bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking microbial infallibility in the metagenomics era
Authors: O'Malley Maureen A , Walsh David A
Published: June 2021

The ‘principle of microbial infallibility’ was a mainstay of microbial physiology and environmental microbiology in earlier decades. This principle asserts that wherever there is an energetic gain to be made from environmental resources, microorganisms will find a way to take advantage of the situation. Although previously disputed, this claim was revived with the discovery of anammox bacteria and other major contributors to biogeochemistry. Here, we discuss the historical background to microbial infallibility, and focus on its contemporary relevance to metagenomics. Our analysis distinguishes exploration-driven metagenomics from hypothesis-driven metagenomics. In particular, we show how hypothesis-driven metagenomics can use background assumptions of microbial infallibility to enable the formulation of hypotheses to be tested by enrichment cultures. Discoveries of comammox and the anaerobic oxidation of methane are major instances of such strategies, and we supplement them with outlines of additional examples. This overview highlights one way in which metagenomics is making the transition from an exploratory data-analysis programme of research to a hypothesis-testing one. We conclude with a discussion of how microbial infallibility is a heuristic with far-reaching implications for the investigation of life.
The Immunopathobiology of SARS-CoV-2 Infection
Authors: Patel Milankumar , Shahjin Farah , Cohen Jacob D , Hasan Mahmudul , Machhi Jatin , Chugh Heerak , Singh Snigdha , Das Srijanee , Kulkarni Tanmay A , Herskovitz Jonathan , Meigs Douglas D , Chandra Ramesh , Hettie Kenneth S , Mosley R Lee , Kevadiya Bhavesh D , Gendelman Howard E
Published: June 2021

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to coronavirus disease 2019 (COVID-19). Virus-specific immunity controls infection, transmission and disease severity. With respect to disease severity, a spectrum of clinical outcomes occur associated with age, genetics, comorbidities and immune responses in an infected person. Dysfunctions in innate and adaptive immunity commonly follow viral infection. These are heralded by altered innate mononuclear phagocyte differentiation, activation, intracellular killing and adaptive memory, effector, and regulatory T cell responses. All of such affect viral clearance and the progression of end-organ disease. Failures to produce effective controlled antiviral immunity leads to life-threatening end-organ disease that is typified by the acute respiratory distress syndrome. The most effective means to contain SARS-CoV-2 infection is by vaccination. While an arsenal of immunomodulators were developed for control of viral infection and subsequent COVID-19 disease, further research is required to enable therapeutic implementation.
How wind acclimation impacts Pinus pinaster growth in comparison to resource availability
Authors: Dèfossez Pauline , Rajaonalison Fanjamalala , Bosc Alexandre
Published: June 2021

Key message Anthropic and natural disturbances in Pine pinaster forests may induce changes in tree wind exposure and resource availability. The wind acclimation has consequences on P. pinaster growth comparable to resource acquisition after sudden changes in micro-environmental conditions. Context More disturbances occur within the forest, resulting in the creation of inter-tree space. This increases resource availability for the remaining trees but also their wind exposure. Trees have the ability to acclimate to these changes in their micro-environmental conditions by modifying their development. Increase in both resource availability and wind-induced deformations (strains) are known to promote tree radial growth but their relative importance has not been previously analysed in field conditions. Aims This paper aims to study the Pinus pinaster growth in response to a sudden change in wind loading in comparison to a rapid increase in resource availability. Methods An experiment was established in a 16-year-old P. pinaster to create different conditions of wind loading and resources by guying trees with wires and removing their neighbours. The increase in trunk volume below 4 m was monitored for 3 years by measuring the stem radial growth at three stem heights. Results Acclimation to wind has important consequences for stem growth, comparable to that of the effect of greater resource availability after an increase in inter-tree spacing. The increase in trunk volume below 4 m induced by wind and by having more resources were quantitatively close and were equivalent after 3 years of treatment, to the trunk volume increase during the year before experiment. The observed wind acclimation was interpreted in terms of tree mechanical reinforcement by calculating the gain in the stem flexural rigidity: mechanical strength gains of 13.8 and 20.3% of swaying trees were observed in comparison to guyed trees for both high and low resource levels, respectively. Our analysis suggests that the relative effects of wind loading or higher resource are not modified over time by seasonable growth modulation. Both the effects of the wind acclimation and the higher resource were found to be independent and are likely to be cumulative. Conclusion This study highlights the importance of considering wind acclimation in the regulation of growth in forests after a sudden change in environmental conditions.
Comparing one-step full-spectrum inversion with two-step splitting function inversion in normal mode tomography
Authors: Jagt Lisanne , Deuss Arwen
Published: June 2021

