Autophagy signaling in hypertrophied muscles of diabetic and control rats.

Autophagy plays a vital role in cell homeostasis by eliminating nonfunctional components and promoting cell survival. Here, we examined the levels of autophagy signaling proteins after 7 days of overload hypertrophy in the extensor digitorum longus (EDL) and soleus muscles of control and diabetic rats. We compared control and 3-day streptozotocin-induced diabetic rats, an experimental model for type 1 diabetes mellitus (T1DM). EDL muscles showed increased levels of basal autophagy signaling proteins. The diabetic state did not affect the extent of overload-induced hypertrophy or the levels of autophagy signaling proteins (p-ULK1, Beclin-1, Atg5, Atg12-5, Atg7, Atg3, LC3-I and II, and p62) in either muscle. The p-ULK-1, Beclin-1, and p62 protein expression levels were higher in the EDL muscle than in the soleus before the hypertrophic stimulus. On the contrary, the soleus muscle exhibited increased autophagic signaling after overload-induced hypertrophy, with increases in Beclin-1, Atg5, Atg12-5, Atg7, Atg3, and LC3-I expression in the control and diabetic groups, in addition to p-ULK-1 in the control groups. After hypertrophy, Beclin-1 and Atg5 levels increased in the EDL muscle of both groups, while p-ULK1 and LC3-I increased in the control group. In conclusion, the baseline EDL muscle exhibited higher autophagy than the soleus muscle. Although TDM1 promotes skeletal muscle mass loss and strength reduction, it did not significantly alter the extent of overload-induced hypertrophy and autophagy signaling proteins in EDL and soleus muscles, with the two groups exhibiting different patterns of autophagy activation.

Effects of lysine levels on performance, blood parameters, and nutrient digestibility of Duroc barrows in the starter phase.

The objective of this study was to evaluate the effects of different levels of digestible lysine, at fixed amino acid ratios, in performance, blood parameters and diet digestibility of barrows from 15 to 30 kg. Fifty barrows of the Duroc breed with an average initial body weight of 14.95±3.22 kg were assigned to five treatments in a completely randomized experimental design with five replicates and of two animals per experimental unit. Treatments consisted of crude protein and lysine levels, maintaining a fixed ratio with the other digestible amino acids (8.4, 9.4, 10.4, 11.4, and 12.4 g kg-1lysine/kg of diet). The feed conversion decreased linearly according to lysine levels. The apparent digestibility coefficients of dry matter and crude protein increased linearly, and the same response was observed for serum total protein and urea. The results indicate that digestible lysine level for Duroc barrows in the starter phase is 12.4 g kg-1 of diet, as it improved feed conversion ratio and apparent nutrient digestibility.

ß-micrustoxin (Mlx-9), a PLA2 from Micrurus lemniscatus snake venom: biochemical characterization and anti-proliferative effect mediated by p53.

Background: Endogenous phospholipases A2 (PLA2) play a fundamental role in inflammation, neurodegenerative diseases, apoptosis and cellular senescence. Neurotoxins with PLA2 activity are found in snake venoms from the Elapidae and Viperidae families. The mechanism of action of these neurotoxins have been studied using hippocampal and cerebellar neuronal cultures showing [Ca2+]i increase, mitochondrial depolarization and cell death. Astrocytes are rarely used as a model, despite being modulators at the synapses and responsible for homeostasis and defense in the central nervous system. Preserving the cell division ability, they can be utilized to study the cell proliferation process. In the present work cultured astrocytes and glioblastoma cells were employed to characterize the action of ß-micrustoxin (previously named Mlx-9), a PLA2 isolated from Micrurus lemniscatus snake venom. The ß-micrustoxin structure was determined and the cell proliferation, cell cycle phases and the regulatory proteins p53, p21 and p27 were investigated. Methods: ß-micrustoxin was characterized biochemically by a proteomic approach. Astrocytes were obtained by dissociation of pineal glands from Wistar rats; glioblastoma tumor cells were purchased from ATCC and Sigma and cultured in DMEM medium. Cell viability was evaluated by MTT assay; cell proliferation and cell cycle phases were analyzed by flow cytometry; p53, p21 and p27 proteins were studied by western blotting and immunocytochemistry. Results: Proteomic analysis revealed fragments on ß-micrustoxin that aligned with a PLA2 from Micrurus lemniscatus lemniscatus previously identified as transcript ID DN112835_C3_g9_i1/m.9019. ß-micrustoxin impaired the viability of astrocytes and glioblastoma tumor cells. There was a reduction in cell proliferation, an increase in G2/M phase and activation of p53, p21 and p27 proteins in astrocytes. Conclusion: These findings indicate that ß-micrustoxin from Micrurus lemniscatus venom could inhibit cell proliferation through p53, p21 and p27 activation thus imposing cell cycle arrest at the checkpoint G2/M.

