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CNR Institute of Molecular Biology and ... Publications | LitMetric

148 results match your criteria: "CNR Institute of Molecular Biology and Pathology[Affiliation]"

Genetic Polymorphisms of Prokineticins and Prokineticin Receptors Associated with Human Disease.

Life (Basel)

October 2024

Department of Biochemical Sciences "A. Rossi Fanelli", CNR-Institute of Molecular Biology and Pathology, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185 Rome, Italy.

Article Synopsis
  • * Genetic variations (polymorphisms) in the PKs and PKR genes have been associated with conditions like infertility, neuroendocrine disorders, Hirschsprung's syndrome, central precocious puberty, and Kallmann syndrome.
  • * The study aims to highlight how these genetic variations impact disease development and outcomes, positioning the PK system as a potential target for therapy and a marker for diagnosis in related health issues.
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Toxoplasmosis persists as a prevalent disease, facing challenges from parasite resistance and treatment side effects. Consequently, identifying new drugs by exploring novel protein targets is essential for effective intervention. Cyclosporin A (CsA) possesses antiparasitic activity against Toxoplasma gondii, with cyclophilins identified as possible targets.

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Oxidative Stress in Transthyretin-Mediated Amyloidosis: An Exploratory Study.

Antioxidants (Basel)

August 2024

Center for Rare Neuromuscular Diseases, Department of Human Neuroscience, Sapienza University of Rome, Viale dell'Università 30, 00185 Rome, Italy.

Transthyretin-mediated amyloidosis (ATTR) is a systemic disease with protein precipitation in many tissues, mainly the peripheral nerve and heart. Both genetic (ATTRv, "v" for variant) and wild-type (ATTRwt) forms are known. Beyond the steric encumbrance, precipitated transthyretin seems to have a toxic effect.

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Preserving Genome Integrity: Unveiling the Roles of ESCRT Machinery.

Cells

August 2024

Department of Biology and Biotechnologies "Charles Darwin", Sapienza University, 00185 Rome, Italy.

The endosomal sorting complex required for transport (ESCRT) machinery is composed of an articulated architecture of proteins that assemble at multiple cellular sites. The ESCRT machinery is involved in pathways that are pivotal for the physiology of the cell, including vesicle transport, cell division, and membrane repair. The subunits of the ESCRT I complex are mainly responsible for anchoring the machinery to the action site.

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The escalating drug resistance among microorganisms underscores the urgent need for innovative therapeutic strategies and a comprehensive understanding of bacteria's defense mechanisms against oxidative stress and antibiotics. Among the recently discovered barriers, the endogenous production of hydrogen sulfide (HS) via the reverse transsulfuration pathway, emerges as a noteworthy factor. In this study, we have explored the catalytic capabilities and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa (PaCGL), a multidrug-opportunistic pathogen chiefly responsible for nosocomial infections.

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Conformational and dynamic properties of the KH1 domain of FMRP and its fragile X syndrome linked G266E variant.

Biochim Biophys Acta Proteins Proteom

July 2024

Department of Biochemical Sciences, Sapienza University of Rome, P.le Aldo Moro 5, Rome 00185, Italy. Electronic address:

The Fragile X messenger ribonucleoprotein (FMRP) is a multi-domain protein involved in interactions with various macromolecules, including proteins and coding/non-coding RNAs. The three KH domains (KH0, KH1 and KH2) within FMRP are recognized for their roles in mRNA binding. In the context of Fragile X syndrome (FXS), over-and-above CGG triplet repeats expansion, three specific point mutations have been identified, each affecting one of the three KH domains (KH0, KH1, and KH2) resulting in the expression of non-functional FMRP.

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Hydrogen sulfide (HS) has been proposed to protect bacteria from antibiotics, pointing to HS-producing enzymes as possible targets for the development of antibiotic adjuvants. Here, MIC assays performed with mutants producing altered HS levels demonstrate that HS does not affect antibiotic resistance in this bacterium. Moreover, correlation analyses in a large collection of cystic fibrosis isolates argue against the protective role of HS from antibiotic activity during chronic lung infection.