Earth’s normal modes, or whole Earth oscillations, provide important constraints on Earth’s large-scale 3-D structure. In addition to constraining shear and compressional wave velocities, they are the only seismic data sensitive to density perturbations. Density is particularly difficult to determine, and previous studies have found contradicting results, hence the method chosen to invert normal mode data for 3-D structure becomes important. In the problem of inverting the measured frequency spectra for an earth model, we can take two approaches: (i) a one-step full-spectrum inversion, where normal mode spectra are directly inverted for a mantle model and (ii) a two-step splitting function inversion, where first the spectra are inverted for splitting functions, which are then inverted for a mantle model. Here we compare the methodology and results of both approaches, continuing the work done by Li et al. and Durek & Romanowicz, and extending it to higher spherical harmonic degrees. Using exactly the same normal mode data set, we use both inversion approaches to make 3-D shear wave velocity mantle models. Both approaches give models consistent with previous tomographic studies, although spectral misfits are consistently lower for the one-step full-spectrum inversion. We also show that we cannot draw any conclusions on odd-degree structure in the lower mantle with the currently available normal mode data sets.
Digital storytelling within the Australian mining industry: worker engagement and health literacy indicator effects
Authors: Shannon Hugh A , Parker Anthony W
Published: June 2021

The mining industry is a demanding context for workplace health education due to a range of factors including productivity targets, workforce diversity and work roster schedules. This project investigated the impact of digital story health communication on worker engagement and its effect on interactive and critical health literacy indicators. The study comprised a quasi-experimental parallel time series research design, with control and intervention groups at each of the mine sites (n = 2). Workers in the intervention group (n = 85) received a ‘toolbox talk’ presentation incorporating a digital story featuring a mining industry worker and a leading cardiovascular health expert. The control group (n = 90) received equivalent health information communicated in a non-narrative manner, reflective of typical practices within the mining industry. A significantly greater effect was evident for worker engagement within the intervention group, with substantial maintenance over the follow-up period, compared with no significant effect at follow-up within the control group. Significant effects on interactive health literacy indicators (n = 3) were evident for the intervention group with corresponding lower level or nil effects within the control group. The findings highlight the benefits of evidence-based digital stories as an efficient and efficacious worker-centred health communication strategy for complex industrial workplace environments.
Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth
Authors: Karahoda Rona , Robles Morgane , Marushka Julia , Stranik Jaroslav , Abad Cilia , Horackova Hana , Tebbens Jurjen Duintjer , Vaillancourt Cathy , Kacerovsky Marian , Staud Frantisek
Published: June 2021

Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here, we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n = 39) and 167 preterm deliveries (PTL, n = 38 and PPROM, n = 129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory markers (such as maternal serum C-reactive protein and white blood cell count). We show that preterm birth is associated with significant changes in placental tryptophan metabolism. Multifactorial analysis revealed similarities in expression patterns associated with multiple phenotypes of preterm delivery. Subsequent correlation computations and mediation analyses identified links between intra-amniotic and maternal inflammatory markers and placental serotonin and kynurenine pathways of tryptophan catabolism. Collectively, the findings suggest that a hostile inflammatory environment associated with preterm delivery underlies the mechanisms affecting placental endocrine/transport functions and may contribute to disruption of developmental programming of the fetal brain.
Development and Validation of a Pediatric MRI-Based Perianal Crohn Disease (PEMPAC) Index—A Report from the ImageKids Study
Authors: Choshen Sapir , Turner Dan , Pratt Li-Tal , Precel Ronit , Greer Mary-Louise , Castro Denise A , Assa Amit , Martínez-León María I , Herman-Sucharska Izabela , Coppenrath Eva , Konen Osnat , Davila Jorge , Bekhit Elhamy , Alsabban Zehour , Focht Gili , Gavish Matan , Griffiths Anne , Cytter-Kuint Ruth
Published: June 2021

Background

As part of the prospective multicenter ImageKids study, we aimed to develop and validate the pediatric MRI-based perianal Crohn disease (PEMPAC) index.

Methods

Children with Crohn disease with any clinical perianal findings underwent pelvic magnetic resonance imaging at 21 sites globally. The site radiologist and 2 central radiologists provided a radiologist global assessment (RGA) on a 100 mm visual analog scale and scored the items selected by a Delphi group of 35 international radiologists and a review of the literature. Two weighted multivariable statistical models were constructed against the RGA.

Results

Eighty children underwent 95 pelvic magnetic resonance imaging scans; 64 were used for derivation and 31 for validation. The following items were included: fistula number, location, length and T2 hyperintensity; abscesses; rectal wall involvement; and fistula branching. The last 2 items had negative beta scores and thus were excluded in a contending basic model. In the validation cohort, the full and the basic models had the same strong correlation with the RGA (r = 0.75; P < 0.01) and with the adult Van Assche index (VAI; r = 0.93 and 0.92; P < 0.001). The correlation of the VAI with the RGA was similar (r = 0.77; P < 0.01). The 2 models and the VAI had a similar ability to differentiate remission from active disease (area under the receiver operating characteristic curve, 0.91-0.94). The PEMPAC index had good responsiveness to change (area under the receiver operating characteristic curve, 0.89; 95% confidence interval, 0.69-1.00).

