Cardiac pathology in neuronal ceroid lipofuscinoses (NCL): More than a mere co-morbidity
Publication date: Available online 19 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Katja Rietdorf, Emily E. Coode, Angela Schulz, Eva Wibbeler, Martin D. Bootman, John R. OstergaardAbstractThe neuronal ceroid lipofuscinoses (NCLs) are mostly seen as diseases affecting the central nervous system, but there is accumulating evidence that they have co-morbidities outside the brain. One of these co-morbidities is a decline in cardiac function. This is becoming increasingly recognised in teenagers and adolescents with juvenile CLN3, but it may also occur in individuals with othe...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 20, 2019 Category: Molecular Biology Source Type: research

The transcriptional repressor SNAI2 impairs neuroblastoma differentiation and inhibits response to retinoic acid therapy
Publication date: Available online 17 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Kirsten S. Vrenken, Britt M.T. Vervoort, Dorette S. van Ingen Schenau, Yvonne H.W. Derks, Liesbeth van Emst, Pavlo G. Grytsenko, Jeroen A.J. Middelbeek, Frank N. van LeeuwenAbstractNeuroblastoma is the most common extracranial solid tumor in children and originates from poorly differentiated neural crest progenitors. High-risk neuroblastoma patients frequently present with metastatic disease at diagnosis. Despite intensive treatment, patients often develop refractory disease characterized by...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 18, 2019 Category: Molecular Biology Source Type: research

Current status of stem cell research: An editorial
This article summarizes contributions of research into stem cell therapies. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 18, 2019 Category: Molecular Biology Source Type: research

Mitochondrial remodeling in human skin fibroblasts from sporadic male Parkinson's disease patients uncovers metabolic and mitochondrial bioenergetic defects
Publication date: Available online 20 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Cláudia M. Deus, Susana P. Pereira, Teresa Cunha-Oliveira, Francisco B. Pereira, Nuno Raimundo, Paulo J. OliveiraAbstractParkinson's Disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra. The exact mechanism by which dopaminergic neurodegeneration occurs is still unknown; however, mitochondrial dysfunction has long been implicated in PD pathogenesis. To investigate the sub-cellular events that lead to disease progression and to develop personalized in...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 14, 2019 Category: Molecular Biology Source Type: research

Betaine/GABA transporter-1 (BGT-1) deficiency in mouse prevents acute liver failure in vivo and hepatocytes apoptosis in vitro
Publication date: Available online 9 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Zhenze Liu, Qing Li, Ruling Shen, Lei Ci, Zhipeng Wan, Jiahao Shi, Qin Huang, Xu Yang, Mengjie Zhang, Hua Yang, Ruilin Sun, Zhugang Wang, Fang Huang, Tianfei Lu, Jian FeiAbstractBetaine/γ-aminobutyric acid (GABA) transporter 1 (BGT-1 or Slc6a12) is a transporter for the neurotransmitter GABA and osmolyte betaine. To date, most studies on BGT-1 have focused on its functions in the nervous system and renal osmotic homeostasis. Despite its dominant distribution in the liver, the function o...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 10, 2019 Category: Molecular Biology Source Type: research

Overexpression of Na+-HCO3– cotransporter contributes to the exacerbation of cardiac remodeling in mice with myocardial infarction by increasing intracellular calcium overload
Publication date: Available online 26 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Zhenhuan Chen, Lu Chen, Kaitong Chen, Hairuo Lin, Mengjia Shen, Lin Chen, Hailin Zhu, Yingqi Zhu, Qiancheng Wang, Fang Xi, Xiaobo Huang, Yuegang Wang, Wangjun Liao, Jianping Bin, Masanori Asakura, Jie Liu, Masafumi Kitakaze, Yulin LiaoAbstractThe role of the cardiac isoform of the electrogenic sodium-bicarbonate ion cotransporter (NBCe1) in cardiac remodeling is not fully understood. The aim of this study was to assess the effects of NBCe1 overexpression on cardiac remodeling induced by myoc...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2019 Category: Molecular Biology Source Type: research

