Mechanosensory neuron regeneration in adult Drosophila.

Auditory and vestibular mechanosensory hair cells do not regenerate following injury or aging in the adult mammalian inner ear, inducing irreversible hearing loss and balance disorders for millions of people. Research on model systems showing replacement of mechanosensory cells can provide mechanistic insights into developing new regenerative therapies. Here, we developed lineage tracing systems to reveal the generation of mechanosensory neurons in the Johnston's organ (JO) of intact adult Drosophila, which are the functional counterparts to hair cells in vertebrates. New JO neurons develop cilia and target central brain circuitry. Unexpectedly, mitotic recombination clones point to JO neuron self-replication as a likely source of neuronal plasticity. This mechanism is further enhanced upon treatment with experimental and ototoxic compounds. Our findings introduce a new platform to expedite research on mechanisms and compounds mediating mechanosensory cell regeneration, with nascent implications for hearing and balance restoration.

Effect of alpha linolenic acid on membrane fluidity and respiration of liver mitochondria in normoglycemic and diabetic Wistar rats.

The omega 3 fatty acids (ω3FA) have been recommended for the treatment of Type 2 Diabetes Mellitus (T2DM) and its complications, but there are studies questioning those beneficial effects. In this research, we supplemented the short-chain ω3FA, alpha-linolenic acid (ALA), to a model of rats with T2DM and normoglycemic controls, for 5 months. We were mainly interested in studying the effects of diabetes and ALA on the physicochemical properties of mitochondrial membranes and the consequences on mitochondrial respiration. We found that the Respiratory Control (RC) of diabetic rats was 46% lower than in control rats; in diabetic rats with ALA supplement, it was only 23.9% lower, but in control rats with ALA supplement, the RC was 29.5% higher, apparently improving. Diabetes also decreased the membrane fluidity, changed the thermotropic characteristics of membranes, and increased the proportion of saturated fatty acids. ALA supplement partially kept regulated the physicochemical properties of mitochondrial membranes in induced rats. Our data indicate that diabetes decreased the membrane fluidity through changes in the fatty acids composition that simultaneously affected the RC, which means that the mitochondrial respiration is highly dependent on the physicochemical properties of the membranes. Simultaneously, it was followed the effects of ALA on the progress of diabetes and we found also that the supplementation of ALA helped in controlling glycaemia in rats induced to T2DM; however, in control non-induced rats, the supplementation of ALA derived in characteristics of initial development of diabetes.

The role of nitric oxide signaling in pulmonary circulation of high- and low-altitude newborn sheep under basal and acute hypoxic conditions.

Nitric oxide (NO) is the main vasodilator agent that drives the rapid decrease of pulmonary vascular resistance for the respiratory onset during the fetal to neonatal transition. Nevertheless, the enhanced NO generation by the neonatal pulmonary arterial endothelium does not prevent development of hypoxic pulmonary hypertension in species without an evolutionary story at high altitude. Therefore, this study aims to describe the limits of the NO function at high-altitude during neonatal life in the sheep as an animal model without tolerance to perinatal hypoxia. We studied the effect of blockade of NO synthesis with l-NAME in the cardiopulmonary response of lowland (580 m) and highland (3600 m) newborn lambs basally and under an episode of acute hypoxia. We also determined the pulmonary expression of proteins that mediate the actions of the NO vasodilator pathway in the pulmonary vasoactive tone and remodeling. We observed an enhanced nitrergic function in highland lambs under basal conditions, evidenced as a markedly greater increase in basal mean pulmonary arterial pressure (mPAP) and resistance (PVR) under blockade of NO synthesis. Further, acute hypoxic challenge in lowland lambs infused with l-NAME markedly increased their mPAP and PVR to values greater than baseline, whilst in highland animals under NO synthesis blockade, these variables did not show additional increase in response to low PO2. Highland animals showed increased pulmonary RhoA expression, decreased PSer188-RhoA fraction, increased PSer311-p65-NFÒ›ß fraction and up-regulated smooth muscle α-actin, relative to lowland controls. Taken together our data suggest that NO-mediated vasodilation is important to keep a low pulmonary vascular resistance under basal conditions and acute hypoxia at low-altitude. At high-altitude, the enhanced nitrergic signaling partially prevents excessive pulmonary hypertension but does not protect against acute hypoxia. The decreased vasodilator efficacy of nitrergic tone in high altitude lambs could be in part due to increased RhoA signaling that opposes to NO action in the hypoxic pulmonary circulation.

