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Katayama, T.

Publications and source records attributed to Katayama, T..

At least 19 recordsLinked to original sources

A representative of a ubiquitous bacterial lineage parasitically feeds on host RNA

Cellular metabolism is widely understood as an integrated network of redox reactions, energy conservation, and biosynthetic pathways. Here we show that across diverse prokaryotic lineages, loss of redox-associated functions is coupled with loss of nucleotide biosynthesis, raising a fundamental question of how such metabolically reduced organisms sustain cell growth. One of the most widespread and diverse lineages of prokaryotes--Minisyncoccota or Patescibacteriota--constitutes the majority of lineages exhibiting this pattern. To investigate how such organisms persist, we cultivated and characterized a representative of this lineage from a deep aquifer. The organism attaches to and penetrates growing bacterial host cells, and directly uptakes host RNA, concomitant with its depletion in the host. The metabolically reduced parasite cleaves host-derived RNA to directly supply cellular energy currencies and precursors for RNA/DNA synthesis, NTPs, without invoking canonical metabolic pathways. Codon usage in the parasite is complementary to that of its host, potentially minimizing translation of host-derived mRNA. Comparative genomics and phylogenetics indicate that these features are widespread and likely ancestral across the lineage. Exploitation of host RNA as a metabolic resource reveals a previously unrecognized metabolic strategy that demonstrates cellular metabolism can be sustained through direct utilization of informational macromolecules and thereby taps into an omnipresent energy reservoir, potentially supporting the environmental ubiquity of the metabolically reduced lineage.

microbiology↗

A Structural Domain in the genomic RNA of SARS-CoV-2 Folds into a Compact Granular Structure without the N protein: A Single-Molecule Fluorescence Spectroscopic Investigation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) packages its single-stranded genomic RNA (gRNA) having about 30,000 nucleotides into virions by forming 35-40 granular ribonucleoprotein (RNP) units. Each RNP unit has a diameter of [~]15 nm. While it is generally assumed that the assembly of these RNPs is driven by the binding of the nucleocapsid (N) protein to the gRNA in the cytoplasm, the precise molecular mechanism remains to be fully elucidated. In this study, we develop an experimental strategy based on single-molecule fluorescence and fluorescence correlation spectroscopies to examine the formation of long-range base pairing within a candidate structural domain corresponding to nt 12230-12686 of the gRNA (gRNA12k). Our results demonstrate that the 5 and 3 regions of gRNA12k autonomously form long-range base pairing in near-physiological buffers containing mono- and divalent cations, independently of the N protein. This domain possesses an extensive secondary structure, is compact, and can unfold and refold reversibly upon heat treatment and cooling. Notably, the addition of the N protein melts the long-range base pairs, and causes the aggregation of multiple molecules of gRNA12k. Based on these observations, we propose a refined mechanism for the genome assembly in SARS-CoV-2: gRNA initially forms autonomous granular structures, which are subsequently reorganized and condensed by the N protein to chaperone the assembly of the entire gRNA. SignificanceSARS-CoV-2 organizes its exceptionally long genomic RNA (gRNA) having about 30,000 nt into 35-40 granular ribonucleoprotein (RNP) units for viral packaging. It has been assumed that the nucleocapsid (N) protein drives the formation of the RNP granules. In this study, we challenge this prevailing view by demonstrating that a specific region of the gRNA sequence inherently encodes the information to fold into a compact, granular architecture independently of any proteins. Unexpectedly, we found that the N protein partially melts the autonomous structures, suggesting that it acts as an RNA chaperone to facilitate flexible genome assembly. Our findings redefine the interplay between viral proteins and gRNA, offering a new perspective on the mechanism of coronavirus replication.

biophysics↗

Vitronectin defines a differentiation-restraining extracellular matrix state in myogenic cells

Skeletal muscle differentiation is classically triggered by reducing serum-derived mitogenic cues; however, the extracellular matrix-associated factors that actively maintain a proliferative, differentiation-resistant state remain poorly defined. Here, we identify vitronectin (VN) as a key extracellular matrix gatekeeper that controls myogenic cell fate. VN is abundant in fetal bovine serum but largely absent from horse serum, rapidly declines upon differentiation induction, and selectively suppresses myogenic differentiation while sustaining proliferation through integrin v{beta}3-dependent signaling. VN maintains growth factor receptor activity and cell-cycle progression even under differentiation conditions, thereby preventing myoblast commitment. These effects extend to three-dimensional culture and primary embryonic chicken myogenic cells, indicating evolutionary conservation. Importantly, VN progressively accumulates during long-term passaging, coinciding with replicative senescence and impaired differentiation, and inhibition of v{beta}3 signaling partially restores myogenic competence in senescent cells. Together, our findings redefine a long-standing myoblast culture paradigm by identifying a serum-derived extracellular matrix protein as a decisive regulator linking extracellular environment, proliferative niche maintenance, and age-associated decline in myogenic competence.

