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IntroductionPeanut allergy (PA) in children is a major concern. There is a need for better biological material for both diagnosis and oral immunotherapy (OIT) treatments. The unique state of seeds at early reproductive stages may affect the allergenicity of storage proteins, and impact clinical diagnostic and OIT protocols. The objective of this study was to evaluate the major allergen content in sequential seed developmental stages and monitor allergenicity via specific IgE binding quantification and skin prick testing.MethodsSeeds were collected from peanut plants and sorted into five developmental stages: initial (S1), developing (S2), full-size without coloration (S3), full-size with coloration (S4), and fully mature (S5) seeds. Samples were characterized by RNA-Seq, ELISA, and immunohistochemistry. Lyophilized, ground preparations were used for evaluation of skin test responses in sixty challenge-proven PA children.ResultsGene expression, protein content, and specific IgE binding of allergenic proteins increased throughout seed maturation and development. An expression bias towards the less allergenic A-genome copy of the major allergen Ara h 2 was found in earlier stages, especially in stage S2. Immunohistochemical staining showed that Ara h 2 is more dispersed in the cell and less accumulated within organized bodies at stage S2 versus stage S4. Significant differences were found in mean wheal responses between the commercial peanut extract (equivalent to stage S5) and stages S1 and S2, but not with stage S4, upon skin prick testing in subjects with PA.DiscussionThe observed decrease in peanut-specific IgE binding of immature peanut seeds may be a result not only of decreased amounts of allergenic proteins, but also of profound changes in seed composition and conformation. This may be significant for developing a safer and more effective peanut OIT protocol.

Abstract The purpose of this study was to investigate whether endothelin‐A receptor (ETAR) inhibition in non‐Hispanic Black (NHB) and White (NHW) young adults depends on biological sex. We recruited females during low hormone (n = 22) and high hormone (n = 22) phases, and males (n = 22). Participants self‐identified as NHB (n = 33) or NHW (n = 33). Participants were instrumented with two microdialysis fibers: (1) lactated Ringer's (control) and (2) 500 nM BQ‐123 (ETAR antagonist). Local heating was used to elicit cutaneous vasodilation, and an infusion of 20 mM L‐NAME to quantify NO‐dependent vasodilation. At control sites, NO‐dependent vasodilation was lowest in NHB males (46 ± 13 %NO) and NHB females during low hormone phases (47 ± 12 %NO) compared to all NHW groups. Inhibition of ETAR increased NO‐dependent vasodilation in NHB males (66 ± 13 %NO), in both groups of females during low hormone phases (NHW, control: 64 ± 12 %NO, BQ‐123: 85 ± 11 %NO; NHB, BQ‐123: 68 ± 13 %NO), and in NHB females during high hormone phases (control: 61 ± 11 %NO, BQ‐123: 83 ± 9 %NO). There was no effect for ETAR inhibition in NHW males or females during high hormone phases. These data suggest the effect of ETAR inhibition on NO‐dependent vasodilation is influenced by biological sex and racial identity.

Abstract Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma. FP-RMS histologically resembles developing muscle yet occurs throughout the body in areas devoid of skeletal muscle highlighting that FP-RMS is not derived from an exclusively myogenic cell of origin. Here we demonstrate that P3F reprograms mouse and human endothelial progenitors to FP-RMS. We show that P3F expression in aP2-Cre expressing cells reprograms endothelial progenitors to functional myogenic stem cells capable of regenerating injured muscle fibers. Further, we describe a FP-RMS mouse model driven by P3F expression and Cdkn2a loss in endothelial cells. Additionally, we show that P3F expression in TP53-null human iPSCs blocks endothelial-directed differentiation and guides cells to become myogenic cells that form FP-RMS tumors in immunocompromised mice. Together these findings demonstrate that FP-RMS can originate from aberrant development of non-myogenic cells driven by P3F.