Appetitive behavior of the honey bee Apis mellifera in response to phenolic compounds naturally found in nectars.

The honey bee is the most frequently used species in pollination services for diverse crops. In onion crops (Allium cepa), however, bees avoid visiting certain varieties, being attracted differently to male sterile (MS) and fertile (OP) lines. These differences might be based on the phenolic profiles of the cultivars' nectars. To understand the relationship between nectar composition and pollinator attraction to different onion lines, we tested sensory and cognitive abilities and palatability in honey bees exposed to MS and OP onion nectars and sugar solutions mimicking them. We evaluated the proboscis extension response (PER) after antennal contact (unconditioned response) to MS or OP onion nectars, finding no statistical differences, which indicates similar gustatory perception for the two nectars. We also performed food uptake assays to test palatability of different artificial nectars, considering their flavonoids and potassium content. The presence of potassium decreased the palatability of the artificial nectars. Finally, we evaluated the bees' cognitive abilities when the reward (unconditioned stimulus) offered during conditioning PER assays presents differences in composition. We found that potassium by itself impaired learning; however, such impairment was even higher when naringenin and quercetin were added in the unconditioned stimulus (MS nectar mimic). Interestingly, potassium together with luteolin (OP nectar mimic) improved learning. Our study demonstrates that the differences in the nectars' flavonoid profiles combined with their high potassium content could explain the previously reported differences in attractiveness between onion lines, suggesting an important role of nectar compounds other than sugars for the attractiveness of flowers to pollinators.

The role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn llamas.

KEY POINTS: Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas. We show that high- compared to lowland newborn llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn llama. ABSTRACT: Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas. The cardiopulmonary function of newborn llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, as NO blockade reverted the effect and the pulmonary arterial dilatator response to SNP was significantly enhanced in highland neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were lower in high-altitude llamas. Conversely, MYPT1 was up-regulated whilst PSer695-MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were insufficient to prevent pulmonary arterial remodelling. Combined, the data strongly support that in the highland newborn llama reduced ROCK, increased MYPT1 expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic pulmonary hypertensive responses may be an adaptive mechanism to life at high altitude.

Liver mitochondrial membrane fluidity at early development of diabetes and its correlation with the respiration.

The biological membranes are important in cell function but, during development of diseases such as diabetes, they are impaired. Consequently, membrane-associated biological processes are impaired as well. The mitochondria are important organelles where oxidative phosphorylation takes place, a process closely related with the membranes. In general, it is accepted that the development process of diabetes decreases membrane fluidity. However, in some cases, it has been found to increase membrane fluidity of mitochondria but to decrease the Respiratory Control (RC) index. In this study we found an increase of membrane fluidity and an increase of the RC at an early phase of the development of a type 2 diabetes model. We measured the lipoperoxidation, analyzed the fatty acids composition by gas chromatography, and assessed membrane fluidity using three fluorescent monitors located at different depths inside the bilayer, dipyrenilpropane (DPyP), diphenylhexatriene (DPH), and trimethylammonium diphenylhexatriene (TMA-DPH). Our findings indicate that in the initial stage of diabetes development, when lipoperoxidation still is not significant, the membrane fluidity of liver mitochondria increases because of the increment in the unsaturated to saturated fatty acids ratio (U/S), thus producing an increase of the RC. The membrane fluidity is not the same at all depths in the bilayer. Contrary to the results obtained in mitochondria, the diabetes induced a decrease in the U/S fatty acids ratio of liver total lipids, indicating that the mitochondria might have an independent mechanism for regulating its fatty acids composition.