cell biology↗

Metabolic Trans-Omic Analysis Reveals Key Regulatory Disruption of Energy Metabolism in Alzheimer's Disease

Alzheimers disease (AD), a leading cause of dementia, has been recognized as a disease with profound metabolic dysregulation. However, a systems-level view of metabolic regulation across multiple omic modalities in AD remains elusive. Here, we integrated public multi-omic datasets (transcriptome, proteome, and metabolome) from the dorsolateral prefrontal cortex of AD patients and controls. By leveraging existing molecular biological knowledge, we reconstructed a multi-layered metabolic regulatory network to systematically map the potential interplay among mRNAs, proteins, and metabolites in AD. Our analysis revealed a putative coordinated downregulation of energy producing pathways, including the TCA cycle, oxidative phosphorylation, and ketone body metabolism, driven by reduced enzyme abundance and inhibitory allosteric effects. In contrast, the glycolysis pathway appeared to be influenced by opposing enzymatic and allosteric regulations. These findings highlight key metabolic dysregulations that may contribute to the bioenergetic deficits in AD.

systems biology↗

Gut mucin fucosylation dictates the entry of botulinum toxin complexes

Botulinum toxins (BoNTs) are the most potent known bacterial toxins. The BoNT complex from Clostridium botulinum B-Okra (large progenitor toxin complex (L-PTC)/BOkra, hyper-oral-toxic) exerts at least 80-fold higher oral toxicity1 in mice compared with that from serotype A1 (L-PTC/A62A, non-hyper-oral-toxic). Here, we showed that L-PTC/BOkra was predominantly absorbed through enterocytes, whereas L-PTC/A62A targeted intestinal microfold cells. Furthermore, we demonstrated that 1,2-fucosylation of intestinal mucin determined the oral toxicity of L-PTCs as well as their entry routes; more specifically, these routes were governed by the carbohydrate-binding spectrum of hemagglutinin (HA) complex, which is one of the L-PTC components. Disruption of fucosylation in fucosyltrasferase-2 (Fut2)-null mice hindered the intestinal mucin penetration of L-PTC/BOkra via HA and reduced the susceptibility to its oral intoxication. Our data establish the molecular mechanism by which the oral toxicity of BoNTs is increased after they cross intestinal mucus layers.

microbiology↗

Dynamic DnaA-DnaB interactions at oriC coordinate the loading and coupled translocation of two DnaB helicases for bidirectional replication

Bidirectional replication is a conserved principle requiring the coordinated loading and activation of two replicative helicases at the origin. In Escherichia coli, the initiator protein DnaA constructs a higher-order initiation complex at the origin oriC which locally unwinds the DNA, and recruits DnaB helicase-DnaC loader complexes to the unwound region. We previously demonstrated that the two DnaA subcomplexes formed on oriC bind a specific DNA strand of the unwound origin, and tether individual DnaB-DnaC complexes via stable interactions between DnaA domain I and DnaB. A low-affinity DnaA-DnaB interaction mediated by DnaA domain III His136 is essential for DnaB-dependent origin unwinding. Here, we identified DnaB Thr86 as the critical residue mediating this low-affinity interaction. Structural modelling suggests that Thr86 is surface-exposed near the DNA entry site of DnaB. Functional analyses revealed that DnaB Thr86 was specifically required for DnaB loading onto the DnaA-bound strand of the unwound oriC. Furthermore, this strand-specific DnaB loading was required for enabling translocation of the opposing DnaB helicase loaded on the DnaA-free strand. Our findings define a novel regulatory mechanism of strand-specific helicase loading, mediated by the low-affinity DnaA-DnaB interactions, which ensures the coordinated loading and translocation of DnaB helicases for bidirectional replication from oriC.

