bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of bioorthogonal muramyl glycans that illuminate and track bacterial peptidoglycan
Authors: DeMeester Kristen E. , Liang Hai , Jones Zachary , Taylor Jenny A. , Siegrist M. Sloan , Salama Nina R. , Leimkuhler‐Grimes Catherine L.
Published: June 2021

The bacterial cell wall is composed of a thick, web‐like polymer known as peptidoglycan (PG). This structure is critical for bacterial survival, as it protects the cell from changes in osmotic pressure and environmental insults. PG structures are essential for complex chemical and biological processes related to human health, as antibiotics are designed to target its destruction while the innate immune system responds to small molecules teased out of the PG network. While the overall chemical composition of PG is conserved throughout all species of bacteria, specifically peptides and two carbohydrate units N‐acetyl glucosamine (NAG) and N‐acetyl muramic acid (NAM), the glycan immunoactivating molecular calling cards derived from this polymer vary among pathogenic and commensal strains of bacteria. Immune misrecognition of these PG fragments can lead to the development of inflammatory bowel diseases. Information regarding the biological identity and the generation of these NAM‐containing fragments, either via host or pathogen machinery, and the cellular location of these events is limited. We sought out to developed new tools that may be used to uncover NAM containing immunostimulatory PG molecules. We recently report methodology to synthetically and chemoenzymatically access bioorthogonal NAM PG building blocks, which were then metabolically incorporated into the PG and subsequently labeled via in both gram positive and negative bacterial cells. We are currently expanding this methodology into both pathogenic and commensal strains of bacteria and utilizing the bioorthogonal handle to install fluorescent affinity tags to track and identify innate immune processing of NAM containing PG derivatives produced by these bacteria both in the presence and absence of macrophages. This work summarizes efforts toward illuminating host‐microbial molecular space by taking a multidisciplinary organic and chemical biology approach to access bioorthogonal NAMs and utilizing these substrates to metabolically label commensal and pathogenic bacterial PG in whole to fluorescently track innate immune processing of NAM containing PG derivatives produced by bacteria in the microbiome.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of HMGB1 in Hepatocytes by MyD88 and Type‐I interferon (IFN‐I) During Ehrlichia‐induced acute liver injury.
Authors: Kader Muhamuda , Scott Melanie , Yates Cecelia , Ismail Nahed
Published: June 2021

Background

Liver is the major target organ in Human Monocytic ehrlichiosis (HME), an undifferentiated febrile illness that is life‐threatening and caused by intracellular bacterial pathogen, Ehrlichia, that target liver and infect macrophages, hepatocytes and endothelial cells. Severe Hepatic inflammation is the common cause of acute liver injury following systemic infection with Ehrlichia. Our previous studies have shown that Myeloid differentiation primary response gene 88 (MYD88) and type I IFN (IFN‐I) promotes excessive inflammation and liver damage following fatal Ehrlichia infection. In this study, we explored the role of the MyD88 and IFN‐I in liver inflammation.

Results

In this study, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein and damage‐associated molecular patterns (DAMPs), plays a role in the regulation of innate responses and autophagy during Ehrlichia infection. Wild‐type (WT) mice infected with virulent Ehrlichia develop sepsis and liver injury marked by excessive systemic production of pro‐inflammatory cytokines and chemokines as well as HMGB1. To determine the cellular source of HMGB1 and regulatory mechanisms, we infected hepatocytes (HC) from WT and MYD88−/− knockout mice with virulent Ehrlichia. To mimic paracrine effect of IFN‐I cytokines produced by immune cells on HC response to Ehrlichia infection, we cultured infected HC in the presence or absence of IFN‐β (100 IU/mL). Our data indicate that in‐vitro infected HC produces low levels of IFN‐beta compared to uninfected cells. Exogenous stimulation of infected HC with IFN‐β induced elevated expression and cytoplasmic translocation of HMGB1 in WT‐HC. This was associated with increased autophagy and higher expression of IL‐23R, IFNAR, and heightened JAK/STAT signaling. Importantly, the effect of high dose IFN‐I on autophagy and HMGB1 was MYD88‐dependent. Interestingly, infection of MYD88−/− HC with Ehrlichia, in the absence of exogenous IFN‐β, enhanced autophagy induction and cytosolic translocation of HMGB1, suggesting that MYD88 negatively regulate HMGB1 and autophagy in HC in the absence of the paracrine effect of IFN‐β.

Conclusion

Together, our data suggest that autophagy regulation and HMGB1 response in hepatocytes during Ehrlichia‐induced sepsis is controlled by the strength of IFN‐I signaling and dependent on interplay between MYD88 and IFN‐I pathways.