2-AMINOETHYLDIPHENYLBORINATE MODIFIES THE PULMONARY CIRCULATION IN PULMONARY HYPERTENSIVE NEWBORN LAMBS WITH PARTIAL GESTATION AT HIGH ALTITUDE.

Calcium signaling through store operated channels (SOC) is involved in hypoxic pulmonary hypertension. We determined whether a treatment with 2-aminoethyldiphenylborinate (2-APB), a compound with SOC blocker activity, reduces pulmonary hypertension and vascular remodeling. Twelve newborn lambs exposed to perinatal chronic hypoxia were studied, 6 of them received a 2-APB treatment and the other 6 received vehicle treatment, for 10 days in both cases. Throughout this period, we recorded cardiopulmonary variables and on day 11 we evaluated the response to an acute hypoxic challenge. Additionally, we assessed the vasoconstrictor and vasodilator function in isolated pulmonary arteries as well as their remodeling in lung slices. 2-APB reduced pulmonary arterial pressure at the third and tenth days, cardiac output between the fourth and eighth days, and pulmonary vascular resistance at the tenth day of treatment. The pulmonary vasoconstrictor response to acute hypoxia was reduced by the end of treatment. 2-APB also decreased maximal vasoconstrictor response to the thromboxane mimetic U46619 and endothelin-1 and increased maximal relaxation to 8-Br-cGMP. The maximal relaxation and potency to phosphodiesterase-5 and Rho-kinase inhibition with sildenafil and fasudil respectively, were also increased. Finally, 2-APB reduced the medial and adventitial layers' thickness, the expression of α-actin and the percentage of Ki67+ nuclei of small pulmonary arteries. Taken together, our results indicate that 2-APB reduces pulmonary hypertension, vasoconstrictor responses and pathological remodeling in pulmonary hypertensive lambs. We conclude that SOC targeting may be a useful strategy for the treatment of neonatal pulmonary hypertension, however, further testing of specific blockers is needed.

Enhanced Stature in the Elderly: The Immediate Impact of Acute Postural Exercises.

This study investigates the immediate effects of acute postural exercises on the stature of seniors, focusing on changes in both upright and supine stature measurements. A within-subject design with repeated measures was applied, involving seniors participating in continuous exercises aimed at enhancing core musculature strength and promoting muscle relaxation. Stature measurements were recorded pre- and post-exercise in both upright and supine positions, alongside assessments of body mass index (BMI) category classifications. The results revealed a post-exercise increase in stature ranging from 0.9 to 6.0 cm and from 0.2 to 7.2 cm in upright and supine positions, respectively, with an average increase of approximately 3.5 cm in both upright and supine positions. Statistically significant and clinically relevant changes were observed (p < 0.05), including a modification of BMI by approximately two units, reclassifying 55% of participants from overweight or obese to normal weight or overweight. Furthermore, the similarity between post-exercise upright stature and pre-exercise supine stature suggested that the supine position might provide a more accurate measure of stature in seniors. Conclusively, acute postural exercises have an immediate positive impact on the stature of seniors, suggesting their potential utility in clinical settings for accurate stature measurement. However, BMI results should be interpreted with caution because they are only related to the acute change in stature and therefore may lead to the misinterpretation of the study findings, so future studies focused on evaluating the chronic effect of postural exercises integration on the health outcomes of older adults are needed to demonstrate their potential utility in clinical settings to improve postural health and general well-being.

Store-operated channels in the pulmonary circulation of high- and low-altitude neonatal lambs.

