An early global role for Axin is required for correct patterning of the anterior-posterior axis in the sea urchin embryo.

Activation of Wnt/ß-catenin (cWnt) signaling at the future posterior end of early bilaterian embryos is a highly conserved mechanism for establishing the anterior-posterior (AP) axis. Moreover, inhibition of cWnt at the anterior end is required for development of anterior structures in many deuterostome taxa. This phenomenon, which occurs around the time of gastrulation, has been fairly well characterized, but the significance of intracellular inhibition of cWnt signaling in cleavage-stage deuterostome embryos for normal AP patterning is less well understood. To investigate this process in an invertebrate deuterostome, we defined Axin function in early sea urchin embryos. Axin is ubiquitously expressed at relatively high levels in early embryos and functional analysis revealed that Axin suppresses posterior cell fates in anterior blastomeres by blocking ectopic cWnt activation in these cells. Structure-function analysis of sea urchin Axin demonstrated that only its GSK-3ß-binding domain is required for cWnt inhibition. These observations and results in other deuterostomes suggest that Axin plays a crucial conserved role in embryonic AP patterning by preventing cWnt activation in multipotent early blastomeres, thus protecting them from assuming ectopic cell fates.

Relationship between cognitive function and weight-adjusted waist index in people ≥ 60 years old in NHANES 2011-2014.

BACKGROUND: Widespread attention has been given to the detrimental effects of obesity on cognitive function. However, there is no evidence on the connection between low cognitive performance and the WWI (weight-adjusted waist index). This study looked into the connection between poor cognitive performance and the WWI in senior Americans. METHODS: A cross-sectional research study was carried out with information from the NHANES 2011-2014. With multivariate linear regression models, the pertinence between the WWI and low cognitive function in persons older than 60 years was examined. The nonlinear link was described using threshold effect analyses and fitted smoothed curves. Interaction tests and subgroup analysis were also conducted. RESULTS: The study had 2762 individuals in all, and subjects with higher WWI values were at greater risk for low cognitive function. In the completely adjusted model, the WWI was positively connected with low cognitive performance assessed by CERAD W-L (OR = 1.22, 95% CI 1.03-1.45, p = 0.0239), AFT (OR = 1.30, 95% CI 1.09-1.54, p = 0.0029), and DSST (OR = 1.59, 95% CI 1.30-1.94, p < 0.0001). The effect of each subgroup on the positive correlation between the WWI and low cognitive performance was not significant. The WWI and low cognitive performance as determined by CERAD W-L and AFT had a nonlinear connection (log-likelihood ratio < 0.05). CONCLUSION: Among older adults in the United States, the risk of low cognitive performance may be positively related to the WWI.

Horizontally transferred genes as RNA interference targets for aphid and whitefly control.

RNA interference (RNAi)-based technologies are starting to be commercialized as a new approach for agricultural pest control. Horizontally transferred genes (HTGs), which have been transferred into insect genomes from viruses, bacteria, fungi or plants, are attractive targets for RNAi-mediated pest control. HTGs are often unique to a specific insect family or even genus, making it unlikely that RNAi constructs targeting such genes will have negative effects on ladybugs, lacewings and other beneficial predatory insect species. In this study, we sequenced the genome of a red, tobacco-adapted isolate of Myzus persicae (green peach aphid) and bioinformatically identified 30 HTGs. We then used plant-mediated virus-induced gene silencing (VIGS) to show that several HTGs of bacterial and plant origin are important for aphid growth and/or survival. Silencing the expression of fungal-origin HTGs did not affect aphid survivorship but decreased aphid reproduction. Importantly, although there was uptake of plant-expressed RNA by Coccinella septempunctata (seven-spotted ladybugs) via the aphids that they consumed, we did not observe negative effects on ladybugs from aphid-targeted VIGS constructs. To demonstrate that this approach is more broadly applicable, we also targeted five Bemisia tabaci (whitefly) HTGs using VIGS and demonstrated that knockdown of some of these genes affected whitefly survival. As functional HTGs have been identified in the genomes of numerous pest species, we propose that these HTGs should be explored further as efficient and safe targets for control of insect pests using plant-mediated RNA interference.

Effects of new hypoglycemic drugs on cardiac remodeling: a systematic review and network meta-analysis.