Current nutritional and pharmacological anti-aging interventions
Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Manuel Ros, José María CarrascosaAbstractAging is the main risk factor for chronic diseases and disablement in human societies with a great impact in social and health care expenditures. So far, aging and, eventually, death are unavoidable. Nevertheless, research efforts on aging-associated diseases with the aim not only to extend life span but also to increment health span in an attempt to delay, stop and even reverse the aging process have not stopped growing. Caloric restrict...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2019 Category: Molecular Biology Source Type: research

Differential phenotypic and functional profile of epitope-specific cytotoxic CD8+ T cells in benznidazole-treated chronic asymptomatic Chagas disease patients
Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Adriana Egui, Manuel Carlos López, Inmaculada Gómez, Marina Simón, Manuel Segovia, M. Carmen ThomasAbstractOne of the greatest challenges in Chagas disease research is the search for tools that will enable the assessment of pharmacological treatment efficacy. A recently described set of serological biomarkers composed of four parasite antigens and established criteria of treatment efficacy allowed the evaluation of the impact of benznidazole treatment a short/medium time ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2019 Category: Molecular Biology Source Type: research

Notch signaling in the pathogenesis of thoracic aortic aneurysms: A bridge between embryonic and adult states
Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Anna Malashicheva, Aleksandra Kostina, Anna Kostareva, Olga Irtyuga, Vladimir UspenskyAbstractAneurysms of the thoracic aorta are a “silent killer” with no evident clinical signs until the fatal outcome. Molecular and genetic bases of thoracic aortic aneurysms mainly include transforming growth factor beta signaling, smooth muscle contractile units and metabolism genes, and extracellular matrix genes. In recent studies, a role of Notch signaling, among other pathways, has emerged ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2019 Category: Molecular Biology Source Type: research

The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria
We describe the phenotype of the Prodh2 knock out mouse model and show that the lack of HYPDH in PH mouse models results in lower levels of urinary oxalate excretion, consistent with our previous metabolic tracer and siRNA-based knockdown studies. The double knockout mouse, Grhpr KO (PH2 model) and Prodh2 KO, prevented calcium-oxalate crystal deposition in the kidney, when placed on a 1% Hyp diet. These observations support the use of the Grhpr KO mice to screen HYPDH inhibitors in vivo. Altogether these data support HYPDH as an attractive therapeutic target for PH2 and PH3 patients.Graphical abstract (Source: Biochimica e...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2019 Category: Molecular Biology Source Type: research

High fat diet consumption results in mitochondrial dysfunction, oxidative stress, and oligodendrocyte loss in the central nervous system
Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Monica R. Langley, Hyesook Yoon, Ha-Neui Kim, Chan-Il Choi, Whitney Simon, Laurel Kleppe, Ian R. Lanza, Nathan K. LeBrasseur, Aleksey Matveyenko, Isobel A. ScarisbrickAbstractMetabolic syndrome is a key risk factor and co-morbidity in multiple sclerosis (MS) and other neurological conditions, such that a better understanding of how a high fat diet contributes to oligodendrocyte loss and the capacity for myelin regeneration has the potential to highlight new treatment targets. Results demonstr...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2019 Category: Molecular Biology Source Type: research

The LRRK2-RAB axis in regulation of vesicle trafficking and α-synuclein propagation
Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Eun-Jin Bae, Seung-Jae LeeAbstractLRRK2 and SNCA, the gene for α-synuclein, are the two of the most important genetic factors of Parkinson's disease (PD). A-synuclein is aggregated and accumulated in neurons and glia in PD and considered the pathogenic culprit of the disease. A-synuclein aggregates spread from a few discrete regions of the brain to larger areas as the disease progresses through cell-to-cell propagation mechanism. LRRK2 is involved in the regulation of vesicle traffickin...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2019 Category: Molecular Biology Source Type: research

