bluuebunny/crossref_metadata_2025 huggingface dataset:
Existence of theoretical ribosomal protein mass fingerprints in bacteria, archaea and eukaryotes
Authors: Ng Wenfa
Published: February 2018

Ribosomes are highly conserved given the importance of protein synthesis to cell survival. Although small differences in structure and functions exists in ribosomes from different species of bacteria, archaea and eukaryotes, the general structure and function remains conserved across species in the same domain of life. Thus, are ribosomal proteins that constitute ribosomes highly conserved between species in the same domain or do they possess sufficient sequence variation that help identify individual species? Having differentiated sequence would mean that ribosomal proteins from different species might account for differences in structure and function of the ribosomes in different species. Using ribosomal protein amino acid sequence information from Ribosomal Protein Gene Database for calculating molecular mass of ribosomal proteins, this study sought to determine if the molecular mass of a set of ribosomal proteins from a species could constitute a unique ribosomal protein mass fingerprint. In addition, the question of whether unique ribosomal protein mass fingerprint exists between different species in the three domains of life was also examined. Results revealed that distinct molecular mass of individual ribosomal protein could aggregate into a unique ribosomal protein mass fingerprint for individual bacterial, archaeal and eukaryotic species. Such ribosomal protein mass fingerprints could potentially find use in microbial identification through gel-free matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling of solubilized ribosomal proteins. Obtained ribosomal protein mass spectrum could be compared with those catalogued in a reference database of known microorganisms where pattern recognition algorithms could determine a match. Additionally, existence of theoretical ribosomal protein mass fingerprint across species in the three domains of life also pointed to the presence of small differences in structure and function of both the large and small ribosome subunit. Such differences could reveal possible differentiated ribosomal structure and function in different species even though the general structure and function of the ribosome is conserved across species. Collectively, distinct molecular mass of individual ribosomal proteins in species pointed to a unique ribosomal protein mass fingerprint that could find use in microbial identification through gel-free mass spectrometry analysis of solubilized ribosomal proteins. Differences in mass of ribosomal proteins across species also highlighted existence of ribosomes of differentiated structure and function between different species even though the general structure and function of the ribosome remains highly conserved.
Desiccation resistance: effect of cuticular hydrocarbons and water content inDrosophila melanogasteradults
Authors: Ferveur Jean-Francois , Cortot Jérôme , Rihani Karen , Cobb Matthew , Everaerts Claude
Published: February 2018

Background

The insect cuticle covers the whole body and all appendages and has bi-directionnal selective permeability: it protects against environmental stress and pathogen infection and also helps to reduce water loss. The adult cuticle is often associated with a superficial layer of fatty acid-derived molecules such as waxes and long chain hydrocarbons that prevent rapid dehydration. The waterproofing properties of cuticular hydrocarbons (CHs) depend on their chain length and desaturation number.DrosophilaCH biosynthesis involves an enzymatic pathway including several elongase and desaturase enzymes.

Methods

The link between desiccation resistance and CH profile remains unclear, so we tested (1) experimentally selected desiccation-resistant lines, (2) transgenic flies with altered desaturase expression and (3) natural and laboratory-induced CH variants. We also explored the possible relationship between desiccation resistance, relative water content and fecundity in females.

Results

We found that increased desiccation resistance is linked with the increased proportion of desaturated CHs, but not with their total amount. Experimentally-induced desiccation resistance and CH variation both remained stable after many generations without selection. Conversely, flies with a higher water content and a lower proportion of desaturated CHs showed reduced desiccation resistance. This was also the case in flies with defective desaturase expression in the fat body.

Discussion

We conclude that rapidly acquired desiccation resistance, depending on both CH profile and water content, can remain stable without selection in a humid environment. These three phenotypes, which might be expected to show a simple relationship, turn out to have complex physiological and genetic links.
Genus-level phylogeny of cephalopods using molecular markers: current status and problematic areas
Authors: Sanchez Gustavo , Setiamarga Davin H.E. , Tuanapaya Surangkana , Tongtherm Kittichai , Winkelmann Inger E. , Schmidbaur Hannah , Umino Tetsuya , Albertin Caroline , Allcock Louise , Perales-Raya Catalina , Gleadall Ian , Strugnell Jan M. , Simakov Oleg , Nabhitabhata Jaruwat
Published: February 2018

