Species abundance distributions (SADs) follow one of ecology's oldest and most universal laws - every community shows a hollow curve or hyperbolic shape on a histogram with many rare species and just ...a few common species. Here, we review theoretical, empirical and statistical developments in the study of SADs. Several key points emerge. (i) Literally dozens of models have been proposed to explain the hollow curve. Unfortunately, very few models are ever rejected, primarily because few theories make any predictions beyond the hollow-curve SAD itself. (ii) Interesting work has been performed both empirically and theoretically, which goes beyond the hollow-curve prediction to provide a rich variety of information about how SADs behave. These include the study of SADs along environmental gradients and theories that integrate SADs with other biodiversity patterns. Central to this body of work is an effort to move beyond treating the SAD in isolation and to integrate the SAD into its ecological context to enable making many predictions. (iii) Moving forward will entail understanding how sampling and scale affect SADs and developing statistical tools for describing and comparing SADs. We are optimistic that SADs can provide significant insights into basic and applied ecological science.
Males of most species are more aggressive than females, but the neural mechanisms underlying this dimorphism are not clear. Here, we identify a neuron and a gene that control the higher level of ...aggression characteristic of Drosophila melanogaster males. Males, but not females, contain a small cluster of FruM+ neurons that express the neuropeptide tachykinin (Tk). Activation and silencing of these neurons increased and decreased, respectively, intermale aggression without affecting male-female courtship behavior. Mutations in both Tk and a candidate receptor, Takr86C, suppressed the effect of neuronal activation, whereas overexpression of Tk potentiated it. Tk neuron activation overcame reduced aggressiveness caused by eliminating a variety of sensory or contextual cues, suggesting that it promotes aggressive arousal or motivation. Tachykinin/Substance P has been implicated in aggression in mammals, including humans. Thus, the higher aggressiveness of Drosophila males reflects the sexually dimorphic expression of a neuropeptide that controls agonistic behaviors across phylogeny.
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•A single class of neurons is identified that promotes aggression in male flies•These neurons are FruM+ and sexually dimorphic but do not control courtship•These neurons promote aggressive arousal via release of a neuropeptide, DTK•Tk is a neuropeptide gene that controls aggression in both flies and mammals
A small group of Drosophila neurons that are detectable in male, but not female, brains promote high levels of aggression via the release of a neuropeptide, Tachykinin. Homologs of this neuropeptide are implicated in mammalian aggression.
Haematopoietic stem cells drive blood production, but their population size and lifetime dynamics have not been quantified directly in humans. Here we identified 129,582 spontaneous, genome-wide ...somatic mutations in 140 single-cell-derived haematopoietic stem and progenitor colonies from a healthy 59-year-old man and applied population-genetics approaches to reconstruct clonal dynamics. Cell divisions from early embryogenesis were evident in the phylogenetic tree; all blood cells were derived from a common ancestor that preceded gastrulation. The size of the stem cell population grew steadily in early life, reaching a stable plateau by adolescence. We estimate the numbers of haematopoietic stem cells that are actively making white blood cells at any one time to be in the range of 50,000-200,000. We observed adult haematopoietic stem cell clones that generate multilineage outputs, including granulocytes and B lymphocytes. Harnessing naturally occurring mutations to report the clonal architecture of an organ enables the high-resolution reconstruction of somatic cell dynamics in humans.
