bluuebunny/crossref_metadata_2025 huggingface dataset:
A role for miR‐471 in cardiac ischemia‐reperfusion injury
Authors: Chun Byeong jo , Kidd Michael W. , Eguchi Akiko , Moreno Ana L. , Dowdy Steven F , Patel Piyush M. , Roth David M. , Patel Hemal H.
Published: June 2021

MicroRNAs (miRNAs) are involved in translational and transcriptional regulation of gene and protein expression. Specific miRNA patterns and targets have been identified for cardiac pathologies such as cardiac hypertrophy, angiogenesis, and heart failure. However, a role for miRNA in ischemia‐reperfusion injury is not clear. Preliminary miRNA array studies revealed a subset of miRNAs induced by ischemic preconditioning, with miR‐471 showing the largest fold‐change. We hypothesized that infusion of miR‐471 will induce cardiac protection. Pure, synthesized miR‐471 was conjugated to a peptide transduction domain‐dsRNA binding domain fusion protein (vehicle). The conjugated miR‐471 or vehicle alone was injected into a Langendorff‐perfused mouse heart model before the onset of global ischemia‐reperfusion. Left ventricular developed pressure (LVDP) was continuously measured. Our results show that miR‐471 significantly increased LVDP and rate of recovery of LVDP normalized to pre‐ischemia as compared to vehicle‐injected controls. Our data suggest that miR‐471 plays an important role in protection of the myocardium against ischemia‐reperfusion injury and may represent a novel therapeutic target.
High Fat Feeding inhibits the Hypothalamo‐Pituitary Gonadal (HPG) Axis and ovulation In Diet‐ Induced Obese Rats
Authors: Balasubramanian Priya , Jagannathan L.K. , Gilbreath E.T. , Subramanian M. , Mohankumar P.S. , Mohankumar S.M.J.
Published: June 2021

Obesity is known to interfere with HPG functions, but the mechanisms involved are not clear. We hypothesized that a high fat (HF) diet would affect norepinephrine (NE) levels in the hypothalamus to impact luteinizing hormone (LH) release and ovulation in obesity. To test this, adult female diet‐induced obese (DIO) and diet resistant (DR) rats were fed chow or HF diet for 6 wks. Estrous cyclicity was monitored and hourly blood samples were collected from 1000–1900h for LH measurement on the day of proestrous. Animals were sacrificed on proestrous and plasma was processed for estradiol and leptin concentrations. Ovarian sections were subjected to morphological analysis. The medial preoptic area (MPA) and suprachiasmatic nucleus (SCN) of the hypothalamus that regulate LH secretion, were analyzed for NE levels. Leptin levels increased while estradiol levels were significantly reduced in the HF‐fed DIO group. NE levels (Mean±SE; pg/μg of protein) in the SCN dropped significantly in DIO HF (14.8±1.8) vs. chow‐fed DR rats (26.1±3.7; p<0.05). LH surge levels (ng/ml) in DIO HF was significantly lower compared to DR chow group (0.82±0.2 vs. 8.4±3.5; p<0.05). Ovaries from DIO HF animals had degenerating cystic follicles and no corpora lutea indicating anovulation. These results indicate that HF feeding inhibits the HPG axis in DIO rats possibly by increasing leptin levels to decrease ovarian estradiol synthesis. This leads to reduced NE levels in the hypothalamus causing suppression of the LH surge and anovulation.
A SYSTEMATICALLY CONSTRUCTED CONCEPTUAL MODEL OF CHOLESTEROL METABOLISM
Authors: de Graaf Albert , van de Pas Niek CA , Soffers Ans EM , Woutersen Ruud A , van Ommen Ben , Rietjens Ivonne MC
Published: June 2021

Elevated plasma cholesterol is an important marker for cardiovascular disease risk. The plasma cholesterol concentration is the result of a complex set of interacting metabolic reactions in different organs. We aimed to develop a physiologically based kinetic (PBK) computational model that can be used for in vitro‐in vivo extrapolation, interspecies translation and for explaining and predicting the effect of cholesterol lowering therapies and diets. As a first step, we report on the systematic construction of a suitable conceptual model specifying the important cholesterol‐related processes that need to be included in such a PBK model. The model is based on key genes determining plasma cholesterol concentrations. These were obtained from published data on the plasma cholesterol concentrations of mouse knockout models included in the Mouse Genome Database. From the catalytic functions associated with these key genes, a conceptual model containing 20 reactions, 8 different pools and 4 body compartments was constructed. The new model is similar but definitely not identical to conceptual models published so far. After choosing simple but suitable reaction kinetics, first simulations indicate that a PBK cholesterol model based on this conceptual model can correctly predict whether a given gene knockout results in lowered or increased plasma cholesterol in the mouse.
Profiling across species for the identification of optimal animal models of dyslipidemia
Authors: Strack Alison M , Carballo‐Jane E , Mendoza V H , Gagen K , McNamara L , Gorski J , Eiermann G , Petrov A , Akiyama T , Kulick A , Donnelly M , Voronin G , Rosa R , Cumiskey A‐M , Bekkari K , Mitnaul L , Puig O , Koblan K S , Hubbard Brian K
Published: June 2021

