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"Watson, Billy"
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Billy Stuart and the Zintrepids
\"In this illustrated novel for middle-grade readers, Billy Stuart and his loyal Scout group get lost on a hike and inadvertently travel through time\"-- Provided by publisher.
Book
Evidence for Fgf and Wnt regulation of Lhx2 during limb development via two limb-specific Lhx2-associated cis-regulatory modules
In vertebrate limb morphogenesis, wingless-related integration site (Wnt) proteins and fibroblast growth factors (Fgfs) secreted from the apical ectodermal ridge (AER) coordinate proximodistal outgrowth. Fgfs also sustain sonic hedgehog (Shh) in the zone of polarizing activity (ZPA). Shh directs anteroposterior patterning and expansion and regulates AER-
, establishing a positive regulatory feedback loop that is vital in sustaining limb outgrowth. The transcription factor LIM homeodomain 2 (Lhx2) is expressed in the distal mesoderm and coordinates AER and ZPA signals that control cellular proliferation, differentiation, and shaping of the developing limb. Yet how Lhx2 is transcriptionally regulated to support such functions has only been partially characterized.
We have identified two limb-specific
-regulatory modules (CRMs) active within the
expression domain in the limb. Chromatin conformation analysis of the
locus in mouse embryonic limb bud cells predicted CRMs-
promoter interactions. Single-cell RNA-sequencing analysis of limb bud cells revealed co-expression of several Fgf-related
and Wnt-related
transcripts in
-expressing cells. Additionally, disruption of Ets and Tcf/Lef binding sites resulted in loss of reporter-driven CRM activity. Finally, binding of β-catenin to both
-associated CRMs supports the associated binding of Tcf/Lef transcription factors.
These results suggest a role for Ets and Tcf/Lef transcription factors in the regulation of
expression through these limb-specific
-associated CRMs. Moreover, these CRMs provide a mechanism for Fgf and Wnt signaling to localize and maintain distal
expression during vertebrate limb development.
Journal Article
Billy Stuart and the sea of a thousand dangers
\"In this illustrated novel for middle-grade readers, Billy Stuart and his loyal Scout group have inadvertently traveled through time and have to cross an ocean full of danger.\"-- Provided by publisher.
Book
LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development
During limb development, fibroblast growth factors (Fgfs) govern proximal–distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal–distal and anterior–posterior axes by maintaining Sonic hedgehog (Shh) expression in cells of the zone of polarizing activity (ZPA) in the distal posterior mesoderm. Shh, in turn, maintains Fgfs in the apical ectodermal ridge (AER) that caps the distal tip of the limb bud. Crosstalk between Fgf and Shh signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well-characterized. Implantation of Fgf beads in the proximal posterior limb bud can maintain SHH expression in the former ZPA domain (evident 3 h after application), while prolonged exposure (24 h) can induce SHH outside of this domain. Although temporally and spatially disparate, comparative analysis of transcriptome data from these different populations accentuated genes involved in SHH regulation. Comparative analysis identified 25 candidates common to both treatments, with eight linked to SHH expression or function. Furthermore, we demonstrated that LHX2, a LIM Homeodomain transcription factor, is an intermediate in the FGF-mediated regulation of SHH. Our data suggest that LHX2 acts as a competency factor maintaining distal posterior SHH expression subjacent to the AER.
Journal Article
Mental health and well-being during the COVID-19 pandemic: longitudinal analyses of adults in the UK COVID-19 Mental Health & Wellbeing study
The effects of coronavirus disease 2019 (COVID-19) on the population's mental health and well-being are likely to be profound and long lasting.
To investigate the trajectory of mental health and well-being during the first 6 weeks of lockdown in adults in the UK.
A quota survey design and a sampling frame that permitted recruitment of a national sample was employed. Findings for waves 1 (31 March to 9 April 2020), 2 (10 April to 27 April 2020) and 3 (28 April to 11 May 2020) are reported here. A range of mental health factors was assessed: pre-existing mental health problems, suicide attempts and self-harm, suicidal ideation, depression, anxiety, defeat, entrapment, mental well-being and loneliness.