BACKGROUND: In recent years, the incidence of diabetes mellitus has been increasing annually, and cardiovascular complications secondary to diabetes mellitus have become the leading cause of death in diabetic patients. Considering the high incidence of type 2 diabetes (T2DM) combined with cardiovascular disease (CVD), some new hypoglycemic agents with cardiovascular protective effects have attracted extensive attention. However, the specific role of these regimens in ventricular remodeling remains unknown. The purpose of this network meta-analysis was to compare the effects of sodium glucose cotransporter type 2 inhibitor (SGLT-2i), glucagon-like peptide 1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 inhibitor (DPP-4i) on ventricular remodeling in patients with T2DM and/or CVD. METHODS: Articles published prior to 24 August 2022 were retrieved in four electronic databases: the Cochrane Library, Embase, PubMed, and Web of Science. This meta-analysis included randomized controlled trials (RCTs) and a small number of cohort studies. The differences in mean changes of left ventricular ultrasonic parameters between the treatment and control groups were compared. RESULTS: A total of 31 RCTs and 4 cohort studies involving 4322 patients were analyzed. GLP-1RA was more significantly associated with improvement in left ventricular end-systolic diameter (LVESD) [MD = -0.38 mm, 95% CI (-0.66, -0.10)] and LV mass index (LVMI) [MD = -1.07 g/m2, 95% CI (-1.71, -0.42)], but significantly decreased e' [MD = -0.43 cm/s 95% CI (-0.81, -0.04)]. DPP-4i was more strongly associated with improvement in e' [MD = 3.82 cm/s, 95% CI (2.92,4.7)] and E/e'[MD = -5.97 95% CI (-10.35, -1.59)], but significantly inhibited LV ejection fraction (LVEF) [MD = -0.89% 95% CI (-1.76, -0.03)]. SGLT-2i significantly improved LVMI [MD = -0.28 g/m2, 95% CI (-0.43, -0.12)] and LV end-diastolic diameter (LVEDD) [MD = -0.72 ml, 95% CI (-1.30, -0.14)] in the overall population, as well as E/e' and SBP in T2DM patients combined with CVD, without showing any negative effect on left ventricular function. CONCLUSION: The results of the network meta-analysis provided high certainty to suggest that SGLT-2i may be more effective in cardiac remodeling compared to GLP-1RA and DPP-4i. While GLP-1RA and DPP-4i may have a tendency to improve cardiac systolic and diastolic function respectively. SGLT-2i is the most recommended drug for reversing ventricular remodeling in this meta-analysis.

Analysis of clinical characteristics and prognosis of 68 patients with primary pulmonary choriocarcinoma.

BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is a highly malignant intrapulmonary tumor with a notorious prognosis. Few clinical studies have been undertaken to investigate the clinical characteristics and prognosis of PPC. MATERIAL AND METHODS: We systematically conducted a retrospective analysis of patients with PPC in the literature published in PubMed and CNKI databases until March 31, 2022. The primary outcome was all-cause mortality. Survival curves were depicted using the Kaplan‒Meier method and compared using the stratified log-rank test. A Cox proportional hazards model was used to estimate the prognostic factors. RESULTS: A total of 68 patients were included, which consisted of 32 females and 36 males, with an average age of (44.5 ± 16.8) years old, ranging from 19 to 77 years. The clinical characteristics were mostly cough (49.2%), dyspnea (22.2%), hemoptysis (39.7%) and chest pain (39.7%). Kaplan‒Meier analysis showed that sex, age, hemoptysis, metastasis and treatment combining surgery with chemotherapy had a significant effect on survival. There were no effects on other outcomes. Furthermore, univariate and multivariable Cox regression analyses showed that the impact of the treatment combining surgery with chemotherapy on OS showed independent prognostic significance. CONCLUSION: PPC is a rare disease that lacks specific clinical features. Early diagnosis with optimal management is a significant goal. Surgery followed by adjuvant chemotherapy may be the best treatment for PPC.

Acylsugars protect Nicotiana benthamiana against insect herbivory and desiccation.

