In Vitro Characterization of Sumoylation of HR Proteins.
Abstract In vitro analysis of posttranslational modifications such as sumoylation provides a great tool to not only identify the target proteins but also to characterize the specific effects of this modification on the protein features and uncover possible regulatory mechanism. In this chapter, we will describe the purification of yeast SUMO machinery proteins and their use to identify SUMO modification of target proteins in vitro. Furthermore, we will show several examples characterizing the effect of sumoylation on the biochemical activities of various proteins involved in homologous recombination (HR) that help...
Source: Molecular Medicine - August 27, 2020 Category: Molecular Biology Authors: Altmannova V, Krejci L Tags: Methods Mol Biol Source Type: research
Adenosine-to-Inosine RNA Editing Enzyme ADAR and microRNAs.
Abstract RNA is subjected to over 100 different types of chemical modifications inside the cell. These modifications have various effects on its function and expression, resulting in RNA diversity. RNA editing or conversion of adenosine to inosine (A-to-I) in a double-stranded RNA is a type of RNA modification that can introduce mutations into the precursor of microRNA (miRNA). It can also regulate miRNA processing independently of A-to-I RNA editing. This chapter outlines the role of an A-to-I RNA editing enzyme ADAR in miRNA processing and the experimental systems used to analyze the interaction between miRNAs a...
Source: Molecular Medicine - July 31, 2020 Category: Molecular Biology Authors: Yuting K, Ding D, Iizasa H Tags: Methods Mol Biol Source Type: research
RNA Editing in Neurological and Neurodegenerative Disorders.
Abstract The brain is one of the organs that are preferentially targeted by adenosine-to-inosine (A-to-I) RNA editing, a posttranscriptional modification. This chemical modification affects neuronal development and functions at multiple levels, leading to normal brain homeostasis by increasing the complexity of the transcriptome. This includes modulation of the properties of ion channel and neurotransmitter receptors by recoding, redirection of miRNA targets by changing sequence complementarity, and suppression of immune response by altering RNA structure. Therefore, from another perspective, it appears that the b...
Source: Molecular Medicine - July 31, 2020 Category: Molecular Biology Authors: Costa Cruz PH, Kawahara Y Tags: Methods Mol Biol Source Type: research
Identifying novel sphingosine kinase 1 inhibitors as therapeutics against breast cancer.
This study provides a significant understanding of SphK1 inhibitors that can be used in the development of potential therapeutics against breast cancer. PMID: 31752564 [PubMed - in process] (Source: Molecular Medicine)
Source: Molecular Medicine - November 24, 2019 Category: Molecular Biology Authors: Khan FI, Lai D, Anwer R, Azim I, Khan MKA Tags: J Enzyme Inhib Med Chem Source Type: research
Staphylococcal Cassette Chromosome mec (SCCmec) Analysis of MRSA.
Abstract Methicillin-susceptible S. aureus changes to methicillin-resistant S. aureus (MRSA) upon the acquisition of staphylococcal cassette chromosome mec (SCCmec), a genomic island that encodes methicillin resistance. SCCmec elements in S. aureus are classified into different types based on the combination of mec gene complexes and ccr gene complexes, which share variations, five classes in mec and eight in ccr. To date, at least 13 types of SCCmec elements have been identified and each SCCmec type has individual characteristics. It is known that hospital-associated MRSA strains carry SCCmec elements of types, I...
Source: Molecular Medicine - September 18, 2019 Category: Molecular Biology Authors: Yamaguchi T, Ono D, Sato A Tags: Methods Mol Biol Source Type: research
Using RNA Sequencing to Characterize the Tumor Microenvironment.
Abstract RNA sequencing (RNA-seq) is an integral tool in immunogenomics, allowing for interrogation of the transcriptome of a tumor and its microenvironment. Analytical methods to deconstruct the genomics data can then be applied to infer gene expression patterns associated with the presence of various immunocyte populations. High quality RNA-seq is possible from formalin-fixed, paraffin-embedded (FFPE), fresh-frozen, and fresh tissue, with a wide variety of sequencing library preparation methods, sequencing platforms, and downstream bioinformatics analyses currently available. Selection of an appropriate library ...
Source: Molecular Medicine - September 11, 2019 Category: Molecular Biology Authors: Smith CC, Bixby LM, Miller KL, Selitsky SR, Bortone DS, Hoadley KA, Vincent BG, Serody JS Tags: Methods Mol Biol Source Type: research
Methods to Detect Immunogenic Cell Death In Vivo.