We determined whether store-operated channels (SOC) are involved in neonatal pulmonary artery function under conditions of acute and chronic hypoxia, using newborn sheep gestated and born either at high altitude (HA, 3,600 m) or low altitude (LA, 520 m). Cardiopulmonary variables were recorded in vivo, with and without SOC blockade by 2-aminoethyldiphenylborinate (2-APB), during basal or acute hypoxic conditions. 2-APB did not have effects on basal mean pulmonary arterial pressure (mPAP), cardiac output, systemic arterial blood pressure, or systemic vascular resistance in both groups of neonates. During acute hypoxia 2-APB reduced mPAP and pulmonary vascular resistance in LA and HA, but this reduction was greater in HA. In addition, isolated pulmonary arteries mounted in a wire myograph were assessed for vascular reactivity. HA arteries showed a greater relaxation and sensitivity to SOC blockers than LA arteries. The pulmonary expression of two SOC-forming subunits, TRPC4 and STIM1, was upregulated in HA. Taken together, our results show that SOC contribute to hypoxic pulmonary vasoconstriction in newborn sheep and that SOC are upregulated by chronic hypoxia. Therefore, SOC may contribute to the development of neonatal pulmonary hypertension. We propose SOC channels could be potential targets to treat neonatal pulmonary hypertension.

Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis.

BACKGROUND & AIMS: We performed a meta-analysis to evaluate the effects of ursodeoxycholic acid (UDCA) on pruritus, liver test results, and outcomes of babies born to women with intrahepatic cholestasis of pregnancy (ICP). METHODS: We performed a systematic review of 9 published, randomized controlled trials (3 double blinded) that compared the effects of UDCA to other drugs, placebo, or no specific treatment (controls) in patients with ICP. We analyzed data from 454 patients: 207 received only UDCA, 70 received only placebo, 42 received cholestyramine, 36 received dexamethasone for 1 week and then placebo for 2 weeks, 65 received S-adenosyl-methionine, and 34 received no specific treatment. To achieve consistency among end points, a standard questionnaire was sent to all corresponding authors. For each end point, we performed pooled analysis that compared the effects of UDCA with those of all controls and UDCA with those of placebos. RESULTS: In pooled analyses that compared UDCA with all controls, UDCA was associated with total resolution of pruritus (odds ratio [OR], 0.23; 95% confidence interval [CI], 0.07-0.74; P < .01), reduced pruritis (OR, 0.27; 95% CI, 0.13-0.55; P < .0001), normalization of serum levels of alanine aminotransferase (ALT) (OR, 0.23; 95% CI, 0.10-0.50; P < .001), decreased serum level of ALT (OR, 0.24; 95% CI, 0.11-0.52; P < .0001), reduced serum levels of bile acids (OR, 0.37; 95% CI, 0.19-0.75; P < .001), fewer premature births (OR, 0.44; 95% CI, 0.24-0.79; P < .01), reduced fetal distress (OR, 0.46; 95% CI, 0.25-0.86; P < .01), less frequent respiratory distress syndrome (OR, 0.30; 95% CI, 0.12-0.74; P < .01), and fewer neonates in the intensive care unit (OR, 0.49; 95% CI, 0.25-0.98; P = .046). In pooled analyses that compared the effects of UDCA with placebo, UDCA reduced pruritus (OR, 0.21; 95% CI, 0.07-0.62; P < .01), normalized (OR, 0.18; 95% CI, 0.06-0.52; P < .001) or decreased serum levels of ALT (OR, 0.12; 95% CI, 0.05-0.31; P < .0001), and reduced serum levels of bile acids (OR, 0.30; 95% CI, 0.12-0.73; P < .01). CONCLUSIONS: Based on a meta-analysis, UDCA is effective in reducing pruritus and improving liver test results in patients with ICP; UDCA therapy might also benefit fetal outcomes.

Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria.

