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Objetivos: Conocer la situación actual, en cuanto a utilización de medicamentos, realización de controles, estado de salud y percepción que tienen sobre su enfermedad los diabéticos españoles que acuden a las farmacias comunitarias. Métodos: Estudio descriptivo transversal (enero-marzo 2014) en farmacias comunitarias españolas. Sujetos: personas diagnosticadas de diabetes, que acudían a la farmacia para retirar su tratamiento. La hoja de registro de datos incluía utilización de medicamentos, realización de controles periódicos, cuestionario de conocimiento sobre la enfermedad (Berbés), de conocimiento y cumplimiento del tratamiento y de satisfacción con la medicación (DTSQ). El tamaño muestral mínimo se estimó en 385 personas diabéticas. Resultados: 652 pacientes diabéticos, 49,5% hombres y 50,5% mujeres, 54,6% mayores de 65 años, 73,0% con dos o más factores de riesgo cardiovascular. El 84,1% utilizan ADO, el 38,0% insulina y el 22,9% ambos. 146 pacientes presentaron uno o más episodios de hipoglucemia en el último año. El 65,3% de los pacientes con insulina reutiliza las agujas. El 91,6% manifiesta no tener ningún problema en la realización del autoanálisis y el 72,8% reutiliza las lancetas. Conocían adecuadamente su tratamiento 196 (34,1%) y lo cumplían 432 (76,3%). La satisfacción con el tratamiento es buena (24,6±6,6 puntos sobre 36) (82,8% de pacientes satisfechos). Conclusiones: La utilización de medicamentos no se adecúa suficientemente a las guías clínicas. Las revisiones y los autocontroles que realizan son insuficientes. El conocimiento sobre la enfermedad y la medicación es bajo. El cumplimiento y la satisfacción con los tratamientos es alta, menor en los usuarios de insulina.

The energy sector is a major contributor to global greenhouse gas emissions, necessitating a transition to renewable energy sources. The photovoltaic industry plays a crucial role in this transition by harnessing solar energy, a clean and abundant resource. However, the high cost of solar panels remains a challenge. Organic solar cells (OSCs) offer a promising alternative to conventional silicon-based cells due to their low production costs and flexibility. In this study, we focus on optimizing the performance of OSCs by investigating the influence of solvent volume in the hole transport layer. By gradually increasing the volume of dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and tetrahydrofuran (THF) in the PEDOT:PSS layer, we analyse the impact on power conversion efficiency (PCE) and assess the economic and environmental implications. Our results demonstrate the potential for enhancing the PCE of OSCs through solvent optimization, thereby advancing the greening of the photovoltaic industry while considering economic viability and environmental sustainability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

We aimed to identify patterns of cognitive differences and characterize subgroups of Mexican children and adolescents with three neurodevelopmental disorders (NDD): intellectual disability (ID), autism spectrum disorders (ASD) and attention deficit/hyperactivity disorder (ADHD). The sample included 74 children and adolescents 6-15 years; 34% had ID, ASD or ADHD, 47% had ID in comorbidity with ASD, ADHD or both, 11% had ASD + ADHD, 8% were children without NDD. We applied WISC-IV, Autism Diagnostic Interview-Revised, Mini-International Neuropsychiatric Structured Interview, Child Behavior Checklist, and UNICEF Child Functioning Module. We evaluated the normality of the WISC-IV sub-scales using the Shapiro-Francia test, then conducted a latent class analysis and assessed inter-class differences in terms of household, parent and child characteristics. The following four-class solution best fit the data: "Lower Cognitive Profile" (LCP), "Lower Working Memory" (LWM), "Higher Working Memory" (HWM), "Higher Cognitive Profile" (HCP). LCP included most of the children with ID, who had a low Working Memory (WM) index score. LWM included mainly children with ASD or ID + ADHD; their Perceptual Reasoning (PR) and Processing Speed (PS) index scores were much higher than those for Verbal Comprehension (VC) and WM. HWM included children with ASD or ADHD; their scores for PR, PS and VC were high with lower WM (although higher than for LWM). HCP included children without NDD and with ASD or ADHD or both and had the highest scores on all indices. Children with NDD show cognitive heterogeneity and thus require individualized treatment plans., (© 2021. The Author(s).)

The membrane domain of eukaryotic HMG-CoA reductase (HMGR) has the conserved capacity to induce endoplasmic reticulum (ER) proliferation and membrane association into Organized Smooth Endoplasmic Reticulum (OSER) structures. These formations develop in response to overexpression of particular proteins, but also occur naturally in cells of the three eukaryotic kingdoms. Here, we characterize OSER structures induced by the membrane domain of Arabidopsis HMGR (1S domain). Immunochemical confocal and electron microscopy studies demonstrate that the 1S:GFP chimera co-localizes with high levels of endogenous HMGR in several ER compartments, such as the ER network, the nuclear envelope, the outer and internal membranes of HMGR vesicles and the OSER structures, which we name ER-HMGR domains. After high-pressure freezing, ER-HMGR domains show typical crystalloid, whorled and lamellar ultrastructural patterns, but with wide heterogeneous luminal spaces, indicating that the native OSER is looser and more flexible than previously reported. The formation of ER-HMGR domains is reversible. OSER structures grow by incorporation of ER membranes on their periphery and progressive compaction to the inside. The ER-HMGR domains are highly dynamic in their formation versus their disassembly, their variable spherical-ovoid shape, their fluctuating borders and their rapid intracellular movement, indicating that they are not mere ER membrane aggregates, but active components of the eukaryotic cell.

In this study, poly(9-vinylcarbazole) (PVK)-based LEDs doped with reduced graphene oxide (rGO) and cadmium sulphide (CdS) nanocrystals were fabricated by spin-coating. The hybrid LED structure was a layer sequence of glass/indium tin oxide (ITO)/PEDOT:PSS|rGO/PVK/Al. rGO was included in the poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) layer due to its energy bands being close to PEDOT:PSS bands, and the possibility of using water for dispersing both polymer and flakes. Optical properties such as photoluminescence and UV-Vis absorption were not affected by the addition of rGO to the PEDOT:PSS solution. However, PVK-based LEDs with rGO showed increased current density compared to those without rGO in the hole transporting layer. Higher electroluminescence intensities were observed for rGO-enriched LEDs, although the shape of the spectrum was not modified. LEDs including CdS nanocrystals in the poly(9-vinylcarbazole) emissive layer did not show such dependence on the rGO presence. Though the addition of rGO to PEDOT:PSS still produces a slightly higher current density in CdS doped LEDs, this growth is no longer proportional to the rGO load.

