Models to predict nitrogen excretion from beef cattle fed a wide range of diets compiled from South America.

The objective of this meta-analysis was to develop and evaluate models for predicting nitrogen (N) excretion in feces, urine, and manure in beef cattle in South America. The study incorporated a total of 1,116 individual observations of N excretion in feces and 939 individual observations of N excretion in feces and in urine (g/d), representing a diverse range of diets, animal genotypes, and management conditions in South America. The dataset also included data on dry matter intake (DMI; kg/d) and nitrogen intake (NI; g/d), concentrations of dietary components, as well as average daily gain (ADG; g/d) and average body weight (BW; kg). Models were derived using linear mixed-effects regression with a random intercept for the study. Fecal N excretion was positively associated with DMI, NI, nonfibrous carbohydrates, average BW, and ADG and negatively associated with EE and CP concentration in the diet. The univariate model predicting fecal N excretion based on DMI (model 1) performed slightly better than the univariate model, which used NI as a predictor variable (model 2) with a root mean square error (RMSE) of 38.0 vs. 39.2%, the RMSE-observations SD ratio (RSR) of 0.81 vs. 0.84, and concordance correlation coefficient (CCC) of 0.53 vs. 0.50, respectively. Models predicting urinary N excretion were less accurate than those derived to predict fecal N excretion, with an average RMSE of 43.7% vs. 37.0%, respectively. Urinary and manure N excretion were positively associated with DMI, NI, CP, average BW, and ADG and negatively associated with neutral detergent fiber concentration in the diet. As opposed to fecal N excretion, the univariate model predicting urinary N excretion using NI (model 10) performed slightly better than the univariate model using DMI (model 9) as predictor variable with an RMSE of 36.0% vs. 39.7%, RSR 0.85 vs. 0.93, and CCC of 0.43 vs. 0.29, respectively. The models developed in this study are applicable for predicting N excretion in beef cattle across a broad spectrum of dietary compositions and animal genotypes in South America. The univariate model using DMI as a predictor is recommended for fecal N prediction, while the univariate model using NI is recommended for predicting urinary and manure N excretion because the use of more complex models resulted in little to no benefits. However, it may be more useful to consider more complex models that incorporate nutrient intakes and diet composition for decision-making when N excretion is a factor to be considered. Three extant equations evaluated in this study have the potential to be used in tropical conditions typical of South America to predict fecal N excretion with good precision and accuracy. However, none of the extant equations are recommended for predicting urine or manure N excretion because of their high RMSE, and low precision and accuracy.

The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

A Comparative Investigation of Axon-Blood Vessel Growth Interaction in the Regenerating Sciatic and Optic Nerves in Adult Mice.

The vascular and the nervous systems share similarities in addition to their complex role in providing oxygen and nutrients to all cells. Both are highly branched networks that frequently grow close to one another during development. Vascular patterning and neural wiring share families of guidance cues and receptors. Most recently, this relationship has been investigated in terms of peripheral nervous system (PNS) regeneration, where nerves and blood vessels often run in parallel so endothelial cells guide the formation of the Büngner bands which support axonal regeneration. Here, we characterized the vascular response in regenerative models of the central and peripheral nervous system. After sciatic nerve crush, followed by axon regeneration, there was a significant increase in the blood vessel density 7 days after injury. In addition, the optic nerve crush model was used to evaluate intrinsic regenerative potential activated with a combined treatment that stimulated retinal ganglion cells (RGCs) regrowth. We observed that a 2-fold change in the total number of blood vessels occurred 7 days after optic nerve crush compared to the uncrushed nerve. The difference increased up to a 2.7-fold change 2 weeks after the crush. Interestingly, we did not observe differences in the total number of blood vessels 2 weeks after crush, compared to animals that had received combined treatment for regeneration and controls. Therefore, the vascular characterization showed that the increase in vascular density was not related to the efficiency of both peripheral and central axonal regeneration.

Flint corn silage management: influence of maturity stage, inoculation with Lentilactobacillus buchneri, and storage time on fermentation pattern, aerobic stability, and nutritional characteristics.

