bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apnea of Prematurity: Caffeine Dose Optimization
Authors: Francart Suzanne J. , Allen Megan K. , Stegall-Zanation Jennifer 
Published: April 2013

OBJECTIVES
The primary objective was to evaluate the correlation between maintenance dose and response rates in neonates less than 28 weeks gestational age. Secondary objectives included clinical indicators of response (number of weight adjustments, dose increases, and mini-loads) and tachycardia associated with caffeine therapy.

METHODS
This study was a retrospective analysis of neonates admitted to the North Carolina Children's Hospital from August 2009 to August 2011. Patients included were less than 28 weeks postmenstrual age and were treated with caffeine for apnea of prematurity. Patients were excluded if they were older than 28 weeks postmenstrual age, receiving caffeine therapy for other indications, or experiencing apnea from other conditions, or if therapy was initiated more than 7 days after birth.

RESULTS
A total of 89 neonates with a mean birth weight of 0.844 kg (range: 0.391 to 1.306 kg) and median gestational age of 26 2/7 weeks (range: 23 to 27 6/7 weeks) were evaluated. The median initial maintenance dose of caffeine citrate was 7.9 mg/kg/day, and 94.1% of neonates receiving ≤7.9 mg/kg/day required a clinical intervention during therapy compared with 76.3% in those receiving &gt;7.9 mg/kg/day. Absolute incidence of tachycardia was low, and caffeine levels collected ranged from 16.6 to 34.4 μg/mL.

CONCLUSIONS
In neonates less than 28 weeks gestational age, doses of caffeine citrate greater than 7.9 mg/kg/day are safe and are associated with a decreased need for clinical interventions.
Blood–Brain Barrier
Authors: Peterson Darryl R 
Published: April 2013

AbstractThe blood–brain barrier consists of endothelial cells lining brain capillaries. It serves to restrict and control the movement of substances between the general circulation and brain extracellular fluid. It participates in regulating the volume and composition of fluid surrounding the brain through specific transport processes, and thus contributes to homoeostasis of the central nervous system. Some of these processes may be regulated hormonally, or modulated by adjacent cells including astrocytes. The barrier function of the blood–brain barrier is due to: (1) tight junctions that restrict movement of substances between the endothelial cells, (2) specific transport proteins that determine which substances can cross the barrier transcellularly and (3) enzymes that may degrade or alter substances prior to passage. Systemically administered drugs intended to treat neurological disorders must be designed to bypass the restrictive elements of the blood–brain barrier. Pathological conditions associated with the central nervous system may alter blood–brain barrier function.Key Concepts:The blood–brain barrier regulates brain extracellular fluid.Brain capillaries form a tight barrier except in specialised areas.Tight junctions restrict paracellular movement of substances across the blood–brain barrier.Astrocytes contribute to differentiation of the blood–brain barrier.Transport across the blood–brain barrier may be passive or active.Enzymes contribute a metabolic barrier to the blood–brain barrier.A strategy must be developed to deliver drugs to the brain.Altered blood–brain barrier function in disease.Structural and functional properties of the blood–brain barrier.
Cerebellum: Anatomy and Organisation
Authors: Hawkes Richard 
Published: April 2013

Abstract

The cerebellum is a highly stereotyped cortical structure in the hindbrain of all vertebrates from fish to primates. The circuitry of the cerebellar cortex is built around the large, inhibitory Purkinje cells, which are the focus of all afferent input to the cerebellar cortex and are modulated by several classes of inhibitory interneuron (basket, stellate, Golgi and Lugaro cells). Despite the apparent homogeneity of the cerebellar circuitry, the cerebellum is highly modular, comprising several hundred discrete and reproducible anatomical and physiological units (‘stripes’). Each stripe receives precise afferent inputs – climbing fibres directly to the Purkinje cells and mossy fibres indirectly via the granule cells. In turn, the Purkinje cells send efferent projections to specific targets in the cerebellar and vestibular nuclei. As a result, within the cerebellum a wide variety of sensory information is brought together and integrated, primarily to aid in motor control.

Key Concepts:

Cerebellar circuitry is built around the Purkinje cell.

The cerebellar cortex is divided into an array of transverse zones and parasagittal stripes.

The cerebellar cortex receives two major afferent inputs – climbing fibres and mossy fibres.

Purkinje cells are the sole efferent projections of the cerebellar cortex.