Support or Funding Information

This work was supported by grants from NIAMS, NIGMD, and NIAID (AR68317 CCY, RO1‐GM102146 MS, and R56A1097679 NI)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A discovery platform to identify novel beneficial bacteria
Authors: Darby Trevor , Owens Joshua , Saeedi Bejan , Luo Liping , Robinson Brian , Jones Rheinallt
Published: June 2021

The use of beneficial bacteria known as ‘probiotics' to promote health is widely practiced. However, experimental evidence corroborating the efficacy of many bacteria promoted with such claims remains limited. We directly address this gap by establishing a discovery platform to identify novel beneficial bacteria that dampen intestinal inflammation and limit tissue damage. We employed the Drosophila animal model to assess the capacity candidate beneficial bacteria to defend the fly gut from induced oxidative damage. From this screen, we identified a number of novel bacteria that elicited potent cytoprotective activity in the gut. In addition, using the murine model, we also demonstrate that the same strains confers powerful anti‐inflammatory activity in a gut colitis model, and cytoprotective influences against radiological damage. Importantly, the beneficial activities of these strains in the murine intestine were substantially stronger in comparison to other currently marketed beneficial bacteria. In summary, we demonstrate that capacity of beneficial bacteria to elicit potent anti‐inflammatory and cytoprotective properties in the gut, and propose that newly discovered probiotic strains of bacteria may be used as a therapeutic interventions to promote intestinal health.

Support or Funding Information

NIH Grants R01DK098391

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Picosecond Active‐Site Dynamics Correlate with the Temperature Dependence of KIEs in Enzyme‐Catalyzed Hydride Transfer
Authors: Cheatum Christopher M.
Published: June 2021

Picosecond time scale motions in enzymes have often been invoked to explain the temperature dependence of primary kinetic isotope effects (KIE) in enzyme‐catalyzed hydride transfer reactions, but these experiments come short of actually measuring the dynamics in these systems on timescales relevant to the making and breaking of bonds. Similar to other enzymes, wild‐type Formate dehydrogenase (FDH) from Candida boidinii exhibits a temperature independent KIE that becomes temperature dependent when space is opened up in the active site via mutation of the V123 residue to alanine and glycine. Transition state analog complexes of FDH bound to azide offer a unique opportunity to investigate how these mutations influence active site dynamics. With a combination of 2D IR spectroscopy, X‐ray crystallography, and molecular dynamic simulations, we report a comprehensive view of fast motions of the active site and their relationship to the hydride transfer. Azide bound to FDH exhibits oscillatory frequency fluctuations on the ps timescale, and the amplitude of these fluctuations increases when the active site space increases in correlation with the temperature dependence of the KIE. Both the kinetic and dynamic phenomena can be modeled computationally. These results provide the first means of directly connecting temperature dependence of KIE's to dynamic motion in the active site in an enzyme‐catalyzed reaction.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identifying the Cause of Young Women Diagnosed with Locally Advanced Cervical Cancer Despite Routine Screening
Authors: Jewlal Elizabeth , D'Souza David , Shaddick Heather , Patel Nikhilesh , Leung Eric , Sugimoto Akira , McGee Jacob , Prefontaine Michael
Published: June 2021

Background

Screening programs for cervical cancer in developed countries have led to a marked reduction in mortality given their ability to detect early stage disease. Despite this success, there remains a concerning number of women compliant with regular screening that are diagnosed with advanced disease – a particularly devastating diagnosis for young women given the sexual and reproductive consequences. To explore the reasons behind this shortcoming, the present study sought to identify diagnostic commonalities amongst young women compliant with screening who presented to a tertiary cancer hospital with locally advanced cervical cancer (LACC).

Methods

A review of all women (age<50) with LACC receiving definitive chemoradiation between Sept/10‐Dec/12 at our institution was performed to identify those with a routine Pap test done ≤2y prior to diagnosis. Eligible women were offered semi‐structured, face‐to‐face interviews focusing on 4 areas: presenting symptoms, experience with the health care system, feelings after diagnosis, and perception of their future. Interviews were audiotaped, transcribed and a constant comparison analysis was performed to identify key themes. Thirteen out of 38 women (34%) with LACC were compliant with screening prior to diagnosis and met the other study criteria (median age: 38 (27–49)). All had a normal Pap, except one, completed 11 months prior to diagnosis. Ten consented to participate in an interview.

Results

Several key themes were identified: a lack of understanding about the symptoms/diagnosis of cervical cancer and a belief that LACC does not occur in those compliant with screening, reluctance from health care providers to perform pelvic examinations, the emotional burden of diagnosis on both the patient and their families and lessons learned with a different outlook for the future.