Closed-loop organic waste management systems for family farmers in Brazil.

Family farmers in Brazil could diversify their sources of income and improve agriculture practices by adopting circular economy principles on their farms. Closed-loop technological systems can be used to manage organic waste and produce fertiliser and biogas thereby generating revenue. Anaerobic Digestion (AD) is a proven technology that can produce digestate (i.e. fertiliser) and biogas from organic waste, although digestate application in soil and crops without treatment can have adverse effects. However, in practice, there is a lack of knowledge about the benefits of recycling organic waste in farming communities in Brazil. Therefore, the main aim of this paper is to provide conceptual design configurations of closed-loop systems that manage organic waste and generate revenue for small farms in Brazil. A literature review of selected technologies and interviews with Brazilian family farmers were used to inform the components of the proposed conceptual designs. The proposed designs are based on circular economy principles, incorporating AD, pyrolysis for biochar, hydroponics and vermifiltration in various configurations. A complete closed-loop system consisting of a 7.5 m3 digester, pyrolysis unit, a combined hydroponic and vermifilter unit and a shredder is estimated to cost around USD$1600 (R$ 6600). The flexibility of the proposed systems has the potential to increase resilience and income for small-scale farmers, whilst encouraging good practices for waste management. The conceptual designs can be used as a basis for further research and development of small-scale organic waste management solutions in Brazil.

ß-micrustoxin (Mlx-9), a PLA2 from Micrurus lemniscatus snake venom: biochemical characterization and anti-proliferative effect mediated by p53

Background: Endogenous phospholipases A2 (PLA2 ) play a fundamental role in inflammation, neurodegenerative diseases, apoptosis and cellular senescence. Neurotoxins with PLA2 activity are found in snake venoms from the Elapidae and Viperidae families. The mechanism of action of these neurotoxins have been studied using hippocampal and cerebellar neuronal cultures showing [Ca2+]i increase, mitochondrial depolarization and cell death. Astrocytes are rarely used as a model, despite being modulators at the synapses and responsible for homeostasis and defense in the central nervous system. Preserving the cell division ability, they can be utilized to study the cell proliferation process. In the present work cultured astrocytes and glioblastoma cells were employed to characterize the action of ß-micrustoxin (previously named Mlx-9), a PLA2 isolated from Micrurus lemniscatus snake venom. The ß-micrustoxin structure was determined and the cell proliferation, cell cycle phases and the regulatory proteins p53, p21 and p27 were investigated. Methods: ß-micrustoxin was characterized biochemically by a proteomic approach. Astrocytes were obtained by dissociation of pineal glands from Wistar rats; glioblastoma tumor cells were purchased from ATCC and Sigma and cultured in DMEM médium. Cell viability was evaluated by MTT assay; cell proliferation and cell cycle phases were analyzed by flow cytometry; p53, p21 and p27 proteins were studied by western blotting and immunocytochemistry. Results: Proteomic analysis revealed fragments on ß-micrustoxin that aligned with a PLA2 from Micrurus lemniscatus lemniscatus previously identified as transcript ID DN112835_C3_g9_i1/m.9019. ß-micrustoxin impaired the viability of astrocytes and glioblastoma tumor cells. There was a reduction in cell proliferation, an increase in G2/M phase and activation of p53, p21 and p27 proteins in astrocytes. Conclusion: These findings indicate that ß-micrustoxin from Micrurus lemniscatus venom could inhibit cell proliferation through p53, p21 and p27 activation thus imposing cell cycle arrest at the checkpoint G2/M.(AU)

Evaluation of different cooling management strategies for lactating Holstein × Gir dairy cows.