Abstract In response to selected stressors, cancer cells can undergo a form of regulated cell death that-in immunocompetent syngeneic hosts-is capable of eliciting an adaptive immune response specific for dead cell-associated antigens. Thus, such variant of regulated cell death manifests with robust antigenicity and adjuvanticity. As compared to their normal counterparts, malignant cells are highly antigenic per se, implying that they express a variety of antigens that are not covered by central tolerance. However, the precise modality through which cancer cells die in response to stress has a major influence on a...
Source: Molecular Medicine - September 11, 2019 Category: Molecular Biology Authors: Yamazaki T, Martinez AB, Rybstein M, Chen J, Sato A, Galluzzi L Tags: Methods Mol Biol Source Type: research
Analysis of Immunological Treatment Effects of Virotherapy in Tumor Tissue.
Abstract In addition of being directly tumoricidal, oncolytic viruses have emerged as potent partners for established and investigational immunotherapies due to their immune-stimulatory effects. The shifting focus on virus-mediated immune modulation calls for a comprehensive analysis of the tumor microenvironment (TME) and the factors orchestrating the antiviral and antitumor immune response. The oncolytic VSV-GP studied in our lab is a safe and potent antitumor agent with a fast replication cycle and killing of a broad range of different cancer types. It induces a robust local inflammatory conversion of the TME a...
Source: Molecular Medicine - September 7, 2019 Category: Molecular Biology Authors: Das K, Urbiola C, Spiesschaert B, Mueller P, Wollmann G Tags: Methods Mol Biol Source Type: research
In Vivo Bioimaging for Monitoring Intratumoral Virus Activity.
Abstract In vivo studies are the mainstay of translational immune-oncology and virotherapy research. In general oncology, bioluminescence imaging provides a convenient and reliable tool to visualize disseminated tumors and monitor growth kinetics or treatment effects. Unique aspects of this method in the field of oncolytic viruses are tracing the process of tumor-specific targeting, assessing potential off-target replication, and visualizing intratumoral spread. In addition, the longitudinal monitoring of virus activity kinetics over time is a very powerful feature supporting the subsequent, often elaborate, ...
Source: Molecular Medicine - September 7, 2019 Category: Molecular Biology Authors: Schreiber LM, Urbiola C, Erlmann P, Wollmann G Tags: Methods Mol Biol Source Type: research
Evaluation of caffeine as inhibitor against collagenase, elastase and tyrosinase using in silico and in vitro approach.
Abstract Skin ageing results from enhanced activation of intracellular enzymes such as collagenases, elastases and tyrosinase, stimulated by intrinsic ageing and photoageing factors. Recently, caffeine-based cosmetics are introduced that demonstrates to slow down skin photoageing process. However, no attempts have been done so for to understand caffeine functional inhibitory activity against photoageing related enzymes. Hence, this study established the caffeine molecular interaction and inhibition activity profiles against respective enzymes using in silico and in vitro methods, respectively. Results from in sili...
Source: Molecular Medicine - May 3, 2019 Category: Molecular Biology Authors: Eun Lee K, Bharadwaj S, Yadava U, Gu Kang S Tags: J Enzyme Inhib Med Chem Source Type: research
EANM Focus 1: one small step for two men, one giant leap for a specialty.
PMID: 31016331 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 24, 2019 Category: Molecular Biology Authors: Fanti S, Oyen WJG Tags: Eur J Nucl Med Mol Imaging Source Type: research
Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients.
CONCLUSIONS: Impaired TRPM3 activity was validated in NK cells isolated from CFS/ME patients using different pharmacological tools and whole-cell patch-clamp technique as the gold standard for ion channel research. This investigation further helps to establish TRPM3 channels as a prognostic marker and/ or a potential therapeutic target for CFS/ME. PMID: 31014226 [PubMed - in process] (Source: Molecular Medicine)
Source: Molecular Medicine - April 23, 2019 Category: Molecular Biology Authors: Cabanas H, Muraki K, Balinas C, Eaton-Fitch N, Staines D, Marshall-Gradisnik S Tags: Mol Med Source Type: research
Inflammasomes in neuroinflammatory and neurodegenerative diseases.
Abstract Neuroinflammation and neurodegeneration often result from the aberrant deposition of aggregated host proteins, including amyloid-β, α-synuclein, and prions, that can activate inflammasomes. Inflammasomes function as intracellular sensors of both microbial pathogens and foreign as well as host-derived danger signals. Upon activation, they induce an innate immune response by secreting the inflammatory cytokines interleukin (IL)-1β and IL-18, and additionally by inducing pyroptosis, a lytic cell death mode that releases additional inflammatory mediators. Microglia are the prominent innate imm...
