Biology subjects

Garcia, G.

Publications and source records attributed to Garcia, G..

57 records · Page 4Linked to original sources

bioRxiv2017

Super-Resolution Microscopy Reveals That Disruption Of Ciliary Transition Zone Architecture Is A Cause Of Joubert Syndrome

Diverse human ciliopathies, including nephronophthisis (NPHP), Meckel syndrome (MKS) and Joubert syndrome (JBTS), can be caused by mutations affecting components of the transition zone, a ciliary domain near its base. The transition zone controls the protein composition of the ciliary membrane, but how it does so is unclear. To better understand the transition zone and its connection to ciliopathies, we defined the arrangement of key proteins in the transition zone using two-color stochastic optical reconstruction microscopy (STORM). This mapping revealed that NPHP and MKS complex components form nested rings comprised of nine-fold doublets. The NPHP complex component RPGRIP1L forms a smaller diameter transition zone ring within the MKS complex rings. JBTS-associated mutations in RPGRIP1L disrupt the architecture of the MKS and NPHP rings, revealing that vertebrate RPGRIP1L has a key role in organizing transition zone architecture. JBTS-associated mutations in TCTN2, encoding an MKS complex component, also displace proteins of the MKS and NPHP complexes from the transition zone, revealing that RPGRIP1L and TCTN2 have interdependent roles in organizing transition zone architecture. To understand how altered transition zone architecture affects developmental signaling, we examined the localization of the Hedgehog pathway component SMO in human fibroblasts derived from JBTS-affected individuals. We found that diverse ciliary proteins, including SMO, accumulate at the transition zone in wild type cells, suggesting that the transition zone is a way station for proteins entering and exiting the cilium. JBTS-associated mutations in RPGRIP1L disrupt SMO accumulation at the transition zone and the ciliary localization of SMO. We propose that the disruption of transition zone architecture in JBTS leads to a failure of SMO to accumulate at the transition zone, disrupting developmental signaling in JBTS.

cell biology↗

bioRxiv2017

Pathogenesis of Zika Virus Infection via Rectal Route

Introduction Introduction Methods Competing interests References Zika virus (ZIKV) is a mosquito-borne flavivirus originally confined to Africa and Asia that has spread to islands located in Southeast Asia, and most recently to the Americas and the Caribbean. Approximately 80% of infected individuals are asymptomatic, while the remaining infected population exhibit mild febrile syndrome such as rash, conjunctivitis, and arthralgia. In some adults, ZIKV causes neurotropic Guillain-Barre syndrome1. Vertical transmission of ZIKV in infected mothers causes fetal growth restriction, microcephaly, and congenital eye disease2-5. Cases of ZIKV sexual transmission from male to female6-8, male to male9, ...

microbiology↗

bioRxiv2016

A Phylogenetic Analysis of Shape Covariance Structure in the Anthropoid Skull

Phenotypic traits evolve in a coordinated manner due to developmental and functional interactions, mediated by the dynamics of natural selection; the dependence between traits arising from these three factors is captured by genetic (G) and phenotypic (P) covariance matrices. Mammalian skull development produces an intricate pattern of tissue organization and mutual signaling that integrates this structure, although the set of functions it performs is quite disparate. Therefore, the interplay between these interactions, and their relationships with the adaptive landscape may thus influence divergence in covariance structure among sister lineages. Here, we evaluate the stability of phenotypic covariance structure in skull size and shape along the diversification of Anthropoid Primates under a explicit phylogenetic framework. We estimate diversity in covariance structure, testing hypotheses concerning the phylogenetic distribution of P-matrix variation and pinpoint which traits are associated with this variation. We find that most changes occurred in the basal split between Platyrrhini and Catarrhini, and that these changes occurred within both Orbital and Basicranial trait sets, while Oral, Nasal and Vault trait sets present stable associations along the Anthropoid phylogeny. Therefore, changes in P-matrix structure among Anthropoids are restricted to trait sets whose functional significance is associated with the accommodation of the two precursor tissues that compose the skull, while the stability in the remaining regions hints at the stability of the underlying functional relationships imposed by the adaptive landscape.

evolutionary biology↗