In this article, we compare two different kinds of commercial light-emitting diodes (LEDs) in transmission and organic photodetectors based on poly(3-hexylthiophene) (P3HT) and a phenyl-C61-butyric acid methyl ester (PCBM) blend used as active layer in reception. Photovoltaic cells based on massive heterojunctions of semiconductor polymers have focused the attention of researchers due to their several potential advantages over their inorganic counterparts, such as their simplicity, low cost, and ability to process large area devices, even on flexible substrates. Furthermore, in logistics, storage management systems require the implementation of technological solutions that allow the control of merchandise in real time by means of light-emitting diode signals that send information about the product. However, the slow response time of these organic photodetectors should not be critical for this application, where the light intensity changes are very slow, which limits the speed of data transmission compared to inorganic based systems that use wireless optical communications. Finally, we show a low-cost visible light communication system based on organic photodetectors with a frame based on on-off keying with Manchester encoding to support device-to-device connections., Competing Interests: The authors declare no conflict of interest.

Objective: To evaluate early childhood development (ECD) and its determinants in 12 to 59 months old children residents of communities <100 000 inhabitants., Materials and Methods: The Encuesta Nacional de Salud y Nutrición of communities <100 000 inhabitants (Ensanut 100k) evaluated language level, access to ECD care services and standardized indicators of the eight quality of the development environment. We report indicator prevalence and standardized language scores according to variables of interest., Results: 20.7% of children attended eight wellchild care visits within the first year of life, 13.0% received an ECD assessment, 75.0% receive support for learning, 23.4% have books and 57.7% experiment violent discipline. Improved language levels are associate with socioeconomic capacities, maternal education, preschool attendance, support for learning and household books. Children exposed to more protective factors present a language level 1.5 standard deviations higher than their peers exposed to more risk factors., Conclusions: There is a need to increase the coverage of ECD care services and to improve early development opportunities within households., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

Immiscibility between dimethyl sulfoxide (DMSO) and polar solvents used for poly( N -vinylcarbazole) (PVK) solutions, leads to failed light-emitting diodes when colloidal cadmium sulfide (CdS) nanoparticles capped with thiophenol are incorporated to their active layer. To prevent this, a heat treatment is applied to the CdS nanoparticles in order to evaporate DMSO solvent. After evaporation most of the nanoparticles increased their size, and some of them show hexagonal crystalline structure instead of the original cubic zinc-blende observed in colloidal pre-treated nanoparticles. Nevertheless, enhanced electronic properties are measured in light-emitting devices when DMSO-free nanoparticles are embedded in the poly( N -vinylcarbazole) active layer. Light emission from these hybrid devices comprises the whole visible range of wavelengths as searched for white LEDs. Moreover, electroluminescence from both types of CdS nanoparticles (smaller cubic and bigger hexagonal) has been discriminated and interpreted through Gaussian deconvolution.

Emotional dysregulation is one of the main features of Borderline Personality Disorder (BPD). Therefore, it constitutes a central therapeutic objective of the interventions that have proven to be effective for these patients, including the Acceptance and Commitment Therapy (ACT). However, benefits on emotional regulation have been evaluated through self-report instruments, and an anatomically based, objective, and precise measurement of the ability to change the type, duration and frequency of emotions is still needed., Objective: To assess facial emotion expression, valence and arousal during an ACT based intervention, between initial, middle and final therapeutic sessions for BPD patients., Method: Using the FaceReader 7.0, 29 recordings of individual therapeutic sessions for BPD patients during an ACT intervention trial were analyzed., Results: Happiness and fear intensity increase from the beginning to the end of the sessions, while sadness decreases. Emotional valence exhibits a significant decrease in its negative value during sessions from -0.13 (S.D. = 0.12) at the initial part of the sessions to -0.06 (S.D. = 0.08) by the end of the sessions, with a moderate effect size (Cohen d = 0.69). Emotional arousal increased from the beginning to the end of sessions and whole intervention., Conclusion: The emotional valence and arousal differed according to the psychotherapeutically process involved during ACT intervention, suggesting that the systematic analysis of facial expressions allows a rigorously examination of the relations between emotions, physiological processes, and instrumental behavior experimented though a psychotherapeutically process., (Copyright © 2019. Published by Elsevier Ltd.)

Hospital emergency departments are often overcrowded, resulting in long wait times and a public perception of poor attention. Delays in transferring patients needing further treatment increases emergency department congestion, has negative impacts on their health and may increase their mortality rates. A model built around a Markov decision process is proposed to improve the efficiency of patient flows between the emergency department and other hospital units. With each day divided into time periods, the formulation estimates bed demand for the next period as the basis for determining a proactive rather than reactive transfer decision policy. Due to the high dimensionality of the optimization problem involved, an approximate dynamic programming approach is used to derive an approximation of the optimal decision policy, which indicates that a certain number of beds should be kept free in the different units as a function of the next period demand estimate. Testing the model on two instances of different sizes demonstrates that the optimal number of patient transfers between units changes when the emergency patient arrival rate for transfer to other units changes at a single unit, but remains stable if the change is proportionally the same for all units. In a simulation using real data for a hospital in Chile, significant improvements are achieved by the model in key emergency department performance indicators such as patient wait times (reduction higher than 50%), patient capacity (21% increase) and queue abandonment (from 7% down to less than 1%).

Diel activity rhythms in mammals are regulated by an endogenous (circadian) timing system which is synchronized by environmental 24-hr periodicities called zeitgebers. Additional direct responses to stochastic environmental factors ensure the fine-tuning to the actual situation and may mask the circadian time course. Following an observational study on behavioral effects of visitor activities in a group of spider monkeys (Ateles geoffroyi) kept free-ranging on a small island of Lake Catemaco, Veracruz, Mexico, we analyzed the effect of weekly varying numbers of visiting tourist boats on the monkeys' diel activity rhythm. With small accelerometer-data logger devices we recorded the monkeys' locomotor activity continuously for several months each. Then we compared the data with those from spider monkeys living without tourist contact. Neither the duration of the monkeys' activity time (α) nor its phase relationship to the 24-hr solar day did change on different weekdays in either site. However, their activity level showed a clear 7-day rhythm. The monkeys of the tourist site showed highest activity on Saturday and Sunday, when the frequency of visiting tourist boats was highest, whereas those of the non-tourist site were least active on Sunday and Monday, when human activities were lowest there. While the monkeys of the non-tourist site usually displayed a distinct bimodal activity pattern peaking in the morning and late afternoon, the pattern in those of the tourist site mostly lacked a morning peak and varied more over time. Based on our results, we suggest that circadian entrainment is not involved in the differences between the diel activity rhythms of the spider monkeys from the two keeping sites and the differing 7-day variation in their activity level. Rather, these differences seemingly reflect direct responses to the differing human activities and thus may correspond to circadian masking effects., (© 2018 Wiley Periodicals, Inc.)