Conclusions

Using a blended judgmental and mathematical approach, we developed and validated an index for quantifying the severity of perianal disease in children with CD. The adult VAI may also be used with confidence in children.
Exceptional Collection of Objects on Some Fake Projective Planes
Authors: Lai Ching-Jui , Yeung Sai-Kee
Published: June 2021

The purpose of this article is to explain a new method to establish the existence of an exceptional collection of length three for a fake projective plane $M$ with nontrivial automorphism group, related to a conjecture of Galkin–Katzarkov–Mellit–Shinder in 2015. Our method shows that thirty fake projective planes support such a sequence, most of which are new. In particular, this provides many new $H$-phantom categories.
Electronic consultations and economies of scale: a qualitative study of clinician perspectives on scaling up e-consult delivery
Authors: Anderson Ekaterina , Rinne Seppo T , Orlander Jay D , Cutrona Sarah L , Strymish Judith L , Vimalananda Varsha G
Published: June 2021

Objective

To explore Veterans Health Administration clinicians’ perspectives on the idea of redesigning electronic consultation (e-consult) delivery in line with a hub-and-spoke (centralized) model.

Materials and Methods

We conducted a qualitative study in VA New England Healthcare System (VISN 1). Semi-structured phone interviews were conducted with 35 primary care providers and 38 specialty care providers, including 13 clinical leaders, at 6 VISN 1 sites varying in size, specialist availability, and e-consult volume. Interviews included exploration of the hub-and-spoke (centralized) e-consult model as a system redesign option. Qualitative content analysis procedures were applied to identify and describe salient categories.

Results

Participants saw several potential benefits to scaling up e-consult delivery from a decentralized model to a hub-and-spoke model, including expanded access to specialist expertise and increased timeliness of e-consult responses. Concerns included differences in resource availability and management styles between sites, anticipated disruption to working relationships, lack of incentives for central e-consultants, dedicated staff’s burnout and fatigue, technological challenges, and lack of motivation for change.

Discussion

Based on a case study from one of the largest integrated healthcare systems in the United States, our work identifies novel concerns and offers insights for healthcare organizations contemplating a scale-up of their e-consult systems.

Conclusions

Scaling up e-consults in line with the hub-and-spoke model may help pave the way for a centralized and efficient approach to care delivery, but the success of this transformation will depend on healthcare systems’ ability to evaluate and address barriers to leveraging economies of scale for e-consults.
Cannabinoids Tetrahydrocannabinol, Cannabinol, Cannabidiol, Tetrahydrocannabivarin and 11-nor-9-carboxy-∆9-THC in Hair
Authors: Hill Virginia A , Schaffer Michael I , Paulsen Ryan B , Stowe G Neil
Published: June 2021

The cannabinoids tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabinol (CBN) and (-)-11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH) were determined in 4,773 hair samples. Confirmation of THC-COOH was by GC–MS-MS (gas chromatography--mass spectrometry-mass spectrometry). Confirmation of THC, THCV, CBN and CBD was by LC–MS-MS (liquid chromatoraphy--mass spectrometry-mass spectrometry) on an AB Sciex QTRAP 6500+ LC–MS-MS. The purpose of this work was not to utilize any analyte other than THC-COOH as indicative of ingestion, but to assess the absence or presence, and relative concentrations, of the other cannabinoid analytes in hair of marijuana users vs. primarily CBD users. In this regard, 10% of samples contained significantly higher concentrations of CBD relative to THC than the other 90%. A concentration of CBD that is five times greater than that of THC was proposed as good evidence of primarily CBD ingestion. THC concentrations in the samples ranged from below the limit of detection (5 pg/mg) to 47,808 pg/mg hair, varying widely in the relationship between parent THC and the metabolite THC-COOH. CBN was present in most samples, but concentrations relative to THC decreased with increasing THC concentrations. Only 26% of the samples contained THCV detectable by the method. When present, THCV concentrations averaged 1.77% of THC. A limitation of this study is the lack of subject histories to determine the types and amounts of products used and the mode of ingestion. Also, not all THC from external contamination may be removed. Nonetheless, the data provide a useful guide as to what cannabinoids may be found in hair, at what concentrations and under conditions of marijuana use vs. likely primarily CBD use.
Preferential import of queuosine-modified tRNAs into Trypanosoma brucei mitochondrion is critical for organellar protein synthesis
Authors: Kulkarni Sneha , Rubio Mary Anne T , Hegedűsová Eva , Ross Robert L , Limbach Patrick A , Alfonzo Juan D , Paris Zdeněk
Published: June 2021

