A high-density narrow-field inhibitory retinal interneuron with direct coupling to Müller glia.

Amacrine cells are interneurons composing the most diverse cell class in the mammalian retina. They help encode visual features such as edges or directed motion by mediating excitatory and inhibitory interactions between input (i.e. bipolar) and output (i.e. ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, metabolic regulation and neurovascular control. Here, we report that in mouse retina (of either sex), an abundant, though previously unstudied inhibitory amacrine cell is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed chemical synapses with known retinal cell types and extensive associations with Müller glia, the processes of which often completely ensheathe the neurites of this amacrine cell. Microinjecting small tracer molecules into the somas of these amacrine cells led to selective labelling of nearby Müller glia, leading us to suggest the name "Müller glia-coupled amacrine cell," or MAC. Our data also indicate that MACs release glycine at conventional chemical synapses, and viral retrograde transsynaptic tracing from the dorsal lateral geniculate nucleus (dLGN) showed selective connections between MACs and a subpopulation of RGC types. Visually-evoked responses revealed a strong preference for light increments; these "ON" responses were primarily mediated by excitatory chemical synaptic input and direct electrical coupling with other cells. This initial characterization of the MAC provides the first evidence for neuron-glia coupling in the mammalian retina and identifies the MAC as a potential link between inhibitory processing and glial function.Significance Statement:Gap junctions between pairs of neurons or glial cells are commonly found throughout the nervous system and play multiple roles, including electrical coupling and metabolic exchange. In contrast, gap junctions between neurons and glia cells have rarely been reported and are poorly understood. Here we report the first evidence for neuron-glia coupling in the mammalian retina, specifically between an abundant (but previously unstudied) inhibitory interneuron and Müller glia. Moreover, viral tracing, optogenetics and serial electron microscopy provide new information about the neuron's synaptic partners and physiological responses.

Distinct plastid fructose bisphosphate aldolases function in photosynthetic and non-photosynthetic metabolism in Arabidopsis.

Plastid metabolism is critical in both photoautotrophic and heterotrophic plant cells. In chloroplasts, fructose-1,6-bisphosphate aldolase (FBA) catalyses the formation of both fructose 1,6-bisphosphate and sedoheptulose 1,7-bisphosphate within the Calvin-Benson cycle. Three Arabidopsis genes, AtFBA1-AtFBA3, encode plastidial isoforms of FBA, but the contribution of each isoform is unknown. Phylogenetic analysis indicates that FBA1 and FBA2 derive from a recently duplicated gene, while FBA3 is a more ancient paralog. fba1 mutants are phenotypically indistinguishable from the wild type, while both fba2 and fba3 have reduced growth. We show that FBA2 is the major isoform in leaves, contributing most of the measurable activity. Partial redundancy with FBA1 allows both single mutants to survive, but combining both mutations is lethal, indicating a block of photoautotrophy. In contrast, FBA3 is expressed predominantly in heterotrophic tissues, especially the leaf and root vasculature, but not in the leaf mesophyll. We show that the loss of FBA3 affects plastidial glycolytic metabolism of the root, potentially limiting the biosynthesis of essential compounds such as amino acids. However, grafting experiments suggest that fba3 is dysfunctional in leaf phloem transport, and we suggest that a block in photoassimilate export from leaves causes the buildup of high carbohydrate concentrations and retarded growth.

Comparative Proteomic Analysis of Plant Acclimation to Six Different Long-Term Environmental Changes.