Comprising more than 800 extant species, the class Cephalopoda (octopuses, squid, cuttlefish, and nautiluses) is a fascinating group of marine conchiferan mollusks. Recently, the first cephalopod genome (of Octopus bimaculoides) was published, providing a genomic framework, which will enable more detailed investigations of cephalopod characteristics, including developmental, morphological, and behavioural traits. Meanwhile, a robust phylogeny of the members of the subclass Coleoidea (octopuses, squid, cuttlefishes) is crucial for comparative and evolutionary studies aiming to investigate the group’s traits and innovations, but such a phylogeny has proven very challenging to obtain. Here, we present the results of phylogenetic inference at the genus level using mitochondrial and nuclear marker sequences available from public databases. Topologies are presented which show support for (1) the monophyly of the two main superorders, Octobrachia and Decabrachia, and (2) some of the interrelationships at the family level. We have mapped morphological characters onto the tree and conducted molecular dating analyses, obtaining congruent results with previous estimates of divergence in major lineages. Our study also identifies unresolved phylogenetic relationships within the cephalopod phylogeny and insufficient taxonomic sampling among squids excluding the Loliginidae in the Decabrachia and within the Order Cirromorphida in the Octobrachia. Genomic and transcriptomic resources should enable resolution of these issues in the relatively near future. We provide our alignment as an open access resource, to allow other researchers to reconstruct phylogenetic trees upon this work in the future.
The effect of supragingival glycine air polishing on periodontitis during maintenance therapy: a randomized controlled trial
Authors: Lu Hongye , He Lu , Zhao Yibing , Meng Huanxin
Published: February 2018

Background

Glycine air polishing has been proved to be safe, comfortable and time-saving. Whether it could substitute ultrasonic scaling to remove dental plaque biofilm during periodontal maintenance remains unclear. The purposes of this study were to evaluate the effect of supragingival glycine air polishing (SGAP) on the subgingival periodontal pathogens during maintenance therapy and to check the association of periodontal pathogens and clinical parameters.

Methods

Twenty-three chronic periodontitis patients during their maintenance therapy were enrolled in the 12-week study. According to randomized split-mouth design, the test side was treated with SGAP (65 μm), while the control side was treated with supragingival ultrasonic scaling and polishing (SUSP) with rubber cup. Clinical examination including plaque index (PLI), probing depth (PD), bleeding index (BI) were performed at baseline and 12 weeks post-treatment. Sampling of the subgingival plaque at each investigational site (mesiobuccal site of the mandibular first molar) was performed at baseline and 2, 4, 8, 12 weeks after maintenance treatment. Four periodontal pathogens including Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Fusobacterium nucleatum were detected by 16S rDNA polymerase chain reaction.

Results

Clinical status generally improved after treatment in both groups. PLI in both groups, PD in SGAP group and bleeding on probing (%) in SUSP group significantly decreased after treatment (p < 0.05). There was no significant difference of clinical parameters between two groups before and after treatment. The detection rates of P. gingivalis, T. denticola in both groups, T. forsythia in SUSP group and F. nucleatum in SGAP group decreased after maintenance treatment in both groups, although no significant difference was found, and it rebound to baseline level at 12 weeks after maintenance treatment. There was no significant difference between SGAP group and SUSP group at any time point. T. denticola-positive sites had significantly greater BI than T. denticola-negative sites (p < 0.05).

Discussion

Supragingival glycine air polishing had a reliable effect in removing subgingival dental plaque biofilm during maintenance period, and three months may be a proper maintenance interval for pockets not more than 5 mm.
Evidence of sinks and sources in the phospholipase C‐activated PIP2 cycle
Authors: Suratekar Rohit , Panda Aniruddha , Raghu Padinjat , Krishna Sandeep
Published: February 2018

In many eukaryotic signalling cascades, receptor‐mediated phospholipase C (PLC) activity triggers phosphatidylinositol‐4,5‐bisphosphate (PIP2) hydrolysis, leading to information transfer. Coupled with PLC activation is a sequence of reactions spread across multiple compartments which resynthesize PIP2, a process essential for supporting sustained PLC signalling. The biochemical strategies coordinating these reactions and, in particular, whether this is a closed cycle with no net addition or loss of metabolites, are poorly understood. Using mathematical models, we find that most closed PIP2 cycles cannot explain experimentally observed changes in key metabolic intermediates in particular mutants. Thus, we propose that the PIP2 cycle likely includes at least one metabolic source and one sink whose net activity results in the experimentally observed regulation of this key signalling pathway.
Cross‐talk between sphingosine‐1‐phosphate and EGFR signaling pathways enhances human glioblastoma cell invasiveness
Authors: Cattaneo Maria Grazia , Vanetti Claudia , Samarani Maura , Aureli Massimo , Bassi Rosaria , Sonnino Sandro , Giussani Paola
Published: February 2018

We show that glioblastoma multiform (GBM) cells overexpressing the constitutively active form of the epidermal growth factor receptor [epidermal growth factor receptor variant III (EGFRvIII) and U87MG human GBM cell line overexpressing EGFRvIII (EGFR+) cells] possess greater invasive properties and have higher levels of extracellular sphingosine‐1‐phosphate (S1P) and increased sphingosine kinase‐1 (SK1) activity than the empty vector‐expressing cells. Notably, the inhibition of SK1 or S1P receptors decreases the invasiveness of EGFR+ cells. Moreover, EGFR and MEK1 inhibitors reduce both SK1 activation and cell invasion, suggesting that the enhanced invasiveness observed in the EGFR+ cells depends on the increased S1P secretion, downstream of the EGFRvIII‐ERK‐SK1‐S1P pathway. Altogether, the results of the present study indicate that, in GBM cells, EGFRvIII is connected with the S1P signaling pathway to enhance cell invasiveness and tumor progression.
Midlatitude Cirrus Clouds at the SACOL Site: Macrophysical Properties and Large‐Scale Atmospheric States
Authors: Ge Jinming , Zheng Chuang , Xie Hailing , Xin Yue , Huang Jianping , Fu Qiang
Published: February 2018

