bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian Programmes in Cyanobacteria
Authors: Johnson Carl Hirschie
Published: April 2013

Cyanobacteria are prokaryotes that express circadian (daily) rhythms. In rhythmic environments, the fitness of cyanobacteria is improved when this clock is operational and when its circadian period is similar to the period of the environmental cycle. In cyanobacteria, three key proteins (KaiA, KaiB and KaiC) form a core molecular clockwork that orchestrates global gene expression by modulating chromosomal topology. The three‐dimensional structures of these proteins have been determined. KaiA, KaiB and KaiC form a multiprotein nanomachine that can reconstitute a circadian oscillator

in vitro

, and this oscillator appears to function as a post‐translational oscillator (PTO)

in vivo

. Because this PTO regulates rhythmic transcription and translation, the entire circadian system comprises both the PTO and a transcriptional/translational feedback loop. Models of the complete

in vivo

system have important implications for our understanding of circadian clocks in higher organisms, including mammals.

Key Concepts:

Prokaryotic cyanobacteria have a circadian timekeeping system that enhances fitness.

These cells exhibit pervasive circadian regulation of gene expression, possibly mediated by cyclic changes of chromosomal topology.

A circadian rhythm of the phosphorylation of the central clock protein KaiC can be reconstituted
in vitro
with three proteins derived from cyanobacteria (KaiA, KaiB and KaiC) and ATP.

KaiA, KaiB and KaiC are the only circadian clock proteins for which the 3‐D structure of full‐length proteins is known.

Structural, biochemical and biophysical methods have been used to study the mechanism by which KaiC is rhythmically phosphorylated and dephosphorylated.

Mathematical modelling that has been applied to the
in vitro
and
in vivo
systems indicate the existence of a core biochemical post‐translational oscillator (PTO) that controls a larger transcription/translation feedback loop (TTFL).
Endosymbionts
Authors: Jeon Kwang W
Published: April 2013

Endosymbionts are smaller symbiotic partners living inside a host organism, establishing endosymbiosis. The symbionts may live within the host's cells (intracellular) or outside cells (extracellular) in multicellular hosts. A symbiotic relationship may be parasitic (one partner harming the other), commensal (usually not affecting each other) or beneficial (unilaterally or mutually). Examples of intracellular endosymbionts include bacteria and single‐celled algae living inside free‐living cells or cells of various multicellular organisms. It is believed that cellular organelles such as mitochondria and chloroplasts arose within eukaryotic cells by a series of intracellular endosymbioses. Some bacteria live in various marine invertebrates and in insects as extracellular endosymbionts. Many of both intracellular and extracellular endosymbionts form obligate endosymbioses, in which neither the endosymbionts nor their hosts can live without the other. Recent genetic studies have shown that lateral gene transfers occur between symbionts and hosts. In some cases, the transferred symbionts’ genes are expressed in the progeny of multicellular hosts.

Key Concepts:

Endosymbiosis is a wide‐spread phenomenon in nature.

Endosymbionts may live inside host cells or outside cells in multicellular hosts.

Hosts provide suitable habitat to established endosymbionts.

Cellular organelles arose within eukaryotic cells by a series of intracellular endosymbioses.

Genes are transferred laterally between endosymbionts and hosts.

Transferred endosymbionts’ genes may be expressed in the hosts and their progenies.
Halophiles
Authors: DasSarma Shiladitya , DasSarma Priya
Published: April 2013

Halophiles are salt‐loving organisms that flourish in saline environments and can be classified as slightly, moderately or extremely halophilic, depending on their requirement for sodium chloride. Although most marine organisms are slight halophiles, moderate and extreme halophiles are generally more specialised microbes, which inhabit hypersaline environments with salinity higher than in the sea. Hypersaline environments are found all over the world, in arid, coastal, and deep‐sea locations, underground salt mines, and artificial salterns. Halophilic microorganisms include a variety of heterotrophic, phototrophic, and methanogenic archaea, photosynthetic, lithotrophic, and heterotrophic bacteria, and photosynthetic and heterotrophic eukaryotes. Examples of well‐adapted and widely distributed extremely halophilic microorganisms include archaea for example,Halobacteriumsp. NRC‐1, cyanobacteria such asAphanothece halophytica, and the green algaDunaliella salina. Multicellular halophilic eukaryotic organisms include brine shrimp and the larvae of brine flies. Halophilic organisms either accumulate internal organic compatible solutes to balance the osmotic stress of the environment or produce acidic proteins to increase solvation and improve function in high salinity.

Key Concepts:

Halophiles are salt‐loving organisms that inhabit saline and hypersaline environments and include prokaryotic (archaeal and bacterial) and eukaryotic organisms.

Many halophiles accumulate compatible solutes in cells to balance the osmotic stress in their environment.

