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X-Inactivation01:58

X-Inactivation

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The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
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Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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Paracrine Signaling01:21

Paracrine Signaling

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Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
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Intrinsically Disordered Proteins02:18

Intrinsically Disordered Proteins

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Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
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Endocrine Signaling01:45

Endocrine Signaling

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Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
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Bacterial Signaling01:30

Bacterial Signaling

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Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
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Related Experiment Video

Updated: Jan 30, 2026

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder
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Inactivating PTH/PTHrP Signaling Disorders.

Giovanna Mantovani, Francesca M Elli

    Frontiers of Hormone Research
    |January 15, 2019
    PubMed
    Summary

    Pseudohypoparathyroidism (PHP) and related disorders involve hormone resistance due to impaired signaling pathways. A new term, inactivating PTH/PTHrP signaling disorder (iPPSD), unifies these conditions under a common mechanism.

    Area of Science:

    • Endocrinology
    • Genetics
    • Molecular Biology

    Background:

    • Pseudohypoparathyroidism (PHP) and related disorders present with diverse physical and laboratory abnormalities, including hormone resistance.
    • These conditions stem from disruptions in the cyclic adenosine monophosphate (cAMP)-mediated signal transduction pathway, particularly the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) signaling pathway.
    • Genetic mutations or alterations in genes like GNAS, PRKAR1A, PDE4D, and PDE3A underlie these disorders.

    Purpose of the Study:

    • To review the pathophysiology of PHP and related disorders over the past 30 years.
    • To introduce and describe a novel nomenclature and classification for these conditions.
    • To propose the term "inactivating PTH/PTHrP signaling disorder" (iPPSD) to unify these heterogeneous diseases.

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    Main Methods:

    • Literature review of research on PHP and related disorders over the last three decades.
    • Analysis of the common pathophysiological mechanisms.
    • Development and proposal of a new classification system.

    Main Results:

    • Significant progress has been made in understanding the pathophysiology of these disorders.
    • A new unifying term, "inactivating PTH/PTHrP signaling disorder" (iPPSD), has been proposed.
    • iPPSD defines the shared signaling pathway defect, does not necessitate a confirmed genetic defect, avoids ambiguous terminology, and resolves clinical/molecular overlap.

    Conclusions:

    • The proposed iPPSD classification offers a more accurate and unified approach to understanding these hormone resistance disorders.
    • This new nomenclature reflects the common underlying molecular mechanism.
    • iPPSD simplifies diagnosis and research by addressing the heterogeneity and overlap seen in previous classifications.