bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium Channels
Authors: Lampert Angelika , Stühmer Walter , Waxman Stephen G 
Published: January 2015

Abstract

Excitable cells, such as neurons or cardiomyocytes, communicate with each other via action potentials. This fast change in membrane voltage is initiated by the rapid opening of voltage‐gated sodium selective channels, of which to date nine subtypes are known (Nav1.1–Nav1.9). These large membrane spanning proteins undergo gating changes on a timescale ranging from milliseconds to minutes. Depolarization past threshold leads to activation and sodium ions flow into the cell. Within milliseconds the inactivation particle blocks the pore, current flow is interrupted and the channel is fast inactivated. Channels need to recover from fast inactivation at negative potentials to be able to reopen anew.
Recent data on crystal structures shape our 3D picture of sodium channels and mutagenesis studies help understanding their structure–function relation. Sodium channels are major regulators of membrane excitability and play an important role in pain, arrhythmias and muscle diseases, and subtype‐specific blockers have been currently developed.

Key Concepts

The fast upstroke of the action potential (AP) is initiated by the opening of voltage‐gated sodium channels (Navs).

Navs are large transmembrane proteins consisting of four homologous domains (DI–DIV).

Each domain consists of six transmembrane segments S1–S6, which form a voltage sensor (S1–S4) and parts of the pore module (S5–S6).

The domains are connected by intracellular linkers. The DIII–DIV linker contains the inactivation particle.

Upon depolarization, Navs open quickly, sodium ions flow into the cell, and within milliseconds, fast inactivation occurs.

Slow inactivation happens on a much slower timescale (seconds to minutes) and involves other parts of the channel protein.

Recently, crystal structures of bacterial sodium channels have helped explicate the changes in 3D structure that accompany gating.

Navs are involved in the generation of pain, arrhythmias and myopathies (among others).
Adenoviruses
Authors: Echavarría Marcela 
Published: January 2015

AbstractAdenoviruses (AdVs) are non‐envelopedDNAviruses that can cause a wide range of clinical manifestations including respiratory, gastrointestinal and ocular, as well as hepatic, renal and disseminated diseases. Outcomes can range from mild and self‐limited to severe life‐threatening conditions and death. Higher morbidity and mortality is observed with certain AdVs serotypes and among immunocompromised patients. AdVs are capable of evading the immune response and they can produce persistent or latent infections. Therefore, reactivation can occur during immunosuppression. Conventional and molecular methods are used for diagnosis, although the last ones are more sensitive and can be used for quantification. Antivirals, such as ribavirin and cido‐fovir, are used in some patients, especially stem cell transplant recipients. AdV vaccine against serotypes 4 and 7 is available forUSmilitary recruits. Early diagnosis of AdVs infections is critical for patient management and infection control measurements.Key ConceptsAdenoviruses can cause a variety of clinical manifestations because of high number of serotypes and their wide cell tropism.The implementation of molecular methods for adenovirus diagnosis has increased their awareness in the clinical setting as severe and emerging pathogens.AdV serotypes are defined by neutralisation and haemagglutination assays using specific antisera.Adenoviruses are very stable and highly resistant to inactivation at room temperature.Adenovirus species C can establish a latent infection in lymphocytes of the tonsils and adenoid tissue.Clinical manifestations depend on the host and the serotypes involved and can affect the respiratory, gastrointestinal or ocular tract and the liver, kidney or nervous central system.Severe infections and fatal cases are more frequent in immunocompromised patients such as stem cell transplant recipients.Adenovirus diagnosis in blood requires the use of molecular methods.An oral attenuated live adenovirus vaccine against serotypes 4 and 7 is available for US militaries to prevent respiratory disease.
Phosphoryl Transfer Reactions
Authors: Hengge Alvan C 
Published: January 2015

