconoce la relación de las mismas con la actividad de caries. En este estudio nuestros objetivos son identificar y caracterizar fenotípica y genotípicamente las cepas de estreptococos del grupo mutans circulantes en la provincia de Córdoba. La población de estudio estará constituida por escolares, urbano–marginales de la capital y del interior de la provincia. Se determinarán los serotipos de las mismas a través de de amplificaciones por PCR de tipo multiplex y luego se secuenciarán 8 genes a través de la técnica de tipado multilocus, con el fin de realizar estudios de sistemática molecular, y de estimar la estructura genética de S. mutans. Una vez que se hayan caracterizado los patrones de diversidad y distribución geográfica de S. mutans del centro de Argentina, se intentará dilucidar cómo se relacionan la diversidad genética con la experiencia de caries de los niños del estudio. Se analizarán de forma conjunta nuestros resultados con los publicados por otros autores. De esta forma se logrará una mejor comprensión de los factores históricos y ecológicos que han moldeado su distribución y aportar conocimientos a la sistemática del grupo “mutans” en relación a otras bacterias del género Streptococcus. Dental caries is an infectious, chronic and transmissible disease, characterized by demineralization of the hard tissues of the teeth, produced by the action of acids resulting from the metabolic activity of biofilm developed on the teeth. Although the etiology of caries would be polymicrobial, the streptococci of the mutans group are identified as the major responsible in the initiation of the carious lesion. In the cell wall there are proteins involved in adhesion, aggregation and co-aggregation processes, as well as polysaccharides that present different antigenic specificities, which allow the distinction of four serotypes c, e, f and k. There is little information about the antigenic characteristics of the Streptococcus mutans strains and the relationship of those characteristics with the caries activity is unknown. In the present study our goals are to identify and characterize the phenotypic and genotypic strains of streptococci of the mutans group circulating in the province of Cordoba. The study population will consist of urban and rural scholar children from Cordoba city and from the interior of the province. In order to study the molecular systematic, and the genetic structure of S. mutans, different serotypes will be determined by multiplex PCR amplifications and eight genes will be sequenced by using the multilocus typing technique. Once the diversity and the geographical distribution patterns of S. mutans from the center of Argentina is characterized, we will attempt to clarify how the genetic diversity is related with the caries experience in the children of the study. Our results will be analyzed together with those published by other authors. This will achieve a better understanding of the historical and ecological factors that shaped the bacteria’s distribution and will contribute to the knowledge of the systematic of the mutans group in relation to other bacteria of the genus Streptococcus.

Seasonal variability on the structure of sublittoral macrozoobenthic association in the Patos Lagoon estuary, southern Brazil

The aim of this study is to analyze and relate the spatial-temporal variability of macrozoobenthic assemblages to bottom characteristics and salinity fluctuations, in an estuarine shallow water region of Patos Lagoon. Monthly samples, between September 2002 and August 2003, were taken on six sampling stations (distant 90 m). Three biological samples with a 10 cm diameter corer, one sample for sediment analysis, fortnightly bottom topography measurements, and daily data of temperature and salinity were taken from each station. Two biotic and environmental conditions were identified: the first corresponding to spring and summer months, with low macrozoobenthos densities, low values of salinity, small variations in bottom topographic level and weak hydrodynamic activity. A second situation occurred in the months of fall and winter, which showed increased salinity, hydrodynamics and macrobenthos organisms. These results which contrast with previous studies carried out in the area, were attributed to failure in macrozoobenthos recruitments during summer period, especially of the bivalve Erodona mactroides Bosc, 1802 and the tanaid Kalliapseuses schubartii Mañe-Garzón, 1949. This results showed that recruitments of dominant species were influenced by salinity and hydrodynamic conditions.