KEY MESSAGE: Nicotiana benthamiana acylsugar acyltransferase (ASAT) is required for protection against desiccation and insect herbivory. Knockout mutations provide a new resource for investigation of plant-aphid and plant-whitefly interactions. Nicotiana benthamiana is used extensively as a transient expression platform for functional analysis of genes from other species. Acylsugars, which are produced in the trichomes, are a hypothesized cause of the relatively high insect resistance that is observed in N. benthamiana. We characterized the N. benthamiana acylsugar profile, bioinformatically identified two acylsugar acyltransferase genes, ASAT1 and ASAT2, and used CRISPR/Cas9 mutagenesis to produce acylsugar-deficient plants for investigation of insect resistance and foliar water loss. Whereas asat1 mutations reduced accumulation, asat2 mutations caused almost complete depletion of foliar acylsucroses. Three hemipteran and three lepidopteran herbivores survived, gained weight, and/or reproduced significantly better on asat2 mutants than on wildtype N. benthamiana. Both asat1 and asat2 mutations reduced the water content and increased leaf temperature. Our results demonstrate the specific function of two ASAT proteins in N. benthamiana acylsugar biosynthesis, insect resistance, and desiccation tolerance. The improved growth of aphids and whiteflies on asat2 mutants will facilitate the use of N. benthamiana as a transient expression platform for the functional analysis of insect effectors and resistance genes from other plant species. Similarly, the absence of acylsugars in asat2 mutants will enable analysis of acylsugar biosynthesis genes from other Solanaceae by transient expression.

Octopamine modulates insect mating and Oviposition.

The neuro-mechanisms that regulate insect reproduction are not fully understood. Biogenic amines, including octopamine, are neuromodulators that have been shown to modulate insect reproduction in various ways, e.g., promote or inhibit insect mating or oviposition. In this study, we examined the role of octopamine in regulating the reproduction behaviors of a devastating underground insect pest, the dark black chafer (Holotrichia parallela). We first measured the abundance of octopamine in different neural tissues of the adult chafer pre- and post-mating, demonstrating that octopamine decreased in the abdominal ganglia of females but increased in males post-mating. We then fed the adult H. parallela with a concentration gradient of octopamine to test the effects on insect reproductive behaviors. Compared with its antagonist mianserin, octopamine at the concentration of 2 µg/mL resulted in the highest increase in males' preference for sex pheromone and females' oviposition, whereas the mianserin-treatment increased the survival rate and prolonged the lifespan of H. parallela. In addition, we did not observe significant differences in egg hatchability between octopamine and mianserin-treated H. parallela. Our results demonstrated that octopamine promotes H. parallela mating and oviposition with a clear low dosage effect, illustrated how neural substrates modulate insect behaviors, and provided insights for applying octopamine in pest management.

Trading amino acids at the aphid-Buchnera symbiotic interface.

Plant sap-feeding insects are widespread, having evolved to occupy diverse environmental niches despite exclusive feeding on an impoverished diet lacking in essential amino acids and vitamins. Success depends exquisitely on their symbiotic relationships with microbial symbionts housed within specialized eukaryotic bacteriocyte cells. Each bacteriocyte is packed with symbionts that are individually surrounded by a host-derived symbiosomal membrane representing the absolute host-symbiont interface. The symbiosomal membrane must be a dynamic and selectively permeable structure to enable bidirectional and differential movement of essential nutrients, metabolites, and biosynthetic intermediates, vital for growth and survival of host and symbiont. However, despite this crucial role, the molecular basis of membrane transport across the symbiosomal membrane remains unresolved in all bacteriocyte-containing insects. A transport protein was immunolocalized to the symbiosomal membrane separating the pea aphid Acyrthosiphon pisum from its intracellular symbiont Buchnera aphidicola The transporter, A. pisum nonessential amino acid transporter 1, or ApNEAAT1 (gene: ACYPI008971), was characterized functionally following heterologous expression in Xenopus oocytes, and mediates both inward and outward transport of small dipolar amino acids (serine, proline, cysteine, alanine, glycine). Electroneutral ApNEAAT1 transport is driven by amino acid concentration gradients and is not coupled to transmembrane ion gradients. Previous metabolite profiling of hemolymph and bacteriocyte, alongside metabolic pathway analysis in host and symbiont, enable prediction of a physiological role for ApNEAAT1 in bidirectional host-symbiont amino acid transfer, supplying both host and symbiont with indispensable nutrients and biosynthetic precursors to facilitate metabolic complementarity.

Immune-related genes of the larval Holotrichia parallela in response to entomopathogenic nematodes Heterorhabditis beicherriana LF.