Conclusions

There is a need to educate physicians and the public about cervical cancer, even where screening is available. Delay in diagnosis has detrimental effects on quality of life and likely prognosis.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Design and Development of a Lumbar Puncture Simulation Model
Authors: Kamala Lakshmi , Zhang Sarah , Farias Anna , Kalajdzic Besim , Khayat Andre , Schuelke‐Leech Beth‐Anne , Urbanic Jill
Published: June 2021

Traditionally, medical trainees have been taught how to perform clinical skills on patients, moving directly from observation of senior physicians to carrying out the procedure themselves. In recent years, there has been a shift in medical education towards including simulation‐based teaching methods, which has been associated with reduced learner discomfort and improved patient outcomes. Simulation models are currently used to train medical students on lumbar punctures. The aim of this project is to improve upon existing models by creating a lumbar puncture simulation model with flexibility in the spine, with anatomically accurate physical measurements and mechanical properties, where required. Clinicians were interviewed to gather input on the initial design of the model, and will be interviewed again after testing the prototype to obtain feedback on how to further modify the model for increased clinical accuracy. A parametric CAD model was based on anatomic data collected by cadaveric experiments and measurements obtained from a literature search of imaging, cadaveric and in vivo studies. We will discuss the current prototype of the lumbar puncture model and the mechanical properties, physical measurements and clinician input incorporated in the design. Improved anatomic accuracy of the finalized model will allow trainees to translate their lumbar puncture skills more readily from practicing on the simulation model to performing on patients, leading to increased patient safety.

Support or Funding Information

Schulich ‐ UWindsor Opportunities for Research Excellence Program (SWORP)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
INNOVATION IN FUNCTIONAL ANATOMY EDUCATION: The Anatomy Lesson of Dr Tulp from the past to the Present
Authors: Tulp Orien L. , Ortiz‐Bustillo Manuel LEE , Einstein George P. , Sainvil Frantz , Konyk Carla M. , Branly Rolando L. , Brown Tony L.
Published: June 2021

In recent decades, there have been many technological innovations and improvement in the pedagogy of medical education. We have applied some of these developments to one of the most important and most fundamental elements in modern medical education, while combining traditional and innovative approaches. Gross anatomy is a core course for first year medical and some graduate students from the beginnings of time, since Nicholaes Tulp was first depicted by Rembrandt in the now classic painting “The Anatomy Lesson of Dr Tulp”. In the now famous Rembrandt, Dr Tulp is shown dissecting an unembalmed cadaver, while paid onlookers viewed the dissection of the cadaver with great interest. At USAT, the anatomy dissection begins with didactic lectures, much along the traditional lines, but with the exception that the discussion is orientated toward a clinical setting for each phase of the lectures. This is followed by lectures in Organ Systems Pathophysiology, Medical Biophysics, and finally by Introduction to the dissection laboratory. All dissections utilize fresh, unembalmed cadavers, all safety tested for hazards or pre‐existing infectious diseases before the start of the dissection, which takes place in a state of the art facility. Prior to the dissection, important sensitivity instruction is given, including acceptable respect, appropriate laboratory and clinical attire [scrubs, surgical gowns, and all needed instruments are provided each student], proper and expected personal demeanor during the dissection. During the dissections, which last for several days on each cadaver, key surgical and medical procedures that are likely to be needed during PGY‐I are demonstrated on each cadaver, including insertion of chest tubes, spinal taps, Intubation, topical and cosmetic suturing, endoscopy, 3‐D imaging, surgical technique, and others. The culmination of the dissection ends with each student being able to demonstrate the above procedures to standard, and with a complete functional dissection of the cadaver. At the conclusion of the lab body parts are recon our curricukum.nected and prepared for disposal and the ashes returned to the family that donated the cadaver. As an outcome, USAT anatomy lab has become one of the most sought after courses in the first year curriculum, with many student requesting to retake it multiple more times.

Support or Funding Information

Supported by Institutional Resources of the College of Medicine, USAT Montserrat

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Value of Traditional Lecture in Medical Gross Anatomy
Authors: Klender Sara Marie , Notebaert Andrew
Published: June 2021