molecular biology↗

Biomechanics of static roll posture control by body flexion in adult zebrafish

Posture control is crucial for animals. Static posture control in fish remains poorly explored. Recent studies have shown that larval zebrafish perform body flexion during slight roll tilts: the body flexion displaces a gas-filled swim bladder, generating counter-rotation torque for postural recovery through misalignment of gravity and buoyancy forces. Swim bladder deflation impairs this postural recovery, suggesting its critical role. This static posture control strategy may be utilized by many fish species. However, adult fish differ from larvae in morphology and behavior, raising questions about the generality of this mechanism. Our behavioral analysis showed that adult zebrafish also flexed their body during roll tilts, with flexion persisting until recovery to an upright posture. Similarly to larvae, swim bladder deflation impaired postural recovery. These results demonstrate that adult fish employ static roll posture control through body flexion and suggest the generality of this mechanism in fish species.

zoology↗

The increase in cell volume and nuclear number of the koji-fungus Aspergillus oryzae contributes to its high enzyme productivity

While the ratio of nuclei to cell volume is well regulated, it remains largely unexplored in multinucleate organisms. The koji-fungus Aspergillus oryzae, traditionally used in Japanese brewing and fermentation for over a thousand years, is now widely utilized in modern biotechnology as a host for enzyme production. We discovered that, over time in culture, hyphae become thicker, resulting in a tenfold increase in cell volume, and the number of nuclei in hyphal cells also increases tenfold, exceeding 200. The increase in cell volume and nuclear number is unique among the investigated Aspergillus species and correlates with its high enzyme production capabilities. Since nuclear number and cell volume are correlated, both must increase simultaneously for either to expand. Our analyses identified genetic factors and nutritional environmental signals involved in each of these increases. Increases in nuclear number and cell volume were also observed in other fungi bred for industrial use. This study not only deepens our understanding of the evolutionary processes that promote high enzyme productivity through fungal breeding, but also provides insights into the molecular mechanisms regulating cell volume and nuclear number in multinucleate organisms.

microbiology↗

Extraction of biological terms using large language models enhances the usability of metadata in the BioSample database

BioSample is a comprehensive repository of experimental sample metadata, playing a crucial role in providing a comprehensive archive and enabling experiment searches regardless of type. However, the difficulty in comprehensively defining the rules for describing metadata and limited user awareness of best practices for metadata have resulted in substantial variability depending on the submitter. This inconsistency poses significant challenges to the findability and reusability of the data. Given the vast scale of BioSample, which hosts over 40 million records, manual curation is impractical. Rule-based automatic ontology mapping methods have been proposed to address this issue, but their effectiveness is limited by the heterogeneity of BioSample metadata. Recently, large language models (LLMs) have gained attention in natural language processing and have been expected as promising tools for automating metadata curation. In this study, we evaluated the performance of LLMs in extracting cell line names from BioSample descriptions using a gold-standard dataset derived from ChIP-Atlas, a secondary database of epigenomics experiment data, which manually curates samples. Our results demonstrated that LLM-assisted methods outperformed traditional approaches, achieving higher accuracy and coverage. We further extended this approach to extraction of information about experimentally manipulated genes from metadata where manual curation had not yet been applied in ChIP-Atlas. This also yielded successful results for the usage of the database, which facilitates more precise filtering of data and prevents misinterpretation caused by inclusion of unintended data. These findings underscore the potential of LLMs to improve the findability and reusability of experimental data in general, significantly reducing user workload and enabling more effective scientific data management.

bioinformatics↗

Uptake of fucosylated type I human milk oligosaccharide blocks by Bifidobacterium longum subsp. infantis

Human milk oligosaccharides (HMOs) are uniquely rich in the type 1 building block disaccharide lacto-N-biose I (LNB, Gal{beta}1,3GlcNAc), as compared to other mammals. Most HMOs are fucosylated, e.g., 1,2 and 1,4 fucosylations on LNB blocks, resulting in H type 1 (H1) and Lewis a (Lea) epitopes, respectively. The dominance of Bifidobacterium in breastfed infant guts hinges on efficient uptake of HMOs by specific ATP-binding cassette (ABC) importers. However, molecular insight into uptake of fucosylated LNB blocks is lacking. Here, we analyzed the uptake of LNB and its fucosylated H1 and Lea trisaccharides, as well as the mucin-derived disaccharide galacto-N-biose (GNB, Gal{beta}1,3GalNAc) by an ABC importer form the HMO-utilization specialist Bifidobacterium longum subsp. infantis. Structural analyses and molecular dynamics simulations explained how fucosylated and non-fucosylated LNB forms are recognized with similar affinities by the binding protein of this importer. Strikingly, we showed that two ABC importers confer to the uptake of LNB, while the Lea trisaccharide is efficiently internalized by a single importer in B. infantis. Phylogenetic and structural analyses of bifidobacterial ABC-associated binding proteins showed that the Lea clade harbors homologues possessing internal cavities, which allows for the accommodation of branched oligosaccharides. Our work provides unique insight into the evolution and molecular basis of capture and uptake of key HMO and host-derived saccharide blocks, highlighting these compounds as hitherto unexplored candidates for fortification of infant formula. ImportanceThe assembly of the gut microbiota in early life is critical to the health trajectory of human hosts. Breast feeding selects for a Bifidobacterium-rich community, adapted to efficiently utilize HMOs from mothers milk. Industrial scale production of HMOs for infant formula fortification has mainly considered fucosyllactoses, whereas fucosylated type 1 HMO blocks have hitherto not been explored. Our work sheds light on the uptake facet, central to the utilization of fucosylated HMOs with type 1 LNB building blocks. These type I blocks are efficiently internalized and assimilated by B. infantis, which has been recently shown to secrete immune-modulatory aromatic-lactate metabolites that mediate immune-priming of hosts in early life. This study contributes to our understanding of the utilization of HMOs and highlights fucosylated LNB blocks, as hitherto unexplored prebiotic candidates that support the growth of B. infantis and other beneficial bacteria in early life.