Impaired complex III activity and reactive oxygen species (ROS) generation in mitochondria have been identified as key events leading to renal damage during diabetes. Due to its high content of oleic acid and antioxidants, we aimed to test whether avocado oil may attenuate the alterations in electron transfer at complex III induced by diabetes by a mechanism related with increased resistance to lipid peroxidation. 90 days of avocado oil administration prevented the impairment in succinate-cytochrome c oxidoreductase activity caused by streptozotocin-induced diabetes in kidney mitochondria. This was associated with a protection against decreased electron transfer through high potential chain in complex III related to cytochromes c + c1 loss. During Fe(2+)-induced oxidative stress, avocado oil improved the activities of complexes II and III and enhanced the protection conferred by a lipophilic antioxidant against damage by Fe(2+). Avocado oil also decreased ROS generation in Fe(2+)-damaged mitochondria. Alterations in the ratio of C20:4/C18:2 fatty acids were observed in mitochondria from diabetic animals that not were corrected by avocado oil treatment, which yielded lower peroxidizability indexes only in diabetic mitochondria although avocado oil caused an augment in the total content of monounsaturated fatty acids. Moreover, a protective effect of avocado oil against lipid peroxidation was observed consistently only in control mitochondria. Since the beneficial effects of avocado oil in diabetic mitochondria were not related to increased resistance to lipid peroxidation, these effects were discussed in terms of the antioxidant activity of both C18:1 and the carotenoids reported to be contained in avocado oil.

Analytical tools for elucidating the biological role of melatonin in plants by LC-MS/MS.

Melatonin (MT) presence in higher plants was recently discovered and the knowledge of its function in vivo is limited. Several studies have recently shown the occurrence of MT and related compounds in grapes and wines. The analysis of MT in plants and foods represents a highly challenging task due to its wide concentration range, the difficulty in the selection of the extraction solvents because of its amphipathic nature, and the fact that it reacts quickly with other matrix components. Thus, sample processing factors; preparation/cleanup procedures; and chromatographic/detection parameters, such as HILIC and reverse phase (C(8) and C(18)) chromatographic modes, ESI, and atmospheric pressure chemical ionization (APCI) in both negative and positive modes were evaluated. Taken together, we have demonstrated that optimal conditions were quite different for each of the matrices under study. A sonication-mediated extraction step was necessary for grape skin (100% v/v methanol) and plant tissues (50% v/v methanol), while wine and must required a SPE preconcentration step. HILIC-(+) APCI ionization was better for MT standards, while C(8) -(+) APCI was the best choice for grape skin and C(18) -(+ESI) was suitable for wine. On the other hand, C(8) -(+)ESI was the most appropriate for vegetal tissues of Arabidopsis thaliana. Proposed methods were validated and the LODs were in the low picogram levels range. The optimized approaches were applied to the determination of MT and its isomer in different vegetal/food samples; levels found within the range: 4.9-440 ng/g.

A putative siderophore receptor of Gallibacterium anatis 12656-12 under Fur control also binds hemoglobin.

Pasteurellaceae family members obtain iron directly from host proteins or through siderophore-dependent mechanisms. Although Gallibacterum anatis expresses different virulence factors, its response to growth under iron restriction is unknown. G. anatis cultured in the presence of 2,2'-dipyridyl, up-expressed an approximately 65 kDa protein and repressed the expression of a 70 kDa protein. MALDI-TOF analysis of those proteins indicated homology with CirA (65 kDa), a protein involved in iron-siderophore acquisition in Mannheimia succinoproducens and a TonB-dependent receptor (70 kDa protein), a protein that binds chicken hemoglobin; however, G. anatis siderophore production was not detected by chromo azurol S (CAS)-BHI agar determination. This putative G. anatis siderophore receptor is under Fur control, but not the hemoglobin binding protein, as observed in G. anatis 12656-12 fur mutant (Ω fur 126.13) grown in the presence or not of 2,2'-dipyridyl. The addition of FeCl3 to the culture medium diminished the growth and biofilm production in approximately 30% and 35%, respectively, in the wild-type strain, but the growth of Ω fur 126.13 strain was not affected and biofilm production increased in 35%. G. anatis Ω fur 126.13 presented lower virulence when it was inoculated to 35-day-old chickens in comparison to the wild-type strain. The induction of more than one iron uptake mechanism could benefit pathogenic microorganisms such as Gallibacterium.