Two‐year observations of a Ka‐band Zenith Radar at the Semi‐Arid Climate and Environment Observatory of Lanzhou University (SACOL) are used to document the midlatitude cirrus cloud macroproperties. Generally, cirrus occurs 41.6% of the observation time and most frequently appear at about 7.2 km above ground level. The cirrus macroproperties are strongly coupled with large‐scale atmospheric states; thus, its occurrence and location over the SACOL have significant seasonal variations. A k‐mean clustering method is used to classify cirrus into four distinct regimes without a prior knowledge about the meteorological process. Contrasting to the different cirrus physical properties in each regime, the cirrus event of each regime has a distinct seasonal distribution and the synoptic conditions from the ERA‐Interim reanalysis responsible for each cirrus regime are also quite different. Since global climate models typically overestimate cirrus cloud thickness due to inadequate parameterization or coarse grid resolution, we examined the probability density functions of large‐scale vertical velocity associated with each cirrus regime and the relationship between cirrus thickness and vertical velocity. It is found that the differences of the vertical velocity probability density functions among the cirrus regimes are as distinct as their macroproperties and a significant correlation exists between cirrus thickness and the vertical velocity, although the large‐scale vertical motion is nearly as likely to be descending as ascending when cirrus clouds are observed. This may imply that large‐scale vertical velocity can be used to constrain the variations of cirrus thickness simulated by global climate models.
Immunity to Protozoa
Authors: Velazquez Carlos , Dominguez Victor , Garzon Thania , Rascon Raul
Published: February 2018

Protozoan parasites are microorganisms that live and feed at the expense of a host. Parasites can cause diseases in humans and are worldwide distributed, causing high morbidity and mortality. This article describes the most important defence mechanisms against protozoan parasites of clinical relevance (Plasmodiumspp.,Leishmaniaspp.,Toxoplasma gondii,Trypanosoma cruzi,Entamoeba histolyticaandGiardia lamblia). Protozoans exhibit a high heterogeneity in morphologies and antigenic expression, which is reflected in the different immune responses induced during the infection process. The first line of defence is the mechanisms of the innate immune response as physical and chemical barriers. However, in most cases, the adaptive humoural and cellular responses are implicated in controlling the infection. On the other hand, parasites have developed mechanisms to evade the immune response, hindering the development of vaccines, which offers a broad spectrum of protection among species.

Key Concepts

Parasitosis comprises a set of very diverse diseases, caused by different types of parasitic microorganisms.

Protozoan infections can be acquired either through direct contact or through vectors.

Malaria is the deadliest protozoan infection worldwide.

The immune response is divided into two branches: innate and adaptive immunity.

Protozoan parasites have developed strategies to evade the immune response.

To date, there has been an imminent necessity to develop efficient vaccines against main protozoan infections.
Bone Marrow
Authors: Marlein Christopher R , Rushworth Stuart A
Published: February 2018

The bone marrow is a highly dynamic organ located within the cavities of bones. The main role of the bone marrow is to facilitate the production of all the blood cells required for normal bodily homeostasis. These cells include lymphocytes, granulocytes, macrophages, red blood cells and plasma cells. The bone marrow is composed of many cell types that provide support for haematopoiesis, the blood cell production process. As with any major organ, many diseases can arise from errors in bone marrow function, including nonmalignant disorders such as anaemia and malignant disorders such as leukaemias. Transplantation of the bone marrow can be carried out, providing treatment options to patients suffering from bone marrow‐related disorders. This article will explore the anatomy and the role of the bone marrow, whilst providing an insight into the disorders created by errors in normal bone marrow function.

Key Concepts

The bone marrow is composed of red and yellow marrow and is the site of haematopoiesis.

The primary function of the bone marrow is haematopoiesis – haematopoietic stem cells (HSC) lead to the generation of all blood cells

All myeloid and lymphoid cells are generated in the bone marrow, crucial for the innate and adaptive immune systems, along with blood clotting and oxygen circulation.

Nonhaematopoietic cells provide key molecules to regulate the process of haematopoiesis.

Errors in the bone marrow can results in bone marrow‐related disorders, such as anaemia and leukaemia.
Virus and Host Plant Interactions
Authors: Wang Aiming
Published: February 2018

Plant viruses infect almost all crops and cause serious diseases worldwide. Currently, viral pathogens account for the largest proportion of newly emerging plant diseases and as such, are considered a major constraint to agriculture, threatening global food security. All plant viruses have relatively small genomes with limited coding capacity. They must co‐opt cellular pathways and recruit host proteins and metabolites to complete their infection cycle. To combat virus infection, plants have evolved sophisticated defence mechanisms. In order to establish infection, viruses have also evolved virulence strategies to suppress host defence. A successful infection by a plant virus requires compatible molecular interplays between the host plant and the invading virus. A better understanding of the complex virus–plant interactions will assist in the development of novel antiviral strategies.