Some halophiles produce acidic proteins that are able to function in high salinity by increasing solvation and preventing aggregation, precipitation and denaturation.
Measles Virus
Authors: Rima Bertus K , Duprex W Paul
Published: April 2013

Measles virus(MV) is responsible for a childhood infection characterised by a maculopapular rash, dry cough, coryza, conjunctivitis and photophobia. Although mild in developed countries, the infection is associated with significant morbidity in developing countries and still kills more than 200 000 children per annum even though it is a vaccine preventable disease. The virus replication cycle is well understood and the molecular description of the virus has progressed to a stage where the main emphasis of research has reverted towards understanding the pathogenesis and molecular basis of virus attenuation. Such knowledge will assist in the development of new vaccines and serve to increase our understanding of epidemiology and transmission. Our ability to make recombinant viruses that express autofluorescent proteins from additional transcription units within the genome has created a paradigm shift in changing our view of MV from simply a ’respiratory infection‘ causing agent to one that affects the immune system in a serious and potentially dangerous manner. Identification of the early target cells as alveolar macrophages and/or dendritic cells in the deep lung alongside understanding the early events in viral pathogenesis helps shed light on how this highly infectious agent establishes such a profoundly immunosuppressive disease in the host.

Key Concepts:

Measles is a relatively simple enveloped, negative‐sensed RNA virus which contains only six genes.

Measles virus is a highly infectious agent, which causes a profound immunosuppression and a severe disease in susceptible individuals.

The molecular basis of the immunosuppression is unknown.

A highly efficacious vaccine has been developed, although the molecular basis of the attenuation remains an enigma.

It is essential to vaccinate 95% of the birth cohort as the virus is so infectious and when vaccine uptake levels decrease in disease‐free regions importations from endemic parts of the world often occur.

The vaccine is exceptionally thermolabile and this is challenging for those involved in delivering the product to remote areas of the developing world and in areas where conflict is rife.

Recombinant measles viruses have helped to define the early steps in the establishment of an infection.

Measles has been considered for eradication although the potential for cross‐species infection is being considered due to the cross‐protective morbillivirus antibodies which are elicited.
Prion Diseases
Authors: Ryou Chongsuk
Published: April 2013

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are transmissible degenerative disorders of the central nervous system in mammals. TSEs are fatal and are caused by the proteinaceous infectious particles, termed prions that lack informational nucleic acids. TSEs include Creutzfeldt–Jakob disease in humans, scrapie in sheep, bovine spongiform encephalopathy or ‘mad cow disease’ in cattle and chronic wasting disease in deer and elk. These diseases manifest spongiform degeneration, reactive gliosis, and deposition of prion aggregates in the brain. The aetiology of TSEs is sporadic, genetic, or acquired. The primary structure of PrP
C
, conformational diversity of PrP
Sc
, and their interplay influence intra‐ and inter‐species prion transmission. The role of lymphoreticular system is pivotal in early prion pathogenesis and neuroinvasion, whereas neuronal damage caused by prion infection could be achieved by several different mechanisms. Despite the potential risk for public health, diagnosis and therapy for prion diseases are currently unavailable.

Key Concepts:

Prion diseases represent a group of human and animal diseases that include sporadic, inherited, and acquired Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker syndrome (GSS), and fatal familial insomnia (FFI) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, feline spongiform encephalopathy (FSE) in cats, and exotic ungluate encephalopathy (EUE) in exotic ungulates.

Prion diseases are fatal neurological disorders and caused by the unconventional proteinaceous pathogen, termed prion.

Prion diseases manifest characteristic clinical and neuropathological features.

Prion diseases are transmissible within and between the species.

Transmission of prion diseases is determined by the amino acid sequence variability of PrP
C
and prion strains conferred by conformational diversity of PrP
Sc
.

The lymphoreticular system is crucial in prion pathogenesis and neuroinvasion.

Gain of pathologic PrP
Sc
function and/or loss of neuroprotective PrP
C
function facilitate neuronal damages in the central nervous system by direct or indirect mechanism associated with astrocyte and microglial cells.

Atypical TSEs and human‐to‐human transmission of vCJD have been identified.

Diagnosis and therapy for prion disease are not available.
Respiratory Syncytial Virus
Authors: Rawling Joanna , Melero José A
Published: April 2013

Human respiratory syncytial virus (HRSV) is a ubiquitous
ribonucleic acid
(RNA) virus that represents the leading cause of acute lower respiratory infections (mainly bronchiolitis and pneumonia) in infants and young children worldwide. HRSV belongs to the
Pneumovirinae
subfamily within the
Paramyxoviridae
family of enveloped, negative‐strand RNA viruses. Epithelial cells lining the nasal passages and respiratory tract are the primary target of HRSV infection, although alveolar macrophages and dendritic cells are also infected. Infected cells respond by producing a variety of cytokines, chemokines and interferons that are involved in the inflammatory response to HRSV. Although primary HRSV infection occurs at an early age, immunity is short‐lived or incomplete and re‐infections occur throughout life. Initial efforts to develop a vaccine based on formalin‐inactivated HRSV resulted in vaccine‐enhanced disease, and there is still no licensed prophylactic HRSV vaccine available.

Key Concepts:

Human respiratory syncytial virus (HRSV) is the leading cause of serious respiratory tract disease in children and infants worldwide.

HRSV belongs to the
Pneumovirinae
subfamily within the
Paramyxoviridae
family of negative‐strand RNA viruses.

The HRSV genome comprises 10 genes that encode 11 viral proteins.

HRSV derives its name from the formation of multinucleated, fused cells (syncytia), which are the hallmark of infection of cultured cells or lung tissue.