Transfer RNAs (tRNAs) are key players in protein synthesis. To be fully active, tRNAs undergo extensive post-transcriptional modifications, including queuosine (Q), a hypermodified 7-deaza-guanosine present in the anticodon of several tRNAs in bacteria and eukarya. Here, molecular and biochemical approaches revealed that in the protozoan parasite Trypanosoma brucei, Q-containing tRNAs have a preference for the U-ending codons for asparagine, aspartate, tyrosine and histidine, analogous to what has been described in other systems. However, since a lack of tRNA genes in T. brucei mitochondria makes it essential to import a complete set from the cytoplasm, we surprisingly found that Q-modified tRNAs are preferentially imported over their unmodified counterparts. In turn, their absence from mitochondria has a pronounced effect on organellar translation and affects function. Although Q modification in T. brucei is globally important for codon selection, it is more so for mitochondrial protein synthesis. These results provide a unique example of the combined regulatory effect of codon usage and wobble modifications on protein synthesis; all driven by tRNA intracellular transport dynamics.
Authorial Intention, Readers’ Creation, and Reference Shift
Authors: Lee Jeonggyu
Published: June 2021

This paper deals with the identity problems of fictional objects, focusing on Anthony Everett's and Stuart Brock's leading criticisms against fictional creationism, the view that fictional objects are abstract objects created by our acts involving literary practices. My primary aim is to argue that creationism based on referentialism has enough resources to individuate fictional objects and hence can address the alleged identity problems: every alleged problematic case regarding the identity of fictional objects is well explained in terms of the notions of authorial intention, gappy proposition, inadvertent creation, and reference shift.
Financialization and corporate downsizing as a shareholder value strategy
Authors: Jung Jiwook , Lee Yin
Published: June 2021

How has financialization contributed to the changing nature of employment relations? Using the case of downsizing, we provide a cultural explanation of how the growing influence of the financial sector has reshaped employment relations at non-financial firms. We focus on the role of financial professionals in promoting the norm of shareholder value maximization around which financial market expecatations are formed and imposed upon firms. Our analysis of downsizing announcements made by the largest US firms shows that firms downsize when they miss earnings forecasts of securities analysts—a clear indication that firms fail to maximize shareholder value. We also show that institutional investors and financial executives promoted downsizing after missed analyst forecasts while labor unions resisted it. Despite the latter group’s resistance, in the context of the declining countervailing influence of labor, our findings suggest that downsizing has become institutionalized as a shareholder value strategy in the era of financialization.
Sleep’s short-term memory preservation and long-term affect depotentiation effect in emotional memory consolidation: behavioral and EEG evidence
Authors: Zeng Shengzi , Lin Xuanyi , Wang Jingxuan , Hu Xiaoqing
Published: June 2021

Study Objectives

Sleep plays a pivotal role in the off-line processing of emotional memory. However, much remains unknown for its immediate vs. long-term influences. We employed behavioral and electrophysiological measures to investigate the short- and long-term impacts of sleep vs. sleep deprivation on emotional memory.

Methods

Fifty-nine participants incidentally learned 60 negative and 60 neutral pictures in the evening and were randomly assigned to either sleep or sleep deprivation conditions. We measured memory recognition and subjective affective ratings in 12- and 60-h post-encoding tests, with EEGs in the delayed test.

Results

In a 12-h post-encoding test, compared to sleep deprivation, sleep equally preserved both negative and neutral memory, and their affective tones. In the 60-h post-encoding test, negative and neutral memories declined significantly in the sleep group, with attenuated emotional responses to negative memories over time. Furthermore, two groups showed spatial-temporally distinguishable ERPs at the delayed test: while both groups showed the old-new frontal negativity (300–500 ms, FN400), sleep-deprived participants additionally showed an old-new parietal, Late Positive Component effect (600–1000 ms, LPC). Multivariate whole-brain ERPs analyses further suggested that sleep prioritized neural representation of emotion over memory processing, while they were less distinguishable in the sleep deprivation group.

Conclusions

These data suggested that sleep’s impact on emotional memory and affective responses is time-dependent: sleep preserved memories and affective tones in the short term, while ameliorating affective tones in the long term. Univariate and multivariate EEG analyses revealed different neurocognitive processing of remote, emotional memories between sleep and sleep deprivation groups.
How to Balance the Many Roles of tRNAs During the Creation of New Genetic Codes
Authors: Ellington Andrew , Maranhao Andre , Baldridge Kevin , Tack Drew , Thyer Ross , Contreras Lydia
Published: June 2021

Transfer RNA is a remarkable molecule, in that it sits at the crossroads between many competing functions, including charging, loading onto the ribosome, interacting with the ribosome for peptide bond formation. In all of these functions, it is competing with other tRNAs of similar shape and function, and must both be efficient in the production of proteins, but also highly specific in decoding the genetic code. For these reasons, tRNA molecules are likely under heavy selection pressure, and engineering them unsurprisingly can lead to large fitness costs for an organism.