Heat stress negatively impacts production, reproduction, and health of ruminants and strategies to alleviate these losses are warranted. Therefore, four experiments evaluated different cooling strategies on vaginal temperature (VT) of Holstein × Gir cows. Experiment 1 compared different amounts of water (2- or 4-L) over a 1-hour period from 1000 to 1100 h and 1600 to 1700 h. Experiment 2 evaluated the effects of sprinkling duration (in hours; 1- or 2-H), whereas Experiment 3 evaluated the effects of water amount (4- or 8-L) applied for 1- or 2-H. Lastly, the effects of a cooling strategy on specific hours of the day, starting at either 0700 (T-1) or 1100 h (T-2; Experiment 4), were evaluated. In all experiments, 12 Holstein × Gir cows were used in a 2 × 2 Latin Square Design containing two periods of 6 days each. Temperature and humidity index (THI) were recorded hourly and VT was recorded every 10-min throughout the experiments. As expected, an hour effect was observed for THI (P < 0.0001), which peaked early in the afternoon. In Experiment 1, a treatment × hour interaction was observed (P < 0.0001) for VT, as animals assigned to receive 4-L had a reduced VT at 1100, 1600, 1700, and 2300 h (P ≤ 0.03). During the cooling applications, cows receiving 4-L for 1 h had a reduced VT from 60 to 150 min (P ≤ 0.04). In Experiment 2, a treatment × hour interaction was observed (P < 0.0001) for VT, as animals assigned to receive 4-L of water for 2-H had a reduced VT at 1200 h (P = 0.05). Moreover, during the cooling process, VT was reduced for 2-H cows from 140 to 170 min after the beginning of the cooling process (P ≤ 0.05). In Experiment 3, animals assigned to receive 4-L + 2H had a reduced VT at 1200, 1700, 1800, and 1900 h (P < 0.001). A treatment × hour interaction was observed (P < 0.0001), as VT was reduced for 4-L + 2-H cows from 130 to 180 min after the beginning of the cooling process (P ≤ 0.05). In Experiment 4, by the time when the first cooling cycle of T-1 was applied (0700 h), T-1 cows consistently had (P ≤ 0.05) a reduced VT up to the hottest hours and greatest THI of the day (1400 and 1500 h). This pattern was maintained until the end of the last cooling cycle, whereas T-2 cows had a reduced VT. In summary, 4 L of water over a 5-min cycle for a period of 2 hours twice a day maintained VT of Holstein × Gir cows at lower levels. Moreover, the hour at which the first cooling cycle starts also should be considered when evaluating the efficacy of a cooling strategy for an entire day.

Training Programs Designed for Muscle Hypertrophy in Bodybuilders: A Narrative Review.

Bodybuilding is a sport that requires adequate training strategies in order to maximize skeletal muscle hypertrophy. The purpose of the present review was to perform a narrative assessment of the training routines designed for muscle hypertrophy used by bodybuilders. A search was carried out in the databases Pubmed/MEDLINE, Scielo, EBSCO, LILACS, SportDiscus, Web of Science, and CINAHL with the words "Resistance training" and "hypertrophy" in bodybuilders and their variations that involve the respective outcomes. Fourteen studies were identified that investigated the long-term training routines of bodybuilders. These studies demonstrate a pattern in the training organization, whereby there is a separation of training into four distinct periods: off-season, pre-contest, peak week, and post-contest. Each period has a specific spectrum of intensity load, total training volume, and exercise type (multi- or single-joint). We conclude that bodybuilding competitors employed a higher intensity load, lower number of repetitions, and longer rest intervals in the off-season than pre-contest.

Pasta waste in the feeding of meat quail.

This study was undertaken to investigate the performance, carcass characteristics, and economic viability of diets including pasta waste in meal form (PWM) for quail. A total of 450 unsexed meat quail (Coturnix coturnix coturnix) were distributed into five treatments (0, 10, 20, 30, and 40% inclusion of PWM) in a completely randomized design with six replicates, each with 15 birds. The following rearing periods were evaluated: Phase 1 - 1 to 21 days; and period of 1 to 42 days. In Phase 1, the PWM levels did not influence feed intake (FI), and the PWM inclusion levels for optimal weight gain (WG) and feed conversion (FC) were estimated at 20.70% and 22.8%, respectively. In the cumulative period of 1 to 42 days, the PWM levels did not lead to differences in FI, WG, or FC. The yields of carcass and cuts were not influenced by the treatments; however, abdominal fat yield decreased as the PWM levels in the diets were increased. Economic analysis showed a reduction of the feeding cost in the studied phases. Pasta waste meal can be included up to the level of 40% without incurring losses in the performance or carcass yield of meat quail.