In an attempt to understand the predictivity of various animal models for study of dyslipidemia, we analyzed lipid and metabolic profiles across 5 mouse strains, 6 other non‐primate species and 4 primates. Plasma fatty acid composition, lipoproteins and phospholipoproteins were examined through lipidomics and additional metabolic parameters. Given the importance of statins as therapeutics in humans, 2‐week responsiveness to simvastatin was assessed in each model. When examining the relative proportion of lipids contained within the 3 major lipid biosynthetic pathways, the species that most reflect humans are primates and hamsters. When absolute levels of cholesterol and other lipids are measured, most historical literature models for atherosclerosis and dyslipidemia (mouse and rabbit) fall out of the range of humans; primates, pig, dog, and hamster are the models that most resemble humans. Subsequent dendogram analyses of the 8 lipid classes measured demonstrated primates clustered together most closely to humans, followed by dog and hamster. Most non‐rodent species exhibited decreases in plasma cholesterol and other lipids in response to simvastatin. Overall, primates are the model that most reflects humans. For practical utility in routine studies, the data point to the hamster and dog as potential models for target validation and lead identification. Research supported by Merck Research Labs.
Effect of surgical isolation of pituitary from hypothalamic influences on corticotroph development in fetal sheep
Authors: Schwartz Jeff , Sandhu Mansur , Farrand Kirsten , Szarek Eva , McMillen Caroline , Houghton Daniel , Young Ross , Saleh Nurul‐Arina
Published: June 2021

During development, corticotrophs (ACTH‐secreting cells) undergo changes that alter the secretory products they release. In vivo, the ratio of plasma concentrations of ACTH to its biosynthetic precursors (which are ACTH antagonists at adrenals) increases over gestation, and the change is prevented by surgical hypothalamo‐pituitary disconnection (HPD). The present study aimed to determine whether the gestational changes observed in intact and HPD sheep fetuses are mirrored in changes in individual corticotrophs. Pituitaries were harvested from (1) adult sheep and fetuses at 110d gestation (2, term ~ 147d) or at 140d following sham (3) or HPD (4) surgery at 110d. Pituitary sections were simultaneously immunostained for full length POMC, the parent molecule of ACTH, and ACTH(1‐39). The fraction of pituitary cells containing only POMC decreased from 110d (8.8±1.45%) to adulthood (2.8±0.7%), with 140d sham pituitaries indistinguishable from adult, and 140d HPD indistinguishable from 110d. The fractions of cells containing only ACTH(1‐39) or ACTH+POMC were similar in all intact groups, but significantly higher in HPD pituitaries. These results suggest a linear progression over the final third of gestation into adulthood whereby more corticotrophs acquire the capacity to process POMC to ACTH(1‐39). This process is influenced in late gestation by signals from the hypothalamus.
Comparison of the effects of growth hormone on MAC‐T cells and primary mammary cells
Authors: McDonnell Lisa , Johnson Tasha , Peterson Daniel G
Published: June 2021

The ability of growth hormone (GH) to increase milk yield through somatomedins is well characterized, however recent studies utilizing mammary epithelial cell (MEC) lines have indicated a possible direct effect on MEC. In the mammary alveolar cell‐T (MAC‐T) line, relative abundance of mRNA for two milk protein genes, α‐lactalbumin and αS1‐casein, and GH receptor was increased by GH. MAC‐T cells were compared to bovine mammary tissue explants and primary MEC isolated from raw milk through culture in classical lactation medium (dexamethasone, insulin, prolactin) with 0 or 10 ng/mL GH. Explant and primary cell mRNA abundance showed a similar pattern to MAC‐T indicating that the effects observed in cell lines may be relevant in vivo. To begin to understand the nature of the effects of GH in MEC, global protein expression in MAC‐T cells was analyzed by 2‐D gel electrophoresis, finding the abundance of 40 proteins altered by inclusion of 10ng/mL GH. Proteins were identified using MALDI‐TOF with tandem MS and include enzymes involved in glycolysis, lipogenesis, protein processing and transport. Research funded by California State University Agricultural Research Initiative award #07‐3‐011.
The Changing Landscape of Medical Neuroscience Education: From Integrating Modules in the Brain to the Curriculum
Authors: Wong Donald
Published: June 2021

The explosive growth in the neurosciences has dictated divergent paths in graduate and medical education of the nervous system. Course design at many medical schools remains largely driven by departmental teaching missions to impart scientific knowledge and research advances. Yet, at schools with newly mandated integrated curriculums, modules have been developed requiring close partnership between basic and clinical faculty with shared responsibility in training medical students in both scientific and clinical knowledge. The departmental‐based neuroanatomy or neuroscience course, single or team‐taught primarily by basic scientists, will be examined for its multi‐disciplinary merit and limited clinical relevance. The organ‐ or theme‐based brain and behavior module that requires collaborative efforts of both basic scientists and clinicians will also be examined for its merit in integrating foundational knowledge directly with clerkship expectancies, as well as integrating vertically across the medical curriculum The organizational principles governing their design along syllabus content, learning environment (PBL, lecture, lab) position in curriculum, time allocation, educational resources, and assessment will be discussed. I will share the unique opportunity for comparison of different course designs across state‐wide regional campuses of the Indian University School of Medicine. Subsequent symposium speakers will showcase their integrated modules to provide direction and practical insights to those at the doorstep of mandated curriculum revision, or those seeking greater course integration through wider scope of faculty participation in preparation for the impending changes in standardized assessment.
Effective Strategies for Integration of Basic & Clinical Neuroscience: A Clerkship Director Leads the Charge!
Authors: Lynn Joanne
Published: June 2021

