Publications by authors named "Pin J"

A phyllodes tumor (PT) is a biphasic fibroepithelial lesion that is most commonly found in breast tissue, whereas it is uncommon in ureter tissue. Only one case has been documented so far. There are some similarities in histology and clinical characteristics between this type of tumor and PT of the female breast: the lesions can be surgically removed, but some recur locally and invade directly into the breast.

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Article Synopsis
  • The study investigates the structural basis of allosteric interactions in heterodimeric G protein-coupled receptors (GPCRs), specifically focusing on metabotropic glutamate (mGlu) receptors, which are crucial for synaptic regulation.
  • Researchers utilized cryo-electron microscopy to reveal four distinct structures of the mGlu2-4 heterodimer, showcasing different activation states, including inactive, intermediate, and active forms.
  • Findings indicate that agonist binding to just one subunit isn't enough for full activation of the dimer, highlighting the asymmetric nature of mGlu receptor activation, where only mGlu4 activates G proteins.
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Background: Idiopathic intracranial hypertension (IIH) is defined as elevated intracranial pressure and consequent symptoms (mainly headache and visual deterioration) occurring in the absence of secondary causes. Surgical and interventional radiology procedures should be considered for refractory IIH and mainly include cerebrospinal fluid (CSF) diversion techniques, optic nerve sheath fenestration (ONSF), and venous sinus stenting (VSS). Our study aims to review the current literature on the application of these techniques in clinical practice.

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Metabotropic glutamate receptors (mGlu) regulate multiple functions in the nervous systems and are involved in several neurological disorders. However, selectively targeting individual mGlu subtypes with spatiotemporal precision is still an unmet need. Photopharmacology can address this concern through the utilization of photoswitchable compounds such as optogluram, which is a positive allosteric modulator (PAM) of mGlu that enables the precise control of physiological responses using light but does not have an optimal selectivity profile.

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Identified 40 years ago, the metabotropic glutamate (mGlu) receptors play key roles in modulating many synapses in the brain, and are still considered as important drug targets to treat various brain diseases. Eight genes encoding mGlu subunits have been identified. They code for complex receptors composed of a large extracellular domain where glutamate binds, connected to a G protein activating membrane domain.

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Background: Cerebral venous thrombosis (CVT) is a cerebrovascular disorder that accounts for 20% of perinatal strokes. CVT incidence ranges from 0.67 to 1.

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Metabotropic glutamate (mGlu) receptors play a key role in modulating most synapses in the brain. The mGlu7 receptors inhibit presynaptic neurotransmitter release and offer therapeutic possibilities for post-traumatic stress disorders or epilepsy. Screening campaigns provided mGlu7-specific allosteric modulators as the inhibitor (Gee et al.

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G protein-coupled receptors naturally oscillate between inactive and active states, often resulting in receptor constitutive activity with important physiological consequences. Among the class C G protein-coupled receptors that typically sense amino-acids and their derivatives, the calcium sensing receptor (CaSR) tightly controls blood calcium levels. Its constitutive activity has not yet been studied.

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There is an urgent need for alternative therapies targeting human dendritic cells (DCs) that could reverse inflammatory syndromes in many autoimmune and inflammatory diseases and organ transplantations. Here, we describe a bispecific antibody (bsAb) strategy tethering two pathogen-recognition receptors at the surface of human DCs. This cross-linking switches DCs into a tolerant profile able to induce regulatory T-cell differentiation.

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G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterologous cells. However, GPCR responses may differ in their native environment.

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The world has witnessed a revolution in therapeutics with the development of biological medicines such as antibodies and antibody fragments, notably nanobodies. These nanobodies possess unique characteristics including high specificity and modulatory activity, making them promising candidates for therapeutic applications. Identifying their binding mode is essential for their development.

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Metabotropic glutamate receptor 2 (mGlu) attracts particular attention as a possible target for a new class of antipsychotics. However, the signaling pathways transducing the effects of mGlu in the brain remain poorly characterized. Here, we addressed this issue by identifying native mGlu interactome in mouse prefrontal cortex.