AbstractPhosphoryl transfer is the name given to the chemical process of the transfer of the phosphoryl group (PO3) from a phosphate ester or anhydride to a nucleophile. Nucleophilic attack by water on a phosphate monoester gives the hydrolysis product inorganic phosphate. This net dephosphorylation reaction is the process catalysed by phosphatases. Although the reaction is thermodynamically favourable, it has a very high kinetic barrier, making the uncatalysed hydrolysis of phosphate esters extremely slow. The opposite process, the formation of phosphate esters, is termed phosphorylation and is accomplished in biological systems by kinases. The balance between phosphatase and kinase activities in biology serves to regulate the phosphorylation level of many enzymes and other proteins in the cell, forming an important regulatory mechanism that is found throughout the biological world.Key ConceptsThe post‐translational phosphorylation levels of proteins are regulated by the complimentary actions of phosphatases and kinases.The uncatalysed hydrolysis of phosphate esters has a very high kinetic barrier, making phosphatases among the most efficient enzymes known.The various families of phosphatases use different catalytic machinery and mechanisms to carry out phosphate ester hydrolysis.
XenopusEmbryo: Mesoderm Induction
Authors: Dale Leslie , Wardle Fiona C 
Published: January 2015

AbstractDuring early embryogenesis, the three germ layers, mesoderm, endoderm and ectoderm, must form in the correct positions for normal development to proceed. In the amphibian embryo, mesoderm is induced from cells of the marginal zone, at the equator of the spherical embryo, by signals emanating from the vegetal region. Later, during gastrulation, mesoderm is further patterned by signals from the dorsal organiser. Here, we review our current knowledge of mesoderm formation, highlighting the importance of the transforming growth factor‐beta (TGF‐β) family of extracellular signalling molecules in mesoderm induction and the role of maternal factors in activating these molecules. We also discuss mechanisms of limiting induction to the marginal zone by TGF‐β inhibitors in the animal hemisphere, the role of FGF signalling in maintaining the mesoderm and the role of BMP and BMP antagonists in patterning mesoderm during gastrulation.Key ConceptsMesoderm is induced to form from marginal zone cells of theXenopusembryo in response to signals secreted from the vegetal hemisphere.Mesoderm is induced by members of the Nodal/Activin sub‐family of the transforming growth factor‐beta (TGF‐β) family of secreted signalling factors.Fibroblast growth factor (FGF) family members maintain mesoderm.Mesoderm induction is limited to the marginal zone of the embryo by TGF‐β signalling inhibitors expressed in the animal region.Maternal transcription factors, such as VegT and β‐catenin, activate expression of TGF‐β genes.Mesoderm is further patterned during gastrulation through both activation and inhibition of BMP signalling.
Cytomegalovirus Infections in Humans
Authors: Griffiths Paul D , Lumley Sheila 
Published: January 2015

Abstract

Cytomegalovirus (
CMV
) is a herpes virus that causes severe disease in the immunocompromised because virus replication is normally held in check by cell‐mediated immune responses in patients with past infection. Patients receiving immunosuppressive drugs to allow allo‐transplantation, patients with
AIDS
(acquired immunodeficiency syndrome) or foetuses with immature immune responses are therefore at risk of developing
CMV
end‐organ disease. A high viral load is required for
CMV
end‐organ disease to develop. Ganciclovir is a potent inhibitor of
CMV
replication and can be used either for prophylaxis or for pre‐emptive therapy (administering the drug when
CMV
is detected in the blood). Both of these strategies effectively control
CMV
end‐organ disease in transplant patients. Three new drugs have recently completed phase II clinical trials (maribavir, brincidofovir and letermovir). Phase
II
studies of prototype
CMV
vaccines have recently published encouraging results, suggesting that
CMV
infection may ultimately be preventable by means of universal immunisation.

Key Concepts

CMV viraemia precedes CMV end‐organ disease.

Prompt treatment of CMV viraemia prevents end‐organ disease.

The probability of end‐organ disease is non‐linear with respect to viral load.

This threshold relationship is seen also in babies with congenital CMV infection and hearing loss.