Source: Molecular Medicine - April 23, 2019 Category: Molecular Biology Authors: Voet S, Srinivasan S, Lamkanfi M, van Loo G Tags: EMBO Mol Med Source Type: research
Mutating chikungunya virus non-structural protein produces potent live-attenuated vaccine candidate.
Abstract Currently, there are no commercially available live-attenuated vaccines against chikungunya virus (CHIKV). Here, CHIKVs with mutations in non-structural proteins (nsPs) were investigated for their suitability as attenuated CHIKV vaccines. R532H mutation in nsP1 caused reduced infectivity in mouse tail fibroblasts but an enhanced type-I IFN response compared to WT-CHIKV Adult mice infected with this nsP-mutant exhibited a mild joint phenotype with low-level viremia that rapidly cleared. Mechanistically, ingenuity pathway analyses revealed a tilt in the anti-inflammatory IL-10 versus pro-inflammatory IL-1&b...
Source: Molecular Medicine - April 23, 2019 Category: Molecular Biology Authors: Chan YH, Teo TH, Utt A, Tan JJ, Amrun SN, Abu Bakar F, Yee WX, Becht E, Lee CY, Lee B, Rajarethinam R, Newell E, Merits A, Carissimo G, Lum FM, Ng LF Tags: EMBO Mol Med Source Type: research
Time for new imaging and therapeutic approaches in cardiac amyloidosis.
PMID: 31016330 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 23, 2019 Category: Molecular Biology Authors: Slart RHJA, Glaudemans AWJM, Noordzij W, Bijzet J, Hazenberg BPC, Nienhuis HLA Tags: Eur J Nucl Med Mol Imaging Source Type: research
Identification of a complex genomic rearrangement in TMPRSS3 by massively parallel sequencing in Chinese cases with prelingual hearing loss.
CONCLUSION: Our study expanded the mutational spectrum of TMPRSS3 to include complex genomic rearrangements. It showcased the importance of an integrative approach to investigate CNVs and their contribution to HL. PMID: 31016883 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 23, 2019 Category: Molecular Biology Authors: Li X, Tan B, Wang X, Xu X, Wang C, Zhong M, Zhao Q, Bao Z, Peng W, Zhang L, Cheng J, Lu Y, Wu P, Yuan H Tags: Mol Genet Genomic Med Source Type: research
Expanding the phenotype for the recurrent p.Ala391Glu variant in FGFR3: Beyond crouzon syndrome and acanthosis nigricans.
CONCLUSIONS: This finding illustrates the first reported case of a child with an overlap with Pfeiffer syndrome to have the p.Ala391Glu variant. PMID: 31016899 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 23, 2019 Category: Molecular Biology Authors: Rymer K, Shiang R, Hsiung A, Pandya A, Bigdeli T, Webb BT, Rhodes J Tags: Mol Genet Genomic Med Source Type: research
Crosstalk between Oxidative Stress and Tauopathy.
Abstract Tauopathy is a collective term for neurodegenerative diseases associated with pathological modifications of tau protein. Tau modifications are mediated by many factors. Recently, reactive oxygen species (ROS) have attracted attention due to their upstream and downstream effects on tauopathy. In physiological conditions, healthy cells generate a moderate level of ROS for self-defense against foreign invaders. Imbalances between ROS and the anti-oxidation pathway cause an accumulation of excessive ROS. There is clear evidence that ROS directly promotes tau modifications in tauopathy. ROS is also highly upre...
Source: Molecular Medicine - April 22, 2019 Category: Molecular Biology Authors: Haque MM, Murale DP, Kim YK, Lee JS Tags: Int J Mol Sci Source Type: research
Pseudoprogression on PSMA PET imaging of a mCRPC patient under anti-PD1 treatment.
PMID: 31011768 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 22, 2019 Category: Molecular Biology Authors: Costa LB, Queiroz MA, Barbosa FG, Nunes RF, Marin JFG, Dzik C, Buchpiguel CA Tags: Eur J Nucl Med Mol Imaging Source Type: research
Adrenal tracer uptake by 18F-FDOPA PET/CT in patients with pheochromocytoma and controls.
