bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiofrequency promotes more collagen synthesis than low level laser in experimental tendineous lesion (914.4)
Authors: Akamatsu Flávia , Teodoro Walcy , Saleh Samir , Hojaij Flávio , Camillo Gina , Martinez Carlos , Andrade Mauro , Jacomo Alfredo
Published: June 2021

BACKGROUND: Tendon injuries are common consequences of sports trauma and costly in terms of surgery and rehabilitation. Several therapeutic approaches have been employed to repair the tendon fibrilar matrix and restore its function. We compared the action of Low Level Laser Therapy (LLLT) and Radiofrequency (RF) after experimental lesions in rats.

METHODS: Sixty adult male Wistar rats weighing 250 to 300 g were submitted to bilateral partial transverse section of the calcaneous tendon. On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each which the right tendon were treated with LLLT (Konf, Aculas ‐ HB 750) and other three treated with monopolar RF (Tonederm™). The rats were sacrificed on the 7th, 14th and 28th days. The total amount of collagen synthesized was assessed through 4‐hidroxyprolin content. The left tendon served as control in all groups.

RESULTS: Collagen content in the lesions did not change at the end of the first four weeks of treatment irrespective of the method employed, even compared to controls. However RF was more effective to promote collagen synthesis than LLLT and controls after 7 (p< 0.0001) and 14 days (p < 0.05).

CONCLUSION: RF increases collagen production in the first two weeks of treatment whereas LLLT does not. Further evaluation to ascertain the importance of this fact in the healing process in experimental tendon lesions is needed.
The prevalence of cryptorchidism among male infants of Nigerian population: a case study of Imo State (915.1)
Authors: Ihentuge Churchill , Ugochukwu Chioma
Published: June 2021

INTRODUCTION: Cryptorchidism or undescended testes is one of the most frequent developmental abnormalities in males and may be a prominent cause of infertility in men. It is a condition in which one or both testes are not fully descended to the scrotum.

OBJECTIVE: To determine the frequency of cryptorchidism in male infants of Imo State Nigeria.

METHOD: This study took place in the three geographical zones of Imo state between July 2010 and June 2013. Three thousand five hundred and thirty three (3533) male infants were randomly selected for this study. Consent and ethical clearance was obtained. The subjects were carefully examined clinically for this anomaly. The birth weight, gestational age, history of pregnancy, parental education and occupation was considered. The data was analyzed using the SPSS version 20.0 software.

RESULTS: The prevalence of cryptorchidism in this study was 1.53%. 16.68% of cases were bilateral while 38.88% and 44.44% occurred on the right and left sides respectively. 68% of cases were not palpable, 14% were palpated around the inguinal region while 22% were found on the suprascrotal area. There is no significant difference between one geographical zone and another (p<0.05).

CONCLUSION: The prevalence of cryptorchidism in this study is 1.53%. Birth weight and maternal health were contributory but the maternal education and occupation as well as geographical distribution was not implicated.
Unilateral variant motor innervations of flexor compartment of arm (915.10)
Authors: Purushothama Chethan
Published: June 2021

Variations in the nerves of the upper limb are very important in routine surgeries, where these nerves are more prone for injuries; these variations may also help in interpretation of a nervous compression having unexplained clinical symptoms. The musculocutaneous nerve usually branches out from the lateral cord of brachial plexus. It innervates the coracobrachialis, biceps brachii and brachialis muscles and continues as the lateral cutaneous nerve of forearm without exhibiting any communication with the median nerve or any other nerve. We report a unilateral variation in motor innervations of the right arm in a 72‐year‐old Female cadaver. The musculocutaneous nerve was found to be piercing coracobrachialis muscle, supplying it and later continue as lateral cutaneous nerve of forearm. A muscular branch of the median nerve was supplying the short and long head of biceps muscle. In the middle of arm, the median nerve was found to be giving a separate branch, which supplied the brachialis muscle and continued in the cubital fossa with normal relation to biceps tendon and brachial artery. There was no variation seen in distribution of median nerve in the flexor compartment of forearm and hand. Knowledge of such anatomical variation is of interest to the anatomist and surgeons.
Duplicate caudate lobe of liver with oblique fissure and hypoplastic left lobe of liver (915.2)
Authors: Singh Rajani
Published: June 2021

The aim of study is to report a new anatomical variant of human liver and associated clinical significance. During routine dissection of abdomen, a liver of 55 year aged male cadaver was found to have multiple anomalies. Measurements of shape and size of these anomalies were taken.

The caudate lobe was uncommonly duplicated by a angular fissure of length 2.5 cm and an oblique fissure of length 2 cm on this lobe placed inferiorly was also observed in this specimen. There was vertical furrow of length 6 cm and depth 2 mm on the right lateral surface of liver besides above malformations. The left lobe of liver was hypoplastic. These are new variants in the normal morphology of liver.