Abstract We assessed the combined effect of superoxide and iNOS inhibition on microvascular function in non‐Hispanic Black and non‐Hispanic White participants (n = 15 per group). Participants were instrumented with four microdialysis fibers: (1) lactated Ringer's (control), (2) 10 μM tempol (superoxide inhibition), (3) 0.1 mM 1400 W (iNOS inhibition), (4) tempol + 1400 W. Cutaneous vasodilation was induced via local heating and NO‐dependent vasodilation was quantified. At control sites, NO‐dependent vasodilation was lower in non‐Hispanic Black (45 ± 9% NO) relative to non‐Hispanic White (79 ± 9% NO; p

Advances in high-throughput technologies have enhanced our ability to describe microbial communities as they relate to human health and disease. Alongside the growth in sequencing data has come an influx of resources that synthesize knowledge surrounding microbial traits, functions, and metabolic potential with knowledge of how they may impact host pathways to influence disease phenotypes. These knowledge bases can enable the development of mechanistic explanations that may underlie correlations detected between microbial communities and disease. In this review, we survey existing resources and methodologies for the computational integration of broad classes of microbial and host knowledge. We evaluate these knowledge bases in their access methods, content, and source characteristics. We discuss challenges of the creation and utilization of knowledge bases including inconsistency of nomenclature assignment of taxa and metabolites across sources, whether the biological entities represented are rooted in ontologies or taxonomies, and how the structure and accessibility limit the diversity of applications and user types. We make this information available in a code and data repository at: https://github.com/lozuponelab/knowledge-source-mappings. Addressing these challenges will allow for the development of more effective tools for drawing from abundant knowledge to find new insights into microbial mechanisms in disease by fostering a systematic and unbiased exploration of existing information.

The genus Dracunculus contains numerous species of subcutaneous parasites of mammals and reptiles. In North America, there are at least three mammal-infecting species of Dracunculus. Reports of Dracunculus infections have been reported from river otters (Lontra canadensis) since the early 1900s; however, little is known about the species infecting otters or their ecology. Most reports of Dracunculus do not have a definitive species identified because females, the most common sex found due to their larger size and location in the extremities of the host, lack distinguishing morphological characteristics, and few studies have used molecular methods to confirm identifications. Thus, outside of Ontario, Canada, where both D. insignis and D. lutrae have been confirmed in otters, the species of Dracunculus in river otters is unknown. In the current study, molecular characterization of nematodes from river otters revealed a high diversity of Dracunculus species. In addition to confirming D. insignis infections, two new clades were detected. One clade was a novel species in any host and the other was a clade previously detected in Virginia opossums (Didelphis virginiana) from the USA and a domestic dog from Spain. No infections with D. lutrae were detected and neither new lineage was genetically similar to D. jaguape, which was recently described from a neotropical otter (Lontra longicaudis) from Argentina. These data also indicate that Dracunculus spp. infections in otters are widespread throughout Eastern North America. Currently the life cycles for most of the Dracunculus spp. infecting otters are unknown. Studies on the diversity, life cycle, and natural history of Dracunculidae parasites in wildlife are important because the related parasite, D. medinensis (human Guinea worm) is the subject of an international eradication campaign and there are increasing reports of these parasites in new geographic locations and new hosts, including new species in humans and domestic dogs.

Abstract The aim of this study was to assess cutaneous sensory nerve function, independent of nitric oxide, in non‐Hispanic Black and White young adults. We tested the hypothesis that cutaneous reactive hyperaemia and sensory nerve‐mediated vasodilatation would be lower in non‐Hispanic Black young adults relative to non‐Hispanic White young adults. Twenty‐four participants who self‐identified as non‐Hispanic Black (n = 12) or non‐Hispanic White (n = 12) were recruited. All participants underwent three bouts of reactive hyperaemia. An index of skin blood flow was measured continuously using laser‐Doppler flowmetry at a control site and at a site treated with topical 4% lignocaine to inhibit sensory nerve function. Peak reactive hyperaemia was lower in non‐Hispanic Black relative to non‐Hispanic White participants (P

