Summary
Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia. Pathological ...tau is hyperphosphorylated and aggregates to form neurofibrillary tangles. The molecular mechanisms leading to tau accumulation remain unclear and more needs to be done to elucidate them. Age is a major risk factor for all tauopathies, suggesting that molecular changes contributing to the aging process may facilitate tau accumulation and represent common mechanisms across different tauopathies. Here, we use multiple animal models and complementary genetic and pharmacological approaches to show that the mammalian target of rapamycin (mTOR) regulates tau phosphorylation and degradation. Specifically, we show that genetically increasing mTOR activity elevates endogenous mouse tau levels and phosphorylation. Complementary to it, we further demonstrate that pharmacologically reducing mTOR signaling with rapamycin ameliorates tau pathology and the associated behavioral deficits in a mouse model overexpressing mutant human tau. Mechanistically, we provide compelling evidence that the association between mTOR and tau is linked to GSK3β and autophagy function. In summary, we show that increasing mTOR signaling facilitates tau pathology, while reducing mTOR signaling ameliorates tau pathology. Given the overwhelming evidence that reducing mTOR signaling increases lifespan and healthspan, the data presented here have profound clinical implications for aging and tauopathies and provide the molecular basis for how aging may contribute to tau pathology. Additionally, these results provide preclinical data indicating that reducing mTOR signaling may be a valid therapeutic approach for tauopathies.
Perirhinal cortex is a brain area that has been considered crucial for the object recognition memory (ORM). However, with the use of an ORM enhancer named RGS14414 as gain‐in‐function tool, we show ...here that frontal association cortex and not the Perirhinal cortex is essential for the ORM of objects with complex features that consisted of detailed drawing on the object surface (complex ORM). An expression of RGS14414, in rat brain frontal association cortex, induced the formation of long‐term complex ORM, whereas the expression of the same memory enhancer in Perirhinal cortex failed to produce this effect. Instead, RGS14414 expression in Perirhinal cortex caused the formation of ORM of objects with simple features that consisted of the shape of object (simple ORM). Further, a selective elimination of frontal association cortex neurons by treatment with an immunotoxin Ox7‐SAP completely abrogated the formation of complex ORM. Thus, our results suggest that frontal association cortex plays a key role in processing of a high‐order recognition memory information in brain.
An activation of frontal association cortex through overexpression of RGS14414 led to the formation of long‐term simple and complex ORM (object recognition memory); however, same treatment in perirhinal cortex failed to induce the formation of long‐term complex ORM.
Dinoflagellates are main primary producers in the oceans, the cause of algal blooms and endosymbionts of marine invertebrates. Much remains to be understood about their biology, including their ...peculiar crystalline chromosomes. We assembled 94 chromosome-scale scaffolds of the genome of the coral endosymbiont Symbiodinium microadriaticum and analyzed their organization. Genes are enriched towards the ends of chromosomes and are arranged in alternating unidirectional blocks. Some chromosomes are enriched for genes involved in specific biological processes. The chromosomes fold as linear rods and each is composed of a series of structural domains separated by boundaries. Domain boundaries are positioned at sites where transcription of two gene blocks converges and disappear when cells are treated with chemicals that block transcription, indicating correlations between gene orientation, transcription and chromosome folding. The description of the genetic and spatial organization of the S. microadriaticum genome provides a foundation for deeper exploration of the extraordinary biology of dinoflagellates and their chromosomes.
Dinoflagellates are unicellular algae that are ubiquitously abundant in aquatic environments. Species of the genus Symbiodinium form symbiotic relationships with reef-building corals and other marine ...invertebrates. Despite their ecologic importance, little is known about the genetics of dinoflagellates in general and Symbiodinium in particular. Here, we used 454 sequencing to generate transcriptome data from two Symbiodinium species from different clades (clade A and clade B). With more than 56,000 assembled sequences per species, these data represent the largest transcriptomic resource for dinoflagellates to date. Our results corroborate previous observations that dinoflagellates possess the complete nucleosome machinery. We found a complete set of core histones as well as several H3 variants and H2A.Z in one species. Furthermore, transcriptome analysis points toward a low number of transcription factors in Symbiodinium spp. that also differ in the distribution of DNA-binding domains relative to other eukaryotes. In particular the cold shock domain was predominant among transcription factors. Additionally, we found a high number of antioxidative genes in comparison to non-symbiotic but evolutionary related organisms. These findings might be of relevance in the context of the role that Symbiodinium spp. play as coral symbionts.Our data represent the most comprehensive dinoflagellate EST data set to date. This study provides a comprehensive resource to further analyze the genetic makeup, metabolic capacities, and gene repertoire of Symbiodinium and dinoflagellates. Overall, our findings indicate that Symbiodinium possesses some unique characteristics, in particular the transcriptional regulation in Symbiodinium may differ from the currently known mechanisms of eukaryotic gene regulation.