The unmet medical need for Trypanosoma cruzi-infected patients: Monitoring the disease status
Publication date: Available online 4 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Maan Zrein, Eric ChatelainAbstractPatients infected by Trypanosoma cruzi are typically diagnosed by detecting specific antibodies in serological assays. Persistence of the parasitic infection increases the risk of morbidity and mortality. There are indications that anti-parasitic therapies help to reduce these risks when comparing treated and untreated populations. However, at present, treatment efficacy cannot be properly evaluated on an individual patient basis by available laboratory metho...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 4, 2019 Category: Molecular Biology Source Type: research

Stem cells for treatment of musculoskeletal conditions orthopedic/sports medicine applications
Publication date: Available online 30 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Mimi Zumwalt, Arubala P. ReddyAbstractA myriad of musculoskeletal conditions afflicts a vast number of the world's population from birth to death. Countless pathological diseases and traumatic injuries (acute and chronic) contribute to different human disabilities, causing a tremendous financial toll on the economy of healthcare. The medical field is continually searching for novel ways to combat orthopedically related conditions. The immediate goal is the restoration of anatomy then ultimat...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 1, 2019 Category: Molecular Biology Source Type: research

Erratum to “Tetrahydrobiopterin enhances mitochondrial biogenesis and cardiac contractility via stimulation of PGC1α signaling” [Volume 1865, Issue 11, 1 November 2019, 165524]
Publication date: Available online 29 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Hyoung Kyu Kim, Jouhyun Jeon, In-Sung Song, Hae Jin Heo, Seung Hun Jeong, Le Thanh Long, Vu Thi Thu, Tae Hee Ko, Min Kim, Nari Kim, Sung Ryul Lee, Jae-Seong Yang, Mi Seon Kang, Jung-Mo Ahn, Je-Yoel Cho, Kyung Soo Ko, Byoung Doo Rhee, Bernd Nilius, Nam-Chul Ha, Ippei Shimizu (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 29, 2019 Category: Molecular Biology Source Type: research

Protective effect of metformin against palmitate-induced hepatic cell death
In this study, we aim to understand the molecular mechanism of the protective effect of metformin in NAFLD, focusing on lipotoxicity. Cell death was studied in HepG2 cells and primary rat hepatocytes exposed to palmitate and metformin. Metformin ameliorated palmitate-induced necrosis and apoptosis (decreased caspase-3/7 activity by 52% and 57% respectively) in HepG2 cells. Metformin also reduced palmitate-induced necrosis in primary rat hepatocytes (P 
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 29, 2019 Category: Molecular Biology Source Type: research

Matrix stiffness modulates ILK-mediated YAP activation to control the drug resistance of breast cancer cells
In this study, we configured polyacrylamide hydrogels of varying stiffness [low (10 kPa), intermediate (38 kPa) and high (57 kPa)] to simulate tissue physical matrix stiffness across different stages of breast cancer. After treatment with doxorubicin, cell survival rates on intermediate stiffness substrate are significantly higher. We find that high expression of ILK and YAP reduces the survival rates of breast cancer patients. Drug resistance is closely associated with the inactivation of the hippo pathway protein Merlin/MST/LATS and the activation of YAP. These results not only highlight the understanding of drug r...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 28, 2019 Category: Molecular Biology Source Type: research

Minor C allele of the SNP rs7873784 associated with rheumatoid arthritis and type-2 diabetes mellitus binds PU.1 and enhances TLR4 expression
Publication date: Available online 28 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Kirill V. Korneev, Ekaterina N. Sviriaeva, Nikita A. Mitkin, Alisa M. Gorbacheva, Aksinya N. Uvarova, Alina S. Ustiugova, Oleg L. Polanovsky, Ivan V. Kulakovskiy, Marina A. Afanasyeva, Anton M. Schwartz, Dmitry V. KuprashAbstractToll-like receptor 4 (TLR4) is an innate immunity receptor predominantly expressed on myeloid cells and involved in the development of various diseases, many of them with complex genetics. Here we present data on functionality of single nucleotide polymorphism rs7873...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 28, 2019 Category: Molecular Biology Source Type: research