Multiple interneurons modulate Purkinje cell firing patterns.
Oestrogen Regulation of Sexual Behaviour, Mood and Cognition
Authors: Almeida Osborne FX , Condé Gillian L , Sousa Nuno 
Published: April 2013

AbstractOestrogens are steroid hormones that act through specific receptors in the brain to influence sexual behaviour, as well as mood and cognition. Oestrogen actions include alterations of neuronal excitability, neurotransmitter synthesis and metabolism, neuronal circuitry and neuronal survival, one or all of which may contribute to their effects on mood and cognition. Oestrogens act on a wide variety of peripheral tissues such as breast, bone, liver and heart tissues. Although they have found widespread use for the management of menopausal symptoms, the current consensus is that oestrogen replacement therapy should be used at the lowest possible doses, for a limited duration and with careful consideration of the individual woman's treatment goals and risks. Oestrogens regulate gene transcription, resulting in long‐lasting biochemical changes that can impact adversely on health. The development of improved selective oestrogen receptor modulators that target specific tissues may eventually help circumvent some of the undesired effects of oestrogens.Key Concepts:Oestrogens serve important physiological roles in the brain and in peripheral organ systems.Oestrogens and oestrogen‐like compounds bind to oestrogen receptors; oestrogen receptors occur as two isoforms, known as oestrogen receptor, ERα and ERβOestrogens modulate gene activity, cellular structure and function and ultimately, regulate complex behaviours after binding to specific oestrogen receptors in the brain.Oestrogen secretion starts during early development, varies cyclically from puberty onwards, and gradually diminishes with age (menopause in women).Oestrogen‐like compounds that raise health issues are increasingly found in our modern environment as well as in plants; the potency and safety of the latter, especially as dietary supplements, is however questionable.The therapeutic use of oestrogens in menopausal women should be tailored to an individual woman's needs and should be limited in order to avoid health‐related reductions in quality of life.
Bacterial Ecology
Authors: Fenchel Tom 
Published: April 2013

AbstractBacterial ecology is concerned with the interactions between bacteria and their biological and nonbiological environments and with the role of bacteria in biogeochemical element cycling. Many fundamental properties of bacteria are consequences of their small size. Thus, they can efficiently exploit very dilute solutions of organic matter and their potential growth rates are very high. Bacteria do not have a cytoskeleton and they are covered by a rigid cells wall. Therefore they can only take up dissolved low‐molecular‐weight compounds from their surroundings; when bacteria exploit polymeric compounds these must first be undergo extracellular hydrolysis. Bacteria have a great diversity with respect to types of metabolism that far exceeds the metabolic repertoire of eukaryotic organisms. Bacteria play a fundamental role in the biosphere and certain key processes such as, for example, the production and oxidation of methane, nitrate reduction and fixation of atmospheric nitrogen are exclusively carried out by different groups of bacteria. Some bacterial species – ‘extremophiles’ – thrive in extreme environments in which no eukaryotic organisms can survive with respect to temperature, salinity or pH.Key Concepts:Fundamental properties of bacteria are related to their small size and lack of cytoskeleton.Bacteria display a great diversity in types of metabolism.Bacteria play a key role in the biosphere in terms of transfer of matter and energy.A number of fundamental biogeochemical processes are carried exclusively by bacteria.Bacteria play an important role in all types of habitats including some that cannot support eukaryotic life.
Nematophagous Fungi
Authors: Nordbring‐Hertz Birgit , Jansson Hans‐Börje , Tunlid Anders 
Published: April 2013

Abstract

Nematophagous fungi are microfungi that can capture, kill and digest nematodes. They use special mycelial structures, the so‐called traps, or spores to trap vermiform nematodes or hyphal tips to attack nematode eggs and cysts before penetration of the nematode cuticle, invasion and digestion. The more than 200 species known differ in saprophytic/parasitic ability. Although many of the trap‐forming and egg‐parasitic fungi can survive in soil saprophytically, the endoparasites are mostly more dependent on nematodes as nutrients. Molecular data have greatly improved our understanding of the function of the fungi in respect of their taxonomy, their physiological/biochemical activity and their ecology, including their function as biocontrol agents.

Key Concepts:

There are three major groups of nematophagous fungi: the nematode‐trapping fungi that capture free‐living nematodes using specialised morphological structures (i.e. traps), the endoparasitic fungi that infect nematodes using adhesive spores, and the egg‐ and cyst‐parasitic fungi that infect these stages with their hyphal tips.

The nematophagous growth habit has evolved several times and independently since nematophagous fungi are found in all major groups of fungi.

The nematophagous fungi display a large diversity and extensive plasticity of infection structures. In many species, the formation of trapping‐structures is initiated in response to signals from the environment including compounds secreted by the host nematode.

Isolation of more virulent strains, and the development of better formulations and fermentation techniques have significantly improved the efficiency of nematophagous fungi as biological control agents against plant‐ and animal parasitic nematodes.

Nematophagous fungi infect nematodes through a sequence of events including adhesion of the trapping structures to the host nematode surface, followed by penetration, killing and digestion of the nematode tissues.