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The metabotropic glutamate (Glu) receptors (mGluRs) are G-protein coupled receptors, which play a central role in modulating excitatory neurotransmission in the central nervous system (CNS). Thus, the development of tool compounds thereto, continues to interest the scientific community. In this study, we report the design and synthesis of new conformationally restricted 2-aminoadipic acid (2AA) 2-4, and glutamic acid 5, 6 analogs, which share the cyclopropane ring as the restrictor.

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Serological studies of COVID-19 convalescent patients have identified polyclonal lineage-specific and cross-reactive antibodies (Abs), with varying effector functions against virus variants. Individual specificities of anti-SARS-CoV-2 Abs and their impact on infectivity by other variants have been little investigated to date. Here, we dissected at a monoclonal level neutralizing and enhancing Abs elicited by early variants and how they affect infectivity of emerging variants.

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Metabotropic glutamate (Glu) receptors (mGlu receptors) play a key role in modulating excitatory neurotransmission in the central nervous system (CNS). In this study, we report the structure-based design and pharmacological evaluation of densely functionalized, conformationally restricted glutamate analogue (1,2,3)-2-(()-amino(carboxy)methyl)-3-(carboxymethyl)cyclopropane-1-carboxylic acid (). was synthesized in a stereocontrolled fashion in nine steps from a commercially available optically active epoxide.

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Solvent-based and mechanical recycling technology approaches were compared with respect to each process's decontamination efficiency. Herein, post-consumer polystyrene (PS) feedstock was recycled by both technologies, yielding recycled PS resins (rPS). The process feedstock was subjected to four recycling cycles in succession to assess the technology perennity.

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Article Synopsis
  • The Concise Guide to PHARMACOLOGY 2023/24 offers a summarized overview of approximately 1800 drug targets and around 6000 interactions with 3900 ligands, mostly in a tabular format.
  • It focuses on selective pharmacology and includes links to an open access knowledgebase for more detailed drug information.
  • The guide divides drug targets into six major categories, providing essential summaries and guidance based on the latest pharmacological data available as of mid-2023, while serving as an official resource by the International Union of Basic and Clinical Pharmacology.
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The structural basis of the activation and internalization of EGF receptors (EGFR) is still a matter of debate despite the importance of this target in cancer treatment. Whether agonists induce dimer formation or act on preformed dimers remains discussed. Here, we provide direct evidence that EGF-induced EGFR dimer formation as best illustrated by the very large increase in FRET between snap-tagged EGFR subunits induced by agonists.

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Background: Deep medullary vein (DMV) thrombosis is a rare cause of brain damage in both preterm and full-term neonates. In this study, we aimed to collect data on clinical and radiological presentation, treatment, and outcome of neonatal DMV thrombosis.

Methods: Systematic literature review on neonatal DMV thrombosis was carried out in PubMed, ClinicalTrial.

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Background: Evidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE.

Methods: We described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine.

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Background: Only a few studies have focused on hemiplegic migraine (HM) in children despite its early age of onset. The aim of this review is to describe the peculiar characteristics of pediatric HM.

Methods: This is a narrative review based on 14 studies on pediatric HM selected from 262 papers.

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Allosteric modulators bear great potential to fine-tune neurotransmitter action. Promising targets are metabotropic glutamate (mGlu) receptors, which are associated with numerous brain diseases. Orthosteric and allosteric ligands act in synergy to control the activity of these multidomain dimeric GPCRs.

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G protein-coupled receptors (GPCRs) represent the largest family of membrane proteins and are important drug targets. GPCRs are allosteric machines that transduce an extracellular signal to the cell by activating heterotrimeric G proteins. Herein, we summarize the recent advancements in the molecular activation mechanism of the γ-aminobutyric acid type B (GABA) and metabotropic glutamate (mGlu) receptors, the most important class C GPCRs that modulate synaptic transmission in the brain.

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