Traditional lecture is continuously used in the medical school curricula as it is viewed by some to be the most efficient way to convey vast amounts of material to large groups of students. However, due to the rapid pace of traditional lecture and the constraints of working memory, it is extremely unlikely that most of the information presented in a given lecture is processed by the student in any meaningful capacity. Previous studies have revealed that despite these limitations, students continue to prefer lectures and teachers continue to use them as their primary teaching method. To investigate the value of traditional lecture both from a knowledge retention standpoint and the students' perception of the lecture, a survey of medical gross anatomy students (n=50) was conducted during a standard gross anatomy lecture on the spinal nerve. Immediately following the lecture, a survey was given to the students that asked about their perceptions of traditional lecture by having them rate on a scale of 1–10 (1 being low and 10 being high) how much they felt they learned in lecture, how much lecture guides their studying, and how important it is to attend lecture. In addition to the survey, students were given a short five question quiz to assess their immediate recall of the material that was covered. The results of the post‐lecture quiz were then compared to performance on questions covering the exact same topic on the unit exam. Four of the five questions on the unit exam were identical to questions on the post‐lecture quiz. One question was changed, but still covered content from the spinal nerve lecture. The results of the survey indicated that the students perceived a relatively low level of learning during lecture (m=4.84 ± 1.7 out of a possible 10), but placed a slightly higher value on using lectures to guide studying (m=6.18 ± 2.3 out of 10) and the importance of attending lecture (m=5.96 ± 2.3 out of 10). There was a significant difference in scores on the post‐lecture assessment (m=2.36 ± 1.5 out of a possible 5) and the unit exam (m=4.47 ± 0.9 out of 5); t(46)=−9.3, p < 0.001. This study demonstrates that students see some value in traditional lecture, but maybe less than previous studies have shown. Students' immediate recall after the given lecture was poor, however, performance on the unit exam was high for similar questions. This indicates that the bulk of content learning for exam preparation was done outside of class. These findings provide more evidence that instructors should design lectures that allow for the processing of information during lecture to avoid overloading working memory and potentially increase the perception of value in the lecture experience. This can be achieved by using activities that check for understanding, such as think‐pair‐share, and providing an opportunity for students to work with content immediately after delivery.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparison of traditional and gamified student response systems: does more fun come at a cost?
Authors: Shaffer Justin Franklin , Yabuno Kristen , Luong Ethan
Published: June 2021

Student response systems (often called “clickers”) are typically used in college and medical courses as a form of active learning to increase engagement and promote learning. Recent modifications to student response systems include “gamification” where game‐like elements (such as competitions, earning points for speed, winning medals, etc) are added with the goal of further increasing participation, engagement, and excitement in the classroom. However, little is known about the relative impacts of traditional student response systems compared to those of gamified systems when both are used in the same course. The goal of this study was to compare student performance with and perceptions of a traditional student response system (iClicker) and a gamified version (Kahoot!) that were both used in the same course. Our hypotheses were that student performance from iClickers would be more predictive of exam performance than Kahoot!, but that students would perceive Kahoot! as being more fun and engaging than iClickers. Students from two sections of a large enrollment undergraduate human anatomy course (n = 254) answered in‐class iClicker questions for participation credit and voluntarily answered in‐class Kahoot! questions for no credit. Students also completed end‐of‐course surveys rating their perceptions of both systems. Multiple linear regression models were used to analyze exam performance as a function of student performance on iClicker questions and Kahoot! questions (while controlling for student demographics). The models showed that both iClicker performance and Kahoot! performance were significantly positively correlated with exam performance with nearly identical effect sizes. Additionally, student survey data showed that over 80% of students rated both systems as being both fun and effective ways to learn. However, while >95% of students reported that while iClickers should be used in every day of class, approximately 66% of students reported that Kahoot! should only be played once a week. These results suggest that student performance with traditional and gamified student response systems may be similarly correlated with exam performance but that gamified systems may need to be used more sparingly than traditional systems in order to maintain high levels of engagement.

Support or Funding Information

Funding provided by the UC Irvine Office of the Vice Provost for Teaching and Learning

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of Thoracolumbar Fascia in Planar Spread of Quadratus Lumborum Blocks
Authors: Van Nuland Sonya E. , Langley Natalie R. , Shetty Shreya , Weidner Tiffany , Hangge Patrick , Patel Naresh P. , Young‐Fadok Tonia M.
Published: June 2021

Injections of local anesthetic in the fascial planes around the quadratus lumborum muscle (QL blocks) are performed for postoperative pain control after abdominal surgeries. Multiple approaches of injecting anesthetic in and around the QL have been reported (anterior, posterior, transmuscular, intramuscular and lateral QL blocks). These techniques vary in terms of ease of administration and extent of analgesia. The extent of the anesthetic spread from this ultrasound‐guided procedure is influenced by the fascial layers surrounding the QL. A limited number of studies on small samples using varying amounts of anesthetic have left open questions regarding the extent of spread of local anesthetic and the best approach. This study evaluates the local anesthetic spread of two ultrasound‐guided lateral QL block approaches that have proven effective in controlling postoperative pain. A methylene blue‐dyed saline solution (40mL per QL block) is injected into fresh frozen cadavers (n=10). With the patient in supine position, the needle tip is placed at either (1) the anterolateral border of the QL deep to the transversalis fascia or (2) anterior to the transversus abdominus muscle superficial to its aponeurosis. Anatomic dissection of the injection plane is then performed to determine the extent of spread of the dyed saline. We hypothesize that the continuity between the transversalis fascia and the anterior layer of the thoracolumbar fascia (anterior to the QL) facilitates the cranial spread of the anesthetic under the lateral arcuate ligament to the endothoracic fascia. This would explain our observed analgesic effect past the umbilical region to dermatomes in the epigastric region (T7–T8). Understanding how QL fascial planes facilitate anesthetic spread will enable intraoperative administration of these blocks to be tailored to specific procedures and facilitate post‐operative recovery after abdominal operations. Improved methods of intraoperative pain management may reduce post‐operative opioid use and support the medical community in addressing the opioid epidemic in the United States.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TGF‐β suppresses inflammation through the repression of interleukin‐33 (IL‐33)
Authors: Gerace Marnae M. , Den Haese Jason P. , Bakin Andrei V. , Gervasi Megan E.
Published: June 2021