The syntheses, coordination chemistry, and Mössbauer spectroscopy of hepta-iron(III) complexes using derivatised salicylaldoxime ligands from two categories; namely, ‘single-headed’ (H2L) and ‘double-headed’ (H4L) salicylaldoximes are described. All compounds presented here share a [Fe3-µ3-O] core in which the iron(III) ions are µ3-hydroxo-bridged in the complex C1 and µ3-oxo-bridged in C2 and C3. Each compound consists of 2 × [Fe3-µ3-O] triads that are linked via a central [Fe(µ2-OH)6]3− ion. In addition to the charge balance and microanalytical evidence, Mössbauer measurements support the fact that the triads in C1 are µ3-OH bridged and are µ3-O bridged in C2 and C3.

Abstract The purpose of this case report was to evaluate in vivo endothelial function and nitric oxide (NO)‐dependent vasodilatation before and after the cessation of long‐term (11–12 years) fourth‐generation oral contraceptive pill (OCP) use in one young, healthy and premenopausal woman. This retrospective analysis includes data from six experimental visits: three visits during months 133–144 of fourth‐generation OCP use and three visits 19–22 months after OCP cessation. Endothelium‐dependent and NO‐dependent vasodilatation were assessed in the cutaneous microvasculature using laser‐Doppler flowmetry, a rapid local heating protocol (39°C, 0.1°C/s) and pharmacological perfusion through intradermal microdialysis fibres. The participant had consistent medical history and lifestyle behaviours throughout both hormonal exposures. Data are presented as the mean (SD). Endothelium‐dependent vasodilatation was 42 (10)% of site‐specific maximal cutaneous vascular conductance (CVCmax) during OCP use and 63 (10)%CVCmax after OCP cessation (49% increase). Nitric oxide‐dependent vasodilatation was 70 (5)% contribution of NO during OCP use and 60 (15)%NO after OCP cessation (15% reduction). Baseline blood flow was greater after OCP cessation, but maximal blood flow was reduced. Data from this case report support a substantial increase in cutaneous microvascular endothelial function assessed via local heating after cessation of long‐term use of a fourth‐generation OCP, which does not appear to be attributable to increased NO bioavailability. Overall, these data suggest an improvement in endothelial and microvascular function after the cessation of long‐term use of a fourth‐generation OCP.

Background Clinically relevant aortic dilatation (>40 mm) and increased cardiovascular risk are common among retired professional American‐style football athletes. Among younger athletes, the effect of American‐style football participation on aortic size is incompletely understood. We sought to determine changes in aortic root (AR) size and associated cardiovascular phenotypes across the collegiate career. Methods and Results This was a multicenter, longitudinal repeated‐measures observational cohort study of athletes across 3 years of elite collegiate American‐style football participation. A total of 247 athletes (119 [48%] Black, 126 [51%] White, 2 [1%] Latino; 91 [37%] linemen, 156 [63%] non‐linemen) were enrolled as freshmen and studied at pre‐ and postseason year 1, postseason year 2 (N=140 athletes), and postseason year 3 (N=82 athletes). AR size was measured with transthoracic echocardiography. AR diameter increased over the study period from 31.7 (95% CI, 31.4–32.0) to 33.5 mm (95% CI, 33.1–33.8; P