Abstract CONTEXT: 18F-FDOPA PET/CT accurately localizes pheochromocytoma in patients with an established biochemical diagnosis. However, cut-off 18F-FDOPA levels of standardized uptake values (SUVmax) for both normal adrenal glands and pheochromocytoma are lacking. OBJECTIVE: Objectives of this study were to determine (1) reference maximum standardized uptake values (SUVmax) for normal adrenal 18F-DOPA tracer uptake and (2) the optimal diagnostic approach for pheochromocytoma localization by using 18F-DOPA SUVmax across a series of cut-off points: the affected adrenal gland (inter-individual analysis), the di...
Source: Molecular Medicine - April 22, 2019 Category: Molecular Biology Authors: Noordzij W, Glaudemans AWJM, Schaafsma M, van der Horst-Schrivers ANA, Slart RHJA, van Beek AP, Kerstens MN Tags: Eur J Nucl Med Mol Imaging Source Type: research
Myeloid malignancies-related somatic mutations in aging individuals.
r BCR Abstract We search for the presence of somatic mutations in 12 genes related to MDS, MPN, and AML in a Brazilian cohort composed of 609 elderly individuals from a census-based sample. PMID: 31006989 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 21, 2019 Category: Molecular Biology Authors: Coutinho DF, Zalcberg IR, Monte-Mór BCR Tags: Mol Genet Genomic Med Source Type: research
Methyl-Hispolon from Phellinus lonicerinus (Agaricomycetes) Affects Estrogen Signals in MCF-7 Breast Cancer Cells and Premature Aging in Rats.
Abstract We studied Phellinus lonicerinus to determine the cytotoxic effect and the dual estrogenic activities of methyl-hispolon and their relation to estrogen signals in vivo and in vitro. The Glide scores of methyl-hispolon-estrogen receptor α (ERα) and methyl-hispolon-ERβ docked complexes were -7.29 kcal/mol and -6.68 kcal/mol in docking simulations. Methyl-hispolon had a significant antiproliferative effect for estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen, and it exhibited dual estrogen activities. Methyl-hispolon increased the serum E2 in rats with premature ovarian failur...
Source: Molecular Medicine - April 20, 2019 Category: Molecular Biology Authors: Wang J, Lv H, Chen B, Huang W, Wang A, Liu L, He H, Chen J, Li S, Deng WQ Tags: Int J Med Mushrooms Source Type: research
GSK2801, a BAZ2/BRD9 bromodomain inhibitor, synergizes with BET inhibitors to induce apoptosis in triple-negative breast cancer.
Abstract Screening of an inhibitor library targeting kinases and epigenetic regulators identified several molecules having anti-proliferative synergy with BET bromodomain inhibitors (JQ1, OTX015) in triple-negative breast cancer (TNBC). GSK2801, an inhibitor of BAZ2A/B bromodomains, of the imitation switch chromatin remodeling complexes, and BRD9, of the SWI/SNF complex, demonstrated synergy independent of BRD4 control of P-TEFb-mediated pause-release of RNA polymerase II. GSK2801 or RNAi knockdown of BAZ2A/B with JQ1 selectively displaced BRD2 at promoters/enhancers of ETS-regulated genes. Additional displacement...
Source: Molecular Medicine - April 18, 2019 Category: Molecular Biology Authors: Bevill SM, Olivares-Quintero JF, Sciaky N, Golitz BT, Singh D, Beltran AS, Rashid NU, Stuhlmiller TJ, Hale A, Moorman NJ, Santos CM, Angus SP, Zawistowski JS, Johnson GL Tags: Mol Cancer Res Source Type: research
Clinical benefits of switching to insulin degludec irrespective of previous basal insulin therapy in people with Type 1 or Type 2 diabetes: evidence from a European, multicentre, retrospective, non-interventional study (EU-TREAT).
CONCLUSIONS: Switching to insulin degludec from other basal insulins can improve glycaemic control and/or reduce hypoglycaemia risk in people with diabetes (although there was a nonsignificant reduction in HbA1c and hypoglycaemia rates for the neutral protamine Hagedorn group in Type 1 diabetes) under routine care. This article is protected by copyright. All rights reserved. PMID: 31001865 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 18, 2019 Category: Molecular Biology Authors: Knudsen ST, Lapolla A, Schultes B, Tentolouris N, Catarig AM, Wolden ML, Siegmund T Tags: Diabet Med Source Type: research
Restoration of FVIII expression by targeted gene insertion in the FVIII locus in hemophilia A patient-derived iPSCs.
