bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient‐derived MAFB Missense Mutation Is Associated with Cleft Palate in Mice
Authors: Paul Brian J. , Palmer Kristina , Padilla Crystal , Sharp Jocelyn C. , Pratt C Herbert , Murray Stephen A. , Dunnwald Martine 
Published: June 2021

Non‐syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with complex etiology. Amongst the numerous genes involved, mutations in MAFB (MAF BZIP Transcription Factor B) were recently associated with increased risk for NSCL/P. MAFB, a single‐exon gene of 3.3kb, encodes the protein MAFB, which is a transcription factor expressed in the craniofacial region at time points critical for palatal development. Previous sequencing of MAFB in cases revealed a novel missense mutation which was significantly associated with an increased risk of NSCL/P. This patient‐derived MAFB mutation, leading to the amino acid change H131Q, was knocked‐into the mouse Mafb, resulting in the allele MafbH131Q. In contrast to Mafb nulls, which die shortly after birth, MafbH131Q mice survived into adulthood at Mendelian ratios. MafbH131Q embryos were harvested for serial sectioning and histological characterization at time points critical for craniofacial development. One MafbH131Q/H131Q animal at embryonic day (e) 18.5 (N = 12) exhibited highly abnormal craniofacial morphology that included a cleft palate and shortened snout. At e13.5, our preliminary data indicate the presence of mild oral adhesions in MafbH131Q/+ and MafbH131Q/H131Q mice that were absent in wild type animals. However, immunofluorescence for periderm markers did not indicate altered expression of keratin 6 and keratin 17. These data demonstrate functional significance of the patient‐derived H131Q mutation and its role in the etiology of NSCL/P.Support or Funding InformationMD ‐ NIH/NIAMS AR067739. Additional partial financial support was provided by a grant from the NIH R37DE08559 and by the FaceBase consortium (grants DE020052 and DE020057)CP ‐ Iowa Biosciences Academy, funded by NIH/NIGMS R25GM058939, the University of Iowa (UI) Office of the Vice President for Research, and the UI Chief Diversity Office.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Relationship Between Joint Size and Trabecular Bone Density in Human and Nonhuman Primates
Authors: Chirchir Habiba , Ruff Christopher 
Published: June 2021

Biomechanically, a relationship is expected between loading and joint size, i.e., an organism with greater mechanical loading may have a large joint surface in order to mitigate greater joint stresses. However, among primates, hominoids have large long bone joint surfaces relative to diaphyseal strength, and also demonstrate generally greater joint mobility. Consequently, it has been proposed that relative joint size may also be related to greater joint excursion. Subchondral trabecular bone mass may be more directly influenced by mechanical loading of a joint. Thus, since subchondral trabecular bone density is a function of both joint size (volume) and trabecular bone mass, both mechanical loading and joint excursion could influence it. Although there has been some research investigating the relationship between trabecular bone mass and joint volume, the potential impact of joint size on trabecular bone has not been fully tested across many species in multiple limb elements. This study investigates trabecular bone density (trabecular bone fraction, TBF) in multiple proximal epiphyses in primates with varying modes of locomotion. We used a peripheral Quantitative Computed Tomography (pQCT) scanner to estimate TBF in the femur, humerus, 3rd metatarsal and 3rd metacarpal. This was done in modern humans, chimpanzees, orangutans, vervet monkeys, olive baboons, gelada baboons and patas monkeys. Pearson's correlations were used to test relationships between joint size and trabecular density in each species. The results show that TBF has broadly similar values across a large range of joint sizes. There is no strong correlation between the variables; modern humans, despite having larger joint sizes than the other primates, display low trabecular density, while orangutans and chimpanzees with intermediate joint sizes have relatively low trabecular density compared to the cercopithecines. Olive baboons with larger joints among the cercopithecines have trabecular densities that are most similar to that of vervets and patas monkeys, whose joints are relatively smaller. These results support the proposal that increased joint size is likely correlated with greater joint mobility to increase joint excursion, and is not necessarily a function of increased mechanical loading. Therefore, relationships between subchondral bone density and mechanical loading are not straightforward when compared across taxa with differences in joint excursion.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The relationship of vascular anatomy to thermal physiology: linking anatomical and imaging studies to in vivo non‐invasive infrared thermography of free‐ranging birds
Authors: Porter Wm Ruger , Tattersall Glenn J. , Caggiano Emily G. , Witmer Lawrence M. 
Published: June 2021

