The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke
Keyword(s):  
Current Knowledge ◽  
Future Research ◽  
Transcriptional Level ◽  
Cellular Functions ◽  
Multiple Functions ◽  
Open Questions ◽  
G Quadruplex ◽  
Cellular Pathways ◽  
Nucleic Acid Structures ◽  
Dependent Processes

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.

scholarly journals The Mysteries around the BCL-2 Family Member BOK

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1638
Author(s):  
Raed Shalaby ◽  
Hector Flores-Romero ◽  
Ana J. García-Sáez
Keyword(s):  
Family Member ◽  
Cell Fate ◽  
Current Knowledge ◽  
Structural Features ◽  
Special Focus ◽  
Cellular Functions ◽  
Open Questions ◽  
Apoptotic Protein ◽  
Evolutionarily Conserved ◽  
Apoptosis Regulation

BOK is an evolutionarily conserved BCL-2 family member that resembles the apoptotic effectors BAK and BAX in sequence and structure. Based on these similarities, BOK has traditionally been classified as a BAX-like pro-apoptotic protein. However, the mechanism of action and cellular functions of BOK remains controversial. While some studies propose that BOK could replace BAK and BAX to elicit apoptosis, others attribute to this protein an indirect way of apoptosis regulation. Adding to the debate, BOK has been associated with a plethora of non-apoptotic functions that makes this protein unpredictable when dictating cell fate. Here, we compile the current knowledge and open questions about this paradoxical protein with a special focus on its structural features as the key aspect to understand BOK biological functions.

scholarly journals Engineered Nanomaterials: Knowledge Gaps in Fate, Exposure, Toxicity, and Future Directions

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Arun Kumar ◽  
Prashant Kumar ◽  
Ananthitha Anandan ◽  
Teresa F. Fernandes ◽  
Godwin A. Ayoko ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Engineered Nanomaterials ◽  
Future Research ◽  
Accurate Estimation ◽  
Knowledge Gaps ◽  
Environmental Media ◽  
Toxicity Studies ◽  
Open Questions ◽  
Living Organisms ◽  
Exposure Conditions

The aim of this study is to identify current knowledge gaps in fate, exposure, and toxicity of engineered nanomaterials (ENMs), highlight research gaps, and suggest future research directions. Humans and other living organisms are exposed to ENMs during production or use of products containing them. To assess the hazards of ENMs, it is important to assess their physiochemical properties and try to relate them to any observed hazard. However, the full determination of these relationships is currently limited by the lack of empirical data. Moreover, most toxicity studies do not use realistic environmental exposure conditions for determining dose-response parameters, affecting the accurate estimation of health risks associated with the exposure to ENMs. Regulatory aspects of nanotechnology are still developing and are currently the subject of much debate. Synthesis of available studies suggests a number of open questions. These include (i) developing a combination of different analytical methods for determining ENM concentration, size, shape, surface properties, and morphology in different environmental media, (ii) conducting toxicity studies using environmentally relevant exposure conditions and obtaining data relevant to developing quantitative nanostructure-toxicity relationships (QNTR), and (iii) developing guidelines for regulating exposure of ENMs in the environment.

scholarly journals Cytoplasmic RNA Granules in Somatic Maintenance

Gerontology ◽  
2018 ◽  
Vol 64 (5) ◽  
pp. 485-494 ◽  
Author(s):  
Ossama Moujaber ◽  
Ursula Stochaj
Keyword(s):  
Somatic Cell ◽  
Current Knowledge ◽  
Physiological State ◽  
Physiological Role ◽  
Cellular Functions ◽  
Rna Granules ◽  
Cytoplasmic Rna ◽  
Open Questions ◽  
And Function ◽  
The Impact

Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional “operons”. RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies.

scholarly journals Through 40.000 Years of Human Presence in Southern Europe: The Italian Case Study

2021 ◽  
Author(s):  
Serena Aneli ◽  
Matteo Caldon ◽  
Tina Saupe ◽  
Francesco Montinaro ◽  
Luca Pagani
Keyword(s):  
Bronze Age ◽  
Iron Age ◽  
Current Knowledge ◽  
Western Mediterranean ◽  
Future Research ◽  
Human Occupation ◽  
Hunter Gatherers ◽  
Italian Case ◽  
Open Questions