However, if we are to engineer novel genetic codes to improve the diversity of protein function, it will be essential to seamlessly integrate new tRNAs into these novel genetic codes. To this end, the Ellington lab has undertaken the engineering and directed evolution of tRNA molecules in the context of expanded genetic codes. We will present data on the fitness costs of an expanded 21 amino acid genetic code in which amber codons are decoded as nitrotyrosine, iodotyrosine, or selenocysteine and on the directed evolution of tRNA molecules to better accommodate the encoding of these new amino acids. Surprisingly, the efficient incorporation of the non‐canonical amino acids resulted in a reduction in the production of the tRNAs, and a concomitant catholicism towards modification. These counterintuitive results support the hypothesis that tRNA modifications by and large improve the specificity of protein translation.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dysregulated bile transporters and impaired tight junctions promote chronic liver injury in mice
Authors: Pradhan Tirthadipa , Vats Ravi , Russell Jacqulyne , Singh Sucha , Watkins Simon , Sundd Prithu , Monga Satdarshan Pal
Published: June 2021

Liver fibrosis, hepatocellular necrosis, inflammation and proliferation of liver progenitor cells are the hallmarks of chronic liver injury. Several murine models have been used to mimic the pathophysiology of chronic liver injury. However, the underlying differences in the molecular mechanism driving liver injury in different models remains largely unknown due to our inability to visualize the progression of liver injury in vivo in mice. Here, we use intravital imaging of bile transport and blood‐bile barrier integrity in the intact liver of live mice. We show for the first time that breach of blood‐bile barrier and impairment of bile secretion promotes choline‐deficient‐ethionine‐supplemented (CDE) and 3, 5‐diethoxycarbonyl‐1, 4‐dihydrocollidine (DDC) diets induced chronic liver injury in mice. The impairment in bile secretion was associated with the disruption of the blood‐bile barrier, differential expression of several tight junction adhesion molecules and loss of bile transporters. Surprisingly, the prolonged use of CDE diet led to reappearance of tight junction adhesion molecules as well as bile transporters, which was concomitant to the reestablishment of blood‐bile barrier integrity and rescue of bile secretion. Our findings demonstrate the potential of intravital imaging in elucidating the underlying pathophysiology in mice models of chronic liver injury and identify the loss of bile transporters or tight junction adhesion molecules as two distinct mechanisms contributing to progression of chronic liver injury.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Janus Kinase 3 modulates the tolerogenic immunology of liver through Kupffer cells.
Authors: Kumar Narendra , Das Jugal K. , Mishra Jayshree
Published: June 2021

Background

Janus kinase 3 (Jak3) is a non‐receptor protein kinase involved in a diverse array of processes like differentiation, development, cell‐growth and hematopoietic signaling cascades. We have previously shown that loss of Jak3 exacerbates symptoms of inflammatory bowel disease (IBD) in a murine model of ulcerative colitis. The compromised intestinal barrier functions in ulcerative colitis have been shown to lead to systemic chronic low grade inflammation and subsequent hepatic disease. In this report, we investigated the tissue‐specific role of Jak3 in maintaining hepatic homeostasis during ulcerative colitis.

Methods

In order to test our hypothesis, we used a global Jak3 KO (Jak3−/−) mice model and compared its effect with either the intestinal epithelial specific Jak3 KO (Int Jak3 KO) mice or immune cell specific Jak3 KO (Imm Jak3 KO) mice. These mice were treated with 2.5% 40 kda DSS in our study. The organs were collected at the end of the study period under aseptic conditions and analyzed using a combination of flowcytometric, confocal microscopy, and western analysis techniques.

Results

Our results show increased susceptibility to colitis in DSS‐treated Jak3−/− mice. They also show a high‐degree of association between the disease scores and hepatic inflammation in Imm Jak3 KO mice, indicating a prominent role of hematopoietic Jak3 in maintaining hepatic immunological homeostasis. A differential flowcytometric assay showed an increased influx of monocytes, but reduced differentiation of residential kupffer cells in imm Jak3 KO mice compared to its floxed control during ulcerative colitis. Further, the same group of mice also showed an increased TLR‐4 expression and higher IL‐6, IL‐17 and Tnf‐α as compared to the control mice. Together, these results confirm the lack of Jak3 in immune cells leads to a compromise in the activation of kupffer cells coupled with increased extravasation of the circulating monocytes into the liver. This could lead to liver disease and inflammation in ulcerative colitis. In addition, we also found an increased Th17 effector function and simultaneous suppression of Treg cell proliferation in the absence of immune cell Jak3, when compared to its control mice, on treatment with DSS.

Conclusion

Collectively, these results indicate that Jak3 plays a major role in regulating the macrophage based tolerogenic immunology of the hepatic system.

Support or Funding Information

This study in part was supported by NIH grant R43GM109528

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Enhancing Anatomy Education Through Student‐led Team Dynamics Initiatives
Authors: Sanky Charles , Fallar Robert , Cruz Mateo , Reidenberg Joy S. , Laitman Jeffrey T.
Published: June 2021

Background

In anatomy education, reliance upon fellow classmates and more senior students sharing similar experiences can foster academic success and prepare students for the emotional intensity of cadaver dissection. At the Icahn School of Medicine at Mount Sinai, the first course, Structures, requires medical students to put collaboration into practice. Because of the emotionally and academically challenging nature of the Structures course, students must rely on their teams and supportive peers for psychosocial wellness and academic success.