These anomalies are of paramount importance to clinicians involved in the diagnosis and management of hepatic diseases, anatomists and morphologists for variant morphology, embryologists for new developmental defect and radiologists for misinterpretation of images of liver.
Unilateral absence of the musculocutaneous nerve with subsequent median nerve innervation: a case report with embryological and clinical significance (915.6)
Authors: Shiwlochan Devina , Gopal Sapna , Shiwlochan Amrita , Murlimanju B. , Viswanath Srikanteswara
Published: June 2021

Anatomical variations of the brachial plexus can have important surgical consequences. During a routine dissection procedure for teaching first year medical students, we observed a brachial plexus variation. The variation was found on the right extremity of a Caucasian female cadaver involving the complete absence of the musculocutaneous nerve and the lateral cutaneous nerve of forearm. In place of the musculocutaneous nerve, the median nerve was found to pierce the coracobrachialis and provide subsequent innervation to the biceps brachii and brachialis muscles. We believe this particular variation is relevant in clinical conditions such as correction of paralysis of the flexors of arm and forearm, neurotization, and post mastectomy reconstruction. Previous literature indicates that this embryologically relevant type of variation is much more common in the right upper extremity (fetal dissections).
Y‐chromosome amelogenin isoform peptides found in mature dental enamel (918.1)
Authors: Gerlach Raquel , Molina Gabriela , Issa Joao , Sosovicka Mark , Line Sergio , Vieira Alexandre
Published: June 2021

The dental enamel is the hardest and most calcified tissue in the human body, and most of its structure is unaltered during the time the teeth stay in mouth. The best known enamel specific structural proteins are amelogenin, ameloblastin and enamelin. The ability to recover proteins has enormous value in many fields where the study of proteins preserved from the past could give specific information on diet, life style, and even of biochemical evolution of the proteins themselves, since such information is not encoded in the DNA. So far, only X‐chromosome amelogenin peptides (AMELX) were recovered from mature enamel. Since amelogenin is encoded in the X and Y chromosomes in humans, peptides specific for the Y chromosome might exist in the mature enamel, but they have never been found. In this study we aimed at recovering peptides from male and female teeth, with the objectives of 1) finding Y‐encoded amelogenin peptides (if expressed at all, which is not known at the protein level) and 2) describing the aminoacid sequences of mature dental enamel peptides. Results showed that the Y‐specific amelgonenin (AMELY) sequence WYQSMIRPPY is found in male teeth and that with the enamel etch technique used here followed by nLC/MS/MS, dozens of peptides that are specific for enamel proteins were found (3 AMELX isoforms, 1 AMELY isoform, ameloblastin and enamelin).

This report opens a myriad of possibilities for studying both present and long‐gone species, since dental enamel is a well preserved repository where such peptides can be detected.

Grant Funding Source: Supported by FAPESP (Brazil)
A rhesus model for the study of the sutures at pterion (918.18)
Authors: Wang Qian , Kensler Terry , Maldonado Elizabeth , Zhao Martin
Published: June 2021

The pterion is located at the infratemporal fossa of the skull. The sutural schemes at pterion are dominated by two patterns, the fronto‐temporal type (FT) in which the frontal and temporal bones are in direct contact (Monkey type), and the spheno‐parietal type (SP) in which the sphenoid bone and parietal bone are in direct contact (Human type). It is hypothesized that the sutural patterns at pterion covary with the relationship between cranial and facial skeletons. Previous investigation of suture patterns at petrion in the Rhesus macaques (Macaca mulatta) from Cayo Santiago, Caribbean Primate Research Center (CPRC), has indicated familial aggregation. Here we further identify a Rhesus family in Cayo Santiago with a nearly 25% incidence of Human type (SP) in their skulls from members of eight generations, housed in the CPRC Laboratory of Primate Morphology and Genetics. In addition, a member of eighth generation had premature fusion of the squamosal suture. The descendents of this matrilineal family, including 169 members of three generations, are still living in Cayo Santiago. Thus, this family will be an excellent model for studying sutural morphology, variation, and inheritance patterns. Sutures are important loci of craniofacial growth. The interactions between them and their surrounding tissues need further investigation to elucidate the ontogeny of craniofacial skeletons. To this end, further studies and long term tracking of this Cayo Santiago Rhesus family may contribute to a variety of disciplines, including genetics, embryology, morphology, pathology, and biomechanics of craniofacial skeletons, and help establish protocols in craniofacial reconstructional medicine. Supported by NIH grant P40 RR003640 to CPRC and NSF BCS‐0725183.
Concurrent growth of the skull and aerodigestive tract of human infants: setting a protocol for study (918.25)
Authors: Curcio Daniella , Micham Brittni , Reidenberg Joy , Laitman Jeffrey
Published: June 2021

Vital changes in form and function occur globally in the head and, particularly, in the aerodigestive tract (ADT) in the first months of human postnatal life. This study aims to determine reproducible and readily ascertainable measures that track developmental skull/ADT proportions so as to facilitate better clinical care (eg, endotracheal tube size/placement) and increase recognition of underlying conditions (eg, obstructive sleep apnea, sudden infant death syndrome). We focus here on determining the protocol’s design, prioritizing functional relevance, precision of reading, and ease in assessment. Our hypothesis is that there are correlations between skull and ADT that develop with regularity and, thus, predictability. Our target population will be infants 0‐4 months accessed via MRI and measurements will include those in mid‐sagittal (MS) and axial planes (AP). In the MS plane we will access length and height parameters (eg. ADT length) and determine the level of structures’ position in the neck in relation to the hard palate plane (eg. thyroid level). In AP we will access width and depth measurements (eg. maxillary arch width and depth). It is anticipated that resultant normograms may contribute to the understanding of possible causation between development and growth of head and neck structures.