The Italian Peninsula, a natural pier across the Mediterranean Sea, witnessed intricate population events since the very beginning of human occupation in Europe. In the last few years, an increasing number of modern and ancient genomes from the area has been published by the international research community. This genomic perspective started unveiling the relevance of Italy to understand the post-Last Glacial Maximum (LGM) re-peopling of Europe, the earlier phase of the Neolithic westward migrations, and its linking role between Eastern and Western Mediterranean areas after the Iron Age. However many open questions are still waiting for more data to be addressed in full. With this review, we summarize the current knowledge emerging from the available ancient Italian individuals and, by re-analysing them all at once, we try to shed light on the avenues future research in the area should cover. In particular, open questions concern i) the fate of pre-Villabruna Europeans and to what extent their genomic components were absorbed by the post-LGM hunter-gatherers; ii) the role of Sicily and Sardinia before LGM; iii) to what degree the documented genetic structure within the Early Neolithic settlers can be described as two separate migrations; iv) what are the population events behind the marked presence of an Iranian Neolithic-like component in Bronze Age and Iron Age Italian and Southern European samples.

scholarly journals Bio-Inspired Design: An Overview Investigating Open Questions From the Broader Field of Design-by-Analogy

2014 ◽  
Vol 136 (11) ◽  
Author(s):  
Katherine Fu ◽  
Diana Moreno ◽  
Maria Yang ◽  
Kristin L. Wood
Keyword(s):  
Design Research ◽  
Current Knowledge ◽  
Research Literature ◽  
Future Research ◽  
Cognitive Mechanisms ◽  
Open Questions ◽  
The Future ◽  
Design By Analogy ◽  
Research Questions ◽  
Tools And Methods

Bio-inspired design and the broader field of design-by-analogy have been the basis of numerous innovative designs throughout history; yet there remains much to be understood about these practices of design, their underlying cognitive mechanisms, and preferred ways in which to teach and support them. In this paper, we work to unify the broader design-by-analogy research literature with that of the bio-inspired design field, reviewing the current knowledge of designer cognition, the seminal supporting tools and methods for bio-inspired design, and postulating the future of bio-inspired design research from the larger design-by-analogy perspective. We examine seminal methods for supporting bio-inspired design, highlighting the areas well aligned with current findings in design-by-analogy cognition work and noting important areas for future research identified by the investigators responsible for these seminal tools and methods. Supplemental to the visions of these experts in bio-inspired design, we suggest additional projections for the future of the field, posing intriguing research questions to further unify the field of bio-inspired design with its broader resident field of design-by-analogy.

scholarly journals Through 40,000 years of human presence in Southern Europe: the Italian case study

2021 ◽  
Author(s):  
Serena Aneli ◽  
Matteo Caldon ◽  
Tina Saupe ◽  
Francesco Montinaro ◽  
Luca Pagani
Keyword(s):  
Bronze Age ◽  
Iron Age ◽  
Current Knowledge ◽  
Western Mediterranean ◽  
Future Research ◽  
Human Occupation ◽  
Hunter Gatherers ◽  
Italian Case ◽  
Open Questions

AbstractThe Italian Peninsula, a natural pier across the Mediterranean Sea, witnessed intricate population events since the very beginning of the human occupation in Europe. In the last few years, an increasing number of modern and ancient genomes from the area have been published by the international research community. This genomic perspective started unveiling the relevance of Italy to understand the post-Last Glacial Maximum (LGM) re-peopling of Europe, the earlier phase of the Neolithic westward migrations, and its linking role between Eastern and Western Mediterranean areas after the Iron Age. However, many open questions are still waiting for more data to be addressed in full. With this review, we summarize the current knowledge emerging from the available ancient Italian individuals and, by re-analysing them all at once, we try to shed light on the avenues future research in the area should cover. In particular, open questions concern (1) the fate of pre-Villabruna Europeans and to what extent their genomic components were absorbed by the post-LGM hunter-gatherers; (2) the role of Sicily and Sardinia before LGM; (3) to what degree the documented genetic structure within the Early Neolithic settlers can be described as two separate migrations; (4) what are the population events behind the marked presence of an Iranian Neolithic-like component in Bronze Age and Iron Age Italian and Southern European samples.