Key Concepts

Plant viruses have small genomes that encode a few proteins and thus depend on host factors to establish their infection.

There exist multifaceted defence and counterdefence strategies in the coevolutionary arms race between plants and viruses.

A successful viral infection may induce disease symptoms or remain asymptomatic.

Host factors are implicated in all steps of the viral infection process, and silencing or mutation of host factor gene(s) leads to recessive genetic resistance to viruses.

The majority host factors are also essential for plant viability and some of them may be manipulated to develop genetic resistance through precise mutation to retain their canonical cellular functions but lose the ability to support viral infection.
Vaccination of Animals
Authors: Babiuk Lorne A , Stokka Gerald L , Gaspers James J
Published: February 2018

The practice of vaccination to elicit an immune response has been utilised to reduce the risk of infectious disease for hundreds of years. Regarding the health of livestock, vaccination remains one of the most, if not the most, important management tools for the prevention of infectious diseases. The goal of any vaccine and vaccination protocol is to reduce the risks associated with the development of clinical disease. Various approaches can be employed to improve animal health through vaccination. Owing to the unique management situation faced by different species, each has its own difficulties associated with vaccine delivery and eliciting the proper long‐lived immunologic responses. Understanding these difficulties with vaccine delivery, the pathogens themselves and the specific species immune response to vaccine antigens is critical to further reduce the risks of clinical disease.

Key Concepts

Infectious diseases continue to persist in animal populations and it is critical to understand each individual species from a management standpoint as well as the pathogenesis of the infectious agent in order to illicit the specific immune response required to deliver life‐long protection from clinical disease.

Understanding the passive transfer of immunity from mother to offspring as well its effect on the neonate's ability to produce a proper immune response to vaccine antigens is required.

Anticipating stressful events in an animal's life and applying vaccination protocols before those events take place so that the animal's immune system is effectively able to recognise and combat the antigen(s) is critical to the success of the vaccine and the animal.

Matching economic viability and vaccination principles with vaccination protocols is required to achieve biological control of pathogens.

Understanding various routes of vaccine administration and the specific immune response they illicit is necessary for the success of a vaccine and vaccination protocol.

Understanding the dynamics of pathogen transmission and the concept of herd immunity.

Cooperation among research scientists, veterinarians, owners of the animals and government agencies is critical for the widespread eradication of specific diseases.
Transgenic Animals
Authors: Houdebine Louis M
Published: February 2018

Transgenesis implies that a foreign deoxyribonucleic acid (DNA) fragment is introduced into the genome of a multicellular organism and transmitted to progeny. Transgenesis, therefore, differs from gene transfer into cultured cells (transfection) or into the somatic cells of a patient (gene therapy). The foreign DNA can integrate randomly in host genome leading to gene addition or in a targeted manner making it possible precise endogenous gene inactivation or replacement. Transgenesis allows transferring genes from any source in a single generation. Transgenesis is, therefore, complementary to spontaneous mutations, which take place at each reproduction cycle or which are experimentally induced by mutagenic compounds or irradiation. These conventional approaches must be followed by appropriate selection of animals. Transgenesis has become an essential tool to study gene function especially in the medical and pharmaceutical fields. Improvements of breeding and food are also in course. Recent techniques based on the targeted gene modification make it much easier specific gene knockout and gene replacement in animals. The CRISPR‐Cas9 system is the most currently used system.

Key Concepts

Transgenesis is more precise and more diverse than conventional selection.

Transgenesis and conventional selection are complementary.

Transgenesis is an essential tool to study gene action and control.

Cloning is presently intensively used to generate transgenic farm animals.

Stem cells are currently used for random and targeted gene integration.

Targeted gene integration using double‐strand genomic DNA break provides researchers with exceptionally efficient new tools.

Conventional targeted gene transfer is limited by its low efficiency.

SiRNAs are efficient tools to inhibit gene expression at the mRNA level.

The available tools to generate transgenic animals offer the possibility to develop more relevant biological models and to prepare safer food.

Animal behaviourists must participate in conservation planning to protect the future of biodiversity.
Cleavage and Gastrulation in the Mouse Embryo
Authors: Nahaboo Wallis , Migeotte Isabelle
Published: February 2018

After fertilisation of the oocyte, the mouse zygote divides three times before undergoing compaction, which allows polarisation of the blastomeres, and the first lineage specification between trophectoderm (destined to become placenta) and inner cell mass (ICM). The second lineage specification occurs at the blastocyst stage, when ICM cells become either epiblast (which will give rise to the embryo proper) or primitive endoderm (an extraembryonic lineage). After implantation, the proximal (site of attachment with the uterus)‐distal axis is established, quickly followed by the determination of the anterior–posterior axis. Formation of the three main germ layers, ectoderm, mesoderm and endoderm, then occurs on the posterior side at the primitive streak, site of gastrulation. However, recent advances in mouse embryo live imaging have shown that lineage specification was more flexible than previously thought. It has also become possible to visualise the early stages of human embryo development.