Prompt treatment of congenital CMV infection can reduce the risk of progressive hearing loss.

Quantitative viraemia biomarkers can be used to assess the potency of antiviral drugs in humans.

These same biomarkers can be used to determine if vaccine given pre‐transplant can help control CMV replication post‐transplant.

Although clinically silent, CMV infection is associated with excess mortality in the general public.

Universal immunisation has the potential to provide health benefits greater than appreciated at present.
Rabies: Virus and Disease
Authors: Nadin‐Davis Susan A 
Published: January 2015

Abstract

This article summarises the current literature on rabies and the aetiological agents responsible for this disease, which includes all members of the
Lyssavirus
genus, of which rabies virus (
RABV
) is the prototype species. Members of the orders Chiroptera and Carnivora serve as maintenance reservoirs for all recognised lyssavirus species and knowledge of the diversity, evolution and geographical range of these viruses is continually improving. Many mammalian species, including humans, are susceptible to spill‐over infections from the maintenance hosts. Despite the availability of efficacious prophylactics, once clinical signs develop, the disease is almost invariably fatal. Effective rabies control requires elimination of the disease from animal reservoirs. In developed countries, parenteral dog vaccination and oral vaccination of wildlife have effectively controlled rabies in many regions but socioeconomic factors limit the application of similar measures in many developing countries where the vast majority of human cases are reported. Better understanding of disease pathogenesis and host immune responses is sought in efforts to develop effective therapeutic interventions.

Key Concepts

Rabies is a neurological disease that can affect almost all mammals and is almost invariably fatal once clinical signs develop.

Rabies is caused by all members of the
Lyssavirus
genus, bullet‐shaped neurotropic viruses with small RNA genomes, which are normally transmitted in virus‐laden saliva through bites.

The vast majority of human rabies cases are the result of exposure to rabid animals.

Prevention of human disease is undertaken by a regimen of timely post‐exposure prophylaxis.

Distinct
Lyssavirus
species and variants thereof are maintained in dogs in many developing countries and by several wildlife species including foxes, skunks, raccoons, raccoon dogs, mongooses, jackals and many species of bats throughout much of the world.

Through a series of viral–host interactions, rabies virus (RABV) has evolved mechanisms that maintain the neural network required for its propagation and spread within the infected host while avoiding clearance by the host's immune system.

Knowledge of the diversity of the
Lyssavirus
genus is steadily expanding with increased surveillance and development of molecular tools to enable rapid characterisation of new isolates.

Current vaccines and biologicals are ineffective against the more diverse members of the genus, thereby indicating that novel reagents with broader efficacy may be required for future disease control.

Ultimately, control and eradication of rabies will require elimination of the disease from animal reservoirs through the application of efficacious and cost‐effective methods of animal vaccination.
Marine Communities
Authors: Snelgrove Paul 
Published: January 2015

Abstract

Marine communities are collections of organisms within an area of the ocean that interact with one another more than with other such collections. These organisms may span from microbes to seaweeds to large animals, but their composition changes drastically with habitat. Intertidal environments along the shoreline support low diversity but often high abundances of organisms adapted to highly variable environmental conditions. In contrast, the deep ocean, which is devoid of sunlight and where temperature and salt content vary little, supports low abundances of a high diversity of life. Sediments cover much of the seabed, creating the largest habitat on Earth in area, whereas the thousands of metres of water above the bottom create the largest habitat by volume. Coral reefs, which occur only in shallow tropical waters, support the most species dense habitat in the ocean and possibly on the planet. Highly productive transition zones between land and sea such as salt marshes, mangroves and seagrasses often provide nursery areas for adjacent coastal species. Nonetheless, many coastal habitats face multiple pressures from human activities and already show rapid change.

Key Concepts

Marine communities differ among habitats spanning from low‐diversity intertidal communities adapted to highly variable environments to species‐rich deep‐sea communities that live in far less dynamic environments.