Following attachment to the target cell, entry by HRSV is mediated by fusion of the viral envelope with the host cell plasma membrane at neutral pH.

The entire replication cycle of HRSV takes place in the cytoplasm of the infected cell.

Reverse genetics has permitted the recovery of infectious HRSV from complementary DNA.

HRSV strains disseminate rapidly worldwide, accumulating mutations predominantly in the attachment protein, probably as a consequence of immune selection.

Pathology associated with HRSV infections is not only the result of direct virus injury, but largely the consequence of an aberrant immune/inflammatory response.

Palivizumab, a neutralising monoclonal antibody directed against HRSV fusion protein, is the only product available on the market for prophylactic treatment of children at high risk of severe infection.
Retroviral Replication
Authors: Pedersen Finn Skou , Pyrz Magdalena , Duch Mogens
Published: April 2013

Retroviruses are enveloped animal
ribonucleic acid
(RNA) viruses that replicate via a
deoxyribonucleic acid
(DNA) intermediate, which is integrated into the host genome as a provirus. Interaction of the viral envelope protein with a target cell receptor triggers entry of the viral nucleoprotein core by fusion of viral and cellular membranes. After entry, the viral enzymes
reverse transcriptase
and
integrase
mediate reverse transcription of viral RNA and integration of the resulting double‐stranded DNA copy of the viral genome, respectively. Expression of viral RNA and proteins from proviral DNA utilises the transcription and translation machinery of the host. Retrovirus particles are assembled through protein–protein and protein–lipid interactions, released from the cell by budding, and subsequently matured by a
viral protease
. A provirus can be transmitted through the germline from parents to offspring as an endogenous retrovirus. Host cell restriction factors target multiple steps of retroviral replication in a complex interplay of virus–host interactions.

Key Concepts:

Reverse transcription and integration into the host genome are hallmarks of retroviral replication.

The viral RNA genome contains a packaging signal for selective encapsidation into viral particles and a binding site for a tRNA primer for initiation of reverse transcription.

The integrated virus contains long‐terminal repeats harbouring signals for transciptional initiation and polyadenylation, which define the retroviral transcription unit.

Open reading frames for Gag, Pol and Env are found in all retroviruses, but some retroviruses encode additional proteins such as Tat and Rev of HIV‐1.

A stop‐codon between gag and pol can be bypassed by read‐through or frame‐shifting during translation of retroviral mRNA to make the Gag–Pol polyprotein.

Retroviruses have specialised strategies for export of unspliced genomic‐length viral RNA from the nucleus.

The metastable retroviral envelope protein drives the fusion of viral and cellular membranes by a type I fusion mechanism to allow retroviral entry in a receptor‐dependent manner.

The retroviral protease is required for maturation of viral particles after their release from producer cells by budding.

A retrovirus can integrate into the genome of germ cells and become part of the genetic material transmitted from parents to offspring.

A provirus can be maintained through species diversification as an endogenous retrovirus that may serve as a marker of phylogenetic relationship and evolutionary distance.
Rubella
Virus
Authors: Frey Teryl K , Matthews Jason D
Published: April 2013

Rubella
virus is a human virus belonging to the family
Togaviridae
and the sole member of the rubivirus genus.
Rubella
virus has a small genome composed of single‐stranded RNA and produces only five proteins. The
rubella
virus replication cycle takes place entirely within the cytoplasm of the infected cell.
Rubella
virus establishes a body‐wide or systemic infection that is manifested by mild symptoms including rash, lymph node swelling and low‐grade fever. However,
rubella
virus is an important human pathogen because it causes a spectrum of serious birth defects known collectively as congenital
rubella
syndrome (CRS) when a mother lacking immunity is infected during the first trimester of pregnancy. CRS can include blindness, deafness, mental retardation, heart malformations and endocrine dysfunctions. Before development of effective live, attenuated vaccines,
rubella
virus was the leading teratogenic agent of an infectious nature. Through use of these vaccines,
rubella
and CRS are controlled in much, but not all, of the world and are targeted for elimination in the Western Hemisphere and Europe.

Key Concepts:

Rubella
virus causes a benign systemic illness characterised by a rash, but is a dangerous teratogen when infection occurs during pregnancy.

Fetal infection by
rubella
virus results in congenital rubella syndrome, a constellation of serious birth defects, particularly deafness, blindness and mental retardation.

Rubella
virus is classified in the
Togaviridae
family and is the only member of the rubivirus genus.

Rubella
virions are pleiomorphic, approximately 70 nm in diameter and consist of a quasispherical capsid containing the genome RNA surrounded by an envelope composed of a lipid bilayer from which protrude glycoprotein spikes.

The
rubella
virus genome is a plus‐polarity RNA, 10 000 nucleotides in length, which encodes only five proteins: P150 and P90, both of which participate in RNA replication in the infected cells, and capsid (C) and envelope glycoproteins 1 and 2 (E1 and E2) which comprise the virion.

In the infected cell,
rubella
virus replication takes place entirely within the cytoplasm.

In the infected cell,
rubella
virus RNA replication, which proceeds through an RNA intermediate, takes place in association with cell membranes.

In the infected cell,
rubella
virion formation takes place in association with the Golgi apparatus and virions are released by exocytosis.