Plants are constantly challenged in their natural environment by a range of changing conditions. We investigated the acclimation processes and adaptive plant responses to various long-term mild changes and compared them directly within one experimental set-up. Arabidopsis thaliana plants were grown in hydroponic culture for 10 d under controlled abiotic stress (15°C, 25°C, salt and osmotic) and in nutrient deficiency (nitrate and phosphate). Plant growth was monitored and proteomic experiments were performed. Resource allocation between tissues altered during the plants' response. The growth patterns and induced changes of the proteomes indicated that the underlying mechanisms of the adaptation processes are highly specific to the respective environmental condition. Our results indicated differential regulation of response to salt and osmotic treatment, while the proteins in the changed temperature regime showed an inverse, temperature-sensitive control. There was a high correlation of protein level between the nutrient-deficient treatments, but the enriched pathways varied greatly. The proteomic analysis also revealed new insights into the regulation of proteins specific to the shoot and the root. Our investigation revealed unique strategies of plant acclimation to the different applied treatments on a physiological and proteome level, and these strategies are quite distinct in tissues below and above ground.

[Impact of traditionally managed forest units on the landscape connectivity of Sierra de Los Tuxtlas, Mexico]. / Impacto de las unidades de selva manejada tradicionalmente en la conectividad del paisaje de la Sierra de Los Tuxtlas, México.

The ever-increasing establishment of landscape mosaics is expressed as a surrounding matrix of agricultural activities, which frames patches or remnants of the original vegetation cover. Conservation actions should be aimed to establish or to increase those interactive systems, which help to maintain the land- scape flow through linkages. Spaces occupied by traditional management systems retain and support this func- tion. In this paper, we used Geographic Information Systems to evaluate the importance of traditionally managed forest units ('acahuales'-coffee plantations) and to assess landscape connectivity in the indigenous Popoluca area of Sierra de los Tuxtlas, Mexico. The cartographic material used to establish the types of vegetation and their coverture included the period 1991-2008. At landscape level, four indices were used to assess the general situation of the habitat network, and to identify the patches of high priority. Individually, indices evaluated if patches were important for their area, their potential flow or their connecting function. Results showed that the landscape is functioning as a single system, but having low connectivity. Values improved when traditionally managed forest patches were considered as viable habitat. We detected 367 patches of very high priority, 80% belonging to forests managed traditionally. Patches were important for their potential flow (size and topologi- cal relationships). Only 70 patches were significant for their function as biological corridors between largest forests located at the top of the volcanoes, and are mostly managed forest (75%). We concluded that the units of traditionally managed forest play a significant role in landscape connectivity maintenance.

Molecular Markers, Immune Therapy, and Non-Small Cell Lung Cancer-State-of-the-Art Review for Surgeons.

Background: Lung cancer is a leading cause of cancer deaths in the United States. An increasing understanding of relevant non-small cell lung cancer (NSCLC) biomarkers has led to the recent development of molecular-targeted therapies and immune checkpoint inhibitors that have revolutionized treatment for patients with advanced and metastatic disease. The purpose of this review is to provide surgeons with a state-of-the-art understanding of the current medical and surgical treatment trends and their implications in the future of management of NSCLC. Materials and Methods: A systematic search of PubMed was conducted to identify English language articles published between January 2010 and March 2024 focusing on molecular markers, tumor targeting, and immunotherapy in the diagnosis and treatment of NSCLC. Case series, observational studies, randomized trials, guidelines, narrative reviews, systematic reviews, and meta-analyses were included. Results: There is now increasing data to suggest that molecular-targeted therapies and immune therapies have a role in the neoadjuvant setting. Advances in intraoperative imaging allow surgeons to perform increasingly parenchymal-sparing lung resections without compromising tumor margins. Liquid biopsies can noninvasively detect targetable mutations in cancer cells and DNA from a blood draw, potentially allowing for earlier diagnosis, personalized therapy, and long-term monitoring for disease recurrence. Conclusions: The management of NSCLC has advanced dramatically in recent years fueled by a growing understanding of the cancer biology of NSCLC. Advances in medical therapies, surgical techniques, and diagnostic and surveillance modalities continue to evolve but have already impacted current treatment strategies for NSCLC, which are encompassed in this review.

Non-Destructive Near-Infrared Technology for Efficient Cannabinoid Analysis in Cannabis Inflorescences.

