bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE STIM1 REGULATORS SARAF IN CA2+ SIGNALING IN VIVO
Authors: Son Aran , Ahuja Malini , Muallem Shmuel 
Published: November 2023

Store‐Operated Ca2+ influx(SOCs) is mediated by the pore forming channel Orai1, which is activated and regulated by the ER Ca2+ sensor STIM1. In turn, the function of STIM1 is regulated by the SOC‐Associated Regulatory Factor SARAF. SARAF is an ER protein that interacts with STIM1 to mediate the slow Ca2+ dependent inactivation (SCDI) of Orai1 to inhibit SOC and prevent pathological Ca2+ overload. How SARAF functions in vivo is unknown. In the present work, we developed and partially characterized SARAF deficient (SARAF−/−)mice and investigated the role of SARAF in Ca2+ signaling inpancreatic and salivary gland acinar cells. At 8 weeks of age, the body weight of SARAF−/− mice is about 20% lower and the mice show significant cardiac hypertrophy and increased receptor stimulated fluid and electrolyte secretion by the salivary glands. SARAF−/− pancreatic and salivary glands acini have higher resting free cytosolic Ca2+ ([Ca2+]i) levels, increased SOC‐mediated Ca2+ influx and higher agonist‐evoked Ca2+ oscillation frequency. As a consequence, the SARAF−/− cells have higher resting and receptor‐mediated mitochondrial Ca2+ load. The interaction between STIM1 and SARAF in vitro and in vivo is regulated by stimulus intensity. Physiological stimulus intensity increased interaction of SARAF with STIM1, which remains stable for the duration of cell stimulation. At pathological high stimulus intensity interaction of SARAF with STIM1 is transient, accounting for the sustained activation of Ca2+ influx and cell toxicity. These findings suggest that SARAF plays a critical role as a regulator of SOC‐mediated Ca2+ influx in vivo and aberrant SARAF function maybe associated with Ca2+ overload and associated cytotoxicity.Support or Funding InformationNational Institutes of Health, National Institute for Dental and Craniofacial Research
The Potential of Anatomy Ontology in Anatomy Education
Authors: Barger J. Bradley 
Published: November 2023

Anatomy students frequently use a superficial study strategy when learning anatomy content. Superficial studying is characterized by a reliance on memorization, and a lack of connections between topics. One way to help students form connections and a deeper understanding of anatomy is to explicitly demonstrate the interconnectedness of anatomy topics. This explicit demonstration is rarely used in lectures, or if it is demonstrated, students fail to understand the utility of making mental connections. The Foundational Model of Anatomy is an anatomy ontology which makes explicit the relatedness of anatomical entities. The original purpose of the FMA was to create a computational tool for bioinformatics work, but I believe it has educational significance, and can help students to build a more connected and useful mental framework of anatomy. In the constructivist theory of education, a student must build their own mental framework to make sense of a complicated topic, but many students lack the tools to do this when presented with the seemingly endless content in an introductory anatomy course. Using the FMA as an organizing principle for anatomy content, students may feel less overwhelmed, and will have a starting point for building their own mental frameworks for anatomy content. This presentation will introduce the philosophical concept of ontology, and discuss the background of the FMA. A review of the literature involving the FMA will be included, and pedagogical implications will be discussed.Support or Funding InformationNone to disclose.
Dexmedetomidine and propofol differentially alter human immune cell metabolism
Authors: Schilling Jan M , Singaram Vinod , Dhanani Mehul , Habib Andy M , Bui Jack D , Patel Hemal H , Meier Angela 
Published: November 2023