Introduction: High quality corn silage depends on factors such as corn type, stage of crop development at harvest time, fermentation time, in addition to use or not of inoculants. This study aimed to investigate the impact of maturity stage, bacterial inoculation, and storage time on fermentation, aerobic stability, and nutritional characteristics of flint corn silage and their implications for corn silage management. Methods: A flint corn hybrid was harvested very early, early, and medium (at 250, 300 and 350 g dry matter (DM)/kg as fed, respectively) and ensiled in mini-silos without (control) or with Lentilactobacillus buchneri CNCM I-4323 at 1 × 105 cfu/g for 120, 240 and 360 d to investigate how these factors interact with each other. Results and discussion: There was only a small increase (7 g/kg starch; p = 0.003) in starch digestibility (starch-D) in the silages stored for 360 d when compared to that stored for 240 d, but with no difference for 120 d. Despite the reduced starch-D (526 vs. 694 g/kg starch; p < 0.001), silages produced from medium harvest had higher (p < 0.001) starch content (317 vs. 137 g/kg DM) and higher amount of digestible starch (169 vs. 98.5 g/kg DM; p < 0.001) compared to very early harvest. The 2-way interactions (inoculation × storage time and maturity × storage time) showed that inoculation of corn silage with L. buchneri increased (p < 0.001) the aerobic stability, and that more mature crop silage had higher aerobic stability (140 h; p = 0.036) than the others (118 and 48.5 h for those silages from very early and early harvest). Conclusion: The storage for a longer time (>120 d) with the goal of increasing silage digestibility did not occur. Harvesting whole-crop flint corn with 300 to 350 g/kg DM is desirable to have higher DM yield and starch accumulation. Inoculation with L. buchneri is recommended to preserve the silage against aerobic deterioration. This study has shown the importance of harvesting flint corn at the right time, and the need for inoculation with L. buchneri to ensure greater yield, starch accumulation, and silage preservation, if 120 days of storage are not exceeded.

Feeding 3-nitrooxypropanol reduces methane emissions by feedlot cattle on tropical conditions.

Our objective was to evaluate the effects of feeding 3-nitrooxypropanol (3-NOP; Bovaer, DSM Nutritional Products) at two levels on methane emissions, nitrogen balance, and performance by feedlot cattle. In experiment 1, a total of 138 Nellore bulls (initial body weight, 360 ± 37.3 kg) were housed in pens (27 pens with either 4 or 5 bulls per pen) and fed a high-concentrate diet for 96 d, containing 1) no addition of 3-NOP (control), 2) inclusion of 3-NOP at 100 mg/kg dry matter (DM), and 3) inclusion of 3-NOP at 150 mg/kg DM. No adverse effects of 3-NOP were observed on DM intake (DMI), animal performance, and gain:feed (P > 0.05). In addition, there was no effect (P > 0.05) of 3-NOP on carcass characteristics (subcutaneous fat thickness and rib eye area). In experiment 2, 24 bulls (initial BW, 366 ± 39.6 kg) housed in 12 pens (2 bulls/pen) from experiment 1 were used for CH4 measurements and nitrogen balance. Irrespective of the level, 3-NOP consistently decreased (P < 0.001) animals' CH4 emissions (g/d; ~49.3%), CH4 yield (CH4/DMI; ~40.7%) and CH4 intensity (CH4/average daily gain; ~38.6%). Moreover, 3-NOP significantly reduced the gross energy intake lost as CH4 by 42.5% (P < 0.001). The N retention: N intake ratio was not affected by 3-NOP (P = 0.19). We conclude that feeding 3-NOP is an effective strategy to reduce methane emissions, with no impairment on feedlot cattle performance.

During fiber digestion in the rumen, enteric methane is produced. Methane is a potent greenhouse gas. Recently several studies have focused on developing synthetic compounds and their utilization as specific inhibitors of methanogenesis. 3-Nitrooxypropanol is a structural compound that can help to mitigate CH4 emissions. The objective of this study was to evaluate the effects of feeding 3-nitrooxypropanol (3-NOP; Bovaer, DSM Nutritional Products) at two levels on methane emissions, nitrogen balance, and performance by feedlot cattle. No effect of 3-NOP on animal performance and N balance was found. However, regarding CH4 production 3-NOP consistently decreased (P < 0.001) animals' CH4 emissions (g/d; ~49.3%), methane yield (CH4/dry matter intake; ~40.7%), and CH4 intensity (CH4/average daily gain; ~38.6%). This study provides information on the potential role of 3-NOP on reducing CH4 emissions from feedlot cattle without reducing animal performance.

Long-Term Treatment with Cannabidiol-Enriched Cannabis Extract Induces Synaptic Changes in the Adolescent Rat Hippocampus.