scholarly journals Timing avian long-distance migration: from internal clock mechanisms to global flights

2017 ◽  
Vol 372 (1734) ◽  
pp. 20160252 ◽  
Author(s):  
Susanne Åkesson ◽  
Mihaela Ilieva ◽  
Julia Karagicheva ◽  
Eldar Rakhimberdiev ◽  
Barbara Tomotani ◽  
...  
Keyword(s):  
Annual Cycle ◽  
Environmental Conditions ◽  
Migratory Birds ◽  
Current Knowledge ◽  
Internal Clock ◽  
External Information ◽  
Future Research ◽  
Long Distance ◽  
Open Questions ◽  
Migrating Birds

Migratory birds regularly perform impressive long-distance flights, which are timed relative to the anticipated environmental resources at destination areas that can be several thousand kilometres away. Timely migration requires diverse strategies and adaptations that involve an intricate interplay between internal clock mechanisms and environmental conditions across the annual cycle. Here we review what challenges birds face during long migrations to keep track of time as they exploit geographically distant resources that may vary in availability and predictability, and summarize the clock mechanisms that enable them to succeed. We examine the following challenges: departing in time for spring and autumn migration, in anticipation of future environmental conditions; using clocks on the move, for example for orientation, navigation and stopover; strategies of adhering to, or adjusting, the time programme while fitting their activities into an annual cycle; and keeping pace with a world of rapidly changing environments. We then elaborate these themes by case studies representing long-distance migrating birds with different annual movement patterns and associated adaptations of their circannual programmes. We discuss the current knowledge on how endogenous migration programmes interact with external information across the annual cycle, how components of annual cycle programmes encode topography and range expansions, and how fitness may be affected when mismatches between timing and environmental conditions occur. Lastly, we outline open questions and propose future research directions. This article is part of the themed issue ‘Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals’.

scholarly journals Legionnaires’ Disease: State of the Art Knowledge of Pathogenesis Mechanisms of Legionella

2020 ◽  
Vol 15 (1) ◽  
pp. 439-466 ◽  
Author(s):  
Sonia Mondino ◽  
Silke Schmidt ◽  
Monica Rolando ◽  
Pedro Escoll ◽  
Laura Gomez-Valero ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Severe Form ◽  
Effector Proteins ◽  
Future Research ◽  
Open Questions ◽  
Eukaryotic Origin ◽  
Legionella Species ◽  
Legionnaires Disease

Legionella species are environmental gram-negative bacteria able to cause a severe form of pneumonia in humans known as Legionnaires’ disease. Since the identification of Legionella pneumophila in 1977, four decades of research on Legionella biology and Legionnaires’ disease have brought important insights into the biology of the bacteria and the molecular mechanisms that these intracellular pathogens use to cause disease in humans. Nowadays, Legionella species constitute a remarkable model of bacterial adaptation, with a genus genome shaped by their close coevolution with amoebae and an ability to exploit many hosts and signaling pathways through the secretion of a myriad of effector proteins, many of which have a eukaryotic origin. This review aims to discuss current knowledge of Legionella infection mechanisms and future research directions to be taken that might answer the many remaining open questions. This research will without a doubt be a terrific scientific journey worth taking.

scholarly journals Effective string description of confining flux tubes

2016 ◽  
Vol 31 (22) ◽  
pp. 1643001 ◽  
Author(s):  
Bastian B. Brandt ◽  
Marco Meineri
Keyword(s):  
String Theory ◽  
Current Knowledge ◽  
Future Research ◽  
Lattice Data ◽  
Flux Tubes ◽  
Short Summary ◽  
Open Questions ◽  
Recent Developments ◽  
Effective String Theory ◽  
Theoretical Foundations

We review the current knowledge about the theoretical foundations of the effective string theory for confining flux tubes and the comparison of the predictions to pure gauge lattice data. A concise presentation of the effective string theory is provided, incorporating recent developments. We summarize the predictions for the spectrum and the profile/width of the flux tube and their comparison to lattice data. The review closes with a short summary of open questions for future research.