IntroductionProlonged treatment with sedatives such as dexmedetomidine or propofol is common in the critically ill patient, yet their differential impact on immune cell metabolism, specifically, on mitochondrial function, remains to be elucidated. Here we hypothesize that propofol and dexmedetomidine differentially impact human immune cell mitochondrial function.Material and MethodsBlood was drawn from healthy male and female human donors and peripheral blood mononuclear cells (PBMCs) were isolated and treated with dexmedetomidine and propofol at concentrations achieved in human plasma. Intralipid was used as the control for propofol. Metabolic function (mitochondrial stress and glycolysis) was assessed using the Seahorse XF analyzer.ResultsCells treated with dexmedetomidine showed decreased maximal respiration, reserve capacity, increased non‐mitochondrial respiration, and overall decreased mitochondrial health as determined by an overall decreased respiratory control ratio (RCR) compared to buffer control in a dose dependent manner. Propofol decreased basal respiration, ATP‐linked respiration, reserve capacity, and non‐mitochondrial respiration dose dependently when compared to intralipid control. Glycolysis assay revealed that propofol treated cells had an increased glycolytic rate with glucose treatment compared to intralipid control and this rate could not be further increased upon addition of Oligomycin A, suggesting a potential glycolytic compensation.ConclusionHuman immune cell mitochondrial function is significantly and differentially altered by commonly used clinical sedatives. The phenomenon of “immune cell paralysis” has been shown to be associated with increased mortality in septic patients that are commonly treated with sedatives. Mitochondrial function has been tied to immune cell fate and our finding may therefore pose a relevant consideration when treating patients in the intensive care unit.Support or Funding InformationAngela Meier is supported by the Mentored Research Award of the International Anesthesia Research Society. Furthermore this research was supported by funds from the UCSD Department of Anesthesiology.
Correlation between beta‐arrestin1 and prolactin levels in women with depression during premenstrual dysphoric disorder
Authors: Smith Keisha , Archibong Anthony E , Ansah Twum A , Nayyar Tultul 
Published: November 2023

OBJECTIVEMeasurements of beta‐arrestin1 in women with premenstrual dysphoric disorder (PMDD) may potentially serve for biochemical diagnostic purposes and might be useful as evidence‐based support for questionnaires. A reduction in beta‐arrestin1 protein in peripheral blood mononuclear leukocytes (PBMC) and associated increased levels of plasma testosterone were demonstrated previously, during depression in women with PMDD. Hyperprolactinemia in patients with mood disorders are well evident. The present study extended our previous work by examining whether disturbances in the prolactin level distinguish in women with PMDD from premenstrual syndrome (PMS). PMDD is a severe form of PMS and as such have been suggested that women with PMDD have greater risk for future depression during pregnancy, post‐partum period and perimenopause.DESIGN METHODSStudy participants (n=25) were non‐pregnant women between 18–42 years of age with the symptoms of PMS/PMDD, but not taking any antidepressants and at the luteal phase of menstruation. The protein levels of beta‐arrestin1 in the PBMC were determined by ELISA and the prolactin levels in plasma were measured by radioimmuno assay. The participants were evaluated with Neuropsychiatric Interview (DSMIV‐TR). The severity of depression were determined by the Hamilton Depression Rating Scale scores (HRSD).RESULTSReduction in beta arrestin1 protein levels in mononuclear leukocytes with the increased levels of plasma prolactin concentrations were significantly correlated in women with depression (PMDD) as compared to PMS women.CONCLUSIONThese findings support that reduction in beta‐arrestin1 protein in PBMC are significantly correlated with increased levels of plasma prolactin concentrations during depression in women with PMDD.Support or Funding InformationClinical Research Education and Career Development in Minority R25RR17577 (NCRR/NIMHD) and U54 MD007593 (NIMHD) and U54 RR026140 (NCRR) at NIH.
Effect Of (−)‐Epicatechin On Muscle Atrophy After Spinal Cord Injury In Rat
Authors: Gonzalez‐Ruiz Cristian , Gutierrez‐Salmean Gabriela , Rubio‐Gayosso Ivan , Salgado‐Ceballos Hermelinda , Mondragon‐Lozano Rodrigo , Morales‐Guadarrama Axayacatl , Fabela Omar , Saldaña‐Rodriguez Paula , Najera Nayelli , Villarreal Francisco , Ceballos Guillermo 
Published: November 2023