Key Concepts

Early mouse embryo development proceeds through a sequence of lineages specification events.

Similar signalling pathways are reused at different steps of early development.

Positional and mechanical cues play essential roles for cell lineage specification and morphogenesis.

The initial steps, up to and including gastrulation, are quite conserved between all amniotes.

The main differences at later stages reside in the extraembryonic tissues, as mammals have adapted to internal gestation through the development of a placenta.
Human Leucocyte Antigen (
HLA
) System and Human Disorders
Authors: Traherne James A
Published: February 2018

The major histocompatibility complex (MHC) has been studied in depth because it is associated genetically with more human disorders than any other region in the human genome. In addition to the human leucocyte antigen (HLA) genes, the MHC contains a diverse array of multiallelic genes, many of which are involved in modulating the immune response to pathogens. Advanced mapping and sequencing approaches are helping to define more precisely contributions of MHC variants to disease. Class I or class II molecules are confirmed as the primary influence in most studies, attesting to their functional impact on antigenic peptide presentation to lymphocytes. Regulatory polymorphism controlling cell surface expression of HLA molecules has also been associated with disease. However, the precise causal nature of the majority of associated alleles and haplotypes with disease is still not understood.

Key Concepts

The MHC encodes genes essential for immunity in humans, including the HLA molecules.

With the exception of one gene,
HLA‐DRA
, the classical HLA genes are highly variable.

HLA class I and II genes are associated with many diseases, including infectious diseases, cancers and neuropathies but particularly autoimmunity.

Many HLA variants are concurrently associated with both infectious and autoimmune diseases.

The MHC may be considered as a cluster of genes with integrated functions.

A high proportion of MHC genes are involved in immunity.

The MHC contains nonclassical class I and II genes, such as HLA‐E, F and G, and HLA‐DM, DO, respectively.
DNA
Helicase Deficiency Disorders
Authors: Sidorova Julia M , Monnat Jr Raymond J
Published: February 2018

Deoxyribonucleic acid (DNA) helicases use energy derived from ATP (adenosine triphosphate) hydrolysis to separate the complementary strands of DNA. This article focuses on one family of DNA helicases, the human RECQ helicases, and the syndromes that arise in their absence or following loss of function. The five human RECQ helicases share a common, conserved helicase domain, and all five proteins play important roles in cellular DNA metabolism. Loss of function mutations in three family members cause the human cancer predisposition syndromes Bloom syndrome (BS), Werner syndrome (WS) and Rothmund–Thomson syndrome (RTS). This article outlines clinical features of the RECQ helicase deficiency syndromes, and reviews our understanding of the genetics, biochemistry and function of the syndrome‐associated RECQ helicases. We discuss how the loss of RECQ function may promote genetic instability and disease pathogenesis, and how RECQ helicases may serve as predictors of cancer risk and the response to therapy.

Key Concepts

RECQ helicases are found in all Kingdoms of life.

RECQ helicases use the energy of ATP hydrolysis to unwind the two strands of DNA.

RECQ helicases function in important aspects of DNA metabolism including DNA replication and repair, recombination, transcription and telomere maintenance.

Loss of RECQ helicase function is associated with DNA metabolic defects, genetic instability, reduced cell proliferation and cellular senescence or apoptosis.

Three rare, distinct heritable recessive human RECQ helicase deficiency syndromes have been identified. RECQ helicase‐deficient individuals have an elevated risk of cancer and additional developmental or acquired findings.

Altered RECQ helicase function may be common in adult cancer, and may affect both cell viability and the response to therapy.

RECQ‐specific inhibitors may be therapeutically useful in a subset of human cancers.
Telomeres and Telomerase in Ageing and Cancer
Authors: Ouellette Michel M
Published: February 2018

Telomeres are protective structures that cap the ends of linear chromosomes. In humans, they are made of a repetitive DNA (deoxyribonucleic acid) sequence, (TTAGGG)

n

, and associated proteins. Because DNA polymerases are unable to completely replicate the ends of linear chromosomes, telomeres shorten each time cells divide. This gradual shortening of the telomeres limits their cellular lifespan and contributes to the ageing process. During cancer development, this obstacle to immortality is almost always bypassed by the overexpression of telomerase, a specialised reverse transcriptase that functions to add back telomeric repeats to telomeres. In humans, its expression is limited to rare stem cells of renewal tissues, but a notable exception has been its overexpression in the great majority of cancers. Accordingly, telomerase is being developed as both a novel marker for the detection of cancer cells and a novel target for the treatment of cancers. Herein, we discuss the role of telomeres and telomerase in cancer and ageing, with the emphasis on potential future applications in the treatments of cancers and age‐related diseases.