Damage-responsive neuro-glial clusters coordinate the recruitment of dormant neural stem cells in Drosophila.

Recruitment of stem cells is crucial for tissue repair. Although stem cell niches can provide important signals, little is known about mechanisms that coordinate the engagement of disseminated stem cells across an injured tissue. In Drosophila, adult brain lesions trigger local recruitment of scattered dormant neural stem cells suggesting a mechanism for creating a transient stem cell activation zone. Here, we find that injury triggers a coordinated response in neuro-glial clusters that promotes the spread of a neuron-derived stem cell factor via glial secretion of the lipocalin-like transporter Swim. Strikingly, swim is induced in a Hif1-α-dependent manner in response to brain hypoxia. Mammalian Swim (Lcn7) is also upregulated in glia of the mouse hippocampus upon brain injury. Our results identify a central role of neuro-glial clusters in promoting neural stem cell activation at a distance, suggesting a conserved function of the HIF1-α/Swim/Wnt module in connecting injury-sensing and regenerative outcomes.

The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs.

Calcium signaling is key for the contraction, differentiation, and proliferation of pulmonary arterial smooth muscle cells. Furthermore, calcium influx through store-operated channels (SOCs) is particularly important in the vasoconstrictor response to hypoxia. Previously, we found a decrease in pulmonary hypertension and remodeling in normoxic newborn lambs partially gestated under chronic hypoxia, when treated with 2-aminoethyldiphenyl borinate (2-APB), a non-specific SOC blocker. However, the effects of 2-APB are unknown in neonates completely gestated, born, and raised under environmental hypoxia. Accordingly, we studied the effects of 2-APB-treatment on the cardiopulmonary variables in lambs under chronic hypobaric hypoxia. Experiments were done in nine newborn lambs gestated, born, and raised in high altitude (3,600 m): five animals were treated with 2-APB [intravenous (i.v.) 10 mg kg-1] for 10 days, while other four animals received vehicle. During the treatment, cardiopulmonary variables were measured daily, and these were also evaluated during an acute episode of superimposed hypoxia, 1 day after the end of the treatment. Furthermore, pulmonary vascular remodeling was assessed by histological analysis 2 days after the end of the treatment. Basal cardiac output and mean systemic arterial pressure (SAP) and resistance from 2-APB- and vehicle-treated lambs did not differ along with the treatment. Mean pulmonary arterial pressure (mPAP) decreased after the first day of 2-APB treatment and remained lower than the vehicle-treated group until the third day, and during the fifth, sixth, and ninth day of treatment. The net mPAP increase in response to acute hypoxia did not change, but the pressure area under the curve (AUC) during hypoxia was slightly lower in 2-APB-treated lambs than in vehicle-treated lambs. Moreover, the 2-APB treatment decreased the pulmonary arterial wall thickness and the α-actin immunoreactivity and increased the luminal area with no changes in the vascular density. Our findings show that 2-APB treatment partially reduced the contractile hypoxic response and reverted the pulmonary vascular remodeling, but this is not enough to normalize the pulmonary hemodynamics in chronically hypoxic newborn lambs.

Highest Defoliation Tolerance in Amaranthus cruentus Plants at Panicle Development Is Associated With Sugar Starvation Responses.

