Publications by authors named "Milton M"

The global burden of tuberculosis, particularly multidrug-resistant (MDR) strains of Mycobacterium tuberculosis, necessitates the urgent development of novel and effective therapeutic agents. Natural products derived from plants have long served as an essential resource for drug discovery, offering structurally diverse bioactive compounds. Sphaeranthus indicus, a plant traditionally valued for its medicinal properties, has shown promise as a source of antimicrobial agents.

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What makes a bacterium pathogenic? Since the early days of germ theory, researchers have categorized bacteria as pathogens or non-pathogens, those that cause harm and those that do not, but this binary view is not always accurate. is an exclusive mutualistic symbiont found within the light organs of Hawaiian bobtail squid. This symbiotic interaction requires to utilize a range of behaviors and produce molecules that are often associated with pathogenicity.

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Mosquitoes, as hematophagous ectoparasites, are significant pests and vectors of numerous pathogens, causing diseases such as dengue, lymphatic filariasis, malaria, chikungunya, and Japanese encephalitis in India. This study investigates the potential of natural insecticides derived from plants to combat mosquito populations, focusing on botanical extract from the leave of Sphaeranthus indicus. Specifically, the hexane extract of S.

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Mitochondrial dysfunction plays an important role in Parkinson's disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for mitochondrial health. We investigated the links between blood mtDNA-CN and PD severity and risk using the Accelerating Medicines Partnership program for Parkinson's Disease dataset, replicating our results in the UK Biobank. Our findings reveal that reduced blood mtDNA-CN levels are associated with heightened PD risk and increased severity of motor symptoms and olfactory dysfunction.

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Article Synopsis
  • Mosquitoes can transmit various infectious diseases to humans and animals, prompting research into natural compounds for control.
  • The study focuses on isolating and characterizing andrographolide from the plant Andrographis paniculata, assessing its effects on mosquito eggs, larvae, and pupae.
  • Results show that andrographolide has moderate effects on mosquito egg mortality and strong efficacy against larvae and pupae, suggesting it as a promising alternative to synthetic insecticides for managing mosquito populations.
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Clavulanic acid (CLAV) is a component of Augmentin® that preserves antibiotic efficacy by inhibiting β-lactamase activity. It also enhances cellular glutamate uptake and is a potential CNS therapeutic. Because increased glutamate transmission in brain reward circuits facilitates methamphetamine (METH) locomotor activation and sensitization, we tested the hypothesis that CLAV inhibits acute and sensitized locomotor responses to METH in mice and investigated effects of CLAV on METH-induced changes in glutaminase, the major glutamate-producing enzyme in the brain.

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and dose-limiting complications in chemotherapy patients, with estimates of at least 30% of patients experiencing persistent neuropathy for months or years after treatment cessation. An emerging potential intervention for the treatment of CIPN is cannabinoid-based pharmacotherapies. We have previously demonstrated that treatment with the psychoactive CB1/CB2 cannabinoid receptor agonist Δ-tetrahydrocannabinol (Δ-THC) or the non-psychoactive, minor phytocannabinoid cannabidiol (CBD) can attenuate paclitaxel-induced mechanical sensitivity in a mouse model of CIPN.

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  • Microbial hydrogen cycling is critical for the variety and function of anoxic ecosystems, traditionally linked to [FeFe] hydrogenases found in bacteria and eukaryotes.
  • Recent research shows that anaerobic archaea also possess diverse and active [FeFe] hydrogenases, indicating a broader evolutionary history than previously understood.
  • The study reveals new metabolic adaptations in archaea, introduces a simple hydrogenase in DPANN archaea, and uncovers hybrid hydrogenases formed by mixing [FeFe] and [NiFe] types, suggesting a complex evolutionary relationship between these enzyme groups.
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Two component system bacterial response regulators are typically DNA-binding proteins which enable the genetic regulation of many adaptive bacterial behaviors. Despite structural similarity across response regulator families, there is a diverse array of DNA-binding mechanisms. Bacteria usually encode several dozen two-component system response regulators, but Francisella tularensis only encodes three.

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Understanding tissue biology's heterogeneity is crucial for advancing precision medicine. Despite the centrality of the immune system in tissue homeostasis, a detailed and comprehensive map of immune cell distribution and interactions across human tissues and demographics remains elusive. To fill this gap, we harmonised data from 12,981 single-cell RNA sequencing samples and curated 29 million cells from 45 anatomical sites to create a comprehensive compositional and transcriptional healthy map of the healthy immune system.

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Global biodiversity gradients are generally expected to reflect greater species replacement closer to the equator. However, empirical validation of global biodiversity gradients largely relies on vertebrates, plants, and other less diverse taxa. Here we assess the temporal and spatial dynamics of global arthropod biodiversity dynamics using a beta-diversity framework.

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BOLD, the Barcode of Life Data System, supports the acquisition, storage, validation, analysis, and publication of DNA barcodes, activities requiring the integration of molecular, morphological, and distributional data. Its pivotal role in curating the reference library of DNA barcodes, coupled with its data management and analysis capabilities, makes it a central resource for biodiversity science. It enables rapid, accurate identification of specimens and also reveals patterns of genetic diversity and evolutionary relationships among taxa.

