bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMEM49 induced ovarian cancer via apoptosis pathway
Authors: Hong Jinni , Zheng Lili , Lu Yajing , Jia Jin , Chen Jie 
Published: April 2020

Ovarian cancer was one of the most lethal types of reproductive system tumors and a leading cause of cancer‐related death in women globally. The mechanism of ovarian cancer is poorly defined, in which apoptosis might play an important role. TMEM49, a 406 amino‐acid multi‐pass membrane protein localized to the endoplasmic reticulum‐Golgi intermediate compartment membrane, was identified to be involved in cancer‐relevant processes, and was demonstrated to inhibit proliferation and pulmonary metastasis of hepato‐cellular carcinoma, but little is known about the expression pattern and biological function of TMEM49 in ovarian cancer. Thus, in this study, we tested whether TMEM49 was associated with ovarian cancer and focused on the underlying mechanism by knocking down TMEM49 expression with siRNA in ovarian cells. In vivo, immuno‐histochemistry staining was performed and results showed TMEM49 was highly up‐regulated ovarian tissue of ovarian cancer patient when compared to patient with benign ovarian tumor. In viro,, with flow cytometry and CCK8 methods, SiRNA TMEM49 was demonstrated to inhibit cell proliferation, arrest G1/S transition, and induce cell apoptosis. Furthermore, western blot showed increased expression of apoptosis‐related protein such as Caspase3, Bad, and Bax, while expression metastasis‐related protein such as MMP2, KLF10, and CXCL12 were down‐regulated by TMEM49 knockdown. All these suggested that TMEM49‐related apoptosis play a role in ovarian cancer, and TMEM49 may be a potential therapeutic target in ovarian cancer.Over‐expression of TMEM49 in ovarian cancer. a The mRNA level of TMEM49 in ovarian and normal tissues. b TMEM49 expression was significantly increased inovarian tumor tissues when compared with normal tissues of patients from TCGA dataset. c TMEM49 expression was evaluated by immunohistochemistry inovarian and adjacent tissues.Figure 1
Revealing the function of a linker in the multi‐functional regulatory protein—proline utilization A from Escherichia coli
Authors: Mao Yizi , Arentson Benjamin W. , Becker Donald F. 
Published: April 2020

Proline metabolism is critical for several cellular processes such as serving as carbon and nitrogen sources, preventing osmotic stress especially in plants, scavenging reactive oxygen species, and promoting pathogen virulence. In all organisms proline is oxidized into glutamate by the coordinated activities of the flavin‐dependent enzyme L‐proline dehydrogenase (PRODH) and NAD+‐dependent enzyme L‐glutamate‐γ‐semialdehyde (GSAL) dehydrogenase (GSALDH). In gram‐negative bacteria, these two enzymes are encoded on one polypeptide called proline utilization A (PutA). PutA from certain bacteria such as Escherichia coli (EcPutA), also includes a ribbon‐helix‐helix (RHH) DNA binding domain at the N‐terminus that is tethered to the PRODH domain by a 35 amino acid linker corresponding to residues 50–85 of the total 1320 in EcPutA. The RHH domain enables PutA to function as a transcription repressor of the put regulon (putP and putA genes) in addition to its enzymatic roles. This study aims to understand the role of the linker in the redox regulation of PutA and its functions. As conformational changes are required for PutA to switch between transcriptional repressor and enzymatic functions, the linker is proposed to be important for optimal arrangement of the RHH and PRODH domains. Partial and total linker deletion mutants, Δ50–73 EcPutA and Δ50–85 EcPutA, respectively, were characterized. Purified Δ50–85 EcPutA was shown to behave similarly to wild‐type PutA as assessed by enzyme activity and DNA binding assays. The Δ50–85 EcPutA mutant depleted of the full linker region, however, was unable to function as a transcription repressor in cell based assays indicating that the linker is necessary for EcPutA to bind to DNA in vivo. Work is ongoing to determine whether the transcription repressor activity of EcPutA is restored in partial linker mutant Δ50–73 EcPutA.Support or Funding InformationNIH grants R01GM061068 and P30GM103335. Department of Biochemistry and Redox Biology Center, University of Nebraska‐Lincoln.Model for regulation of put regulon.sFigure 1Domain structure and small angle X‐ray scattering model of EcPutA. Adapted from "Structure, function, and mechanism of proline," by L. Liu, J. J. Tanner, and D. F. Becker. 2017, Archives of Biochemistry and Biophysics, 632, p. 142. Copyright 2019 by 2019 Elsevier B.V.Figure 2
Exosome‐Encapsulated Persistent Luminescence Nanoparticles Enabled Medicinal Product‐Based Drug Delivery System
Authors: Chan Ming-Hsien , Lee L. James , Hsiao Michael 
Published: April 2020

