-
Mashup Score: 1
Altered regulatory interactions during development likely underlie a large fraction of phenotypic diversity within and between species, yet identifying specific evolutionary changes remains challenging. Analysis of single-cell developmental transcriptomes from multiple species provides a powerful framework for unbiased identification of evolutionary changes in developmental mechanisms. Here, we leverage a “natural experiment” in developmental evolution in sea urchins, where a major life history switch recently evolved in the lineage leading to Heliocidaris erythrogramma, precipitating extensive changes in early development. Comparative analyses of scRNA-seq developmental time courses from H. erythrogramma and Lytechinus variegatus (representing the derived and ancestral states respectively) reveals numerous evolutionary changes in embryonic patterning. The earliest cell fate specification events, and the primary signaling center are co-localized in the ancestral dGRN but remarkably, in
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 0
Many organisms inhabiting the interface between land and sea have evolved biological clocks corresponding to the period of the semilunar (14.77d) or the lunar (29.53d) cycle. Since tidal amplitude is modulated across the lunar cycle, these circasemilunar or circalunar clocks allow organisms to adapt to the tides. Biological clocks are synchronized to external cycles via environmental cues called zeitgebers . Here, we explore how light at night sets the circalunar and circasemilunar clocks of Clunio marinus , a marine insect that relies on these clocks to control timing of emergence. We first characterized how moonlight intensity is modulated by the tides by measuring light intensity in the natural habitat of C. marinus . In laboratory experiments, we then explored how different moonlight treatments set the phase of the clocks of two C. marinus strains, one with a lunar rhythm and one with a semilunar rhythm. Light intensity alone does not affect the phase or strength of the lunar rhyth
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 3The enzyme glutamate-cysteine ligase (GCL) is a target for ferroptosis induction in cancer - 9 hour(s) ago
Despite glutathione’s long-recognized role as a major cellular antioxidant and its central role in ferroptosis defense, inhibition of glutathione biosynthetic enzymes has received little attention as a target for the therapeutic induction of ferroptosis. Here, we report that small-molecule inhibition of glutamate-cysteine ligase (GCL), the rate-limiting enzyme of glutathione biosynthesis, selectively and potently kills cancer cells by ferroptosis. We further describe novel GCL inhibitors including KOJ-1 and KOJ-2, compounds with excellent cellular potency and pharmacological properties, representing valuable tools to study the biology of ferroptosis and glutathione. ### Competing Interest Statement V.S.V is a co-founder and equity holder of Kojin Therapeutics. All authors are equity holders of Kojin Therapeutics and are either current or past employees of Kojin Therapeutics. J.K.E, L.F., J.H.J. and V.S.V. are inventors of patents related to ferroptosis and GCL.
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 3
Heat stress is one of the major threats to maize (Zea mays) production globally. Heat shock transcription factors (HSFs) play vital roles in plant heat stress responses. However, the molecular and genetic basis of HSFs in maize thermotolerance remain largely unknown. In this study, we reveal that the alternative splicing of Hsf23 in maize modulates heat stress tolerance. Hsf23 produces two functional transcripts, the full-length transcript Hsf23b and the heat-inducible transcript Hsf23a. The two Hsf23 transcripts differ by the presence of a cryptic mini exon in Hsf23a, which is spliced out in Hsf23b. Both Hsf23a and Hsf23b were intensely expressed in response to heat stress. The overexpression of Hsf23b, not Hsf23a, enhanced heat stress tolerance, while loss-of-function mutations of Hsf23a and Hsf23b exhibited remarkably increased sensitivity to heat stress. Transcriptome analysis revealed that Hsf23b activates broader heat-responsive genes than Hsf23a, and Hsf23a and Hsf23b modulate h
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 1
Propionibacterium freudenreichii (PFR) DSM 20271 is a bacterium known for its ability to thrive in diverse environments and to produce vitamin B12. Despite its anaerobic preference, recent studies have elucidated its ability to prosper in the presence of oxygen, prompting a deeper exploration of its physiology under aerobic conditions. Here, we investigated the response of DSM 20271 to aerobic growth by employing comparative transcriptomic and surfaceome analyses alongside metabolite profiling. Cultivation under controlled partial pressure of oxygen (pO2) conditions revealed significant increases in biomass formation and altered metabolite production, notably of B12 vitamin, pseudovitamin-B12, propionate and acetate, under aerobic conditions. Transcriptomic analysis identified differential expression of genes involved in lactate metabolism, TCA cycle, and electron transport chain, suggesting metabolic adjustments to aerobic environments. Moreover, surfaceome analysis unveiled growth en
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 1DNA damage and senescence in the aging and Alzheimer's disease cortex are not uniformly distributed - 1 day(s) ago