Hypothesis

Student‐led initiatives focusing on team dynamics enhance anatomy education of medical students.

Methods

First‐year medical students (n=140) participated in a student‐developed and led team dynamics session during orientation week, immediately before Structures began. Students met their teams for the course, collaborated in team activities, and discussed how teams foster psychoemotional well‐being and academic performance. During Structures, second‐year medical students conducted review sessions and debriefed Structures teams regarding their performance. Self‐reported team assessments (n=81) throughout the course and a final course evaluation (n=74) gauged team performance and efficacy of student‐led initiatives.

Results

Students reported that the orientation session was helpful before the Structures course began, and subsequent course evaluations revealed continued consciousness about the team dynamics they experienced. Team self‐assessments revealed that team dynamics tended to improve from the beginning to the end of the course, especially along domains of conflict resolution (p=0.017) and learning and development (p=0.035). At the end of Structures, most respondents (71/74, 95.95%) expressed feeling more comfortable working as a part of a team.

Conclusions

These findings suggest the importance of student‐led team dynamics initiatives in anatomy education and in encouraging collaboration. This approach toward medical education also holds broad implications for patient safety, quality of care, and health improvement, areas in which collaboration serves a major role. Further investigation correlating academic performance on team practical exams and quality of team collaboration may underscore these findings. Student‐driven curricular enhancements in team dynamics may facilitate fellow students' success in anatomy education and beyond.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Medical Student Learning Experiences in Organ System Course Sessions using a Histology and Embryology Team‐taught Integrated Format
Authors: Attardi Stefanie M. , Venuti Judith M.
Published: June 2021

Medical schools accredited by the Liaison Committee on Medical Education are required to enhance their medical curriculum in a coherent and coordinated manner. Content integration, which is one characteristic of this requirement, involves linking concepts from different subjects and building from them so they can be more deeply understood and applied by students. At the relatively new Oakland University William Beaumont School of Medicine, the preclinical medical curriculum is integrated horizontally within each organ system course. However, the appropriate basic science disciplines are generally presented in separate sessions delivered by different content experts.

In an effort to enhance the integration of the basic sciences, histology and embryology sessions were delivered in select organ system courses as integrated, team‐taught lectures for a two‐year period. Histology and embryology professors were both present during the same session to present the content and the relationship between the two disciplines was emphasized with embryological concepts forming a foundation for interpreting histological images.

Studies of team teaching in higher education suggest it enhances the learning environment; however, the research is predominately anecdotal, from the instructors' perspectives, and lacks measurement of benefits and costs. This qualitative study aimed to identify variables for measuring outcomes of team‐taught integrated sessions in medical histology and embryology. The specific objectives were to determine why students might prefer the team or traditional segregated format, to compile student‐recommended best practices for team lecturers, and to identify other disciplines that may be conducive to the team‐teaching format. A phenomenological approach to qualitative inquiry was employed, where medical students' perceptions about team lectures were generalized to describe their shared experience of the learning environment. Qualitative data were collected from second year medical students during audio‐recorded focus groups and from organ system course evaluations. Open coding analyses will be performed on the focus group transcripts and course evaluation comments to generate themes and identify variables of interest. This study serves as the first phase of an exploratory sequential mixed methods research project in that the results will drive the development of future quantitative studies on the benefits and costs of team‐taught integrated sessions in medical education.

Support or Funding Information

OUWB Fellowship in Medical Education

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
“Exploring the Regulation of Photosynthesis in Single‐Cell Lineages at Sub‐Cellular Resolution”
Authors: Cameron Jeffrey C.
Published: June 2021

Photosynthesis is regulated in response to many diverse stimuli including light intensity and wavelength, nutrient availability, and temperature. Understanding how photosynthesis is regulated is critical if we are to increase photosynthetic efficiency for the benefit of society and the environment. While decades of research have revealed the structures and mechanisms of isolated photosynthetic complexes at molecular resolution, little is known about how these complexes interact and are regulated in the context of the dynamic cellular environment.

To investigate how photosynthesis is regulated in single‐cells, we utilized long‐term, quantitative time‐lapse fluorescence microscopy to visualize the growth dynamics of wild‐type and mutant cyanobacterial strains following diverse environmental, chemical, and genetic perturbations. Quantitative image processing with custom algorithms enabled us to track individual cells across single‐cell derived lineages for multiple generations and monitor cellular physiology at sub‐cellular resolution.