Interleukin-6 plays a critical role in aldosterone-induced macrophage recruitment and infiltration in the myocardium
In conclusion, interleukin-6 played an important role in aldosterone-induced macrophage recruitment and infiltration in the myocardium. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 28, 2019 Category: Molecular Biology Source Type: research

The contribution of multicellular model organisms to neuronal ceroid lipofuscinosis research
Publication date: Available online 26 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Robert J. Huber, Stephanie M. Hughes, Wenfei Liu, Alan Morgan, Richard I. Tuxworth, Claire RussellAbstractThe NCLs (neuronal ceroid lipofuscinosis) are forms of neurodegenerative disease that affect people of all ages and ethnicities but are most prevalent in children. Commonly known as Batten disease, this debilitating neurological disorder is comprised of 13 different subtypes that are categorized based on the particular gene that is mutated (CLN1-8, CLN10-14). The pathological mechanisms ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 27, 2019 Category: Molecular Biology Source Type: research

Genes of the cGMP-PKG-Ca2+ signaling pathway are alternatively spliced in cardiomyopathy: Role of RBFOX2
Publication date: Available online 25 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Xianxiu Wan, KarryAnne Belanger, Steven G. Widen, Muge N. Kuyumcu-Martinez, Nisha J. GargAbstractAberrations in the cGMP-PKG-Ca2+ pathway are implicated in cardiovascular complications of diverse etiologies, though involved molecular mechanisms are not understood. We performed RNA-Seq analysis to profile global changes in gene expression and exon splicing in Chagas disease (ChD) murine myocardium. Ingenuity-Pathway-Analysis of transcriptome dataset identified 26 differentially expressed gene...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 26, 2019 Category: Molecular Biology Source Type: research

Metformin reduces TRPC6 expression through AMPK activation and modulates cytoskeleton dynamics in podocytes under diabetic conditions
In this study, we demonstrated that metformin normalized TRPC6 expression via AMPKα1 activation in podocytes exposed to high glucose concentrations. A quantitative analysis showed that metformin increased the colocalization of TRPC6 and AMPKα1 subunits from 42% to 61% in standard glucose (SG) medium and from 29% to 52% in high glucose (HG) medium. AMPK activation was also necessary for maintaining appropriate levels of Rho-family small GTPase activity in HG conditions. Moreover, metformin through AMPK activation remodeled cytoskeleton dynamics, and consequently, reduced filtration barrier permeability in diabet...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 26, 2019 Category: Molecular Biology Source Type: research

Overexpression of Na+–HCO3– Cotransporter contributes to the exacerbation of cardiac remodeling in mice with myocardial infarction by increasing intracellular calcium overload
Publication date: Available online 26 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Zhenhuan Chen, Lu Chen, Kaitong Chen, Hairuo Lin, Mengjia Shen, Lin Chen, Hailin Zhu, Yingqi Zhu, Qiancheng Wang, Fang Xi, Xiaobo Huang, Yuegang Wang, Wangjun Liao, Jianping Bin, Masanori Asakura, Jie Liu, Masafumi Kitakaze, Yulin LiaoAbstractThe role of the cardiac isoform of the electrogenic sodium-bicarbonate ion cotransporter (NBCe1) in cardiac remodeling is not fully understood. The aim of this study was to assess the effects of NBCe1 overexpression on cardiac remodeling induced by myoc...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 26, 2019 Category: Molecular Biology Source Type: research

Membrane transporters and receptors in pregnancy metabolic complications
Publication date: Available online 23 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Luis Sobrevia (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 24, 2019 Category: Molecular Biology Source Type: research