Collaboration strategies and technological innovation: a contractual perspective of the relationship between firms and techonological centers

In this paper, a theoretical framework for analyzing the selection of governance structures for implementing collaboration agreements between firms and Technological Centers is presented and empirically discussed. This framework includes Transaction Costs and Property Rights’ theoretical assumptions, though complemented with several proposals coming from the Transactional Value Theory. This last theory is used for adding some dynamism in the governance structure selection. As empirical evidence of this theoretical explanation, we analyse four real experiences of collaboration between firms and one Technological Center. These experiences are aimed to represent the typology of relationships which Technological Centers usually face. Among others, a key interesting result is obtained: R&D collaboration activities do not need to always be organized through hierarchical solutions. In those cases where future expected benefits and/or reputation issues could play an important role, the traditional more static theories could not fully explain the selected governance structure for managing the R&D relationship. As a consequence, these results justify further research about the adequacy of the theoretical framework presented in this paper in other contexts, for example, R&D collaborations between firms and/or between Universities or Public Research Centers and firms.

Endogenous capacity utilization and the asymmetric effects of monetary policy

This paper investigates the role of variable capacity utilization as a source of asymmetries in the relationship between monetary policy and economic activity within a dynamic stochastic general equilibrium framework. The source of the asymmetry is directly linked to the bottlenecks and stock-outs that emerge from the existence of capacity constraints in the real side of the economy. Money has real effects due to the presence of rigidities in households' portfolio decisions in the form of a Luces-Fuerst 'limited participation' constraint. The model features variable capacity utilization rates across firms due to demand uncertainty. A monopolistic competitive structure provides additional effects through optimal mark-up changes. The overall message of this paper for monetary policy is that the same actions may have different effects depending on the capacity utilization rate of the economy.

Urban spatial structure and suburbanisation. The case of the Barcelona Metropolitan

The metropolitan spatial structure displays various patterns, sometimes monocentricity and sometimes multicentricity, which seems much more complicated than the exponential density function used in classic works such as Clark (1961), Muth (1969) or Mills (1973) among others, can effectively represent. It seems that a more flexible density function,such as cubic spline function (Anderson (1982), Zheng (1991), etc.) to describe the density-accessibility relationship is needed. Also, accessibility, the fundamental determinant of density variations, is only partly captured by the inclusion of distance to the city centre as an explanatory variable. Steen (1986) has proposed to correct that miss-especification by including an additional gradient for distance to the nearest transportation axis. In identifying the determinants of urban spatial structure in the context of inter-urban systems, some of the variables proposed by Muth (1969), Mills (1973) and Alperovich (1983) such as city age or population, make no sense in the case of a single urban system. All three criticism to the exponential density function and its determinants apply for the Barcelona Metropolitan Region, a polycentric conurbation structured on well defined transportation axes.

Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients

Background: Cerebral cholinergic transmission plays a key role in cognitive function and anticholinergic drugs are associated with impaired cognitive functions [1]. In the perioperative phase many substances with anticholinergic effects are administered and disturbed cholinergic transmission is a hypothetical cause of postoperative cognitive dysfunction (POCD). Serum anticholinergic activity (SAA; pmol/ml) may be measured as a summary marker of anticholinergic activity in an individual patient's blood. We hypothesised that an increase in SAA from preoperatively to one week postoperatively is associated with POCD in elderly patients. Methods: Thirty-two patients aged >65 yrs undergoing elective major surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl) were investigated. Cognitive functions were measured preoperatively and 7 days postoperatively using the extended version of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery. POCD was defined as a postoperative decline >1 z-score in at least 2 cognitive domains. SAA was measured preoperatively and 7 days postoperatively at the time of cognitive testing. Results: 50% of the investigated patients developed POCD. There were no statistically significant differences between patients with and without POCD regarding age, education, baseline cognitive function, duration of anaesthesia, SAA preoperatively (median (range) 1.0 (0.3 to 5.0) vs 1.5 (0.4 to 5.0), SAA 7 days postoperatively (median (range) 1.3 (0.1 to 7.0) vs 1.4 (0.6 to 5.5) or changes in SAA (median (range) 0.1 (-1.6 to 2.2) vs 0.2 (-1.4 to 2.8). The variability of SAA in individual patients was considerable and marked changes in SAA between the two examinations were observed in some patients. However, there was no significant relationship between changes in SAA and changes in cognitive function. Conclusion: In this preliminary analysis of a small group of patients, changes in SAA in the perioperative phase were highly variable. SAA was not associated with POCD suggesting that POCD is not simply caused by anticholinergic medications administered in the perioperative phase. A further analysis of a larger group of patients is in progress.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

D-amphetamine fails to increase extracellular dopamine levels in mice lacking alpha 1b-adrenergic receptors: relationship between functional and nonfunctional dopamine release.