Intra-atrial re-entrant tachycardia (IART) is a severe complication in patients with congenital heart disease (CHD). Cavotricuspid isthmus (CTI)-related IART is the most frequent mechanism. However, due to fibrosis and surgical scars, non-CTI-related IART is frequent. The main objective of this study was to describe the types of IART, circuit locations, and to analyze predictors of CTI versus non-CTI-related IART. This is an observational study that includes all consecutive patients with CHD who underwent a first IART ablation in a single referral tertiary hospital from January 2009 to December 2015 (94 patients; 39.4% women; age: 36.55 ± 14.9 years, 40.4% with highly complex cardiac disease). During the study, 114 IARTs were ablated (1.21 ± 0.41 IARTs per patient). CTI-related IART was the only arrhythmia in 51% (n = 48) of patients; non-CTI-related IART was the only mechanism in 27.7% (n = 26), and 21.3% of patients (n = 20) presented the two types of IART. Severe dilation of the systemic ventricle, absence of severe dilation of the venous atrium, highly complex cardiac defects, and nontypical electrocardiography (ECG) were related to non-CTI-related IART in univariate analysis. In multivariate analysis, nontypical ECG (odds ratio 3.64; 1.01 to 4.9; p = 0.049) and grade III CHD complexity (odds ratio 9.43; 1.44 to 11.7; p = 0.001) were predictors of non-CTI-related IART. In conclusion, in our population with a high proportion of complex CHD, CTI-related IART was the most frequent mechanism, although non-CTI-related IART was present in 49% (alone or with concomitant CTI-related IART). High-grade CHD complexity and nontypical ECG were strongly related to non-CTI IART., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Numerous studies have shown that emotion recognition is impaired in individuals with a history of violent offenses, especially in those diagnosed with psychopathy. However, in criminological contexts, there is insufficient research regarding the role of empathy and facial emotion recognition abilities of personnel employed in correction centers. Accordingly, we sought to explore facial emotion recognition abilities and empathy in administrative officers and security guards at a center for institutionalized juvenile offenders. One hundred twenty-two Mexican subjects, including both men and women, were recruited for the study. Sixty-three subjects were administrative officers, and 59 subjects were security guards at a juvenile detention center. Tasks included "Pictures of Facial Affect" and the "Cambridge Behavior Scale." The results showed that group and gender had an independent effect on emotion recognition abilities, with no significant interaction between the two variables. Specifically, administrative officers showed higher empathy than security guards. Moreover, women in general exhibited more empathy than men. This study provides initial evidence of the need to study emotion recognition and empathy among professionals working in forensic settings or criminological contexts.

Background: Intra-atrial re-entrant tachycardia (IART) is a frequent and severe complication in patients with congenital heart disease (CHD). Cavotricuspid isthmus (CTI)-related IART is the most frequent mechanism. However, due to fibrosis and surgical scars, non-CTI-related IART is also frequent., Objective: The main objective of this study was to describe the types of IART and circuit locations and to define a cut-off value for unhealthy tissue in the atria., Methods and Results: This observational study included all consecutive patients with CHD who underwent a first ablation procedure for IART from January 2009 to December 2015 (94 patients, 39.4% female, age: 36.55 ± 14.9 years, 40.4% with highly complex cardiac disease). During the study, 114 IARTs were ablated (1.21 ± 0.41 IARTs per patient). Cavotricuspid isthmus-related IART was the only arrhythmia in 51% (n = 48) of patients, non-CTI-related IART was the only mechanism in 27.7% (n = 26), and 21.3% of patients (n = 20) presented both types of IART. In cases of non-CTI-related IART, the most frequent location of IART isthmus was the lateral or posterolateral wall of the venous atria, and a voltage cut-off value for unhealthy tissue in the atria of 0.5 mV identified 95.4% of IART isthmus locations., Conclusion: In our population with a high proportion of complex CHD, CTI-related IART was the most frequent mechanism, although non-CTI-related IART was present in 49% of patients (alone or with concomitant CTI-related IART). A cut-off voltage of 0.5 mV could identify 95.4% of the substrates in non-CTI-related IART., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Glycogen synthase (GS) and glycogen phosphorylase (GP) are the key enzymes that control, respectively, the synthesis and degradation of glycogen, a multi-branched glucose polymer that serves as a form of energy storage in bacteria, fungi and animals. An abnormal glycogen metabolism is associated with several human diseases. Thus, GS and GP constitute adequate pharmacological targets to modulate cellular glycogen levels by means of their selective inhibition. The compound 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) is a known potent inhibitor of GP. We studied the inhibitory effect of DAB, its enantiomer LAB, and 29 DAB derivatives on the activity of rat muscle glycogen phosphorylase (RMGP) and E. coli glycogen synthase (EcGS). The isoform 4 of sucrose synthase (SuSy4) from Solanum tuberosum L. was also included in the study for comparative purposes. Although these three enzymes possess highly conserved catalytic site architectures, the DAB derivatives analysed showed extremely diverse inhibitory potential. Subtle changes in the positions of crucial residues in their active sites are sufficient to discriminate among the structural differences of the tested inhibitors. For the two Leloir-type enzymes, EcGS and SuSy4, which use sugar nucleotides as donors, the inhibitory potency of the compounds analysed was synergistically enhanced by more than three orders of magnitude in the presence of ADP and UDP, respectively. Our results are consistent with a model in which these compounds bind to the subsite in the active centre of the enzymes that is normally occupied by the glucosyl residue which is transferred between donor and acceptor substrates. The ability to selectively inhibit the catalytic activity of the key enzymes of the glycogen metabolism may represent a new approach for the treatment of disorders of the glycogen metabolism.