Apolipoprotein A-I primes beta cells to increase glucose stimulated insulin secretion
Publication date: Available online 22 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Oktawia Nilsson, Rita Del Giudice, Mototsugu Nagao, Caitriona Grönberg, Lena Eliasson, Jens O. LagerstedtAbstractThe increase of plasma levels of high-density lipoproteins and Apolipoprotein A-I (ApoA-I), its main protein component, has been shown to have a positive action on glucose disposal in type 2 diabetic patients. The current study investigates the unexplored function of ApoA-I to prime beta cells for improved insulin secretion.INS-1E rat clonal beta cells as well as isolated mur...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 24, 2019 Category: Molecular Biology Source Type: research

In-depth phenotyping reveals common and novel disease symptoms in a hemizygous knock-in mouse model (Mut-ko/ki) of mut-type methylmalonic aciduria
Publication date: Available online 23 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Marie Lucienne, Juan Antonio Aguilar-Pimentel, Oana V. Amarie, Lore Becker, Julia Calzada-Wack, Patricia da Silva-Buttkus, Lillian Garrett, Sabine M. Hölter, Philipp Mayer-Kuckuk, Birgit Rathkolb, Jan Rozman, Nadine Spielmann, Irina Treise, Dirk H. Busch, Thomas Klopstock, Carsten Schmidt-Weber, Eckhard Wolf, Wolfgang Wurst, Merima Forny, Déborah MathisAbstractIsolated methylmalonic aciduria (MMAuria) is primarily caused by deficiency of methylmalonyl-CoA mutase (MMUT or MUT). Bi...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 24, 2019 Category: Molecular Biology Source Type: research

Deciphering the role of protein kinase CK2 in the maturation/stability of F508del-CFTR
Publication date: Available online 15 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Claudio D'Amore, Christian Borgo, Valentina Bosello-Travain, Jordi Vilardell, Valentina Salizzato, Lorenzo A. Pinna, Andrea Venerando, Mauro SalviAbstractF508del-CFTR, the most common mutation in cystic fibrosis (CF) patients, impairs CFTR trafficking to plasma membrane leading to its premature proteasomal degradation. Several post-translational modifications have been identified on CFTR with multiple roles in stability, localization and channel function, and the possibility to control the e...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 22, 2019 Category: Molecular Biology Source Type: research

Pyridox(am)ine 5′-phosphate oxidase (PNPO) deficiency in zebrafish results in fatal seizures and metabolic aberrations
Publication date: Available online 21 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jolita Ciapaite, Monique Albersen, Sanne M.C. Savelberg, Marjolein Bosma, Federico Tessadori, Johan Gerrits, Nico Lansu, Susan Zwakenberg, Jeroen P.W. Bakkers, Fried J.T. Zwartkruis, Gijs van Haaften, Judith J. Jans, Nanda M. Verhoeven-DuifAbstractPyridox(am)ine 5′-phosphate oxidase (PNPO) catalyzes oxidation of pyridoxine 5′-phosphate (PNP) and pyridoxamine 5′-phosphate (PMP) to pyridoxal 5′-phosphate (PLP), the active form of vitamin B6. PNPO deficiency results in n...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 22, 2019 Category: Molecular Biology Source Type: research

Mitochondrial remodeling in human skin fibroblasts from sporadic PD male patients uncovers metabolic and mitochondrial bioenergetics defects
Publication date: Available online 20 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Cláudia M. Deus, Susana P. Pereira, Teresa Cunha-Oliveira, Francisco B. Pereira, Nuno Raimundo, Paulo J. OliveiraAbstractParkinson's Disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra. The exact mechanism by which dopaminergic neurodegeneration occurs is still unknown; however, mitochondrial dysfunction has long been implicated in PD pathogenesis. To investigate the sub-cellular events that lead to disease progression and to develop personalized in...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 21, 2019 Category: Molecular Biology Source Type: research