The Neural Science Block at The Ohio State University College of Medicine is a 12 week interdisciplinary module that integrates basic and clinical science material across multiple disciplines (anatomy, physiology, pharmacology, radiology, pathology, neurology, psychiatry, ophthalmology, ENT). Our preclinical neuroscience course spans the last nine weeks of the first year and the first three weeks of the second year. Challenges related to the positioning of a neuroscience course at the end of the first year will be discussed. A major purpose of the preclinical course is to prepare students with the prerequisite knowledge and skills to optimally learn from the clinical experiences of third year neurology and psychiatry clerkships as well as from neuropsychiatric patients seen in other clinical rotations. The general features of U.S. neurology clerkships as detailed by a Consortium of Neurology Clerkship Directors (CNCD) survey will be described with additional comments about combined neurology/psychiatry clerkships. The CNCD Neurology Clerkship Core Curriculum Guidelines will be reviewed to give familiarity with the objectives of the clerkship. Special attention will be given to basic science topics that should be emphasized in preclinical neuroscience courses as preparation for clerkships and optimally revisited during the clerkship because of relevance to core clinical topics.
Trenbolone (17B‐hydroxyestra‐4,9,11‐trien‐3‐one) protects against bone loss in gonadectomized male rodents
Authors: Yarrow Joshua F , Conover Christine , Lipinska Judyta , Santillana Cesar , Franz Sarah E. , Wronski Thomas J. , Borst Stephen E.
Published: June 2021

We evaluated the effects of trenbolone‐enanthate (TREN) administration on bone turnover and on trabecular bone mineral density (BMD) in order to test the hypothesis that neither the 5alpha reduction nor the aromatization of androgens is required for bone maintenance. 3 month old male Fisher SAS rats received SHAM surgery + vehicle (V), gonadectomy (GNX) + V, GNX + Low (L) TREN (1.0 mg/week), GNX + Moderate (M) TREN (3.5 mg/week), GNX + High (H) TREN (7.0 mg/week), or GNX + supraphysiological testosterone (T) (7.0 mg/week) for 28 days. GNX completely ablated serum T in all groups except GNX + T, where serum T was 18‐fold above SHAM (p < 0.05). Serum trenbolone increased dose‐dependently in response to the graded doses of TREN (L: 8.3 ± 0.5; M: 50.4 ± 3.2; H: 96.6 ± 7.5 ng/ml; p < 0.05). GNX increased serum C‐telopeptide by 13% and osteocalcin by 40% (p < 0.05), indicating high‐turnover osteopenia; while androgen administration prevented this phenomenon. GNX also reduced total and trabecular BMD at the femoral metaphysis by 12% and 15% compared with SHAM, respectively (p < 0.05); while androgen administration prevented this loss similarly across groups, ultimately resulting in 7–16% greater total and trabecular BMD than GNX (p < 0.05). Our results indicate that TREN prevents hypogonadism induced bone loss and suggest that the bone protective effects of androgens can occur independently of the 5alpha reductase and aromatase enzymes.
ALP Trends in Men and Women
Authors: Wilson Zechariah , Lau Cecilia , Caporaso Fred , Sumida Ken , Frisch Frank
Published: June 2021

Bone‐specific Alkaline phophatase (ALP)is found on the surface of osteoblasts and its levels reflect osteoblastic activity. The purpose of this study was to evaluate the concentrations of ALP in 81 men and women (n=20 and 61, respectively) and match these values to their duel x‐Ray absorptiometry (DEXA) findings. Subjects were identified in three age groups (20–50, 51–70 and >71 years of age for men and 18–40, 41–60 and > 60 years for women). ALP was measured in serum with a monoclonal antibody‐based immunoassay (Tandem®‐R Ostase®; Beckman Coulter). ALP values in men were highest in the youngest age category (14 mcg/L) and decreased to 12 mcg/L in the oldest (p<.098; ns). ALP values in women increased from 8 mcg/L in the youngest group to 12.2 mcg/L in the oldest group (p< .001) Our findings did not show a significant difference between the bone mineral density of our subjects. We did, however observe a inverse (and significant, p<.001) trend in the ALP, suggesting that the mechanisms of bone growth and loss may be gender specific.
Interaction of the effects between estrogen receptor‐alpha polymorphism and physical activity or nutrient on bone mass in Japanese young women
Authors: Kondo Hiroyo , Fujino Hidemi , Murakami Shinichiro , Takeda Isao , Ishihara Akihiko
Published: June 2021

Bone mass is strongly influenced by genetic and/or environmental factors. The estrogen receptor alpha (ESR1) is a good genetic candidate for a prime regulator of bone metabolism. The purpose of this study was to investigate the association between a PvuII or XbaI RFLP of the ESR1 polymorphisms and bone mass in Japanese young women, and the interaction with physical activity or nutrition as a lifestyle factor.

Seventy healthy women (20–23 yr) were genotyped for ESR1. Bone mass was measured by quantitative ultrasound measurement. The ESR1 polymorphisms at intron I (Pvu II and Xba I) were genotyped using the PCR‐RFLP.

