Publications by authors named "Forsythe E"

Article Synopsis
  • - The study explores the essential relationship between nuclear and chloroplast genomes in plants, focusing on how they coevolve to maintain cellular functions despite mutations and selection pressures.
  • - Researchers analyzed 4,894 nuclear genes and 76 chloroplast genes among nine Juglandaceae species, finding that 1,369 (27.97%) of the nuclear genes showed evidence of coevolution, especially within the Ycf1/2 chloroplast partition.
  • - The research indicates significant biological enrichment in processes like leaf development and stress response among these coevolving nuclear genes, with varying evolutionary rates observed across different chloroplast gene partitions.
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  • Bardet-Biedl syndrome (BBS) is a rare genetic disorder characterized by obesity and uncontrollable hunger (hyperphagia), significantly affecting the lives of caregivers.
  • A survey conducted across the US, UK, Canada, and Germany involved 242 caregivers, revealing extensive caregiver burden that impacts their mood, sleep, relationships, and work productivity due to the demands of caring for individuals with BBS.
  • Caregivers reported high personal and family strain along with substantial financial costs, indicating the need for more effective weight management strategies and support resources for those affected by BBS.
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  • Bardet-Biedl syndrome (BBS) significantly impacts both patients and their caregivers, particularly through hyperphagia, which contributes to early-onset obesity and various emotional and physical challenges.
  • The CAREgiver Burden in BBS (CARE-BBS) study surveyed 242 adult caregivers, revealing common behaviors like food negotiation and overnight food-seeking in patients, as well as notable negative effects on mood, sleep, and school attendance.
  • Results indicated that obesity greatly harms aspects of life such as physical comfort, body esteem, and social interaction, with a substantial portion of patients missing school frequently due to their symptoms.
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Unlabelled: Using data from the Current Population Survey, we investigate the distributional consequences of the Covid-19 pandemic and the associated public policy response on labor earnings and unemployment benefits in the United States up until February 2021. We find that year-on-year changes in labor earnings for employed individuals were not atypical during the pandemic months, regardless of their initial position in the earnings distribution. The incidence of job loss, however, was substantially higher among low earners, leading to a dramatic increase in labor income inequality among the set of individuals who were employed prior to the onset of the pandemic.

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Article Synopsis
  • Bardet-Biedl syndrome is a rare genetic disorder causing severe obesity and hyperphagia, and its impact on quality of life has not been well studied.
  • In a Phase 3 trial of 52 weeks of setmelanotide treatment, both children and adults showed significant improvements in health-related quality of life, as measured by the PedsQL for kids and the IWQOL-Lite for adults.
  • The results indicated that after treatment, children had a mean improvement of +11.2 in PedsQL scores, while adults had a mean improvement of +12.0 in IWQOL-Lite scores, with notable correlations found between quality of life and changes in body weight and BMI.
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The authors study the distributional consequences of the COVID-19 pandemic's impact on employment, both during the onset of the pandemic and over subsequent months. Using cross-sectional and matched longitudinal data from the Current Population Survey, they show that the pandemic has exacerbated pre-existing inequalities. Although employment losses have been widespread, they have been substantially larger-and more persistent-in lower-paying occupations and industries.

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There is remarkable variation in the rate at which genetic incompatibilities in molecular interactions accumulate. In some cases, minor changes-even single-nucleotide substitutions-create major incompatibilities when hybridization forces new variants to function in a novel genetic background from an isolated population. In other cases, genes or even entire functional pathways can be horizontally transferred between anciently divergent evolutionary lineages that span the tree of life with little evidence of incompatibilities.

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Article Synopsis
  • Impaired cilial signaling in the MC4R pathway is linked to obesity in patients with Bardet-Biedl and Alström syndromes, prompting a study on the weight-loss effects of setmelanotide in these groups.
  • The study was a multicenter, double-blind, placebo-controlled trial involving 38 patients over 14 weeks, followed by 52 weeks of open-label treatment, assessing the impact of setmelanotide on body weight.
  • Results indicated that 32.3% of patients aged 12 years or older with Bardet-Biedl syndrome experienced at least a 10% weight reduction after 52 weeks on setmelanotide, with skin hyperpigmentation and injection
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Cytonuclear coevolution is a common feature among plants, which coordinates gene expression and protein products between the nucleus and organelles. Consequently, lineage-specific differences may result in incompatibilities between the nucleus and cytoplasm in hybrid taxa. Allopolyploidy is also a common phenomenon in plant evolution.

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Article Synopsis
  • Mitochondrial and plastid functions rely on a balanced expression of proteins from both organellar and nuclear genomes, which can be disrupted in polyploid plants due to nuclear genome doubling.
  • Despite plastid genomes containing less than 1% of the nuclear gene count, they produce the majority of mRNA transcripts (69.9% to 82.3%), while mitochondrial genes contribute a smaller percentage (1.3% to 3.7%) yet maintain higher transcript levels per gene.
  • A study of transcript abundance in polyploid angiosperms reveals that even with cytonuclear imbalances at the RNA level, the coordination of gene expression between nuclear and organellar genomes remains intact, and polyploid plants can
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The chloroplast chaperone CLPC1 unfolds and delivers substrates to the stromal CLPPRT protease complex for degradation. We previously used an in vivo trapping approach to identify interactors with CLPC1 in Arabidopsis thaliana by expressing a STREPII-tagged copy of CLPC1 mutated in its Walker B domains (CLPC1-TRAP) followed by affinity purification and mass spectrometry. To create a larger pool of candidate substrates, adaptors, or regulators, we carried out a far more sensitive and comprehensive in vivo protein trapping analysis.