Grant Funding Source: Supported by American Association of Anatomists, grant: AAA Short Term Visiting Scholarship
Sex dimorphism of the sacroiliac joint and its relation to joint mobility and function (919.14)
Authors: Clements Nicolle , Johnson Marjorie , Mottola Michelle , Gillis Heather
Published: June 2021

The pelvic girdle is the functional connection between the spine and lower limbs, with the sacroiliac joint (SIJ) serving as the articular connection between the spine and hip bones. The SIJ provides load transfer between the axial and appendicular skeleton. It is specifically adapted to deal with these loads by both fibrous structures and morphological characteristics, which allow only limited movement. There is a sex dimorphism in the SIJ in terms of structure and function, with males having a rougher surface compared to females and a lower prevalence of pelvic girdle pain (PGP). There is also a discrepancy between the sexes pertaining to function, with females typically experiencing more issues relating to mobility. The purpose of this study is to compare SIJ articular morphology of males and females through validated measurement. 10 male and 7 female pelvises from embalmed cadavers were dissected and the SIJ opened. Digital calipers and the MicroScribe G2x tool were used to obtain surface area measurements of the joint articular surface and pelvic width dimensions. It was hypothesized that surface area will be greater in males than females, and the convexities/concavities will be more pronounced leading to a more stable joint. Dimensions will also vary between males and females affecting the overall shape of the SIJ. This would substantiate some of the differences in PGP and mobility of the joint between the sexes.
Relative long bone proportions and developmental stress in a modern Thai population (919.2)
Authors: Rectenwald Kristen
Published: June 2021

Research on relative limb proportions has revealed interesting patterns of variability with regards to environment. Since there have been few attempts to correlate variability in limb proportion with unrelated stress indicators, this study examined long bone length ratios and linear enamel hypoplasia (LEH) frequency in a modern Thai population. Inter‐limb indices were calculated for 259 adults (105 F/154 M) and compared with LEH frequency. A Spearman’s correlation coefficient analysis indicated significantly shorter relative distal limb lengths in the lower limbs of individuals with high LEH frequencies. This was strongest in females, with significant correlations in the tibia/femur (p=0.038) and the fibula/femur ratios (p=0.009) of both sides, as well as a high correlation between LEH frequency and stature. In males, only the left fibula/femur ratio (p=0.008) demonstrated a significant relationship with LEH frequencies. No correlation between stature and LEH frequency was found in males, or in the upper limbs of either sex. These findings support the claim that distal limb growth is more affected by developmental stress than proximal growth. The disparity of upper and lower limb response, in addition to the relationship between sex and observed correlations, may have significant implications for our understanding of human limb development and catch‐up growth.
First detailed comparative, developmental and pathological analysis of the relationship between limb soft and hard tissues: muscle configuration is mainly related to the topological position, and not the anlage and/or homeotic identity, of digits (919.5)
Authors: Diogo Rui , Walsh Sean , Smith Christopher , Ziermann Janine
Published: June 2021

In the last decades evolutionary developmental biologists have studied the ontogeny of hard and soft tissues in model organisms such as chicken, axolotl, frogs and mice. However, very few researchers have undertaken detailed analyses about the specific relationships between the soft and hard tissues of the tetrapod limbs and particularly of their autopodia (hand/foot) and zeugopodia (forearm/leg). We have therefore addressed this subject by using a wide range of different techniques in a broad taxonomic sample, including developmental and regenerative studies of GFP salamanders, ontogenetic studies of wildtype frogs, comparative studies of all major groups of tetrapods, and dissections of humans with birth defects involving polydactyly and digit reduction. Interestingly, our results show that in almost all cases of both wildtype and non‐wildtype non‐pentadactyly the identity and configuration of muscles is actually highly predictable and is mainly related to the topological position of the digits (e.g., by being the most ulnar/fibular, or instead the most radial/tibial digits) to which the muscles insert, and not to the ontogenetic anlage from which the digits develop or even the homeotic identity of each digit. We will discuss various case studies illustrating this point, and discuss the broader implications of our results for evolutionary, comparative and developmental biology and for human medicine.

Grant Funding Source: Faculty Start‐Up Package, Howard University College of Medicine
Evolutionary convergence of digit loss by overlapping mechanisms in multiple species of mammals (919.6)
Authors: Cooper Kimberly , Sears Karen , Uygur Aysu , Maier Jennifer , Tabin Cliff
Published: June 2021

Since the origin of tetrapod limbs about 450 million years ago, every Class of land vertebrate ‐ reptiles, birds, amphibians, and mammals ‐ has undergone some degree of digit loss from the ancestral count of five. Even within mammals many species have independently reduced the number of digits as a locomotor adaptation. The repeated convergence on digit loss indicates it is perhaps mechanistically simple, yet little is known of the mechanisms or whether developmental constraints ensure the same mechanisms are re‐deployed in divergent species. Here we show in the three‐toed jerboa, horse, camel, and pig that the mechanisms of digit loss are varied and yet utilize recurring themes. Common characteristics of digit loss include downregulated expression of the growth factor fgf8 in the apical ectodermal ridge in the anterior and posterior limb of all species with reduced digits. We also see massively upregulated cell death in tissue that fails to become digits in the jerboa, horse, and camel. In the three‐toed jerboa, we have identified additional hindlimb specific expression differences that may be responsible for the reduction to three toes on the hindlimb while the forelimb maintains five. We see strong upregulation of bmp4 and its transcriptional target, msx2, in the hindlimb whereas the forelimb expression resembles that of the mouse. Both genes are associated with promoting cell death in mouse and chicken limbs providing a mechanistic connection that makes these two excellent candidates for investigating evolution of cis‐regulatory elements responsible for the loss of digits.
Reconstructing regulatory circuits: lessons from immune cells (92.1)
Authors: Regev Aviv
Published: June 2021