IntroductionRecent studies have found that exosome or extracellular vesicles (EVs) are associated with cancer metastasis, disease progression, diagnosis and treatment, making cell research a hot emerging research area. Instead, cells would send them out via exocytosis. This has also been observed for other rigid nanoparticles such as silica and carbon. Relying on the superior targeting function and biocompatibility of cancer exosomes, they were able to deliver the drug to cancer stem cells deep inside the tumor in mouse models.ChallengeDespite significant efforts made in this relatively new field of exosome research, progress has been held back by challenges such as inefficient separation methods, difficulties in characterization, and lack of specific biomarkers. Moreover, the applications of exosome still need more evaluation for the true condition.ActionPersistent luminescence nanoparticles (PLNs) result in their powerful in vivo near‐infrared fluorescence, thus generating remarkable tumors imaging tracking ability in subcutaneous, orthotopic and metastatic tumors. Our study provides an approach for cancer therapy by using exosome‐biomimetic nanoparticles named PLN@tExo exocytosed by the Transwell channel electroporation (TEP) process. The PLN@tExo can be applied for drug carriers to efficiently deliver the anticancer drug into the center of cancer cells.ResolutionThe biocompatible exosome‐sheathed PLNs (Dox‐PLN@tExo) have been synthesized for targeted cancer chemotherapy. Dox‐PLN@tExos are exocytosed from cells after the TEP process. Following intravenous injection, Dox‐PLN@tExos actively accumulate in the tumor site and cross‐reactive cellular uptake by cancer cells, resulting in augmented in vivo DOX enrichment in tumor cells. Our study clearly demonstrates that exosome‐biomimetic nanoparticles have potential as drug carriers to improve anticancer efficacy.Support or Funding InformationThis research was supported by Academia Sinica [AS‐SUMMIT‐108] to MH and Academia Sinica Joint Program Office [AS‐NTU‐108‐01] to MH.The scheme figure shows the exocytotic pathway can generate therapeutic exosome and encapsulate the nanoparticles as a targeting anticancer nanovehicle.Figure 1The confocal image shows the NEP process actively sends the nanoparticles into the cytosol. Moreover, the transport effect is better than incubated‐nanoparticle directly.Figure 2
Anatomy of the Lateral Pterygoid Muscle and its Relationship with Temporomandibular Disorders. An anatomic review
Authors: Orellana Mathias Ignacio , Valenzuela Juan José , Santana Edmundo Andrés , Gold Marjorie Hanna , de la Paz García Guernica 
Published: April 2020

The lateral pterygoid muscle (LPM) is a chewing muscle that is found bilaterally in the cranial region, anatomically the LPM is made up of two bellies, an upper belly and a lower belly. The anatomical description of the LPM present in the scientific literature, showed that there is an anatomical difference or variation mainly in the insertions of the upper belly of the LPM at the level of the temporomandibular joint and specifically in the disc and articular condyle, although distributions are reported similarly they are not entirely accurate, in smaller quantities some articles reported variations in the insertion of the lower belly, and in others the appearance of a third belly of the LPM or middle belly. As mentioned above, a high number of studies that presented some type of LPM variation was associated with some type of TMD of the joint or some of its intra or extra‐articular components. A review of the literature in scientific databases was carried out after the selection of the scientific articles, which were analyzed in full text and the relationship on the anatomy of the LPM and the TMD was sought.Support or Funding InformationNo conflicts of interest declared.Search AlgorithmFigure 1

Correlation between the anatomical variation of the LPM and the TMD

Bibliographic reference

Anatomic Variation of the LPM

TMJ Dissorder

Antonopoulou M, et al. (2013)

3 insertions in the joint disc.

Dysfunction in the anterior displacement of the articular disc.

Coskun A, et al. (2009)

3 heads of the lateral pterygoid muscle.

Temporomandibular dysfunction

Dergin G, et al (2012)

Provision in patterns of variation in the insertion of the MPL, either in the articular disc and in the condyle.