In the evolving field of cannabis research, scholars are exploring innovative methods to quantify cannabinoids rapidly and non-destructively. This study evaluates the effectiveness of a hand-held near-infrared (NIR) device for quantifying total cannabidiol (total CBD), total delta-9-tetrahydrocannabinol (total THC), and total cannabigerol (total CBG) in whole cannabis inflorescences. Employing pre-processing techniques, including standard normal variate (SNV) and Savitzky-Golay (SG) smoothing, we aim to optimize the portable NIR technology for rapid and non-destructive cannabinoid analysis. A partial least-squares regression (PLSR) model was utilized to predict cannabinoid concentration based on NIR spectra. The results indicated that SNV pre-processing exhibited superior performance in predicting total CBD concentration, yielding the lowest root mean square error of prediction (RMSEP) of 2.228 and the highest coefficient of determination for prediction (R2P) of 0.792. The ratio of performance to deviation (RPD) for total CBD was highest (2.195) with SNV. In contrast, raw data exhibited the least accurate predictions for total THC, with an R2P of 0.812, an RPD of 2.306, and an RMSEP of 1.651. Notably, total CBG prediction showed unique characteristics, with raw data yielding the highest R2P of 0.806. SNV pre-processing emerges as a robust method for precise total CBD quantification, offering valuable insights into the optimization of a hand-held NIR device for the rapid and non-destructive analysis of cannabinoid in whole inflorescence samples. These findings contribute to ongoing efforts in developing portable and efficient technologies for cannabinoid analysis, addressing the increasing demand for quick and accurate assessment methods in cannabis cultivation, pharmaceuticals, and regulatory compliance.

Addressing Racism in Medical Education: A Longitudinal Antiracism Discussion Curriculum for Medical Students.

Although recent efforts have been engaged to combat bias in medical education, minimal attention has been dedicated to developing antiracism curricula for medical students. We developed a year-long discussion curriculum for 175 first-year medical students centered around Ibram X. Kendi's How to be an Antiracist. The discussion curriculum consisted of six, 2 hour seminars. We evaluated students' perceptions regarding discussing and actively addressing racism. Students reported an improved ability and comfort to discuss and address racism within healthcare settings. These data suggest that antiracism discussion curricula may be effective for training medical students to address racism in their future careers.

Long-term post-storage reactivation of a nitrifying sludge in a sequential batch reactor: physiological and kinetic evaluation.

Production, preservation and recovery of sludge with stabilized nitrifying activity over long time can be difficult. Information on the ability of nitrifying sludge to regain its nitrifying activity after long-term storage is still scarce. In this work, the physiological and kinetic changes during the reactivation and stabilization of a nitrifying sludge previously exposed to ampicillin (AMP) were evaluated in a sequential batch reactor (SBR) after its long-term storage (1 year) at 4 °C. After storage, both ammonium and nitrite oxidizing processes were slow, being nitrite oxidation the most affected step. During the reactivation stage (cycles 1-6), physiological and kinetic activity of the nitrifying sludge improved through the operating cycles, in both its ammonium oxidizing and nitrite oxidizing processes. At the end of the reactivation stage, complete nitrifying activity was achieved in 10 h, reaching ammonium consumption efficiencies (ENH4 +) close to 100% and nitrate yields (YNO3 -) of 0.98 mg NO3 --N/mg NH4 +-N consumed without nitrite accumulation. During the stabilization stage (cycles 7-17), results indicated that the sludge could maintain a steady-state respiratory process with restoration percentages of 100% for nitrifying specific rates (qNH4 + and qNO3 -) with respect to their values obtained before storage. Furthermore, during the addition of 15 mg AMP/L (cycles 18-21), the sludge preserved its metabolic capacity to biodegrade 90% of AMP in 2 h. Therefore, long-term storage of nitrifying sludge could be used to preserve nitrifying inocula as bioseeds for bioremediation and bioaugmentation strategies.

Edible and medicinal mushrooms (Pleurotus ostreatus, Ustilago maydis, Ganoderma lucidum) reduce endoplasmic reticulum stress and inflammation in adipose tissue of obese Wistar rats fed with a high fat plus saccharose diet.