The secretion of extracellular enzymes such as serine proteases and chitinases are required for successful parasitism of free‐living nematodes and nematode‐eggs by nematophagous fungi.
Viable but Nonculturable Bacteria
Authors: Stokell Joshua R , Steck Todd R 
Published: April 2013

Abstract

Viable but nonculturable (VBNC) bacteria are not detected using standard microbiological assays, hence environmental samples thought to lack bacteria may in fact contain large numbers of these dormant‐like cells. Though regrowth, or resuscitation, of bacteria remains the most definitive measure of the presence of VBNC cells, growth‐independent viability assays using flow cytometry combined with LIVE/DEAD staining, RT‐qPCR and microarray analysis have been developed to detect VBNC cells in environmental samples. Genes specific for the VBNC state have yet to be identified, however, several genes, including
rpoS
, are reported to be involved in the VBNC condition. Further elucidation of the genetic mechanism causing entry into and resuscitation from the VBNC state will likely coincide with advances in transcriptomic and proteomic technologies. Though controversial, the VBNC state can explain certain environmental microbial phenomena, such as the source of recurrent bacterial infections in plants and animals.

Key Concepts:

The VBNC state is thought to be a long‐term survival mechanism that initiates in response to environmental stress.

A general, but not universal, acceptance of the VBNC condition exists even though the molecular mechanism involved has yet to be elucidated.

Resuscitation of the VBNC state has been observed in only some species of bacteria reported to become VBNC.

Several genes, including
rpoS
,
mreB
and
rpf
have been identified as being involved in the VBNC condition.

Bacteria in the VBNC state may retain pathogenicity.
Dengue Fever Viruses
Authors: Whitehorn James 
Published: April 2013

AbstractDengue viruses are the most important arboviruses causing disease in humans. Approximately 3 billion people live in areas of risk, and there are an estimated 50–100 million cases occurring each year. These estimates reflect an enormous burden of morbidity, predominantly affecting urban centres of the developing world. There is currently no specific treatment and disease control is limited to tackling the vector. Despite considerable scientific attention disease pathogenesis remains incompletely understood. A better understanding of dengue virus biology and disease pathogenesis has the potential to pave the way to successful therapeutic interventions. This article aims to review current understanding of virus and vector biology, disease pathogenesis and clinical manifestations and management. Finally the article will consider novel approaches to clinical management and disease control.Key Concepts:Dengue viruses are the most important arboviruses globally.Dengue viruses are a significant cause of morbidity, particularly in the tropics.The pathogenesis of dengue results from both virus and host factors.Clinical management is limited to parenteral fluids, occasional use of blood products and supportive care.Despite a long gestation and theoretical safety concerns a dengue vaccine may soon be a reality.Novel approaches to vector control may aid global disease control efforts.
Enzymes: Irreversible Inhibition
Authors: McDonald Andrew G , Tipton Keith F 
Published: April 2013

AbstractMany drugs that are in clinical use work by irreversibly inhibiting specific enzymes, either in the individual being treated or in an invading organism. Enzyme inhibitors are also of value for understanding the behaviour of individual enzymes and metabolic systems. Recovery from irreversible inhibition requires the synthesis of new enzyme. Although those irreversible inhibitors that react with specific groups in the enzyme protein generally inhibit more than one enzyme, those that initially form a noncovalent complex with the enzyme, with subsequent reaction within that complex leading to the formation of a covalent bond, can show a high degree of selectivity. Kinetic studies, which are detailed in this account, can be used to distinguish the different types of inhibition and the factors that contribute to effectiveness and selectivity.Key Concepts:Irreversible inhibition cannot be reversed by the removal of the excess inhibitor from the system.Recovery from reversible inhibition depends on the removal of the inhibitor from the system, whereas recovery from irreversible inhibition requires the synthesis of fresh enzyme.Enzyme turnover in the tissues is a balance between the rate of its synthesis and degradation.Nonspecific irreversible inhibitors can react with several groups of the same type in different proteins.Specific irreversible inhibitors form an initial noncovalent complex with the enzyme before the reaction within that complex to form a covalent bond.Active‐site‐directed inhibitors contain a reactive grouping attached to a substrate analogue.Mechanism‐based inhibitors can be highly specific because they depend on the activity of the enzyme to form a reactive intermediate that then reacts irreversibly with the enzyme.Suicide substrates behave as both substrates and irreversible enzyme inhibitors in divergent processes.Dosage schedule for effective therapy with irreversible inhibitors is dependant on the half‐life of enzyme turnover.
Bromoviridae and Allies
Authors: Scott Simon W 
Published: April 2013

Abstract

The family
Bromoviridae
consists of six genera:
Alfamovirus
,
Anulavirus
,
Bromovirus
,
Cucumovirus
,
Ilarvirus
and
Oleavirus
. All viruses in these genera possess tripartite genomes of single‐stranded, linear, positive‐sense ribonucleic acid (RNA), in which expression of the downstream codon of the RNA3 is via a subgenomic messenger RNA (mRNA) (RNA4).
Raspberry bushy dwarf virus
(RBDV) was the sole member of the genus
Idaeovirus
for many years and shares features in common with members of the genus
Ilarvirus
and
Alfamovirus
, but possesses a bipartite genome and is not currently assigned to a family. Members of the genera
Alfamovirus
,
Bromovirus
and
Cucumovirus
have been used extensively as model systems for research on molecular aspects of plant virology.