No correlation was presented.

Desmons S, et al (2007)

Provision in patterns of variation in the insertion of the LPM, either in the articular disc and in the condyle.

Temporomandibular dysfunction

Imanimoghaddam M, et al. (2013)

Provision in patterns of variation in the insertion of the LPM, either in the articular disc and in the condyle

Temporomandibular dysfunction

Kawakami S, et al (2012)

Variation in the insertion of the lower head of the LPM.

Temporomandibular dissorder.

Litko M, et al (2016)

Variation in the insertion of the lower and upper head of the LPM, plus third head of the LPM.

Indirect correlation between insertion and joint disc abnormalities.

Matsunaga, et al (2009)

Variation in the insertion of the lower head of the LPM.

No correlation was presented.

Mazza D, et al (2009)

Variation in the insertion of the upper and lower head of the LPM.

Temporomandibular dysfunction, dislocation of the joint disc.

Omami G, et al (2012)

Variation in the insertion of the upper head of the LPM.

Symptomatic TMJ only with the presence of pain evaluated with VAS.

Melke G, et al (2016)

Variation in the insertion of the upper head of the LPM.

Temporomandibular dysfunction.
Cause and Consequence of MAGEB2 expression in cancer
Authors: Ramanathan Saumya , Colemon Ashley , Jones Angelle , Jackson Richala 
Published: April 2020

Melanoma Antigen Genes (MAGEs) are a family of tumor‐associated genes. MAGE‐A, ‐B and ‐C genes belong to the Type I MAGE subfamily. They are typically expressed in the male germline and then aberrantly expressed in many cancers and therefore referred to as cancer‐testis antigens. Their expression in tumors is often associated with poor patient prognosis. There is a significant gap in understanding the mechanisms that regulate the expression of Type I MAGE genes. While cancers often express more than one MAGE gene, this study focusses on MAGEB2, an exemplary member of the Type I gene family and a bona fide cancer‐testis antigen. We hypothesized that epigenetic mechanisms such as DNA methylation, which regulates the expression of many germline genes also regulates MAGEB2 gene expression. Using bioinformatics and ChIP assays, we have determined the transcription factor networks that regulate MAGEB2 expression. In addition, we show that expressing MAGEB2 gene provides non‐transformed cells with a proliferative advantage by dampening TGFb signaling. Taken together our data indicate that cells use epigenetic memory to express MAGEB2 resulting in shift of the cells’ gene signature to a pro‐proliferative, anti‐apoptotic state that firmly places cells in the path to transformation.Support or Funding InformationNSF Research Initiation Award HRD1764201 to S.R.Graphical AbstractFigure 1
Intracranial Pressure After Soccer Heading
Authors: Lee Justin Hyunwoo , Grace Evan James , Sieker Jeremy , Hargens Alan , Petersen Johan C. G. , Petersen Lonnie G. 
Published: April 2020

OBJECTIVETo evaluate the effect of soccer heading on intracranial pressure (ICP) in trained athletes.METHODSEight subjects (all male, 21.7±1.7 years) were recruited from the UC San Diego soccer team. ICP and cardiovascular variables were recorded before and after 6 repeats of heading a soccer ball kicked from 35 yards away, into a goal. ICP was estimated non‐invasively from acoustical evoked tympanic membrane displacement (Vm), where a more negative volume displacement is correlated with higher ICP. Mean arterial pressure (MAP), heart rate (HR; Nexfin, Netherlands), and ICP were recorded in three different postures, 15° head up tilt (HUT), 0° supine, −15° head down tilt (HDT), in a randomized order.RESULTSMean Vm at 15° HUT was 37.81±133.21 nL at baseline and −20.82±158.27 nL immediately post soccer heading (P=0.0482, paired t test), analogous to an increased ICP. At 0° supine, mean Vm was −46.19±178.50 nL at baseline and −84.27±183.55 nL after impact (P=0.0321, paired t test). At −15° HDT, mean Vm was −148.48±196.07 nL at baseline and −187.02±186.19 nL immediately post soccer heading (P=0.1176, paired t test). MAP and HR did not significantly change between the baseline and post soccer heading measurements.DISCUSSIONAfter repeated soccer ball heading, ICP significantly increased at 15° HUT and 0° supine, while ICP at −15° HDT, MAP and HR did not significantly change. The relative increase in ICP associated with HDT is comparable to previously described trends. Although the measurement technique currently employed does not provide an absolute ICP baseline, the technique has been established as useful in evaluating relative changes. Under that interpretation, these results reflect what may be an elevated ICP related to soccer heading impacts. Accordingly, the results of this study suggest a potential health risk of participation in head contact sports.Support or Funding InformationNASA (80NSSC19K0020) and Novo Nordic Foundation (NNF16OC0019196)Soccer Heading Increases Intracranial Pressure at Head Up Tilt and Supine PositionsVolume displacement of tympanic membrane (Vm), measured non‐invasively from acoustical evoked tympanic membrane displacement, indicated an increase in intracranial pressure (ICP) after soccer heading at 15° head up tilt (HUT) and 0° supine (n = 8, paired t test, *P < 0.05). No significant increase in ICP at −15° head down tilt (HDT) was observed after soccer heading.Figure 1
Human‐derived Bifidobacterium dentium Metabolites Modulate the Mammalian Serotonergic System
Authors: Engevik Melinda A. , Luk Berkley , Ihekweazu Faith D. , Danhof Heather A. , Chang-Graham Alexandra A. , Haag Anthony A. , Britton Robert A. , Hyser Joseph M. , Versalovic James A. 
Published: April 2020