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While the chloroplast (plastid) is known for its role in photosynthesis, it is also involved in many other metabolic pathways essential for plant survival. As such, plastids contain an extensive suite of enzymes required for non-photosynthetic processes. The evolution of the associated genes has been especially dynamic in flowering plants (angiosperms), including examples of gene duplication and extensive rate variation.

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Functional autoantibodies directed to the M2 muscarinic acetylcholine receptor (M2R) could affect the heart rate directly by altering cardiac M2R activity and/or indirectly by changing vagal-mediated cardiac M2R activity. We measured M2R autoantibody activity in sera from 10 subjects with postural tachycardia syndrome (POTS) and 5 healthy control subjects using a cell-based bioassay. Half of the POTS subjects demonstrated presence of elevated M2R autoantibody activity, while no significant M2R autoantibody activity was found in the healthy subjects.

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Background: Ciliary dysfunction underlies a range of genetic disorders collectively termed ciliopathies, for which there are no treatments available. Bardet-Biedl syndrome (BBS) is characterised by multisystemic involvement, including rod-cone dystrophy and renal abnormalities. Together with Alström syndrome (AS), they are known as the 'obesity ciliopathies' due to their common phenotype.

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Background: Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that can be expanded from such biopsies.

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Nuclear and plastid (chloroplast) genomes experience different mutation rates, levels of selection, and transmission modes, yet key cellular functions depend on their coordinated interactions. Functionally related proteins often show correlated changes in rates of sequence evolution across a phylogeny [evolutionary rate covariation (ERC)], offering a means to detect previously unidentified suites of coevolving and cofunctional genes. We performed phylogenomic analyses across angiosperm diversity, scanning the nuclear genome for genes that exhibit ERC with plastid genes.

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Article Synopsis
  • The BCAP31 gene at Xq28 encodes BAP31, which is involved in transporting proteins from the endoplasmic reticulum to the Golgi apparatus, with mutations linked to severe neurological disorders in males.
  • Pathogenic variants result in a spectrum of symptoms, including profound intellectual disability, dystonia, deafness, and a syndrome called deafness, dystonia, and cerebral hypomyelination (DDCH), with females often being asymptomatic or only mildly affected.
  • The study identifies 17 new families with BCAP31-related conditions, confirming that males with loss-of-function variants have a more severe phenotype, while females can exhibit a range of neurological symptoms, and suggests additional complications like elevated liver enzymes in male
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Bardet-Biedl Syndrome (BBS) is a pleiotropic genetic disease caused by the dysfunction of primary cilia. The immune system of patients with ciliopathies has not been investigated. However, there are multiple indications that the impairment of the processes typically associated with cilia may have influence on the hematopoietic compartment and immunity.

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Phylogenomic analyses are recovering previously hidden histories of hybridization, revealing the genomic consequences of these events on the architecture of extant genomes. We applied phylogenomic techniques and several complementary statistical tests to show that introgressive hybridization appears to have occurred between close relatives of Arabidopsis, resulting in cytonuclear discordance and impacting our understanding of species relationships in the group. The composition of introgressed and retained genes indicates that selection against incompatible cytonuclear and nuclear-nuclear interactions likely acted during introgression, whereas linkage also contributed to genome composition through the retention of ancient haplotype blocks.

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We use job vacancy data collected in real time by Burning Glass Technologies, as well as unemployment insurance (UI) initial claims and the more traditional Bureau of Labor Statistics (BLS) employment data to study the impact of COVID-19 on the labor market. Our job vacancy data allow us to track the economy at disaggregated geography and by detailed occupation and industry. We find that job vacancies collapsed in the second half of March.

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Objective: Is polycystic ovary syndrome (PCOS) associated with activating autoantibodies (AAb) to the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR)?

Design And Methods: We retrospectively screened sera from 40 patients with PCOS and 14 normal controls (NCs) with regular menses using enzyme-linked immunosorbent assay (ELISA) for the presence of GnRHR-ECL2-AAb. We obtained similar data from 40 non-PCOS ovulatory but infertile patients as a control group (OIC) of interest. We analyzed GnRHR-ECL2-AAb activity in purified immunoglobulin (Ig)G using a cell-based GnRHR bioassay.

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The telomerase ribonucleoprotein complex (RNP) is essential for genome stability and performs this role through the addition of repetitive DNA to the ends of chromosomes. The telomerase enzyme is composed of a reverse transcriptase (TERT), which utilizes a template domain in an RNA subunit (TER) to reiteratively add telomeric DNA at the ends of chromosomes. Multiple TERs have been identified in the model plant Arabidopsis thaliana.

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Introgressive hybridization results in the transfer of genetic material between species, often with fitness implications for the recipient species. The development of statistical methods for detecting the signatures of historical introgression in whole-genome data has been a major area of focus. Although existing techniques are able to identify the taxa that exchanged genes during introgression using a four-taxon system, most methods do not explicitly distinguish which taxon served as donor and which as recipient during introgression (i.

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Bardet-Biedl syndrome (BBS), a ciliopathy, is a rare genetic condition characterised by retinal degeneration, obesity, kidney failure, and cognitive impairment. In spite of progress made in our general understanding of BBS aetiology, the molecular and cellular mechanisms underlying cognitive impairment in BBS remain elusive. Here, we report that the loss of BBS proteins causes synaptic dysfunction in principal neurons, providing a possible explanation for the cognitive impairment phenotype observed in BBS patients.

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