Rubella
virus isolates worldwide cluster into 13 genotypes that fit into two distinct clades with an overall diversity at the nucleotide level of approximately 10%, a very low level for an RNA virus.

Live, attenuated
rubella
virus vaccines, available since approximately 1970, have been used successfully to control or eliminate rubella in developed countries whereas implementation of these vaccines is progressing, but not complete, in undeveloped countries of the world.
Bacterial Origins
Authors: Koch Arthur L
Published: April 2013

One line of descent from the Last Universal Ancestor generated a group of organisms now called Bacteria and another called the Archaea. Both groups are quite diverse and each is quite different; they are collectively called prokaryotes. Before they arose the original first organism had to be able to reproduce and differentiate. This cell must have been able to execute selected chemical reactions to do this. These must have included: (1) a system to energise biosynthesis in order to drive chemical reactions in the biologically useful direction (which could often be in the nonspontaneous direction); (2) a system to duplicate nucleic acids chains by semiconservative replication and (3) an ability for these chains to serve as catalysts for specific biosynthesis. Therefore at least three facilities had to function inside the closed vesicle that then became the First Cell.

Key Concepts:

Few elements were needed for life to start.

More features are common to all life today.

Woese's deductions from ribosome studies of the ontogeny of life led to a breakthrough allowing a more stable taxonomy and phylogeny.

Bacteria are phylogenetically separated from Archaea/Eukarya.

In many cases the phenotypic properties of different organisms correlate with the phylogeny.

Lateral Transfer of Genes was important, but complicates studies of early life.
Codes of Nomenclature
Authors: Krichevsky Micah I
Published: April 2013

Codes of Nomenclature are the agreed conventions for naming biological groups. The various Codes define the rules for constructing the names of biological entities. Different organisations within the The International Council for Science (ICSU) control the individual Codes for zoology, botany, prokaryotes (bacteria and archea) and viruses. With the single exception of viruses, the Codes allow for competing taxonomies. In the other Codes, the competition arises because no judicial systems exist for choosing among the competitors. Only usage dictates the winners. Some organism groups are redundant in coverage between Codes. The Codes differ in defining examples of organism deposit and availability as benchmarks for species. Other codes have been proposed, such as Biocode (treat rationalisation of the ICSU recognised Codes) and PhyloCode (basing the code on phylogenetic criteria).

Key Concepts:

An inherent tension exists between stability of names and changes resulting from further study.

The various rules of nomenclature define the construction of the names of species, albeit somewhat differently in details.

With the exception of viruses, benchmark examples (Types, Type Specimens, Type Cultures, Type Descriptions, etc.) are required to allow for species comparison and identification.

The published description of a new taxon rarely, if ever, indicates the boundaries of the taxon.

Taxonomies function as useful indexing systems to locate members in biological space and are not absolute.

Both among and within taxa at all levels new information causes changes in views of the centres and borders of taxa.
Catabolic Plasmids
Authors: Schmidt Radomir , Ahmetagic Adnan , Philip Daniel S , Pemberton John M
Published: April 2013

Catabolic plasmids are large (80→1100 kb) linear or circular, accessory deoxyribonucleic acid elements present in the cytoplasm of bacteria from virtually every ecological niche on Earth. Many have a broad host range and can be transferred by cell‐to‐cell contact to a wide range of bacteria. The large catabolic gene clusters carried by these plasmids play a central role in the Earth's carbon cycle, enabling their hosts to degrade and recycle complex naturally occurring molecules such as lignin, the second most abundant plant biopolymer on Earth after cellulose. More recently catabolic gene clusters have evolved the ability to degrade and recycle most man made molecules, including the most toxic and the most recalcitrant environmental pollutants, providing a biological solution to environmental pollution. Catabolic genes have been used to construct novel strains of bacteria which produce biopharmaceuticals such as antibiotics and anticancer agents, biofuels such as ethanol, industrial dyes such as indigo and biodegradable plastics. The very first patent for a genetically modified organism was for the use of catabolic plasmids to degrade oil.

Key Concepts:

Catabolic plasmids are giant bacterial plasmids that encode vast arrays of catabolic gene clusters. They play a central and indispensible role in the Earth's carbon cycle.

Catabolic plasmids are essential for the degradation and recycling of abundant, naturally occurring yet chemically complex plant materials such as lignin.

In addition, there are catabolic plasmids, which enable bacteria to degrade and recycle the most complex, most toxic and the most polluting man‐made molecules including most carcinogens, teratogens and mutagens.

Degradation and recycling of such complex molecules at room temperature and pressure, so called ‘green or eco‐friendly’ chemistry, requires many different enzymes encoded in large arrays of gene clusters. To accommodate these genes on catabolic plasmids they must be very large. Some are in excess of 1000 kb.

Many catabolic plasmids are transferable from one bacterial cell to another by cell‐to‐cell contact. They have an extraordinarily broad host range being able to rapidly confer their catabolic activities on large populations of soil bacteria.

Novel catabolic functions can be produced by rearranging existing pathway genes, combining genes from different pathways to form a new pathway and by fusing segments from a number of pre‐existing catabolic genes into a new catabolic gene.

The genes encoded by catabolic plasmids have been harnessed by humans to produce antibiotics and anticancer drugs, to synthesise biofuels such as ethanol from lignin and to degrade and recycle man‐made environmental pollutants.