In this study, we describe a universal genome correction strategy to restore FVIII expression in induced pluripotent stem cells (iPSCs) derived from a patient with hemophilia A by the human elongation factor 1 alpha (EF1α)-mediated normal FVIII gene expression in the FVIII locus of the patient. We used the CRISPR/Cas9-mediated homology-directed repair (HDR) system to insert the B-domain deleted from the FVIII gene with the human EF1α promoter. After gene targeting, the FVIII gene was correctly inserted into iPSC lines at a high frequency (81.81%), and these cell lines retained pluripotency after knock-in and ne...
Source: Molecular Medicine - April 17, 2019 Category: Molecular Biology Authors: Sung JJ, Park CY, Leem JW, Cho MS, Kim DW Tags: Exp Mol Med Source Type: research
A novel splicing mutation of PTCH1 in a Chinese family with nevoid basal cell carcinoma syndrome.
Abstract Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease characterized by the development of multiple jaw keratocysts and basal cell carcinomas (BCC) and accompanied by diverse phenotypes. The establishment of diagnosis lies on the identification of a heterozygous germline pathogenic variant in the patched homolog 1 gene (PTCH1). PTCH1 has alternative splicing and selective initial coding exon, leading to three types of encoding proteins (PTCHL, PTCHM and PTCHS). The expression of each protein in NBCCS remains ambiguous, especially the importance of the first two exons in translat...
Source: Molecular Medicine - April 17, 2019 Category: Molecular Biology Authors: Zhou J, Zhang G, Shi M, Liu Z, Xiao M, Fu S, Gong X, Shi X Tags: Med Mol Morphol Source Type: research
Associations of intercellular adhesion molecule-1 rs5498 polymorphism with ischemic stroke: A meta-analysis.
In this study, a meta-analysis was performed to better assess the relationship between ICAM-1rs5498 polymorphism and IS. METHODS: PubMed, Medline, Embase, and CNKI were searched for eligible studies. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate associations between ICAM-1 rs5498 polymorphism and IS. RESULTS: Totally 16 studies with 2,596 cases and 11,800 controls were analyzed. A significant association with IS was observed for rs5498 polymorphism in GG versus AA + AG (recessive model, p = 0.009, OR = 1.62, 95% CI 1.13-2.32, I2 = 76%) in o...
Source: Molecular Medicine - April 17, 2019 Category: Molecular Biology Authors: Gao H, Zhang X Tags: Mol Genet Genomic Med Source Type: research
Non-Proteasomal UbL-UbA Family of Proteins in Neurodegeneration.
Abstract Ubiquitin-like/ubiquitin-associated proteins (UbL-UbA) are a well-studied family of non-proteasomal ubiquitin receptors that are evolutionarily conserved across species. Members of this non-homogenous family facilitate and support proteasomal activity by promoting different effects on proteostasis but exhibit diverse extra-proteasomal activities. Dysfunctional UbL-UbA proteins render cells, particularly neurons, more susceptible to stressors or aging and may cause earlier neurodegeneration. In this review, we summarized the properties and functions of UbL-UbA family members identified to date, with an emp...
Source: Molecular Medicine - April 17, 2019 Category: Molecular Biology Authors: Jantrapirom S, Lo Piccolo L, Yamaguchi M Tags: Int J Mol Sci Source Type: research
Low-Grade Inflammation Is Associated with Apathy Indirectly via Deep White Matter Lesions in Community-Dwelling Older Adults: The Sefuri Study.
Abstract Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white...
Source: Molecular Medicine - April 17, 2019 Category: Molecular Biology Authors: Yao H, Mizoguchi Y, Monji A, Yakushiji Y, Takashima Y, Uchino A, Yuzuriha T, Hashimoto M Tags: Int J Mol Sci Source Type: research
Random gene sets in predicting survival of patients with hepatocellular carcinoma.
In conclusion, we demonstrate that using "swarm intelligence" of multiple gene sets for prognosis prediction may not only be superior but also more robust for predictive purposes. KEY MESSAGES: Molecular signatures predicting HCC have not yet been integrated into clinical routine Depending on the selected size, 4.7 to 23.5% of all random gene sets exhibit prognostic potential; independent of the technical platform (microarray, RNASeq) Using "swarm intelligence" resulted in a significantly improved predictability In these patients, approx. 70% of all random 50-gene containing gene sets resulted in equal ...
Source: Molecular Medicine - April 17, 2019 Category: Molecular Biology Authors: Itzel T, Spang R, Maass T, Munker S, Roessler S, Ebert MP, Schlitt HJ, Herr W, Evert M, Teufel A Tags: J Mol Med (Berl) Source Type: research
TRESK (K2P18.1) Background Potassium Channel is Activated by Novel-Type Protein Kinase C via Dephosphorylation.
