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Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

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Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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Rab Cascades01:25

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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Cascaded Op Amps01:16

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Amplifying Signals via Enzymatic Cascade01:22

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
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A Preclinical Murine Model of Hepatic Metastases
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The Massachusetts Hepatitis C Testing Cascade, 2014-2016.

Quynh T Vo1, Shauna Onofrey1, Daniel Church1

  • 1Bureau of Infectious Disease and Laboratory Sciences, Massachusetts Department of Public Health, Boston, MA, USA.

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|July 2, 2019
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Summary
This summary is machine-generated.

Hepatitis C testing in Massachusetts shows that 61% of those with a positive antibody test received a follow-up RNA test, confirming active infection in 79%. Gaps in care exist, particularly by birth cohort and race/ethnicity.

Keywords:
hepatitis Csurveillancetesting cascade

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Area of Science:

  • Public Health
  • Infectious Disease Epidemiology
  • Health Services Research

Background:

  • Hepatitis C virus (HCV) infection remains a significant public health concern.
  • Understanding the HCV testing cascade is crucial for effective disease control and elimination strategies.
  • Massachusetts data provides a localized perspective on HCV testing patterns.

Purpose of the Study:

  • To analyze the hepatitis C testing cascade in Massachusetts from 2014-2016.
  • To identify factors influencing progression through the HCV testing and diagnosis pathway.
  • To inform stakeholders on improving care for individuals with hepatitis C.

Main Methods:

  • Retrospective analysis of laboratory reports for anti-HCV antibody positive individuals (2014-2016).
  • Evaluation of subsequent nucleic acid tests (RNA) or genotype tests as outcomes.
  • Logistic regression to identify factors associated with testing cascade progression.

Main Results:

  • 61% (13,194) of anti-HCV antibody positive cases had a subsequent RNA-based test.
  • 79% (10,374) of these cases confirmed active HCV infection.
  • Significant variations in testing cascade progression were observed based on birth cohort and race/ethnicity.

Conclusions:

  • Active HCV infection confirmation rates are substantial among those tested.
  • Disparities in accessing confirmatory testing and genotyping exist across demographic groups.
  • Enhanced demographic data capture in surveillance is essential for achieving health equity in HCV diagnosis and care linkage.