Our results suggest that mechanical interactions with the physical environment can lead to attenuation of photosynthesis and can play a major role in governing cellular fitness and productivity in cyanobacteria. The mechanistic basis of this phenomenon was investigated using mathematical modeling, electron microscopy, mutational analysis, and CRISPRi‐based dynamic gene regulation. These results provide insight into how photosynthetic organisms navigate the physical environment and a new perspective on source‐sink regulation of photosynthesis.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CXCR3 Regulates CD4+ T Cell Cardiotropism and Maladaptive Cardiac Remodeling Through Mechanisms Involving ICAM1‐Mediated Adhesion
Authors: Ngwenyama Njabulo , Salvador Ane , Nevers Tania , Velázquez Francisco , Aronovitz Mark , Alcaide Pilar
Published: June 2021

Left ventricular (LV) dysfunction and heart failure (HF) progression are associated in humans and mice with increased levels of circulating chemokines CXCL9 and CXCL10, and increased frequency of T cells expressing their receptor CXCR3. CXCR3 signaling upon chemokine recognition in T cells results in integrin activation and T cell adhesion to endothelial cells. We recently reported that the integrin ligand ICAM1 is significantly upregulated in the LV endothelium of mice with HF, and that Icam1−/− mice have decreased LV T cell recruitment and HF. Additionally, we reported that Th1 cells, which highly express CXCR3, are major drivers of maladaptive cardiac remodeling. Thus, we hypothesized that chemokine signaling through CXCR3 regulates integrin dependent adhesion to ICAM1 and contributes to Th1 cell recruitment to the LV and HF. We used the mouse model of Transverse Aortic Constriction (TAC) to induce LV remodeling and HF in WT and CXCR3−/− mice, and in vitro adhesion studies to evaluate WT and CXCR3−/− Th1 cell chemokine‐mediated integrin‐dependent adhesion to ICAM1. WT mice expressed increased levels of CXCL9 and CXCL10 in the LV during the course of TAC. Activation of CD4+ T cells occurred in the mediastinal lymph nodes (mLN), which drain the heart, of both WT and CXCR3−/− mice; however T cell infiltration in the LV only occurred in WT but not CXCR3−/− mice, and heart infltrated T cells expressed high levels of CXCR3 and the ligand of ICAM‐1, LFA1. Moreover, CXCR3−/− TAC mice did not develop cardiac fibrosis, hypertrophy or inflammation and had preserved systolic and diastolic function as compared to WT TAC mice. Mechanistically, both CXCL9 and CXCL10 induced Th1 cell adhesion to ICAM1 under shear flow conditions in vitro in a CXCR3‐dependent manner. Our data support a CXCL9/CXCL10‐CXCR3‐ICAM1 axis regulating CD4+ T cell LV recruitment, and may represent a novel pathway potentially targetable in non‐ischemic HF.

Support or Funding Information

NIH R01 HL123658‐01, T32AI007077‐34

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Muscle‐specific regulation of right ventricular transcriptional responses to chronic hypoxia induced heart failure by the Muscle Ring Finger‐1 (MuRF1) ubiquitin ligase in vivo
Authors: Willis Monte S. , Oakley Robert H. , Parry Traci L. , Cidlowski John A. , Campen Matthew J.
Published: June 2021

Background

We recently identified a role for the muscle‐specific ubiquitin ligase MuRF1 (Muscle Ring Finger‐1) in right‐sided heart failure secondary to pulmonary hypertension induced by chronic hypoxia (CH). MuRF1−/− challenged to chronic hypoxia for three weeks were resistant to CH induced changes in right ventricle (RV) weight, ejection fraction, and volume (systolic and diastolic) and provided significantly increased perfusion to skeletal muscle. In contrast, MuRF1 Tg+ mice exhibited significant decreases in RV weight and ejection fraction indicative of a maladaptive dilated phenotype (heart failure), consistent with the significant decreases in skeletal muscle perfusion observed. The present study was undertaken to understand the underlying transcriptional alterations in the right ventricle of MuRF1−/− and MuRF1 Tg+ mice using microarray analysis.

Results

After three weeks of chronic hypoxia (15% O2) exposure, right ventricular total RNA was isolated, labeled, and hybridized to microarray chips. Microarray analysis of the MuRF1−/− right ventricle identified 37,095 defined genes with signals, with 590 found to be significantly different (p<0.01) from WT controls. Analysis of the 70 top differentially expressed genes (>2 fold or <−2 fold) revealed their function in 1) transcriptional regulation; and 2) oxidoreductase function. Analysis of these differentially expressed genes for common transcription factor promoter regions identified homeobox (HOX) D12 and HOXC13 transcription factors, along with RREB‐1. Microarray analysis of the MuRF1 Tg+ right ventricle identified 37,095 defined genes with signals, with 150 found to be significantly different (p<0.01) from WT controls. Analysis of the 46 top differentially expressed genes (>3 fold or <−3 fold) revealed their function in 1) oxidoreductase‐metabolic regulation, 2) glycoprotein‐transmembrane integral protein structure, and 3) alternative splicing / splice variants.

