Biology

Transgenic potato event Vic.172, expressing three naturally occurring resistance genes (R genes) conferring complete protection against late blight disease, was evaluated for resistance to late blight, phenotypic characterization, and agronomic performance in field conditions at three locations during three seasons in Uganda. These trials were conducted by comparison to the variety Victoria from which Vic.172 derives, using identical fungicide treatment, except when evaluating disease resistance. During all seasons, the transgenic event Vic.172 was confirmed to have complete resistance to late blight disease, whereas Victoria plants were completely dead by 60–80 days after planting. Tubers from Vic.172 were completely resistant to LB after artificial inoculation. The phenotypic characterization included observations of the characteristics and development of the stems, leaves, flowers, and tubers. Differences in phenotypic parameters between Vic.172 and Victoria were not statistically significant across locations and seasons. The agronomic performance observations covered sprouting, emergence, vigor, foliage growth, and yield. Differences in agronomic performance were not statistically significant except for marketable yield in one location under high productivity conditions. However, yield variation across locations and seasons was not statistically significant, but was influenced by the environment. Hence, the results of the comparative assessment of the phenotype and agronomic performance revealed that transgenic event Vic.172 did not present biologically significant differences in comparison to the variety Victoria it derives from. Full article

Aloesin is an aromatic chromone with increasing applications in the cosmetic and health food industries. To optimize its extraction from the Aloe vera leaf rind, the independent variables time (10–210 min), temperature (25–95 °C) and organic solvent composition (0–100%, w/w) were combined in a central composite design coupled with response surface methodology. The solvents consisted of binary mixtures of water with ethanol, propylene glycol, or glycerol. The aloesin levels quantified in each extract were used as response for optimization. The theoretical models were fitted to the experimental data, statistically validated, and used to obtain the optimal extraction conditions. Then, a dose–response analysis of the solid/liquid ratio (S/L) was performed under the optimal conditions determined for each alcohol–water system and revealed that a linear improvement in extraction efficiency can be achieved by increasing the S/L ratio by up to 40 g/L. This analysis also allowed to experimentally validate the predictive models. Furthermore, the aloesin-rich extracts revealed antioxidant activity through thiobarbituric acid reactive substances (TBARS) formation inhibition, antimicrobial effects against bacterial and fungal strains, and no toxicity for PLP2 cells. Overall, this study provided optimal extraction conditions for the recovery of aloesin from Aloe vera rind through an eco-friendly extraction process and highlighted its bioactive potential. Full article

Biomarkers remain a valuable tool for the diagnosis and management of Neuroendocrine tumors (NETs). Traditional monoanalyte biomarkers such as Chromogranin A (CgA) and 5-Hydrocyondoleacetic acid (5-HIAA) have been widely used for many years as diagnostic, predictive and prognostic biomarkers in the field of NETs. However, the clinical utility of these molecules often has limitations, mainly inherent to the heterogeneity of NETs and the fact that these tumors can often be non-secretory. The development of new molecular multianalyte biomarkers, especially the mRNA transcript based “NETest”, has rapidly evolve the field and gives the ability for a “liquid biopsy” which can reliably assess disease status in real time. In this review we discuss the use of established and novel biomarkers in the diagnosis and management of small intestine NETs and carcinoid heart disease. Full article

Yak adipose tissue may have evolved a unique energy metabolism manner to accommodate the organism’s seasonal growth rhythms. MiRNAs regulate multiple biological processes including systemic metabolism and energy homeostasis through post-transcriptional regulations. Rare reports have shown that miRNAs regulate lipid metabolism in domestic yaks. Therefore, we investigated the regulatory mechanisms of bta-miR-2400 in modulating yak preadipocytes proliferation and differentiation. We found that bta-miR-2400 was highly expressed in adipose tissue. Overexpression of bta-miR-2400 in yak preadipocytes significantly enhanced cell proliferation, increased the number of EdU fluorescence-stained cells, and promoted the expression of proliferation marker genes (CDK2, CDK4 and PCNA). Besides, overexpression of bta-miR-2400 repressed the expression of adipogenesis-related marker genes, and the content of cellular triglyceride was substantially reduced. Conversely, inhibition of bta-miR-2400 showed opposite effects compared to those of bta-miR-2400 overexpression in yak preadipocytes. Further, luciferase reporter assays revealed that SUMO1 is a target gene of bta-miR-2400, with bta-miR-2400 being able to down-regulate SUMO1 mRNA and protein expression. In conclusion, bta-miR-2400 regulates lipid metabolism and energy homeostasis in yak preadipocytes by directly targeting SUMO1 to promote cell proliferation and inhibit differentiation. Full article