Two major trends could be demonstrated for the ESR1 polymorphisms. Body weight, BMI and physical activity are significantly associated with bone mass in the subjects carrying CT heterozygote or TT homozygote (P<0.01). Furthermore, fish intake is significantly associated with bone mass in the subjects carrying AG heterozygote (P<0.01).

These results suggest that physical activity and/or calcium intake are more important for bone mass metabolism in young women carrying T allele or AG heterozygote in estrogen receptor alpha gene, respectively.

Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, No. 19700529.
ALP to PTH Ratio in Young and Old Females
Authors: Wilson Zechariah , Lau Cecilia , Caporaso Fred , Sumida Ken , Frisch Frank
Published: June 2021

For the purpose of establishing a clearer age‐related profile of bone health our aim was to evaluate the ratio of osteoblastic marker bone‐specific alkaline phosphatase (ALP) to circulating parathyroid hormone (PTH) concentrations in 119 healthy women in two age groups (16–46, and 47–70 years of age) who were not on bisphosphonates or other osteoporosis therapies. The ALP increases from 8.5 mcg/l in younger women to 11.3 mcg/l (p<.0008). The PTH values also significantly increased (28.1 to 37.4 pg/ml, respectively; p<.020). The ALP:PTH ratio is unchanged (.30) for the two age groups. Our data holds promise for identifying an age‐related profile that can be used to illuminate the metabolic status of bone.
Volatile Constituents of Zanthoxylum schinifolium and Effect on Osteoblastic MC3T3E1 Cells
Authors: Kim Gun Hee , Chang Kyung‐Mi , Choi Eun‐Mi
Published: June 2021

The volatile chemical constituents of Zanthoxylum schinifolium, an aromatic medicinal herbaceous plant, were separated by the steam distillation extraction method using a Clevenger‐type apparatus, and were analyzed by gas chromatography‐mass spectrometry (GC/MS). β‐Phellandrene (22.54%), citronellal (16.48%), and geranyl acetate (11.39%) were the predominantly abundant components of Z. schinifolium. The effects of the essential oil from Zanthoxylum schinifolium on the function of osteoblastic MC3T3‐E1 cells were tested. It increased the collagen and mineralization of osteoblasts (P<0.05), indicating that Zanthoxylum schinifolium may help prevent osteoporosis.
The Biology Scholars Program Research Residency
Authors: Krontiris‐Litowitz Johanna
Published: June 2021

A major challenge for faculty interested in biology education reform is determining how teaching methods improve student learning. Experimental design at the bench is familiar to most science faculty. However, these same faculty may be uncertain about designing an experiment to measure student learning. In response to this challenge, life sciences professional societies have established the Biology Scholars Program (BSP) to enhance biologists’ understanding and practice of evidenced‐based teaching and learning. The Program is a multiyear leadership program for life science faculty, which utilizes the virtual residency model, combining intensive, face‐to‐face, multi‐day training institutes with on‐going learning communities using electronic communication. During the program Biology Scholars are introduced to evidence‐based research in biology education, learn skills needed to create and design experiments to assess student learning, and participate in faculty community building activities. Program information will be presented at EB 2010 and applications for the 2011–2012 BSP are available at www.biologyscholars.org. FASEB member affiliates of the program include the American Physiological Society and the American Society for Biochemistry and Molecular Biology. The Program is managed by the American Society for Microbiology and is supported by a grant from the National Science Foundation.
Teaching socialization and graduate student preparation for the biomedical professoriate: divergent graduate student paths and perspectives of teaching during PhD training
Authors: Bunker Aaron , Clark Catharine
Published: June 2021

The socialization (SC) process of doctoral students for the professoriate (PF) ideally should reflect the career they aspire to enter. However university needs for research dollars often supersede graduate student educational demands. Higher educational research suggests rethinking of the academy's values and structural organization is needed to address the issue of insufficient departmental graduate student PF SC. Even so, many research intensive departments at major land grant universities do not require graduate students to teach, creating a gap in necessary training tools. To bridge this gap, graduates students become responsible for seeking out teaching opportunities, independent of their graduate program or department. Two different testimonies are presented here of biomedical graduate students’ self‐SC for the PF and illustrate a divergent track of choices and options that ultimately lead to a common goal of gaining valuable teaching experience. These testimonies expand on the variety of opportunities available (ranging from formal training in a Minor in College Teaching Program to practical experience gained from part‐time teaching at the university and at other surrounding private colleges), the experiences gained, and the lessons learned.
Application of a pedagogical method for using non‐scientific literature to increase interest in the content taught in an undergraduate animal physiology course
Authors: Daggett Melissa A. F.
Published: June 2021

Animal Physiology at Missouri Western State University is a 4 credit lecture/laboratory undergraduate biology course. In addition to fulfilling the physiology requirement for multiple B.S. degrees within the Biology department, this course is critical for postgraduate work in several fields. Because the range of students taking the course varies from Wildlife Conservation and Management majors to those applying to professional health programs, the level of rigor and the presentation of selected materials for students to find both academically useful and personally interesting, can be a challenge. For the past two years, this course has included the adaptation and implementation of a pedagogical method that incorporates non‐scientific literature as a mechanism for introducing societal, cultural and ethical issues related to the study of physiology into this difficult and content heavy undergraduate biology course. An overview of the method, its implementation and its effect on overall student performance in the animal physiology course will be presented.
Preparative reading improves learning in an Anatomy & Physiology course
Authors: Krontiris‐Litowitz Johanna
Published: June 2021

Students often resist reading their textbooks, causing faculty to prepare their lectures accordingly. The question that arises is “Does preparative reading improve learning?”. This project examines the impact of pre‐class reading on student learning in a one semester Anatomy & Physiology course.

