72 research outputs found
Contextual Effects on the Gendered Division of Housework: a Cross-Country and Cross-Time Analysis
Individuals who espouse an egalitarian gender ideology as well as economically independent women benefit from a more egalitarian division of housework. Although these two individual-level characteristics affect the gender division of housework, each suggests a different mechanism; the former is anchored within an economic logic and the latter within a cultural one. Using data of 25 countries from the 2002 and 2012 "Family and Changing Gender Roles" modules of the International Social Survey Program, we examine whether a country’s mean gender ideology and women’s labor force participation (WLFP) rate have a distinct contextual effect beyond these individual-level effects. We predict that the division of housework between married or cohabitating partners will be more egalitarian in countries with higher WLFP rates and in countries with more egalitarian attitudes, even after controlling for the two variables at the individual level. Given the cross-country convergence in WLFP, but not in gender ideology, we expect the effect of WLFP to decline over time and the effect of gender ideology to remain salient. Indeed, our multi-level analysis indicates that the net effect of WLFP, which was evident in 2002, had disappeared by 2012. By contrast, the net contextual effect of gender ideology, which was not significant in 2002, had become an important determinant of housework division by 2012. We conclude that further changes will depend on a country’s prevalent gender ideology because the equalizing effect of WLFP on the division of housework may have reached its limit
Tissue resident stem cells: till death do us part
Aging is accompanied by reduced regenerative capacity of all tissues and organs and dysfunction of adult stem cells. Notably, these age-related alterations contribute to distinct pathophysiological characteristics depending on the tissue of origin and function and thus require special attention in a type by type manner. In this paper, we review the current understanding of the mechanisms leading to tissue-specific adult stem cell dysfunction and reduced regenerative capacity with age. A comprehensive investigation of the hematopoietic, the neural, the mesenchymal, and the skeletal stem cells in age-related research highlights that distinct mechanisms are associated with the different types of tissue stem cells. The link between age-related stem cell dysfunction and human pathologies is discussed along with the challenges and the future perspectives in stem cell-based therapies in age-related diseases
Biased exonization of transposed elements in duplicated genes: A lesson from the TIF-IA gene
Background: Gene duplication and exonization of intronic transposed elements
are two mechanisms that enhance genomic diversity. We examined whether there is
less selection against exonization of transposed elements in duplicated genes
than in single-copy genes. Results: Genome-wide analysis of exonization of
transposed elements revealed a higher rate of exonization within duplicated
genes relative to single-copy genes. The gene for TIF-IA, an RNA polymerase I
transcription initiation factor, underwent a humanoid-specific triplication,
all three copies of the gene are active transcriptionally, although only one
copy retains the ability to generate the TIF-IA protein. Prior to TIF-IA
triplication, an Alu element was inserted into the first intron. In one of the
non-protein coding copies, this Alu is exonized. We identified a single point
mutation leading to exonization in one of the gene duplicates. When this
mutation was introduced into the TIF-IA coding copy, exonization was activated
and the level of the protein-coding mRNA was reduced substantially. A very low
level of exonization was detected in normal human cells. However, this
exonization was abundant in most leukemia cell lines evaluated, although the
genomic sequence is unchanged in these cancerous cells compared to normal
cells. Conclusion: The definition of the Alu element within the TIF-IA gene as
an exon is restricted to certain types of cancers; the element is not exonized
in normal human cells. These results further our understanding of the delicate
interplay between gene duplication and alternative splicing and of the
molecular evolutionary mechanisms leading to genetic innovations. This implies
the existence of purifying selection against exonization in single copy genes,
with duplicate genes free from such constrains
Development of a highly sensitive liquid biopsy platform to detect clinically-relevant cancer mutations at low allele fractions in cell-free DNA.