The endocannabinoid system (eCS) is widely distributed in mammalian tissues and it is classically formed by cannabinoid receptors, endogenous bioactive lipids and its synthesis and degradation enzymes. Due to the modulatory role of eCS in synaptic activity in the Central Nervous System (CNS), phytocannabinoids have been increasingly used for the treatment of neurological disorders, even though little is known in terms of the long-term effect of these treatments on CNS development, mainly in the timeframe that comprises childhood and adolescence. Furthermore, an increased number of clinical trials using full-spectrum Cannabis extracts has been seen, rather than the isolated form of phytocannabinoids, when exploring the therapeutical benefits of the Cannabis plant. Thus, this study aims to evaluate the effect of cannabidiol (CBD)-enriched Cannabis extract on synaptic components in the hippocampus of rats from adolescence to early adulthood (postnatal day 45 to 60). Oral treatment of healthy male Wistar rats with a CBD-enriched Cannabis extract (3 mg/kg/day CBD) during 15 days did not affect food intake and water balance. There was also no negative impact on locomotor behaviour and cognitive performance. However, the hippocampal protein levels of GluA1 and GFAP were reduced in animals treated with the extract, whilst PSD95 levels were increased, which suggests rearrangement of glutamatergic synapses and modulation of astrocytic features. Microglial complexity was reduced in CA1 and CA3 regions, but no alterations in their phagocytic activity have been identified by Iba-1 and LAMP2 co-localization. Collectively, our data suggest that CBD-enriched Cannabis treatment may be safe and well-tolerated in healthy subjects, besides acting as a neuroprotective agent against hippocampal alterations related to the pathogenesis of excitatory and astrogliosis-mediated disorders in CNS.

Activation of cannabinoid type 1 receptor (CB1) modulates oligodendroglial process branching complexity in rat hippocampal cultures stimulated by olfactory ensheathing glia-conditioned medium.

The endocannabinoid system (ECS) refers to a complex cell-signaling system highly conserved among species formed by numerous receptors, lipid mediators (endocannabinoids) and synthetic and degradative enzymes. It is widely distributed throughout the body including the CNS, where it participates in synaptic signaling, plasticity and neurodevelopment. Besides, the olfactory ensheathing glia (OEG) present in the olfactory system is also known to play an important role in the promotion of axonal growth and/or myelination. Therefore, both OEG and the ECS promote neurogenesis and oligodendrogenesis in the CNS. Here, we investigated if the ECS is expressed in cultured OEG, by assessing the main markers of the ECS through immunofluorescence, western blotting and qRT-PCR and quantifying the content of endocannabinoids in the conditioned medium of these cells. After that, we investigated whether the production and release of endocannabinoids regulate the differentiation of oligodendrocytes co-cultured with hippocampal neurons, through Sholl analysis in oligodendrocytes expressing O4 and MBP markers. Additionally, we evaluated through western blotting the modulation of downstream pathways such as PI3K/Akt/mTOR and ERK/MAPK, being known to be involved in the proliferation and differentiation of oligodendrocytes and activated by CB1, which is the major endocannabinoid responsive receptor in the brain. Our data show that OEG expresses key genes of the ECS, including the CB1 receptor, FAAH and MAGL. Besides, we were able to identify AEA, 2-AG and AEA related mediators palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in the conditioned medium of OEG cultures. These cultures were also treated with URB597 10-9 M, a FAAH selective inhibitor, or JZL184 10-9 M, a MAGL selective inhibitor, which led to the increase in the concentrations of OEA and 2-AG in the conditioned medium. Moreover, we found that the addition of OEG conditioned medium (OEGCM) enhanced the complexity of oligodendrocyte process branching in hippocampal mixed cell cultures and that this effect was inhibited by AM251 10-6 M, a CB1 receptor antagonist. However, treatment with the conditioned medium enriched with OEA or 2-AG did not alter the process branching complexity of premyelinating oligodendrocytes, while decreased the branching complexity in mature oligodendrocytes. We also observed no change in the phosphorylation of Akt and ERK 44/42 in any of the conditions used. In conclusion, our data show that the ECS modulates the number and maturation of oligodendrocytes in hippocampal mixed cell cultures.

Improving the accuracy of beef cattle methane inventories in Latin America and Caribbean countries.