Defoliation tolerance (DT) in Amaranthus cruentus is known to reach its apex at the panicle emergence (PE) phase and to decline to minimal levels at flowering (FL). In this study, defoliation-induced changes were recorded in the content of non-structural carbohydrates and raffinose family oligosaccharides (RFOs), and in the expression and/or activity of sugar starvation response-associated genes in plants defoliated at different vegetative and reproductive stages. This strategy identified sugar-starvation-related factors that explained the opposite DT observed at these key developmental stages. Peak DT at PE was associated with increased cytosolic invertase (CI) activity in all organs and with the extensive induction of various class II trehalose-phosphate synthase (TPS) genes. Contrariwise, least DT at FL coincided with a sharp depletion of starch reserves and with sucrose (Suc) accumulation, in leaves and stems, the latter of which was consistent with very low levels of CI and vacuolar invertase activities that were not further modified by defoliation. Increased Suc suggested growth-inhibiting conditions associated with altered cytosolic Suc-to-hexose ratios in plants defoliated at FL. Augmented cell wall invertase activity in leaves and roots, probably acting in a regulatory rather than hydrolytic role, was also associated with minimal DT observed at FL. The widespread contrast in gene expression patterns in panicles also matched the opposite DT observed at PE and FL. These results reinforce the concept that a localized sugar starvation response caused by C partitioning is crucial for DT in grain amaranth.

Milk, social acceptance of a new food in Europe: Catalonia, 19th-20th centuries.

In this article we analyse the time course of the consumption of fresh milk in different regions of Europe between the 1870s and 1930s. Working from the case of Catalonia, we affirm that the increasing consumption of milk in that period must be especially linked to the spreading of new scientific knowledge in microbiology and nutrition that followed Pasteur's discoveries. We particularly highlight the information dissemination activities in this direction carried out by health sector professionals (medical doctors and pharmacists), governing local institutions and the milk industry. The initiatives developed by these groups changed people's preferences--fresh milk became accepted as a necessary food-stuff, and demand for it increased. However, the evolution of consumption was not the same in all regions of Europe due to their different environmental and agronomic conditions.

Characterization of Extremely Drug-Resistant and Hypervirulent Acinetobacter baumannii AB030.

Acinetobacter baumannii is an important nosocomial bacterial pathogen. Multidrug-resistant isolates of A. baumannii are reported worldwide. Some A. baumannii isolates display resistance to nearly all antibiotics, making treatment of infections very challenging. As the need for new and effective antibiotics against A. baumannii becomes increasingly urgent, there is a need to understand the mechanisms of antibiotic resistance and virulence in this organism. In this work, comparative genomics was used to understand the mechanisms of antibiotic resistance and virulence in AB030, an extremely drug-resistant and hypervirulent strain of A. baumannii that is a representative of a recently emerged lineage of A. baumannii International Clone V. In order to characterize AB030, we carried out a genomic and phenotypic comparison with LAC-4, a previously described hyper-resistant and hypervirulent isolate. AB030 contains a number of antibiotic resistance- and virulence-associated genes that are not present in LAC-4. A number of these genes are present on mobile elements. This work shows the importance of characterizing the members of new lineages of A. baumannii in order to determine the development of antibiotic resistance and virulence in this organism.

Neuronal Nitric Oxide Synthase in Cultured Cerebellar Bergmann Glia: Glutamate-Dependent Regulation.

Glutamate exerts its actions through the activation of membrane receptors expressed in neurons and glia cells. The signaling properties of glutamate transporters have been characterized recently, suggesting a complex array of signaling transactions triggered by presynaptic released glutamate. In the cerebellar molecular layer, glutamatergic synapses are surrounded by Bergmann glia cells, compulsory participants of glutamate turnover and supply to neurons. Since a glutamate-dependent increase in cGMP levels has been described in these cells and the nitric oxide-cGMP signaling cascade increases their glutamate uptake activity, we describe here the Bergmann glia expression of neuronal nitric oxide synthetase. An augmentation of neuronal nitric oxide synthase was found upon glutamate exposure. This effect is mediated by glutamate transporters and is related to an increase in the stability of the enzyme. These results strengthen the notion of a complex regulation of glial glutamate uptake that supports neuronal glutamate signaling.