Higher rates of peanut allergy have been observed in countries that commonly roast peanuts prior to consumption. Despite the importance of understanding the role of thermal processing in allergy and on peanut composition, studies toward generating signatures that identify molecular contents following processing are scant. Here, we identified spectral signatures to track changes and differences in the molecular composition of peanuts under raw, roasted, and high-pressure and high-temperature autoclaved conditions. We analyzed both the solid flesh of the seed and solutions derived from soaking peanuts using High-Resolution Magic Angle Spinning (HR-MAS) and solution 1H Nuclear Magnetic Resonance (NMR) spectroscopy, respectively. The NMR spectra of intact peanuts revealed triglycerides as the dominant species, assigned on the basis of multiplets at 4.1 and 4.3 ppm, and corresponding defatted flours revealed the presence of sugars. Sucrose assigned based on a doublet at 5.4 ppm (anomeric proton), and triglycerides were the most abundant small molecules observed, with little variation between conditions. Soaked peanut solutions were devoid of lipids, and their resulting spectra matched the profiles of defatted peanuts. Spectral signatures resulting from autoclaving differed strikingly between those from raw and roasted peanuts, with considerable line-broadening in regions corresponding to proteins and amino-acid side chains, from 0.5 to 2.0 ppm and 6.5 to 8.5 ppm. Taken together, by using complementary NMR methods to obtain a fingerprint of the molecular components in peanuts, we demonstrated that autoclaving led to a distinct composition, likely resulting from the hydrolytic cleavage of proteins, the most important molecule of the allergic reaction.

Abstract Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea, and emerging evidence has linked dietary components with CDI pathogenesis, suggesting that dietary modulation may be an effective strategy for prevention. Here, we show that mice fed a high-fat/low-fiber “Western-type” diet (WD) had dramatically increased mortality in a murine model of antibiotic-induced CDI compared to a low-fat/low-fiber (LF/LF) diet and standard mouse chow controls. We found that the WD had a pro- C. difficile bile acid composition that was driven in part by higher levels of primary bile acids that are produced to digest fat, and a lower level of secondary bile acids that are produced by the gut microbiome. This lack of secondary bile acids was associated with a greater disturbance to the gut microbiome with antibiotics in both the WD and LF/LF diet compared to mouse chow. Mice fed the WD also had the highest level of toxin TcdA just prior to the onset of mortality, but not of TcdB or increased inflammation. These findings indicate that dietary intervention to decrease fat may complement previously proposed dietary intervention strategies to prevent CDI in high-risk individuals.

PTEN copy number loss is found in 25% of fusion-negative rhabdomyosarcomas (FN-RMS). Here, the authors use a Hedgehog-driven FN-RMS mouse model to show that PTEN loss drives the expression of core transcription factor PAX7 and its transcriptional axis, which determines FN-RMS tumour identity.

Thoracic outlet syndrome (TOS) describes compression of the neurovascular bundle of the brachial plexus, subclavian artery, and/or subclavian vein as they leave the thoracic outlet. A 40-year-old female with history of thoracic outlet syndrome status-post left first rib resection presented in 2021 with symptoms of recurrent TOS due to the presence of a residual first rib. A transaxillary approach was performed and a partial second rib resection was required to remove the residual first rib. At 4½-month follow-up, there was improvement in all symptoms.

Background Ventricular–arterial (VA) coupling is defined as the ratio between arterial elastance (EA) and left ventricular elastance (ELV). VA uncoupling, as occurs in hypertensive heart disease, is associated with adverse outcomes. This study sought to determine the relationship between American football (AF)–associated hypertension and VA uncoupling. Methods and Results This was a multicenter, longitudinal, and repeated measures observational study of collegiate AF athletes across 3 years of AF participation. Of 200 freshman athletes initially enrolled, 142 (67 Black [47%]/75 White [53%], 58 linemen [41%]/84 nonlinemen [59%]) were prospectively studied with echocardiography and applanation tonometry. Primary echocardiographic VA coupling outcome measures were EA/ELV and ΔEA/ELV, with increased EA/ELV indicating VA uncoupling. Adjusting for race and player position, AF athletes demonstrated increased EA/ELV (mean [95% CI]Δ, 0.10 [0.04–0.15]; P=0.001) and systolic blood pressure (SBP) (mean [95% CI]Δ, 11.4 [8.3–14.5] mm Hg, P

Fusion-negative rhabdomyosarcoma (FN-RMS) is molecularly heterogeneous with few universal alterations except for Phosphatase and tensin homolog (PTEN) promoter hypermethylation. We demonstrate that losing Pten in FN-RMS engages an aberrant transcriptional program key in tumor maintenance and cell identity. These results highlight the importance between transcriptional state, cell of origin, and genetic perturbation in tumorigenesis.