Obesity is an increasing global public health problem. A strategy to treat obesity is the use of functional foods. Edible and medicinal mushrooms contain diverse bioactive compounds showing important antihyperlipidemic, antioxidant, and prebiotic properties. We analysed the effects of adding (10%) of Pleurotus ostreatus (Po, basidiomata), Ganoderma lucidum (Gl, basidiomata), or Ustilago maydis (Um, galls), milled, to a high fat plus saccharose diet (HFD + S) for 6 months in a model of obesity with Wistar rats. We assessed weight gain, body composition, lipid parameters, endoplasmic reticulum stress (proteins and inflammatory markers: BiP, XBP-1, JNK, p-JNK, TNF-α), and adiponectin in subcutaneous adipose tissue (SAT). The consumption of edible and medicinal mushrooms decreased weight gain (-17.2-30.1%) and fat mass (-23.7-43.1%), maintained fat-free mass, reduced levels of serum biochemical parameters (TC: -40.1-44.1%, TG: -37.7-51.6%, LDL-C: -64.5-71.1%), and prevented adipocyte hypertrophy (-30.9-36.9%) and collagen deposition (-70.9-73.7%) in SAT. Compared with the HFD + S group, mushroom consumption by Wistar rats significantly reduced the expression of proteins associated with endoplasmic reticulum stress and inflammation (BiP: -72.2-88.2%; XBP-1: -71.5-81.8%; JNK: -71.2-90.0%; p-JNK: -37.3-81.0%; TNF-α: -80.7-91.5%), whereas significantly increased adiponectin protein expression (246.4-654.2%) in SAT. These effects outperformed those obtained through the commercial lipid-lowering drug atorvastatin, contributing synergistically to prevent further obesity-related dysfunctions, such as insulin resistance derived from inflammation and ER stress in adipose tissue. Bioactive compounds from edible, functional and medicinal mushrooms represent new emerging therapies for obesity treatments using natural products.

Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study.

Well-characterized and standardized extracts of a Mexican genotype of Ganoderma lucidum (Gl), a medicinal mushroom, cultivated on oak sawdust (Gl-1) or oak sawdust plus acetylsalicylic acid (Gl-2, ASA), have been shown to exert antioxidant, hypocholesterolemic, anti-inflammatory, prebiotic, and anticancer properties. However, toxicity analyses still need to be carried out. Different doses of these Gl-1 or Gl-2 extracts were administered to Wistar rats for 14 days in a repeated dose oral toxicity study. We assessed the external clinical signs, biochemical parameters, liver and kidney tissues, injury and inflammation biomarkers, gene expression, inflammatory responses, proinflammatory mediators, and gut microbiota. Gl extracts had no significant adverse, toxic or harmful effects on male and female rats compared to the control groups. No injury or dysfunction were recorded in the kidney or liver, as there were no significant abnormal variations in organ weight, tissue histopathology, serum biochemical parameters (C-reactive protein, creatinine, urea, glucose, ALT and AST transaminases, TC, LDL-c, TG, HDL-c), urinary parameters (creatinine, urea nitrogen, albumin, the albumin-to-creatinine ratio, glucose), injury and inflammatory biomarkers (KIM-1/TIM-1, TLR4, and NF-кB protein expression; IL-1ß, TNF-α and IL-6 gene expression), or the expression of genes linked to cholesterol metabolism (HMG-CoA, Srebp2, Ldlr). Gl-1 and Gl-2 extracts showed prebiotic effects on the gut microbiota of male and female Wistar rats. Bacterial diversity and relative bacterial abundance (BRA) increased, positively modulating the Firmicutes/Bacteroidetes ratio. The ASA (10 mM) added to the substrate used for mushroom cultivation changed properties and effects of the Gl-2 extract on Wistar rats. The no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg body weight/day of Gl-1 or Gl-2 extracts. Clinical trials are recommended for further exploring the potential therapeutic applications of studied extracts.