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Article Synopsis
  • DNA damage is identified as a significant contributor to heart disease, particularly involving cardiomyocytes and smooth muscle cells, though the details are not fully understood.
  • Research focused on a factor called Ft1 in mice and AKTIP in humans, revealing that its depletion leads to telomere instability and DNA damage, impacting heart health.
  • Two mouse models with varying Ft1 depletion showed that both developed cardiac issues like hypertrophy and fibrosis, but the smooth muscle-targeted model exhibited milder, age-exacerbated symptoms, suggesting Ft1 deficiency is a key factor in cardiac disease progression.
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The control of non-coding repeated DNA by DNA methylation plays an important role in genomic stability, contributing to health and healthy aging. Mind-body practices can elicit psychophysical wellbeing via epigenetic mechanisms, including DNA methylation. However, in this context the effects of movement meditations have rarely been examined.

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Molecular insights into RmcA-mediated c-di-GMP consumption: Linking redox potential to biofilm morphogenesis in Pseudomonas aeruginosa.

Microbiol Res

December 2023

Laboratory affiliated to Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Rome, Italy. Electronic address:

The ability of many bacteria to form biofilms contributes to their resilience and makes infections more difficult to treat. Biofilm growth leads to the formation of internal oxygen gradients, creating hypoxic subzones where cellular reducing power accumulates, and metabolic activities can be limited. The pathogen Pseudomonas aeruginosa counteracts the redox imbalance in the hypoxic biofilm subzones by producing redox-active electron shuttles (phenazines) and by secreting extracellular matrix, leading to an increased surface area-to-volume ratio, which favors gas exchange.

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HAX1 is a novel binding partner of Che-1/AATF. Implications in oxidative stress cell response.

Biochim Biophys Acta Mol Cell Res

January 2024

CNR-Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy. Electronic address:

HAX1 is a multifunctional protein involved in the antagonism of apoptosis in cellular response to oxidative stress. In the present study we identified HAX1 as a novel binding partner for Che-1/AATF, a pro-survival factor which plays a crucial role in fundamental processes, including response to multiple stresses and apoptosis. HAX1 and Che-1 proteins show extensive colocalization in mitochondria and we demonstrated that their association is strengthened after oxidative stress stimuli.

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Role of myristoylation in modulating PCaP1 interaction with calmodulin.

Plant Physiol Biochem

October 2023

Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134, Verona, Italy.

Plasma membrane-associated Cation-binding Protein 1 (PCaP1) belongs to the plant-unique DREPP protein family with largely unknown biological functions but ascertained roles in plant development and calcium (Ca) signaling. PCaP1 is anchored to the plasma membrane via N-myristoylation and a polybasic cluster, and its N-terminal region can bind Ca/calmodulin (CaM). However, the molecular determinants of PCaP1-Ca-CaM interaction and the functional impact of myristoylation in the complex formation and Ca sensitivity of CaM remained to be elucidated.

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Article Synopsis
  • Epilepsy commonly occurs alongside Alzheimer's disease (AD) and often appears before noticeable memory decline, suggesting a potential link worth studying in early AD stages.
  • Research on Tg2576 mice showed that repeated seizures led to memory impairment and increased amyloid-β (Aβ) levels specifically in those with pre-symptomatic AD, indicating a connection between seizures and AD pathology.
  • The antiepileptic drug lamotrigine was effective in reversing the neuronal changes and memory deficits caused by seizures, suggesting it could help mitigate the progression of AD in its early stages.
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SMN Deficiency Destabilizes ABCA1 Expression in Human Fibroblasts: Novel Insights in Pathophysiology of Spinal Muscular Atrophy.

Int J Mol Sci

February 2023

CNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.

The deficiency of survival motor neuron protein (SMN) causes spinal muscular atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins.

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Special Issue "G Protein-Coupled Receptors: Molecular Mechanisms Involved in Receptor Activation and Selectivity".

Life (Basel)

January 2023

Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185 Rome, Italy.

Welcome to the Special Issue of Life entitled "G Protein-Coupled Receptors: Molecular Mechanisms in Receptor Activation and Selectivity" [...

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The RNA-Binding Protein SMN as a Novel Player in Laryngeal Squamous Cell Carcinoma.