Alzheimer’s disease (AD) is a neurodegenerative illness with a typical age of onset exceeding 65 years of age. The age-dependency of the condition led us to track the appearance of DNA damage in the frontal cortex of individuals who died with a diagnosis of AD. The focus on DNA damage was motivated by evidence that increasing levels of irreparable DNA damage are a major driver of the aging process. The connection between aging and the loss of genomic integrity is compelling because DNA damage has also been identified as a possible cause of cellular senescence. The number of senescent cells has been reported to increase with age, and their senescence-associated secreted products are likely contributing factors to age-related illnesses. We tracked DNA damage with 53BP1 and cellular senescence with p16 immunostaining of human post-mortem brain samples. We found that DNA damage is significantly increased in the BA9 region of the AD cortex when compared to the same region of unaffected cont
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 1Disorganized Inhibitory Dynamics and Functional Connectivity in Hippocampal area CA1 of 22q11.2 Deletion Mutant Mice - 1 day(s) ago
Individuals with the 22q11.2 deletion syndrome, one of the strongest genetic risk factors for schizophrenia, demonstrate cognitive impairments such as episodic memory dysfunction. Place cell dynamics in the hippocampus supporting episodic memory are also impaired in a mouse model for the 22q11.2 deletion (Df(16)A+/-). While hippocampal neural dynamics are under strong inhibitory control, there is no available information about functional alterations of molecularly identified inhibitory circuits in mouse models for the 22q11.2 deletion. Here, we examined interneuron subtype-specific activity dynamics in hippocampal area CA1 of Df(16)A+/- mice performing random foraging and goal-oriented reward learning tasks. We found that Df(16)A+/- inhibitory interneurons carry markedly reduced spatial information during random foraging. Mutant mice perseverate at rewarded locations during reward learning, and multiple interneuron types exhibit aberrant responses to reward locations. We observe task-d
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 0
Objective Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a white matter disease characterized by myelin vacuolization and swollen perivascular astrocyte processes. Neuronal activity has been implicated as primary cause of myelin vacuolization and astrocyte swelling. Since acute and excessive increases in neuronal activity occur in MLC during seizures, we investigated whether seizure activity leads to the acute development of myelin vacuoles and swollen astrocyte processes. Methods Glialcam -null mice (an established MLC mouse model) and wild-type mice received repeated i.p. low dose (5 mg / kg) kainic acid (KA) injections until severe seizures developed. Following a 60-minute period of severe seizure activity, mice were terminated and brains were fixed and processed. Brain tissue was analyzed for myelin vacuolization and astrocyte process thickness using H&E and GFAP stains, respectively. Results Repeated low-dose injections of KA resulted in prolonged severe seizu
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 1MmpL3, Wag31 and PlrA are involved in coordinating polar growth with peptidoglycan metabolism and nutrient availability - 1 day(s) ago
Cell growth in mycobacteria involves cell wall expansion that is restricted to the cell poles. The DivIVA homolog Wag31 is required for this process, but the molecular mechanism and protein partners of Wag31 have not been described. In this study of Mycobacterium smegmatis, we identify a connection between wag31 and trehalose monomycolate (TMM) transporter mmpl3 in a suppressor screen, and show that Wag31 and polar regulator PlrA are required for the polar localization of MmpL3 . In addition, the localization of PlrA and MmpL3 are responsive to nutrient and energy deprivation and inhibition of peptidoglycan metabolism. We show that inhibition of MmpL3 causes delocalized cell wall metabolism, but does not delocalize MmpL3 itself. We found that cells with an MmpL3 C-terminal truncation, which is defective for localization, have only minor defects in polar growth, but are impaired in their ability to downregulate cell wall metabolism under stress. Our work suggests that, in addition to it
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
-
Mashup Score: 1Evaluation of extraction solvents for untargeted metabolomics to decipher the DOM of Antarctic cryoconite holes - 1 day(s) ago
Cryoconite holes (CHs) are biological hotspots with a high biogeochemical turnover rate, contributing significantly to the glacial ecosystem′s overall carbon cycles and net fluxes. There is limited information regarding the composition of low molecular weight (LMW) molecules formed through the metabolic processes of cryoconite-dwelling microbes. These molecules constitute a substantial portion of the dissolved organic matter (DOM) within cryoconite holes. Here, we evaluated different solvents to extract low molecular weight (LMW) compounds for untargeted metabolomics using reverse phase liquid chromatography (RP-LC) coupled with high-resolution tandem mass spectrometry in positive- and negative-ionization modes. We prepared single, binary, and ternary mixtures of highly polar to relatively non-polar solvents like water, methanol, and acetonitrile to extract intra- and extracellular metabolites from CHs sediment. The biological replicates (n=4) of each identical solvent showed high repr
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
Single-cell transcriptomics reveals evolutionary reconfiguration of embryonic cell fate specification in the sea urchin Heliocidaris erythrogramma https://t.co/LyNsuxANJG #bioRxiv