In this protocol, 4 classroom quizzes were offered during the course. For 2 of the quizzes (READ) students were expected to read the textbook to learn the material for the quiz and the quiz topic was not discussed in class. For the other 2 quizzes (NOREAD) the quiz topic was discussed in class and students were expected to review lecture notes to learn the material. Student performance on 4 essay exam questions evaluated the effect of preparative reading on learning and communication.

Students performed better on READ essay questions than on NOREAD questions. Mean scores on READ essay questions were higher than on NOREAD essay questions. Almost all students answered READ essay questions but 10–20% of the students did not answer NOREAD essay questions. In addition, students communicated their understanding better on READ exam questions that on NOREAD exam questions by writing longer essays, incorporating more ideas, and more clearly verbalized the relationship between their answer and the essay question.

This project suggests that preparative reading can improve learning and communication of understanding.
Regulation of ameloblastin expression via gap junctional communication
Authors: Yamada Aya , Iwamoto Tsutomu , Nakamura Takashi , Fukumoto Satoshi
Published: June 2021

Ameloblastin is a tooth‐specific glycoprotein that represents the most abundant enamel matrix protein, and plays an important role in maintaining the differentiation state of ameloblasts, serves as a cell adhesion molecule, and inhibits the proliferation of the dental epithelium. Our aim was to analyze the regulatory mechanism of ameloblastin expression via gap junctional communication using Gja1 null‐mice. Gja1 is one of the gap junctional proteins and highly expressed in tooth germ. Gja1 null‐mice showed disturbance of tooth germ, salivary gland, and lung morphogenesis, as similar to the phenotype of oculodento‐digital dysplasia. Inner dental epithelium in Gja1‐null mutants formed multiple cell layers. This phenotype was similar to that of ameloblastin mutant mice. Further, ameloblastin expression was dramatically decreased in Gja1‐null ameloblasts. TGF‐β1 administration induced ameloblastin expression in dental epithelial cell culture. On the other hand, Gap junction inhibitor 18α‐Gry and Oleamide inhibited the expression of ameloblastin induced by TGF‐β1. These results suggest that Gap junctional communication via Gja1 is important for the expression of ameloblastin and the differentiation of ameloblasts.

Grant Funding Source: Ministry of Education, Culture, Sports, Science and Technology of Japan
Characterizations of human discomallear ligament and articular disc of temporomandibular joint
Authors: SATO Iwao , MIWA Yoko , SUNOHARA Masataka , SHIMADA Kazuyuki
Published: June 2021

The discomallear ligament (DML) runs through a narrow space of bony petrotympanic fissure, which joins the articular disc of temporomandibular joint (TMJ) and the malleus in the tympanic cavity. We defined its morphological features using the cone beam CT (CBCT), anatomical dissection and immunohistochemical observation (extracellular matrices; fibronectin, collagen I, and III, and tenascin) of Japanese cadavers. Petrotympanic fissure and DML in fourteen (8 males and 6 females) cadavers were observed. Wide tunnel‐like structure was found on CBCT images in the middle region of the petrotympanic fissure to the malleus in the tympanic cavity was consisting of mainly four types and immunohitochemical staining for extracellular matrices were found in the TMJ with DML with different distribution for reactions. We also find these structures between the entrance of the petrotympanic fissure and the exit at the tympanic cavity are important to define limited movement of the malleus.
Determination of inferior alveolar nerve position via anatomical dissection and micro‐CT: A view towards dental implants
Authors: Massey Natalie Diana , Galil Khadry , Wilson Timothy
Published: June 2021

Hundreds of thousands of dental implants are performed each year. Precise knowledge of inferior alveolar nerve (IAN) location prior to dental implant placement is necessary to avoid complications of nerve damage such as sensory disturbances. The IAN courses anteriorly within the body of the mandible providing sensory nerve supply to the mandibular teeth. Current imaging modalities used to visualize the position of the IAN prior to dental implant placement may not be accurate. This study provides new information for locating the nerve more accurately. Micro‐CT images were acquired at a slice thickness of 154μm from 8 cadaveric mandibles. The same specimens were bisected and each hemi‐mandible was divided into 5 sections according to pre‐defined molar and pre‐molar width measurements. Superior, inferior, buccal and lingual bone distance measurements surrounding the mandibular canal were obtained by direct digital caliper measurements, and compared with corresponding μCT measurements obtained using the AMIRA segmentation and measuring software. Preliminary results suggest substantial variability in bone distance superior to the mandibular canal depending on the length of time since tooth loss. This finding highlights the importance of using an imaging modality that provides the highest spatial accuracy, when determining IAN location during the pre‐implantation stage of dental implant placement.