Phosphatase and tensin homolog (PTEN) encodes a tumor-suppressive phosphatase with both lipid and protein phosphatase activity. The tumor-suppressive functions of PTEN are lost through a variety of mechanisms across a wide spectrum of human malignancies, including several rare cancers that affect pediatric and adult populations. Originally discovered and characterized as a negative regulator of the cytoplasmic, pro-oncogenic phosphoinositide-3-kinase (PI3K) pathway, PTEN is also localized to the nucleus where it can exert tumor-suppressive functions in a PI3K pathway-independent manner. Cancers can usurp the tumor-suppressive functions of PTEN to promote oncogenesis by disrupting homeostatic subcellular PTEN localization. The objective of this review is to describe the changes seen in PTEN subcellular localization during tumorigenesis, how PTEN enters the nucleus, and the spectrum of impacts and consequences arising from disrupted PTEN nuclear localization on tumor promotion. This review will highlight the immediate need in understanding not only the cytoplasmic but also the nuclear functions of PTEN to gain more complete insights into how important PTEN is in preventing human cancers.

ABSTRACT For camera‐trap studies to produce accurate data, cameras should have reliable detection of animals within their field of view. We reviewed 1,503,330 pictures obtained from August–September 2016 and February–March 2017 in North Carolina, USA, using 36 Reconyx® PC900 HyperFire cameras (Reconyx, Holmen, WI, USA). We evaluated factors related to temperature, wind speed, and whether specific detection band(s) and zone(s) may have increased the probability of triggering cameras. We focused on 10 species to determine species‐specific reasons for not triggering the camera. The odds of triggering the camera increased when an animal was detected in more zones. Additionally, there were more triggers than expected if an animal was observed in both detections bands as opposed to none. Triggered events were species‐dependent, seeming to favor larger species. The Passive Infrared Motion Detector (PIR) missed 14–16% of the independent events of bears (Ursus americanus), coyotes (Canis latrans), bobcats (Lynx rufus), and red wolves (C. rufus), and were overall ineffective at triggering for squirrels (92%; Sciurus spp.) and rabbits (80%; Sylvilagus spp.). Many (47–64%) of the independent events of gray fox (Urocyon cinereoargenteus), raccoons (Procyon lotor), white‐tailed deer (Odocoileus virginianus), and opossums (Didelphis virginiana) would have been missed if only the PIR function was used. The lack of detection of these species may underestimate occupancy and abundance estimates of these populations. Our results suggest that Reconyx HyperFire PC900 cameras have limitations as a broad, catch‐all system for monitoring wildlife as a result of the layout of their infrared detection zones. © 2019 The Wildlife Society.

Background:. Legislature directly impacts the practice of physicians across multiple specialties. The goal of our study is to investigate the political engagement and opinions of plastic surgery trainees, and how they perceive legislation impacts future practice. Methods:. A 24-question survey was designed and distributed to all program directors and Resident Council members within the American Society of Plastic Surgeons. This initiative was driven by the board and directors and supported by the Resident Council. The Resident Council is a trainee-driven committee within the American Society of Plastic Surgeons that communicates with the Board of Directors. Results:. This survey generated a 10.3% response rate with 118 responses out of 1143 trainees in ACGME accredited institutions. When asked in an open-ended fashion to list the most important reason why one planned to vote in the 2020 election, only 6.8% listed healthcare as a factor. Eighty-four percent of respondents believe that their vote impacts future legislation and regulation. Ninety-four percent strongly agree or agree that political legislation affects reimbursement. Conclusions:. With only 10.3% of trainees responding, there is a concern that political activity is not a priority for plastic surgery trainees. Plastic surgery trainees are attending summits, meeting with politicians, writing letters, and attending fundraisers. Respondents are overwhelmingly voting and planning to vote in elections, though few list healthcare as a reason. A future goal must be to motivate trainees to consider the intersection between healthcare and plastic surgery.