A total of 3077 adults in the UK completed the survey at wave 1. Suicidal ideation increased over time. Symptoms of anxiety, and levels of defeat and entrapment decreased across waves whereas levels of depressive symptoms did not change significantly. Positive well-being also increased. Levels of loneliness did not change significantly over waves. Subgroup analyses showed that women, young people (18-29 years), those from more socially disadvantaged backgrounds and those with pre-existing mental health problems have worse mental health outcomes during the pandemic across most factors.
The mental health and well-being of the UK adult population appears to have been affected in the initial phase of the COVID-19 pandemic. The increasing rates of suicidal thoughts across waves, especially among young adults, are concerning.
Journal Article
Mental health and well-being during the second wave of COVID-19: longitudinal analyses of the UK COVID-19 Mental Health and Wellbeing study (UK COVID-MH)
Waves 1 to 3 (March 2020 to May 2020) of the UK COVID-19 Mental Health and Wellbeing study suggested an improvement in some indicators of mental health across the first 6 weeks of the UK lockdown; however, suicidal ideation increased.
To report the prevalence of mental health and well-being of adults in the UK from March/April 2020 to February 2021.
Quota sampling was employed at wave 1 (March/April 2020), and online surveys were conducted at seven time points. Primary analyses cover waves 4 (May/June 2020), 5 (July/August 2020), 6 (October 2020) and 7 (February 2021), including a period of increased restrictions in the UK. Mental health indicators were suicidal ideation, self-harm, suicide attempt, depression, anxiety, defeat, entrapment, loneliness and well-being.
A total of 2691 (87.5% of wave 1) individuals participated in at least one survey between waves 4 and 7. Depressive symptoms and loneliness increased from October 2020 to February 2021. Defeat and entrapment increased from July/August 2020 to October 2020, and remained elevated in February 2021. Well-being decreased from July/August 2020 to October 2020. Anxiety symptoms and suicidal ideation did not change. Young adults, women, those who were socially disadvantaged and those with a pre-existing mental health condition reported worse mental health.
The mental health and well-being of the UK population deteriorated from July/August 2020 to October 2020 and February 2021, which coincided with the second wave of COVID-19. Suicidal thoughts did not decrease significantly, suggesting a need for continued vigilance as we recover from the pandemic.
Journal Article
Outbreak of Human Trichinellosis — Arizona, Minnesota, and South Dakota, 2022
Trichinellosis is a parasitic zoonotic disease transmitted through the consumption of meat from animals infected with
spp. nematodes. In North America, human trichinellosis is rare and is most commonly acquired through consumption of wild game meat. In July 2022, a hospitalized patient with suspected trichinellosis was reported to the Minnesota Department of Health. One week before symptom onset, the patient and eight other persons shared a meal that included bear meat that had been frozen for 45 days before being grilled and served rare with vegetables that had been cooked with the meat. Investigation identified six trichinellosis cases, including two in persons who consumed only the vegetables. Motile
larvae were found in remaining bear meat that had been frozen for >15 weeks. Molecular testing identified larvae from the bear meat as
, a freeze-resistant species. Persons who consume meat from wild game animals should be aware that that adequate cooking is the only reliable way to kill
parasites and that infected meat can cross-contaminate other foods.
Journal Article
Characterization of FGF-Mediated Sonic Hedgehog Expression During Limb Development
Crosstalk between Fibroblast Growth Factors (FGFs) and Sonic hedgehog (SHH) is essential for proper limb development; however, the molecular mechanisms involved in this process remain unclear. Via comparative transcriptome analysis and gene knockdown and overexpression studies, we identified the transcription factor Lim homeobox 2 (LHX2) as an intermediate in FGF-directed SHH expression. We determined that FGF signaling was necessary for LHX2 expression and demonstrated that LHX2 is a primary transcription target of FGF signaling through the RAS and AKT pathways. Additionally, loss of LHX2 in the distal limb results in decreased SHH expression and a truncated limb within 24 hours of treatment, while overexpression of LHX2 in the presence of ectopic FGF leads to increased SHH expression. While LHX2 is insufficient alone to induce SHH, we conclude that it likely serves as a competency factor for endogenous SHH expression, keeping it juxtaposed to the distal apical ectodermal ridge during limb outgrowth.
Dissertation