Vertebrates use the blood vascular system to moderate the temperature of specific anatomical regions. However, in many groups, such as birds, fundamental thermoregulatory mechanisms—the actual link between physiological function (heating and cooling) and the underlying vascular “plumbing”—have largely remained obscure, challenging our understanding of issues ranging from organismal responses to climate change to the human health consequences of vascular disease. In vivo physiological testing typically involves highly invasive procedures that may impose confounding artifacts due to stress responses mediated by the sympathetic nervous system. Fortunately, high‐resolution infrared (IR) thermal imaging provides a non‐invasive means of in vivo physiological measurement of surface temperatures in free‐ranging, normally behaving animals. In our study, thermal imaging was used to document heat maps of freely ranging birds (e.g., vultures, pelicans) in South Carolina and Florida. Quantitative thermographic data were analyzed to assess sites of heat exchange. Thermal data were compared to existing and new anatomical data based on microCT scanning of radio‐opaque (barium‐latex) vascular injections on legally obtained cadaveric bird specimens. Specific regions of the head where vascular devices in birds are suspected to be important for shedding heat as well as for cooling venous blood destined for the brain and eye were analyzed for anatomical and physiological correlations. This study seeks to establish the mechanistic links that ultimately allow birds to manage thermal stressors. Thermal images of investigated sites of thermal exchange indicated heat flow was found to correspond to the location of known blood vessels. These blood vessels were discernable in times of both heating and cooling. For example, in pelicans, the location of the ophthalmic rete corresponds to the location of a cool spot located behind the eye. Blood vessels in the pelican's pouch correspond to a streak of high temperature in the pouch. These results indicate that blood vessels play an active role in the thermophysiology of free‐ranging and unstressed birds and that the details of thermoregulatory mechanisms are discernable with non‐invasive methods.Support or Funding InformationUnited States National Science Foundation (IOB‐0517257, IOS‐1050154), Ohio University Heritage College of Osteopathic Medicine, Ohio University Research Committee, Natural Sciences and Engineering Research Council of Canada, and the National Geographic Society.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Using Cadaver Specimens to Better Understand Ulnar Nerve to Median Nerve Transfers
Authors: Dorius Geoffrey T. , Morton David A. , Mahan Mark A. 
Published: June 2021

The recurrent branch of the median nerve innervates the thenar muscles. Therefore, injury to the median nerve as it courses from the axilla to the hand has profound negative effects on the functional use of the thumb. The surgical procedure of peripheral nerve transplants in order to regain function in denervated muscle is well documented. Using the lumbrical branch of the ulnar nerve to the 4th digit as a nerve transplant with the recurrent branch of the median nerve in order to regain function is not well documented. As such, the capacity of grafting these ulnar nerve branches from their anatomical position including neuron count of each nerve and their ability to be spliced together was investigated. Cadaveric dissections were performed to document the distribution of the deep branch of the ulnar nerve as it enters the lumbrical musculature and the recurrent branch of the median nerve as it courses through the carpal tunnel. After the dissection was completed, the ulnar branch to the lumbrical muscle was drawn towards the recurrent branch of the median nerve. Using a digital camera, and electronic calipers the nerves were photographed for visual confirmation of the ability to transfer and measured to compare the size of the nerves. Sections of each branch were then studied for a comparison of neuron counts. Data suggests the nerve transfer to be a viable option, and could assist neurosurgeons in performing surgeries to help patients regain functionality in their thenar muscles. A continuation of data collection will allow greater insight into the number of neurons that can potentially re‐innervate the thenar muscles as well as assist in desired surgical outcomes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Non‐Invasive Brain Stimulation for Negative Symptoms in Schizophrenia: An Updated Systematic Review and Meta‐Analysis
Authors: Barros Mirna Duarte , Osoegawa Caio duarte , Cordeiro Quirino duarte , Gomes July Silveira , Brietzke Elisa duarte , Trevizol Alisson Paulino 
Published: June 2021

