Mostrando las entradas de 2018

Physical biology of human brain development

Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular …

HIV-associated synaptic degeneration

Human immunodeficiency virus (HIV) infection induces neuronal injuries, with almost 50% of infected individuals developing HIV-associated neurocognitive disorders (HAND). Although highly activate antiretroviral therapy (HAART) has significantly reduced the incidence of severe dementia, the overall prevalence of HAND remains high. Synaptic degeneration is emerging as one of the most relevant neuropathologies associate with HAND. Previous studies have reported critical roles of viral proteins and inflammatory responses in this pathogenesis. Infected cells, including macrophages, microglia and astrocytes, may release viral proteins and other neurotoxins to stimulate neurons and cause excessive calcium influx, overproduction of free radicals and disruption of neurotransmitter hemostasis. The dysregulation of neural circuits likely leads to synaptic damage and loss. Identification of the specific mechanism of the synaptic degeneration may facilitate the development of effective therapeuti…

Guillain–Barré syndrome, transverse myelitis and infectious diseases

Guillain–Barré syndrome (GBS) and transverse myelitis (TM) both represent immunologically mediated polyneuropathies of major clinical importance. Both are thought to have a genetic predisposition, but as of yet no specific genetic risk loci have been clearly defined. Both are considered autoimmune, but again the etiologies remain enigmatic. Both may be induced via molecular mimicry, particularly from infectious agents and vaccines, but clearly host factor and co-founding host responses will modulate disease susceptibility and natural history. GBS is an acute inflammatory immune-mediated polyradiculoneuropathy characterized by tingling, progressive weakness, autonomic dysfunction, and pain. Immune injury specifically takes place at the myelin sheath and related Schwann-cell components in acute inflammatory demyelinating polyneuropathy, whereas in acute motor axonal neuropathy membranes on the nerve axon (the axolemma) are the primary target for immune-related injury. Outbreaks of GBS …

Complete genome sequence from Zika Virus, from Oaxaca, México

Zika virus (ZIKV) is an emerging arthropod-borne flavivirus associated with severe congenital malformations and neurological complications. Although the ZIKV genome is well characterized, there is limited information regarding changes after cell isolation and culture adaptation. We isolated, and passaged in Vero cells, ZIKV from the serum of a symptomatic male patient and compared the viral genomes before and after culture. Single nucleotide polymorphisms were characteristic among serum-circulating genomes, while such diversity decreased after cell culture.

Boukadida, Celia et al. “Complete Genome Sequences, before and after Mammalian Cell Culture, of Zika Virus Isolated from the Serum of a Symptomatic Male Patient from Oaxaca, Mexico.” Genome Announcements 5.12 (2017): e00072–17. PMC. Web. 18 Jan. 2018.