Spinal Cord Injury (SCI) is a condition that produces a partial or total loss of physiological functions below the lesion. SCI typically leads to severe muscle atrophy, which limits the recovery from SCI. With muscle atrophy, the muscle fiber size diameter is reduced as cell mass decreases through increased protein turnover/degradation, loss of organelles and cytoplasm. Muscle atrophy after SCI can produce a diversity of system stressors, including neural inactivity, elevated glucocorticoid levels and notable metabolic imbalances. Treatment of such sequelae is limited. In the recent past, we have demonstrated that treatment with the flavanol (−)‐epicatechin (Epi) can trigger multiple positive effects in skeletal muscle including a decrease in the expression of myostatin and increased expression of follistatin, markers of regeneration and multiple mitochondrial proteins suggesting the activation of skeletal muscle repair and/or growth. To determinate the effect of (−)‐epicatechin on muscle atrophy after SCI in rats. Adult female Long Evans rats (250–300 g body weight) were anesthetized with ketamine and xylazine and a laminectomy was performed at T9 vertebra level, followed by spinal cord transection. After recovery from surgery, rats were randomly divided into 2 groups, 1) control group (water) and, 2) (−)‐epicatechin treated (1 mg/kg/day by oral gavage) and evaluated at 7, 30 and 60 days after lesion. Anthropometric measurements of gastrocnemius and soleus sections were performed in hindlimbs with a Vernier caliper and using conventional magnetic resonance spectroscopy. Basso, Beattie and Bresnahan (BBB) functional (locomotor) assessments were performed at 1, 7, 14, 28 days and scoring was evaluated using a circular open field. MRI evidences a 25% less decrease in crosssectional area in hindlimb muscles of Epi treated rats vs. controls. Likewise treated animals demonstrate higher BBB scores. In conclusion, Epi decreases muscle loss after SCI and appears to promote functional recovery in ratsSupport or Funding InformationNIH grants # K98717, DK92154 to FV and IPN grants # 20161576 and 2016118 and CONACyT grant # 253769
Rodent Model of Diffuse Acute and Chronic Gastritis with Translational Relevance
Authors: Csekő Kata , Deng Xiaoming , Pécsi Dániel , Hegedűs Ivett , Perkecz Anikó , Szabó Imre , Helyes Zsuzsanna , Szabó Sándor 
Published: November 2023

ObjectiveStress & anti‐inflammatory drugs induce focal superficial erosions or ulcers, however, there has been no animal model of diffuse gastritis. Sulfhydryl (SH) groups offer gastroprotection, therefore we postulated that drinking water containing SH alkylators may cause diffuse lesions in rats by depleting glutathione (GSH). Transient Receptor Potential Vanilloid 1 (TRPV1) & Ankyrin 1 (TRPA1) ion channels play role in inflammation, but their functions in gastritis have not been investigated. After demonstrating decreased TRPV1 expression in human chronic gastritis biopsies of, we wanted to optimalize and characterize a translational animal model to gain insight into the molecular mechanisms of gastritis.Aims1) Test the gastritis‐inducing effect of the SH alkylator iodoacetamide (IA); 2)observe potential strain differences in the inflammatory reactions; 3)investigate TRPV1/A1 expression alterations in comparison with human samples.MethodsWe administered 0.05% & 0.2% IA to the drinking water of Wistar & CFY male rats (8–12‐week‐old) for 7 & 14days. Body weight & water consumption were recorded daily. Macroscopic lesions were scored by the extent of hyperemia, erosions/ulcers & sections were taken for histological assessment. TRPV1/A1 mRNA expressions were determined by qPCR.ResultsIA intake resulted in concentration‐dependent weight loss & reduced water consumption. Diffuse hyperemia & erosions were observed macroscopically after 7 days in all IA‐exposed rats & in 14 days ulcers were induced by both concentrations. Microscopically submucosal edema was observeable followed by leukocytic & lymphocytic infiltration. Susequently, superficial, often hemorrhagic mucosal erosions were seen after 7 days, followed by ulcers in 14 days. In CFY rats, TRPV1 & TRPA1 mRNA expressions were significantly lower in the antrum, similarly to human biopsies. In Wistar rats TRPV1 expression did not change, but a markedTRPA1 increase was seen in both time intervals.Conclusions1) IA ingestion for 7 & 14 days caused diffuse acute & chronic gastritis, associated with hemorrhagic erosions & ulcers. 2) Ion channel expression showed a strain difference; TRPA1 mRNA level increased in Wistar rats with both IA‐concentrations & at both time intervals. 3) Since TRPV1/A1 expression in CFY rats was similar to the human gastritis, this strain has translational value to investigate the pathophysiological role of these channels in chronic gastritis.Support or Funding InformationUniversity funds and grant from Hungary Academy of Science.
Multipronged Therapeutic Effects of Chinese Herbal Medicine Sini San in the Treatment of Depressive Disorder
Authors: Wang Yong , Bai Yiqin , Nugent Colleen A. , Zhu Lixin , Wang Tian , Zhu Ruixin , Wang Wei 
Published: November 2023