Iodinated contrast-induced Stevens-Johnson syndrome: A report of a rare complication for a common imaging agent.

Steven-Johnson syndrome (SJS) is a rare condition commonly associated with exposure to antibiotics. We have presented the case of a 76-year-old man with end-stage renal disease who had developed SJS after endovascular thrombectomy of hemodialysis access. He had developed epithelial erosions of the mucosal membranes, hemorrhagic bullae to the palmar and plantar surfaces, and erosions of the genitalia. The findings from biopsies of the lip and palm were suggestive of a drug reaction. He developed SJS three times after exposure to iodinated contrast. The one time he did not develop SJS, he had undergone open thrombectomy with no contrast exposure.

Benign Finding or Malignancy: von Meyenburg Complexes Found during Laparoscopic Cholecystectomy.

Von Meyenburg complexes are benign bile duct hamartomas that arise as cystic nodules of the liver. Von Meyenburg complexes are often asymptomatic and thus typically discovered incidentally on imaging or autopsy. They can also be encountered at the time of surgery where they often appear as scattered white liver lesions concerning for malignancy. Here, we present a case in which white hepatic nodules were found incidentally during laparoscopic cholecystectomy in a 36 -year-old female. Pathologic analysis confirmed the diagnosis of von Meyenburg complexes. The operating surgeon proceeded with laparoscopic cholecystectomy without complication. We report this case to encourage awareness of this benign entity. The finding of scattered hepatic lesions found intra-operatively can create concern for metastatic neoplastic processes. An awareness of von Meyenburg complexes and their gross appearance can better guide surgeons' intraoperative decision-making when encountering these characteristic hepatic lesions.

Dietary Supplementation with Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes), Reduces Visceral Fat and Hyperlipidemia in Inhabitants of a Rural Community in Mexico.

The abandonment of traditional foods in the Mexican diet is one of the causes for the increase in diseases associated with obesity. Edible mushrooms have been a part of the Mexican diet since pre-Hispanic times. There is clear evidence that Pleurotus ostreatus (Po) contains bioactive compounds that have beneficial health effects. In the present study, we carried out a 3-month nutritional intervention in which we randomized 30 participants into two groups: one that consumed a healthy diet with regional foods without the inclusion of edible mushrooms (HD, n = 15) and one that consumed a healthy diet with regional foods alongside 1 kg of P. ostreatus (four portions of 250 g) per week (HD+ P. ostreatus, n = 15). We evaluated anthropometric measurements, lipid parameters, glucose levels, and blood pressure in inhabitants of San Miguel Tianguistenco, Puebla, a rural area of Mexico. For the HD group, the triglyceride levels decreased in women and the glucose levels decreased in men, and in the HD+ P. ostreatus group, visceral fat, glucose, triglyceride, and cholesterol levels decreased in women, and glucose and triglyceride levels decreased in men. Analysis of the intake of macro- and micronutrients in the community showed a high intake of energy, fat, and sugar, and a low intake of fiber, B complex vitamins, and minerals, indicators of an unbalanced diet. It is essential to create strategies that promote the inclusion of edible mushrooms as a part of a heathy diet in rural areas of Mexico to improve the actual health and nutrition of the residents.

Nitrate and ammonium differ in their impact on δ13C of plant metabolites and respired CO2 from tobacco leaves.

The carbon isotopic composition (δ13C) of foliage is often used as proxy for plant performance. However, the effect of N O 3 - vs. N H 4 + supply on δ13C of leaf metabolites and respired CO2 is largely unknown. We supplied tobacco plants with a gradient of N O 3 - to N H 4 + concentration ratios and determined gas exchange variables, concentrations and δ13C of tricarboxylic acid (TCA) cycle intermediates, δ13C of dark-respired CO2, and activities of key enzymes nitrate reductase, malic enzyme and phosphoenolpyruvate carboxylase. Net assimilation rate, dry biomass and concentrations of organic acids and starch decreased along the gradient. In contrast, respiration rates, concentrations of intercellular CO2, soluble sugars and amino acids increased. As N O 3 - decreased, activities of all measured enzymes decreased. δ13C of CO2 and organic acids closely co-varied and were more positive under N O 3 - supply, suggesting organic acids as potential substrates for respiration. Together with estimates of intra-molecular 13C enrichment in malate, we conclude that a change in the anaplerotic reaction of the TCA cycle possibly contributes to 13C enrichment in organic acids and respired CO2 under N O 3 - supply. Thus, the effect of N O 3 - vs. N H 4 + on δ13C is highly relevant, particularly if δ13C of leaf metabolites or respiration is used as proxy for plant performance.