Molecular circuits are the information processing devices of cells and organisms, transforming extra‐ and intra‐cellular signals into coherent cellular responses. While there has been hope that genomic approaches would make it possible to systematically reconstruct circuitry, genomic studies have largely been observational and rarely involve large‐scale testing and refinement of models.

We develop a systematic computational and experimental approach to reconstruct circuitry by profiling the circuit’s output or internal state along a relevant time course, learning a computational model that explains the observed data, perturbing every key component proposed by our model, and repeating the process, until data and model converge.

All circuits are dynamic, and rewire in response to perturbation, at time scales from minutes to eons, as cells respond to new environmental conditions, differentiate, or evolve. We focus on a carefully selected model system at each time scale, from minutes to eons. In this talk, I will focus on describing our studies in immune cells, especially DCs and T cells, showing how we can dissect transcriptional and signaling circuits and their functionality in key physiological responses.
Three‐dimensional analysis of basic multicellular units using micro‐computed tomography: Does morphology indicate behavior? (920.2)
Authors: Harrison Kimberly , Tsukamoto Suyoko , Cooper David
Published: June 2021

Basic Multicellular Units (BMUs) are groups of cells responsible for the coordination of resorption and formation in cortical bone remodeling. Due to a lack of three‐dimensional (3D) methods, relatively little is known regarding BMU spatio‐temporal ‘behavior’. It has, for example, been hypothesized that all remodeling events are targeted towards microdamage and thus BMU ‘steering’ is an essential aspect of this process. A previous 2D study involving Ursus americanus (black bear) bone revealed extensive active remodeling spaces; thus providing a unique platform for the current study. We sought to characterize the 3D morphology of BMUs to assess the extent of steering as indicated by sudden changes in trajectory. Micro‐CT of metacarpal and metatarsal diaphyses (n=4) provided an unprecedented number of BMUs (3,144) for analysis. Results indicated that majority of BMUs were oriented along the longitudinal axes of the diaphysis. Overwhelmingly, BMUs had a roughly linear course with little evidence of sudden changes in course or branching. This suggests that the BMUs observed were largely untargeted or targeting is tightly associated with the initiation rather than progression of BMUs.

Grant Funding Source: Supported by the CIHR Training grant in Health Research Using Synchrotron Techniques
Investigation of the role of calcaneal dimensions in pes cavus and pes planus (920.4)
Authors: Van Osch Kylen , Johnson Marjorie , Balsdon Megan , Dombroski Colin , Jenkyn Thomas
Published: June 2021

Background: Disruption in the medial longitudinal arch (MLA) of the foot can lead to pes cavus (high arched foot) or pes planus (low arched foot). The importance of the calcaneus in MLA structure can be inferred in the treatment of severe pes planus, where alteration of calcaneal length is performed if conservative treatments have failed.

Purpose: To our knowledge, no previous study has investigated whether variations in calcaneal size can be correlated to MLA height. The purpose of this study was to compare calcaneal dimensions between pes cavus, normal MLA, and pes planus groups.

Methods: Utilizing OsiriX software, several dimensions of 3D calcanei were compared between pes cavus, normal MLA, and pes planus subjects.

Results: The pes cavus, normal MLA, and pes planus groups did not show any significant differences between group means for all calculated dimensions. Although not statistically significant, calcaneal length (p=0.140), talar articular surface width (p=0.228), and calcaneal tuberosity height (p=0.087) exhibited increasing size with increasing MLA height. This study should be repeated with a larger population to further verify this trend.

Conclusion: There is no significant difference in these specific calcaneal dimensions between pes cavus, normal MLA, and pes planus groups. This study provides evidence that calcaneal lengthening procedures may be altering a normally sized calcaneus.
Extracellular matrix protection factor treatment in a rat model of osteoarthritis slows the progress of cartilage and bone destruction associated with the disease (922.10)
Authors: Chmielewski Sarah , Cho Ellen , Lukashova Lyudmila , Friedrich Sarah , Althauser Samuel , Selim Abdulhafez , D'Angelo Marina
Published: June 2021

Osteoarthritis (OA) is a disease of the joints caused by an imbalance between extracellular matrix destruction and production. We have developed an innovative disease modifying therapeutic technology to treat OA. Extracellular matrix protection factor (ECPF‐1) is a novel, safe and effective intra‐articular injection effective in alleviating tissue pathology associated with OA. Knees of rats in an OA model were treated with ECPF‐1 peptide or BMP‐7 protein as a control because BMP‐7 has been shown to be chondroprotective in a rabbit model of OA. Micro computed tomography (uCT) indicates the amount of bone volume present in the samples and the areas of mineralization. Since healthy cartilage is not normally mineralized, one would expect a low bone volume in these samples and a higher bone volume in cartilage of OA. ECPF‐1 treated OA joints contained the lowest bone volume after four weekly injections of peptide. Trabecular thickness indicates the strength of the bone, and the ECPF‐1 treated animals had the best trabecular thickness numbers following 4 weekly injections of peptide. This data provides critical proof of concept that ECPF‐1 acts as a disease modifying therapeutic in a rat model of OA.