BackgroundSchizophrenia is a mental disorder with significant social and economic burden. Although current pharmacological treatments are effective for controlling the positive symptoms, medications have small‐to‐no effect for the treatment of negative symptoms.ObjectiveTo assess the efficacy of non‐invasive brain stimulation (NIBS) for negative symptoms in schizophrenia in randomized clinical trials (RCTs).MethodsA systematic review in the Medline and Cochrane Library databases was performed up to May 31, 2017. The primary outcome was the Hedges' g for continuous scores in a random‐effects model. Heterogeneity was evaluated with the I2 and the χ2 test. Publication bias was assessed using the Begg's funnel plot. Meta‐regression was performed using the random‐effects model modified by Knapp and Hartung.ResultsWe included 31 RCTs (n=1272); most with small‐to‐modest sample sizes. Active stimulation was significantly superior over sham for negative symptoms (Hedges' g = 0.23; 95% CI 0.11 – 0.34). The funnel plot and the Eggers test showed that heterogeneity and the risk of publication bias were low (I2=2.3%, p=0.429 for the χ2 test; p=0.179 for the Egger's test). Meta‐regression showed no influence of any variable on the results found. Both transcranial magnetic stimulation and transcranial direct current stimulation were superior to sham. In a subgroup analysis, no trial was alone responsible for the positive results observed.ConclusionNIBS active was superior to sham stimulation for the amelioration of negative symptoms in schizophrenia. We found no considerable heterogeneity or publication bias in our analysis, corroborating to the strength of our findings. Further RCTs with larger sample sizes are needed to clarify the precise impact of NIBS in negative symptoms in schizophrenia.
Towards A Structural Characterization of The Leopard Gecko Cerebellum: Purkinje Cells And Cells of The External Granular Layer
Authors: Bradley Stefanie , Bailey Craig D.C. , Vickaryous Matthew 
Published: June 2021

The cerebellum is a major component of the hindbrain, and plays important roles in motor coordination, posture, and cognitive functions. Although the gross anatomy and histological organization of the cerebellum has been documented across many species, less is known about the contributing cell types, especially among non‐mammals. Here we focus on Purkinje cells (PC) and cells of the External Granular Layer (EGL) in a representative lizard, the leopard gecko (Eublepharis macularius). PC serve as the major motor output of the cerebellum. Similar to other vertebrates, gecko PC are large, calbindin‐immunopositive neurons located at the junction between the molecular layer and the granular layer. Golgi‐cox impregnation reveals a dendritic arborization broadly comparable with that of alligators (and distinct from that of mammals). There is typically a single, lengthy primary dendrite that passes towards the molecular layer. This primary dendrite divides into multiple short dendritic branches that conclude in thin spiny branchlets with abundant, closely packed spines. Adult geckos also retain an EGL, a progenitor cell population that characteristically disappears prior to adulthood in mammals. Cells of the gecko EGL are immunopositive for the transcription factor SOX2, a hallmark protein of neural stem/progenitor cells, and the intermediate filament (and radial glia marker) glial fibrillary acid protein, but are immunonegative for NeuN, a marker of mature neurons. Using a bromodeoxyuridine pulse‐chase strategy, we determined that a subset of gecko EGL cells were label retaining after a 140 day chase period. Combined, these data provide important new information about the evolutionary variability of the cerebellum, with implications for functional adaptations in a species capable of tail loss.Support or Funding InformationNatural Sciences and Engineering Research Council Discovery Grant #400358 (MKV), #436190 (CDCB) and The Canada Foundation for Innovation #25371 (MKV) and #30381 (CDCB)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Catalytic functions of RECQ1 helicase are important in defying genomic stress and maintaining cell proliferation
Authors: Parvathaneni Swetha , Lu Xing , Sharma Sudha 
Published: June 2021