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Article Synopsis
  • * Researchers discovered that the archaeon Acidianus brierleyi can consume H and CO, aiding ATP production and survival across a temperature range of 10 to 70 °C.
  • * The study indicates that trace gas oxidation may be a widespread feature among Sulfolobales archaea, which could support their survival and growth in various environments, including temperate ones.
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Recombinant adeno-associated virus (AAV) vectors are the leading delivery vehicle used for gene therapies. Anti-AAV antibodies (AAV Abs) can interact with the viral capsid component of an AAV-based gene therapy (GT). Therefore, patients with preexisting AAV Abs (seropositive patients) are often excluded from GT trials to prevent treatment of patients who are unlikely to benefit or may have a higher risk for adverse events outweighing treatment benefits.

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  • Despite evidence supporting comprehensive oncogeriatric assessments for older cancer patients, specialized programs are underutilized in the UK due to a lack of detailed clinic structures and patient data.
  • A study at the Royal Marsden Hospital screened 244 patients using the SAOP3 tool to identify geriatric impairments and factors influencing resource utilization.
  • Results showed a median participant age of 77, with a high prevalence of geriatric impairments (86.5%), predominantly among those undergoing palliative treatment, highlighting the need for improved multidisciplinary referrals in geriatric oncology.
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Purpose: The purpose of this study was to evaluate the effectiveness of Pisonia alba Span commonly known as lettuce tree or bird catcher tree leaf extracts in controlling Aedes aegypti and Culex quinquefasciatus mosquitoes, which transmit several severe illnesses, such as dengue, Zika, chikungunya, yellow fever, West Nile virus, lymphatic filariasis and Japanese encephalitis.

Methods: Sequential extraction of P. alba leaves was done using n-hexane, chloroform, and methanol.

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Mosquitoes are the vectors of several diseases like dengue, chikungunya, malaria etc. The three important mosquito species in India are Aedes aegypti, Culex quinquefasciatus and Anopheles stephensi. Several plant extracts have been tested for their anti-mosquito activity.

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Mosquito control is vital for combating mosquito-borne diseases, but concerns exist regarding the use of synthetic insecticides. This study aimed to explore eco-friendly alternatives derived from natural sources. The larvicidal, pupicidal, and ovicidal activities of various fractions obtained from the hexane leaf extract of Sphaeranthus indicus were investigated against two important mosquito vectors, Aedes aegypti and Culex quinquefasciatus.

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Emerging evidence links interleukin-17A (IL-17A) to anxiety and stress. Circulating levels of IL-17A are elevated in patients with anxiety disorders, and pharmacological blockade of IL-17 signaling or genetic deletion of IL-17 reduces anxiety-like behaviors in mice. Given that IL-17 is one of the most conserved cytokines among animal phyla, we tested the hypothesis that anti-IL-17 treatments reduce defensive responding in planarians, the simplest animal with bilateral symmetry and a CNS with cephalization.

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This article reports on the findings of a study that explores the utility of digital storytelling as a narrative practice and learning tool for social work in an Australian secure forensic mental health hospital. The short digital stories, or Digital Bytes Project, centered on capturing the lived experience, hopes and perspectives of the hospital's service users by giving voice to their experiences through digital technology. The project was collaboratively designed and co-delivered with social work students, hospital staff, and service users.

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The number of approved or investigational late phase viral vector gene therapies (GTx) has been rapidly growing. The adeno-associated virus vector (AAV) technology continues to be the most used GTx platform of choice. The presence of pre-existing anti-AAV immunity has been firmly established and is broadly viewed as a potential deterrent for successful AAV transduction with a possibility of negative impact on clinical efficacy and a connection to adverse events.

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Anti-sigma factor antagonists SpoIIAA and RsbV from are the archetypes for single-domain STAS proteins in bacteria. The structures and mechanisms of these proteins along with their cognate anti-sigma factors have been well studied. SpoIIAA and RsbV utilize a partner-switching mechanism to regulate gene expression through protein-protein interactions to control the activity of their downstream anti-sigma factor partners.

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Anagrelide (ANG) is a widely used drug for the treatment of essential thrombocytosis and myeloproliferative neoplasms. Recently, a new oxidative degradant was identified when the drug product capsule underwent stress testing. Full structural characterization of this previously unidentified degradant was conducted.

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Bacterial biofilms are notorious for their ability to protect bacteria from environmental challenges, most importantly the action of antibiotics. Bacillus subtilis is an extensively studied model organism used to understand the process of biofilm formation. A complex network of principal regulatory proteins including Spo0A, AbrB, AbbA, Abh, SinR, SinI, SlrR, and RemA, work in concert to transition B.

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Multidrug-resistant bacteria cause immense public health concerns as once effective antibiotics no longer work against even common infections. Concomitantly, there has been a decline in the discovery of new antibiotics, and the current global clinical pipeline is woefully inadequate, especially against resistant Gram-negative bacteria. One major contribution to Gram-negative resistance is the presence of a protective outer membrane.

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