BackgroundRecent work has identified an essential role for the gut microbiota in regulating host‐derived serotonin (5‐hydroxytryptamine; 5‐HT) from enterochromaffin cells. Studies using germ‐free mice have revealed impaired 5‐HT levels and signaling in the absence of microbes. While it is known that addition of microbial communities to germ‐free mice restores 5‐HT levels, information on which microbes directly influence 5‐HT remains unknown. Commensal Bifidobacterium species produce acetate, a short chain fatty acid known to stimulate 5‐HT release in vitro. We hypothesize that B. dentium, a model Bifidobacterium species, secretes acetate and modulates the serotonergic system.Methods & ResultsAdult germ‐free mice were mono‐associated with acetate producing B. dentium, propionate producing Bacteroides ovatus, or heat killed B. dentium. Mass spectrometry of cecal and fecal samples revealed elevated levels of acetate in B. dentium mono‐associated mice and increased ileal, colonic, fecal and serum 5‐HT compared to all other groups. No increases in acetate or 5‐HT were observed in heat‐killed B. dentium or B. ovatus treated mice compared to germ‐free controls, as assessed by mass spec, immunostaining, and qPCR. Using mouse and human enteroids, we observed that addition of B. dentium metabolites and acetate stimulated release of 5‐HT in a dose‐dependent manner. Depletion of acetate in B. dentium secreted products reduced the amount of 5‐HT released from enteroids. We also confirmed our findings using a novel NGN3 over‐expression system in human enteroids, which increased the number of enterochromaffin cells. In addition to 5‐HT alterations, we found increased expression of 5‐HT receptors 2a and 4 in B. dentium mono‐associated mouse ileum and colon. RNA in situ hybridization revealed a similar increase in 5‐HT receptor 2a in the hippocampus of B. dentium treated mice compared to germ‐free controls. Functionally, live B. dentium modulated species typical behavior previously shown to be linked to 5‐HT receptor 2a.ConclusionCollectively, these data indicate that B. dentium, and the bacterial metabolite acetate, regulate key components of the serotonergic system.B. dentium colonizes the intestinal mucus layer (left) and it’s metabolites stimulate serotonin release in mouse organoids (right).Figure 1
Microbiome Signatures Associated with Rodent Model of Traumatic Brain Injury vs. Psychological Stress
Authors: Chakraborty Nabarun , Gautam Aarti , Demar James , Hammamieh Rasha , Long Joseph , Jett Marti 
Published: April 2020