PF4 antagonizes retinal neovascularization via inhibiting PRAS40 phosphorylation in a mouse model of oxygen-induced retinopathy
This study, for the first time, links PF4's anti-RNV function to an intracellular signaling molecule PRAS40 and its phosphorylation. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 16, 2019 Category: Molecular Biology Source Type: research

Mechanisms of extracellular vesicle uptake in stressed retinal pigment epithelial cell monolayers
ConclusionsIn summary, while EVs from both stressed cells and control contain cargo to communicate stress messages to naive RPE cells, stress EVs contain surface ligands that confer rapid uptake by recipient cells. We propose that EVs potentially contribute to RPE dysfunction in aging and disease. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 16, 2019 Category: Molecular Biology Source Type: research

Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling
Publication date: Available online 16 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Firdos Ahmad, Dhanendra Tomar, Smriti Aryal A C, Adel B. Elmoselhi, Manfred Thomas, John W. Elrod, Douglas G. Tilley, Thomas ForceAbstractNicotinamide riboside kinase-2 (NRK-2), a muscle-specific β1 integrin binding protein, predominantly expresses in skeletal muscle with a trace amount expressed in healthy cardiac tissue. NRK-2 expression dramatically increases in mouse and human ischemic heart however, the specific role of NRK-2 in the pathophysiology of ischemic cardiac diseases is u...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 16, 2019 Category: Molecular Biology Source Type: research

Agonist-induced 4-1BB activation prevents the development of Sjӧgren's syndrome-like sialadenitis in non-obese diabetic mice
Publication date: Available online 15 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jing Zhou, BoRa You, Qing YuAbstractActivation of costimulatory receptor 4-1BB enhances T helper 1 (Th1) and CD8 T cell responses in protective immunity, and prevents or attenuates several autoimmune diseases by increasing Treg numbers and suppressing Th17 or Th2 effector response. We undertook this study to elucidate the impact of enforced 4-1BB activation on the development of SS-like sialadenitis in non-obese diabetic (NOD) model of this disease. An anti-4-1BB agnostic antibody was intrap...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2019 Category: Molecular Biology Source Type: research

Deciphering the role of protein kinase CK2 in the maturation/stability of CFTR F508del
Publication date: Available online 15 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Claudio D'Amore, Christian Borgo, Valentina Bosello-Travain, Jordi Vilardell, Valentina Salizzato, Lorenzo A. Pinna, Andrea Venerando, Mauro SalviAbstractF508del-CFTR, the most common mutation in cystic fibrosis (CF) patients, impairs CFTR trafficking to plasma membrane leading to its premature proteasomal degradation. Several post-translational modifications have been identified on CFTR with multiple roles in stability, localization and channel function, and the possibility to control the e...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2019 Category: Molecular Biology Source Type: research

Selective inhibition of PKR improves vascular inflammation and remodelling in high fructose treated primary vascular smooth muscle cells
ConclusionIn conclusion PKR activation plays an important role in the pathogenesis of vascular inflammation and remodelling, and therapeutically targeting PKR could be an effective approach to treat the abnormalities associated with vascular complications. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 1 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1866, Issue 1Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2019 Category: Molecular Biology Source Type: research

Liver-specific deletion of Ngly1 causes abnormal nuclear morphology and lipid metabolism under food stress
In this study, we focus on the physiological function of Ngly1 in liver (hepatocyte)-specific Ngly1-deficient mice generated using the cre-loxP system. We found that hepatocyte-specific Ngly1-deficient mice showed abnormal hepatocyte nuclear size/morphology with aging but did not show other notable defects in unstressed conditions. This nuclear phenotype did not appear to be related to the function of the only gene currently reported to rescue Ngly1-deficient murine lethality so far, endo-β-N-acetylglucosaminidase. We also found that under a high fructose diet induced stress, the hepatocyte-specific Ngly1-deletion res...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2019 Category: Molecular Biology Source Type: research