Key Concepts

Telomeres are protective structures that cap the ends of chromosomes.

Human telomeres are made of TTAGGG DNA repeats and associated proteins.

Because of ‘end replication problems’, telomeres shorten each time cells divide, and this shortening limits cellular lifespan and contributes to the ageing process.

Telomerase is a specialised reverse transcriptase that functions to add back telomeric repeats to the ends of telomeres, thereby extending cellular lifespan.

Telomerase expression in humans is limited to rare stem cells of renewal tissues (gastrointestinal track, blood and skin).

Telomerase is almost always aberrantly overexpressed in cancer. This overexpression is detected in 85% of all cancers, irrespective of the tumour type.

Telomerase is being developed as a marker to allow the detection of cancer cells in otherwise telomerase‐negative normal tissues.

Inhibitors of telomerase are being developed to limit tumour growth and reduce the incidence of recurrences following conventional cancer therapy.

Strategies for transient telomerase reactivation are also being developed for the treatment of degenerative diseases and age‐related diseases.
Lissencephaly, Genetics of
Authors: Passemard Sandrine , Chalard François , Verloes Alain , Gressens Pierre
Published: February 2018

The term lissencephaly (literally ‘smooth brain’) covers rare malformations of the brain characterised by a paucity of normal gyri and sulci with absent (agyria) or abnormally wide gyri (pachygyria) associated with an abnormal cortical layering. Different forms of lissencephalies have been described: classical lissencephalies (also called type I) and their variants, and cobblestone lissencephalies (also called type II). Classical lissencephalies include lissencephalies with mutations inLIS1,DCX,ARXorTUBA1genes, isolated lissencephalies without any identified genetic defect, lissencephalies with severe microcephaly (microlissencephaly) and lissencephalies associated with syndromes including multiple malformations. The cobblestone lissencephaly is observed in three related syndromes characterised by an overmigration of neurons and glial cells into the arachnoid space: Walker–Warburg, Fukuyama and muscle–eye–brain (MEB) syndromes, caused by mutations in genes involved inO‐glycosylation ofα‐dystroglycan.

Key Concepts

Lissencephaly is defined by a ‘smooth brain’ with absent (agyria) or abnormal wide gyri (pachygyria).

Lissencephaly is caused by abnormal neuronal migration during corticogenesis.

Neuropathological analysis distinguishes several types of lissencephalies: classical lissencephalies and cobblestone lissencephalies.

Classical lissencephalies are caused by mutations inLIS1,DCX,ARXandTubulingenes.

Cobblestone lissencephalies are caused by defects inO‐glycosylation ofα‐dystroglycan.

Microlissencephalies are caused by dysfunctions of centrosomal‐dependent neuronal progenitor proliferation and of neuronal migration.
Synthetic Biology: Molecular Tools for Engineering Organisms
Authors: Ducat Daniel C
Published: February 2018

Synthetic biology is a biological engineering discipline based on abstracting living systems through the lens of physical engineering concepts. In particular, synthetic biology places an emphasis on the characterisation of simple parts that can be modularly assembled into configurations that give rise to complex, higher‐order behaviours. Within the past two decades, this approach has enabled the development number of new molecular biology tools for modifying living systems in order to investigate fundamental processes or imbuing functions into cells that do not exist in nature. While specific synthetic biology applications span a huge range of seemingly unrelated disciplines (from biofuel producing microbes, to malaria‐resistant mosquitoes, to living medical therapies), these distinct examples derive from reuse and rearrangement of relatively limited set of cell engineering technologies. The continuing development of these core molecular biology tools for controlling gene expression, protein activity and signalling networks can promote evermore ambitious biological engineering projects.

Key Concepts

Synthetic biology is a discipline for biological engineering using principles of physical engineering.

Complex biological systems can be abstracted as a set of core ‘parts’ with separable functions.

A biological part is modular when it confers a discrete function, which can be repurposed and rearranged in many different contexts while maintaining fidelity.

Biological systems naturally display many modular features that are evident at many different scales.

Synthetic biology attempts to identify, characterise and repurpose biological modules to build devices with novel functions.

The field has created several new molecular biology tools for controlling living systems through exploiting the recombination of modular parts.

The tools of synthetic biology are frequently used to imbue organisms with technologically useful traits.

As synthetic biology expands beyond model microbes, its potential to contribute to our fundamental understanding of biology continues to increase.
Stomata
Authors: He Jingjing , Liang Yun‐Kuan
Published: February 2018

As adjustable pores, each delimited by a pair of guard cells, stomata are central determinants of plant photosynthesis, transpirational cooling and ecological adaptability, which have huge impact on global water and carbon cycles, plant competitiveness and nutrients in foods. The specialised guard cell anatomy and membrane ion transport enable plants to adapt stomatal aperture rapidly to hormone and environment changes. In contrast to the highly conserved simple structure across land plants, the stomatal size, density and distribution patterns vary substantially among species or genotypes within a species providing ample genetic resources on which selection can operate. Study of the development and function of stomata is crucial to understand cell fate specification, signal transduction and plant–environment interactions and inform approaches to breed ‘climate change ready’ crop varieties with improved agricultural capacity and food nutrients.

