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An atlas of human siglecs integrates expression, affinity, and cis/trans sialoglycan recognition profiles
von Willebrand Factor fibers formed at pathological high shear provide a scaffold for α-synuclein binding and aggregation
IFNγ blockade in Mycobacterium tuberculosis infected macaques alters the granuloma environment but not bacterial control
Abstract IFNγ is considered the primary mediator of adaptive immunity to Mycobacterium tuberculosis (Mtb) infection. In mice, control of Mtb requires IFNγ. In humans, IFNγ is critical for resistance to infection with non-tuberculous mycobacteria (NTM), but its relative requirement for control of pulmonary tuberculosis (TB) is less clear. Here we block IFNγR1 signaling in macaques at different times following Mtb infection. IFNγ blockade from day 45 to 49 post-infection rapidly reduced 18 FDG-PET/CT scores and broadly enhanced anti-viral-like inflammatory responses. Strikingly, IFNγR1 blockade for the first three months of infection had no impact on bacterial loads despite suppression of bioactive IFNγ in granulomas and changes to host immune responses and granuloma structure. We find individuals from Mtb endemic regions with anti-IFNγ neutralizing autoantibodies who develop NTM disease and not TB despite evidence of previous exposure to Mtb. Lastly, we show that mice over-estimate the importance IFNγ in host resistance to TB due to a species-specific induction of iNOS by IFNγ. Thus, while IFNγ has immunoregulatory effects in granulomas, normal resistance to TB in macaques and humans likely requires little IFNγR1 signaling during infection, indicating that the major mechanisms of adaptive immunity to Mtb infection remain unknown.
Meals that heal: a randomized controlled trial testing the feasibility of commercial meal delivery as a convenient dietary intervention for depression
Aged differentiated cells reverse into native stemness-like state by niche cytokines to sustain lifelong homeostasis and tissue repair
An in vitro collagen gel contraction assay to assess the relaxing effect of potential pharmacological alternatives to oxytetracycline on foals’ tendons
Abstract Oxytetracycline has been successfully used to treat flexural limb deformities in foals. However, its antimicrobial properties and potential adverse side effects warrant the investigation of alternatives. Inhibition of matrix metalloproteinases (MMPs) or collagen cross-linking have been suggested as possible mechanisms of action. This study assessed the influence of potential alternative substances lacking antimicrobial properties on collagen gel contraction by juvenile equine myofibroblasts in vitro . Myofibroblasts were isolated from forelimb SDFTs and inferior check ligaments from foals euthanised for reasons unrelated to this study, and seeded in collagen gels containing oxytetracycline, MMP-inhibitors incyclinide, ilomastat, aprotinin, and pentoxifylline, β-aminopropionitrile fumarate (BAPN), and control medium. The gels were measured in photographs up to 96 h after release, and differences in contraction were evaluated. Compared to control, BAPN and incyclinide induced significant inhibition ( p < 0.05) of collagen gel contraction by myofibroblasts at all time points, and the inhibition was more potent than that observed with oxytetracycline. Consequently, the inhibitory capacity of BAPN and incyclinide on myofibroblast-mediated collagen gel contraction, which demonstrates their effect on tractional structuring of collagen, makes them promising candidates as potential substitutes for oxytetracycline. Further investigations into their side effects, pharmacodynamics, pharmacokinetics, and application methods in juvenile equine patients are needed.