Key Concepts:

Although all members of the
Bromoviridae
have similar particle morphologies (quasi‐spherical and bacilliform) and possess tripartite genomes, a range of different strategies is used to express the products of the different genomes.

The phenomenon of genome activation by the coat protein was unique to the ilarviruses and
Alfalfa mosaic virus
but has recently been demonstrated for RBDV.

The natural host ranges of
Cucumber mosaic virus
and
Alfalfa mosaic virus
are extensive whereas many other viruses described in this article have an extremely limited natural host range.

Complete genomic nucleotide sequences are available from GenBank for the majority of viruses referred to in this article.
Plant Viruses with Rod‐Shaped Virions
Authors: Chapman Sean N 
Published: April 2013

Abstract

Plant viruses that form rigid, rod‐shaped particles are found in eight genera. All of these viruses have single‐stranded
ribonucleic acid
(RNA) genomes that, with one exception, are positive‐sense. Most plant viruses with rod‐shaped particles are found in the six genera that form the
Virgaviridae
family with approximately half of all the definitive species in the
Tobamovirus
genus. The virus particles are formed from single structural proteins that encapsidate the genomic RNAs in nonenveloped, helical arrays. Despite their morphological similarities these viruses have diverse molecular and biological properties. While the tobamoviruses have nonsegmented genomes and are mechanically transmitted, the other viruses have segmented genomes and are transmitted by a variety of mechanisms: seed transmission, nematode vectors and plasmodiophorid vectors. Many of the viruses are important disease agents of crop species.

Key Concepts:

Aside from the anomalous
Varicosavirus
genus, all viruses with rod‐shaped virions are single‐stranded, positive‐sense ribonucleic acid (RNA) viruses that replicate in the cytoplasm of host plant cells.

The rod‐shaped virions are formed from helical arrays of a single form of coat protein subunit and their length is dependent on the size of the encapsidated RNAs.

Apart from species within the
Tobamovirus
genus, all viruses with rod‐shaped virions have segmented genomes divided between multiple RNAs.

The plant viruses with rod‐shaped virions use a variety of mechanisms to translate the multiple open reading frames in their genomes, including leaky‐readthrough translation, the use of 3′ coterminal subgenomic RNAs and leaky‐initiation of translation by scanning ribosomes.

The intercellular movement of these viruses within host plants is achieved through the use of a single
Tobacco mosaic virus
‐like movement protein or a ‘triple gene block’ of movement proteins.

The principle mechanism of transmission for all species within a genus varies between genera: the species within four genera are primarily plasmodiophorid transmitted, whereas those in three other genera are primarily mechanically transmitted, seed transmitted or nematode transmitted.

All the genera containing viruses with rod‐shaped virions include species that cause economically important diseases that are controlled through the use of virus‐free seed/vegetative stocks, good sanitary practices and resistant crop cultivars.
Regulation of Neuronal Subtype Identity in the Vertebrate Neural Tube (Neuronal Subtype Identity Regulation)
Authors: Bushati Natascha , Briscoe James 
Published: April 2013

Abstract

The vertebrate nervous system consists of many different neuronal cell types. Each has its own properties, axon projections and connection patterns. This diversity is established early during development and is required for the complex neuronal circuits that characterise the central nervous system. In the spinal cord, a series of events generates different neuronal subtypes, starting with the spatial patterning of neural progenitors. Extrinsic signals provide progenitors in the forming neural tube with positional identity, such that distinct types of progenitors express a unique combination of transcription factors. This transcriptional code determines neural progenitor identity. As progenitors differentiate, they generate distinct neuronal subtypes that are also characterised by a combinatorial transcriptional code. In addition to spatial patterning, other mechanisms contribute to the further diversification of differentiating neurons.

Key Concepts:

Secreted molecules provide positional information to neural progenitors in the developing neural tube.

Progenitors at different positions in the neural tube acquire distinct identities.

The identity of a progenitor is defined by the combination of transcription factors it expresses, which determines the gene expression profile of the progenitor.

An interplay between extrinsic signalling and the downstream gene network produces spatially discrete switches in progenitor identity.

Progenitors with distinct identities differentiate into post‐mitotic neurons with different subtype identities.

The identity of a neuron is determined by the transcriptional code of its progenitor and is itself defined by a separate transcriptional code.

In addition to spatial pattern, temporal changes in progenitor identity and signalling between differentiating cells increases neuronal diversity.