BACKGROUND: Entomopathogenic nematodes (EPNs) emerge as compatible alternatives to conventional insecticides in controlling Holotrichia parallela larvae (Coleoptera: Scarabaeidae). However, the immune responses of H. parallela against EPNs infection remain unclear. RESULTS: In present research, RNA-Seq was firstly performed. A total of 89,427 and 85,741 unigenes were achieved from the midgut of H. parallela larvae treated with Heterorhabditis beicherriana LF for 24 and 72 h, respectively; 2545 and 3156 unigenes were differentially regulated, respectively. Among those differentially expressed genes (DEGs), 74 were identified potentially related to the immune response. Notably, some immune-related genes, such as peptidoglycan recognition protein SC1 (PGRP-SC1), pro-phenoloxidase activating enzyme-I (PPAE-I) and glutathione s-transferase (GST), were induced at both treatment points. Bioinformatics analysis showed that PGRP-SC1, PPAE-I and GST were all involved in anti-parasitic immune process. Quantitative real-time PCR (qRT-PCR) results showed that the three immune-related genes were expressed in all developmental stages; PGRP-SC1 and PPAE-I had higher expressions in midgut and fat body, respectively, while GST exhibited high expression in both of them. Moreover, in vivo silencing of them resulted in increased susceptibility of H. parallela larvae to H. beicherriana LF. CONCLUSION: These results suggest that H. parallela PGRP-SC1, PPAE-I and GST are involved in the immune responses to resist H. beicherriana LF infection. This study provides the first comprehensive transcriptome resource of H. parallela exposure to nematode challenge that will help to support further comparative studies on host-EPN interactions.

Diphenyl diselenide protects motor neurons through inhibition of microglia-mediated inflammatory injury in amyotrophic lateral sclerosis.

Microglia-mediated neuroinflammatory response and neuron damage are considered as a self-propelling progressive cycle, being strongly implicated in the progression of neurodegeneration in amyotrophic lateral sclerosis (ALS). Diphenyl diselenide (DPDS), a simple organoselenium compound, has been known to possess multiple pharmacological properties. The purpose of this study was to explore the neuroprotective effects of DPDS against microglia-mediated neuroinflammatory injury in ALS models. We found that DPDS pretreatment inhibited LPS-induced activation of IκB/NF-κB pathway and subsequent release of proinflammatory factors from activated primary hSOD1G93A microglia. Moreover, DPDS suppressed NLRP3 inflammasome activation by decreasing protein nitration via reduction in NO and ROS levels, whose low levels are related to NF-κB inhibition responsible for iNOS and NOX2 down-regulations, respectively. Notably, DPDS-mediated ROS attenuation was not linked to Nrf2 activation in this cellular model. Furthermore, in the absence of activated microglia, DPDS has no significant effect on the individual hSOD1G93A-NSC34 cells; however, in in vitro neuron-microglia conditional culture and co-culture experiments, DPDS protected motor neurons from neurotoxic damage caused by LPS or BzATP-stimulated microglia activation. Above observations suggest that DPDS-afforded neuroprotection is linked to inhibition of microglia-mediated neuroinflammation in ALS, which was further verified in vivo as shown by improvements of motor deficits, prolonged survival, and reduction of motor neuron loss and reactive microgliosis in hSOD1G93A transgenic mouse. Altogether, our results show that DPDS elicited neuroprotection in ALS models through inactivation of microglia by inhibiting IκB/NF-κB pathway and NLRP3 inflammasome activation, suggesting that DPDS may be a promising candidate for potential therapy for ALS.

The genome sequence of the grape phylloxera provides insights into the evolution, adaptation, and invasion routes of an iconic pest.