Objective: Hypothyroidism is a common complication when radiotherapy is part of the treatment for head and neck tumours. This study aimed to show the incidence of hypothyroidism and possible risk factors in these patients., Methods: Factors related to the population, tumour, treatment and occurrence of hypothyroidism were analysed in 241 patients diagnosed with head and neck carcinoma., Results: Approximately 53 per cent of patients were diagnosed with radiation-induced hypothyroidism. Its occurrence was related to: tumour location, laryngeal surgery type, neck dissection type, post-operative complications, cervical radiotherapy and radiotherapy unit type (linear particle accelerator or telecobalt therapy technology)., Conclusion: Control of thyroid function should be standardised for several years after treatment, particularly in patients with risk factors, such as those treated with telecobalt therapy, those with post-operative complications and for whom the thyroid parenchyma is included in the irradiated area (laryngeal or pharyngeal location and bilateral cervical radiation).

Glycogen is a polymer of α-1,4- and α-1,6-linked glucose units that provides a readily available source of energy in living organisms. Glycogen synthase (GS) and glycogen phosphorylase (GP) are the two enzymes that control, respectively, the synthesis and degradation of this polysaccharide and constitute adequate pharmacological targets to modulate cellular glycogen levels, by means of inhibition of their catalytic activity. Here we report on the synthesis and biological evaluation of a selective inhibitor that consists of an azobenzene moiety glycosidically linked to the anomeric carbon of a glucose molecule. In the ground state, the more stable (E)-isomer of the azobenzene glucoside had a slight inhibitory effect on rat muscle GP (RMGP, IC50 = 4.9 mM) and Escherichia coli GS (EcGS, IC50 = 1.6 mM). After irradiation and subsequent conversion to the (Z)-form, the inhibitory potency of the azobenzene glucoside did not significantly change for RMGP (IC50 = 2.4 mM), while its effect on EcGS increased 50-fold (IC50 = 32 μM). Sucrose synthase 4 from potatoes, a glycosyltransferase that does not operate on glycogen, was only slightly inhibited by the (E)-isomer (IC50 = 0.73 mM). These findings could be rationalized on the basis of kinetic and computer-aided docking analysis, which indicated that both isomers of the azobenzene glucoside mimic the EcGS acceptor substrate and exert their inhibitory effect by binding to the glycogen subsite in the active center of the enzyme. The ability to selectively photoregulate the catalytic activity of key enzymes of glycogen metabolism may represent a new approach for the treatment of glycogen metabolism disorders.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) has a key regulatory role in the mevalonate pathway for isoprenoid biosynthesis and is composed of an endoplasmic reticulum (ER)-anchoring membrane domain with low sequence similarity among eukaryotic kingdoms and a conserved cytosolic catalytic domain. Organized smooth endoplasmic reticulum (OSER) structures are common formations of hypertrophied tightly packed ER membranes devoted to specific biosynthetic and secretory functions, the biogenesis of which remains largely unexplored. We show that the membrane domain of plant HMGR suffices to trigger ER proliferation and OSER biogenesis. The proliferating membranes become highly enriched in HMGR protein, but they do not accumulate sterols, indicating a morphogenetic rather than a metabolic role for HMGR. The N-terminal MDVRRRPP motif present in most plant HMGR isoforms is not required for retention in the ER, which was previously proposed, but functions as an ER morphogenic signal. Plant OSER structures are morphologically similar to those of animal cells, emerge from tripartite ER junctions, and mainly build up beside the nuclear envelope, indicating conserved OSER biogenesis in high eukaryotes. Factors other than the OSER-inducing HMGR construct mediate the tight apposition of the proliferating membranes, implying separate ER proliferation and membrane association steps. Overexpression of the membrane domain of Arabidopsis (Arabidopsis thaliana) HMGR leads to ER hypertrophy in every tested cell type and plant species, whereas the knockout of the HMG1 gene from Arabidopsis, encoding its major HMGR isoform, causes ER aggregation at the nuclear envelope. Our results show that the membrane domain of HMGR contributes to ER morphogenesis in plant cells., (© 2015 American Society of Plant Biologists. All Rights Reserved.)

The timing and pattern of mammalian behavioral activities are regulated by an evolutionary optimized interplay of the genetically based biological (circadian) clock located in the brain's suprachiasmatic nuclei and direct responses to environmental factors that superimpose and thus mask the clock-mediated effects, the most important of which is the photically induced phase-setting (synchronization) of the circadian rhythmicity to the 24-hour solar day. In wild and captive animals living under the natural conditions prevailing in their habitat, to date, only a few attempts have been made to analyze the role of these two regulatory mechanisms in the species' adaptation to the time structure prevailing in their habitat. We studied the impact of housing conditions and season on the daily timing and pattern of activity in Mexican spider monkeys (Ateles geoffroyi). To this end, we carried out long-term activity recordings with Actiwatch® AW4 accelerometer/data-logger devices in 11 adult Ateles living under identical natural lighting and climatic conditions in either a large wire netting cage or a 0.25 ha forest enclosure in the primatological field station of Veracruz State University near Catemaco, Mexico. In a gravid female in the forest enclosure, we obtained first-hand information on the effect of late pregnancy and parturition on the monkey's activity rhythm. The Ateles behaved strictly diurnal and undertook about 90% of daily total activity during this activity time. Due to a higher second activity peak in late afternoon, the bimodal activity pattern was more pronounced in monkeys living in the forest enclosure. Although the spider monkeys kept there had an earlier activity onset and morning activity peak than their conspecifics in the cage, no consistent differences were found in the parameters characterizing the phase-setting of the circadian system to the environmental 24-h periodicity, either by comparison or correlation with the external time markers of sunrise (SR) and sunset (SS). The most obvious effect of late pregnancy, parturition and lactation was a distinct reduction of the activity level during the week of parturition and the next. Seasonal variations in the form of significant differences between the long-day summer half year and the short-day winter half year were established in the phase-angle differences of the morning activity peak to SR, in the evening activity peak and activity offset to SS, as well as in the activity time and the peak-to-peak interval, but not in the phase position of activity onset to SR or in the height of the morning and evening activity peak. These findings in combination with a high variability of the phase angle differences indicate that in A. geoffroyi, a relatively weak circadian component and strong masking direct effects of environmental factors are involved in the regulation of the daily activity rhythm.

