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Seminars in Cell & Developmental Biology

Kaidi D Zhang, Thomas M Coate
In hearing, mechanically sensitive hair cells (HCs) in the cochlea release glutamate onto spiral ganglion neurons (SGNs) to relay auditory information to the central nervous system (CNS). There are two main SGN subtypes, which differ in morphology, number, synaptic targets, innervation patterns and firing properties. About 90-95% of SGNs are the type I SGNs, which make a single bouton connection with inner hair cells (IHCs) and have been well described in the canonical auditory pathway for sound detection. However, less attention has been given to the type II SGNs, which exclusively innervate outer hair cells (OHCs)...
October 16, 2016: Seminars in Cell & Developmental Biology
Siniša Urban
Rhomboid proteins are considered to be the most widespread membrane proteins across all forms of life. This superfamily comprises both active intramembrane serine proteases that catalyze the release of factors from the membrane, and a eukaryotic subset of non-catalytic members in which rhomboid architecture supports deviating functions. Although rhomboid was discovered in genetic studies of insect development, rhomboid research has broadened dramatically over the past 15 years; rhomboid enzymes are now the best biophysically understood of all intramembrane proteases, and are considered promising therapeutic targets for diseases ranging from parasitic infections to Parkinsonian neurodegeneration...
October 14, 2016: Seminars in Cell & Developmental Biology
Aida Costa, Lynn M Powell, Sally Lowell, Andrew P Jarman
The proneural gene, Atoh1, is necessary and in some contexts sufficient for early inner ear hair cell development. Its function is the subject of intensive research, not least because of the possibility that it could be used in therapeutic strategies to reverse hair cell loss in deafness. However, it is clear that Atoh1's function is highly context dependent. During inner ear development, Atoh1 is only able to promote hair cell differentiation at specific developmental stages. Outside the ear, Atoh1 is required for differentiation of a variety of other cell types, for example in the intestine and cerebellum...
October 14, 2016: Seminars in Cell & Developmental Biology
James P B O'Connor
There is interest in identifying and quantifying tumor heterogeneity at the genomic, tissue pathology and clinical imaging scales, as this may help better understand tumor biology and may yield useful biomarkers for guiding therapy-based decision making. This review focuses on the role and value of using x-ray, CT, MRI and PET based imaging methods that identify, measure and map tumor heterogeneity. In particular we highlight the potential value of these techniques and the key challenges required to validate and qualify these biomarkers for clinical use...
October 4, 2016: Seminars in Cell & Developmental Biology
Mengjia Qian, Bijun Zhu, Xiangdong Wang, Michael Liebman
Patients are diagnosed as anaplastic lymphoma kinase (ALK) positive, i.e. exhibiting the ALK rearrangement, and comprise 3-7% of non-small-cell lung cancer (NSCLC) cases. Three generations of ALK inhibitors have been developed and used in targeted therapy, although there are still improving spaces of drug resistance at the initiation of each treatment. The current review discusses the pathophysiology of ALK-positive NSCLC and the role of three generations of ALK target inhibitors including crizotinib, ceritinib, alectinib and lorlatinib, as well as the mechanisms of the secondary resistance...
September 29, 2016: Seminars in Cell & Developmental Biology
Jeannette Abplanalp, Michael O Hottiger
ADP-ribosylation is an evolutionarily conserved complex posttranslational modification that alters protein function and/or interaction. Intracellularly, it is mainly catalyzed by diphtheria toxin-like ADP-ribosyltransferases (ARTDs), which attach one or several ADP-ribose residues onto target proteins. Several specific mono- and poly-ADP-ribosylation binding modules exist; hydrolases reverse the modification. The best-characterized ARTD family member, ARTD1, regulates various DNA-associated processes. Here, we focus on the role of ARTD1-mediated chromatin ADP-ribosylation in development, differentiation, and pluripotency, and the recent development of new methodologies that will enable more insight into these processes...
September 28, 2016: Seminars in Cell & Developmental Biology
Berta Alsina, Tanya T Whitfield
The vertebrate inner ear is a precision sensory organ, acting as both a microphone to receive sound and an accelerometer to detect gravity and motion. It consists of a series of interlinked, fluid-filled chambers containing patches of sensory epithelia, each with a specialised function. The ear contains many different differentiated cell types with distinct morphologies, from the flask-shaped hair cells found in thickened sensory epithelium, to the thin squamous cells that contribute to non-sensory structures, such as the semicircular canal ducts...
