Biology subjects

Sanchez, S. E.

Publications and source records attributed to Sanchez, S. E..

3 recordsLinked to original sources

bioRxiv2023

Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease

Telomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition and de novo elongation with unprecedented resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance. We find that human aging is accompanied by a progressive loss of long telomeres and an accumulation of shorter telomeres. In patients with defects in telomere maintenance, the accumulation of short telomeres is more pronounced and correlates with phenotypic severity. We apply machine learning to train a binary classification model that distinguishes healthy individuals from those with telomere biology disorders. This sequencing and bioinformatic pipeline will advance our understanding of telomere maintenance mechanisms and the use of telomere length as a clinical biomarker of aging and disease.

genetics↗

bioRxiv2022

Evaluating UV-C sensitivity of Coxiella burnetii in Skim Milk using a Bench-Scale Collimated Beam System and Comparative Study with High-Temperature Short-Time Pasteurization

Coxiella burnetii is a zoonotic Gram-negative obligate intracellular bacterial pathogen and the causative agent of Query (Q) fever in humans. Contamination of milk by C. burnetii as a consequence of livestock infection is a significant public health concern. Effective methods to inactivate C. burnetii in milk is a critical aspect of food safety. In this study, we measured optical light attenuation factors; absorption, scattering, and reflection of skim milk (SM) and considered for evaluation of delivered UV dose under stirred conditions. The accuracy of the method followed for the estimation of delivered UV dose in SM was verified by comparative studies of Escherichia coli ATCC 25922 inactivation in phosphate buffer (transparent fluid), and humic acid (opaque fluid). Absorption, scattering coefficient, and the reflectance of SM at 254 nm was measured as 19 {+/-} 0.3/cm. 26 {+/-} 0.5/cm and 10.6 %, respectively. SM inoculated with C. burnetii was irradiated using a collimated beam device equipped with a low-pressure UV-C254 nm lamp at doses from 0 - 12 mJ{middle dot}cm-2. Results showed a log-linear inactivation of C. burnetii in SM with UV-C sensitivity (D10) value of 4.1 {+/-} 0.04 mJ{middle dot}cm-2. Similar inactivation kinetics was observed with Salmonella enterica serovar Muenchen ATCC BAA 1674 in SM and thereby suggested as a suitable surrogate to C. burnetii for pilot scale UV-C processing studies of SM.

microbiology↗

bioRxiv2022

PICLN modulates alternative splicing and ensures adaptation to light and temperature changes in plants

Plants undergo transcriptome reprogramming to adapt to daily and seasonal fluctuations in light and temperature conditions. While most efforts have focused on the role of master transcription factors, the importance of splicing factors modulating these processes is now emerging. Efficient pre-mRNA splicing depends on proper spliceosome assembly, which in plants and animals requires the methylosome complex. PICLN is part of the methylosome complex in both humans and Arabidopsis thaliana, and we show here that the human PICLN ortholog rescues phenotypes of A. thaliana picln mutants. Altered photomorphogenic and photoperiodic responses in A. thaliana picln mutants are associated with changes in pre-mRNA splicing, which partially overlap with those in prmt5 mutants. Mammalian PICLN also acts in concert with the Survival Motor Neuron (SMN) complex component GEMIN2 to modulate the late steps of UsnRNP assembly, and many alternative splicing events regulated by PICLN but not PROTEIN-ARGININE METHYL TRANSFERASE 5 (PRMT5), the main protein of the methylosome, are controlled by A. thaliana GEMIN2. As with GEMIN2 and SME1/PCP, low temperature, which increases PICLN expression, aggravates morphological and molecular defects of picln mutants. Taken together, these results establish a key role for PICLN in the regulation of pre-mRNA splicing and in mediating plant adaptation to daily and seasonal fluctuations in environmental conditions.

plant biology↗