This paper presents the electrical characteristics of solution-processed organic photodetectors based on poly(3-hexylthiophene-2,5-diyl) semiconducting polymer layers deposited by spin-coating on interdigitated metal electrodes. Four different electrode shapes have been used for this study in order to appraise the optimum electrode geometry. The measurement of the resistance as a function of the temperature reveals a transition from negative to positive temperature coefficient material around 80 °C for the polymer layers. Besides, slow reversible changes in the photodetectors conductivity were observed when moved from vacuum to the air and under illumination with a xenon lamp, which can be explained by the formation of charge transfer complexes with molecular oxygen and the polymer. The photogenerated current-light power ratio was found to be approximately linear in the 200 to 550 mW/cm2 range.

Decarboxylation of malonyl-CoA to acetyl-CoA by malonyl-CoA decarboxylase (MCD; EC 4.1.1.9) is an essential facet in the regulation of fatty acid metabolism. The structure of human peroxisomal MCD reveals a molecular tetramer that is best described as a dimer of structural heterodimers, in which the two subunits present markedly different conformations. This molecular organization is consistent with half-of-the-sites reactivity. Each subunit has an all-helix N-terminal domain and a catalytic C-terminal domain with an acetyltransferase fold (GNAT superfamily). Intersubunit disulfide bridges, Cys-206-Cys-206 and Cys-243-Cys-243, can link the four subunits of the tetramer, imparting positive cooperativity to the catalytic process. The combination of a half-of-the-sites mechanism within each structural heterodimer and positive cooperativity in the tetramer produces a complex regulatory picture that is further complicated by the multiple intracellular locations of the enzyme. Transport into the peroxisome has been investigated by docking human MCD onto the peroxisomal import protein peroxin 5, which revealed interactions that extend beyond the C-terminal targeting motif.

Introduction: Major depression and insomnia are among the most frequent neuropsychiatric syndromes in the geriatric population. Although most SSRI antidepressants affect sleep continuity, mirtazapine has been found to improve sleep continuity in patients with depression. The aim of the present study was to assess by actigraphic recordings changes in sleep patterns of geriatric patients with major depression before and during treatment with mirtazapine (30 mg)., Methods: Patients aged 60 years or more with major depressive disorder were recruited at the outpatient service of a specialized mental health centre. Severity of depression was rated with the Montgomery-Asberg depression rating scale and subjective perception of sleep was assessed with the Pittsburgh sleep quality index (PSQI). Actigraphic parameters were registered 4 days before the onset of mirtazapine treatment (patients were drug free in this period of time) and recorded at day 60 of treatment with mirtazapine., Results: A significant decrease was observed in the sleep fragmentation index. While a significant improvement was observed in the subjective assessment of quality after treatment with mirtazapine, actigraphic measures of sleep parameters did not show changes in line with mirtazapine treatment., Discussion: Mirtazapine produces minimal changes on actigraphic measures in the sleep of elderly outpatients. Sleep produced by mirtazapine indicates a more pronounced effect in ≥ 80-year-old patients. This differential response should be considered during treatment of this clinical population., (© Georg Thieme Verlag KG Stuttgart · New York.)

Despite the biological relevance of glycosyltrasferases (GTs) and the many efforts devoted to this subject, the catalytic mechanism through which a subclass of this large family of enzymes, namely those that operate with net retention of the anomeric configuration, has not been fully established. Here, we show that in the absence of an acceptor, an archetypal retaining GT such as Pyrococcus abyssi glycogen synthase (PaGS) reacts with its glucosyl donor substrate, uridine 5'-diphosphoglucose (UDP-Glc), to produce the scission of the covalent bond between the terminal phosphate oxygen of UDP and the sugar ring. X-ray diffraction analysis of the PaGS/UDP-Glc complex shows no electronic density attributable to the UDP moiety, but establishes the presence in the active site of the enzyme of a glucose-like derivative that lacks the exocyclic oxygen attached to the anomeric carbon. Chemical derivatization followed by gas chromatography/mass spectrometry of the isolated glucose-like species allowed us to identify the molecule found in the catalytic site of PaGS as 1,5-anhydro-D-arabino-hex-1-enitol (AA) or its tautomeric form, 1,5-anhydro-D-fructose. These findings are consistent with a stepwise S(N) i-like mechanism as the modus operandi of retaining GTs, a mechanism that involves the discrete existence of an oxocarbenium intermediate. Even in the absence of a glucosyl acceptor, glycogen synthase (GS) promotes the formation of the cationic intermediate, which, by eliminating the proton of the adjacent C2 carbon atom, yields AA. Alternatively, these observations could be interpreted assuming that AA is a true intermediate in the reaction pathway of GS and that this enzyme operates through an elimination/addition mechanism., (Copyright © 2012 Wiley Periodicals, Inc.)

Glycogen synthase, a central enzyme in glucose metabolism, catalyzes the successive addition of α-1,4-linked glucose residues to the non-reducing end of a growing glycogen molecule. A non-catalytic glycogen-binding site, identified by x-ray crystallography on the surface of the glycogen synthase from the archaeon Pyrococcus abyssi, has been found to be functionally conserved in the eukaryotic enzymes. The disruption of this binding site in both the archaeal and the human muscle glycogen synthases has a large impact when glycogen is the acceptor substrate. Instead, the catalytic efficiency remains essentially unchanged when small oligosaccharides are used as substrates. Mutants of the human muscle enzyme with reduced affinity for glycogen also show an altered intracellular distribution and a marked decrease in their capacity to drive glycogen accumulation in vivo. The presence of a high affinity glycogen-binding site away from the active center explains not only the long-recognized strong binding of glycogen synthase to glycogen but also the processivity and the intracellular localization of the enzyme. These observations demonstrate that the glycogen-binding site is a critical regulatory element responsible for the in vivo catalytic efficiency of GS.