microbiology↗

Phased genome assemblies and pangenome graphs of human populations of Japan and Saudi Arabia

The selection of a reference sequence in genome analysis is critical, as it serves as the foundation for all downstream analyses. Recently, the pangenome graph has been proposed as a data model that incorporates haplotypes from multiple individuals. Here we present JaSaPaGe, a pangenome graph reference for Saudi Arabian and Japanese populations, both of which have been significantly underrepresented in previous genomic studies. We constructed JaSaPaGe from high-quality phased diploid assemblies which were made utilizing PacBio high-fidelity long reads, Nanopore long reads, and Hi-C short reads of 9 Saudi and 10 Japanese individuals. Quality evaluation of the pangenome graph by variant calling showed that our pangenome outperformed earlier linear reference genomes (GRCh38 and T2T-CHM13) and showed comparable performance to the pangenome graph provided by the Human Pangenome Reference Consortium (HPRC), with more variants found in Japanese and Saudi samples using their population-specific pangenomes. This pangenome reference will serve as a valuable resource for both the research and clinical communities in Japan and Saudi Arabia.

genomics↗

Primosomal protein PriC rescues replication initiation stress by bypassing the DnaA-DnaB interaction step for DnaB helicase loading at oriC

In Escherichia coli, replisome and replication fork assembly is initiated by DnaB helicase loading at the chromosomal origin oriC via its interactions with the DnaA initiator and the DnaC helicase loader. Upon replication fork arrest, the replisome including DnaB dissociates from the stalled fork. Replication fork progression is rescued by primosomal protein PriA- or PriC-dependent pathway in which PriA and PriC promote reloading of DnaB in different mechanisms. However, the mechanism responsible for rescue of blocked replication initiation at oriC remains unclear. Here, we found that PriC rescued blocked replication initiation in cells expressing an initiation-specific DnaC mutant, in mutant cells defective in DnaA-DnaB interactions, and in cells containing truncated oriC sequence variants. PriC rescued DnaB loading at oriC even in the absence of Rep helicase, a stimulator of the PriC-dependent replication fork restart pathway. These and results of in vitro reconstituted assays concordantly suggest that this initiation-specific rescue mechanism provides a bypass of the DnaA-DnaB interaction for DnaB loading by PriC-promoted loading of DnaB to the unwound oriC region. These findings expand understanding of mechanisms sustaining the robustness of replication initiation and specific roles for PriC in the genome maintenance.

microbiology↗

Identification of Core Yeast Species and Microbe-Microbe Interactions Impacting Larval Growth of Drosophila in the Wild

Microbiota consisting of various fungi and bacteria have a significant impact on the physiological functions of the host. However, it is unclear which species are essential to this impact and how they affect the host. This study analyzed and isolated microbes from natural food sources of Drosophila larvae, and investigated their functions. Hanseniaspora uvarum is the predominant yeast responsible for larval growth in the earlier stage of fermentation. As fermentation progresses, Acetobacter orientalis emerges as the key bacterium responsible for larval growth, although yeasts and lactic acid bacteria must coexist along with the bacterium to stabilize this host-bacterial association. By providing nutrients to the larvae in an accessible form, the microbiota contributes to the upregulation of various genes that function in larval cell growth and metabolism. Thus, this study elucidates the key microbial species that support animal growth under microbial transition.