Beyond MPB engineering: enhanced piezoelectricity and thermal stability assisted by high-entropy design
Clinico-epidemiological determinants for empirical antibiotic prescriptions in suspected urinary tract infection cases attending peripheral hospitals of West Bengal, India- a cross sectional analysis
Cyromazine accelerates the dissemination of antimicrobial resistance genes by promoting the conjugative transfer of the SXT integrative conjugative element
SIRT1-mediated deacetylation of HMGB1 promotes the progression of endometriosis by regulating autophagy
Engineered conductive pili enable high-efficiency photosynthetic electron extraction in biophotovoltaics
Abstract The efficient extraction of electrons from photosynthetic microorganisms remains a critical challenge in living biophotovoltaics (BPV). While nanomaterials can facilitate electron transport, their stochastic adsorption leads to inefficient material-wasteful interfaces. Here, we demonstrate a controllable approach to direct the targeted assembly of gold nanoparticles (AuNPs) onto the type IV pili of Synechocystis sp. PCC 6803 by using a genetically encoded gold-binding peptide. This approach creates a spatially precise conductive nano-bio interface on the cell envelope that serves as a dedicated electron conduit between photosynthetic electron transport chains (PETCs) and electrodes. This nano-bio interface enhances electron transfer through synergistic improvements in interfacial charge transfer and biofilm density, ultimately yielding a four-fold increase in photocurrent density, while using two orders of magnitude less gold than non-targeted strategies. Moreover, the AuNPs can be transferred from inactivated to fresh cells, indicating a potential pathway for long-term stability. This work establishes a generalizable strategy for the rational design of conductive interfaces on living cells, with implications for biophotovoltaics, microbial electrosynthesis, and next-generation biohybrid devices.
In ovo versus ex ovo incubation differentially shapes chorioallantoic membrane maturation, angiogenesis, and tumor growth
Cryo-EM structures of the CDK11-cyclin L-SAP30BP complex reveal mechanisms of CDK11 regulation
Abstract The cyclin-dependent kinase CDK11 functions in transcription, mitotic progression, and mRNA splicing. Specifically, spliceosome activation during the B to B act transition depends on phosphorylation of the U2 snRNP component SF3B1 by the CDK11-cyclin L-SAP30BP complex. Here, we present the structure of this spliceosome-activating CDK-cyclin complex, determined by cryogenic electron microscopy at 2.3 Å resolution. Our structure and biochemical experiments show that SAP30BP forms extensive interactions with cyclin L2, thereby stabilising it, and forms critical interactions with the C-terminal kinase lobe of CDK11 that promote complex assembly. Destabilisation of cyclin L2 in the absence of SAP30BP suggests that these principles are applicable to all CDK11-cyclin L complexes. Furthermore, we identify a pseudo-substrate sequence near the CDK11 C-terminus and provide evidence for a role of this segment in CDK11 auto-regulation. Finally, the structure of the CDK11-cyclin L-SAP30BP complex bound to the clinical high-affinity CDK11 inhibitor OTS964 and a comparison to OTS964-bound off-target complexes provide insight into the mechanism of OTS964 selectivity and specificity.
Multi-analytical characterization of Stevia rebaudiana powder: nutritional, phytochemical, antioxidant, and NMR-based profiling
Memristive crossbar array-based hardware framework for compressed sensing and event-driven neuromorphic processing
Spirulina based DFNS/Cellulose nano hybrid as a bioactive reinforcement for durable foamed concrete
Core conformation of arrestin coupling to parathyroid hormone type 1 receptor
Profiling the tumor immunological status in Japanese solid cancers using the tumor immune status scoring algorithm
Mechanochemically functionalized waste plastics for NO2 sensing
Abstract Low-entropy non-depolymerizing upcycling of waste plastics into value-added products is promising, as it can avoid energy-intensive depolymerization process. Here, we report a mechanochemical approach for the direct functionalization of plastics with polyoxometalate (POM) molecules. The resulting POM-plastic composites retain integrated plastic chains and exhibit strong potential for NO 2 sensing. Among the composites, phosphotungstic acid/polyethylene terephthalate (PW 12 -PET) achieves a low limit of detection (10.52 ppb) and fast response/recovery times (19.2 s/13.5 s at 5.0 ppm), and shows practical applicability after device assembly. Moreover, it exhibits high selectivity against ten interfering gases. Mechanistic studies reveal that PET transfers multiple charges to PW 12 . It not only activates new bridge-oxygen sites on PW 12 but also maintains a moderate adsorption strength, enabling rapid NO 2 response. This work represents a promising example of direct non-depolymerizing upcycling of waste plastics into value-added functional materials.