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Related Concept Videos

Cranial and Spinal Meninges01:19

Cranial and Spinal Meninges

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The cranial and spinal meninges are complex protective structures surrounding the central nervous system (CNS), consisting of the brain and spinal cord. These meninges consist of the dura mater, the arachnoid mater, and the pia mater. They protect the CNS, provide structural support, and aid in circulating cerebrospinal fluid (CSF).
Cranial Meninges
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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
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When a voltage is applied to a conductor, an electrical field is generated, and charges in the conductor feel the force due to the electrical field. The current density that results depends on the electrical field and the properties of the material. In some materials, including metals at a given temperature, the current density is approximately proportional to the electrical field. In these cases, the current density can be modeled as:
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Resistance01:19

Resistance

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When a current moves through any conductor, the conductor causes some level of difficulty for the current to flow. The measure of that difficulty is known as the resistance of the material and is represented by R. Every material has its own resistance. In the case of conductors, heat is emitted whenever a current passes through them. Resistance depends on the resistivity of the material. Resistivity is a characteristic of the material used to fabricate electrical components, whereas the...
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Dynamic Equilibrium

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A reversible chemical reaction represents a chemical process that proceeds in both forward (left to right) and reverse (right to left) directions. When the rates of the forward and reverse reactions are equal, the concentrations of the reactant and product species remain constant over time and the system is at equilibrium. A special double arrow is used to emphasize the reversible nature of the reaction. The relative concentrations of reactants and products in equilibrium systems vary greatly;...
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Updated: Jan 30, 2026

Automated Measurement of Cryptococcal Species Polysaccharide Capsule and Cell Body
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Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis.

Neil Rh Stone1, Johanna Rhodes2, Matthew C Fisher2

  • 1Centre for Global Health, Institute for Infection and Immunity, St. George's, University of London, United Kingdom.

The Journal of Clinical Investigation
|January 29, 2019
PubMed
Summary

Fluconazole resistance in cryptococcal meningitis emerges due to aneuploidy, but combination therapy with flucytosine suppresses this resistance. This finding is crucial for improving treatment outcomes in affected patients.

Keywords:
AIDS/HIVDrug therapyFungal infectionsInfectious disease

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Area of Science:

  • Mycology
  • Infectious Diseases
  • Genetics

Background:

  • Cryptococcal meningitis (CM) is a major cause of death, particularly in sub-Saharan Africa.
  • Current treatment often involves fluconazole (FLC) monotherapy, with observed relapses linked to drug resistance.
  • Mechanisms of FLC resistance emergence in human CM, including heteroresistance (HetR), are poorly understood.

Purpose of the Study:

  • To investigate the presence and emergence of FLC heteroresistance in HIV-associated CM.
  • To understand the genetic mechanisms driving FLC resistance in Cryptococcus spp.
  • To evaluate the impact of combination therapy (FLC + 5FC) on FLC heteroresistance.

Main Methods:

  • Prospective observation of 20 HIV-associated CM patients in Tanzania.
  • Quantification of total and resistant Cryptococcus spp. subpopulations in cerebrospinal fluid (CSF).
  • Whole genome sequencing and phenotypic characterization of isolates.

Main Results:

  • Heteroresistance was detected in all patients at baseline.
  • FLC monotherapy led to an increase in resistant subpopulations within 2 weeks.
  • Combination therapy with FLC and 5FC suppressed detectable resistant subpopulations by day 14.
  • Aneuploidy, particularly Chr1 disomy involving ERG11 and AFR1, was associated with heteroresistance and relapse isolates.
  • In vitro efflux levels correlated with heteroresistance levels.

Conclusions:

  • Demonstrated aneuploidy-driven FLC heteroresistance in human CM for the first time.
  • Established an association between efflux levels and heteroresistance.
  • Showed successful suppression of heteroresistance using 5FC/FLC combination therapy.