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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.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
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Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

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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

Cystic Fibrosis: Pathogenesis

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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.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
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Pneumonia II: Pathophysiology01:29

Pneumonia II: Pathophysiology

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The pathophysiology of pneumonia involves the following steps:
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Stages of Infection01:26

Stages of Infection

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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

Defense Against Bacterial Pathogens

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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.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
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Video Experimental Relacionado

Updated: Jan 8, 2026

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Ciencia básica y patogénesis

Yuriko Katsumata1, Khine Zin Aung2, Xian Wu2

  • 1Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Este estudio exploró variantes genéticas multialélicas asociadas con la proteinopatía TDP-43 relacionada con la demencia utilizando datos de secuenciación del genoma completo. Varias variantes mostraron asociaciones sugerentes, particularmente en genes como PLXNA4, lo que justifica una mayor investigación.

Palabras clave:
proteinopatía TDP-43demenciasecuenciación del genoma completovariantes multialélicasPLXNA4neurogenética

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Área de la Ciencia:

  • Neurogenética
  • Medicina Genómica
  • Neuropatología

Sus antecedentes:

  • Investigaciones previas identificaron vínculos genéticos con proteinopatías relacionadas con la demencia.
  • Se utilizó el modelado generalizado de crédito parcial multidimensional para crear puntuaciones de biomarcadores para la neuropatología de TDP-43, Ab/Tau y alfa-sinucleína.
  • Los sitios genéticos multialélicos, que son variantes complejas que no se codifican fácilmente con métodos estándar, no se evaluaron previamente.

Objetivo del estudio:

  • Realizar análisis de variantes multialélicas a nivel de genoma utilizando datos de secuenciación del genoma completo (WGS) del Proyecto de Secuenciación de la Enfermedad de Alzheimer (ADSP).
  • Investigar posibles asociaciones genéticas con la proteinopatía TDP-43 utilizando modelos estadísticos avanzados.

Principales métodos:

  • Se utilizaron datos de neuropatología del National Alzheimer's Coordinating Center (NACC) vinculados a datos de WGS ADSP.
  • Se analizaron 672.004 variantes multialélicas en los cromosomas 1-22 después del filtrado de calidad.
  • Se emplearon pruebas de puntuación dentro de un marco de modelo lineal generalizado, ajustando por covariables, para calcular valores p globales.

Principales resultados:

  • Se incluyeron 392 participantes con datos de neuropatología NACC y datos de WGS ADSP.
  • Se encontraron asociaciones sugerentemente significativas (p < 1x10^-5) para variantes cerca de RPRD1A, PLXNA4, una región intergénica en el cromosoma 6 y RGS6 con la patología TDP-43.
  • Las asociaciones principales incluyeron variantes en chr18:35995261 (RPRD1A) y chr7:132612663 (PLXNA4).

Conclusiones:

  • Las variantes multialélicas muestran asociaciones sugerentes con la proteinopatía TDP-43.
  • El gen PLXNA4, previamente relacionado con la enfermedad de Alzheimer, es un hallazgo notable.
  • Se necesitan datos de cohortes independientes para confirmar estas asociaciones genéticas.