INTRODUCTION: Detection and monitoring of circulating tumor DNA (ctDNA) is rapidly becoming a diagnostic, prognostic and predictive tool in cancer patient care. A growing number of gene targets have been identified as diagnostic or actionable, requiring the development of reliable technology that provides analysis of multiple genes in parallel. We have developed the InVision™ liquid biopsy platform which utilizes enhanced TAm-Seq™ (eTAm-Seq™) technology, an amplicon-based next generation sequencing method for the identification of clinically-relevant somatic alterations at low frequency in ctDNA across a panel of 35 cancer-related genes. MATERIALS AND METHODS: We present analytical validation of the eTAm-Seq technology across two laboratories to determine the reproducibility of mutation identification. We assess the quantitative performance of eTAm-Seq technology for analysis of single nucleotide variants in clinically-relevant genes as compared to digital PCR (dPCR), using both established DNA standards and novel full-process control material. RESULTS: The assay detected mutant alleles down to 0.02% AF, with high per-base specificity of 99.9997%. Across two laboratories, analysis of samples with optimal amount of DNA detected 94% mutations at 0.25%-0.33% allele fraction (AF), with 90% of mutations detected for samples with lower amounts of input DNA. CONCLUSIONS: These studies demonstrate that eTAm-Seq technology is a robust and reproducible technology for the identification and quantification of somatic mutations in circulating tumor DNA, and support its use in clinical applications for precision medicine
Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program
Summary Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer’s and Parkinson’s disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans
Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma
Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients
Biostimulation in Desert Soils for Microbial-Induced Calcite Precipitation
Microbial-induced calcite precipitation (MICP) is a soil amelioration technique aiming to mitigate different environmental and engineering concerns, including desertification, soil erosion, and soil liquefaction, among others. The hydrolysis of urea, catalyzed by the microbial enzyme urease, is considered the most efficient microbial pathway for MICP. Biostimulated MICP relies on the enhancement of indigenous urea-hydrolyzing bacteria by providing an appropriate enrichment and precipitation medium, as opposed to bioaugmentation, which requires introducing large volumes of exogenous bacterial cultures into the treated soil along with a growth and precipitation medium. Biostimulated MICP in desert soils is challenging as the total carbon content and the bacterial abundance are considerably low. In this study, we examined the biostimulation potential in soils from the Negev Desert, Israel, for the purpose of mitigation of topsoil erosion in arid environments. Incubating soil samples in urea and enrichment media demonstrated effective urea hydrolysis leading to pH increase, which is necessary for calcite precipitation. Biostimulation rates were found to increase with concentrations of energy (carbon) source in the stimulation media, reaching its maximal levels within 3 to 6 days. Following stimulation, calcium carbonate precipitation was induced by spiking stimulated bacteria in precipitation (CaCl2 enriched) media. The results of our research demonstrate that biostimulated MICP is feasible in the low-carbon, mineral soils of the northern Negev Desert in Israel
Transient abnormal liver enzyme level in the early stage after renal transplantation in children
Aim: The study aim was to evaluate the prevalence, risk factors, and clinical importance of abnormal elevation in liver enzyme levels in children after renal transplantation. Materials and Methods: The files of all 62 patients (mean age 10.2 years), who underwent renal transplantation at a tertiary pediatric medical center in 2001-2013, were reviewed for clinical data, including: Postoperative liver function, tacrolimus level, and serology for cytomegalovirus (CMV) and hepatitis B and C viruses. Results: The most common indication for transplantation (53%) was dysplastic hypoplastic kidney. Liver enzyme levels were abnormal in 7 patients (11%) before transplantation and 42 (67.7%) during the first 6 months following, with a peak on day 14 (P < 0.001). Seroconversion was documented during the first post-transplantation year in 9 patients (14.5%), of whom 8 (89%) were CMV IgG negative. Post-transplant abnormal levels were highest in patients who also had abnormally high-level pre-transplant levels (100%), CMV seroconversion (89%), and dysplastic kidney or nephronophthisis (80%). An abnormally elevated liver enzyme level was significantly correlated with high blood tacrolimus level, but only on post-transplant day 3 (P < 0.001). Conclusion: High liver enzyme levels are common in pediatric kidney transplant recipients, usually starting in the first post-transplant month. The etiology is probably multifactorial; drug hepatotoxicity, previous liver injury, and acute viral infection or reactivation are all likely possibilities. About 10-20% of cases are related to CMV infection
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