Conclusions

The differentially expressed genes in MuRF1−/− and MuRF1 Tg+ RV after CH exposure have common functional annotations related to oxidoreductase (including antioxidant) and transmembrane component functions. Moreover, the functionally‐enhanced MuRF1−/− hearts regulate genes related to transcription, homeobox proteins, and kinases/phosphorylation. These studies also reveal potential indirect effects MuRF1 may have with known substrates such as SFR and PPARalpha by regulating RREB‐1 and reveal for the first time mechanisms by which MuRF1 may transcriptionally regulate anti‐oxidant systems in the face of right heart failure.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Feeding in Marine Mammals: An Integration of Evolution and Ecology through Time
Authors: Berta Annalisa , Lanzetti Agnese
Published: June 2021

Marine mammals are a key component of aquatic ecosystems. Four major feeding strategies: suction, biting, filter feeding and grazing are identified in extant marine mammals (cetaceans, pinnipeds, sirenians, marine otters, and the polar bear) and associated with anatomical specializations of the head (e.g. rostrum, palate, temporomandibular joint, teeth/baleen, and mandible). Genetic and ontogenetic evidence of skull and tooth morphology provide the mechanisms that underlie patterns of feeding diversity. Based on a comprehensive diversity data set we provide an integrated analysis of the evolution of feeding, trophic structure and habitat (e.g. marine, riverine, estuarine) in fossil and extant marine mammals. We explore the origin and timing of particular feeding strategies over the last 50 million years. We find that the greatest diversity of pinnipedimorphs, cetaceans and extinct desmostylians occurred during the middle Miocene (11–15 million years ago, Ma). Sirenians reached their greatest diversity slightly earlier during the early Miocene (16–23 Ma). These historical data are used as a framework to inform the structure and trophic interactions of past, present and future marine ecosystems. We show that marine mammal generic diversity tracks diet with the greatest diversity of carnivores and herbivores in the middle Miocene. The drivers of diet and feeding patterns are both environmental (e.g. sea level fluctuations, climate change) and biotic (e.g. anatomical specializations, competition, predator‐prey) changes. The influence of these different processes on paleodiversity varies depending on taxonomic group, timing and geographic scale.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Therapeutic inhibition of RIP1 improves metabolic dysfunction and inhibits atherosclerosis in mouse models of cardiometabolic diseases
Authors: Karunakaran Denuja , Nguyen My Anh , Geoffrion Michele , Lister Zachary , Kandiah Joshua , Wyatt Hailey , Mompeon Ana , deKemp Ella , Lee Richard , Rayner Katey
Published: June 2021

Introduction

Chronic activation of the innate immune system drives inflammation and contributes directly to obesity, insulin resistance and atherosclerosis. Previously we showed that necroptosis, a pro‐inflammatory form of programmed cell death, is activated in the vessel wall and drives atherosclerosis via activation of RIP3 and MLKL. We sought to determine upstream genetic regulators of necroptosis in atherosclerosis and metabolic disease, and hypothesized that gene expression of RIP1, a key regulatory kinase upstream of NFkB activation, apoptosis and necroptosis, drives macrophage inflammation in cardiometabolic diseases.

Methods

RIP1 anti‐sense oligonucleotides (ASOs, 2 unique sequences) were used to reduce RIP1 expression in 2 mouse models: i) atherosclerotic model [ApoE−/− mice fed a western diet for 8wks] and ii) diet‐induced obesity (DIO) model [C57Bl/6 male mice fed a high fat diet for 24 wks]. Mice were given weekly injections of RIP1 ASOs (50 or 100mg/kg) or control ASO (non‐targeting).

Results

RIP1 ASO treated ApoE−/− mice had a marked reduction in aortic sinus and en face lesion areas (47.2% or 58.8% decrease relative to control, p<0.01) and plasma inflammatory cytokines (IL‐1a, IL‐17A, p<0.05). RIP1 knockdown in macrophages decreased inflammatory gene expression (NFkB, TNFa, IL‐1a) and in vivo LPS‐induced NFkB activation. In obese mice, RIP1 ASOs strikingly decreased body weight (25% decrease versus control p<0.001) and total fat mass (50–65% decrease versus control, p<0.001). Further, insulin resistance was improved in RIP1 ASO treated mice (fasted blood glucose: 10.9mM in control versus 8.5±mM in RIP1 ASO, p<0.001; GTT and ITT both p<0.001). In humans, we identified 5 novel SNPs in strong linkage disequilibrium in or nearby RIP1 gene exon 5. Notably, in a cohort of >1,800 people, individuals carrying the minor allele of these RIP1 SNPs have a 75–89% increase in the risk of developing obesity (adjusted odds ratios: 1.75–1.89, p<10−5) and a significant increase in RIP1 mRNA expression in adipose tissue (eQTL association in METSIM cohort, p=10−23).

Conclusions

: We have identified RIP1 as central a driver of insulin resistance, obesity, and atherosclerosis and demonstrate the potential of RIP1 as a novel therapeutic target.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.