BackgroundThe traditional Chinese medicine (TCM) Sini San has been known to be effective in depressive disorder treatment. Clinical studies and preclinical researches in human and animal models have confirmed the effects of Sini San on depressive disorder. However, the molecular mechanism of how Sini San affecting depressive disorder is still unclear. This study aimed to reveal the therapeutic mechanism of Sini San in depression by global transcriptomics analysis, and to understand the traditional Chinese medical theory “homogeny of liver and brain” for Sini San from the molecular level.MethodsWe performed systematical analysis on RNA expression profiles in hippocampus, hypothalamus and hepatic tissue with a depression Sprague‐Dawley (SD) rats model induced by chronic unpredictable mild stress (CUMS). We compared the depression model group (N=20) with naive rats as controls (N=20) and with the depression model with Sini San treatment group (N=20) respectively. Bioinformatics methods including differential expression analysis, gene enrichment and expression correlation analysis were conducted.ResultsWe found that the expression of 77, 724, 173 genes were influenced by Sini San treatment in depression individuals in hippocampus, hypothalamus and hepatic tissue respectively. Function of these differentially expressed genes (DEGs) covered depression‐associated genes and was consistent with established depression pathology. Among these DEGs, expression of 496 genes were reversed by Sini San, which made the expression profiles of Sini San treatment groups more similar to healthy controls than to depression model groups. Specifically, a multi‐target mechanism involving immune response and steroid synthesis was proposed to explain how Sini San exerts positive influence on depressive disorder. Hub genes like Ciita, Lcp2 and Dusp2 in immunity, and Hmgcr and Cyp1a2 in steroid metabolism exhibited significant response to Sini San treatment. Moreover, to explore the TCM theory which holds that liver in Chinese Medicine includes both anatomical liver and brain, the correlation between brain and liver in depressive disorder treated by in Sini San was investigated. Lcp2 and Cyp1a2 are highly correlated genes in brain and liver, and therefore also identified as the most important components of the therapeutic mechanism of Sini San.ConclusionThe results of the study for the first time provide a systematic molecular insight into the therapeutic mechanism of Sini San in alleviating depressive disorder.Support or Funding InformationThis work was financially supported, in part, by the Grants from the National Natural Science Foundation of China (No. 81302908, 81530100, 81473456, 81503379 and 81470191), Beijing Natural Science Foundation (No.7142099), Fok Ying Tung Education Foundation (No. 151044), and excellent young scientist foundation of BUCM (No.2016‐JYB‐XJ003, 2015‐JYB‐QNJSZX001 and 2015‐JYB‐XYQ001).
Effect of combined resveratrol plus metformin therapy in db/db diabetic mice
Authors: Duarte‐Vázquez Miguel Angel , Gómez‐Solis Antonieta , Gómez‐Cansino Rocio , Reyes‐Esparza Jorge , Rosado Jorge Luis , Rodriguez‐Fragoso Lourdes 
Published: November 2023

The prevalence of Type 2 Diabetes mellitus in the world is associated with other conditions that trigger metabolic syndrome. Although there are several studies on benefits of resveratrol, few have assessed in combination of metformin. The aim of this study was to investigate at the effects of combined therapy (metformin/resveratrol) on body weight gain, biochemical clinical findings, liver and renal function of db/db diabetic mice. Diabetic mice were treated whit resveratrol (20 mg/kg/day), metformin (150 mg/kg/day) and combined therapy for 5 weeks. Histopathological tissues analyses and biochemical parameters (glucose, insulin, triglycerides and cholesterol), functional liver enzymes (AP, AST and GGT) and renal parameters (urea and uric acid) were examined. Our results clearly showed that combined therapy of resveratrol and metformin therapy reduced obesity, glucose and triglyceride levels, as well as improving renal function and partially improving liver function in diabetic mice. The combined therapy may enhance remedial effects in diabetic patients and also in other metabolic disorders as such as metabolic syndrome.Support or Funding InformationCONACYT‐PEI Mexico for its financial support (Project 231344).
Phage Display cDNA Screens Reveal a Specific Region of Plasmodium falciparum Glutamic Acid‐rich Protein that Binds to Human Red Blood Cells. A Functional Role in Malaria Pathogenesis
Authors: Almukadi Haifa S. , Hanada Toshihiko , Chishti Athar H. 
Published: November 2023