Eukaryotic glycogen synthase activity is regulated by reversible phosphorylation at multiple sites. Of the two GS isoforms found in mammals, the muscle enzyme (muscle glycogen synthase) has received more attention and the relative importance of every known phosphorylation site in the control of its activity and intracellular distribution has been previously addressed. We have analyzed the impact of the dephosphorylation at the homologous sites of the glycogen synthase liver (LGS) isoform. Serine residues at these sites were replaced by non-phosphorylatable alanine residues, singly or in pairs, and the resultant LGS variants were expressed in cultured cells using adenoviral vectors. The sole mutation at site 2 (Ser7) yielded an enzyme that was almost fully active and able to induce glycogen deposition in primary hepatocytes incubated in the absence of glucose and in FTO2B cells, a cell line that does not normally synthesize glycogen. Mutation at site 2 was also sufficient to trigger the aggregation and translocation of LGS from the cytoplasm to the hepatocyte cell cortex in the absence of glucose. However, this redistribution was not observed in hepatocytes incubated without glucose when an additional mutation (E509A), which renders the enzyme inactive, was introduced. This result suggests that LGS translocation is strictly dependent on glycogen synthesis.

Glycogen and starch synthases are retaining glycosyltransferases that catalyze the transfer of glucosyl residues to the non-reducing end of a growing alpha-1,4-glucan chain, a central process of the carbon/energy metabolism present in almost all living organisms. The crystal structure of the glycogen synthase from Pyrococcus abyssi, the smallest known member of this family of enzymes, revealed that its subunits possess a fold common to other glycosyltransferases, a pair of beta/alpha/beta Rossmann fold-type domains with the catalytic site at their interface. Nevertheless, the archaeal enzyme presents an unprecedented homotrimeric molecular arrangement both in solution, as determined by analytical ultracentrifugation, and in the crystal. The C-domains are not involved in intersubunit interactions of the trimeric molecule, thus allowing for movements, likely required for catalysis, across the narrow hinge that connects the N- and C-domains. The radial disposition of the subunits confers on the molecule a distinct triangular shape, clearly visible with negative staining electron microscopy, in which the upper and lower faces present a sharp asymmetry. Comparison of bacterial and eukaryotic glycogen synthases, which use, respectively, ADP or UDP glucose as donor substrates, with the archaeal enzyme, which can utilize both molecules, allowed us to propose the residues that determine glucosyl donor specificity.

Muscle glycogen synthase (MGS) presents a nuclear speckled pattern in primary cultured human muscle and in 3T3-L1 cells deprived of glucose and with depleted glycogen reserves. Nuclear accumulation of the enzyme correlates inversely with cellular glycogen content. Although the glucose-induced export of MGS from the nucleus to the cytoplasm is blocked by leptomycin B, and therefore mediated by CRM1, no nuclear export signal was identified in the sequence of the protein. Deletion analysis shows that the region comprising amino acids 555-633 of human MGS, which encompasses an Arg-rich cluster involved in the allosteric activation of the enzyme by Glc6P, is crucial for its nuclear concentration and aggregation. Mutation of these Arg residues, which desensitizes the enzyme towards Glc6P, interferes with its nuclear accumulation. In contrast, the known phosphorylation sites of MGS that regulate its activity are not involved in the control of its subcellular distribution. Nuclear human MGS co-localizes with the promyelocytic leukaemia oncoprotein and p80-coilin, a marker of Cajal bodies. The subnuclear distribution of MGS is altered by incubation with transcription inhibitors. These observations suggest that, in addition to its metabolic function, MGS may participate in nuclear processes.

Glycogen synthase catalyzes the transfer of glucosyl residues from ADP- or UDP-glucose to the non-reducing end of a growing alpha-1,4-glucan chain. To date, no crystallographic structure of an animal/fungal glycogen synthase (family 3 of the glycosyl transferases) or a bacterial/plant glycogen/starch synthase (family 5) has been reported. This paper describes the recombinant expression, crystallization and preliminary X-ray analysis of the glycogen synthase from the hyperthermophilic archaeon Pyrococcus abyssi, the smallest enzyme of the members of families 3 and 5 of the glycosyl transferases. Crystals from this protein and from its selenomethionyl variant were grown in 100 mM sodium citrate pH 5.6 containing 20% PEG and 20% dioxane by the hanging-drop vapour-diffusion method at 293 K. The crystals, which grew as thin needles, diffracted to 3.5 A resolution and belong to space group C2, with unit-cell parameters a = 202, b = 73, c = 149 A, beta = 131 degrees. The crystallographic and biochemical data are consistent with either a dimer or a tetramer in the crystal asymmetric unit and a volume solvent content of 70 or 39%, respectively.

We characterized a novel protein of the Ras family, p19 (H-RasIDX). The c-H-ras proto-oncogene undergoes alternative splicing of the exon termed IDX. We show that the alternative p19 mRNA is stable and as abundant as p21 (p21 H-Ras4A) mRNA in all of the human tissues and cell lines tested. IDX is spliced into stable mRNA in different mammalian species, which present a high degree of nucleotide conservation. Both the endogenous and the transiently expressed p19 protein are detected in COS-1 and HeLa cells and show nuclear diffuse and speckled patterns as well as cytoplasmic localization. In yeast two-hybrid assays, p19 did not interact with two known p21 effectors, Raf1 and Rin1, but was shown to interact with RACK1, a scaffolding protein that promotes multiprotein complexes in different signaling pathways. This observation suggests that p19 and p21 play differential and complementary roles in the cell.

Traditionally, glycogen synthase (GS) has been considered to catalyze the key step of glycogen synthesis and to exercise most of the control over this metabolic pathway. However, recent advances have shown that other factors must be considered. Moreover, the control of glycogen deposition does not follow identical mechanisms in muscle and liver. Glucose must be phosphorylated to promote activation of GS. Glucose-6-phosphate (Glc-6-P) binds to GS, causing the allosteric activation of the enzyme probably through a conformational rearrangement that simultaneously converts it into a better substrate for protein phosphatases, which can then lead to the covalent activation of GS. The potency of Glc-6-P for activation of liver GS is determined by its source, since Glc-6-P arising from the catalytic action of glucokinase (GK) is much more effective in mediating the activation of the enzyme than the same metabolite produced by hexokinase I (HK I). As a result, hepatic glycogen deposition from glucose is subject to a system of control in which the 'controller', GS, is in turn controlled by GK. In contrast, in skeletal muscle, the control of glycogen synthesis is shared between glucose transport and GS. The characteristics of the two pairs of isoenzymes, liver GS/GK and muscle GS/HK I, and the relationships that they establish are tailored to suit specific metabolic roles of the tissues in which they are expressed. The key enzymes in glycogen metabolism change their intracellular localization in response to glucose. The changes in the intracellular distribution of liver GS and GK triggered by glucose correlate with stimulation of glycogen synthesis. The translocation of GS, which constitutes an additional mechanism of control, causes the orderly deposition of hepatic glycogen and probably represents a functional advantage in the metabolism of the polysaccharide.