Men who have sex with men (MSM), regardless of HIV infection status, have an intestinal microbiome that is compositionally distinct from men who have sex with women (MSW) and women. We recently showed HIV-negative MSM have elevated levels of intestinal CD4+ T cells expressing CCR5, a critical co-receptor for HIV. Whether elevated expression of CCR5 is driven by the altered gut microbiome composition in MSM has not been explored. Here we used in vitro stimulation of gut Lamina Propria Mononuclear Cells (LPMCs) with whole intact microbial cells isolated from stool to demonstrate that fecal bacterial communities (FBCs) from HIV-positive/negative MSM induced higher frequencies of CCR5+ CD4+ T cells compared to FBCs from HIV-negative MSW and women. To identify potential microbial drivers, we related the frequency of CCR5+ CD4+ T cells to the abundance of individual microbial taxa in rectal biopsy of HIV-positive/negative MSM and controls, and Holdemanella biformis was strongly associated with increased frequency of CCR5+ CD4+ T cells. We used in vitro stimulation of gut LPMCs with the type strain of H. biformis, a second strain of H. biformis and an isolate of the closely related Holdemanella porci , cultured from either a HIV-positive or a HIV-negative MSM stool. H. porci elevated the frequency of both CCR5+ CD4+ T cells and the ratio of TNF-α/IL-10 Genomic comparisons of the 3 Holdemanella isolates revealed unique cell wall and capsular components, which may be responsible for their differences in immunogenicity. These findings describe a novel mechanism potentially linking intestinal dysbiosis in MSM to HIV transmission and mucosal pathogenesis.

Many studies of vascular function limit the testing of premenopausal female participants to periods when female sex hormones, either endogenous or exogenous, are at their lowest concentration. This practice, when not part of the specific research question, may limit data surrounding the predominant physiological state of premenopausal females and pose a threat to external validity. In this Perspective, we briefly review the literature on the effect of female sex hormones on vascular function and discuss when limiting experimental testing to a certain phase of the menstrual cycle (MC) or oral contraceptive (OC) use may be appropriate. The goal of this Perspective is to open a dialog that may enhance data validity and the overall understanding of vascular function in premenopausal females.

Abstract Relative to non‐Hispanic Whites, non‐Hispanic Blacks are disproportionately affected by elevated blood pressure (BP). It is unknown whether race or subclinical increases in BP affect the ability of cutaneous sensory nerves to induce cutaneous microvascular vasodilation. Sixteen participants who self‐identified as non‐Hispanic Black (n = 8) or non‐Hispanic White (n = 8) were subgrouped as normotensive or prehypertensive. Participants were instrumented with three intradermal microdialysis fibers: (a) control, (b) 1 μM sodium nitroprusside (SNP), an exogenous nitric oxide (NO) donor, and (c) 20 mM NG‐nitro‐l‐arginine methyl ester (L‐NAME), a non‐selective NO synthase inhibitor. A slow local heating protocol (33–40°C, 0.1°C/min) was used to assess the onset of cutaneous sensory nerve‐mediated vasodilation (temperature threshold) and skin blood flow was measured using laser‐Doppler flowmetry. At control sites, the temperature threshold occurred at a higher temperature in non‐Hispanic Blacks (normotensive: 37.2 ± 0.6°C, prehypertensive: 38.9 ± 0.5°C) compared to non‐Hispanic Whites (normotensive: 35.2 ± 0.8°C, prehypertensive: 35.2 ± 0.9°C). L‐NAME shifted the temperature threshold higher in non‐Hispanic Whites (normotensive: 37.8 ± 0.7°C, prehypertensive: 38.2 ± 0.8°C), but there was no observed effect in non‐Hispanic Blacks. SNP did not affect temperature threshold in non‐Hispanic Whites, but shifted the temperature threshold lower in non‐Hispanic Blacks (normotensive: 34.6 ± 1.2°C, prehypertensive: 34.8 ± 1.1°C). SNP mitigated differences in temperature threshold across all groups. There was no effect found for BP status in either the non‐Hispanic Black or non‐Hispanic White groups. These data suggest that reduced NO bioavailability affects the ability of cutaneous sensory nerves to induce microvascular vasodilation in young, otherwise healthy non‐Hispanic Blacks.