Grant Funding Source: Supported by intramural funds
Interaction between rhBMP‐2 and different types of bone grafts (922.18)
Authors: Issa Joao Paulo , Dias Fernando , Fazan Valeria , Ervolino Edilson , Iyomasa Mamie , Gerlach Raquel , Kotake Bruna Gabriela , Gonzaga Miliane
Published: June 2021

This study evaluated the bone healing process in surgical defects on rat skulls using different bone grafts, associated or not with rhBMP ‐2 (5 µg).

It was used 112 rats (♂, 250g) euthanized at 4 or 6 weeks, divided into 8 groups: G1. autologous bone graft; G2. homologous bone graft; G3. heterologous bone graft (lyophilized bovine bone); G4. autologous bone graft + rhBMP‐2; G5. homologous bone graft + rhBMP‐2 and G6. heterologous bone graft + rhBMP‐2; G7. rhBMP‐2; G8. surgical bone defect. The following methodologies were used for evaluation of the new bone formation: histological, radiographic, immunohistochemical, zymographic, and mineral quantity (Ca).

After 4 weeks, the zymographic analyses revealed increased production of MMP‐2, the MMP‐9 levels remained consistently in both surgical times. The G1 group shows better results, followed by G2 and G3 respectively, however the addition of rhBMP‐2 on the graft (G4, G5, G6) does not appear to influence the MMP‐2 and MMP‐9 levels. The Ca dose revealed that G1 and G2 were the most mineralized, the other groups had lower Ca levels that decreasing after 6 weeks. The histological and radiographic analyses demonstrated that the bone grafts improve the bone repair specially when associated with rhBMP‐2, increasing the new bone formation after 4 and 6 weeks, without significant statistical differences between G4, G5 and G6. Immunohistochemistry for osteogenic and angiogenic growth factors showed positive identification for all groups, particularly for G4 , G5 and G6.
Susceptibility of the aging thorax to motor vehicle crash injuries (922.2)
Authors: Sochor Mark , Heltzel Sara , Kent Richard
Published: June 2021

Susceptibility of the Aging Thorax to Motor Vehicle Crash Injuries Objective: Evaluate the appearance of the phenomenon that the aging thorax ribs become more horizontally oriented. It is hypothesized that the more horizontal orientation of the rib cage appears to cause more rib fractures in the elderly population when exposed to crash forces through a seat belt. It is well documented that thoracic injury tolerance decreases with age. Cadaver and field data (National Automotive Sampling System) have shown that older subjects generally sustain more rib fractures for a similar impact severity.

Methods: Full thorax computed tomography (CT) scans of 60 patients age 18 to 89 years were analyzed to quantify the angle of the ribs in the sagittal plane. A standardized method of measuring the angle of the rib in relation to the thoracic spine was developed. Additionally, height, weight and Body Mass Index (BMI) were combined in a dataset to look for the relationship between these different factors.

Results: Slope of the regression line with age was significantly different than zero with rib angle increasing with increasing age. Average increase in rib angle was about 4 degrees from young adult 18 years to elderly adult 88 years. Surprisingly, Weight and BMI were found to be significantly related to rib angle (p<.001). The rib angles increased from 45 degrees at 40kg to 68 degrees at 160kg.

Conclusions: Rib angles become more horizontal with increasing age but this increase appears to be minimal (<5 degrees). What appears to actually drive rib angle more horizontally is weight. Limitations of the study is obviously geometric change of the thorax is not the only change in the elderly thorax as kyphosis and osteoporosis also occur simultaneously and will also have large effects.
Consequence of various wrist angulations at impact on the severity of Colles’ fractures (922.4)
Authors: Baral Sumit , Chatterjee Depaul , Caceres Noel , Feuer Gavriel , Hayes Westley , Jones Colton , Saha Subrata , Marquez Samuel
Published: June 2021

A Colles’ fracture, eponymously named after Irish surgeon Abraham Colles, is a transverse break of the distal radius (2.5 cm from the radio‐carpal joint) with dorsal displacement of the carpus and hand. It is most commonly a consequence of falling onto outstretched hands. As the exact angle of the wrist changes with each fall, this study tested for correlation between wrist angulation at impact and the severity of the resulting Colles’ fracture. A sample of 15 cadaveric upper limbs exhibiting no evidence of traumatic injuries on gross observation was used to study this relationship. Specimens were cut transversely at mid‐forearm and randomly assigned to either the 90 degree wrist extension group (n=7) or the 45 degree wrist extension group (n=8). Specimens were secured and a drop‐weight impactor was used to apply force to the extended palms, recreating a scenario of falling. After impact, each specimen was radiographed and assessed for evidence and severity of fracture graded via Frykman’s classification system. Results showed that falling with the wrist extended 90 degrees was more likely to produce a Colles’ fracture while falling onto a wrist extended 45 degrees produced extensive damage to the ulna and carpus. Better understanding of the relationship between carpal angulation and likelihood/severity of fractures may aid preventative approaches for populations at high‐risk for falls such as the elderly and athletes.

