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Mashup Score: 1
In response to the challenge of nutrient-deficient sandy soils and water scarcity due to excessive evaporative water loss in arid regions, we developed and tested two complementary soil amendment technologies: Superhydrophobic sand (SHS) mulch and an enriched date palm biochar. In a greenhouse pot experiment, we investigated the independent and synergistic effects of SHS mulch (10 mm thickness) and biochar (2% w/w) on Moringa oleifera plants under normal (N, 100% field capacity) and reduced (R, 50% of N) irrigation scenarios. Under N and R, SHS mulch reduced evaporation by 71% and 64%, respectively; while SHS+biochar reduced evaporation by 61% and 47%, respectively, in comparison with the control (p < 0.05). Total transpiration significantly increased in SHS plants by 311% and 385% under N and R, respectively. Compared with the control, transpiration increased in biochar plants by 103% and 110%; whereas, its combination with SHS increased transpiration by 288% and 301% under N and R, r
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 2The Ccm3-GckIII signaling axis regulates Rab11-dependent recycling to the apical compartment - 4 hour(s) ago
Kinase cascades underlie many signaling pathways and are key regulators of development and morphogenesis. We have characterized a Hippo-like kinase cascade consisting of Thousand and One kinase (Tao), Germinal Center Kinase III (GckIII/Wheezy), and Tricornered (Trc) that plays an essential role in morphogenesis of tracheal terminal cell tubes in Drosophila. In this cascade, GckIII is the central kinase and is thought to act together with its binding partner, Cerebral Cavernous Malformations 3 (Ccm3). As suggested by its name, Drosophila Ccm3 is the ortholog of a human vascular disease gene. As such, defining the Ccm3 pathway is critical to understanding both normal development and disease. Here we generate and characterize a null allele of Ccm3 in Drosophila. We uncover a maternal contribution of Ccm3 to embryonic development, show that maternal/zygotic null embryos have defective multicellular tracheal tubes, and that tracheal terminal cells derived from zygotic clones that also lack
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Mashup Score: 1
The transcriptional coactivators EP300 and CREBBP are critical regulators of gene expression that share high sequence identity but exhibit non-redundant functions in basal and pathological contexts. Here, we report the development of a bifunctional small molecule, MC-1, capable of selectively degrading EP300 over CREBBP. Using a potent aminopyridine-based inhibitor of the EP300/CREBBP catalytic domain in combination with a VHL ligand, we demonstrate that MC-1 preferentially degrades EP300 in a proteasome-dependent manner. Mechanistic studies reveal that selective degradation cannot be predicted solely by target engagement or ternary complex formation, suggesting additional factors govern paralogue-specific degradation. MC-1 inhibits cell proliferation in a subset of cancer cell lines and provides a new tool to investigate the non-catalytic functions of EP300 and CREBBP. Our findings expand the repertoire of EP300/CREBBP-targeting chemical probes and offer insights into the determinants
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 1Label-free Assessment of Complement-Dependent Cytotoxicity of Therapeutic Antibodies via a Whole-Cell MALDI Mass Spectrometry Bioassay - 8 hour(s) ago
Potency assessment of monoclonal antibodies or corresponding biosimilars in cell-based assays is an essential prerequisite in biopharmaceutical research and development. However, cellular bioassays are still subject to limitations in sample throughput, speed, and often need costly reagents or labels as they are based on an indirect readout by luminescence or fluorescence. In contrast, whole-cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry (MS) has emerged as a direct, fast and label-free technology for functional drug screening being able to unravel the molecular complexity of cellular response to pharmaceutical reagents. However, this approach has not yet been used for cellular testing of biologicals. In this study, we have conceived, developed and benchmarked a label-free MALDI-MS based cell bioassay workflow for the functional assessment of complement-dependent cytotoxicity (CDC) of Rituximab antibody. By computational evaluation of respo
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Mashup Score: 0Crystal Structure of Caryolan-1-ol Synthase, a Sesquiterpene Synthase Catalyzing an Initial Anti-Markovnikov Cyclization Reaction - 8 hour(s) ago
In a continuing effort to understand reaction mechanisms of terpene synthases catalyzing initial anti-Markovnikov cyclization reactions, we solved the X-ray crystal structure of (+)-caryolan-1-ol synthase (CS) from Streptomyces griseus, with and without an inactive analog of the FPP substrate, 2-fluorofarnesyl diphosphate (2FFPP), bound in the active site of the enzyme. The CS-2FFPP complex was solved to 2.65 angstrom resolution and showed the ligand in a linear, elongated orientation, incapable of undergoing the initial cyclization event to form a bond between carbons C1 and C11. Intriguingly, the apo CS structure (2.2 angstrom) also had electron density in the active site, in this case density that was well fit with a curled-up tetraethylene glycol molecule presumably recruited from the crystallization medium. The density was also well fit by a molecule of farnesene suggesting that the structure may mimic an intermediate along the reaction coordinate. The curled-up conformation of te
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Mashup Score: 0Evolutionary rate covariation is pervasive between glycosylation pathways and points to potential disease modifiers - 9 hour(s) ago