Intertidal communities are the best‐studied marine community because of their ease of access and relative simplicity.

Estuarine habitats, where freshwater and seawater mix, often support high productivity and complex habitats such as mangroves and salt marshes that are important nurseries for a community of juvenile fishes and invertebrates.

Coral reefs are highly diverse and productive habitats but human activities threaten reef communities in many parts of the world where coral reefs are in sharp decline.

Scientists have sampled only a tiny fraction of the deep ocean and the potential for new discoveries of species and processes remains very high.
Lung Development
Authors: Havrilak Jamie A , Shannon John M 
Published: January 2015

AbstractEarly respiratory development begins with the specification of the lung cell fate, followed by the emergence of lung buds from the ventral foregut endoderm. The respiratory tree is then elaborated through branching morphogenesis, and proliferation and differentiation of specialised cell types along the proximal–distal axis produces airways and alveoli, respectively. Lung development is orchestrated through crosstalk between the epithelium and the mesenchyme; morphogenesis and differentiation of the lung relies on diffusible signalling molecules that cross tissue layers to activate a complex network of transcription factors to drive development. Significant progress has been made in understanding the molecular regulation of lung morphogenesis through paracrine signalling pathways and transcription factors essential for lung development.Key ConceptsFollowing specification of respiratory progenitor cells that are committed to the respiratory lineage, the lung buds emerge from the ventral foregut endoderm and subsequently elaborate the pulmonary tree through branching morphogenesis.Reciprocal interactions between the epithelium and the mesenchyme govern lung organogenesis and are mediated by diffusible factors.Critical signalling pathways known to be involved in lung development include Fgfs, Shh, Wnts, RA and TGF‐β superfamily. These factors are diffusible and act as means of communication and instruction between the tissue layers to drive development.The lung comprises specialised cell types that function to protect the lung, secrete surfactant or allow for gas exchange.
Cucurbitaceae (Vine Crops)
Authors: Kousik Chandrasekar S , Levi Amnon , Wehner Todd C , Maynard Donald N 
Published: January 2015

Abstract

The Cucurbitaceae or vine crop family is a distinct family without any close relatives and includes many important vegetables such as cucumber, melon, watermelon, squash, pumpkin and gourds. Plants within Cucurbitaceae consist of 95 genera classified into 15 tribes. Cucurbits are trailing or vining tendril‐bearing annual plants. The plants are mostly monoecious with separate male and female flowers and require various insect, especially bees for pollination. The fruit come in various shapes and sizes, of which the pumpkin plants produce some of the largest known fruits among flowering plants and are often used in contests. Gourd fruits are used for preparing food, making musical instruments, containers and other decorative pieces. Watermelon is considered the most popular among the cucurbits whose delicious fruit are widely consumed throughout the world.

Key Concepts

Cucumber, watermelon, melon, pumpkin, squash and gourds belong to the family Cucurbitaceae.

Cucurbits are mainly trailing or vining tendril‐bearing annual plants.

Cucurbit plants are mostly monoecious, that is, they have separate male and female flowers.

Pumpkin plants produce some of the largest know fruits among flowering plants.

Watermelon is the most popular cucurbit and its delicious fruits are consumed worldwide.

The red pigment responsible for watermelon flesh colour is an anticancer agent. Watermelon fruit have more lycopene than tomato.

Bottle gourds are considered to be some of the earliest domesticated plant species.
Segmental Duplications: A Source of Diversity, Evolution and Disease
Authors: Catacchio Claudia R , Chiatante Giorgia , Anaclerio Fabio , Ventura Mario 
Published: January 2015

Abstract

Genome mutations represent a source of variability on which selective pressure acts: negative changes are purged from the populations, whereas positive and neutral changes may be fixed. Segmental duplications (
SDs
) in the human genome trigger mutations such as structural rearrangements (duplications, deletions, inversions and translocations), thus playing a crucial role in human disease and genome evolution. Several human diseases (genomic disorders) are caused by non‐allelic homologous recombination (
NAHR
) between highly similar
SDs
, as well as gene‐containing
SDs
were crucial to survival and adaptation of human species during evolution. Moreover, both from a pathological and an evolutionary point of view, SDs represent critically important regions for acentric fragment rescue during neocentromerization process. In this light, disease and evolution can be considered as ‘two sides of the same coin’, where the coin represents the
SD
‐mediated chromosomal rearrangements.