Grant Funding Source: Internal
POSITION OF NUTRIENT FORAMEN ON FIBULA, ITS VARIATIONS AND DISTANCE FROM THE STYLOID PROCESS AND ITS CLINICAL APPLICATION IN FIBULAR FLAP IN A MANDIBULAR RECONSTRUCTION
Authors: Sivakumar Girija , Mohan Mathan
Published: June 2021

The main aim of the present work is to study the position and variation in nutrient foramen in relation to styloid process and its distance from the the styloid process which is most important in a fibular flap during mandibular reconstruction. Fibula is one of the long bones present on the lateral side of leg. It receives its own neuro‐vascular bundle apart from the muscles attached to it. The upper end of the fibula with its nutrient artery and nerve entering its nutrient foramen along with muscles attached to it is preferred in most of the mandibular reconstruction and is called as fibular flap. While doing the fibular flap, care is being taken to avoid damage to neuro‐vascular bundle to fibula. The aim of the present work is study the position of nutrient foramen and its distance from the styloid process. The nutrient artery to fibula arises from the peroneal artery which winds around the neck of fibula and descends down along the fibula deep Flexor Hallucis Longus. Near the middle of fibula, it gives off nutrient artery which enters the nutrient foramen, and ramify within the fibula. The study has been carried out in 50 dry specimen (fibula) and radiological study has been carried out in 30 normal individuals. Various parameters like position and direction of nutrient foramen, distance from the styloid process were studied in the dry fibula and the same study was carried out in the radiology of fibula of normal individuals. The results have been tabulated and compared between the dry specimen and the normal individuals. These results were later correlated with the clinical application while tracing the nutrient foramen with the artery during mandibular reconstruction.
Papionin models for the functional relationship between the face and osseous nasopharyngeal boundaries
Authors: Pagano Anthony Santino , Yang David , Laitman Jeffrey T
Published: June 2021

With many similarities to humans, primate models are valuable for studying the functional relationships of the upper airway. This study uses baboons and related species to test the hypothesis that extreme facial prognathism is related to tall, narrow choanae and nasopharynges. 3D landmark data were collected along the face and upper respiratory tracts of Papio, Mandrillus, and other relatively orthognathic papionins (Macaca, Cercocebus, Lophocebus). Coordinate data were subjected to Procrustes fitting, which optimally superimposes and scales sets of coordinates between individuals. This allows for direct comparison of distance, area, and volume measures. All papionins displayed marked sexual dimorphism with males possessing tall, narrow choanae, long palates, and narrow basicrania. No dimorphism was found in choanal area and nasopharyngeal depth and volume. Over ontogeny, all papionins displayed similar schedules of growth change. When pooling adult males into genera, Papio and Mandrillus possess taller, narrower choanae and nasopharynges more shallow, narrow, and voluminous (vertically) than those of other papionins (p<.05). However, in pairwise comparisons, not all species of Papio and Mandrillus were significantly (p<.05) different from the other papionin species. The results support the hypothesis and suggest that facial prognathism is related to vertical expansion of the nasopharynx.

Grant Funding Source: NSF IGERT NYCEP Graduate Student Support
Evidence Based Analysis: Discussion of the relationship between prophylactic management of predisposing risk factors and non contact ACL injuries with female athletes
Authors: Bukoskey Thomas Patrick , Graves Mark , Humphreys Ryan
Published: June 2021

Objective

The purpose of this project was to determine if the number of non‐contact ACL injuries could be reduced in female soccer athletes with predisposing risk factors to an ACL injury.

Methods

A peer reviewed literature search was conducted using databases such as the British Journal of Sports Medicine, Journal of the APTA, and CINATHOL. Article inclusion was based on level of evidence and key words that were related to the clinical question.

Results

Five of the 23 articles selected discussed risk factors, 9 discussed neuromuscular control, 6 discussed hyperpronation of the subtalar joint, 2 discussed anterior knee laxity, and 1 discussed male versus female athletic differences.

Conclusions

A synthesis of the evidence identifying hyperpronation of the subtalar joint, anterior knee laxity, and neuromuscular control deficits as treatments to decrease the number of non‐contact ACL injuries in female athletes. The literature also suggested treatment should include prophylactic management to include Low‐Dye taping, insertion of a medial wedge orthotic, and preseason neuromuscular control‐training regime lasting six weeks. The neuromuscular training should include exercises that focused on feed forward techniques. According to the literature, these techniques were comprised of flexibility, muscular strengthening, plyometrics, core strengthening, sport related drills, and balance exercises.

Relevance

This evidence based research project reinforces anatomical concepts as the basis for treatment of non‐contact ACL injuries. Combining an understanding of the anatomy and applying the techniques identified in the literature the number of ACL injuries, amount of time lost during sport participation, and amount of health care dollars spent may be reduced for the identified population.
Flutamide does not mediate testosterone effects on BMP4 response in wild‐type rabbit bone cells
Authors: Cray James , Lensie Emily , Smalley Melissa , Finegold David , Siegel Michael , Losee Joseph , Mooney Mark , Cooper Gregory
Published: June 2021

We previously reported that a treatment of testosterone (T) and BMP4 led to decreased proliferation and differentiation in rabbit calvarial bone cells. A primary sex difference was noted; males exhibited greater differentiation for suture bone and females for non‐suture bone. Those results suggested that T decreased response for BMP4 treated cells. We hypothesized that this effect is mediated through the androgen receptor (AR). Cells were treated with the AR blocker, flutamide (F), along with T and BMP4 to determine cellular response. Calvarial cells (suture or non‐suture) from New Zealand White rabbits (N=14) were stimulated with 50ng/ml BMP4 and T (10–16 dose), with or without F treatments (10‐8, ‐10 or ‐12 dose). Proliferation and differentiation were assessed after 7 days. Differences between F treatments by dose, sex, and bone‐type were analyzed. F did not effect BMP4 alone, p>.05. The dose response was biphasic, p<.05. Non‐suture bone was more susceptible to this F‐dependent decrease in proliferation p<.05, and male derived cells exhibited a greater decrease, p<.05. F did not effect differentiation p>.05, by dose, cell type, or sex, p>.05. These results suggest the effect T has on reducing BMP4‐induced differentiation may not be mediated through the AR pathway. An alternative pathway (e.g., MAPK) should be explored for the direct effect of T on normal calvarial bone cell response.