Traditional Mushroom Consumption Associated to Lower Levels of Triglycerides and Blood Pressure in an Indigenous Peasant Community from Oaxaca, Mexico.

Traditional consumption of edible mushrooms is supported by ethnomycological studies worldwide. However, the potential impact of mushroom consumption on the nutritional and health status of remote rural communities has not yet been studied. We carried out these initial standard studies in the indigenous peasant community of Benito Juarez, Oaxaca, Mexico. Participant adults (45) were grouped as follows: optimal body mass index (BMI: 17.8%), overweight (48.9%), obesity type I (24.5%), obesity type II (4.4%), and obesity type III (4.4%). A high proportion of women (90.3%) and men (64.3%) had a high risk of cardiovascular disease (WHI: waist/hip index). Most women (93.6%) and men (57.1%) showed abdominal obesity. In biochemical parameters, subjects had hypertriglyceridemia (75.6%), hypercholesterolemia (26.7%), hyperglycemia (53.3%), and hypertension (46.7%). There was an excessive intake in the diet of energy, proteins, carbohydrates, sugar, and lipids, as well as a deficiency in the consumption of several vitamins and minerals. A high frequency of mushroom consumption (> 3 times per week) was significantly correlated to lower energy, lipids, saturated fatty acids (SFA), and sodium intake, as well as to higher intake of cobalamin and zinc. The levels of triglycerides and diastolic blood pressure were significantly lower in adults consuming edible mushrooms every day. Total cholesterol also tended to be lower. These associations allow to promote healthier diets in remote indigenous communities by keeping or increasing the consumption of edible mushrooms, either wild or cultivated. Edible mushrooms can play a more important role in community nutrition and health, considering their unique functional and medicinal properties.

Mexican Ganoderma Lucidum Extracts Decrease Lipogenesis Modulating Transcriptional Metabolic Networks and Gut Microbiota in C57BL/6 Mice Fed with a High-Cholesterol Diet.

Prevention of hyperlipidemia and associated diseases is a health priority. Natural products, such as the medicinal mushroom Ganoderma lucidum (Gl), have demonstrated hypocholesterolemic, prebiotic and antidiabetic properties. However, the underlying transcriptomic mechanisms by which Gl exerts bioactivities are not completely understood. We report a comprehensive hepatic and renal transcriptome profiling of C57BL/6 mice under the consumption of a high-cholesterol diet and two standardized Gl extracts obtained from basidiocarps cultivated on conventional substrate (Gl-1) or substrate containing acetylsalicylic acid (ASA; Gl-2). We showed that Gl extracts modulate relevant metabolic pathways involving the restriction of lipid biosynthesis and the enrichment of lipid degradation and secretion. The Gl-2 extract exerts a major modulation over gene expression programs showing the highest similarity with simvastatin druggable-target-genes and these are enriched more in processes related to human obesity alterations in the liver. We further show a subset of Gl-modulated genes correlated with Lactobacillus enrichment and the reduction of circulating cholesterol-derived fats. Moreover, Gl extracts induce a significant decrease of macrophage lipid storage, which occurs concomitantly with the down-modulation of Fasn and Elovl6. Collectively, this evidence suggests a new link between Gl hypocholesterolemic and prebiotic activity, revealing thereby that standardized Mexican Gl extracts are a novel transcriptome modulator to prevent metabolic disorders associated with hypercholesterolemia.