Introduction
Ear acupuncture carried out in primary care by trained midwives, with no specialist training in acupuncture, may be effective in alleviating pregnancy‐related lower back and/or posterior ...pelvic girdle pain (LBPGP). The objective of this study was to assess the effect of ear acupuncture associated with standard obstetric care, in the primary‐care setting, on LBPGP experienced by pregnant women.
Material and methods
This four‐group, multicenter, randomized controlled trial was conducted at 18 public primary care centers in three regions in Spain, with the participation of 220 pregnant women at 24‐36 weeks of gestation, aged 18 years or more, diagnosed with pregnancy‐related LBPGP and who had not previously received ear acupuncture. The trial was conducted from March 2014 to December 2016. Participants were randomly assigned (1:1:1:1) to receive standard obstetric care plus two sessions (over 2 weeks) of verum ear acupuncture, or nonspecific ear acupuncture, or placebo ear acupuncture, or standard obstetric care alone. The primary outcome was change in pain intensity, assessed using a visual analog scale (0‐100 mm) from baseline to the end of treatment (T2). Secondary outcomes included change or presence of pain at 3 months (T3) and at 1 year (T4) postpartum, and changes in responses to the Roland‐Morris disability questionnaire (RMDQ) and Short Form‐12 Health Survey (SF‐12) at the end of treatment.
Results
A total of 55 women were randomized to each group, and 205 completed the study. With respect to baseline values, the reduction in pain intensity among the verum ear acupuncture group vs standard obstetric care was significantly greater, both at T2 (65.8%, 95%CI 56.2‐75.3 vs 25.1%, 95%CI 15.3‐34.9) and at T3 (93.8%, 95%CI 88.7‐99.0 vs 67.9%, 95%CI 55.3‐80.5). Moreover, significant changes were found in the verum ear acupuncture group vs standard obstetric care at T2, in reduced RMDQ scores (70.9%, 95%CI 61.8‐80.1 vs 21.2%, 95%CI 8.6‐33.7) and in increased SF‐12 scores on the physical scale (40.5%, 95%CI 31.5‐49.4 vs 8.1%, 95%CI 0.8‐15.5).
Conclusions
After 2 weeks of treatment, ear acupuncture applied by midwives and associated with standard obstetric care significantly reduces lumbar and pelvic pain in pregnant women, improves quality of life and reduces functional disability.
The global loss and degradation of coral reefs, as a result of intensified frequency and severity of bleaching events, is a major concern. Evidence of heat stress affecting corals through loss of ...symbionts and consequent coral bleaching was first reported in the 1930s. However, it was not until the 1998 major global bleaching event that the urgency for heat stress studies became internationally recognized. Current efforts focus not only on examining the consequences of heat stress on corals but also on finding strategies to potentially improve thermal tolerance and aid coral reefs survival in future climate scenarios. Although initial studies were limited in comparison with modern technological tools, they provided the foundation for many of today's research methods and hypotheses. Technological advancements are providing new research prospects at a rapid pace. Understanding how coral heat stress studies have evolved is important for the critical assessment of their progress. This review summarizes the development of the field to date and assesses avenues for future research.
The world is currently experiencing a loss and degradation of coral reef as frequency and severity of bleaching events over the last decades have intensified. Recent advancements in next‐generation sequencing technologies have shifted the field's attention to molecular approaches to find solutions for saving coral reefs. This review explores the past and present of coral heat stress studies, to summarize the development of the field and assess how these could influence future progress.