Abstract TRESK (K2P18.1) background K+ channel is a major determinant of the excitability of primary sensory neurons. It has been reported that human TRESK is activated by the protein kinase C (PKC) activator PMA (phorbol 12-myristate 13-acetate) in Xenopus oocytes. In the present study, we investigated the mechanism of this PKC-dependent TRESK regulation. We show that TRESK is activated by the coexpression of the novel-type PKC isoforms eta and epsilon. The effect of PKC is not mediated by calcineurin phosphatase, which is known to evoke the calcium-dependent TRESK activation. The mutations of the calcineurin-bin...
Source: Molecular Medicine - April 16, 2019 Category: Molecular Biology Authors: Pergel E, Lengyel M, Enyedi P, Czirjak G Tags: Mol Pharmacol Source Type: research
Phosphoregulation of the oncogenic protein regulator of cytokinesis 1 (PRC1) by the atypical CDK16/CCNY complex.
In conclusion, we identified PRC1 as the first substrate of the CDK16/CCNY complex and demonstrated that the proliferative function of CDK16 is mediated by PRC1 phosphorylation. As CDK16 is emerging as a critical node in cancer, our study reveals novel potential therapeutic targets. PMID: 30992425 [PubMed - in process] (Source: Molecular Medicine)
Source: Molecular Medicine - April 16, 2019 Category: Molecular Biology Authors: Hernández-Ortega S, Sánchez-Botet A, Quandt E, Masip N, Gasa L, Verde G, Jiménez J, Levin RS, Rutaganira FU, Burlingame AL, Wolfgeher D, Ribeiro MPC, Kron SJ, Shokat KM, Clotet J Tags: Exp Mol Med Source Type: research
Development of a patient-derived xenograft model of glioblastoma via intravitreal injection in mice.
In this study, a novel PDX model of glioblastoma was developed via intravitreal injection to facilitate tumor formation in a brain-mimicking microenvironment with improved visibility and fast development. Glioblastoma cells were prepared from the primary and recurrent tumor tissues of a 39-year-old female patient. To demonstrate the feasibility of intracranial tumor formation, U-87 MG and patient-derived glioblastoma cells were injected into the brain parenchyma of Balb/c nude mice. Unlike the U-87 MG cells, the patient-derived glioblastoma cells failed to form intracranial tumors until 6 weeks after tumor cell injection. ...
Source: Molecular Medicine - April 16, 2019 Category: Molecular Biology Authors: Lee J, Jo DH, Kim JH, Cho CS, Han JE, Kim Y, Park H, Yoo SH, Yu YS, Moon HE, Park HR, Kim DG, Kim JH, Paek SH Tags: Exp Mol Med Source Type: research
Role of BDNF in the development of an OFC-amygdala circuit regulating sociability in mouse and human.
Abstract Social deficits are common in many psychiatric disorders. However, due to inadequate tools for manipulating circuit activity in humans and unspecific paradigms for modeling social behaviors in rodents, our understanding of the molecular and circuit mechanisms mediating social behaviors remains relatively limited. Using human functional neuroimaging and rodent fiber photometry, we identified a mOFC-BLA projection that modulates social approach behavior and influences susceptibility to social anxiety. In humans and knock-in mice with a loss of function BDNF SNP (Val66Met), the functionality of this circuit ...
Source: Molecular Medicine - April 16, 2019 Category: Molecular Biology Authors: Li A, Jing D, Dellarco DV, Hall BS, Yang R, Heilberg RT, Huang C, Liston C, Casey BJ, Lee FS Tags: Mol Psychiatry Source Type: research
IgG4-related disease: Association with a rare gene variant expressed in cytotoxic T cells.
CONCLUSIONS: The presence of a shared deleterious variant and homozygous common variant in FGFBP2 in the proband and sons strongly implicates this cytotoxic T cell product in the pathophysiology of IgG4-RD. The high prevalence of a common FGFBP2 variant in sporadic IgG4-RD supports the likelihood of participation in disease. PMID: 30993913 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 16, 2019 Category: Molecular Biology Authors: Newman JH, Shaver A, Sheehan JH, Mallal S, Stone JH, Pillai S, Bastarache L, Riebau D, Allard-Chamard H, Stone WM, Perugino C, Pilkinton M, Smith SA, McDonnell WJ, Capra JA, Meiler J, Cogan J, Xing K, Mahajan VS, Mattoo H, Hamid R, Phillips JA, Undiagnose Tags: Mol Genet Genomic Med Source Type: research
Identification of novel mutations in preaxial polydactyly patients through whole-exome sequencing.