Microglia act as the immune cells of the central nervous system (CNS). They play an important role in maintaining brain homeostasis but also in mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for neuroimmune regulation and subsequent effects on CNS integrity. However, the molecular mechanisms of neuron-glia communication in regulating microglia function are not fully understood. One recently described means of this intercellular communication is via nano-sized extracellular vesicles (EVs) that transfer a large diversity of molecules between neurons and microglia, such as proteins, lipids, and nucleic acids. To determine the effects of neuron-derived EVs (NDEVs) on microglia, NDEVs were isolated from the culture supernatant of rat cortical neurons. When NDEVs were added to primary cultured rat microglia, we found significantly improved microglia viability via inhibition of apoptosis. Additionally, application of NDEVs to cultured microglia also inhibited the expression of activation surface markers on microglia. Furthermore, NDEVs reduced the LPS-induced proinflammatory response in microglia according to reduced gene expression of proinflammatory cytokines (TNF-α, IL-6, MCP-1) and iNOS, but increased expression of the anti-inflammatory cytokine, IL-10. These findings support that neurons critically regulate microglia activity and control inflammation via EV-mediated neuron–glia communication. (Supported by R21AA025563 and R01AA025591). Full article

Decapod crustaceans are a very diverse group and have evolved to suit a wide variety of diets. Alpha-amylases enzymes, responsible for starch and glycogen digestion, have been more thoroughly studied in herbivore and omnivore than in carnivorous species. We used information on the α-amylase of a carnivorous lobster as a connecting thread to provide a more comprehensive view of α-amylases across decapods crustaceans. Omnivorous crustaceans such as shrimps, crabs, and crayfish present relatively high amylase activity with respect to carnivorous crustaceans. Yet, contradictory results have been obtained and relatively high activity in some carnivores has been suggested to be a remnant trait from ancestor species. Here, we provided information sustaining that high enzyme sequence and overall architecture conservation do not allow high changes in activity, and that differences among species may be more related to number of genes and isoforms, as well as transcriptional and secretion regulation. However, recent evolutionary analyses revealed that positive selection might have also occurred among distant lineages with feeding habits as a selection force. Some biochemical features of decapod α-amylases can be related with habitat or gut conditions, while less clear patterns are observed for other enzyme properties. Likewise, while molt cycle variations in α-amylase activity are rather similar among species, clear relationships between activity and diet shifts through development cannot be always observed. Regarding the adaptation of α-amylase to diet, juveniles seem to exhibit more flexibility than larvae, and it has been described variation in α-amylase activity or number of isoforms due to the source of carbohydrate and its level in diets, especially in omnivore species. In the carnivorous lobster, however, no influence of the type of carbohydrate could be observed. Moreover, lobsters were not able to fine-regulate α-amylase gene expression in spite of large changes in carbohydrate content of diet, while retaining some capacity to adapt α-amylase activity to very low carbohydrate content in the diets. In this review, we raised arguments for the need of more studies on the α-amylases of less studied decapods groups, including carnivorous species which rely more on dietary protein and lipids, to broaden our view of α-amylase in decapods crustaceans. Full article

In the current study, we aimed to investigate the associations between the natural variability in hyperactivity and inattention scores, as well as their combination with EEG oscillatory responses in the Stop-Signal task in a sample of healthy children. During performance, the Stop-Signal task EEGs were recorded in 94 Caucasian children (40 girls) from 7 to 10 years. Hyperactivity/inattention and inattention scores positively correlated with RT variability. Hyperactivity/inattention and inattention scores negatively correlated with an increase in beta spectral power in the first 200 ms after presentation of the Go stimulus. Such results are in line with the lack of arousal model in ADHD children and can be associated with less sensory arousal in the early stages of perception in children with symptoms of inattention. The subsequent greater increase in theta rhythm at about 300 ms after presentation of the Go stimulus in children with higher inattention scores may be associated with increased attention processes and compensation for insufficient vigilance in the early stages of perception. Full article