RecQ helicases are an important class of DNA repair proteins with critical roles in genome maintenance. RECQ1, a structure‐specific DNA helicase and the most abundant RecQ homolog in humans, is frequently upregulated in rapidly proliferating cells and has dual roles in genome maintenance and transcription regulation. RECQ1's function as well as expression levels modulates patient survival and response to anti‐cancer therapy. More recently germline mutations in RECQ1 have been linked to breast cancer susceptibility. However, the mechanism by which altered RECQ1 expression or mutations in functional domains of RECQ1 modulate response to chemotherapy and increase cancer risk is unclear. Our study aimed at generating a RECQ1 knockout cell line using CRISPR‐Cas9 technology to investigate phenotypes of cells that lack RECQ1 expression completely or express breast cancer risk associated RECQ1 mutants in an isogenic background. Our results demonstrate that we have successfully generated a human RECQ1 knockout MDA‐MB‐231 breast cancer cell line using the CRIPSR‐Cas9 technique which recapitulates previously established phenotypes of RECQ1 knockdown resulting in reduced cell proliferation, growth and migration as well as increased sensitivity to camptothecin. We further demonstrate that the missense mutations in the evolutionarily conserved residues within the catalytic core of RECQ1 that predispose individuals to breast cancer, also lead to impaired cell proliferation, increased sensitivity to replication stress and accumulation of spontaneous DNA damage indicating that defective helicase functions of RECQ1 may eventually contribute to genomic instability and drive cancer progression.Support or Funding InformationThis work was funded by the NIGMS/NIH grant SC1GM093999 to Sudha SharmaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Generating and characterizing resistance to ionizing radiation in experimentally evolved populations of Escherichia coli.
Authors: Trimarco Joseph D. , Bruckbauer Steven T. , Cox Michael M. 
Published: June 2021

Efficient and accurate DNA repair processes are essential to maintaining genomic integrity. While most DNA repair mechanisms are remarkably effective, extreme sources of DNA damage can overwhelm these processes. One such source is ionizing radiation (IR). Our lab has developed a novel approach to determining the molecular basis of bacterial IR resistance. Using directed evolution, we have generated four populations of IR‐resistant E. coli with high‐energy electron beam IR delivered via a clinical linear accelerator (Linac). The Linac administers controllable and consistent doses of ionizing radiation, allowing for accurate and repeatable conditions of selective pressure. Now at round 90 of selection, we have generated the most IR‐resistant organisms ever produced within a laboratory. Using whole‐population genomic sequencing, we have identified mutations in proteins conducting and regulating DNA repair, transcription, anaerobic metabolism, cell wall biogenesis and amelioration of reactive oxygen species. We have shown mutations in DNA double strand break repair machinery (RecA, RecBCD, RecN) and RNA polymerase (RpoB, RpoC) to confer IR resistance. Using these mutations and others, we describe genetic modifications necessary for nascent mechanisms of IR resistance.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Phototherapy on Gene Expression in the Treatment of Psoriasis
Authors: Abdo Salam N. , Tulp Orien L. , Einstein George P. 
Published: June 2021

Proliferative skin disorders such as psoriasis have been an enigma in medicine for many years with cutaneous and systemic manifestations that vary in severity. Moreover, therapeutic approaches range from over‐the‐counter topical ointment to systemic biologics which may place patients at risk of death due to immune suppression. While phototherapy has been utilized in the treatment of psoriasis, previous research studies have focused on utilizing ultraviolet radiation and other wavelengths without investigating a specific emission/absorption pattern of psoriasis patient DNA. As psoriasis affects approximately 2% of population, the results of this study will affect the treatment and improve the quality of life of numerous psoriasis patients. The purpose of this study is to analyze the effects of phototherapy on the DNA of psoriasis patients. There have been numerous studies that have conducted the genetic analysis of the psoriatic patient DNA to identify gene consequence that may be associated with a disease while others attempted ultraviolet spectrophotometric analysis of the DNA. We are seeking access to the National Psoriasis Foundation samples for analysis of pre‐and post‐ultraviolet (UVB/UVA) exposure. We will record any change in absorbance due to the exposure to UVB/UVA in a qualitative and quantitative assay using DNA Quantitation Biotechnology Spectrophotometer.Support or Funding InformationSupported by Institutional Resources of USAT‐Montserrat and the Einstein Medical Institute, North Palm Beach, FLThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The regulation of curcumin on cacinogenesis and modulation through Wnt/β‐catenin signaling in ovarian cancer cell line
Authors: Liu Chinyu , Yen Hsingyu , Tsao Chihwei , Kuo ChihChi , Lin Yawen 
Published: June 2021