Traumatic brain injury (TBI) and post‐traumatic stress disorder (PTSD) are two signature illnesses of modern warfare. Discrimination between psychological stress and TBI using a knowledge‐driven unbiased panel of biomarker signatures will be essential for designing precise care management. Recent data suggest a role of alterations of the gut micobiome architecture susceptible to both brain injury and psychological disorders. The present study was conducted to identify factors discriminating between psychological stress and TBI in the fecal microbiome of rats and further to study the effect of diets enriched with varied polyunsaturated fat compositions.A closed‐head TBI model consisting of blast overpressure (BOP) wave exposure coupled with a weight drop concussion (Marmarou method) was used on a group of adult male rats (N=12 each exposed and sham). In parallel, an independent group of rats (N=12 each exposed and sham) was subjected to an underwater trauma (UWT) stressor model that consisted of 30s of swimming and habituation, followed by 30s of forced whole body immersion. Prior to the stress types (BOP or UWT), animals were maintained for six weeks and continued thereafter on two different diets (N=4 per diet group): Standard house chow and custom chow. Unlike the house chow, the custom diets contained no long chain ω‐3 polyunsaturated fatty acids to offset their high Linoleic acid content. The fecal bacterial populations were characterized by identification of 16S ribosomal RNA.Principal coordinate analysis showed clear separation between taxonomic phylogenetic profiles linked to the stress types from their corresponding shams. Within each stress type, the rodents fed on house chow showed different fecal microbial population from the customized diet. Firmicutes, Proteobacteria, and Cyanobacteria were those phyla of interest that showed significant population variance caused by the stress and diet variants. We integrated this microbial profile with rodent blood and brain genomic profile assayed in parallel. The result suggested a significant contribution of gut‐microbiome in energy networks related to the stress response, and diet emerged as a strong candidate in regulating resilience. This outcome could lead in identifying novel customized treatment of TBI and psychological stress.Support or Funding InformationThe project was funded by DoD‐MOMRPThe differential impact of two neurological stress models on different component of gut‐brain axisFigure 1
An allosteric hot spot in the tandem SH2 domain of ZAP‐70 regulates T‐cell signaling
Authors: Gangopadhyay Kaustav , Roy Swarnendu , Debnath Olivia , Kumari Sunitha , Das Rahul 
Published: April 2020

The T‐Cell signaling commences with the binding of Antigen Presenting Cell with T‐cell Receptor (TCR) Complex leading to the recruitment of a non‐receptor tyrosine kinase, Zeta Associated Protein‐70 (ZAP‐70), to the membrane. ZAP‐70 is comprised of the tandem SH2 domain (tSH2), which is made up of N‐terminal SH2 (N‐SH2) and C‐terminal SH2 (C‐SH2) domains, and a carboxy‐terminal kinase domain. The two SH2 domains cooperatively bind to the doubly‐phosphorylated ITAM (ITAM‐Y2P) motif resulting in a conformational rearrangement in the whole of the regulatory module, thereby releasing the autoinhibitory conformation of the kinase domain. However, the structural mechanism of how the two SH2 domain cross‐talk during ITAM‐Y2P binding and dissociation from the membrane are poorly understood. We observed that the tSH2 domain undergoes a biphasic structural transition while binding to the doubly‐phosphorylated ITAM‐ ζ1 (ITAM‐Y2P‐ ζ1) peptide. The C‐SH2 binds first to one of the phosphotyrosine in ITAM‐Y2P motifs, leading to the formation of an encounter complex which further leads to the binding by N‐SH2 domain. NMR titration and Network analysis studies show that an intra‐residue network, which allosterically interconnects the N‐SH2 and C‐SH2 binding sites, plays a central role in ITAM‐Y2P binding. Further, a mutation in the allosteric network (F117A, W165C) uncouples the two binding sites, causing autoimmune arthritis in SKG mice. The allosteric coupling in ZAP‐70 is found to be unique and thus plays a significant role in T‐cell regulation.Support or Funding InformationAuthors are thankful to Prof. John Kuriyan and Prof. David E. Wemmer for access to the 900 MHz NMR spectrometer at the University of California, Berkeley. Dr. Jeffrey G. Pelton and Dr. Patrick R. Visperas at the University of California, Berkeley for NMR data collection and sample preparation. Authors thank Prof. Gautam Basu and Mr. Barun Majumder at Bose Institute, India for access to 700 MHz NMR spectrometer. Authors are thankful to Dr. Ashima Bhattacharjee, Dr. Pradip K. Tarafdar, and Prof. Pradipta Purkayastha for access to ITC and fluorimeter. Authors thank Prof. Giuseppe Melacini and Prof. Maitrayee DasGupta for helpful discussion. The authors thanks research funding from IISER Kolkata, infrastructural facilities supported by IISER Kolkata and DST‐FIST (SR/FST/LS‐II/2017/93(c)). This work is supported by grant from SERB (ECR/2015/000142) and DBT Ramalingaswami Fellowship (BT/RFF/Re‐entry/14/2014) to Rahul Das.Figure 1