Severe malaria caused by Plasmodium falciparum is a serious disease that affects a large number of people regardless of the mode of treatment with currently existing antimalarial drugs. In 2015, the Centers for Disease Control and Prevention (CDC) estimated nearly 214 million cases of malaria infection worldwide resulting in ~400,000 deaths mainly in sub‐Saharan Africa. Infection of red blood cells (RBCs) by P. falciparum, the most lethal species among the human malaria parasites, leads to several complications such as cytoadherence, which involves binding of infected red blood cells (iRBCs) to endothelial receptors, and rosetting, which is the binding of iRBCs to uninfected RBCs. These features contribute to specific organ damage and exacerbate disease pathogenesis. To elucidate the biological mechanisms of P. falciparum infection in human RBCs, we are currently investigating the virulence phenomena including parasite invasion and rosetting. Using phage display technology, we previously identified several novel ligand‐receptor interactions at the blood stage of malaria infection. Here, we used two independent phage display cDNA library screens and identified P. falciparum glutamic acid‐rich protein (Pf‐GARP) as a novel parasite ligand that binds to the surface of human RBCs. Specifically, we screened phage display cDNA libraries constructed from P. falciparum FCR‐3 and 3D7 strains and identified several overlapping Pf‐GARP clones expressing peptides that bind to intact RBCs. Two phage clones encoding Pf‐GARP392–437 and Pf‐GARP356–552 revealed a specific binding region located nearly in the middle of full length Pf‐GARP1–673. Using bioinformatics tools, we chemically synthesized a codon‐optimized segment, Pf‐GARP370–444, located within the overlapping phage clones. The phage cDNA inserts were cloned into pET‐32b vector, and recombinant peptides were expressed in E. coli. Recombinant fusion proteins encoded by all three Pf‐GARP cDNA were confirmed to bind human RBCs in vitro. The codon‐optimized Pf‐GARP370–444 was cloned into the pRE4 vector, and expressed on the surface of Chinese hamster ovary (CHO) cells. The transfected CHO cells formed rosette‐like clusters in the presence of uninfected human RBCs in vitro. Importantly, direct biochemical interaction between purified Pf‐GARP370–444 protein and human RBCs was abolished upon treatment of RBCs with chymotrypsin but not with trypsin and neuraminidase. These results indicate that a centrally‐located segment of Pf‐GARP recognizes a specific chymotrypsin‐sensitive receptor(s) on the surface of host RBCs. Our findings suggest a functional role of Pf‐GARP in the rosetting and invasion phenomena with implications in inter‐membrane transport and vaccine development against malaria.Support or Funding InformationFunding source: NIH‐HL060961
Virtual Surgical Planning & 3D Printing in Prosthetic Orbital Reconstruction with Percutaneous Implants: A Technical Case Report
Authors: Huang Yu‐hui 
Published: November 2023

Osseointegrated titanium implants to the cranial skeleton for retention of facial prostheses have proved to be a reliable replacement for adhesive systems. However, improper placement of the implants can jeopardize prosthetic outcomes, and long‐term success of an implant‐retained prosthesis.3D computer imaging, virtual planning and 3D printing have become accepted components of the preoperative planning and design phase of treatment. Computer‐aided design (CAD) and computer‐assisted manufacture (CAM) that employ cone‐beam computed tomography (CBCT) data offer benefits to patient treatment contributing to greater predictability and improved treatment efficiencies with more reliable outcomes in surgical and prosthetic reconstruction.3D Printing enables transfer of the virtual surgical plan to the operating room by fabrication of surgical guides. Previous studies have shown that accuracy is considerably improved with guided implantation when compared to conventional template or freehand implant placement.This clinical case report demonstrates the use of a 3D technological pathway for preoperative virtual planning through prosthesis fabrication, utilizing 3D Printing, for a patient with an acquired orbital defect which was restored with an implant‐retained silicone orbital prosthesis.Support or Funding InformationThis work was partially funded by financial support from Face the Future Foundation.