CONCLUSION: Our study highlights the important roles of primary cilia in limb development, and helps to further understand the molecular mechanisms for polydactyly formation. PMID: 30993914 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 16, 2019 Category: Molecular Biology Authors: Wang T, Xuan Z, Dou Y, Liu Y, Fu Y, Ren J, Lu L Tags: Mol Genet Genomic Med Source Type: research
Endorsement of International Consensus Radiochemistry Nomenclature Guidelines.
PMID: 30989249 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 16, 2019 Category: Molecular Biology Authors: Elsinga P, Delaloye AB, Chiti A, Vandenberghe S, Giammarile F, Carrio I Tags: Eur J Nucl Med Mol Imaging Source Type: research
Isotopic Labeling and Quantitative Proteomics of Acetylation on Histones and Beyond.
Abstract Lysine acetylation is an important posttranslational modification (PTM) that regulates the function of proteins by affecting their localization, stability, binding, and enzymatic activity. Aberrant acetylation patterns have been observed in numerous diseases, most notably cancer, which has spurred the development of potential therapeutics that target acetylation pathways. Mass spectrometry (MS) has become the most adopted tool not only for the qualitative identification of acetylation sites but also for their large-scale quantification. By using heavy isotope labeling in cell culture combined with MS, it ...
Source: Molecular Medicine - April 15, 2019 Category: Molecular Biology Authors: Lund PJ, Kori Y, Zhao X, Sidoli S, Yuan ZF, Garcia BA Tags: Methods Mol Biol Source Type: research
Correction to: 18F-DOPA PET/CT in brain tumors: impact on multidisciplinary brain tumor board decisions.
Abstract Jérôme Barriere was inadvertently missing in the original version of this article. He has participated to the study design, protocol writing and inclusion of a significant number of patients. PMID: 30980100 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 13, 2019 Category: Molecular Biology Authors: Humbert O, Bourg V, Mondot L, Gal J, Bondiau PY, Fontaine D, Barriere J, Saada-Bouzid E, Paquet M, Chardin D, Almairac F, Vandenbos F, Darcourt J Tags: Eur J Nucl Med Mol Imaging Source Type: research
Benefits of a factorial design focusing on inclusion of female and male animals in one experiment.
h A Abstract Disease occurrence, clinical manifestations, and outcomes differ between men and women. Yet, women and men are most of the time treated similarly, which is often based on experimental data over-representing one sex. Accounting for persisting sex bias in biomedical research is the misconception that the analysis of sex-specific effects would double sample size and costs. We designed an analysis to test the potential benefits of a factorial study design in the context of a study including male and female animals. We chose a 2 × 2 factorial design approach to study the effect of treat...
Source: Molecular Medicine - April 13, 2019 Category: Molecular Biology Authors: Buch T, Moos K, Ferreira FM, Fröhlich H, Gebhard C, Tresch A Tags: J Mol Med (Berl) Source Type: research
Optical Regulation of Class C GPCRs by Photoswitchable Orthogonal Remotely Tethered Ligands.
Abstract G protein-coupled receptors (GPCRs) respond to a wide range of extracellular cues to initiate complex downstream signaling cascades that control myriad aspects of cell function. Despite a long-standing appreciation of their importance to both basic physiology and disease treatment, it remains a major challenge to understand the dynamic activation patterns of GPCRs and the mechanisms by which they modulate biological processes at the molecular, cellular, and tissue levels. Unfortunately, classical methods of pharmacology and genetic knockout are often unable to provide the requisite precision needed to pro...
Source: Molecular Medicine - April 12, 2019 Category: Molecular Biology Authors: Acosta-Ruiz A, Broichhagen J, Levitz J Tags: Methods Mol Biol Source Type: research
LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) distinctly regulate neutrophil extravasation through hotspots I and II.
Abstract Precise spatiotemporal regulation of leukocyte extravasation is key for generating an efficient immune response to injury or infection. The integrins LFA-1(CD11a/CD18) and Mac-1(CD11b/CD18) play overlapping roles in neutrophil migration because they bind the same as well as different ligands in response to extracellular signaling. Using two-photon intravital imaging and transmission electron microscopy, we observed the existence of preferred sites for neutrophil entrance into the endothelial cell monolayer and exit from the basement membrane and pericyte sheath during neutrophil extravasation, namely, hot...
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Hyun YM, Choe YH, Park SA, Kim M Tags: Exp Mol Med Source Type: research
Rab5C enhances resistance to ionizing radiation in rectal cancer.