Mutations in glycosylation pathways, such as N-linked glycosylation, O-linked glycosylation, and GPI anchor synthesis, lead to Congenital Disorders of Glycosylation (CDG). CDGs typically present with seizures, hypotonia, and developmental delay but display large clinical variability with symptoms affecting every system in the body. This variability suggests modifier genes might influence the phenotypes. Because of the similar physiology and clinical symptoms, there are likely common genetic modifiers between CDGs. Here, we use evolution as a tool to identify common modifiers between CDG and glycosylation genes. Protein glycosylation is evolutionarily conserved from yeast to mammals. Evolutionary rate covariation (ERC) identifies proteins with similar evolutionary rates that indicate shared biological functions and pathways. Using ERC, we identified strong evolutionary rate signatures between proteins in the same and different glycosylation pathways. Genome-wide analysis of proteins sho
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Mashup Score: 2Structural basis of Spliced Leader RNA recognition by the Trypanosoma brucei cap-binding complex - 10 hour(s) ago
Kinetoplastids are a clade of eukaryotic protozoans that include human parasitic pathogens like trypanosomes and Leishmania species. In these organisms, protein-coding genes are transcribed as polycistronic pre-mRNAs, which need to be processed by the coupled action of trans-splicing and polyadenylation to yield monogenic mature mRNAs. During trans-splicing, a universal RNA sequence, the spliced leader RNA (SL RNA) mini-exon, is added to the 5′-end of each mRNA. The 5′-end of this mini-exon carries a hypermethylated cap structure and is bound by a trypanosomatid-specific cap-binding complex (CBC). The function of three of the kinetoplastid CBC subunits is unknown, but an essential role in cap binding and trans-splicing has been suggested. Here, we report cryo-EM structures that reveal the molecular architecture of the Trypanosoma brucei CBC (TbCBC) complex. We find that TbCBC interacts with two distinct features of the SL RNA. The TbCBP20 subunit interacts with the m7G cap while TbCBP6
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Mashup Score: 1Deletion of an sRNA primes development in a multicellular bacterium - 10 hour(s) ago
Small non-coding RNAs (sRNAs) are essential in regulating gene expression during many biological processes. The myxobacteria gene pxr encodes an sRNA known to block fruiting-body development, an aggregative multicellular process triggered by starvation. Deletion of pxr allows Myxococcus xanthus cells to develop in the presence of nutrients. However, potential Pxr binding targets and most genes regulated by Pxr remain unknown. Here, we found that the absence of pxr expression dramatically alters the temporal dynamics of development, thus suggesting an important new role of this sRNA in myxobacterial ecology. We transcriptionally profiled vegetative cells of M. xanthus strains possessing vs lacking pxr and found that over half of the genes impacted by pxr deletion during growth are linked to development, including known and potentially novel critical regulators. Many other genes are associated with general metabolic processes, which Pxr regulates positively. Our study discovers new pheno
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 1A metabolic atlas of mouse aging - 10 hour(s) ago
Humans are living longer, but this is accompanied by an increased incidence of age-related chronic diseases. Many of these diseases are influenced by age-associated metabolic dysregulation, but how metabolism changes in multiple organs during aging in males and females is not known. Answering this could reveal new mechanisms of aging and age-targeted therapeutics. In this study, we describe how metabolism changes in 12 organs in male and female mice at 5 different ages. Organs show distinct patterns of metabolic aging that are affected by sex differently. Hydroxyproline shows the most consistent change across the dataset, decreasing with age in 11 out of 12 organs investigated. We also developed a metabolic aging clock that predicts biological age and identified alpha-ketoglutarate, previously shown to extend lifespan in mice, as a key predictor of age. Our results reveal fundamental insights into the aging process and identify new therapeutic targets to maintain organ health. ### Comp
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Mashup Score: 1Synchronization between chloroplastic and cytosolic protein synthesis for photosynthesis complex assembly - 10 hour(s) ago
Through symbiosis, subunits of chloroplastic complexes are encoded in distinct genomes in the nucleus and organelles. For plant cells to maintain the stoichiometry of subunits and respond to environmental cues, orchestration of the nuclear and organellar gene expression systems is an essential task. However, the mechanism maintaining chloroplastic complexes remains largely enigmatic. Here, we simultaneously assessed the translatomes of the chloroplast and the cytoplasm via ribosome profiling and revealed the differential mechanisms employed by these two systems to cope with acute light/dark transitions: in chloroplasts, translational regulation is employed, whereas in the cytoplasm, control of the mRNA abundance is employed. This strategy is widely conserved in land plants (Arabidopsis and the grass plant Brachypodium) and green algae (Chlamydomonas). The translational control in chloroplasts may be established on the basis of organelle symbiosis; the primitive chloroplast in Glaucophy
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Superhydrophobic Sand Mulch and Date Palm Biochar Dramatically Boost Growth of Moringa oleifera in Sandy Soil: Insights into Evapotranspiration Budgeting and Metabolomic Profiling https://t.co/mr04lN3OfH #bioRxiv