Grant Funding Source: Internal
In vivo analysis of integrin transport in adult CNS axons
Authors: Andrews Melissa Renee’ , Bensadoun Jean‐Charles , Schneider Bernard , Aebischer Patrick , Fawcett James W
Published: June 2021

During the transition from early development to adulthood, several proteins critical for the regenerative ability of neurons, are downregulated or silenced. However, when downregulated integrin receptors are reintroduced in adult neurons in vitro, neurite outgrowth is enhanced on inhibitory substrates. Previously we show in vivo forced expression of the alpha9 integrin subunit (tenascin‐C receptor) enhances axon regeneration after dorsal rhizotomy or dorsal column crush injury for short distances compared to controls. An important finding in our study was the disparity observed between the substantial in vitro effect and the modest in vivo result. Therefore, the current study examines in vivo localization/transport of different integrin subunits following forced expression of a YFP‐tagged integrin using lentivirus injected into uninjured adult rat sensorimotor cortex. Initial results with integrin alpha 6 (laminin receptor, α6) show that α6‐YFP remains mostly in neuronal cell bodies with some observed within the immediate processes, with cervical spinal injury not affecting transport of α6‐YFP. We are now examining differences in integrin transport that may exist between adult, developing central nervous system (CNS), and peripheral NS to determine whether this correlates to regenerative ability. These findings will further our understanding of cellular mechanisms involved in CNS regeneration.
Restorative and Compensatory Respiratory Plasticity Following Cervical Spinal Cord Injury (SCI)
Authors: Lane Michael Aron , Meyer John W. , Mercier Lynne M , Vavrousek Jennie C. , Salazar Krystal , O'steen Barbara E , Fuller David D , Reier Paul J
Published: June 2021

Spontaneous recovery of diaphragm function ipsilateral to a complete lateral C2 hemisection (C2Hx) is an established example of “restorative respiratory plasticity”. The extent of recovered ipsilateral phrenic motoneuron activity is limited, however, and its impact on breathing has not been extensively investigated. The present study was conducted to test the hypothesis that contralateral “compensatory plasticity” plays a much greater role and is accompanied by connectivity changes associated with the contralateral phrenic circuitry.

Using combined anterograde and transneuronal retrograde tracing (with biotin dextran amine (BDA) and pseudorabies virus (PRV), respectively), we recently demonstrated that cells within the medulla innervate the phrenic motoneurons (PhMNs) both directly and indirectly (via interneurons; INs). More recent experiments have revealed reduced bulbospinal inputs to PhMNs ipsilateral to injury, as well as to associated pre‐phrenic INs. PRV tracing phrenic pathways ipsilateral to injury also showed decreased IN‐PhMN connectivity. In contrast, PRV tracing of phrenic pathways contralateral to injury demonstrate some bilateral recruitment of INs at C1 which are not infected under similar labeling conditions in normal rats. These results indicate neural substrate changes that may underlie restorative versus compensatory ventilatory behavior after high cervical SCI.

Grant Funding Source: NIH; Craig H. Neilsen Foundation; Anne & Oscar Lackner Chair in Neuroscience
D‐Glucose Attenuation of 1‐Methyl‐4‐Phenylpyridinium ion (MPP+) Toxicity in C6 Glial Cells
Authors: Ramesh Badisa , Darling‐Reed Selina , Soliman Karam F
Published: June 2021

Impaired mitochondrial function in the substantia nigra is one of the most likely cause of Parkinson's disease. In the present study, we investigated the protective effects of glucose against MPP+ toxicity. Results obtained indicate that MPP+ caused significant cell death in 2 mM glucose, while 10 mM glucose showed significant protection against MPP+ effects. Morphological observations revealed that MPP+ treated cells in 2 mM glucose significantly changed cell shape and size, while in 10 mM glucose; cells appeared similar to the control. MPP+ in 2 mM glucose decreased significant mitochondrial respiration, membrane potential and glutathione levels in a dose dependent manner while 10 mM glucose significantly restored them. Moreover, MPP+ in 2 mM glucose arrested the cells at G0/G1 and G2/M phases, demonstrating its dual inhibitory nature. However, in 10 mM glucose, MPP+ caused G0/G1 arrest only. The protective effects of glucose were not observed with cocaine, demonstrating that this protection is compound specific. In summary, the results obtained indicate that the loss of cell viability in 2 mM glucose group with MPP+ treatment was primarily related with significant decrease in mitochondrial respiration, membrane potential, total glutathione levels, and dual arrest of cell phases, while 10 mM glucose rescues glial cells from MPP+ induced toxicity by restoring these factors.(Supported by NIH grant RR 03020)
Mass transfer is significant factor in vascular intima signaling ‐ its relevance to AMPK
Authors: Vandrangi Prashanthi , Sun Wei , Shyy John J Y , Rodgers Victor G J
Published: June 2021