The very first patent to be granted for a genetically modified organism was for catabolic plasmids that encoded the degradation of environmental oil spills.
Vaccines: Presentation
Authors: Hochrein Hubertus , O'Keeffe Meredith
Published: April 2013

Vaccines have been the success story of immunology and medicine, saving millions of lives by employing nature's own powerful armoury against pathogens. This armoury known as the immune system has been shaped and optimised for millions of years by coevolution between higher organisms and pathogens including viruses, bacteria, fungi and parasites. The adaptive immune system, which includes antibody‐producing B‐cells and T‐cells, is so powerful that it is able to fight against all foreign intruders, and in most cases controls pathogens of all kinds. Moreover, it develops an immunological memory which allows quick and effective recall responses against previously encountered pathogens. However, there is a caveat with the effectiveness of adaptive immune responses; when compared with the rapid multiplication of viruses and bacteria (hours), adaptive immune responses need a considerable length of time to be effective (days to weeks). The principle of vaccination is to expose the immune system with components of the pathogens it may encounter, allowing the immune system to mount effective measures and immunological memory and thus be prepared to fight the real pathogen if it comes along.

Key Concepts:

The adaptive immune system is able to fight against all types of pathogens.

Vaccinations allow the adaptive immune system to mount effective memory responses without the full pathologies caused by the pathogen.

For optimal immune responses vaccines should contain both foreign material and a danger signal.

Dendritic cells are an important cellular component of danger recognition, and they direct the type of adaptive immune response mounted.

Danger signals are recognised at the molecular level by pattern recognition receptors, for example, TLR, NLR, RLH and C‐type lectins.
Antibody‐dependent Cellular Cytotoxicity (ADCC)
Authors: Teillaud Jean‐Luc
Published: April 2013

Antibody‐dependent cell‐mediated cytotoxicity (ADCC) is the killing of an antibody‐coated target cell by a cytotoxic effector cell through a nonphagocytic process, characterised by the release of the content of cytotoxic granules or by the expression of cell death‐inducing molecules. ADCC is triggered through interaction of target‐bound antibodies (belonging to IgG or IgA or IgE classes) with certain Fc receptors (FcRs), glycoproteins present on the effector cell surface that bind the Fc region of immunoglobulins (Ig). Effector cells that mediate ADCC include natural killer (NK) cells, monocytes, macrophages, neutrophils, eosinophils and dendritic cells. ADCC is a rapid effector mechanism whose efficacy is dependent on a number of parameters (density and stability of the antigen on the surface of the target cell; antibody affinity and FcR‐binding affinity). ADCC involving human IgG1, the most used IgG subclass for therapeutic antibodies, is highly dependent on the glycosylation profile of its Fc portion and on the polymorphism of Fcγ receptors.

Key Concepts:

Antibodies bound to target cells (virus‐infected or tumour cells) and Fc receptors expressed by cytotoxic cells are the major actors of ADCC.

IgG and IgA can trigger ADCC by binding specifically to FcγR and FcαR, respectively.

ADCC mechanisms that lead to target cell death vary depending on effector cells that are recruited by antibodies.

FcγRIIa and FcγRIIIa polymorphism impact ADCC efficacy by IgG1 antibodies.

Engineering FcIgG either by introducing point mutations or by modifying the glycosylation profile allows to optimise IgG1 antibodies for enhanced ADCC.

Bispecific antibodies that bind activating molecules expressed by cytotoxic cells and tumour cells can mimic classical ADCC.
Complement System and Its Role in Immune Responses
Authors: Oikonomopoulou Katerina , Reis Edimara S , Lambris John D
Published: April 2013

The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and adaptive host defence mechanisms, whereas they also participate in various (patho)physiological processes. The primary functions mediated by complement proteins include phagocytosis of foreign elements (bacteria, viruses, particles

etc

.), cell lysis, inflammation, solubilisation of immune complexes, apoptotic cell clearance and enhancement of humoral immune responses. Dysregulation of complement activity has, therefore, been connected to various diseases, including autoimmune conditions, thrombotic pathologies and infections.

Key Concepts:

Complement is a multiprotein network of plasma proteins and cell surface receptors.

Complement is an evolutionary conserved system.

Complement participates in innate and adaptive immunity.

Complement dysregulation and deficiencies are connected to disease.
Transfer
RNA
Structure
Authors: Westhof Eric , Auffinger Pascal
Published: April 2013

Transfer ribonucleic acid (tRNA)
molecules that participate in the elongation step of protein synthesis on the ribosome have a conserved secondary structure, known as the cloverleaf, and fold into a common three‐dimensional architecture. The conservation of the global L‐shaped 3D fold is assessed by the more than 100 available crystal structures showing tRNAs in native states or in complexes where tRNAs are bound to various interacting systems such as cognate synthetases, editing, modification and processing enzymes or full ribosomes. These tRNA crystal structures display a whole range of structural adaptability features encoded in their sequence and underlying their various functions. Thus, as the number of available structural data expands, the concept of a unique tRNA structure fades out for that of an ensemble of interconnected and environmentally dependant tRNA structures.

Key Concepts:

tRNAs display a huge sequence variability.

tRNA molecules fold with a conserved secondary structure.