Key Concepts

Segmental duplications (SDs) create variability in human genome.

Mediating non‐allelic homologous recombination (NAHR) segmental duplications mediate chromosomal unbalance.

Duplicated genes may show pattern of expression different from ancestral gene.

Segmental duplications are the remains of ancestral pericentromeric regions.

Neocentromere can generate at loci where ancestral centromere were located.
HPVVaccines
Authors: Wilkinson Dianna E , Inglis Stephen 
Published: January 2015

AbstractThe discovery in the early 1970s that cervical cancer was caused by infection with human papillomavirus (HPV) stimulated a highly successful vaccine development programme based on the use of recombinant deoxyribonucleic acid (DNA) technology to produce virus proteins in a form that can stimulate powerful and long‐lasting antibody responses. The vaccines have been designed as combinations to target theHPVvirus types that are responsible for most human disease. Clinical trials have shown that it is possible to prevent both genital warts and the early stages of cervical cancer through vaccination and this has led to licensure and use ofHPVvaccines in many countries throughout the world. Progression from initial virus infection to development of invasive cancer is often very slow, however, and so it will be many years before the impact of the vaccine on the overall disease burden is fully understood.Key ConceptsVaccine development for HPV has been complex but highly successful. Successful vaccines were made by recombinant protein expression to produce virus‐like particles (VLPs).Prevention of papillomavirus‐induced disease requires neutralising antibodies at the mucosal site of infection.The main public health priority was to achieve high coverage in vaccinating women with the aim to prevent cervical cancer.Prophylactic HPV vaccine efficacy has been remarkably high.Some cross‐protection is observed between different vaccine types.HPV vaccines have been implemented in populations of young women widely around the world.Access to affordable HPV vaccines in poor countries is a key goal but remains a challenge.The scope of HPV vaccination extends to the prevention of non‐cervical HPV infections and related diseases in both females and males.
Neural Prostheses
Authors: Kasten Michael R , Ievins Aiva M , Moritz Chet T 
Published: January 2015

Abstract

A neural prosthesis is a device that aims to restore or replace the functions of the nervous system that are lost to disease or injury. Examples include devices to improve hearing, vision, motor and cognitive functions. Neural prostheses artificially stimulate the nervous system to convey sensory information, activate paralysed muscles or modulate the excitability of neural circuits to improve conditions such as chronic pain, epilepsy or tremor. Some neuroprostheses also record activity from the nervous system, which can be useful for patients who have difficulty moving or communicating. These devices can decipher the intention of the user or detect ongoing brain events such as seizures by recording neural signals directly from the brain. Emerging neuroprostheses aim to ‘close the loop’ using recorded neural activity to control stimulation delivered elsewhere in the nervous system with the goal of improving function.

Key Concepts

Neural prostheses aim to replace lost function or control activity within the nervous system following injury or disease.

Sensory neural prostheses transduce external events (e.g. sound, light) into artificial stimulation delivered to the nervous system.

Motor neural prostheses aim to restore functional movement to weak or paralysed muscles.

Neuromodulatory devices utilise electrical stimulation to modulate the excitability of neural circuits to improve symptoms of neurological diseases such as pain, tremor and the occurrence of seizures.

Recording neuroprostheses aim to detect the user's intention or brain state in order to enable communication or control of external devices.

Closed‐loop neuroprostheses utilise neural recording to control functional or symptom‐relieving stimulation.

Methods are emerging for optical and magnetic stimulation of the nervous system to supplement the electrical stimulation techniques currently in use.