Glucose 6-phosphate (Glc-6-P) produced in cultured hepatocytes by direct phosphorylation of glucose or by gluconeogenesis from dihydroxyacetone (DHA) was equally effective in activating glycogen synthase (GS). However, glycogen accumulation was higher in hepatocytes incubated with glucose than in those treated with DHA. This difference was attributed to decreased futile cycling through GS and glycogen phosphorylase (GP) in the glucose-treated hepatocytes, owing to the partial inactivation of GP induced by glucose. Our results indicate that the gluconeogenic pathway and the glucokinase-mediated phosphorylation of glucose deliver their common product to the same Glc-6-P pool, which is accessible to liver GS. As observed in the treatment with glucose, incubation of cultured hepatocytes with DHA caused the translocation of GS from a uniform cytoplasmic distribution to the hepatocyte periphery and a similar pattern of glycogen deposition. We hypothesize that Glc-6-P has a major role in glycogen metabolism not only by determining the activation state of GS but also by controlling its subcellular distribution in the hepatocyte.

Incubation of hepatocytes isolated from fasted rats with [14C]glucose for short periods of time showed that the initial stages of glycogen synthesis occur near the plasma membrane. Incubation with [14C]glucose followed by cold glucose demonstrated that glycogen synthesis is always active at the hepatocyte periphery and that previously synthesised glycogen moves towards the centre of the cell, while its place is filled by newly synthesised molecules. However, the reverse experiment, incubation with cold glucose before addition of [14C]glucose, showed that, as glycogen synthesis progresses, it also becomes gradually active in more internal sites of the hepatocyte. These results indicate a spatial order in the synthesis of hepatic glycogen.

Intra-testicular inoculation of an adenoviral vector carrying the fusion gene Aequorea victoria green fluorescence protein/rat-liver glycogen synthase (GFP/LGS) resulted in the presence of GFP/GLS in spermatozoa from 7days to, at least, 16days after inoculation. The GFP/LGS was detected in the sperm heads after an "in vitro" fertilization procedure, either before or after the oocyte penetration. Our results indicate that spermatozoa carrying GFP/LGS protein conserved their fertilizing ability and were also detectable after oocyte penetration. This technique will allow to develop an easy system to follow the fate of mature sperm proteins.

Classically, alpha-1,4-glucan synthases have been divided into two families, animal/fungal glycogen synthases (GS) and bacterial/plant starch synthases (G(S)S), according to differences in sequence, sugar donor specificity and regulatory mechanisms. Detailed sequence analysis, predicted secondary structure comparison and threading analysis show that these two families are structurally related and that some domains of GSs were acquired to meet regulatory requirements. Archaeal G(S)S present structural and functional features that are conserved in one, the other or both families. Therefore, they are the link between GS and G(S)S and harbor the minimal sequence and structural features that constitute the minimum catalytic unit of the alpha-1,4-glucan synthase superfamily.

Using adenovirus-mediated gene transfer into FTO-2B cells, a rat hepatoma cell line, we have overexpressed hexokinase I (HK I), glucokinase (GK), liver glycogen synthase (LGS), muscle glycogen synthase (MGS), and combinations of each of the two glucose-phosphorylating enzymes with each one of the GS isoforms. FTO-2B cells do not synthesize glycogen even when incubated with high doses of glucose. Adenovirus-induced overexpression of HK I and/or LGS, two enzymes endogenously expressed by these cells, did not produce a significant increase in the levels of active GS and the total glycogen content. In contrast, GK overexpression led to the glucose-dependent activation of endogenous or overexpressed LGS and to the accumulation of glycogen. Similarly overexpressed MGS was efficiently activated by the glucose-6-phosphate (Glc-6-P) produced by either endogenous or overexpressed HK I and by overexpressed GK. These results indicate the existence of at least two pools of Glc-6-P in the cell, one of them is accessible to both isoforms of GS and is replenished by the action of GK, whereas LGS is excluded from the cellular compartment where the Glc-6-P produced by HK I is directed. These findings are interpreted in terms of the metabolic role that the two pairs of enzymes, HK I-MGS in the muscle and GK-LGS in the hepatocyte, perform in their respective tissues.

Background: Pneumonia is one of the most common complications of influenza infection. However, its characteristics are not well-known. Our aim was to assess the frequency of community-acquired pneumonia (CAP) associated with influenza virus and to determine its clinical and epidemiological characteristics., Patients and Method: A total of 240 patients with CAP were evaluated and cases with serological evidence of influenza virus infection were identified. Patients in whom there was no evidence of infection by other microbial agents were selected and defined as influenza virus infection-associated CAP (CAP-i). Clinical and epidemiological features of CAP-i patients were compared with the rest of patients with CAP., Results: A microbial diagnosis was achieved in 143 (59.6%) of 240 patients with CAP. In 12 cases (5%) there was serological evidence of infection by influenza A virus. In 8 patients no other respiratory pathogens were detected (CAP-i). In a multivariate analysis, the presence of arthromyalgias (odds ratio [OR] = 30, 68; 95% confidence interval [CI], 1-946), plasmatic sodium < 133 mEq/l (OR = 16.92; 95% CI, 1.48-193), bilateral infiltrates in chest X-ray (OR = 8.83; 95% CI, 1.35-57.6), diagnosis of CAP in January or February (OR = 5.60; 95% CI, 0.87-35.8) and blood neutrophil cell count >= 14,000/l, (OR = 5.23; 95% CI, 0.85-32) were all independently associated with CAP-i. The simultaneous presence of all these characteristics had a positive and negative predictive value of 95% and 99%, respectively, to differentiate CAP-i from other CAP., Conclusions: Influenza virus infection-associated CAP is uncommon. Some clinical and radiographic variables could differentiate CAP-i from other CAP. These parameters could also help identify patients who are more likely to benefit from specific antiviral therapy.