The conservation of the secondary structure originatesbase covariations in Watson–Crick pairs of helices.

The tertiary folds of tRNAs present a striking adaptability.

The structural adaptabilities of tRNAs stem from the molecular neutrality present among the various noncovalent interactions.

Only a minimal number of conserved tertiary interactions are preserved.

The maintenance of some non‐Watson–Crick pairs is key for the three‐dimensional structure.

As a consequence of structural adaptability, tRNAs have acquired a greatdiversity in biological systems.

The structure and function of tRNAs is modulated by the type and concentration of the ions surrounding them.
Drosophilaas an Experimental Organism for Functional Genomics
Authors: Dow Julian AT
Published: April 2013

Although historically the classical model for the understanding of development, the fruit‐flyDrosophila melanogasteris valuable for study for three reasons: as an organism in its own right, as an inexpensive, genetically powerful model for human function and disease, and as a model for economically important or harmful insects, such as vectors of disease. The sophisticated genetic tools that distinguishDrosophilafrom other model organisms or insects allow great spatial and temporal precisions both in genetic intervention, and in the expression of genetically encoded sensors for second messengers or intracellular environmental variables. Combined with other, novel functional readouts, it is now possible to move towards an understanding ofDrosophilaas a metazoan organism composed of distinct and individually tractable tissues that interact and integrate to produce a functioning whole.

Key Concepts:

Drosophila melanogasteris a small, easily reared insect with a short lifecycle.

The key advantages ofDrosophilaare a balance between genetic power and biomedical relevance, and rapidity and low cost of generation and maintenance of mutant and transgenic stocks.

The genetic toolbox available forDrosophilaallows precise intervention in specific, defined cells in an otherwise normal organism, opening unique opportunities for functional biology.

Approximately 70% of human genes have clearDrosophilahomologues, allowing the modelling of many human diseases in flies.

Drosophilaalso shares approximately 70% of its genes withAnopheles gambiae, the mosquito vector of malaria.

Our understanding of fly development is now mature: new phenotypes are required to provide a global functional genomic understanding.

An exciting challenge for the future is functional biology; understanding how the different tissues and control systems interact to make a working, successful organism.
Peptidoglycan
Authors: Young Kevin D
Published: April 2013

Peptidoglycan is the rigid, but flexible, macromolecule that surrounds and protects individual bacterial cells. It supplies the foundation for bacterial cell walls, defines an organism's shape and anchors protein complexes and extracellular organelles to the cell surface, all while remaining porous enough to admit essential nutrients and large compounds. Peptidoglycan fragments trigger neighbouring microorganisms to grow or to modify their own walls, serve as maturation signals for vertebrate immune systems and may be used to manipulate the immune system for the benefit of pathogenic organisms. Because it is unique to bacteria, peptidoglycan is one of the most valuable targets to which antibiotics may be directed. Although the components of peptidoglycan are known and we have a basic understanding of its biosynthesis, there remains a great deal to learn about its three‐dimensional organisation, its biological properties and activities, and how it expands and divides during bacterial growth.

Key Concepts:

Peptidoglycan is the basic component of the bacterial cell wall, which is the protective structure that surrounds and protects most bacteria.

Peptidoglycan is composed of numerous glycan (sugar‐based) polymers that are covalently crosslinked to one another by short peptide side‐chains, creating a single bag‐like macromolecule called the sacculus.

Penicillin‐binding proteins are responsible for the final stages of peptidoglycan synthesis, but additional proteins modify peptidoglycan in numerous ways in different bacteria.

Because of its complexity, the exact three‐dimensional structure of peptidoglycan is not known, but it is thought to look like a net with pores 2–5 nm in diameter.

Large protein complexes and organelles are embedded in or are threaded through peptidoglycan, indicating that enzymes must degrade peptidoglycan in a limited way to create holes in which these structures may be assembled.

Bacteria can change the composition and perhaps the structure of their peptidoglycan, depending on growth conditions and in response to their environmental surroundings.

Peptidoglycan is constantly being broken down, recycled and renewed as bacteria grow and divide.

Bacteria use peptidoglycan fragments to signal or manipulate other microorganisms or even human and animal immune systems.

Because peptidoglycan is unique to bacteria, the enzymes that synthesise it are some of the most important targets for antibiotic therapy.
Bacteriophages
Authors: Maniloff Jack
Published: April 2013

Bacteriophages (phages) are viruses that infect most, if not all, bacteria in the domains Bacteria (eubacteria) and Archaea (archaebacteria). Most (96%) phages have tailed phage morphology, with the rest having a polyhedral, filamentous or pleomorphic morphology. Phage genomes are a single‐ or double‐stranded, linear or circular,
deoxyribonucleic acid (DNA)
or
ribonucleic acid (RNA)
molecule. An exception is the cystovirus genome, which consists of three RNA molecules. Most phages produce a lytic infection, which typically involves phage attachment to the cell surface, injection of phage nucleic acid into the cell, intracellular expression of phage genes to produce nascent phage nucleic acid and proteins, assembly of progeny phages, and cell lysis to release progeny phages. In some situations, instead of a lytic infection, some phages remain latent in infected cells – a process called lysogeny. As bacterial predators, phages affect global biogeochemical cycles.