Pelvic organ prolapse and stress urinary incontinence are common conditions for which approximately 11% of women will undergo surgical intervention in their lifetime. The use of vaginal mesh for pelvic organ prolapse and stress urinary incontinence rose rapidly in the early 2000s as over 100 mesh products were introduced into the clinical armamentarium with little regulatory oversight for their use. US Food and Drug Administration Public Health Notifications in 2008 and 2011, as well as reclassification of transvaginal mesh for prolapse to class III in early 2016, were a response to debilitating complications associated with transvaginal mesh placement in many women. The midurethral sling has not been subject to the same reclassification and continues to be endorsed as the “gold standard” for surgical management of stress urinary incontinence by subspecialty societies. However, litigators have not differentiated between mesh for prolapse and mesh for incontinence. As such, all mesh, including that placed for stress urinary incontinence, faces continued controversy amidst an uncertain future. In this article, we review the background of the mesh controversy, recent developments, and the anticipated role of mesh in surgery for prolapse and stress urinary incontinence going forward.

Instructor Talk--noncontent and nonlogistical language that is focused on shaping the classroom learning environment--is a recently defined variable that may play an important role in how undergraduates experience courses. Previous research characterized Instructor Talk used by faculty teaching in biology lecture classrooms. However, graduate teaching assistants (GTAs) and laboratory classrooms represent critical factors in undergraduate education, and Instructor Talk in this context has yet to be explored. Here, we present findings analyzing Instructor Talk used by GTAs teaching in undergraduate biology laboratory classrooms. We characterized the Instructor Talk used by 22 GTA instructors across 24 undergraduate biology laboratory courses in the context of a single, urban, Hispanic-serving and Asian American and Pacific Islander--serving Institution. We found that Instructor Talk was present in every course studied, GTAs with pedagogical training and prior teaching experience used more Instructor Talk than those without, and GTAs teaching laboratory courses used more Instructor Talk than previous observations of faculty teaching lecture courses. Given the widespread use of Instructor Talk and its varying use across contexts, we predict that Instructor Talk may be a critical variable in teaching, specifically in promoting equity and inclusion, which merits continued study in undergraduate science education.

Lymphatic vessels grow through active sprouting and mature into a vascular complex that includes lymphatic capillaries and collecting vessels that ensure fluid transport. However, the signaling cues that direct lymphatic sprouting and patterning remain unclear. In this study, we demonstrate that chemokine signaling, specifically through CXCL12 and CXCR4, plays crucial roles in regulating lymphatic development. We show that LEC-specific Cxcr4-deficient mouse embryos and CXCL12 mutant embryos exhibit severe defects in lymphatic sprouting, migration and lymphatic valve formation. We also discovered that CXCL12, originating from peripheral nerves, directs the migration of dermal lymphatic vessels to align with nerves in developing skin. Deletion of Cxcr4 or blockage of CXCL12 and CXCR4 activity results in reduced VEGFR3 levels on the LEC surface. This, in turn, impairs VEGFC-mediated VEGFR3 signaling and downstream PI3K and AKT activities. Taken together, these data identify previously unknown chemokine signaling originating from peripheral nerves that guides dermal lymphatic sprouting and patterning. Our work identifies for the first time a neuro-lymphatics communication during mouse development and reveals a previously unreported mechanism by which CXCR4 modulates VEGFC, VEGFR3 and AKT signaling. [ABSTRACT FROM AUTHOR]