It was found recently that locomotor and rewarding effects of psychostimulants and opiates were dramatically decreased or suppressed in mice lacking alpha1b-adrenergic receptors [alpha1b-adrenergic receptor knock-outs (alpha1bAR-KOs)] (Drouin et al., 2002). Here we show that blunted locomotor responses induced by 3 and 6 mg/kg d-amphetamine in alpha1bAR-KO mice [-84 and -74%, respectively, when compared with wild-type (WT) mice] are correlated with an absence of d-amphetamine-induced increase in extracellular dopamine (DA) levels in the nucleus accumbens of alpha1bAR-KO mice. Moreover, basal extracellular DA levels in the nucleus accumbens are lower in alpha1bAR-KO than in WT littermates (-28%; p < 0.001). In rats however, prazosin, an alpha1-adrenergic antagonist, decreases d-amphetamine-induced locomotor hyperactivity without affecting extracellular DA levels in the nucleus accumbens, a finding related to the presence of an important nonfunctional release of DA (Darracq et al., 1998). We show here that local d-amphetamine releases nonfunctional DA with the same affinity but a more than threefold lower amplitude in C57BL6/J mice than in Sprague Dawley rats. Altogether, this suggests that a trans-synaptic mechanism amplifies functional DA into nonfunctional DA release. Our data confirm the presence of a powerful coupling between noradrenergic and dopaminergic neurons through the stimulation of alpha1b-adrenergic receptors and indicate that nonfunctional DA release is critical in the interpretation of changes in extracellular DA levels. These results suggest that alpha1b-adrenergic receptors may be important therapeutic pharmacological targets not only in addiction but also in psychosis because most neuroleptics possess anti-alpha1-adrenergic properties.

Covariation between colony social structure and immune defences of workers in the ant Formica selysi

Several ant species vary in the number of queens per colony, yet the causes and consequences of this variation remain poorly understood. In previous experiments, we found that Formica selysi workers originating from multiple-queen (=polygyne) colonies had a lower resistance to a fungal pathogen than workers originating from single-queen (=monogyne) colonies. In contrast, group diversity improved disease resistance in experimental colonies. This discrepancy between field and experimental colonies suggested that variation in social structure in the field had antagonistic effects on worker resistance, possibly through a down-regulation of the immune system balancing the positive effect of genetic diversity. Here, we examined if workers originating from field colonies with alternative social structure differed in three major components of their immune system. We found that workers from polygyne colonies had a lower bacterial growth inhibitory activity than workers from monogyne colonies. In contrast, workers from the two types of colonies did not differ significantly in bacterial cell wall lytic activity and prophenoloxidase activity. Overall, the presence of multiple queens in a colony correlated with a slight reduction in one inducible component of the immune system of individual workers. This reduced level of immune defence might explain the lower resistance of workers originating from polygyne colonies despite the positive effect of genetic diversity. More generally, these results indicate that social changes at the group level can modulate individual immune defences.

Structure du temps de travail des infirmières de santé publique: effets de l'âge des patients, de la nature des prestations fournies et du lieu du contact. [Structure of work times of public health nurses: effect of the age of patients, nature of care given and location of contact].