Int J Mol Sci

January 2023

CNR-Institute of Biochemistry and Cell Biology, Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma.

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Non-Peptide Agonists and Antagonists of the Prokineticin Receptors.

Curr Issues Mol Biol

December 2022

Department of Biochemical Sciences "A. Rossi Fanelli", CNR-Institute of Molecular Biology and Pathology, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185 Rome, Italy.

The prokineticin family comprises a group of secreted peptides that can be classified as chemokines based on their structural features and chemotactic and immunomodulatory functions. Prokineticins (PKs) bind with high affinity to two G protein-coupled receptors (GPCRs). Prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) are involved in a variety of physiological functions such as angiogenesis and neurogenesis, hematopoiesis, the control of hypothalamic hormone secretion, the regulation of circadian rhythm and the modulation of complex behaviors such as feeding and drinking.

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Circulating U13 Small Nucleolar RNA as a Potential Biomarker in Huntington's Disease: A Pilot Study.

Int J Mol Sci

October 2022

Department of Neurosciences, Mental Health and Sensory Organs, Sant'Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy.

Plasma small RNAs have been recently explored as biomarkers in Huntington’s disease (HD). We performed an exploratory study on nine HD patients, eight healthy subjects (HS), and five psychiatric patients (PP; to control for iatrogenic confounder effects) through an Affymetrix-Gene-Chip-miRNA-Array. We validated the results in an independent population of 23 HD, 15 pre-HD, 24 PP, 28 Alzheimer’s disease (AD) patients (to control the disease-specificity) and 22 HS through real-time PCR.

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Background: Lamins, key nuclear lamina components, have been proposed as candidate risk biomarkers in different types of cancer but their accuracy is still debated. AKTIP is a telomeric protein with the property of being enriched at the nuclear lamina. AKTIP has similarity with the tumor susceptibility gene TSG101.

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For more than a century, abnormal nuclei in tumor cells, presenting subnuclear invaginations and folds on the nuclear envelope, have been known to be associated with high malignancy and poor prognosis. However, current nuclear morphology analysis focuses on the features of the entire nucleus, overlooking the malignancy-related subnuclear features in nanometer scale. The main technical challenge is to probe such tiny and randomly distributed features inside cells.

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AATF/Che-1 localizes to paraspeckles and suppresses R-loops accumulation and interferon activation in Multiple Myeloma.

EMBO J

November 2022

SAFU Laboratory, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Several kinds of stress promote the formation of three-stranded RNA:DNA hybrids called R-loops. Insufficient clearance of these structures promotes genomic instability and DNA damage, which ultimately contribute to the establishment of cancer phenotypes. Paraspeckle assemblies participate in R-loop resolution and preserve genome stability, however, the main determinants of this mechanism are still unknown.

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Prokineticin 2 in cancer-related inflammation.

Cancer Lett

October 2022

Department of Biochemical Sciences "A. Rossi Fanelli" and CNR-Institute of Molecular Biology and Pathology, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Rome, Italy. Electronic address:

Inflammation, which triggers the release of a variety of growth factors, cytokines, and chemokines, is a critical component of tumor progression. Prokineticin 2 belongs to a new family of chemokines bound to two G-protein-coupled receptors called prokineticin receptor 1 and 2 that exert various tissue-specific biological functions. Under pathological conditions, prokineticin 2 can induce the proliferation, migration, and angiogenesis of endothelial cells, suggesting that this molecule plays a role in tumor growth, angiogenesis, and metastasis.

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The Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton. Hence, the dysregulated activity of Gsα due to gain-of-function mutations (R201C/R201H) results in severe architectural and functional derangements of the entire bone/bone marrow organ. While the consequences of gain-of-function mutations of Gsα have been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages, their effect in adipogenically-committed bone marrow stromal cells has remained unaddressed.

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Membrane-enclosed organelle compartmentalization is not the only way by which cell processes are spatially organized. Phase separation is emerging as a new driver in the organization of membrane-less compartments and biological processes. Liquid-liquid phase separation has been indicated as a new way to control the kinetics of molecular reactions and is based on weak multivalent interactions affecting the stoichiometry of the molecules involved.

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