Grant Funding Source: Supported by SUNY Downstate Alumni Association
A comprehensive analysis of zygomatic symmetry and implications for zygomatic bone reconstruction (922.6)
Authors: Belcastro Alexandra , Johnson Marjorie , Galil Khadry , Jenkyn Thomas , Willing Ryan , Yazdani Arjang
Published: June 2021

To assess the validity of the current approach to craniofacial repairs whereby the contralateral hemiface is used as a template for surgical repair, this study aims to provide a comprehensive analysis of facial skeletal symmetry in normal human faces beginning with the zygomatic bone. Three‐dimensional models generated in OsiriX from the CT scans of 30 adult male patients displaying normal skeletal anatomy were used to assess the symmetry at seven bilateral zygomatic landmarks. All landmarks displayed a deviation from perfect symmetry, ranging from 1.41 to 3.13 mm, and statistically significant differences were observed in the asymmetry scores across the seven zygomatic landmarks (F(6,203)=5.951, p<0.005). The zygion demonstrated significantly greater asymmetry than other more medially‐located landmarks including the orbitale, jugale, and frontozygomatic suture. These results suggest that bony asymmetry can be measured and there is a significant degree of asymmetry in the zygomatic bone, particularly in the temporal process and extending into the zygomatic arch. Such deviations may warrant a re‐evaluation of current surgical approaches to the repair of zygomatic bone fractures.
Embryology of extraocular muscles: a new vision (923.7)
Authors: Tréchot Fanny , Tonnelet Romain , Micard Emilien , Labrousse Marc , Angioi Karine , Braun Marc
Published: June 2021

Purpose : To describe the embryology of extraocular muscles through 3D viewing algorithm from Carnegie stage XVII to Carnegie stage XXIII (41st‐57th day of development).

Materials and Method : The work consisted of a scanning and a data processing reconstruction of embryonic histological material. Material came from anatomical universities collections. 12 embryos were selected, and 7 were dedicated to muscle study (from 14.5mm to 54.5mm). This data processing has allowed a study in three spatial planes.

Results : From stage XVII, all extraocular muscles are in place, including levator palpebrae. The study in 3 planes makes their individualization easier. Gilbert (Carnegie Institution) described the origin of inferior rectus and inferior oblique by a common primordium, however from the stage XVII the two muscles are clearly separated. The decussation of the superior oblique is seen from the stage XIX, the trochlea appears at stage XXII. Our work also demonstrates the nerves : optic, oculomotor, trochlear, trigeminal and abducens. The junctions between nerve and muscle are found, especially for the lower branch of the oculomotor nerve.

Conclusion : This new study tool has resulted in explicit images of the development of extraocular muscles in the embryonic period. It helped to provide details with respect to the work already established by the Carnegie Institution.
Novel ubiquitin binding sites of S. cerevisiae polymerase η identified by a genetically encoded photoactive probe (927.4)
Authors: Urban Matthew , Yang Kun , Zhuang Zhihao
Published: June 2021

DNA translesion synthesis is carried out by specialized DNA polymerases such as Polη. Polη contains a ubiquitin‐binding zinc finger (UBZ) domain required for its effective recruitment to the stalled replication fork in response to DNA damages. Our previous study reported a novel ubiquitin‐binding mode of S. cerevisiae Polη in which the C‐terminal portion of Polη binds ubiquitin with 30‐fold higher affinity than the UBZ domain alone. However, the mechanism of such higher binding affinity is not clear. In this study, a genetically encoded photoactive probe, p‐benzoyl‐L‐phenylalanine (pBpa), was incorporated at various positions on ubiquitin to map the interaction sites between Polη and ubiquitin. Data suggests that besides the Ile44 hydrophobic patch which was known to bind UBZ domain of Polη, several other residues at the ubiquitin C‐terminus and a surface opposite from the hydrophobic patch on ubiquitin also bind to Polη. These new binding sites increase the binding affinity between ubiquitin and Polη. Our finding is important for understanding the role of ubiquitin in the recruitment of Polη during DNA translesion synthesis.

Grant Funding Source: Supported by U.S National Science Foundation Grant MCB‐0953764 to Z. Zhuang
Screening nicastrin antibodies for specificity for immunofluorescence (934.2)
Authors: Deshaies Derek , Yu Gang , Dries Daniel
Published: June 2021

Alzheimer’s disease is a type of dementia that can cause problems with memory, learning and behavior. Nicastrin is a component of the protein complex involved in the development of Alzheimer’s disease. In our lab, tissue‐specific nicastrin conditional knockout mice were developed and displayed a striking neurological phenotype. The aim of this research project, then, is to confirm the tissue‐specific knockout by using immunofluorescence. In order to ask this question, we must first identify an immunofluorescence‐compatible antibody that is specific for the nicastrin protein. This is important due to the cross reactivity of many antibodies that are thought to be anti‐nicastrin. In an effort to test for antibody specificity, researchers use pre‐blocking techniques to pre‐absorb (block) their antibodies with antigen before doing their experiment. However, this only proves that the antibody produced is specific for the antigen against which it was raised. Using wild‐type and nicastrin knockout cells, our approach will use a series of anti‐nicastrin antibodies for immunofluorescence to test their specificity towards their intended antigen, rather than staining antigens other than the one against which the antibodies were raised.