On-farm methane (CH4) emissions need to be estimated accurately so that the mitigation effect of recommended practices can be accounted for. In the present study prediction equations for enteric CH4 have been developed in lieu of expensive animal measurement approaches. Our objectives were to: (1) compile a dataset from individual beef cattle data for the Latin America and Caribbean (LAC) region; (2) determine main predictors of CH4 emission variables; (3) develop and cross-validate prediction models according to dietary forage content (DFC); and (4) compare the predictive ability of these newly-developed models with extant equations reported in literature, including those currently used for CH4 inventories in LAC countries. After outlier's screening, 1100 beef cattle observations from 55 studies were kept in the final dataset (∼ 50 % of the original dataset). Mixed-effects models were fitted with a random effect of study. The whole dataset was split according to DFC into a subset for all-forage (DFC = 100 %), high-forage (94 % ≥ DFC ≥ 54 %), and low-forage (50 % ≥ DFC) diets. Feed intake and average daily gain (ADG) were the main predictors of CH4 emission (g d-1), whereas this was feeding level [dry matter intake (DMI) as % of body weight] for CH4 yield (g kg-1 DMI). The newly-developed models were more accurate than IPCC Tier 2 equations for all subsets. Simple and multiple regression models including ADG were accurate and a feasible option to predict CH4 emission when data on feed intake are not available. Methane yield was not well predicted by any extant equation in contrast to the newly-developed models. The present study delivered new models that may be alternatives for the IPCC Tier 2 equations to improve CH4 prediction for beef cattle in inventories of LAC countries based either on more or less readily available data.

Contribution of Müller Cells in the Diabetic Retinopathy Development: Focus on Oxidative Stress and Inflammation.

Diabetic retinopathy is a neurovascular complication of diabetes and the main cause of vision loss in adults. Glial cells have a key role in maintenance of central nervous system homeostasis. In the retina, the predominant element is the Müller cell, a specialized cell with radial morphology that spans all retinal layers and influences the function of the entire retinal circuitry. Müller cells provide metabolic support, regulation of extracellular composition, synaptic activity control, structural organization of the blood-retina barrier, antioxidant activity, and trophic support, among other roles. Therefore, impairments of Müller actions lead to retinal malfunctions. Accordingly, increasing evidence indicates that Müller cells are affected in diabetic retinopathy and may contribute to the severity of the disease. Here, we will survey recently described alterations in Müller cell functions and cellular events that contribute to diabetic retinopathy, especially related to oxidative stress and inflammation. This review sheds light on Müller cells as potential therapeutic targets of this disease.

Visualizing Shifts on Neuron-Glia Circuit with the Calcium Imaging Technique.

Here, we report on selective in vitro models of circuits based on glia (astrocytes, oligodendrocytes, and microglia) and/or neurons from peripheral (dorsal root ganglia) and central tissues (cortex, subventricular zone, organoid) that are dynamically studied in terms of calcium shifts. The model chosen to illustrate the results is the retina, a simple tissue with complex cellular interactions. Calcium is a universal messenger involved in most of the important cellular roles. We explain in a step-by-step protocol how retinal neuron-glial cells in culture can be prepared and evaluated, envisioning calcium shifts. In this model, we differentiate neurons from glia based on their selective response to KCl and ATP. Calcium permeable receptors and channels are selectively expressed in different compartments. To analyze calcium responses, we use ratiometric fluorescent dies such as Fura-2. This probe quantifies free Ca2+ concentration based on Ca2+-free and Ca2+-bound forms, presenting two different peaks, founded on the fluorescence intensity perceived on two wavelengths.

Strategy to Predict High and Low Frequency Behaviors Using Triaxial Accelerometers in Grazing of Beef Cattle.

Knowledge of animal behavior can be indicative of the well-being, health, productivity, and reproduction of animals. The use of accelerometers to classify and predict animal behavior can be a tool for continuous animal monitoring. Therefore, the aim of this study was to provide strategies for predicting more and less frequent beef cattle grazing behaviors. The behavior activities observed were grazing, ruminating, idle, water consumption frequency (WCF), feeding (supplementation) and walking. Three Machine Learning algorithms: Random Forest (RF), Support Vector Machine (SVM) and Naïve Bayes Classifier (NBC) and two resample methods: under and over-sampling, were tested. Overall accuracy was higher for RF models trained with the over-sampled dataset. The greatest sensitivity (0.808) for the less frequent behavior (WCF) was observed in the RF algorithm trained with the under-sampled data. The SVM models only performed efficiently when classifying the most frequent behavior (idle). The greatest predictor in the NBC algorithm was for ruminating behavior, with the over-sampled training dataset. The results showed that the behaviors of the studied animals were classified with high accuracy and specificity when the RF algorithm trained with the resampling methods was used. Resampling training datasets is a strategy to be considered, especially when less frequent behaviors are of interest.

