Finite temperature dynamics of the Mott insulating Hubbard chain

We study the dynamical response of the half-filled one-dimensional(1d) Hubbard model for a range of interaction strengths $U$ and temperatures $T$ by a combination of numerical and analytical techniques. Using time-dependent density matrix renormalization group (tDMRG) computations we find that the single-particle spectral function undergoes a crossover to a spin-incoherent Luttinger liquid regime at temperatures $T \sim J=4t^2/U$ for sufficiently large $U > 4t$. At smaller values of $U$ and elevated temperatures the spectral function is found to exhibit two thermally broadened bands of excitations, reminiscent of what is found in the Hubbard-I approximation. The dynamical density-density response function is shown to exhibit a finite temperature resonance at low frequencies inside the Mott gap, with a physical origin similar to the Villain mode in gapped quantum spin chains. We complement our numerical computations by developing an analytic strong-coupling approach to the low-temperature dynamics in the spin-incoherent regime.Comment: 10 pages, 7 Fig

Математика в определении свойств горных пород

We study the sudden expansion of strongly correlated fermions in a one-dimensional lattice, utilizing the time-dependent density-matrix renormalization group method. Our focus is on the behavior of experimental observables such as the density, the momentum distribution function, and the density and spin structure factors. As our main result, we show that correlations in the transient regime can be accurately described by equilibrium reference systems. In addition, we find that the expansion from a Mott insulator produces distinctive peaks in the momentum distribution function at |k| ~ pi/2, accompanied by the onset of power-law correlations.Comment: 8 pages Revtex4, 7 eps-figures, minor changes, additional references, as publishe

Major hnRNP proteins act as general TDP-43 functional modifiers both in Drosophila and human neuronal cells

Nuclear factor TDP-43 is known to play an important role in several neurodegenerative pathologies. In general, TDP-43 is an abundant protein within the eukaryotic nucleus that binds to many coding and non-coding RNAs and influence their processing. Using Drosophila, we have performed a functional screening to establish the ability of major hnRNP proteins to affect TDP-43 overexpression/depletion phenotypes. Interestingly, we observed that lowering hnRNP and TDP-43 expression has a generally harmful effect on flies locomotor abilities. In parallel, our study has also identified a distinct set of hnRNPs that is capable of powerfully rescuing TDP-43 toxicity in the fly eye (Hrb27c, CG42458, Glo and Syp). Most importantly, removing the human orthologs of Hrb27c (DAZAP1) in human neuronal cell lines can correct several pre-mRNA splicing events altered by TDP-43 depletion. Moreover, using RNA sequencing analysis we show that DAZAP1 and TDP-43 can co-regulate an extensive number of biological processes and molecular functions potentially important for the neuron/motor neuron pathophysiology. Our results suggest that changes in hnRNP expression levels can significantly modulate TDP-43 functions and affect pathological outcomes

WDR79/TCAB1 plays a conserved role in the control of locomotion and ameliorates phenotypic defects in SMA models

SMN (Survival Motor Neuron) deficiency is the predominant cause of spinal muscular atrophy (SMA), a severe neurodegenerative disorder that can lead to progressive paralysis and death. Although SMN is required in every cell for proper RNA metabolism, the reason why its loss is especially critical in the motor system is still unclear. SMA genetic models have been employed to identify several modifiers that can ameliorate the deficits induced by SMN depletion. Here we focus on WDR79/TCAB1, a protein important for the biogenesis of several RNA species that has been shown to physically interact with SMN in human cells. We show that WDR79 depletion results in locomotion defects in both Drosophila and Caenorhabditis elegans similar to those elicited by SMN depletion. Consistent with this observation, we find that SMN overexpression rescues the WDR79 loss-of-function phenotype in flies. Most importantly, we also found that WDR79 overexpression ameliorates the locomotion defects induced by SMN depletion in both flies and worms. Our results collectively suggest that WDR79 and SMN play evolutionarily conserved cooperative functions in the nervous system and suggest that WDR79/TCAB1 may have the potential to modify SMA pathogenesis