Key Concepts

Stomata and active stomata control are a key evolutionary innovation vital for plants to survive and thrive on land.

Plants use stomata for gas exchange, water regulation, mineral transport, spore dispersal and pathogen defence.

Plants produce stomata in organised patterns and in environmentally optimised numbers.

Stomata vary widely in size and responsiveness among species or genotypes within a species.

The specialised guard cell morphology, anatomy and membrane ion transport enable plants to adapt stomatal aperture rapidly to hormone and environment changes.

Stomata have major influence on the growth and fitness of land plants and global environment as well as food security.

Revealing the molecular nature of stomatal regulators will inform us the approaches to breed climate resilient crops.
Genome‐Wide Approaches to Identify the Interplay of Transcription Factors, Regulatory Elements and Target Genes
Authors: Qu Jieqiong , Zhou Huiqing
Published: February 2018

Tightly controlled gene regulation is essential for embryogenic development and homeostasis. One of the key questions in gene regulation is the interplay between transcription factors, regulatory elements and target genes. Recent development of high‐throughput technologies has made analyses of the complex interplay possible at the genome‐wide scale, and provides insights into the molecular mechanism of gene regulation. These state‐of‐the‐art genome‐wide approaches include RNA (ribonucleic acid)‐seq for gene expression, ChIP‐seq (chromatin immunoprecipitation followed by sequencing) for transcription factor binding and histone modifications, and methods for analysing chromatin accessibility and three‐dimensional chromatin conformation. For each of these approaches, we discuss the background, the current working pipeline and ongoing development. As computational analysis packages and methods are essential for interpreting genome‐wide large data sets, the commonly used ones are summarised with the corresponding technologies.

Key Concepts

The complex interplay of transcription factors,
cis
‐regulatory elements and target genes is essential for proper gene regulation.

RNA‐seq analyses have revolutionised gene expression analyses.

ChIP‐seq analyses assess the binding of transcription factor and the occupancy of histone modifications and provide potential
cis
‐regulatory elements and gene regulation in the genome.

Analyses of chromatin accessibility reveal
cis
‐regulatory elements and complement ChIP‐seq analyses.

Analyses of three‐dimensional chromatin conformation provide information on the chromatin domains that facilitate or restrict gene regulation.
Ancient Population Genomics
Authors: Subramanian Sankar
Published: February 2018

Recent advances in genome sequencing technologies and the rapid decline in the cost of sequencing have enabled researchers to study the genomics of ancient populations. In the past decade, ancient population genomic studies led to a number of important discoveries that revealed the (1) relationship between modern and archaic humans such as Neanderthals and Denisovans, (2) contribution of ancient but anatomically modern humans to the ancestry of populations living today, (3) temporal dynamics of ancient population sizes in response to climate change, (4) role of natural selection in shaping the evolution of phenotypes, (5) origins of animal domestication, (6) divergence times between ancient and modern populations and (7) evolution of human pathogens.

Key Concepts

Ancient population genomics revolutionised our understanding about past evolutionary and demographic events.

Rate of evolution could be estimated using time‐stamped ancient samples.

Ancient DNA studies revealed the rise and fall of mammalian population sizes in response to climate change.

Reconstructing extinct genomes helped to decipher the signatures of genetic admixture between archaic and modern humans.

Present‐day Europeans were derived from three ancient human populations.

Ancient genomes helped us to understand the role of adaptive evolution in the past.
Wood Decay Fungi
Authors: Kirker Grant T
Published: February 2018

Wood decay fungi are any species of fungi that utilise the structural components of wood as a source of nutrients. They comprise a very diverse group and have a worldwide distribution normally wherever trees are found. Wood decay fungi are vital to ecosystem functioning as they facilitate the decomposition of woody materials into soil. Wood decay fungi are also major contributors to damage to wood in service in both residential and industrial applications, leading to estimated $1B in losses annually. Wood decay fungi have also been exploited for use in industrial processes ranging from product development to waste breakdown. This article focuses on the taxonomic and physiological diversity of wood decay fungi and their importance both on economic and environmental scales.

Key Concepts

Wood decay fungi are a diverse group of microorganisms that are primarily involved in the breakdown of woody biomass.

These fungi are primary drivers of soil formation and nutrient cycling critical to ecosystem function.

Decay fungi also contribute to substantial damage to wood and wood‐based building materials and are a primary consideration in the use of preservative‐treated wood.

Decay of wood by fungi is typically characterised as either white, brown or soft rot with grey rot being a new and emerging distinction among decay fungi.

Collectively, these fungi possess a wide array of physiological mechanisms adapted to break down the structural components of wood.