Key Concepts:

Bacteriophages (phages) are viruses that infect most, if not all, bacteria in the domains Bacteria (eubacteria) and Archaea (archaebacteria).

Most (96%) phages have tailed phage morphology, with the rest being polyhedral, filamentous or pleomorphic.

Phages genomes are a single‐ or double‐stranded, linear or circular, DNA or RNA molecule, except cystoviruses, which have a genome of three molecules of linear double‐stranded RNA.

Most phages have a lytic infection cycle, in which an infected cell produces nascent phage nucleic acid and proteins, which are assembled into progeny phages and released by cell lysis.

Some phage infections are lysogenic, in which the intracellular phage remains latent and the cell continues to grow.

Bacteria have a type of adaptive immunity, the CPISPR system, against phages and plasmids.

As bacterial predators, phages affect global biogeochemical cycles.
Microviridae: Microviruses and Gokushoviruses
Authors: Cherwa James E , Fane Bentley A
Published: April 2013

Members of theMicroviridaecomprise two subfamilies. The microviruses (Greek for small), which infect free‐living bacteria, are among the fastest known replicating viruses. Gokushoviruses (Japanese for very small) occupy a unique niche, infecting obligate intracellular bacteria, such asChlamydiaandBdellovibrio, or mollicutes, bacteria without a cell wall. All members of the family contain small (4000–6000 bases), circular, single‐strandeddeoxyribonucleic acid(ssDNA) genomes of positive polarity, which are packaged inside small (∼25 nm diameter) T=1 icosahedral capsids. The other icosahedral, ssDNA virus families:Parvoviridae,Circoviridae,NanoviridaeandGeminiviridae; share most of these properties, suggesting a large super family spanning several domains of life. The most well known member of theMicroviridae, ϕX174, has been extensively used to study the fundamental mechanisms of DNA replication and capsid assembly. The latter is uniquely dependent on two scaffolding proteins, and has become a model system for experimental evolution.

Key Concepts:

Whilst overlapping reading frames increase the amount of genetic information encoded in small genomes, they do not appear to significantly impact the ability of the virus to genetically adapt to selective pressures.

Due to the genome's positive polarity, DNA replication must commence before viral genes can be transcribed.

Microvirus DNA replication occurs in three distinct stages: (1) ssDNA is first converted to a double‐stranded molecule, (2) amplification of the double‐stranded molecule, (3) single‐stranded genomic DNA synthesis and packaging.

Genomic DNA synthesis and packaging are concurrent processes; thus, a genome is not synthesised unless there exists a capsid in which to package it.

Gene expression is controlled by the finely tuned interplay ofcis‐acting genetic elements: promoters, ribosome binding sites, mRNA stability sequences and transcription terminators.

Microviruses are distinguished by their two scaffolding protein system, whereas Gokushoviruses utilise a single scaffolding protein.

Capsid assembly is mediated by scaffolding proteins, which induce conformational switches in the viral coat protein to control the timing and fidelity of morphogenesis.

Cell lysis is achieved by inhibiting host cell wall biosynthesis, a mechanism reminiscent of some antibiotics.
Drosophila
Neural Development
Authors: Sprecher Simon
Published: April 2013

The human brain is by far the most complex organ system in terms of cell type variety and interaction between cells. Studies from comparatively simple animal models allow us to genetically dissect the development and function of the nervous system. Advanced molecular genetic tools make the fruit fly

Drosophila melanogaster

a unique and powerful model system to study how during development a complex nervous system develops, how neurons and glia cells are generated and correctly assembled. Many key processes such as proliferation of neural stem cells, neurogenesis, orchestration of spatial and temporal identity, axon guidance and establishment of connectivity have been investigated in fruit flies. Comparative analysis shows that developmental processes as well as genetic pathways acting to build a complex brain are shared between mammals and insects.

Key Concepts:

Along the anteriorposterior and dorsoventral axes transcription factors pattern the nervous system.

Neural stem cells divide asymmetrically to self‐renew and generate committed neural precursors.

Different types of neural stem cells exist to establish different domains of the central nervous system.

Even though the brains of insects and mammals appear quite distinct the overall mode of development are similar.
Genetic Code: Introduction
Authors: Watanabe Kimitsuna , Yokobori Shin‐ichi
Published: April 2013

The genetic code establishes the relationship between all 64 possible arrangements of triplets (codons) of the four nucleotide bases contained in either DNA (A, T, G and C) or RNA (A, U, G and C) and the 20 amino acids that are used to construct proteinsvia‘translation’ system as well as signals of translation initiation and termination. The historical events from 1950s to 1960s that contributed to the deciphering of the genetic code led to the development of the field of molecular biology. In 1960s, the genetic code was established to be ‘universal’ for all living organisms. However, from late 1970s, variations of genetic code have been found in various genetic systems. Variations of genetic code promote studies on the origin and evolution of the genetic code.

Key Concepts:

Genetic code is the correlation between nucleotide triplet and the corresponding amino acid.

Genetic code consists of 64 triplet codons and sometimes ‘degenerate’.

Central dogma states that genetic information flows unidirectionally from DNA to proteinviaRNA as an intermediary.