Drosophila Answers to TDP-43 Proteinopathies

Initially implicated in the pathogenesis of CFTR and HIV-1 transcription, nuclear factor TDP-43 was subsequently found to be involved in the origin and development of several neurodegenerative diseases. In 2006, in fact, it was reported for the first time the cytoplasmic accumulation of TDP-43 in ubiquitin-positive inclusions of ALS and FTLD patients, suggesting the presence of a shared underlying mechanism for these diseases. Today, different animal models of TDP-43 proteinopathies are available in rodents, nematodes, fishes, and flies. Although these models recapitulate several of the pathological features found in patients, the mechanisms underpinning the progressive neuronal loss observed in TDP-43 proteinopathies remain to be characterized. Compared to other models, Drosophila are appealing because they combine the presence of a sophisticated brain with the possibility to investigate quickly and massively phenotypic genetic modifiers as well as possible therapeutic strategies. At present, the development of TDP-43-related Drosophila models has further strengthened the hypothesis that both TDP-43 “loss-of-function” and “gain-of-function” mechanisms can contribute to disease. The aim of this paper is to describe and compare the results obtained in a series of transgenic and knockout flies, along with the information they have generated, towards a better understanding of the mechanisms underlying TDP-43 proteinopathies

Glial TDP-43 regulates axon wrapping, GluRIIA clustering and fly motility by autonomous and non-autonomous mechanisms

Alterations in the glial function of TDP-43 are becoming increasingly associated with the neurological symptoms observed in Amyotrophic Lateral Sclerosis (ALS), however, the physiological role of this protein in the glia or the mechanisms that may lead to neurodegeneration are unknown. To address these issues, we modulated the expression levels of TDP-43 in the Drosophila glia and found that the protein was required to regulate the subcellular wrapping of motoneuron axons, promote synaptic growth and the formation of glutamate receptor clusters at the neuromuscular junctions. Interestingly, we determined that the glutamate transporter EAAT1 mediated the regulatory functions of TDP-43 in the glia and demonstrated that genetic or pharmacological compensations of EAAT1 activity were sufficient to modulate glutamate receptor clustering and locomotive behaviors in flies. The data uncovers autonomous and non-autonomous functions of TDP-43 in the glia and suggests new experimentally based therapeutic strategies in ALS

Dissecting the splicing mechanism of the Drosophila editing enzyme; dADAR

In Drosophila melanogaster, the expression of adenosine deaminase acting on RNA is regulated by transcription and alternative splicing so that at least four different isoforms are generated that have a tissue-specific splicing pattern. Even though dAdar has been extensively studied, the complete adult expression pattern has yet to be elucidated. In the present study, we investigate mature transcripts of dAdar arising from different promoters. Two predominant isoforms of dAdar are expressed in gonads and dAdar is transcribed from both the embryonic and the adult promoters. Furthermore, full-length transcripts containing the alternatively spliced exon-1 are expressed in a tissue-specific manner. The splicing factor B52/SRp55 binds within the alternative spliced exon 3a and plays a role in this alternative splicing event

Gut mycobiome and neuropsychiatric disorders: insights and therapeutic potential

BackgroundThe human gut mycobiome, a minor but integral component of the gut microbiome, has emerged as a significant player in host homeostasis and disease development. While bacteria have traditionally been the focus of gut microbiome studies, recent evidence suggests that fungal communities (mycobiota) may also play a crucial role in modulating health, particularly in neuropsychiatric disorders.ObjectiveThis review aims to provide a comprehensive overview of current knowledge on the relationship between the gut mycobiome and neuropsychiatric disorders, exploring the potential of targeting fungal communities as a novel therapeutic strategy.MethodsWe summarized recent findings from metagenomic analyses that characterize the diversity and composition of gut mycobiota and discuss how these communities interact with the host and other microorganisms via the gut-brain axis. Key methodologies for studying mycobiota, such as high-throughout sequencing and bioinformatics approaches, were also reviewed to highlight advances in the field.ResultsEmerging research links gut mycobiota dysbiosis to conditions such as schizophrenia, Alzheimer’s disease, autism spectrum disorders, bipolar disorder, and depression. Studies indicate that specific fungal populations, such as Candida and Saccharomyces, may influence neuroinflammation, gut permeability and immune responses, thereby affecting mental health outcomes.ConclusionUnderstanding the gut mycobiome’s role in neuropsychiatric disorders opens new avenues for therapeutic interventions, including antifungal treatments, probiotics, and dietary modifications. Future research should integrate multi-omics approaches to unravel the complex interkingdom interactions within the gut ecosystem, paving the way for personalized medicine in mental health care