BACKGROUND: Although native to North America, the invasion of the aphid-like grape phylloxera Daktulosphaira vitifoliae across the globe altered the course of grape cultivation. For the past 150 years, viticulture relied on grafting-resistant North American Vitis species as rootstocks, thereby limiting genetic stocks tolerant to other stressors such as pathogens and climate change. Limited understanding of the insect genetics resulted in successive outbreaks across the globe when rootstocks failed. Here we report the 294-Mb genome of D. vitifoliae as a basic tool to understand host plant manipulation, nutritional endosymbiosis, and enhance global viticulture. RESULTS: Using a combination of genome, RNA, and population resequencing, we found grape phylloxera showed high duplication rates since its common ancestor with aphids, but similarity in most metabolic genes, despite lacking obligate nutritional symbioses and feeding from parenchyma. Similarly, no enrichment occurred in development genes in relation to viviparity. However, phylloxera evolved > 2700 unique genes that resemble putative effectors and are active during feeding. Population sequencing revealed the global invasion began from the upper Mississippi River in North America, spread to Europe and from there to the rest of the world. CONCLUSIONS: The grape phylloxera genome reveals genetic architecture relative to the evolution of nutritional endosymbiosis, viviparity, and herbivory. The extraordinary expansion in effector genes also suggests novel adaptations to plant feeding and how insects induce complex plant phenotypes, for instance galls. Finally, our understanding of the origin of this invasive species and its genome provide genetics resources to alleviate rootstock bottlenecks restricting the advancement of viticulture.

Correction to: The genome sequence of the grape phylloxera provides insights into the evolution, adaptation, and invasion routes of an iconic pest.

An amendment to this paper has been published and can be accessed via the original article.

Wild-type p53-induced phosphatase 1 down-regulation promotes apoptosis by activating the DNA damage-response pathway in amyotrophic lateral sclerosis.

Accumulation of DNA damage has been detected in the spinal cord of patients as well as in the G93A mouse model of amyotrophic lateral sclerosis (ALS). Wild-type p53-induced phosphatase 1 (Wip1) is a p53-inducible serine/threonine phosphatase that terminates DNA-damage responses via dephosphorylation of DNA-damage response proteins, namely ataxia-telangiectasia mutated (ATM) kinase, checkpoint kinase 2, and p53, thus enhancing cell proliferation. However, the role of Wip1, DNA-damage responses, and their interaction in ALS development remains to be elucidated. Here, we showed that Wip1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro. The DNA-damage response was activated in superoxide dismutase 1 (SOD1) G93A-transfected cells. However, increased expression of Wip1 improved cell viability and inhibited the DNA-damage response in mutated SOD1G93A cells. Further studies demonstrated that decreased Wip1 expression reduced cell viability and further activated the DNA-damage response in chronic H2O2-treated NSC34 cells. In contrast, Wip1 promoted cell survival and suppressed DNA damage-induced apoptosis during persistent DNA damage conditions. Over-expression of Wip1 in the central nervous system (CNS) can delay the onset of disease symptoms, extended the survival, decreased MN loss improved motor function and inhibit the DNA-damage response in SOD1 G93A mice. Furthermore, homeodomain-interacting protein kinase 2 (HIPK2) promoted the degradation of Wip1 via the ubiquitin-proteasome system during chronic stress. These findings indicate that persistent accumulation of DNA damage and subsequent chronic activation of the downstream DNA damage-response ATM and p53 pro-apoptotic signaling pathways may trigger neuronal dysfunction and neuronal death in ALS. Wip1 may play a protective role by targeting the DNA-damage response in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS.

Lithium facilitates removal of misfolded proteins and attenuated faulty interaction between mutant SOD1 and p-CREB (Ser133) through enhanced autophagy in mutant hSOD1G93A transfected neuronal cell lines.

Abnormally protein aggregation and deposition are key pathological features of ALS, which may related with dysfunctional cellular autophagy. In the current study, we found that, compared with wtSOD1 cells, serum starvation treatment resulted in significant higher percentage of apoptosis in mutSOD1 cells; Lithium treatment exerted protection for those mutSOD1 cells, with decreased GFP-tagged mutant SOD1 protein aggregates deposition; Whereas, pre-treatment with Baf or 3-MA (autophagy inhibitors) blocked protection of lithium for mutant SOD1 cells, and induced increased GFP-tagged mutant SOD1 protein aggregation. Further, Western blots results showed that lithium treatment led to decrease of mutant hSOD1 protein levels in both Triton X-100 soluble and Triton X-100 insoluble fraction of mutSOD1 cells. Besides, improper binding of mutant SOD1 proteins' aggregates with p-CREB (Ser133) (transcription factor) in mutSOD1 cells were demonstrated; whereas lithium treatment attenuated this fault interaction. In conclusion, our results showed that, in mutSOD1 cells, mutSOD1 protein aggregates were related with abnormal autophagic regulation. Lithium treatment could induce autophagy and enhance clearance of protein aggregates, further exerting protection on mutSOD1 cells. More importantly, we uncovered another distinct pathological role of mutSOD1 protein aggregates, that is abnormal binding with p-CREB (Ser133), an important transcription factor, which may play crucial role in the PI3K-Akt-CREB-AEG-1 signaling pathway.