Previous literature has suggested that mechanical transduction, via shear stress, is the dominant contribution in vascular intima signaling. Cellular processes such as gene transcription, DNA replication in the disturbed flow region, and a sudden spike of ATP generation distal to plaque formation have been correlated to mechanotransduction. Here, we computationally model the significance of mass transfer relative to shear gradients on chemical species under the same experimental conditions prescribed by the work by Korenaga et al. (1997), Chiu et al. (1998), and Choi et al. (2007). The results demonstrate that mass transfer modifications of chemical species were in excellent agreement with the published observations. In addition, our experimental results showed the Ca2+ dependence for eliciting AMPK (AMP activated protein kinase) signal pathway. These results imply that the role of mechanical transduction in similar signaling may be overstated and mass transfer considerations should be carefully examined when studying triggering methods in signaling mechanisms.

Grant Funding Source: CBR (Center for Bioengineering Research), UCR
Examining the Effects of Cardiovascular Effort on Blood Flow Velocity: A Duplex Doppler Ultrasonography Study
Authors: Kershaw Matthew , Ross David A , Stone Michael , Marquez Samuel
Published: June 2021

Ultrasonography (US) is frequently used to investigate anatomical structures in a non‐invasive manner. Duplex US combines conventional US imaging of blood vessels with Doppler US analysis of blood flowing through them, providing an opportunity to acquire data on flow velocities in real‐time. This study compares the blood flow velocity in a resting individual with the velocity measured after cardiovascular activity. Velocity (cm/s) was measured through the abdominal aorta. A mixed‐sex sample of young, healthy volunteers (n=20) from the SUNY Downstate College of Medicine focused on physical activity on the lower limbs for four minutes, after which the post‐effort velocity was obtained. Results showed a mean increase in blood flow velocity of 61.5%, with a maximum increase of 166.5% and minimum positive increase of 21.6%. Standard deviation of the increase in blood flow velocity was 56.4%. An unexpected result was found in two cases, in which the post‐effort flow velocity showed a small decrease instead of the expected increase. These findings suggest that an increase in physical effort in the lower limbs requires a greater supply of blood; thus, the observed flow velocity increases. Duplex US allows for the capture and analysis of data in real‐time in various healthcare settings, without requiring invasive or expensive, radiation‐intense procedures such as MRI.

Grant Funding Source: AAA
Protein Structure Initiative Material Repository (PSI‐MR): An open shared public resource for structural genomics plasmids
Authors: Cormier Catherine , LaBaer Joshua
Published: June 2021

The PSI‐MR (http://psimr.asu.edu) provides centralized storage and distribution for the protein expression plasmids created by PSI researchers. These plasmids are a resource that allows the research community to dissect the biological function of proteins whose structures have been identified by the PSI. The plasmid annotation, which includes the full length sequence, vector information, and associated publications, is stored in a freely available, searchable database called DNASU (http://dnasu.asu.edu), and plasmid samples can be requested directly though the website. We have also developed a novel strategy to avoid the most common concern encountered when distributing plasmids, namely the complexity of material transfer agreement (MTA) processing and the resulting delays this causes. The Expedited Process MTA, in which we created a network of institutions that agree to the terms of transfer in advance of a material request, eliminates these delays. Our hope is that by creating a repository of expression‐ready plasmids and expediting the process for receiving these plasmids, we will help accelerate the accessibility and pace of scientific discovery.

This work was supported by the National Institute of General Medical Sciences, the National Cancer Institute, the National Institute of Allergy and Infectious Disease, and the Virginia G. Piper Charitable Trust.
Functional and structural characterization of the glycine riboswitch
Authors: Ye Jingdong , Elsayed Galal , Elsayed Mohammed , Brinda Bryan , Zhang Wei , Stoner Breena
Published: June 2021

Glycine riboswitch is unique in that the two glycine aptamers bind glycines cooperatively and control downstream gene expression in a more “digital” manner. The exact structural mechanism for this glycine binding cooperativity is not well understood. We hypothesize that the cooperativity is caused by the formation of “Aptamer Disruptor” in the absence of glycine, which involves an interaction between “b” region (on aptamer I) and “c” region (on aptamer II). In‐line probing data on a 5’ extended aptamer II shows reduced glycine binding activity compared to a previously reported aptamer II construct VCII122, consistent with this hypothesis. Sequence analysis identified the candidate regions of “b” and “c”. Breaker Lab reported that VC G17C completely abolished the aptamer I and reduced the aptamer II glycine binding by 1000 fold. According to our hypothesis, this is at least in part due to b/c interaction. Data on a double mutant, VCG17CM1, in which the b/c interaction was abolished by mutation in “b” region, shows that binding of VCG17CM1 with glycine is rescued compared to VCG17C, suggesting the direct involvement of “b” region in the formation of “Aptamer Disruptor”. Further experiment is being carried out to test the “c” region, the linker region and other important locations.

We are also crystallizing the glycine riboswitch using a chaperone approach (CARC; Ye et al. PNAS 2008) for detailed structural elucidation.

Source of research support: start‐up fund provided to JD Ye from University of Central Florida.