Abstract Rectal cancer represents one third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment reducing the risk of local recurrence. However, a pathologic complete response is only achieved in 10-40% of cases and the mechanisms associated with resistance are poorly understood. To identify potential targets for preventing therapy resistance, a proteomic analysis of biopsy specimens collected from stage II and III rectal adenocarcinoma patients before neoadjuvant treatment was performed and compared with residual tumor tissues removed ...
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Baptistella AR, Landemberger MC, Dias MVS, Giudice FS, Rodrigues BR, da Silva PPCE, Cassinela EK, Lacerda TC, Marchi FA, Leme AFP, Begnami MD, Aguiar S, Martins VR Tags: J Mol Med (Berl) Source Type: research
Novel mutations of COL4A3, COL4A4, and COL4A5 genes in Chinese patients with Alport Syndrome using next generation sequence technique.
CONCLUSION: A comparison of the clinical manifestations caused by different types of mutations in COL4A5 suggested that large fragment mutations are relatively more severe than the other missense mutations and AS by some mutations may show inter- and intra-familial phenotypic variability. It is important to consider these transmission patterns in the clinical evaluation according to the results of genetic testing, especially for DI. Twenty two new mutations can expand the genotypic spectrum of AS. PMID: 30968591 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Zhao X, Chen C, Wei Y, Zhao G, Liu L, Wang C, Zhang J, Kong X Tags: Mol Genet Genomic Med Source Type: research
Genotype-phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21-hydroxylase deficiency.
CONCLUSION: Four novel mutations were identified and a high consistency of genotype-phenotype association was found in SW CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease. PMID: 30968594 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Xu C, Jia W, Cheng X, Ying H, Chen J, Xu J, Guan Q, Zhou X, Zheng D, Li G, Zhao J Tags: Mol Genet Genomic Med Source Type: research
Prioritization and comprehensive analysis of genes related to major depressive disorder.
CONCLUSIONS: This work provided a reference for the study of MDD, although future validation by extensive experimentation is still required. PMID: 30968596 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Liu Y, Fan P, Zhang S, Wang Y, Liu D Tags: Mol Genet Genomic Med Source Type: research
Clinical utility in infants with suspected monogenic conditions through next-generation sequencing.
CONCLUSION: This study provides evidence that NGS can yield high success rates in a tertiary pediatric setting, but suggests that the scope of known Mendelian conditions may be considerably broader than currently recognized. PMID: 30968598 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Hong S, Wang L, Zhao D, Zhang Y, Chen Y, Tan J, Liang L, Zhu T Tags: Mol Genet Genomic Med Source Type: research
HDAC4 mutations cause diabetes and induce β-cell FoxO1 nuclear exclusion.
CONCLUSION: Mutations in HDAC4 disrupt the deacetylation of FoxO1, subsequently decrease the β-cell function including insulin secretion, resulting in diabetes. PMID: 30968599 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Gong M, Yu Y, Liang L, Vuralli D, Froehler S, Kuehnen P, Du Bois P, Zhang J, Cao A, Liu Y, Hussain K, Fielitz J, Jia S, Chen W, Raile K Tags: Mol Genet Genomic Med Source Type: research
Prevalence of BRCA1 and BRCA2 gene mutations in Chinese patients with high-risk breast cancer.
CONCLUSION: We found that patients with triple-negative breast cancer had a higher frequency of BRCA1 mutations than those with non-triple-negative breast cancer. In this study, no significant associations between the BRCA1/2 mutation status and age, family history of breast cancer, ovarian cancer, pancreatic cancer and prostate cancer, number of primary lesions, tumor size, or lymph node metastasis were observed. PMID: 30968603 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Wang X, Liu H, Maimaitiaili A, Zhao G, Li S, Lv Z, Wu D, Shi A, Guan X, Jia H, Li M, Song D, Kang L, Han B, Fu T, Yang M, Zhu Z, Du Y, Song Y, Hong J, Fan Z Tags: Mol Genet Genomic Med Source Type: research
Achillea biebersteinni Afan may inhibit scar formation: In vitro study.
CONCLUSION: The results showed that the pattern of changes in the expression of TGFβ1 and bFGF by Achillea biebersteinni Afan extract may inhibit scar formation. PMID: 30968605 [PubMed - as supplied by publisher] (Source: Molecular Medicine)
Source: Molecular Medicine - April 9, 2019 Category: Molecular Biology Authors: Hormozi M, Baharvand P Tags: Mol Genet Genomic Med Source Type: research