The deficiency of NRSF/REST enhances the pro-inflammatory function of astrocytes in a model of Parkinson's disease
Publication date: Available online 7 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Heng Li, Zhaolin Liu, Yufei Wu, Yajing Chen, Jinghui Wang, Zishan Wang, Dongping Huang, Mo Wang, Mei Yu, Jian Fei, Fang HuangAbstractNeuroinflammation, as an important pathological characteristic of Parkinson's disease (PD), is primarily mediated by activated astrocytes and microglia. Neuron-restrictive silencer factor/repressor element 1 (RE1)-silencing transcription factor (NRSF/REST) regulates many genes and signal pathways involved in the inflammatory process in astrocytes. In the present...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 12, 2019 Category: Molecular Biology Source Type: research

The deficiency of NRSF/REST enhances the pro-inflammatory function of astrocytes in the model of Parkinson's disease
Publication date: Available online 7 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Heng Li, Zhaolin Liu, Yufei Wu, Yajing Chen, Jinghui Wang, Zishan Wang, Dongping Huang, Mo Wang, Mei Yu, Jian Fei, Fang HuangAbstractNeuroinflammation, as an important pathological characteristic of Parkinson's disease (PD), is primarily mediated by activated astrocytes and microglia. Neuron-restrictive silencer factor/repressor element 1 (RE1)-silencing transcription factor (NRSF/REST) regulates many genes and signal pathways involved in the inflammatory process in astrocytes. In the present...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 8, 2019 Category: Molecular Biology Source Type: research

Intracellular calcium mishandling leads to cardiac dysfunction and ventricular arrhythmias in a mouse model of propionic acidemia
Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): M. Tamayo, A. Fulgencio-Covián, J.A. Navarro-García, A. Val-Blasco, G. Ruiz-Hurtado, M. Gil-Fernández, L. Martín-Nunez, J.A. Lopez, L.R. Desviat, C. Delgado, E. Richard, M. Fernández-VelascoAbstractPropionic acidemia (PA) is a rare metabolic disease associated with mutations in genes encoding the α and β subunits of the enzyme propionyl-CoA carboxylase. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 1, 2019 Category: Molecular Biology Source Type: research

Treatment of acetaminophen-induced liver failure by blocking the death checkpoint protein TRAIL
Publication date: Available online 30 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Qian Chen, Dehong Yan, Qingmei Zhang, Guizhong Zhang, Meng Xia, Junxin Li, Wugen Zhan, Enyun Shen, Zhihuan Li, Lilong Lin, Youhai H. Chen, Xiaochun WanAbstractAcetaminophen (APAP) is one of the most commonly used drugs worldwide, and APAP-induced liver injury is the most frequent cause of acute liver failure in developed countries. However, the mechanisms of APAP-induced hepatotoxicity are not well understood, and treatment options for the disorder are very limited. Here, we show that TRAIL (...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices
In conclusion, regardless the many common features in pathophysiology of organ fibrosis, PCTS displayed diversity in culture-induced responses and in response to the treatment with TGFβRI kinase inhibitor galunisertib, even though it targets a core fibrosis pathway. A clear understanding of the common and organ-specific features of fibrosis is the basis for developing novel antifibrotic therapies. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

Moving towards a new era of genomics in the neuronal ceroid lipofuscinoses
Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Elisabeth S. Butz, Uma Chandrachud, Sara E. Mole, Susan L. CotmanAbstractThe neuronal ceroid lipofuscinoses (NCL) are a group of disorders defined by shared clinical and pathological features, including seizures and progressive decline in vision, neurocognition, and motor functioning, as well as accumulation of autofluorescent lysosomal storage material, or ‘ceroid lipofuscin’. Research has revealed thirteen distinct genetic subtypes. Precisely how the gene mutations lead to the c...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