Amruthapala (Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter): A Comprehensive Review on Diversity, Therapeutic Uses, and Valorization of Bioactive Constituents

2019 ◽  
Vol 20 (5) ◽  
pp. 376-389 ◽  
Author(s):  
Sonali Mishra ◽  
Nupur Srivastava ◽  
Velusamy Sundaresan ◽  
Karuna Shanker
Keyword(s):  
Secondary Metabolite ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Critical Discussion ◽  
Future Research ◽  
Bioactive Constituents ◽  
Medicinal Uses ◽  
Comprehensive Review ◽  
Therapeutic Uses ◽  
Decalepis Arayalpathra

Background: Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter is used primarily for nutrition besides its therapeutic values. Traditional preparations/formulations from its tuber are used as a vitalizer and blood purifier drink. The folklore medicinal uses cover inflammation, cough, wound healing, antipyretic, and digestive system management. A comprehensive review of the current understanding of the plant is required due to emerging concerns over its safety and efficacy. Objective: The systematic collection of the authentic information from different sources with the critical discussion is summarised in order to address various issues related to botanical identity, therapeutic medicine, nutritional usage, phytochemical, and pharmacological potentials of the D. arayalpathra. Current use of traditional systems of medicine can be used to expand future research opportunities. Materials and Methods: Available scripted information was collected manually, from peered review research papers and international databases viz. Science Direct, Google Scholar, SciFinder, Scopus, etc. The unpublished resources which were not available in database were collected through the classical books of ‘Ayurveda’ and ‘Siddha’ published in regional languages. The information from books, Ph.D. and MSc dissertations, conference papers and government reports were also collected. We thoroughly screened the scripted information of classical books, titles, abstracts, reports, and full-texts of the journals to establish the reliability of the content. Results: Tuber bearing vanilla like signature flavor is due to the presence of 2-hydroxy-4-methoxybenzaldehyde (HMB). Among five other species, Decalepis arayalpathra (DA) has come under the ‘critically endangered’ category, due to over-exploitation for traditional, therapeutic and cool drink use. The experimental studies proved that it possesses gastro-protective, anti-tumor, and antiinflammatory activities. Some efforts were also made to develop better therapeutics by logical modifications in 2-Hydroxy-4-methoxy-benzaldehyde, which is a major secondary metabolite of D. arayalpathra. ‘Amruthapala’ offers the enormous opportunity to develop herbal drink with health benefits like gastro-protective, anti-oxidant and anti-inflammatory actions. Results: The plant has the potential to generate the investigational new lead (IND) based on its major secondary metabolite i.e. 2-Hydroxy-4-methoxy-benzaldehyde. The present mini-review summarizes the current knowledge on Decalepis arayalpathra, covering its phytochemical diversity, biological potentials, strategies for its conservation, and intellectual property rights (IPR) status. Chemical Compounds: 2-hydroxy-4-methoxybenzaldehyde (Pubchem CID: 69600), α-amyrin acetate (Pubchem CID: 293754), Magnificol (Pubchem CID: 44575983), β-sitosterol (Pubchem CID: 222284), 3-hydroxy-p-anisaldehyde (Pubchem CID: 12127), Naringenin (Pubchem CID: 932), Kaempferol (Pubchem CID: 5280863), Aromadendrin (Pubchem CID: 122850), 3-methoxy-1,2-cyclopentanedione (Pubchem CID: 61209), p-anisaldehyde (Pubchem CID: 31244), Menthyl acetate (Pubchem CID: 27867), Benzaldehyde (Pubchem CID: 240), p-cymene (Pubchem CID: 7463), Salicylaldehyde (Pubchem CID: 6998), 10-epi-γ-eudesmol (Pubchem CID: 6430754), α -amyrin (Pubchem CID: 225688), 3-hydroxy-4-methoxy benzaldehyde (Pubchem CID: 12127).

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