Non-threatening familiar sounds can go unnoticed during sleep despite the fact that they enter our brain by exciting the auditory nerves. Extracellular cortical recordings in the primary auditory cortex of rodents show that an increase in firing rate in response to pure tones during deep phases of sleep is comparable to those evoked during wakefulness. This result challenges the hypothesis that during sleep cortical responses are weakened through thalamic gating. An alternative explanation comes from the observation that the spatiotemporal spread of the evoked activity by transcranial magnetic stimulation in humans is reduced during non-rapid eye movement (NREM) sleep as compared to the wider propagation to other cortical regions during wakefulness. Thus, cortical responses during NREM sleep remain local and the stimulus only reaches nearby neuronal populations. We aim at understanding how this behavior emerges in the brain as it spontaneously shifts between NREM sleep and wakefulness. To do so, we have used a computational neural-mass model to reproduce the dynamics of the sensory auditory cortex and corresponding local field potentials in these two brain states. Following the synaptic homeostasis hypothesis, an increase in a single parameter, namely the excitatory conductance ${\overline{g}}_{\mathrm{AMPA}}$, allows us to place the model from NREM sleep into wakefulness. In agreement with the experimental results, the endogenous dynamics during NREM sleep produces a comparable, even higher, response to excitatory inputs to the ones during wakefulness. We have extended the model to two bidirectionally connected cortical columns and have quantified the propagation of an excitatory input as a function of their coupling. We have found that the general increase in all conductances of the cortical excitatory synapses that drive the system from NREM sleep to wakefulness does not boost the effective connectivity between cortical columns. Instead, it is the inter-/intra-conductance ratio of cortical excitatory synapses that should raise to facilitate information propagation across the brain. Full article

Retinal diseases are a leading cause of visual loss and blindness, affecting a significant proportion of the population worldwide and having a detrimental impact on quality of life, with consequent economic burden. The retina is highly metabolically active, and a number of retinal diseases are associated with metabolic dysfunction. To better understand the pathogenesis underlying such retinopathies, new technology has been developed to elucidate the mechanism behind retinal diseases. Metabolomics is a relatively new “omics” technology, which has developed subsequent to genomics, transcriptomics, and proteomics. This new technology can provide qualitative and quantitative information about low-molecular-weight metabolites (M.W. < 1500 Da) in a given biological system, which shed light on the physiological or pathological state of a cell or tissue sample at a particular time point. In this article we provide an extensive review of the application of metabolomics to retinal diseases, with focus on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), glaucoma, and retinitis pigmentosa (RP). Full article

The main objective of this study was to compare the effect of supplementing beef cattle with Desmanthus virgatus cv. JCU2, D. bicornutus cv. JCU4, D. leptophyllus cv. JCU7 and lucerne on in vivo methane (CH₄) emissions measured by open-circuit respiration chambers (OC) or the GreenFeed emission monitoring (GEM) system. Experiment 1 employed OC and utilized sixteen yearling Brangus steers fed a basal diet of Rhodes grass (Chloris gayana) hay in four treatments—the three Desmanthus cultivars and lucerne (Medicago sativa) at 30% dry matter intake (DMI). Polyethylene glycol (PEG) was added to the diets to neutralize tannin binding and explore the effect on CH₄ emissions. Experiment 2 employed GEM and utilized forty-eight animals allocated to four treatments including a basal diet of Rhodes grass hay plus the three Desmanthus cultivars in equal proportions at 0%, 15%, 30% and 45% DMI. Lucerne was added to equilibrate crude protein content in all treatments. Experiment 1 showed no difference in CH₄ emissions between the Desmanthus cultivars, between Desmanthus and lucerne or between Desmanthus and the basal diet. Experiment 2 showed an increase in CH₄ emissions in the three levels containing Desmanthus. It is concluded that on high-quality diets, Desmanthus does not reduce CH₄ emissions. Full article

Gut microbiota contributes to animal health. However, identifying which microorganisms or associated functions are involved remains, still, difficult to assess. In the present study, the microbiota of healthy broiler chickens, under controlled diet and farm conditions, was investigated by 16S rRNA gene sequencing in four intestine segments and at four ages. In detail, 210 Ross-308 male chickens were raised according to the EU guidelines and fed on a commercial diet. The duodenum, jejunum, ileum, and caecum microbiota were analyzed at 11, 24, 35, and 46 days of life. Although the microbial composition was revealed as homogeneous 11 days after chicks hatched, it was found to be similar in the proximal intestine segments and different in ileum and caecum, where almost the same genera and species were detected with different relative abundances. Although changes during the later growth stage were revealed, each genus remained relatively unchanged. Lactobacillus mostly colonized the upper tract of the intestine, whereas the Escherichia/Shigella genus the ileum. Clostridium and Bacteroides genera were predominant in the caecum, where the highest richness of bacterial taxa was observed. We also analyze and discuss the predicted role of the microbiota for each intestine segment and its potential involvement in nutrient digestion and absorption. Full article