Transforming growth factor‐β1 (TGF‐β1) is a member of the TGF‐β superfamily of cytokines, which are involved in a wide variety of biological functions such as proliferation, differentiation, migration, and apoptosis. TGF‐β1 binds to a receptor complex and stimulates a set of signaling events leading to changes in gene expression and cell behavior. TGF‐β1 specifically has been shown to be a key player in wound repair and modulation of the immune response. Microarray analysis of normal mouse mammary epithelial cells (NMuMG) treated with TGF‐β1, indicated that the interleukin‐1 family member interleukin‐33 (IL‐33) is repressed by TGF‐β1. IL‐33 is passively released following tissue damage and functions as an alarmin, alerting the immune system to the presence of tissue damage. The goal of this study was to determine if TGF‐β1 decreased the amount of IL‐33 passively released by cells following tissue damage. We utilized previously established methods of inducing passive release of IL‐33 in cell culture. Pretreatment of cells with TGF‐β1 resulted in significantly lower levels of released IL‐33 following induction of tissue damage.

These studies may identify a novel therapeutic target for treatment of diseases such as psoriasis, asthma and Crohn's disease. All of these diseases are associated with elevated levels of IL‐33 as well as altered TGF‐β responses. Further investigation of the immune cells affected by repression of IL‐33 could provide information into the specific mechanism of action.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective effect of silybin against verapamil‐induced hepatotoxicity in rats
Authors: Hassan Sherif , Rizk Ayman , Motawie Ahmed G. , Abdelfattah Shereen M. , Ramaraj Pandurangan
Published: June 2021

Background

Verapamil (VPA) is considered one of the anticonvulsant and mood‐stabilizing drug used for treating seizures and epilepsy. Several mechanisms have been suggested for VPA hepatotoxicity most of them are associated with oxidative stress. Silybin (silymarin) is a flavonoid known for its anti‐inflammatory, antioxidant properties. It may be possible to use silybin to protect against VPA‐induced hepatotoxicity.

Aim of study

The aim was to study the protective effect of silybin against VPA‐induced hepatotoxicity in rats.

Methods

40 rats were equally divided into 4 equal groups of 10 rats: Group I: (Control), Group II (sham), Group III (VPA), and Group IV (silybin+VPA). Liver sections were subjected to histological and immunohistochemical study. Blood samples were taken to test for liver enzymes. Histomorphometric and statistical analysis were performed.

Results

Liver sections of Group III showed focal areas of degenerated hepatocytes and dilated congested central veins. The hepatocytes revealed small vacuoles, pyknotic nuclei and marked inflammatory cellular infiltrations. There were dilation and congestion of the hepatic sinusoids. The hepatocytes revealed weak PAS reaction and strong Caspase 3 immunostaining. There were marked increase in the liver enzymes including alkaline phosphatase (ALP), aspartate amino transferase (AST) and alanine amino transferase (ALT). Group IV showed remarkable improvement and preservation of the hepatic architecture apart from mild pathological changes. Most hepatocytes were apparently normal. Strong positive PAS reaction and scanty weak Caspase 3 immunostaining were noticed. The liver enzymes were within normal as compared with the control group. The data were analyzed using SPSS and were described as mean ± standard deviation (SD). Then statistical comparison was performed using one‐way analysis of variance. Differences between mean values were assessed using a t test. A P<.05 was considered statistically significant.

Conclusion

Silybin could protect against verapamil‐induced hepatotoxicity in rats.