TDP-43 inhibitory peptide alleviates neurodegeneration and memory loss in an APP transgenic mouse model for Alzheimer's disease
Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Ju Gao, Luwen Wang, Chao Gao, Hiroyuki Arakawa, George Perry, Xinglong WangAbstractAlzheimer's disease (AD) is the leading cause of dementia in the elderly, characterized clinically by progressive decline in cognitive function and neuropathologically by the presence of senile plaques and neuronal loss in the brain. While current drugs for AD are always employed as symptomatic therapies with variable benefits, there is no treatment to delay its progression or halt neurodegeneration. TAR DNA-bi...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

Re-balancing cellular energy substrate metabolism to mend the failing heart
Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jan F.C. Glatz, Miranda Nabben, Martin E. Young, P. Christian Schulze, Heinrich Taegtmeyer, Joost J.F.P. LuikenAbstractFatty acids and glucose are the main substrates for myocardial energy provision. Under physiologic conditions, there is a distinct and finely tuned balance between the utilization of these substrates. Using the non-ischemic heart as an example, we discuss that upon stress this substrate balance is upset resulting in an over-reliance on either fatty acids or glucose, and that ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital Chagas disease
Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Lizette Rios, E. Emanuel Campos, Ramkumar Menon, M. Paola Zago, Nisha J. GargAbstractTrypanosoma cruzi (T. cruzi or Tc) is the causative agent of Chagas disease (CD). It is common for patients to suffer from non-specific symptoms or be clinically asymptomatic with acute and chronic conditions acquired through various routes of transmission. The expecting women and their fetuses are vulnerable to congenital transmission of Tc. Pregnant women face formidable health challenges because the frontl...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

Quorum sensing molecules as a novel microbial factor influencing host skeletal muscle cells
This study resulted in 30 QSM, with effects observed on C2C12 cells. Known producers of the 27 peptide QSM belong to species of the genus Staphylococcus, Streptococcus, Enterococcus, Bacillus, Lactobacillus and Escherichia, while the 3 non-peptide QSM are produced by a broad range of Gram-positive and Gram-negative bacteria. Altogether, these proof-of-concept findings provide the first evidence that QSM produced by microbiota play a role in the gut-muscle axis, opening new perspectives for diagnostic and therapeutic targets in muscle wasting diseases.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

Deficiency of CD73 activity promotes protective cardiac immunity against Trypanosoma cruzi infection but permissive environment in visceral adipose tissue
Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Natalia Eberhardt, Liliana Maria Sanmarco, Gastón Bergero, Martín Gustavo Theumer, Mónica Cristina García, Nicolas Eric Ponce, Roxana Carolina Cano, Maria Pilar AokiAbstractDamaged cells release the pro-inflammatory signal ATP, which is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine (ADO). The balance between ATP/ADO is known to determine the outcome of inflammation/infection. However, modulation of the local immune resp...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

Sex differences in progression of diabetic nephropathy in OVE26 type 1 diabetic mice
ConclusionsThis demonstration of the role of gender, combined with the detailed characterization of DN progression illustrates the value of OVE26 mice for understanding gender effects on DN and provides the basis for researchers to better select the age and sex of OVE26 mice in future studies of type 1 DN.Research in contextWhat is already known about this subject?•OVE26 mice, genetically overexpressing calmodulin in pancreatic beta cells, develop early onset type 1 diabetes.•OVE26 mice are a widely used and valuable rodent model which develop severe, progressive diabetic nephropathy, with features of established...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research

Pathomechanisms in the neuronal ceroid lipofuscinoses
Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Hemanth R. Nelvagal, Jenny Lange, Keigo Takahashi, Marta A. Tarczyluk-Wells, Jonathan D. CooperAbstractThe neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders (LSDs), traditionally grouped together based on shared clinical symptoms. The recent emergence of new forms of NCL along with an improved understanding of endo-lysosomal system function have necessitated the reassessment of their classification and pathogenesis. Novel clinical fin...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research