Productivity and flavor of diverse genotypes of Ustilago maydis "cuitlacoche" for human consumption.

Maize plants infected by Ustilago maydis develop galls known as "cuitlacoche", a food product appreciated in the Mexican gastronomy. The virulence of different U. maydis isolates was assessed, as well as the development of the infection on one commercial maize variety. Sporidia were isolated of wild galls collected in Mexico. Sexual compatibility patterns were determined using the Fuzz reaction, showing a 1:1:1:1 segregation of mating type specificities. Ten U. maydis compatible strains were selected on the basis of their virulence, namely: four wild-type compatible sporidia, one multi-teliosporic strain, two hybrids between wild-type and tester strains, and three tester strains. Maize plants of a commercial hybrid (Tornado XR™) were inoculated with these strains of U. maydis, using a randomized complete block experimental design. Phenological and phenotypic characteristics of plants, as well as production, quality and sensory attributes of the resulting galls, were evaluated. Greater yields of galls were recorded in tester strains (incidence >90 %, severity >80 %, productivity >12 t/ha), a hybrid strain (EM1-6 × FB1) [incidence 82.6 %, severity 51.8 %, productivity 5.6 t/ha] and a wild-type strain (EM4-10 × EM2-4) [incidence 68.2 %, severity 44.0 %, productivity 4.8 t/ha]. Wild-type strains showed better flavor, characterized by less bitterness and acidity, but prevailing sweet, umami and maize flavor.

LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance.

Excitatory hilar mossy cells (MCs) in the dentate gyrus receive inputs from dentate granule cells (GCs) and project back to GCs locally, contralaterally, and along the longitudinal axis of the hippocampus, thereby establishing an associative positive-feedback loop and connecting functionally diverse hippocampal areas. MCs also synapse with GABAergic interneurons that mediate feed-forward inhibition onto GCs. Surprisingly, although these circuits have been implicated in both memory formation (e.g., pattern separation) and temporal lobe epilepsy, little is known about activity-dependent plasticity of their synaptic connections. Here, we report that MC-GC synapses undergo a presynaptic, NMDA-receptor-independent form of long-term potentiation (LTP) that requires postsynaptic brain-derived neurotrophic factor (BDNF)/TrkB and presynaptic cyclic AMP (cAMP)/PKA signaling. This LTP is input specific and selectively expressed at MC-GC synapses, but not at the disynaptic inhibitory loop. By increasing the excitation/inhibition balance, MC-GC LTP enhances GC output at the associative MC-GC recurrent circuit and may contribute to dentate-dependent forms of learning and epilepsy.

Comparison of redox and gene expression changes during vegetative/generative transition in the crowns and leaves of chromosome 5A substitution lines of wheat under low-temperature condition.

The aim of our experiments was to investigate the effect of chromosome 5A on the thiol-dependent redox environment and on the transcription of cold- and vernalization-related genes during the vegetative/generative transition in crowns and leaves of wheat. Chinese Spring, a moderately freezing-tolerant variety, and its more and less tolerant substitution lines - [CS(Ch5A)] and [CS(Tsp5A)], respectively - with different combinations of vernalization alleles were compared. At low temperature, the amount of cystine and glutathione disulphide and the related redox potentials increased in the crowns but not in the leaves. In the crowns of the substitution lines, the concentration and redox state of thiols were different only at the vegetative and double ridge (start of the generative transition) stages. The expression of the vernalization-related VRN1 gene increased significantly during the transition both in the crowns and leaves. The transcription of the freezing tolerance-related CBF14, COR14b and COR39 genes markedly increased in both organs after 2 weeks at 4 °C when the seedlings were still in the vegetative stage. This increment was greater in CS(Ch5A) than in CS(Tsp5A). The Ch5A chromosome in CS genetic background enhanced the expression of CBF regulon even in the generative phase in crown that is the key organ for overwintering and freezing tolerance. At certain developmental stages, both the thiol and the transcript levels differed significantly in the two substitution lines.