Target-based approach for osteoarthritis treatment.

There is still no definitive treatment for knee osteoarthritis (OA). We are certainly far from a consensus on the best form of treatment or on an effective treatment recommendation. There are reasons for the current equivocal treatment recommendations in the face of this very serious health problem. The greatest of these reasons, undoubtedly, is the great complexity of the factors involved in the development and progression of knee OA and the complex pathophysiology including mechanical, inflammatory, metabolic, post-traumatic, molecular, genetic, and psychological changes. For several years, an attempt has been made to correlate different patient phenotypes to different patterns of response to treatment, thus creating the possibility of developing specific treatments for certain groups of patients and theoretically allowing better treatment efficacy. However, in practice we still find totally different responses and evolutions even in individuals belonging to the same phenotype. Thus, classification by phenotypes, despite being an advance, is not sufficient. The present article proposes a fragmented look at each of the many factors or targets involved in the genesis and evolution of OA. Therefore, we propose not the treatment of OA per se but the management of an individual set of targets to achieve personalized OA management. We believe that, paradoxically, by fragmenting the view of the disease we will be able to treat our patients more holistically in an individualized way.

Carbohydrate Loading Practice in Bodybuilders: Effects on Muscle Thickness, Photo Silhouette Scores, Mood States and Gastrointestinal Symptoms.

A common practice among bodybuilders is the use of carbohydrate loading to improve physical appearance during competition, while limited documented data is available about this issue. The aim of the present study was to evaluate muscle thickness, mood states, gastrointestinal symptoms and subjective silhouette assessment following carbohydrate loading in bodybuilders. Twenty-four male bodybuilders were evaluated at the weighing period following three days of carbohydrate depletion (M1), and 24h of carbohydrate loading leading up to the competition (M2), stratified into: no carbohydrate load (NC, n = 9) and carbohydrate loading (CL, n =1 5). The silhouette scale, Brunel mood scale (BRUMS), muscle thickness (ultrasound), circumferences, and gastrointestinal symptoms (GIS) were evaluated at M1 and M2. The NC displayed no differences in muscle thickness and circumferences between M1 and M2. Body mass, muscle thickness (elbow flexors, a combination of biceps brachii/ brachialis muscle, and triceps brachii) and circumferences (chest, hip, thigh, arm, calves, and forearm) increased significantly (p < 0.05) in the CL at M2. There was a significant increase in photo silhouette scores (p < 0.05) in the CL at M2. There was no significant difference in mood states between groups or time. The most reported GIS was constipation: 7/9 (NC) and 9/15 (CL) during M1 and 6/9 (NC), and 5/15 (CL) at M2 with symptoms described as 'moderate' or 'severe'. Diarrhea was reported by 7/15 CL (4/15 as severe). These data suggest that carbohydrate loading may contribute to an acute increase in muscle volume and physical appearance, however, it needs to be better planned to minimize gastrointestinal symptoms in bodybuilders.

New insights into the function of melatonin and its role in metabolic disturbances.

INTRODUCTION: Melatonin is a pineal hormone that has acquired several unique modes of regulating the physiological effects in mammals due to its characteristic phylogenetic history. While melatonin exhibits immediate nocturnal effects, it also has next-day prospective effects that take place in the absence of this hormone. Besides that, the daily repetition and the annual variation in the duration of its synthesis determine its circadian and seasonal effects that characterize melatonin as a chronobiotic, a molecule that encodes time to the internal environment. Additionally, it presents transgenerational effects that are important for fetal programming, leading to a balanced energy metabolism in the adult life. AREAS COVERED: Physiology, pathophysiology and therapeutic value of melatonin in metabolism and metabolic disorders. EXPERT OPINION: The typical mechanisms of action of melatonin (immediate, prospective, chronobiotic and transgenerational) should be considered to adequately understand its physiological effects on the regulation of metabolism in humans and, as a result, to understand the metabolic pathophysiological consequences caused by its synthesis and/or signaling disturbances. That points to the importance of a broader understanding of melatonin actions, besides the classical endocrinological point of view, that would allow the clinician/research to proper interpret its role in health maintenance.