Dengue fever is a viral mosquito-borne infection and a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called antibody-dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: (i) primary dengue infection, (ii) secondary dengue infection with the same (homologous) dengue virus and (iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights into the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines. Full article

Bees (Apoidea), the largest and most crucial radiation of pollinators, play a vital role in the ecosystem balance. Transposons are widely distributed in nature and are important drivers of species diversity. However, transposons are rarely reported in important pollinators such as bees. Here, we surveyed 37 bee genomesin Apoidea, annotated the pogo and Tc1/mariner transposons in the genome of each species, and performed a phylogenetic analysis and determined their overall distribution. The pogo and Tc1/mariner families showed high diversity and low abundance in the 37 species, and their proportion was significantly higher in solitary bees than in social bees. DD34D/mariner was found to be distributed in almost all species and was found in Apis mellifera, Apis mellifera carnica, Apis mellifera caucasia, and Apis mellifera mellifera, and Euglossa dilemma may still be active. Using horizontal transfer analysis, we found that DD29-30D/Tigger may have experienced horizontal transfer (HT) events. The current study displayed the evolution profiles (including diversity, activity, and abundance) of the pogo and Tc1/mariner transposons across 37 species of Apoidea. Our data revealed their contributions to the genomic variations across these species and facilitated in understanding of the genome evolution of this lineage. Full article

The RNA-binding protein HuD (a.k.a., ELAVL4) is involved in neuronal development and synaptic plasticity mechanisms, including addiction-related processes such as cocaine conditioned-place preference (CPP) and food reward. The most studied function of this protein is mRNA stabilization; however, we have recently shown that HuD also regulates the levels of circular RNAs (circRNAs) in neurons. To examine the role of HuD in the control of coding and non-coding RNA networks associated with substance use, we identified sets of differentially expressed mRNAs, circRNAs and miRNAs in the striatum of HuD knockout (KO) mice. Our findings indicate that significantly downregulated mRNAs are enriched in biological pathways related to cell morphology and behavior. Furthermore, deletion of HuD altered the levels of 15 miRNAs associated with drug seeking. Using these sets of data, we predicted that a large number of upregulated miRNAs form competing endogenous RNA (ceRNA) networks with circRNAs and mRNAs associated with the neuronal development and synaptic plasticity proteins LSAMP and MARK3. Additionally, several downregulated miRNAs form ceRNA networks with mRNAs and circRNAs from MEF2D, PIK3R3, PTRPM and other neuronal proteins. Together, our results indicate that HuD regulates ceRNA networks controlling the levels of mRNAs associated with neuronal differentiation and synaptic physiology. Full article

The coenzyme Q10 analogue idebenone is an FDA-approved antioxidant that can cross the blood–brain barrier (BBB). The effects of idebenone on the pathology of Alzheimer’s disease (AD) and the underlying molecular mechanisms have not been comprehensively investigated. Here, we examined the impact of idebenone treatment on AD pathology in 5xFAD mice, a model of AD. Idebenone significantly downregulated Aβ plaque number via multi-directional pathways in this model. Specifically, idebenone reduced the RAGE/caspase-3 signaling pathway and increased levels of the Aβ degradation enzyme NEP and α-secretase ADAM17 in 5xFAD mice. Importantly, idebenone significantly suppressed tau kinase p-GSK3β^Y216 levels, thereby inhibiting tau hyperphosphorylation at Thr231 and total tau levels in 5xFAD mice. Taken together, the present study indicates that idebenone modulates amyloidopathy and tauopathy in 5xFAD mice, suggesting therapeutic potential for AD. Full article