Ovarian cancer (OC) is the most lethal gynecologic malignancy and the top ten cancer of females in Taiwan and all over the world. Oncogenic activation of the Wnt signaling pathway is common in cancers, but mutation of beta‐catenin in ovarian cancer is rare. In addition to genetic events, epigenetic modification of secreted frizzled‐related protein (SFRP) family has been shown to be important in regulating Wnt signaling. The SFRPs act as antagonists of the Wnt ligands and inhibit the Wnt/β‐catenin signaling pathway. In the past research indicated the curcumin rich in curcuma longa has the capacity for anti‐ inflammatory, anti‐ oxidant and anti‐cancer effects as well as involve in the epigenetic regulation. It is helpful for inhibiting the tumor suppressor gene methylated and re‐expression. Therefore, the aim of this study is going to investigate the effects of curcumin on sFRP5 DNA methylation modification in ovarian cancer cell (SKOV3). Cell was treated with DMSO, 10 μM 5‐aza‐2′‐deoxycytidine (DAC), 5 μM DAC, 20 μM curcumin and respectively combined with 5 μM DAC in 96 hours, extracting the RNA and proteins for further analyze. The results of present study show that curcumin combined with 5 μM DAC may inhibit cancer cell colony formation and migration, the total DNMT activity, DNMT3a protein expression, also regulate tumor suppressor gene SFRP5 expression through Wnt/β‐catenin signaling pathway. As a result, it can attenuate or inhibit the ovarian cancer development.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Role of Iron in the Pathogenesis of Idiopathic Pulmonary Fibrosis
Authors: Huang Chaoqun , Xu Dao , Senavirathna Lakmini Kumari , Liu Lin 
Published: June 2021

Iron is a trace element indispensable for nearly all living organisms and participates in a variety of biological processes, including electron transport, oxygen transport, and DNA synthesis. On the other hand, excessive iron can result in tissue damage due to the formation of free radicals. Abnormal iron homeostasis causes a broad spectrum of human diseases. A number of studies suggest that iron is associated with pulmonary fibrosis. However, it is still unclear about molecular mechanisms of iron action in the pathogenesis of pulmonary fibrosis. In the present study, we aimed to investigate the effects of iron on fibroblast activation and global gene expression in pulmonary fibroblasts. LL29 lung fibroblasts were treated with desferrioxamine (DFX) to deplete iron in the cells. Real‐time PCR showed that iron depletion by DFX suppressed TGFβ‐induced mRNA expression of collagens (COL1A1, COL3A1, COL4A1), α‐smooth muscle actin, and fibronectin mRNA expression. To explore the molecular mechanisms of iron action on fibroblast activation, RNA sequencing was employed to study the effects of iron on gene expression profile in LL29 fibroblasts. The expression of 1,203 mRNAs and 198 lncRNAs were found to be significantly changed by DFX. Gene ontology and functional annotation analyses indicated that iron‐downregulated mRNAs were involved in TGFβ and HIF signaling pathways and iron‐upregulated mRNAs were involved in the regulation of cell cycle. Moreover, functional annotation analyses showed that iron‐dysregulated lncRNAs were involved in the regulation of cell proliferation. Iron‐controlled SMURF2, DBF4, and MCM6 genes which contain potential iron response elements were further verified by real‐time PCR. These results suggest that iron may control fibroblast activation by regulating TGFβ signaling pathway and fibroblast proliferation by regulating cell cycle genes.Support or Funding InformationNIH R01HL116876, 1R01HL135152, and P20GM103648This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.