Grant Funding Source: Supported by National Institute of Neurological Disorders and Stroke grant 1R01NS079796
Proteasome inhibition increases expression of angiogenic chemokines in ovarian cancer cells through IKKβ, S536P‐p65 and EGR‐1 dependent pathways (935.1)
Authors: Singha Bipradeb , Gatla Himavanth , Chang Tzu‐Pei , Manna Subrata , Sanacora Shannon , Vancurova Ivana
Published: June 2021

Pro‐inflammatory and pro‐angiogenic chemokines interleukin‐8 (IL‐8), CCL2 (MCP‐1) and CXCL5 (ENA‐78) contribute to ovarian cancer progression through their induction of tumor cell proliferation, survival, angiogenesis and metastasis. Though proteasome inhibition by bortezomib (BZ) has been considered for the treatment of ovarian cancer, it has not been used because of its limited effectiveness; however, the responsible mechanisms remain elusive. Here, we show that proteasome inhibition dramatically increases the expression of IL‐8, CCL2 and CXCL5. The responsible mechanism involves an increased nuclear accumulation of IKKβ, and an increased recruitment of the nuclear IKKβ, p65 phosphorylated at S536, and transcription factor early growth response‐1 (EGR‐1) to the endogenous IL‐8, CCL2 and CXCL5 promoters. Co‐immunoprecipitation studies identified nuclear EGR‐1 associated with IKKβ and with p65, with preferential binding to S536P‐p65. Both IKKβ activity and EGR‐1 expression were required for the increased expression of IL‐8, CCL2 and CXCL5 induced by proteasome inhibition in ovarian cancer cells. These data indicate that the increased expression of IL‐8, CCL2 and CXCL5 may represent one of the underlying mechanisms responsible for the decreased effectiveness of proteasome inhibition in ovarian cancer treatment, and identify IKKβ and EGR‐1 as potential new targets in ovarian cancer therapies.

Grant Funding Source: Supported by NIH grants AI085497 and CA173452 to I.V.
Differential expression patterns of histone modifying enzymes in ovarian cancer in response to estradiol and bisphenol A (942.3)
Authors: Morey Lisa , Weening Allison , Hayes Laura
Published: June 2021

Ovarian cancer is the ninth most common cancer but the fifth leading cause of cancer death for women. It has long been known that ovarian cancer growth and development is dependent upon estrogen. Conversely there is less known about how environmental estrogens influence ovarian cancer development. Estrogenic compounds have been shown to affect the epigenome, yet little is known about the specific mechanisms by which these changes occur. This work focused on the effects of both estradiol and the endocrine disruptor bisphenol A (BPA) on the expression of histone modifying enzymes (HMEs) in two different human ovarian cancer model systems, SKOV3 and OVCAR3. Specifically, the expression of Set8, a histone methyl transferase, and Sirt1, a histone deacetylase, was examined in response to physiological doses of either estrogen or BPA. In addition, the experiments were carried out using physiological conditions. There are differences in the expression pattern of these genes between the two compounds and also between the two model systems. These results imply that environmental estrogens potentially impact global gene expression by changing the expression of HMEs. Furthermore these changes are different depending on the model system analyzed demonstrating a complex effect of these compounds in human ovarian cancer.
Uncovering transcription factor binding pockets in the tail subdomain of the human mediator complex (943.2)
Authors: Polinkovsky Mark , Sierecki Emma , Giles Nichole , Alexandrov Kirill , Gambin Yann
Published: June 2021

The Mediator Complex plays a major role in regulating gene transcription in eukaryotes. One of its fundamental roles is to integrate inputs from a variety of transcription factors to control the gene’s transcriptional state. The majority of these transcription factors are thought to bind to the Mediator’s Tail subdomain. In humans, the Tail is composed of eight subunit proteins, whose structure and arrangement remain unknown, largely due to difficulties in expressing and purifying them. Moreover, only a few interactions between transcription factors and some of the Tail subunits have been found.

To overcome difficulties in protein expression and interaction analysis, we used the Leishmania cell‐free protein expression system and pair‐wise measurements of protein interactions via the AlphaScreen assay. These methods allowed us to build a model of the interactions between protein subunits in the Mediator Tail. As validation, we pulled down all the component proteins in the Tail subdomain from a single cell‐free co‐expression. The same techniques were used to test the binding of various transcription factors to the Tail subunits. Our results show that different families of transcription factors bind to distinct groups of subunits in the Tail. Combined with our model of the Tail, this data reveals binding pockets on the Tail’s surface.