Marine sponges often host diverse and species-specific communities of microorganisms that are critical for host health. Previous functional genomic investigations of the sponge microbiome have ...focused primarily on specific symbiont lineages, which frequently make up only a small fraction of the overall community. Here, we undertook genome-centric analysis of the symbiont community in the model species Ircinia ramosa and analyzed 259 unique, high-quality metagenome-assembled genomes (MAGs) that comprised 74% of the I. ramosa microbiome. Addition of these MAGs to genome trees containing all publicly available microbial sponge symbionts increased phylogenetic diversity by 32% within the archaea and 41% within the bacteria. Metabolic reconstruction of the MAGs showed extensive redundancy across taxa for pathways involved in carbon fixation, B-vitamin synthesis, taurine metabolism, sulfite oxidation, and most steps of nitrogen metabolism. Through the acquisition of all major taxa present within the I. ramosa microbiome, we were able to analyze the functional potential of a sponge-associated microbial community in unprecedented detail. Critical functions, such as carbon fixation, which had previously only been assigned to a restricted set of sponge-associated organisms, were actually spread across diverse symbiont taxa, whereas other essential pathways, such as ammonia oxidation, were confined to specific keystone taxa.
The understanding of host-microbial partnerships has become a hot topic during the last decade as it has been shown that associated microbiota play critical roles in the host physiological functions ...and susceptibility to diseases. Moreover, the microbiome may contribute to host resilience to environmental stressors. The sea anemone Aiptasia is a good laboratory model system to study corals and their microbial symbiosis. In this regard, studying its bacterial microbiota provides a better understanding of cnidarian metaorganisms as a whole. Here, we investigated the bacterial communities of different Aiptasia host-symbiont combinations under long-term heat stress in laboratory conditions. Following a 16S rRNA gene sequencing approach we were able to detect significant differences in the bacterial composition and structure of Aiptasia reared at different temperatures. A higher number of taxa (i.e., species richness), and consequently increased α-diversity and β-dispersion, were observed in the microbiomes of heat-stressed individuals across all host strains and experimental batches. Our findings are in line with the recently proposed Anna Karenina principle (AKP) for animal microbiomes, which states that dysbiotic or stressed organisms have a more variable and unstable microbiome than healthy ones. Microbial interactions affect the fitness and survival of their hosts, thus exploring the AKP effect on animal microbiomes is important to understand host resilience. Our data contributes to the current knowledge of the Aiptasia holobiont and to the growing field of study of host-associated microbiomes.
The most diverse marine ecosystems, coral reefs, depend upon a functional symbiosis between a cnidarian animal host (the coral) and intracellular photosynthetic dinoflagellate algae. The molecular ...and cellular mechanisms underlying this endosymbiosis are not well understood, in part because of the difficulties of experimental work with corals. The small sea anemone Aiptasia provides a tractable laboratory model for investigating these mechanisms. Here we report on the assembly and analysis of the Aiptasia genome, which will provide a foundation for future studies and has revealed several features that may be key to understanding the evolution and function of the endosymbiosis. These features include genomic rearrangements and taxonomically restricted genes that may be functionally related to the symbiosis, aspects of host dependence on alga-derived nutrients, a novel and expanded cnidarian-specific family of putative pattern-recognition receptors that might be involved in the animal-algal interactions, and extensive lineage-specific horizontal gene transfer. Extensive integration of genes of prokaryotic origin, including genes for antimicrobial peptides, presumably reflects an intimate association of the animal-algal pair also with its prokaryotic microbiome.
The analysis of disciplined behaviors and academic performance in a school context has become one of the main concerns within the educational community. Physical Education is highlighted as a key ...subject to analyze students’ behavior. Researchers and Physical Education teachers are interested on the motivational processes that predict positive student outcomes in order to support them. Thus, the main purpose was to determine a predictive model of disciplined behaviors and academic performance in Physical Education students. The Achievement Goal Theory and Self-Determination Theory acted as the theoretical framework. A total of 919 Spanish secondary school students participated in the study. The studied variables were task-oriented motivational climate, basic psychological needs, autonomous motivation, disciplined behavior, and academic performance. Data collection included Spanish validated questionnaires. The Mplus statistical program was used to perform a structural equation model of prediction. It included antecedents (task-oriented climate), motivational processes (basic psychological needs and autonomous motivation), and consequences (disciplined behavior, Physical Education and overall students’ performance). The results revealed that positive outcomes (discipline and academic performance in Physical Education) were positively predicted by autonomous motivation; autonomous motivation was positively predicted by basic psychological needs and these, in addition, by the task-oriented climate. The results highlighted the importance of the task-oriented motivational climate and the mediating role of the basic psychological needs and autonomous motivation in order to generate these positive student outcomes in Physical Education. This study could be a useful resource for teachers, since it offers the motivational variables that lead students to achieve disciplined behaviors and academic performance in Physical Education. Intervention programs based on the results of the present study could be applied in Physical Education classes in order to obtain better behavioral as well as cognitive positive student outcomes.
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