Regeneration is usually regarded as a unique plant or some animal species process. In reality, regeneration is a ubiquitous process in all multicellular organisms. It ranges from response to wounding by healing the wounded tissue to whole body neoforming (remaking of the new body). In a larger context, regeneration is one facet of two reproduction schemes that dominate the evolution of life. Multicellular organisms can propagate their genes asexually or sexually. Here I present the view that the ability to regenerate tissue or whole-body regeneration is also determined by the sexual state of the multicellular organisms (from simple animals such as hydra and planaria to plants and complex animals). The above idea is manifested here by showing evidence that many organisms, organs, or tissues show inhibited or diminished regeneration capacity when in reproductive status compared to organs or tissues in nonreproductive conditions or by exposure to sex hormones. Full article

In their foraging behavior octopuses rely on arm search movements outside the visual field of the eyes. In these movements the environment is explored primarily by the suckers that line the entire length of the octopus arm. In this study, for the first time, we report the complete characterization of a light-sensing molecule, Ov-GRK1, in the suckers, skin and retina of Octopus vulgaris. We sequenced the O. vulgaris GRK1 gene, defining a phylogenetic tree and performing a 3D structure model prediction. Furthermore, we found differences in relative mRNA expression in different sucker types at several arm levels, and localized it through in situ hybridization. Our findings suggest that the suckers in octopus arms are much more multimodal than was previously shown, adding the potential for light sensing to the already known mechanical and chemical sensing abilities. Full article

Sexual and polyploidy size dimorphisms are widespread phenomena in fish, but the molecular mechanisms remain unclear. Loach (Misgurnus anguillicaudatus) displays both sexual and polyploid growth dimorphism phenomena, and are therefore ideal models to study these two phenomena. In this study, RNA-seq was used for the first time to explore the differentially expressed genes (DEGs) between both sexes of diploid and tetraploid loaches in four tissues (brain, gonad, liver, and muscle). Results showed that 21,003, 17, and 1 DEGs were identified in gonad, liver, and muscle tissues, respectively, between females and males in both diploids and tetraploids. Regarding the ploidy levels, 4956, 1496, 2187, and 1726 DEGs were identified in the brain, gonad, liver, and muscle tissues, respectively, between tetraploids and diploids of the same sex. When both sexual and polyploid size dimorphisms were considered simultaneously in the four tissues, only 424 DEGs were found in the gonads, indicating that these gonadal DEGs may play an important regulatory role in regulating sexual and polyploid size dimorphisms. Regardless of the sex or ploidy comparison, the significant DEGs involved in glycolysis/gluconeogenesis and oxidative phosphorylation pathways were upregulated in faster-growing individuals, while steroid hormone biosynthesis-related genes and fatty acid degradation and elongation-related genes were downregulated. This suggests that fast-growing loaches (tetraploids, females) have higher energy metabolism levels and lower steroid hormone synthesis and fatty acid degradation abilities than slow-growing loaches (diploids, males). Our findings provide an archive for future systematic research on fish sexual and polyploid dimorphisms. Full article

Recent studies suggest that Th2 cells play a key role in the pathology of secondary lymphedema by elaborating cytokines such as IL4 and IL13. The aim of this study was to test the efficacy of QBX258, a monoclonal IL4/IL13 neutralizing antibody, in women with breast cancer–related lymphedema (BCRL). We enrolled nine women with unilateral stage I/II BCRL and treated them once monthly with intravenous infusions of QBX258 for 4 months. We measured limb volumes, bioimpedance, and skin tonometry, and analyzed the quality of life (QOL) using a validated lymphedema questionnaire (Upper Limb Lymphedema 27, ULL-27) before treatment, immediately after treatment, and 4 months following treatment withdrawal. We also obtained 5 mm skin biopsies from the normal and lymphedematous limbs before and after treatment. Treatment was well-tolerated; however, one patient with a history of cellulitis developed cellulitis during the trial and was excluded from further analysis. We found no differences in limb volumes or bioimpedance measurements after drug treatment. However, QBX258 treatment improved skin stiffness (p < 0.001) and improved QOL measurements (Physical p < 0.05, Social p = 0.01). These improvements returned to baseline after treatment withdrawal. Histologically, treatment decreased epidermal thickness, the number of proliferating keratinocytes, type III collagen deposition, infiltration of mast cells, and the expression of Th2-inducing cytokines in the lymphedematous skin. Our limited study suggests that immunotherapy against Th2 cytokines may improve skin changes and QOL of women with BCRL. This treatment appears to be less effective for decreasing limb volumes; however, additional studies are needed. Full article