Analysis of Vertical Misfit of Crowns Fabricated with CAD/CAM Technology using Two Scanning Techniques: Direct and Indirect.

AIM: The study evaluated the marginal vertical misfit of feldspathic ceramic crowns fabricated by the computer-aided design (CAD)/computer-aided manufacturing (CAM) technology and compared the two methods of scanning techniques: direct digital impression and indirect digital impression. MATERIALS AND METHODS: The titanium specimens were divided into two groups: scanning with the direct digital impression (DDI) at the milled prosthetic abutment level and indirect digital impression (IDI) at the cast model and after milled feldspathic ceramics blocks. Vertical marginal misfit was analyzed. The t-test was used for the analysis of the comparison factor between the groups and the one-way analysis of variance (ANOVA) test, and post hoc Tukey test was used to compare the variance of crown analysis regions within the group. A significance level of 5% was considered for the analyses. RESULTS: There was no significant difference in vertical marginal misfit between the groups of DDI and IDI (p = 0.345). In relation to each region measured within the studied groups, it was observed the similarity between the six regions analyzed in the DDI group (p >0.05) and IDI group, a significant difference between two areas. CONCLUSION: The vertical marginal adaptation was similar between digital scanning methods. Based on the data evaluated, vertical marginal adaptation indices were within acceptable clinical standards. CLINICAL SIGNIFICANCE: The direct digital scanning in unit bodies was reliable, pointing that the coating of titanium dioxide in the titanium abutment did not negatively influence the vertical marginal adaptation of the feldspathic ceramic crowns.

Strength training improves the respiratory muscle strength and quality of life of elderly with Parkinson disease.

BACKGROUND: The progression of Parkinson disease can lead to respiratory muscle weakness, reduced peak expiratory flow and quality of life (QoL). The aim was to evaluate the effects of strength training on levels of respiratory muscle strength, peak expiratory flow and QoL of elderly with Parkinson disease. METHODS: A total of 28 patients were randomized into one of two groups: the control group (CG) comprised 16 participants, and the strength training group (STG) comprised 12 participants. All subjects maintained the standard pharmacological treatment for Parkinson disease, and the intervention group participated in a 16-week strength training program. The primary outcome was the measurement of respiratory muscle strength. RESULTS: The STG showed improved values of maximum inspiratory pressures (36.11±11.82 to 52.94±24.17; P=0.01), maximum expiratory pressures (56.67±22.08 to 71.04±33.71; P=0.03) and QoL (41.75±20.33 to 34±20.92; P=0.0054); there was no significant difference in the peak expiratory flow (336.11±198.04 to 380±229.57; P=0.09). The CG showed significantly decreased values of peak expiratory flow (336.88±183.40 to 279.37±125.12, P=0.02) and non-significant changes in the other variables. CONCLUSIONS: Sixteen weeks of strength training improves the inspiratory and expiratory muscle strength and QoL of elderly with Parkinson disease. These findings suggest that strength training could be considered an adjunct therapeutic intervention for elderly with Parkinson disease.

Alpha spending for historical versus surveillance Poisson data with CMaxSPRT.

Sequential analysis hypothesis testing is now an important tool for postmarket drug and vaccine safety surveillance. When the number of adverse events accruing in time is assumed to follow a Poisson distribution, and if the baseline Poisson rate is assessed only with uncertainty, the conditional maximized sequential probability ratio test, CMaxSPRT, is a formal solution. CMaxSPRT is based on comparing monitored data with historical matched data, and it was primarily developed under a flat signaling threshold. This paper demonstrates that CMaxSPRT can be performed under nonflat thresholds too. We pose the discussion in the light of the alpha spending approach. In addition, we offer a rule of thumb for establishing the best shape of the signaling threshold in the sense of minimizing expected time to signal and expected sample size. An example involving surveillance for adverse events after influenza vaccination is used to illustrate the method.

A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

Dissipative structures induced by photoisomerization in a dye-doped nematic liquid crystal layer.