A cell‐free protein system contains ribosome, S100 fraction, tRNA, amino acids, ATP, an energy recycling system and a template.

Termination codon consists of UAG (amber codon), UAA (ochre codon) and UGA (opal codon), which code for no amino acid but instead cause protein synthesis to terminate.

Initiation codon is AUG, which initiates protein synthesis with formyl‐methionine in bacteria and phage.

Universal genetic code shows the way of assignment of 64 triplet codons to each of 20 amino acids and 3 termination codons, which is common to almost all extant organisms – bacteria, yeasts, viruses, plants and animals.
Semaphorins
Authors: van Erp Susan , Jeroen Pasterkamp R
Published: April 2013

The semaphorins are an evolutionary conserved family of intercellular signalling proteins known to deliver guidance cues to growing axons and migrating cells during development. Semaphorins bind with high affinity to several distinct receptor families on the cell surface, including the neuropilins and plexins. The interaction of semaphorins and their receptor complexes triggers elaborate intracellular signalling pathways that in many cases regulate the cytoskeleton to control growth cone or cellular morphology. However, semaphorins also regulate cellular processes not directly related to changes in cytoskeletal dynamics such as apoptosis or cytokine release. Defects in semaphorin function have been associated with a variety of human diseases including amyotrophic lateral sclerosis, spinal cord injury and cancer, and studies have been initiated to use semaphorin proteins as therapeutic targets in human disorders.

Key Concepts:

Semaphorins are bi‐functional guidance cues mediating attractive and repulsive chemotactic responses.

Semaphorin receptor complexes are composed of ligand binding, signal‐transducing and modulatory subunits.

Context‐dependent changes in receptor or signalling components determine the downstream effect of semaphorins.

Semaphorins can act as ligands and receptors, a process called bi‐directional signalling.

Secreted and membrane‐associated semaphorins regulate various aspects of neural circuit development.

Signalling cues that function downstream of semaphorin receptors includes protein kinases and small GTPases.

Semaphorins have been implicated in various human diseases and may serve as therapeutic targets.
Ephrins
Authors: Kilari Sreenivasulu , Wilkinson George
Published: April 2013

Ephrins are cell surface proteins which bind to the Eph family of receptor tyrosine kinases. Cell surface‐attached ephrin‐A ligands principally activate EphA receptors, and transmembrane ephrin‐B ligands primarily activate EphB receptors. Ephs and ephrins influence many developmental processes, including compartmentalisation, cellular migration, axon guidance and angiogenesis. These developmental functions arise as Ephrin–Eph interactions shape cellular behaviours, including adhesion, migration and synaptic plasticity. Eph receptors communicate with the cytoskeleton through differential activation of small GTPases downstream of their tyrosine kinase activity. In addition to stimulating Eph receptors, ephrins signal within the cell which expresses them, a phenomenon termed ‘reverse signalling’. Ephrin‐B reverse signalling relies in part on phosphorylation of the cytoplasmic tail and recruitment of cytoplasmic proteins. Both ephrins and Ephs can modify internalisation and trafficking of other cell surface effector molecules.

Key Concepts:

Ephrins are implicated in numerous developmental events centred around cell‐contact‐dependent signalling.

Ephrin ligands and Eph receptors participate in axon guidance, and graded expression of this system is implicated in the topographic mapping of the retinotectal projection.

Ephrins also critically control synaptic function.

In the vasculature, EphB4 and ephrin‐B2 are required for angiogenesic remodelling of the primitive vascular plexus.

Ephrins both stimulate Eph receptor tyrosine kinases and transduce ‘reverse’ signals in the cells which express them.

The specific outcome of Eph–ephrin engagement depends on cellular context and on the involvement of other signalling components.
Idiotypes
Authors: Gavalchin Jerrie
Published: April 2013

Idiotypes are unique determinants of an immunoglobulin or T‐cell receptor that can function as antigens. Responses to idiotypes, which include anti‐idiotypic (Id) antibody (Ab)‐producing B cells and idiotype‐specific T cells, form a network that regulates their production, referred to as the idiotypic network. In an immune response, antibody 1 (Ab1) is produced in response to an antigen, and anti‐Id Ab produced to Ab1 (Ab2) may bind in the antigen‐combining site (Ab2β) or the framework region (Ab2γ) of Ab1. As Ab2β can fit in the paratope of an antigen receptor of B or T cells, it mimics the three‐dimensional structure and is the internal image of antigen, and has the potential to activate Ab1 precursors reactive with the antigen. These findings have led to the use of Ab2β as an immunogen to elicit specific immune responses to foreign pathogens, as probes to study cell surface receptors and as immune therapy for tumours.

Key Concepts:

Idiotypes are unique determinants located in the variable region of antigen receptors on B cells (immunoglobulin, Ig) and T cells (T‐cell receptor, TCR).

Antibody 1 (Ab1) is produced in response to an antigen and Ab2 produced to Ab1 may react with the antigen‐combining site (Ab2β, internal image of antigen) or the framework region (AB2γ) of the antibody molecule.

The interaction of clones of B and T cells that express distinct idiotypic specificities to regulate the immune response is referred to as the idiotypic network.

The idiotypic network can be exploited to elicit specific immune responses to foreign pathogens, to study cell surface receptors and as immune therapy for tumours.