Grant Funding Source: Supported by Australian Research Council
Mutant versions of histone H3 are defective for nucleosome reassembly and histone chaperone recruitment during transcription (944.3)
Authors: Hainer Sarah , Martens Joseph
Published: June 2021

Expression of the Saccharomyces cerevisiae SER3 gene is regulated by transcription interference. In the presence of serine, transcription of SRG1 ncDNA is initiated upstream of the adjacent SER3 gene and extends across the SER3 promoter. Our previous studies provided evidence that during SRG1 transcription, Spt6 and Spt16 histone chaperones reassemble nucleosomes over the SER3 promoter after the passage of RNA Pol II, which then interfere with transcription factor binding resulting in SER3 repression. In response to serine starvation, SRG1 transcription is reduced causing nucleosome depletion over the SER3 promoter, which in turn allows transcription factors to bind the SER3 promoter and activate SER3 transcription. We recently reported the identification of mutations altering eight histone residues that strongly increase SER3 expression without reducing transcription of intergenic SRG1 ncDNA. Nucleosome occupancy across SRG1 in these mutants was reduced to degrees that correlated well with the level of SER3 derepression. Additional analyses of these mutants indicated a broader defect in transcription‐coupled nucleosome occupancy at highly transcribed genes, but not lowly transcribed genes. Taken together, these data defined a new class of histone mutants that are defective for transcription‐dependent nucleosome occupancy. Further analysis focused on a subset of these histone mutants revealed a reduced rate of nucleosome reassembly during transcription in vivo. Moreover, we provide evidence that Spt6 and Spt16 histone chaperones fail to be recruited to genes being transcribed by RNA Pol II in these mutants. These results suggest that amino acids in histone H3 and H4 promote transcription‐coupled nucleosome assembly by facilitating the recruitment or retention of Spt6 and/or Spt16 histone chaperones.

Grant Funding Source: Supported by NIGMS
Acetyltransferase association and histone acetylation at the Myod1 locus during myogenic differentiation (946.13)
Authors: Hamed Munerah , Khilji Saadia , Chen Jihong , Li Qiao
Published: June 2021

Chromatin modifications can provide a useful readout for enhancer activities. However, it is unclear whether these modification marks are a cause or consequence of enhancer activation and transcription factors occupancy. We have examined in details the acetyltransferase associations and histone acetylations at different regulatory regions of the Myod1 locus. Our studies demonstrate that the histone acetyltransferase (HAT) p300 is stepwise enriched at distinct Myod1 regulatory regions during myogenic differentiation. This enrichment of p300 is associated with increased histone acetylation in a distinct pattern. Inhibition of p300 HAT activity delays myogenic differentiation, which is coupled with decreased histone acetylation at specific Myod1 regulatory regions. We show for the first time that p300 is directly involved in the early Myod1 enhancer regulation, and provide molecular insights into how p300 HAT activity and histone acetylation are related to enhancer activation and, consequently, gene transcription

Grant Funding Source: supported by The Ministry of higher Education of Saudi Arabia (to MH) and CIHR grant (to QL)
Iron deposition and ferritin accretion in the ovaries of the yellow fever mosquito, Aedes aegypti (948.9)
Authors: Thai Theresa , Geiser Dawn , Winzerling Joy
Published: June 2021

Malaria and yellow fever are transmitted from mosquitoes to humans through a mosquito bite. Mosquitoes require the essential nutrients from a blood meal, including iron, for oogenesis. Very little research has been conducted to elucidate the effect of iron on mosquito fecundity. Understanding the mechanism of iron deposition in the ovary is important to finding potential strategies to interfere with mosquito fecundity, decrease mosquito populations, and reduce transmission rates of vector‐borne diseases. To this end, Aedes aegypti (yellow fever mosquito) ovaries were dissected from non‐blood fed, 24 h post‐blood meal (PBM), and 72 h PBM animals to measure tissue iron accumulation after a blood meal by iron inductively coupled plasma mass spectrometry (ICP‐MS). Dissected ovaries were also stained with Prussian Blue to visualize ferric iron deposition. Our results indicate that iron is present in the ovary prior to a blood meal and accumulates over time PBM, and the deposition of ferric iron is observed in different areas of the tissue before and after a blood meal. Immunohistochemistry imaging of the ovaries shows three different subunits of the iron storage and transport protein, ferritin, are present and differentially localized in the tissue. Coalescence of ferritin and iron in mosquito ovaries may suggest that the role of ferritin in this tissue is for the deposition of iron in oogenesis and ovarian homeostasis.

Grant Funding Source: Supported by funds from the Arizona Ag Experiment Station, CALS, UBRP and the Honors College
Can bisphenol‐A migrating from canned food contribute to the obesity epidemic? (959.10)
Authors: Gaissert Catherine , Subramany Kevin , Sampoli Benitez Benedetta
Published: June 2021

The prevalence of obesity has increased dramatically in the last two decades. Several studies suggest a link between Bisphenol‐A (BPA) exposure and obesity. Although BPA is banned now in baby bottles, in recent years there has been increasing public awareness and concern about the possible BPA migration into canned foods. This is due largely to the fact that BPA is used as a material for the production of epoxy resins. These resins are used in many professional industries, such as automotive and aviation, but in also the food industry for coating the metal can surfaces which are in contact with food and beverages. Because canned foods are sterilized in the production process, the possibility of BPA migration from the can is high. Indeed, several recent studies that focused on Mexican, Canadian and Belgian markets have shown high amount of BPA leaching from in canned food and coffee products. This study looks at the amount of BPA leaching into canned food products available in the American market. In particular, we examined canned tuna, tomato sauce, and ready‐to‐eat soups and baby formula. The method we use to test these products is based on an indirect enzyme‐linked immounosorbent assay (ELISA), which is highly specific to BPA and allows us to test this chemical directly on the samples without the need of complicated extraction. Preliminary analysis of results and discussion of the proper controls for this study will be presented.

Grant Funding Source: Supported by the Rose M. Badgeley Charitable Trust