The Rosetteless gene controls development in the choanoflagellate S. rosetta.

The origin of animal multicellularity may be reconstructed by comparing animals with one of their closest living relatives, the choanoflagellate Salpingoeca rosetta. Just as animals develop from a single cell-the zygote-multicellular rosettes of S. rosetta develop from a founding cell. To investigate rosette development, we established forward genetics in S. rosetta. We find that the rosette defect of one mutant, named Rosetteless, maps to a predicted C-type lectin, a class of signaling and adhesion genes required for the development and innate immunity in animals. Rosetteless protein is essential for rosette development and forms an extracellular layer that coats and connects the basal poles of each cell in rosettes. This study provides the first link between genotype and phenotype in choanoflagellates and raises the possibility that a protein with C-type lectin-like domains regulated development in the last common ancestor of choanoflagellates and animals

Oral Sapropterin Increases Reflex Vasodilation but Not Cardiac Output During Passive Heating in Older Adults

Please refer to the pdf version of the abstract located adjacent to the title

Renal cell carcinoma metastatic to the duodenum: Treatment by classic pancreaticoduodenectomy and review of the literature

Renal cell cancer (RCC) most commonly metastasizes to the lungs, bones, liver, renal fossa, and brain, although metastases can occur elsewhere. RCC metastatic to the duodenum is especially rare, with only a small number of cases reported in the literature. Herein, we describe a case of an 86-year-old woman with a history of RCC treated by radical nephrectomy 13 years previously. The patient presented with duodenal obstruction and anemia from a solitary duodenal mass invading into the pancreas and was treated via classic pancreaticoduodenectomy. Preoperative imaging and intra-operative assessment showed no evidence of other disease. Pathology confirmed metastatic RCC without lymph node involvement. Our case report and review of the English language literature underscore the rarity of this entity and support aggressive surgical treatment in such patients

Rapid Onset Pressor Response During Isometric Exercise in Postmenopausal Hypertensive Women

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Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution

Exploring the Potential Role of Family History of Hypertension on Racial Differences in Sympathetic Vascular Transduction

The prevalence of hypertension in Non-Hispanic Black (BL) men surpasses all other racial groups. Our laboratory has previously demonstrated exaggerated vasoconstrictor and blood pressure (BP) responses to spontaneous bursts of muscle sympathetic nerve activity (MSNA; sympathetic vascular transduction) in young, healthy BL men compared to their Non-Hispanic White (WH) counterparts. Because a family history of hypertension (FHH) further compounds cardiovascular risk, we wanted to begin to explore the potential impact of a positive (+) FHH on sympathetic vascular transduction. Whether a +FHH influences sympathetic vascular transduction in WH and/or BL men remains unknown. PURPOSE: To begin to explore if +FHH influences sympathetic vascular transduction within and between racial groups. METHODS: 22 men, nine with a +FHH (4 BL men) and 13 without a FHH (-FHH; 6 BL men) were recruited. Beat-to-beat BP (Finometer), femoral artery blood flow (Doppler ultrasound), and MSNA were measured during a 20-minute quiet rest. The mean BP and leg vascular conductance (LVC; blood flow/mean BP) responses to spontaneous bursts of MSNA were quantified via a signal averaging technique. RESULTS: Resting heart rate, BP, and MSNA were not significantly different between groups (all p\u3e0.05). As previously demonstrated by our laboratory, the BL men exhibited an augmented sympathetic vascular transduction compared to the WH men (e.g., peak BP response, WH men: Δ4.1±0.3, BL men: Δ5.6±0.7 mmHg, p=0.04). When accounting for FHH within the groups, the peak BP (WH +FHH: Δ4.4±0.6 vs. WH -FHH: Δ3.8±0.4 mmHg, p=0.4) and nadir LVC responses (WH +FHH: Δ-0.5±0.07 vs. WH -FHH: Δ-0.5±0.09 ml·min-¹·mmHg-¹, p=0.7) were not significantly different between WH men +FHH and WH men –FHH. Likewise, the BL men +FHH exhibited similar peak BP (BL +FHH: Δ6.2±0.7 vs. BL -FHH: Δ5.3±1.1 mmHg, p=0.5) and nadir LVC (BL +FHH: Δ-1.1±0.44 vs. BL -FHH: Δ-0.6±0.10 ml·min-¹·mmHg-¹, p=0.2) responses to bursts of MSNA compared to the BL men –FHH. CONCLUSION: These preliminary findings do not support a role for +FHH in augmented sympathetic vascular transduction, therefore suggesting that racial differences in sympathetic vascular transduction are independent of FHH

Age-specific trends in health-related quality of life among US adults: Findings from National Health and Nutrition Examination Survey, 2001-2016

Purpose Health-related quality of life (HRQoL) is an important indicator of population health, yet no age-specific trend analyses in HRQoL have been conducted with a nationally representative sample since 2004. Therefore, to address this gap, an age-specific trend analysis of HRQoL was conducted using National Health and Nutrition Examination Surveys (NHANES) data. Methods NHANES 2001–2016 data (8 cycles) were examined to evaluate trends in HRQoL by age group (young adults: 21–39, middle-aged: 40–64, older adults: 65+). HRQoL was assessed by self-reported health (SRH) and number of physically unhealthy, mentally unhealthy, and inactive days to due to physical or mental health in the past 30 days. Multiple linear or logistic regression analyses explored trends in HRQoL by age group, adjusting for demographics over time. Results Analysis revealed increasing fair/poor SRH over time for the entire sample (β = 0.34, 95% CI 0.08, 0.60, p = 0.011). However, age-specific analysis identified a bi-annual increase in fair/poor SRH only among young adults (β = 0.49, 95% CI 0.22, 0.76, p \u3c 0.001) and a decrease among older adults (β = − 0.60, 95% CI − 1.14, − 0.06, p = 0.03). Closer inspection revealed increasing fair/poor SRH increased among young women (β = 0.52, 95% CI 0.11, 0.93, p = 0.013) and young men (β = 0.46, 95% CI 0.04, 0.88, p = 0.03) but decreased among older women (β = − 0.81, 95% CI − 1.59, − 0.03, p = 0.042) over time. Analyses also determined that there was a trend for a decreasing number of physically unhealthy days among young adults (p \u3c 0.001), although no trends were observed for the other HRQoL items. Conclusions Although there was a significant trend over time for increasing fair/poor SRH when considering the entire sample, this trend was not consistent between age groups or sexes. Given increasing fair/poor SRH among young adults, there is a need to understand and address factors relating to HRQoL among this age group

Rural-Urban Differences in Caregiver Burden Due to the COVID-19 Pandemic among a National Sample of Informal Caregivers

The objective of this exploratory study was to explore potential associations between changes to caregiver burden (CB) due to the COVID-19 pandemic and rural-urban status using a nationally representative sample of 761 informal caregivers. Tertiles of two measures of rural-urban status were used: Rural-Urban Commuting Areas (RUCAs) and population density. Bivariate and multivariable binary and ordinal logistic regression were used to asses study objectives. Using RUCAs, rural informal caregivers were more than twice as likely as urban informal caregivers to report a substantial increase in CB due to COVID-19 (OR 2.27, 95% CI [1.28–4.02]). Similar results were observed for population density tertiles (OR 2.20, 95% CI [1.22–3.96]). Having a COVID-19 diagnosis was also significantly associated with increased CB. Understanding and addressing the root causes of rural-urban disparities in CB among informal caregivers is critical to improving caregiver health and maintaining this critical component of the healthcare system

High Dietary Sodium Reduces Flow Mediated Dilation in Humans with Salt Sensitive & Salt Resistant BP

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