developmental biology↗

SUMO2 Protects Against Tau-induced Synaptic and Cognitive Dysfunction

Abnormal intracellular accumulation of Tau aggregates is a hallmark of Alzheimers disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD), which can be caused by mutations of Tau. Mutated and pathological Tau can undergo a range of post-translational modifications (PTMs) that might trigger or modulate disease pathology. Recent studies indicate that modification of wild type Tau by Small ubiquitin-like modifier SUMO isoform 1 (SUMO1) controls Tau hyperphosphorylation and aggregation, suggesting that SUMOylation acts as a central regulator of Taus biochemical properties. Besides SUMO1, Tau is modified by SUMO2/3, however the consequences of this modification have not been investigated. Here, using viral approaches on primary hippocampal neurons, transgenic mice expressing mutant Tau and SUMO2, and iPSC-derived neurons from FTD patients, we evaluated whether SUMO2/3 conjugation modifies the neurodegenerative disease pathology associated with the aggregation-prone mutant Tau P301L, P301S, and R406W variants. We found that mutant forms of Tau are targets of SUMO2/3, and SUMO2/3 conjugation is neuroprotective. Importantly, expression of mutant Tau is accompanied by a significant reduction of SUMO2/3 conjugation levels, and restoring levels of SUMO2 reduces mutant Tau aggregation and phosphorylation in all model systems Furthermore, overexpression of SUMO2 restores levels of pre- and post-synaptic markers, associated with a complete rescue of the LTP and memory deficits in transgenic mice expressing mutant Tau. These findings bring to light the potential therapeutic implication of manipulating SUMO conjugation to detoxify Tau through PTM-based approaches.

neuroscience↗

Human Milk Oligosaccharide Utilization in Intestinal Bifidobacteria is Governed by a Global Transcriptional Regulator NagR

Bifidobacterium longum subsp. infantis (B. infantis) is a prevalent beneficial bacterium that colonizes the human neonatal gut and is uniquely adapted to efficiently use human milk oligosaccharides (HMOs) as a carbon and energy source. Multiple studies have focused on characterizing the elements of HMO utilization machinery in B. infantis; however, the regulatory mechanisms governing the expression of these catabolic pathways remain poorly understood. A bioinformatic regulon reconstruction approach used in this study implicated NagR, a transcription factor from the ROK family, as a negative global regulator of genomic loci encoding lacto-N-biose/galacto-N-biose (LNB/GNB), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT) utilization pathways in B. infantis. This conjecture was corroborated by transcriptome profiling upon nagR genetic inactivation and experimental assessment of binding of recombinant NagR to predicted DNA operators. The latter approach also implicated N-acetylglucosamine (GlcNAc), a universal intermediate of LNT and LNnT catabolism, and its phosphorylated derivatives as plausible NagR transcriptional effectors. Reconstruction of NagR regulons in various Bifidobacterium lineages revealed multiple regulon expansion events, suggesting evolution from a local regulator of GlcNAc catabolism in ancestral bifidobacteria to a global regulator controlling foraging of mixtures of GlcNAc-containing host-derived glycans in mammalian gut-colonizing B. infantis and Bifidobacterium bifidum. ImportanceThe predominance of bifidobacteria in the gut of breastfed infants is attributed to the ability of these bacteria to utilize human milk oligosaccharides (HMOs). Thus, individual HMOs such as lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) are considered promising prebiotics that would stimulate the growth of bifidobacteria and confer multiple health benefits to preterm and malnourished children suffering from impaired (stunted) gut microbiota development. However, the rational selection of HMO-based prebiotics is hampered by the incomplete knowledge of regulatory mechanisms governing HMO utilization in target bifidobacteria. This study describes NagR-mediated transcriptional regulation of LNT and LNnT utilization in Bifidobacterium longum subsp. infantis. The elucidated regulatory network appears optimally adapted to simultaneous utilization of multiple HMOs, providing a rationale to add HMO mixtures (rather than individual components) into infant formulas. The study also provides insights into the evolutionary trajectories of complex regulatory networks controlling carbohydrate metabolism in bifidobacteria.

microbiology↗

Mitochondrial fission dysfunction alleviates heterokaryon incompatibility-triggered cell death in the industrial filamentous fungus Aspergillus oryzae