Astrocyte elevated gene-1 is a novel regulator of astrogliosis and excitatory amino acid transporter-2 via interplaying with nuclear factor-κB signaling in astrocytes from amyotrophic lateral sclerosis mouse model with hSOD1G93A mutation.

AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A-positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling. Besides, excitatory amino acid transporter-2 (EAAT2) expression levels were significantly decreased, accompanied by impaired glutamate clearance ability, in mut-SOD1 astrocytes; yin yang 1 (YY1), a transcriptional inhibitor for EAAT2, increased in nucleus of mut-SOD1 astrocytes. AEG-1 silence inhibited translocation of YY1 to nucleus, increased EAAT2 expression levels, and enhanced astrocytic ability of glutamate clearance, ultimately exerted the neuronal protection. Findings from this study implicate potential function of AEG-1 in mut-SOD1 related astrogliosis and the accompanied excitatory cytotoxic mechanism in ALS.

microRNA regulation in an ancient obligate endosymbiosis.

Although many insects are associated with obligate bacterial endosymbionts, the mechanisms by which these host/endosymbiont associations are regulated remain mysterious. While microRNAs (miRNAs) have been recently identified as regulators of host/microbe interactions, including host/pathogen and host/facultative endosymbiont interactions, the role miRNAs may play in mediating host/obligate endosymbiont interactions is virtually unknown. Here, we identified conserved miRNAs that potentially mediate symbiotic interactions between aphids and their obligate endosymbiont, Buchnera aphidicola. Using small RNA sequence data from Myzus persicae and Acyrthosiphon pisum, we annotated 93 M. persicae and 89 A. pisum miRNAs, among which 69 were shared. We found 14 miRNAs that were either highly expressed in aphid bacteriome, the Buchnera-housing tissue, or differentially expressed in bacteriome vs. gut, a non-Buchnera-housing tissue. Strikingly, 10 of these 14 miRNAs have been implicated previously in other host/microbe interaction studies. Investigating the interaction networks of these miRNAs using a custom computational pipeline, we identified 103 miRNA::mRNA interactions shared between M. persicae and A. pisum. Functional annotation of the shared mRNA targets revealed only two over-represented cluster of orthologous group categories: amino acid transport and metabolism, and signal transduction mechanisms. Our work supports a role for miRNAs in mediating host/symbiont interactions between aphids and their obligate endosymbiont Buchnera. In addition, our results highlight the probable importance of signal transduction mechanisms to host/endosymbiont coevolution.

Roles of AEG-1 in CNS neurons and astrocytes during noncancerous processes.

Since its initial identification, Astrocyte Elevated Gene-1 (AEG-1) has been recognized as a "star" gene detected in most of the analyzed cancers; AEG-1 can interact with signaling transduction molecules, such as PI3K/Akt and MAPK, to affect the function and viability of cells. Furthermore, its multiple other functions are also gradually being recognized. AEG-1 participates in several biological processes, including embryonic development, glutamate excitotoxicity, inflammation, and endoplasmic reticulum stress. Most of the noncancerous roles of the AEG-1 were identified in studies of the neurological disorders of the CNS. As an oncogene that promotes aberrant cellular processes within the CNS, AEG-1 may also represent an important therapeutic target for the treatment of neurological disease. However, the exact role of the AEG-1 in CNS under normal conditions is still unknown. This review will focus on the literature describing the role of this molecule in CNS neurons and astrocytes during noncancerous processes. © 2017 Wiley Periodicals, Inc.

Aphid amino acid transporter regulates glutamine supply to intracellular bacterial symbionts.