Both enzymatic and nonenzymatic mechanisms of wood decay have been exploited as industrial processes to break down both man‐made and natural compounds.
Synthetic Viruses
Authors: Stauft Charles B , Wimmer Eckard
Published: February 2018

Advances in the synthesis of oligonucleotides have enabled the production of large DNA (deoxyribonucleic acid) molecules that can be tailored with great precision to the demands of scientists. New fields of the life sciences, synthetic biology, have been born from these advances. Using established methods of molecular cloning and reverse genetics, it has become possible to produce functional viruses using a digital template or design. The use of synthetic biology to construct viruses has proceeded rapidly because of falling costs in oligonucleotide synthesis. Synthetic viruses have been used to develop vaccine candidates, test the veracity of archived sequence data and reconstitute viruses previously thought lost to scientific study. From advent through ascension, synthetic viruses have elicited both scientific promise and public controversy.

Key Concepts

Synthetic virology is the production of live virus using a complete reference sequence. No natural viral copy is necessary – the parent of the virus is the computer.

Synthetic virology combines the technologies of DNA synthesis and reverse genetics.

RNA viruses typically have short genomes that make them ideal for synthesis.

Viruses can be attenuated through rational
in silico
design of novel sequences incorporating hundreds to thousands of silent nucleic acid mutations.

Using modern RNA and DNA extraction methodologies, viral genetic information can be sequenced and used to ‘resurrect’ viruses once thought extinct.
Respiratory Syncytial Virus: Immunisation and Prophylaxis
Authors: Barr Rachael , Drysdale Simon B
Published: February 2018

Respiratory syncytial virus (RSV) is the second most common cause of mortality in infants worldwide after malaria and the leading cause of hospitalisation in infants in many countries. It is also associated with high levels of morbidity and mortality in older adults (those over 60 years of age). These high levels of healthcare utilisation result in huge associated healthcare costs. As such, the development of an RSV vaccine is listed as a leading global priority by the World Health Organization (WHO). There is a monoclonal antibody (palivizumab) licensed to prevent RSV infection, but it is only used in high‐income countries for the most high‐risk infants owing to its very high cost. The development of an RSV vaccine/prophylactic agent has been hampered by an incomplete understanding of the immunopathogenesis of RSV infection, although many are currently undergoing clinical trials. Adding a new vaccine to the existing vaccine schedules will also present many challenges.

Key Concepts

Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in infants, children and older adults.

Agents to prevent severe RSV infection are needed to reduce this burden of disease.

The immunopathogenesis of RSV infection is incompletely understood, hampering the development of a vaccine.

Palivizumab, a monoclonal antibody, is licensed for use in high‐risk infants, but is extremely expensive, and thus newer agents are required.

Many RSV vaccines and novel prophylactic monoclonal antibodies are in development, although a licensed product is likely to still be many years away.

After a vaccine becomes licensed, there is still a need to ensure that it can be incorporated into the existing vaccine schedules.
Calcium and Bioenergetics
Authors: Jadiya Pooja , Tomar Dhanendra
Published: February 2018

Calcium (Ca
2+
) is one of the most abundant divalent cations found in the biological systems and has numerous vital roles in cellular physiology and pathophysiology. It is involved in the regulation of ionic homeostasis in the cytosol and different cellular organelles. The Ca
2+
directly regulates cellular bioenergetics, cell survival/death and acts as a messenger to regulate various cellular signalling events. Mitochondria, the bioenergetics hub of the cell, are one of the major reservoirs of cellular Ca
2+
. The Ca
2+
plays a major role in shaping the metabolic outcome of the mitochondria and whole cell. In recent years, the molecular identity of a mitochondrial Ca
2+
uniporter (MCU) has been revealed along with various regulators. However, the molecular mechanism of uniporter regulation in different stimuli and other determinants of mitochondrial Ca
2+
homeostasis are still elusive. In this article, we present the current understanding of cytosolic/mitochondrial Ca
2+
homeostasis, its role in energy metabolism and cell survival and its involvement in different cell systems and tissue/organ physiology.

Key Concepts

Ca
2+
signalling is the key determinant for cellular metabolism and bioenergetics.

Mitochondrial Ca
2+
([Ca
2+
]
m
) homeostasis is maintained by balanced [Ca
2+
]
m
influx and efflux.

Mitochondria sequester cytosolic Ca
2+
([Ca
2+
]
c
) into the matrix through the mitochondrial Ca
2+
uniporter MCU.

[Ca
2+
]
m
efflux is mediated by mitochondrial Na
+
/Ca
2+
(NCLX).

[Ca
2+
]
m
uptake modulates spatiotemporal patterns of intracellular Ca
2+
(iCa
2+
) signalling.

Under physiological conditions, [Ca
2+
]
m
uptake regulates bioenergetics and promotes ATP production.

Under pathological conditions, impaired [Ca
2+
]
m
exchange or [Ca
2+
]
m
overload leads to cell death depending on the cell type involved.

Defective [Ca
2+
]
m
signalling is associated with many human diseases.