Support or Funding Information

This study is self‐funded

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Facial Distances and Possible Risk of High Blood Pressure: The Analyses of Young and Middle‐ Aged Adult Populations of Northern Nigeria
Authors: Taura Magaji Garba , Adamu Lawan Hassan
Published: June 2021

The objectives of the study were to determine the relationship between the facial distances and blood pressure across different age groups of young adults and middle‐aged population in males and females of northern Nigeria. Secondly, to determine the best facial predictors and discriminators of the blood pressure in the study population. Participants included 397 males and 159 females of northern of Nigeria with mean age of 25.37± 7.78 years. The facial distances were measured using direct anthropometry and blood pressure was determined using standard protocols. Pearson's correlation, step–wise multiple linear regression and receiver operating characteristic curve were employed to analyze the data. Measurements of blood pressure were in mmHg, age in years, bmi in kg/m2 and the remaining facial distances in mm. It was observed that no significant correlation between the facial distances and blood pressure (BP) in younger adult males and females except for lower facial height (LFH) and diastolic BP in males. Above the age of 30 years, significant correlation was noticed between the right ear width (EW), left EW, head length (HL) with both systolic and diastolic BP. The nasal length (NL) and nasal width (NW) correlated significantly with systolic and diastolic BP respectively in males only. For females, bizygomatic distance (BD) correlated only with systolic BP. The best predictors of systolic BP were left EW and HL in males and females respectively, while the best predictors of diastolic BP were left EW and right EW in males and females respectively. LFH was found to predict only the systolic blood pressure component in younger male adults. The best discriminating potential of facial distances with regard to abnormal blood pressure was only observed in the middle‐aged population. In both sexes right EW and left EW had more than 80% discriminating ability of abnormal BP (area under curve > 0.80). However, head width (HW) and HL had more than 80% discriminating ability of abnormal BP in males and females respectively. In conclusion, a significant correlation was observed between the facial distances and BP in middle‐ aged adult population. The facial soft tissue gave best predictors and discriminator in both sexes.

Support or Funding Information

None

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A complex scalenus muscle variant: Case report
Authors: Miller Joseph M. A. , Trelease Robert B.
Published: June 2021

During dissection in a first year dental gross anatomy laboratory, we identified an unusual, complex muscle variant in the left posterior triangle of an 87 year‐old, Caucasian female cadaver. This consisted of the left anterior scalene divided longitudinally into two approximately equal ‘heads', superficial and deep, with the fifth and sixth cervical nerve roots passing between them, along with a small but substantial muscle bundle passing between and attaching to portions of the anterior and middle scalene muscles. This extra muscle bundle passed antero‐medially from the middle of the anterior surface of the middle scalene, to attach inferiorly on the superficial aspect of the deep head of the anterior scalene. This ‘bridging’ muscle also passed anterior to and in contact with the middle trunk (C7) of the brachial plexus. The left subclavian artery was observed to pass as expected between the anterior scalene (both superficial and deep heads) and middle scalene insertions. Scalene muscle anatomy and neurovascular relationships on the right side were observed to be normal. Amidst the numerous reports of morphological variations in scalene muscles, particularly in association with the clinical anatomy of thoracic outlet syndrome, myofascial pain, and upper brachial plexopathies, we were unable to find any accounts of a similar complex scalene muscle variant. Most certainly, our specimen did not fit the accepted morphological descriptions of ‘scalenus anticus', scalenus minimus, or Sibson's muscle variants. Although we had no available clinical records, the muscular variations we described were arranged in configurations that other investigators have recognized as contributing to compression of brachial plexus roots associated with thoracic outlet syndrome.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TOPOGRAPHICAL ANATOMY OF THE ULNAR NERVE AND ITS MUSCULAR BRANCHES RELATED TO SURFACE LANDMARK
Authors: Galdeano Denival Soares , Cricenti Vicente S.
Published: June 2021

Understanding of the anatomy of the ulnar nerve and its branches is vital to the treatment of cubital tunnel syndrome, tennis elbow, ulnar neuropathy, nerve transfer in the surgical management of compression at the elbow, tennis elbow or the restoration of upper extremity function. In the search to add details and pertinent information and ulnar nerve in the region of the forearm, we carry out this work. We have dissected 30 upper extremities from adult cadavers to locate the course of the ulnar nerve and the origins and insertions of the branches of the ulnar nerve using elbow joint like surface landmark. In average, 2.7 (max. 4) branches left the ulnar nerve to Flexor Carpi Ulnaris. 60.24% arose the nerve above elbow joint (AEJ) (−59.21mm above), 30.12% origins in the Proximal Upper Third (PUT) of forearm, 4.82% origin in Distal Upper Third (DUT) and 4.82% in the Proximal Middle Third (PMT), being the most distal origin 100.90 mm below the elbow joint. These branches reach the muscle belly in average in 6 points (max 15). The most proximal penetrated AEJ in 8.29% (−15.31 mm above), 56.91% in PUT, 19.89 % in DUT, 12.7 % in PMT and 2.21% in DMT with the most distal to 132.25 mm below the elbow joint. To Flexor Digitorum Profundus, in average 1.17 (max. 2) branches left the ulnar nerve to muscle. 31.42% left the nerve AEJ (−18.31 mm above), 65.71% in the PUT and 2.87% in DUT, being the most distal origin in 39.13 mm below the elbow joint. These branches penetrated in the muscle belly in average in 3.1 points (max 5). The most proximal penetrated in 52.69% in PUT (4.86 mm), 45.16 % in DUT and 2.15 % in PMT with the most distal 84.09 mm below the elbow joint. In this study we found 5(five) Martin‐Gruber Anastomosis. Using these data, the course of the branches of the ulnar nerve can be estimated by observing the surface of the elbow joint.