Cannabinoid Therapeutics in Chronic Neuropathic Pain: From Animal Research to Human Treatment.

Despite the importance of pain as a warning physiological system, chronic neuropathic pain is frequently caused by damage in the nervous system, followed by persistence over a long period, even in the absence of dangerous stimuli or after healing of injuries. Chronic neuropathic pain affects hundreds of millions of adults worldwide, creating a direct impact on quality of life. This pathology has been extensively characterized concerning its cellular and molecular mechanisms, and the endocannabinoid system (eCS) is widely recognized as pivotal in the development of chronic neuropathic pain. Scientific evidence has supported that phyto-, synthetic and endocannabinoids are efficient for pain management, while strong data arise from the therapeutic use of Cannabis-derived products. The use of medicinal Cannabis products is directed toward not only relieving symptoms of chronic pain, but also improving several aspects of patients' welfare. Here, we review the involvement of eCS, along with other cellular and molecular elements, in chronic neuropathic pain pathology and how this system can be targeted for pain management.

Dopamine signaling impairs ROS modulation by mitochondrial hexokinase in human neural progenitor cells.

Dopamine signaling has numerous roles during brain development. In addition, alterations in dopamine signaling may be also involved in the pathophysiology of psychiatric disorders. Neurodevelopment is modulated in multiple steps by reactive oxygen species (ROS), byproducts of oxidative metabolism that are signaling factors involved in proliferation, differentiation, and migration. Hexokinase (HK), when associated with the mitochondria (mt-HK), is a potent modulator of the generation of mitochondrial ROS in the brain. In the present study, we investigated whether dopamine could affect both the activity and redox function of mt-HK in human neural progenitor cells (NPCs). We found that dopamine signaling via D1R decreases mt-HK activity and impairs ROS modulation, which is followed by an expressive release of H2O2 and impairment in calcium handling by the mitochondria. Nevertheless, mitochondrial respiration is not affected, suggesting specificity for dopamine on mt-HK function. In neural stem cells (NSCs) derived from induced-pluripotent stem cells (iPSCs) of schizophrenia patients, mt-HK is unable to decrease mitochondrial ROS, in contrast with NSCs derived from healthy individuals. Our data point to mitochondrial hexokinase as a novel target of dopaminergic signaling, as well as a redox modulator in human neural progenitor cells, which may be relevant to the pathophysiology of neurodevelopmental disorders such as schizophrenia.

Could forage peanut in low proportion replace N fertilizer in livestock systems?

Palisadegrass [Urochloa brizantha (Hochst. ex A. Rich.) R. D. Webster cv. Marandu] is widely used in Brazil and is typically managed with little or no N fertilizer, which often leads to pasture decline in the long-term. The current relationship between beef price and fertilizer cost in Brazil does not favor fertilizer use in pastures. Legume inclusion is an alternative to adding fertilizer N, but often legumes do not reach a significant proportion (> 30%) in pasture botanical composition. This study evaluated herbage responses to N inputs and pasture species composition, under intermittent stocking. Treatments included palisadegrass-forage peanut (Arachis pintoi Krapov. & W.C. Greg. cv. Amarillo) mixture (mixed), unfertilized palisadegrass (control), and palisadegrass fertilized with 150 kg N ha-1 yr-1 (fertilized). Treatments were applied over two rainy seasons with five growth cycle (GC) evaluations each season. Response variables included herbage biomass, herbage accumulation, morphological components, total aboveground N of forage peanut (TAGNFP), and contribution of biological N2 fixation (BNF). Herbage biomass was greater for fertilized palisadegrass [5850 kg dry matter (DM) ha-1] than for the palisadegrass-forage peanut mixture (3940 kg DM ha-1), while the unfertilized palisadegrass (4400 kg DM ha-1) did not differ from the mixed pasture. Nitrogen fertilizer increased leaf mass of palisadegrass (2490 kg DM ha-1) compared with the control and mixed treatments (1700 and 1310 kg DM ha-1, respectively). The contribution of BNF to the forage peanut ranged from 79 to 85% and 0.5 to 5.5 kg N ha-1 cycle-1. Overall, benefits from forage peanut were minimal because legume percentage was less than 10%, while N input in the system by N-fertilizer increased palisadegrass herbage biomass.