NOS1AP is a novel molecular target and critical factor in TDP-43 pathology

Cappelli et al. reported that Nitric Oxide Synthase 1 Adaptor Protein is a co-regulated transcript of the TAR DNA-binding protein 43 kDa, reduced in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients with TAR DNA-binding protein 43 kDa pathology. Overall, their results highlight Nitric Oxide Synthase 1 Adaptor Protein as a novel druggable disease-relevant gene in TAR DNA-binding protein 43 kDa-related proteinopathies.Many lines of evidence have highlighted the role played by heterogeneous nuclear ribonucleoproteins in amyotrophic lateral sclerosis. In this study, we have aimed to identify transcripts co-regulated by TAR DNA-binding protein 43 kDa and highly conserved heterogeneous nuclear ribonucleoproteins which have been previously shown to regulate TAR DNA-binding protein 43 kDa toxicity (deleted in azoospermia-associated protein 1, heterogeneous nuclear ribonucleoprotein -Q, -D, -K and -U). Using the transcriptome analyses, we have uncovered that Nitric Oxide Synthase 1 Adaptor Protein mRNA is a direct TAR DNA-binding protein 43 kDa target, and in flies, its modulation alone can rescue TAR DNA-binding protein 43 kDa pathology. In primary mouse cortical neurons, we show that TAR DNA-binding protein 43 kDa mediated downregulation of Nitric Oxide Synthase 1 Adaptor Protein expression strongly affects the NMDA-receptor signalling pathway. In human patients, the downregulation of Nitric Oxide Synthase 1 Adaptor Protein mRNA strongly correlates with TAR DNA-binding protein 43 kDa proteinopathy as measured by cryptic Stathmin-2 and Unc-13 homolog A cryptic exon inclusion. Overall, our results demonstrate that Nitric Oxide Synthase 1 Adaptor Protein may represent a novel disease-relevant gene, potentially suitable for the development of new therapeutic strategies

Alterations in phosphatidylethanolamine levels affect the generation of Aβ

Several studies suggest that the generation of Aβ is highly dependent on the levels of cholesterol within membranes' detergent-resistant microdomains (DRM). Indeed, the β-amyloid precursor protein (APP) cleaving machinery, namely β- and γ-secretases, has been shown to be present in DRM and its activity depends on membrane cholesterol levels. Counterintuitive to the localization of the cleavage machinery, the substrate, APP, localizes to membranes' detergent-soluble microdomains enriched in phospholipids (PL), indicating that Aβ generation is highly dependent on the capacity of enzyme and substrate to diffuse along the lateral plane of the membrane and therefore on the internal equilibrium of the different lipids of DRM and non-DRM domains. Here, we studied to which extent changes in the content of a main non-DRM lipid might affect the proteolytic processing of APP. As phosphatidylethanolamine (PE) accounts for the majority of PL, we focused on its impact on the regulation of APP proteolysis. In mammalian cells, siRNA-mediated knock-down of PE synthesis resulted in decreased Aβ owing to a dual effect: promoted α-secretase cleavage and decreased γ-secretase processing of APP. In vivo, in Drosophila melanogaster, genetic reduction in PL synthesis results in decreased γ-secretase-dependent cleavage of APP. These results suggest that modulation of the membrane-soluble domains could be a valuable alternative to reduce excessive Aβ generation. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.Fund for Scientific Research Flanders (FWO); Federal Office for Scientific Affairs; Fondation pour la Recherche sur Maladie d’ Alzheimer; Flemish Government (Methusalem grant); Spanish Government (Ministerio de Ciencia e Innovacion Ingenio-Consolider CSD2010-00064, SAF2010-14906)Peer Reviewe