Support or Funding Information

none

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Associations Between External Forearm Dimensions and Internal Ulnar Nerve Spaces at the Elbow
Authors: Kanwar Kiran , Khan Mustafa Tamim Alam , Khan Tasrif Alam , Khan Mahwish Iqbal , Lovely Rehana Sultana
Published: June 2021

Ulnar nerve injury is frequently seen in athletes such as golfers, baseball pitchers, tennis players and weightlifters, typically in the epicondylar groove or cubital tunnel areas, where it may be subjected to compression, traction and friction during certain rapid sports movements. A relationship between the dimensions of some visually easy‐to‐discern external structures of the forearm, and selected internal elbow structures that the ulnar nerve passes through, might help to predict which sportspersons may be at greater risk for ulnar nerve entrapment, with smaller spaces expected to involve greater risk. Two conspicuous external features are the distance between the olecranon of the ulna (OL) and the medial epicondyle of the humerus (ME); and forearm length measured from the ME to the pisiform carpal bone (PI). It was hypothesized that a positive correlation would exist between either one, or both of, OL‐ME (medial forearm width) and ME‐PI (forearm length); and some or all of: ulnar nerve thickness, inner epicondylar space, OL‐ME line to Osborne ligament, and OL‐ME line to the point of entry of the ulnar nerve into the flexor carpi ulnaris muscle, between its humeral and ulnar heads. Twenty cadavers, ten male and ten female (40 forearms) were measured for the above dimensions, using digital calipers and tape. Forearms were maintained at 30° flexion (measured with a digital goniometer). The most prominent part of the crest of each of ME, OL and PI was used, and the average of three measurements was taken for each variable. A Spearman's correlation (SPSS ver. 24), used for non‐normally distributed data, showed that the inner width of the epicondylar groove was significantly related to the external OL to ME distance (r = .403, p = .01) and to the thickness of the ulnar nerve at the OL‐ME line (r = .32, p = .047). In addition, the distance between ME and PI was significantly correlated with the external OL to ME distance (r = .62, p < .001). It may be concluded that the distance between the OL and the ME, as well as the length of the forearm, might be good indicators of the likely internal space that the ulnar nerve is contained within at the OL‐ME line, as well as of the thickness of the ulnar nerve at that line.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Enhancer epigenomic regulation in differentiation, development and cancer
Authors: Ge Kai
Published: June 2021

Enhancers control cell type‐specific gene expression and are marked by H3K4me1. Active enhancers are further marked by H3K27ac. We previously identified CBP/p300 as major H3K27 acetyltransferases and MLL3/MLL4 as major enhancer H3K4me1 methyltransferases [1, 2]. We show that during differentiation of adipocytes, myocytes and ES cells, MLL3/MLL4 are required for enhancer activation, cell type‐specific gene expression, and cell differentiation [2, 3]. Further, we show that while enhancer‐priming by MLL3/MLL4 is dispensable for cell identity maintenance, it controls cell fate transition by orchestrating CBP/p300‐mediated enhancer activation. MLL4 protein, rather than MLL4‐mediated H3K4me1, controls p300 recruitment to enhancers [3, 4].

Our data suggest a model of sequential actions of epigenomic regulators on enhancers: 1) pioneer TFs and lineage‐determining TFs recruit MLL3/MLL4 to prime enhancer regions and label them with H3K4me1; 2) MLL3/MLL4 facilitate the binding of CBP/p300, which activate enhancers and label them with H3K27ac; 3) H3K27ac and acetylated TFs are recognized by the epigenomic reader Brd4, which recruits Mediator and RNA Pol II to establish enhancer‐promoter interactions and activate cell type‐specific genes (Nat Comm, in press).

MLL3/MLL4 are tumor suppressors frequently mutated in many types of cancers as well as developmental diseases. We show that MLL3/MLL4 are required for the development of adipose, muscle, mammary gland, B cells, T cells, and heart and that depletion of MLL3/MLL4 in mice promotes tumorigenesis [2, 5–9]. Our findings suggest that mutations in MLL3/MLL4 would lead to defects in enhancer activation, cell type‐specific gene expression and cell differentiation. Such a mechanism may contribute to the pathogenesis of these developmental diseases and cancers.