September 26, 2016: Seminars in Cell & Developmental Biology
Melanija Posavec Marjanović, Kerryanne Crawford, Ivan Ahel
Compaction mode of chromatin and chromatin highly organised structures regulate gene expression. Posttranslational modifications, histone variants and chromatin remodelers modulate the compaction, structure and therefore function of specific regions of chromatin. The generation of poly(ADP-ribose) (PAR) is emerging as one of the key signalling events on sites undergoing chromatin structure modulation. PAR is generated locally in response to stresses. These include genotoxic stress but also differentiation signals, metabolic and hormonal cues...
September 24, 2016: Seminars in Cell & Developmental Biology
Antonio L Serrano, Pura Muñoz-Cánoves
Duchenne muscular dystrophy (DMD) is one of the most devastating neuromuscular genetic diseases caused by the absence of dystrophin. The continuous episodes of muscle degeneration and regeneration in dystrophic muscle are accompanied by chronic inflammation and fibrosis deposition, which exacerbate disease progression. Thus, in addition of investigating strategies to cure the primary defect by gene/cell therapeutic strategies, increasing efforts are being placed on identifying the causes of the substitution of muscle by non-functional fibrotic tissue in DMD, aiming to attenuate its severity...
September 23, 2016: Seminars in Cell & Developmental Biology
Krzysztof Jagla, Benoit Kalman, Thomas Boudou, Sylvie Hénon, Sabrina Batonnet-Pichon
The use of the adapted models to decipher patho-physiological mechanisms of human diseases is always a great challenge. This is of particular importance for early-onset myopathies, in which pathological mutations often impact not only on muscle structure and function but also on developmental processes. Mice are currently the main animal model used to study neuromuscular disorders including the early-onset myopathies. However strategies based on simple animal models and on transdisciplinary approaches exploring mechanical muscle cell properties emerge as attractive, non-exclusive alternatives...
September 23, 2016: Seminars in Cell & Developmental Biology
K Martin-Hernandez, J-M Rodriguez-Vargas, V Schreiber, F Dantzer
Cell response to genotoxic stress requires a complex network of sensors and effectors from numerous signaling and repair pathways, among them the nuclear poly(ADP-ribose) polymerase 1 (PARP1) plays a central role. PARP1 is catalytically activated in the setting of DNA breaks. It uses NAD(+) as a donor and catalyses the synthesis and subsequent covalent attachment of branched ADP-ribose polymers onto itself and various acceptor proteins to promote repair. Its inhibition is now considered as an efficient therapeutic strategy to potentiate the cytotoxic effect of chemotherapy and radiation or to exploit synthetic lethality in tumours with defective homologous recombination mediated repair...
September 23, 2016: Seminars in Cell & Developmental Biology
Harald Schuhwerk, Reham Atteya, Kanstantsin Siniuk, Zhao-Qi Wang
Despite more than 50 years of research, the vast majority of the biology of poly(ADP-ribosyl)ation (PARylation) still remains a gross mystery. Originally described to be a part of the DNA repair machinery, poly(ADP-ribose) (PAR) is synthesized immediately by poly(ADP-ribose) polymerases (PARPs, also known as ARTDs) upon DNA damage and then rapidly removed by degrading enzymes. PAR provides a delicate and spatiotemporal interaction scaffold for numerous target proteins. Thus, the multifaceted PARylation system, consisting of PAR itself and its synthesizers and erasers, plays diverse roles in the DNA damage response (DDR), in DNA repair, transcription, replication, chromatin remodelling, metabolism and cell death...
September 21, 2016: Seminars in Cell & Developmental Biology
Penney M Gilbert, Valerie M Weaver
Human tissues are remarkably adaptable and robust, harboring the collective ability to detect and respond to external stresses while maintaining tissue integrity. Following injury, many tissues have the capacity to repair the damage - and restore form and function - by deploying cellular and molecular mechanisms reminiscent of developmental programs. Indeed, it is increasingly clear that cancer and chronic conditions that develop with age arise as a result of cells and tissues re-implementing and deregulating a selection of developmental programs...