Hemopressin as a breakthrough for the cannabinoid field.

Hemopressin (PVNFKFLSH in rats, and PVNFKLLSH in humans and mice), a fragment derived from the α-chain of hemoglobin, was the first peptide described to have type 1 cannabinoid receptor activity. While hemopressin was shown to have inverse agonist/antagonistic activity, extended forms of hemopressin (i.e. RVD-hemopressin, also called pepcan-12) exhibit type 1 and type 2 cannabinoid receptor agonistic/allosteric activity, and recent studies suggest that they can activate intracellular mitochondrial cannabinoid receptors. Therefore, hemopressin and hemopressin-related peptides could have location-specific and biased pharmacological action, which would increase the possibilities for fine-tunning and broadening cannabinoid receptor signal transduction. Consistent with this, hemopressins were shown to play a role in a number of physiological processes including antinociceptive and anti-inflammatory activity, regulation of food intake, learning and memory. The shortest active hemopressin fragment, NFKF, delays the first seizure induced by pilocarpine, and prevents neurodegeneration in an experimental model of autoimmune encephalomyelitis. These functions of hemopressins could be due to engagement of both cannabinoid and non-cannabinoid receptor systems. Self-assembled nanofibrils of hemopressin have pH-sensitive switchable surface-active properties, and show potential as inflammation and cancer targeted drug-delivery systems. Upon disruption of the self-assembled hemopressin nanofibril emulsion, the intrinsic analgesic and anti-inflammatory properties of hemopressin could help bolster the therapeutic effect of anti-inflammatory or anti-cancer formulations. In this article, we briefly review the molecular and behavioral pharmacological properties of hemopressins, and summarize studies on the intricate and unique mode of generation and binding of these peptides to cannabinoid receptors. Thus, the review provides a window into the current status of hemopressins in expanding the repertoire of signaling and activity by the endocannabinoid system, in addition to their new potential for pharmaceutic formulations.

Hemopressin as a breakthrough for the cannabinoid field

Hemopressin (PVNFKFLSH in rats, and PVNFKLLSH in humans and mice), a fragment derived from the α-chain of hemoglobin, was the first peptide described to have type 1 cannabinoid receptor activity. While hemopressin was shown to have inverse agonist/antagonistic activity, extended forms of hemopressin (i.e. RVD-hemopressin, also called pepcan-12) exhibit type 1 and type 2 cannabinoid receptor agonistic/allosteric activity, and recent studies suggest that they can activate intracellular mitochondrial cannabinoid receptors. Therefore, hemopressin and hemopressin-related peptides could have location-specific and biased pharmacological action, which would increase the possibilities for fine-tunning and broadening cannabinoid receptor signal transduction. Consistent with this, hemopressins were shown to play a role in a number of physiological processes including antinociceptive and anti-inflammatory activity, regulation of food intake, learning and memory. The shortest active hemopressin fragment, NFKF, delays the first seizure induced by pilocarpine, and prevents neurodegeneration in an experimental model of autoimmune encephalomyelitis. These functions of hemopressins could be due to engagement of both cannabinoid and non-cannabinoid receptor systems. Self-assembled nanofibrils of hemopressin have pH-sensitive switchable surface-active properties, and show potential as inflammation and cancer targeted drug-delivery systems. Upon disruption of the self-assembled hemopressin nanofibril emulsion, the intrinsic analgesic and anti-inflammatory properties of hemopressin could help bolster the therapeutic effect of anti-inflammatory or anti-cancer formulations. In this article, we briefly review the molecular and behavioral pharmacological properties of hemopressins, and summarize studies on the intricate and unique mode of generation and binding of these peptides to cannabinoid receptors. Thus, the review provides a window into the current status of hemopressins in expanding the repertoire of signaling and activity by the endocannabinoid system, in addition to their new potential for pharmaceutic formulations.

Use of crude glycerine and microbial inoculants to improve the fermentation process of Tifton 85 haylages.