Endosymbiotic associations have played a major role in evolution. However, the molecular basis for the biochemical interdependence of these associations remains poorly understood. The aphid-Buchnera endosymbiosis provides a powerful system to elucidate how these symbioses are regulated. In aphids, the supply of essential amino acids depends on an ancient nutritional symbiotic association with the gamma-proteobacterium Buchnera aphidicola. Buchnera cells are densely packed in specialized aphid bacteriocyte cells. Here we confirm that five putative amino acid transporters are highly expressed and/or highly enriched in Acyrthosiphon pisum bacteriocyte tissues. When expressed in Xenopus laevis oocytes, two bacteriocyte amino acid transporters displayed significant levels of glutamine uptake, with transporter ACYPI001018, LOC100159667 (named here as Acyrthosiphon pisum glutamine transporter 1, ApGLNT1) functioning as the most active glutamine transporter. Transporter ApGLNT1 has narrow substrate selectivity, with high glutamine and low arginine transport capacity. Notably, ApGLNT1 has high binding affinity for arginine, and arginine acts as a competitive inhibitor for glutamine transport. Using immunocytochemistry, we show that ApGLNT1 is localized predominantly to the bacteriocyte plasma membrane, a location consistent with the transport of glutamine from A. pisum hemolymph to the bacteriocyte cytoplasm. On the basis of functional transport data and localization, we propose a substrate feedback inhibition model in which the accumulation of the essential amino acid arginine in A. pisum hemolymph reduces the transport of the precursor glutamine into bacteriocytes, thereby regulating amino acid biosynthesis in the bacteriocyte. Structural similarities in the arrangement of hosts and symbionts across endosymbiotic systems suggest that substrate feedback inhibition may be mechanistically important in other endosymbioses.

Downregulated AEG-1 together with inhibited PI3K/Akt pathway is associated with reduced viability of motor neurons in an ALS model.

Astrocyte elevated gene-1 (AEG-1) has been reported to regulate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and is also regulated by it. This study investigated how AEG-1 participates in the survival pathway of motor neurons in amyotrophic lateral sclerosis (ALS). We found reduced levels of AEG-1 in ALS motor neurons, both in vivo and in vitro, compared to wild type controls. Moreover, AEG-1 silencing demonstrated inhibition of the PI3K/Akt pathway and increased cell apoptosis. Additionally, the PI3K/Akt pathway in mSOD1 cells was unresponsive under serum deprivation conditions compared to wtSOD1 cells. These results suggest that AEG-1 deficiency, together with the inhibited PI3K/Akt pathway was associated with decreased viability of ALS motor neurons. However, the mRNA levels of AEG-1 were still lower in mSOD1 cells compared to the control groups, though the signaling pathway was activated by application of a PI3-K activator. This suggests that in ALS motor neurons, some unknown interruption exists in the PI3K/Akt/CREB/AEG-1 feedback loop, thus attenuating the protection by this signaling pathway. Together, these findings support that AEG-1 is a critical factor for cell survival, and the disrupted PI3K/Akt/CREB/AEG-1cycle is involved in the death of injured motor neurons and pathogenesis of ALS.

A Community-Based Study of the Correlation of Hemorrhagic Stroke Occurrence with Meteorologic Factors.

BACKGROUND: Meteorologic variations may affect hemorrhagic stroke. Thus, the aim of this study was to explore the correlation of daily meteorologic factors with increased incidence of hypertensive intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) in a community-based study. METHODS: In a span of 2 years, 735 patients suffering from hypertensive ICH or SAH were enrolled in the study in Fularji District, Heilongjiang Province, China. Daily meteorologic data were obtained from the Bureau of Meteorology of Qiqihar. Daily meteorologic parameters with and without events were compared with hypertensive ICH and SAH, respectively. Logistic regression was used to assess the correlation of meteorologic factors with hypertensive ICH and SAH. RESULTS: Daily mean ambient temperature (AT) was statistically associated with the onset of primary hypertensive ICH (odds ratio [OR], .983; P < .001) and SAH (OR, .984; P = .046). After adjustment with AT variations, the occurrence of primary hypertensive ICH was not only influenced by daily mean AT (P = .0004) but also by the interaction between the mean temperature and its variation (P = .0082). Interestingly, there was no statistical association between meteorologic factors and recurrent hypertensive ICH. CONCLUSIONS: The higher incidence of primary hypertensive ICH in the late spring and early autumn was because of the influence of daily mean AT and its variation. When temperature changed, suddenly dropping in the hot weather or rising in the cold weather, the incidence of primary hypertensive ICH was also increased. Conversely, the incidence of SAH increased during days with lower temperature.