September 15, 2016: Seminars in Cell & Developmental Biology
Ana-Nicoleta Bondar
Rhomboid proteolysis is an important cellular process that involves cleavage of transmembrane substrates by membrane-embedded rhomboid proteases. Such proteases can cleave substrates with essential roles in the cell, and their action has been implicated in human diseases. The remarkable sensitivity of rhomboid proteolysis to the lipid membrane environment highlights the usefulness of rhomboid proteases as model systems to dissect the role of lipids in reaction mechanisms of membrane proteins, including cleavage of substrates by γ-secretase...
September 15, 2016: Seminars in Cell & Developmental Biology
Tet Woo Lee, Vicky W K Tsang, Evert Jan Loef, Nigel P Birch
It is 27 years since neuroserpin was first discovered in the nervous system and identified as a member of the serpin superfamily. Since that time potential roles for this serine protease inhibitor have been identified in neuronal and non-neuronal systems. Many are linked to inhibition of neuroserpin's principal enzyme target, tissue plasminogen activator (tPA), although some have been suggested to involve alternate non-inhibitory mechanisms. This review focuses mainly on the inhibitory roles of neuroserpin and discusses the evidence supporting tPA as the physiological target...
September 14, 2016: Seminars in Cell & Developmental Biology
Lingyan Wang, Bijun Zhu, Miaomiao Zhang, Xiangdong Wang
Lung cancer development is a complex and dynamic progression with cancer cell mutations itself and its' orchestrate with the tumor microenvironment. Targeted therapies have been stated to heterogeneous lung cancer mutations while have a modest consequence. The tumor immune microenvironment influences lung cancer outcome by balancing the suppressive versus cytotoxic responses. The immune microenvironment heterogeneity may play an important role in lung cancer heterogeneity. In this review, we summarized the immune cells, its related cytokines and partial immune genes diversity in tumor microenvironment and its targeted potential mono and combined therapies...
September 14, 2016: Seminars in Cell & Developmental Biology
Yu Sun, Namratha Sheshadri, Wei-Xing Zong
Human SERPINB3 and SERPINB4 are evolutionary duplicated serine/cysteine protease inhibitors. Genomic analysis indicates that these paralogous genes were encoded from independent loci arising from tandem gene duplication. Although the two molecules share 92% identity of their amino acid sequences, they are distinct in the Reactive Center Loop (RCL) including a hinge region and catalytic sequences which accounts for altered substrate specificity. Elevated expression of the two molecules have been reported to contribute to numerous pathological conditions such as inflammatory diseases and cancer...
September 13, 2016: Seminars in Cell & Developmental Biology
Mengjia Qian, Diane C Wang, Hao Chen, Yunfeng Cheng
Single cell heterogeneity has already been highlighted in cancer classification, diagnosis, and treatment. Recent advanced technologies have gained more ability to reveal the heterogeneity on single cell level. In this review, we listed various detection targets applied in single cell study, including tumor tissue cells, circulating tumor cells (CTCs), disseminated tumor cells (DTCs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and cancer stem cells (CSCs). We further discussed and compared detection methods using these detection targets in different fields to reveal single cell heterogeneity in cancer...
September 13, 2016: Seminars in Cell & Developmental Biology
James J Hsieh, Brandon J Manley, Nabeela Khan, JianJiong Gao, Maria I Carlo, Emily H Cheng
Tumor heterogeneity, encompassing genetic, epigenetic, and microenvironmental variables, is extremely complex and presents challenges to cancer diagnosis and therapy. Genomic efforts on genetic intratumor heterogeneity (G-ITH) confirm branched evolution, support the trunk-branch cancer model, and present a seemingly insurmountable obstacle to conquering cancers. G-ITH is conspicuous in clear cell renal cell carcinoma (ccRCC), where its presence complicates identification and validation of biomarkers and thwarts efforts in advancing precision cancer therapeutics...
September 8, 2016: Seminars in Cell & Developmental Biology
David A Meekins, Michael R Kanost, Kristin Michel
Serpins are the largest known family of serine proteinase inhibitors and perform a variety of physiological functions in arthropods. Herein, we review the field of serpins in arthropod biology, providing an overview of current knowledge and topics of interest. Serpins regulate insect innate immunity via inhibition of serine proteinase cascades that initiate immune responses such as melanization and antimicrobial peptide production. In addition, several serpins with anti-pathogen activity are expressed as acute-phase serpins in insects upon infection...
September 4, 2016: Seminars in Cell & Developmental Biology
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