The increase in haylage production leads to the search for additives that improve its fermentation and nutritional value. This study aimed to assess the effect of adding crude glycerine and microbial additives on losses, fermentation parameters and nutritional value of haylage. The treatments were composed of three doses of crude glycerine (0, 60 and 120 g/kg forage) and three types of inoculation (control (distilled water), SIL (Lactobacillus plantarum 2.6 × 1010 CFU/g and Pediococcus pentosaceus 2.6 × 1010 CFU/g) and INC (Bacillus subtilis 2.0 × 109 CFU/g, Lactobacillus plantarum 8.0 × 109 CFU/g and Pediococcus acidilactici 1.0 × 1010 CFU/g)). A negative linear effect was observed in the fibre fraction contents of the haylages as a function of crude glycerine addition, which contributed to similarly increasing dry matter in vitro digestibility coefficients. The use of inoculants also resulted in haylages with higher digestibility coefficients of 635.1 and 646.8 g/kg dry matter (DM) in the treatments inoculated with INC and SIL, respectively. Fermentation losses were reduced by adding crude glycerine and were not impacted by the microbial inoculants. Higher lactic acid productions were obtained as a function of crude glycerine doses. Acetic acid productions decreased from 29.3 g/kg DM to 19.2 g/kg DM between crude glycerine doses of 0 and 120 g/kg forage, respectively. SIL led to the highest lactic acid productions compared to INC and the control. Crude glycerine improves the fermentation parameters and nutritional value of haylages. However, the microbial inoculants had little impact on the parameters assessed.

Human Cerebral Organoids and Fetal Brain Tissue Share Proteomic Similarities.

The limited access to functional human brain tissue has led to the development of stem cell-based alternative models. The differentiation of human pluripotent stem cells into cerebral organoids with self-organized architecture has created novel opportunities to study the early stages of the human cerebral formation. Here we applied state-of-the-art label-free shotgun proteomics to compare the proteome of stem cell-derived cerebral organoids to the human fetal brain. We identified 3,073 proteins associated with different developmental stages, from neural progenitors to neurons, astrocytes, or oligodendrocytes. The major protein groups are associated with neurogenesis, axon guidance, synaptogenesis, and cortical brain development. Glial cell proteins related to cell growth and maintenance, energy metabolism, cell communication, and signaling were also described. Our data support the variety of cells and neural network functional pathways observed within cell-derived cerebral organoids, confirming their usefulness as an alternative model. The characterization of brain organoid proteome is key to explore, in a dish, atypical and disrupted processes during brain development or neurodevelopmental, neurodegenerative, and neuropsychiatric diseases.

Methane production and nitrogen balance of dairy heifers grazing palisade grass cv. Marandu alone or with forage peanut.

Livestock production systems are an essential agribusiness activity in Brazil, but a critical challenge of Brazilian farmers is to maintain the equilibrium of the ecosystem, using herbage resources efficiently with a minimum impact on the environment. Nitrogen (N) fertilization and the inclusion of forage legumes into tropical grass pastures are management strategies which increase the productivity and nutritive value of pastures and may also affect methane (CH4) production by ruminants. The objective of this study was to examine the effects of either fertilizing palisade grass pastures with N or including the forage peanut (Arachis pintoi) into grass pastures on enteric CH4 emission, microbial protein production in the rumen via purine derivatives in the urine, and N balance. Twenty-one nonlactating crossbred dairy heifers were used in a completely randomized design with 3 treatments. The treatments consisted of pastures of palisade grass without N fertilization (control), fertilized with urea (fertilized), and palisade grass mixed with forage peanut (mixed). Seven animals (replications) were used to evaluate dry matter intake, digestibility, CH4 emission, urea, purine derivatives, and volume of urine, and N ingestion and excretion. Four paddocks (replications) were used to measure herbage mass; morphological, botanical, and chemical composition of herbage; and herbage allowance. The CH4 emissions were determined using the sulfur hexafluoride (SF6) tracer gas technique. The efficiency of N utilization (ENU) was calculated using the N balance data. Crude protein (CP) concentration of herbage increased with fertilization or legumes inclusion (P < 0.0001) while neutral detergent fiber (NDF) concentration decreased (P = 0.0355). The leaf allowance was higher in the fertilized treatment (P = 0.0294). Only uric acid excretion increased with N fertilization (P = 0.0204). The ENU was not affected by fertilized or mixed compared to control and averaged 55% (P = 0.8945). The enteric CH4 production was similar between treatments and averaged 129 g/d (P = 0.3989). We concluded that the changes in chemical composition of herbage provided by N fertilization or the inclusion of the legume showed no reduction in enteric CH4 emissions, but the ENU was more significant than previous studies with palisade grass, suggesting that different management strategies might alter the ENU under grazing conditions.