Hydroperoxidases (HP) are normally large haem-containing bifunctional enzymes capable of acting as both catalases and peroxidases. The C-terminal domain of HPI from Escherichia coli (KatG), extending from residue Tyr422 to Leu726, was found to be resistant to trypsin proteolysis. The segment of katG encoding this domain was cloned and overexpressed to produce a haemless protein that is soluble even at concentrations above 30 mg ml(-1). This protein shows a 25% sequence identity with cytochrome c peroxidase (CCP) from Saccharomyces cerevisae, despite lacking the characteristic catalytic and iron-binding residues. Crystals from this protein were grown in 0.6 M sodium citrate buffered to pH 7.5 with HEPES by the hanging-drop vapour-diffusion method at 293 K. These crystals diffracted beyond 2.0 A resolution and belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 84.2, b = 98.7, c = 302.8 A. Three pseudo-origin peaks in the Patterson maps indicate an unusual packing compatible with the presence of three molecules in the crystal asymmetric unit and a solvent content of about 80% by volume.

The clinical benefit brought about by HMG-CoA reductase inhibitors (statins) may not entirely be due to their lipid-lowering effect. Further investigation is necessary in order to determine the significance of ancillary effects to the clinical benefit of statin treatment. We studied 27 polygenic hypercholesterolaemia (PHC) patients before and 3 and 6 months after fluvastatin treatment. A control group of 38 normal, sex and age matched, subjects were also studied. The following parameters were measured: haematimetry, serum lipids and general biochemistry, apo-A/B and lipoproteins, fibrinogen, blood filterability, red blood cell aggregation, blood and plasma viscosity. PHC patients showed lower blood filterability (16.00+/-0.99 vs 19.90+/-2.90 microl/s), higher plasma fibrinogen (274.8+/-41.5 vs 241.6+/-43.2 mg/dl), increased erythrocyte aggregation at low shear stress (8.10+/-1.15 vs 7.19+/-1.29) and increased plasma viscosity (1.26+/-0.06 vs 1.23+/-0.05 mPa.s). Notable lipid changes after 6 months fluvastatin treatment were not accompanied by measurable changes in the haemorheological alterations of the PHC patients.

Changes in the intracellular distribution of liver glycogen synthase (GS) might constitute a new regulatory mechanism for the activity of this enzyme at cellular level. Our previous studies indicated that incubation of isolated hepatocytes with glucose activated GS and resulted in its translocation from a homogeneous cytosolic distribution to the cell periphery. These studies also suggested a relationship with insoluble elements of the cytoskeleton, in particular actin. Here we show the translocation of GS in a different experimental model that allows the analysis of this phenomenon in long-term studies. We describe the reversibility of translocation of GS and its effect on glycogen distribution. Incubation of cultured rat hepatocytes with glucose activated GS and triggered its translocation to the hepatocyte periphery. The relative amount of the enzyme concentrated near the plasma membrane increased with time up to 8 h of incubation with glucose, when the glycogen stores reached their maximal value. The lithium-induced covalent activation of GS was not sufficient to cause its translocation to the cell periphery. The intracellular distribution of GS closely resembled that of glycogen. Our results showed an interaction between GS and an insoluble element of the hepatocyte matrix. Although no co-localization between actin filaments and GS was observed in any condition, disruption of actin cytoskeleton resulted in a significantly lower percentage of cells in which the enzyme translocated to the cell periphery in response to glucose. This observation suggests that the microfilament network has a role in the translocation of GS.

We have used recombinant adenoviruses (AdCMV-RLGS and AdCMV-GK) to overexpress the liver isoforms of glycogen synthase (GS) and glucokinase (GK) in primary cultured rat hepatocytes. Glucose activated overexpressed GS in a dose-dependent manner and caused the accumulation of larger amounts of glycogen in the AdCMV-RLGS-treated hepatocytes. The concentration of intermediate metabolites of the glycogenic pathway, such as glucose 6-phosphate (Glc-6-P) and UDP-glucose, were not significantly altered. GK overexpression also conferred on the hepatocyte an enhanced capacity to synthesize glycogen in response to glucose, as described previously [Seoane, Gómez-Foix, O'Doherty, Gómez-Ara, Newgard and Guinovart (1996) J. Biol. Chem. 271, 23756-23760], although, in this case, they accumulated Glc-6-P. When GS and GK were simultaneously overexpressed, the accumulation of glycogen was enhanced in comparison with cells overexpressing either GS or GK. Our results are consistent with the hypothesis that liver GS catalyses the rate-limiting step of hepatic glycogen synthesis. However, hepatic glycogen deposition from glucose is submitted to a system of shared control in which the 'controller', GS, is, in turn, controlled by GK. This control is indirectly exerted through Glc-6-P, which 'switches on' GS dephosphorylation and activation.

The detailed catalytic mechanism by which glycosyltransferases catalyze the transfer of a glycosyl residue from a donor sugar to an acceptor is not known. Through the multiple alignment of all known eukaryotic glycogen synthases we have found an invariant 17-amino acid stretch enclosed within the most conserved region of the members of this family. This peptide includes an E-X(7)-E motif, which is highly conserved in four families of retaining glycosyltransferases. Site-directed mutagenesis was performed in human muscle glycogen synthase to analyze the roles of the two conserved Glu residues (Glu-510 and Glu-518) of the motif. Proteins were transiently expressed in COS-1 cells as fusions to green fluorescence protein. The E510A and E518A mutant proteins retained the ability to translocate from the nucleus to the cytosol in response to glucose and to bind to intracellular glycogen. Although the E518A variant had approximately 6% of the catalytic activity shown by the green fluorescence protein-human muscle glycogen synthase fusion protein, the E510A mutation inactivated the enzyme. These results led us to conclude that the E-X(7)-E motif is part of the active site of eukaryotic glycogen synthases and that both conserved Glu residues are involved in catalysis. We propose that Glu-510 may function as the nucleophile and Glu-518 as the general acid/base catalyst.

We have studied the intracellular distribution in vivo of glucokinase (GK) and glucokinase regulatory protein (GKRP) in livers of fasted and refed rats, using specific antibodies against both proteins and laser confocal fluorescence microscopy. GK was found predominantly in the nucleus of hepatocytes from starved rats. GK was translocated to the cytoplasm in livers of 1- and 2-h refed animals, but returned to the nucleus after 4 h. GKRP concentrated in the hepatocyte nuclei and its distribution did not change upon refeeding. These results show that, in physiological conditions, GKRP is present predominantly in the nuclei of hepatocytes and that the translocation of hepatic GK from and to the nucleus is operative in vivo.