In the framework of health services research sponsored by the Swiss National Science Foundation, a research was undertaken of the activity of the large majority of the public health nurses working in the Swiss cantons of Vaud and Fribourg (total population 700,000). During one week, 130 nurses gathered, with a specially devised instrument, data on 4165 patient visits. Studying the duration of the contacts, one has distinguished contact duration per se (DC), duration of the travel time preceding the contact (DD), and total duration in relation with the contact (DTC-addition of the first two). It was noted that the three durations increased significantly with patient age (as regard travel time, this is explained by the higher proportion of home visits in higher age groups, as compared with visits at a health center). Examined according to location of the visit, contact duration per se (without travel) is higher for visits at home and in nursing homes than for those taking place at a health center. Looked at in respect to the care given (technical care, or basic nursing care, or both simultaneously), our data show that the provision of basic nursing care (alone or with technical care) doubles contact duration (from 20 to 42-45'). The analyses according to patient age shows that, at an advanced age (beyond 80 years particularly), there is an important increase of the visits where both types of care are given. However, contact duration per se shows a significant raise with age only for the group "technical care only"; it can be demonstrated that this is due to the fact that older patients require more complex technical acts (e.g., bladder care, as compared with simpler acts such as injection). A model of the relationships between patient age and contact duration is proposed: it is because of the increase in the proportions of home visits, of visits including basic nursing care, and of more complex technical acts that older persons require more of the working time of public health nurses.

Effectiveness of three different walking prescription durations on total physical activity in normal- and overweight women.

OBJECTIVE: While there is a dose-response relationship between physical activity (PA) and health benefit, little is known about the effectiveness of different PA prescriptions on total daily PA. AIM: To test, under real-life conditions and using an objective, non-invasive measurement technique (accelerometry), the effect of prescribing additional physical activity (walking only) of different durations (30, 60 and 90 min/day) on compliance (to the activity prescribed) and compensation (to total daily PA). Participants in each group were prescribed 5 sessions of walking per week over 4 weeks. METHODS: 55 normal-weight and overweight women (mean BMI 25 ± 5 kg/m(2), height 165 ± 1 cm, weight 68 ± 2 kg and mean age 27 ± 1 years) were randomly assigned to 3 prescription groups: 30, 60 or 90 min/day PA. RESULTS: Walking duration resulted in an almost linear increase in the number of steps per day during the prescription period from an average of about 10,000 steps per day for the 30-min prescription to about 14,000 for the 90-min prescription. Compliance was excellent for the 30-min prescription but decreased significantly with 60-min and 90-min prescriptions. In parallel, degree of compensation subsequent to exercise increased progressively as length of prescription increased. CONCLUSION: A 30-min prescription of extra walking 5 times per week was well tolerated. However, in order to increase total PA further, much more than 60 min of walking may need to be prescribed in the majority of individuals. While total exercise 'volume' increased with prescriptions longer than 30 min, compliance to the prescription decreased and greater compensation was evident. © 2014 S. Karger GmbH, Freiburg.

Mutations of the Serine Protease CAP1/Prss8 Lead to Reduced Embryonic Viability, Skin Defects, and Decreased ENaC Activity.

CAP1/Prss8 is a membrane-bound serine protease involved in the regulation of several different effectors, such as the epithelial sodium channel ENaC, the protease-activated receptor PAR2, the tight junction proteins, and the profilaggrin polypeptide. Recently, the V170D and the G54-P57 deletion mutations within the CAP1/Prss8 gene, identified in mouse frizzy (fr) and rat hairless (fr(CR)) animals, respectively, have been proposed to be responsible for their skin phenotypes. In the present study, we analyzed those mutations, revealing a change in the protein structure, a modification of the glycosylation state, and an overall reduction in the activation of ENaC of the two mutant proteins. In vivo analyses demonstrated that both fr and fr(CR) mutant animals present analogous reduction of embryonic viability, similar histologic aberrations at the level of the skin, and a significant decrease in the activity of ENaC in the distal colon compared with their control littermates. Hairless rats additionally had dehydration defects in skin and intestine and significant reduction in the body weight. In conclusion, we provided molecular and functional evidence that CAP1/Prss8 mutations are accountable for the defects in fr and fr(CR) animals, and we furthermore demonstrate a decreased function of the CAP1/Prss8 mutant proteins. Therefore, fr and fr(CR) animals are suitable models to investigate the consequences of CAP1/Prss8 action on its target proteins in the whole organism.