Support or Funding Information

This work was supported by the Intramural Research Program of the NIDDK, NIH.

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 a transcriptional regulation model governing a cis‐antisense small RNA in Vibrio cholerae
Authors: Zhang Mark Guangde , Wang Jessica J. , Lang Theodore , Liu Jane M.
Published: June 2021

Cholera disease, a gastrointestinal ailment caused by the Gram‐negative bacterium Vibrio cholerae, remains a global health burden affecting an estimated 3–5 million people annually. V. cholerae's capacity to persist in different environments stems from its adaptability to a variety of sugar sources, including the six‐carbon sugar alcohol mannitol. Produced by algae metabolism, mannitol is transported into V. cholerae through the mannitol transporter MtlA, whose production is downregulated at the post‐transcriptional level by the small RNA (sRNA) MtlS. Currently, little is known surrounding what governs the transcription of mtlS, other than that mtlS expression is equally robust in non‐mannitol sugars. We examined the hypothesis that mtlS expression is subject to transcriptional interference from the divergently transcribed mtlA. Because MtlS is a cis‐encoded sRNA transcribed directly antisense to mtlA, transcriptional activity from mtlA could pose a hindrance to mtlS transcription occurring in the opposite direction. To test this model, we grew V. cholerae in different sugar conditions and stimulated mtlA expression by knocking out mtlR (a transcriptional repressor of mtlA) or by adding exogenous mannitol. We then measured MtlS sRNA levels by northern blot analysis. Our results indicate a strict inverse relationship between mtlA expression and mtlS expression, whereby the degree to which mtlA expression increases correlates with the extent to which mtlS expression decreases. In glucose, knocking out mtlR restores MtlA levels to 30% of maximum expression (n=3, p<0.05) and decreases MtlS levels by 33% (n=2, p=0.1). In non‐mannitol, non‐glucose sugars such as mannose, knocking out mtlR restores MtlA levels to 50% of maximum expression (n=3, p<0.05) and decreases MtlS levels by nearly 95% (n=3, p<0.01). These findings support a transcriptional regulation model regarding cis‐antisense RNAs, known as the transcriptional interference model, for which there exist few characterized examples. Ultimately, this project has contributed to our understanding of how V. cholerae deploy sRNAs as an adaptive mechanism to buffer against environmental flux.

Support or Funding Information

NIH R15 AI090606

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Determining the Effects of N‐Terminal Acetylation on the Microtubule‐associated Protein Tau
Authors: Lally Anna , Holmes William
Published: June 2021

The microtubule‐associated protein tau is notably associated with neurodegenerative diseases such as Alzheimer's Disease and more recently the disease found in deceased NFL players, Chronic Traumatic Encephalopathy (CTE). Aggregation of the protein tau causes these diseases, which endogenously stabilizes microtubules in neurons. Tau is a target for the most common mammalian post‐translational modification (PTM), N‐terminal acetylation. This modification alters the structure of a protein by changing the positive N‐terminus to a neutral one by adding an acetyl functional group. Any alteration to the structure of a protein also affects the function, and the N‐terminus of tau has been implicated with aggregation rates. Since tau and N‐terminal acetylation have never been studied together before, the effects are unknown. Historically, tau has been efficiently expressed and purified out of Escherichia coli and studied in vitro, however, N‐terminal acetylation is a eukaryotic specific PTM, but occurs in a prokaryotic system when the catalytic acetyltransferase complex is co‐expressed with tau. This project determines the effects of N‐terminal acetylation on the microtubule‐associated protein tau by assessing the differences between acetylated and unacetylated tau. Expression, purification, and precipitation of tau with around 98% purity occurs by lysing and boiling samples. Various tests determine that tau is N‐terminally acetylated, estimated by SDS‐PAGE and Western blot, and confirmed by mass spectrometry and isoelectric gel electrophoresis. Furthermore, various environments can have an effect on aggregation, and exposing fibers made from the purified protein to different stressors can give insight into optimized aggregation conditions. Increased amounts of thioflavin T evaluates aggregation, an assay measured by florescent spectroscopy. Also, tubulin stability in the presence of acetylated and unacetylated tau can give insight into microtubule stability in the cell. The microtubule‐associated protein tau has been widely associated with neurodegenerative diseases because of its tendency to aggregate. Proteins aggregate because of their structure, so exploring structural and functional changes to tau is important to understanding why it aggregates. This system looks specifically at one post‐translational modification and how it affects the protein tau, and studying tau with the correct PTMs will give a more correct understanding of the protein, and by extension the neurodegenerative diseases it causes.

Support or Funding Information

RI‐INBRE

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