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Infection01:20

Infection

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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
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Urinary Tract Infection II: Pathophysiology01:25

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The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
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Cystic Fibrosis: Pathogenesis01:23

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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
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Pneumonia II: Pathophysiology01:29

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Stages of Infection01:26

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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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Defense Against Bacterial Pathogens01:31

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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
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Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Ciencia básica y patogénesis

Alexander V Soloviev1, Felipe Luiz Pereira1, Renata Elaine Paraizo Leite2,3

  • 1Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Los investigadores identificaron diferencias moleculares entre las neuronas RORB vulnerables y resilientes en la enfermedad de Alzheimer (EA). Estos hallazgos en la corteza entorrinal pueden explicar la vulnerabilidad neuronal selectiva y guiar futuros tratamientos para la EA.

Palabras clave:
Enfermedad de AlzheimerNeuronasCorteza entorrinalVulnerabilidad neuronalVías molecularesGenómicaBiología molecularNeurocienciaProteínas tauProteostasis

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Área de la Ciencia:

  • Neurociencia
  • Genómica
  • Biología molecular

Sus antecedentes:

  • La enfermedad de Alzheimer (EA) se caracteriza por una vulnerabilidad neuronal selectiva, particularmente en las neuronas excitatorias RORB-positivas en la corteza entorrinal (EC).
  • Comprender la base molecular de esta vulnerabilidad selectiva es fundamental para desarrollar terapias dirigidas para la EA.
  • No todas las neuronas RORB-positivas presentan vulnerabilidad, lo que sugiere diferencias moleculares intrínsecas entre los subtipos.

Objetivo del estudio:

  • Identificar las vías moleculares que distinguen los subtipos de neuronas excitatorias RORB-positivas vulnerables de las resilientes en las etapas tempranas de la EA.
  • Aprovechar los datos de secuenciación de ARN de núcleo único (snRNA-seq) para descubrir firmas transcriptómicas asociadas con la vulnerabilidad neuronal en la EA.

Principales métodos:

  • Análisis de datos de snRNA-seq de tejido de EC post-mortem de controles sanos y pacientes con EA.
  • Se utilizó el análisis de trayectoria Monocle3 para mapear la progresión del estado celular a través de las etapas de Braak.
  • Se realizó un análisis de expresión génica diferencial (DEG) comparando los transcriptomas de neuronas RORB resilientes (Q1) y vulnerables (Q4).

Principales resultados:

  • Se identificaron dos poblaciones distintas de neuronas RORB-positivas en la EC.
  • Se descubrieron 537 genes con expresión diferencial entre neuronas RORB resilientes y vulnerables.
  • Las neuronas vulnerables mostraron vías de señalización reguladas al alza en la organización de fibras supramoleculares y vías de señalización reguladas a la baja en la traducción de proteínas y el control de calidad.

Conclusiones:

  • Las firmas transcriptómicas resaltan las vías involucradas en la organización del citoesqueleto y la proteostasis como factores clave en la vulnerabilidad de las neuronas RORB en la EA temprana.
  • Estas diferencias moleculares pueden subyacer a la acumulación de tau y la pérdida neuronal en la EA.
  • Una mayor investigación sobre estas subpoblaciones de RORB podría refinar la comprensión de los mecanismos de vulnerabilidad neuronal selectiva en la EA.