In filamentous fungi, cell-to-cell recognition is a fundamental requirement for the formation, development, and maintenance of complex hyphal networks. Basically, self/compatible individuals within the fungal species are capable of fusing together, a step important for crossbreeding, which results in the formation of viable vegetative heterokaryons. Conversely, the fusion of incompatible individuals does not result in the formation of viable hyphal networks, but it often leads to growth inhibition or cell death. Even though a number of studies have been conducted to investigate such incompatibility, the understanding of the associated molecular mechanism is still limited, and this restricts the possibility of crossbreeding incompatible individuals. Therefore, in this study, the characteristics of compatibility/incompatibility in the industrial filamentous fungus, Aspergillus oryzae, were comprehensively investigated. Protoplast fusion and co-culture assays indicated the existence of a correlation between strain phylogeny and compatibility/incompatibility features. Time-course fluorescence observations were employed to investigate the types of incompatible responses that are induced at different cellular levels upon incompatible cell fusion, which eventually lead to cell death. Propidium iodide-indicated cell death, ROS accumulation, and mitochondrial fragmentation were identified as the major responses, with mitochondrial fragmentation showing the most significant subcellular change immediately after incompatible cell fusion. Furthermore, the deletions of mitochondrial fission-related genes Aofis1 and Aodnm1 in incompatible pairing alleviated cell death, indicating that mitochondrial fission is an important mechanism by which incompatibility-triggered cell death occurs. Therefore, this study provides new insights about heterokaryon incompatibility. IMPORTANCEFor a long time, it was believed that as an asexual fungus, A. oryzae does not exhibit any sexual cycle. However, the fungus has two mating types, indicating the potential for sexual reproduction besides a known parasexual cycle. Therefore, given that viable heterokaryon formation following cell fusion is an important step required for genetic crossing, we explored the mechanism of incompatibility, which restricts the possibility of cell fusion in A. oryzae. Protoplast fusion and co-culture assays led to the identification of various vegetative compatible groups. Mitochondrial fragmentation was found to be the most significant incompatible cellular response that occurred in organelles during incompatible pairing, while the deletion of mitochondrial fission-related genes was identified as a strategy used to alleviate incompatibility-triggered cell death. Thus, this study revealed a novel mechanism by which mitochondrial fission regulates incompatible responses.

microbiology↗

AMPK regulates cell shape of cardiomyocytes by modulating turnover of microtubules through CLIP-170

AMP-activated protein kinase (AMPK) is a multifunctional kinase that regulates microtubule (MT) dynamic instability through CLIP-170 phosphorylation; however, its physiological relevance in vivo remains to be elucidated. In this study, we identified an active form of AMPK localized at the intercalated discs in the heart, a specific cell-cell junction present between cardiomyocytes. A contractile inhibitor, MYK-461, prevented the localization of AMPK at the intercalated discs, and the effect was reversed by the removal of MYK-461, suggesting that the localization of AMPK is regulated by mechanical stress. Time-lapse imaging analysis revealed that the inhibition of CLIP-170 Ser-311 phosphorylation by AMPK leads to the accumulation of MTs at the intercalated discs. Interestingly, MYK-461 increased the individual cell area of cardiomyocytes in CLIP-170 phosphorylation-dependent manner. Moreover, heart-specific CLIP-170 S311A transgenic mice demonstrated elongation of cardiomyocytes along with accumulated MTs, leading to progressive decline in cardiac contraction. In conclusion, these findings suggest that AMPK regulates the cell shape and aspect ratio of cardiomyocytes by modulating the turnover of MTs through homeostatic phosphorylation of CLIP-170 at the intercalated discs.

cell biology↗

Butyrate producing Clostridiales utilize distinct human milk oligosaccharides correlating to early colonization and prevalence in the human gut

The early life human gut microbiota exerts life-long health effects on the host, but the mechanisms underpinning its assembly remain elusive. Particularly, the early colonization of Clostridiales from the Roseburia-Eubacterium group, associated with protection from colorectal cancer, immune- and metabolic disorders is enigmatic. Here we unveil the growth of Roseburia and Eubacterium members on human milk oligosaccharides (HMOs) using an unprecedented catabolic apparatus. The described HMO pathways and additional glycan utilization loci confer co-growth with Akkermansia muciniphilia via cross-feeding and access to mucin O-glycans. Strikingly, both, HMO and xylooligosaccharide pathways, were active simultaneously attesting an adaptation to a mixed HMO-solid food diet. Analyses of 4599 Roseburia genomes underscored the preponderance of HMO pathways and highlighted different HMO utilization phylotypes. Our revelations provide a possible rationale for the early establishment and resilience of butyrate producing Clostridiales and expand the role of specific HMOs in the assembly of the early life microbiota.

microbiology↗