Order-disorder phase transitions driven by temperature or light in soft matter materials exhibit complex dissipative structures. Here, we investigate the spatio-temporal phenomena induced by light in a dye-doped nematic liquid crystal layer. Experimentally, for planar anchoring of the nematic layer and high enough input power, photoisomerization processes induce a nematic-isotropic phase transition mediated by interface propagation between the two phases. In the case of a twisted nematic layer and for intermediate input power, the light induces a spatially modulated phase, which exhibits stripe patterns. The pattern originates as an instability mediated by interface propagation between the modulated and the homogeneous nematic states. Theoretically, the phase transition, emergence of stripe patterns and front dynamics are described on the basis of a proposed model for the dopant concentration coupled with the nematic order parameter. Numerical simulations show quite a fair agreement with the experimental observations.This article is part of the theme issue 'Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology (part 2)'.

Nutritional Evaluation of Non-Conventional Vegetables in Brazil.

The objective of this study was to characterize the nutritional compounds of interest present in vegetables known as non-conventional, in Brazil. The following evaluations were carried out: antioxidant activity, phenolic compounds, vitamin C, calories, carbohydrates, humidity, lipids, proteins, fiber, acidity and quantification of minerals (P, K, Ca, Mg, S, Cu, Fe, Mn, Zn and B). The species studied were Amaranthus hybridus L., Amaranthus viridis L., Basella alba L., Eryngium campestre L., Hibiscus sabdariffa L., Lactuca canadensis L., Rumex acetosa L., Stachys byzantina K. Koch, Tropaeolum majus L. and Xanthosoma sagittifolium L. Representative samples of plant structures of interest were harvested from each species suitable for human consumption such as leaves, flowers and flower buds. The results were submitted to multivariate analysis - principal components analysis (PCA). All the species present nutritional compounds of interest in different levels among the evaluated structures.

Palmitoleic acid (16:1n7) increases oxygen consumption, fatty acid oxidation and ATP content in white adipocytes.

BACKGROUND: We have recently demonstrated that palmitoleic acid (16:1n7) increases lipolysis, glucose uptake and glucose utilization for energy production in white adipose cells. In the present study, we tested the hypothesis that palmitoleic acid modulates bioenergetic activity in white adipocytes. METHODS: For this, 3 T3-L1 pre-adipocytes were differentiated into mature adipocytes in the presence (or absence) of palmitic (16:0) or palmitoleic (16:1n7) acid at 100 or 200 µM. The following parameters were evaluated: lipolysis, lipogenesis, fatty acid (FA) oxidation, ATP content, oxygen consumption, mitochondrial mass, citrate synthase activity and protein content of mitochondrial oxidative phosphorylation (OXPHOS) complexes. RESULTS: Treatment with 16:1n7 during 9 days raised basal and isoproterenol-stimulated lipolysis, FA incorporation into triacylglycerol (TAG), FA oxidation, oxygen consumption, protein expression of subunits representing OXPHOS complex II, III, and V and intracellular ATP content. These effects were not observed in adipocytes treated with 16:0. CONCLUSIONS: Palmitoleic acid, by concerted action on lipolysis, FA esterification, mitochondrial FA oxidation, oxygen consumption and ATP content, does enhance white adipocyte energy expenditure and may act as local hormone.

Ethylene signaling triggered by low concentrations of ascorbic acid regulates biomass accumulation in Arabidopsis thaliana.

Ascorbic acid (AA) is a major redox buffer in plant cells. The role of ethylene in the redox signaling pathways that influence photosynthesis and growth was explored in two independent AA deficient Arabidopsis thaliana mutants (vtc2-1 and vtc2-4). Both mutants, which are defective in the AA biosynthesis gene GDP-L-galactose phosphorylase, produce higher amounts of ethylene than wt plants. In contrast to the wt, the inhibition of ethylene signaling increased leaf conductance, photosynthesis and dry weight in both vtc2 mutant lines. The AA-deficient mutants showed altered expression of genes encoding proteins involved in the synthesis/responses to phytohormones that control growth, particularly auxin, cytokinins, abscisic acid, brassinosterioids, ethylene and salicylic acid. These results demonstrate that AA deficiency modifies hormone signaling in plants, redox-ethylene interactions providing a regulatory node controlling shoot biomass accumulation.

A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals.

OBJECTIVE: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. SUBJECTS AND METHODS: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. RESULTS: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. CONCLUSIONS: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.