Summary
Paracetamol has a central analgesic effect that is mediated through activation of descending serotonergic pathways. Debate exists about its primary site of action, which may be inhibition of ...prostaglandin (PG) synthesis or through an active metabolite influencing cannabinoid receptors. Prostaglandin H2 synthetase (PGHS) is the enzyme responsible for metabolism of arachidonic acid to the unstable PGH2. The two major forms of this enzyme are the constitutive PGHS‐1 and the inducible PGHS‐2. PGHS comprises of two sites: a cyclooxygenase (COX) site and a peroxidase (POX) site. The conversion of arachidonic acid to PGG2 is dependent on a tyrosine‐385 radical at the COX site. Formation of a ferryl protoporphyrin IX radical cation from the reducing agent Fe3+ at the POX site is essential for conversion of tyrosine‐385 to its radical form. Paracetamol acts as a reducing cosubstrate on the POX site and lessens availability of the ferryl protoporphyrin IX radical cation. This effect can be reduced in the presence of hydroperoxide‐generating lipoxygenase enzymes within the cell (peroxide tone) or by swamping the POX site with substrate such as PGG2. Peroxide tone and swamping explain lack of peripheral analgesic effect, platelet effect, and anti‐inflammatory effect by paracetamol. Alternatively, paracetamol effects may be mediated by an active metabolite (p‐aminophenol). p‐Aminophenol is conjugated with arachidonic acid by fatty acid amide hydrolase to form AM404. AM404 exerts effect through cannabinoid receptors. It may also work through PGHS, particularly in areas of the brain with high concentrations of fatty acid amide hydrolase.
Propofol administered in conjunction with an opioid such as remifentanil is used to provide total intravenous anesthesia for children. Drugs can be given as infusion controlled manually by the ...physician or as automated target-controlled infusion that targets plasma or effect site. Smart pumps programmed with pharmacokinetic parameter estimates administer drugs to a preset plasma concentration. A linking rate constant parameter (keo) allows estimation of effect site concentration. There are two parameter sets, named after the first author describing them, that are commonly used in pediatric target-controlled infusion for propofol (Absalom and Kataria) and one for remifentanil (Minto). Propofol validation studies suggest that these parameter estimates are satisfactory for the majority of children. Recommended target concentrations for both propofol and remifentanil depend on the type of surgery, the degree of surgical stimulation, the use of local anesthetic blocks, and the ventilatory status of the patient. The use of processed electroencephalographic monitoring is helpful in pediatric total intravenous anesthesia and target-controlled infusion anesthesia, particularly in the presence of neuromuscular blockade.
1.There is a nonlinear relationship between structure and functional processes and the mass of living organisms. Allometric scaling of body mass provides a theory based method for predictions of mass ...related biological characteristics.2.Numerous empirical methods have been proposed to link the mass of living organisms with the size which is the driver for structure and function.3.Normal fat mass is a size descriptor based on allometric theory that partitions total body mass into fat free mass and fat mass. The relative influence of fat mass as a predictor of size compared to fat free mass is described by the fraction of fat mass that makes fat equivalent to fat free mass in terms of allometric size. This fraction will differ for each drug and each parameter affected by body size (e.g. clearance and volume of distribution).4.The use of normal fat mass based on allometric theory provides a principle based approach linking size and body composition to structure and function.5.Normal fat mass can be used to improve drug dosing.
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Traumatic spinal cord injury (SCI) results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared ...axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns) were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+) and CD24(-/lo) population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.
hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.
The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for intervention.
Growth and development are two major aspects of children not readily apparent in adults. Clearance in the paediatric population should be investigated using models that describe size, maturation and ...organ function influences. Size is the primary covariate and although lean body weight is argued as a better measure than total body weight, the use of different fractions of fat mass to explain how pharmacokinetic parameters vary with body composition has been proposed. Allometric scaling using an empiric power exponent of 3/4 is superior to scaling using body surface area. The sigmoid hyperbolic model has proven useful to describe maturation. An extra parameter that describes asymmetry can be incorporated into this model. These descriptors are used to illustrate creatinine, morphine and paracetamol clearance in children. Simultaneous investigation of pooled GFR, paracetamol and morphine data enabled testing for shared common features of maturation processes. Results suggest that GFR matures before paracetamol or morphine clearance, consistent with phase II conjugation processes that convert xenobiotics to water soluble forms that can subsequently be eliminated from the body through the renal system. The use of such mechanistic approaches improves understanding of paediatric pharmacokinetics; improving dosing predictions and allowing projection in exploratory drug development.
We use observations from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, in orbit around Mercury, to investigate interplanetary coronal mass ejections ...(ICMEs) near 0.3 AU. MESSENGER is the first spacecraft since Helios 1 and 2 in the 1980s to make in situ measurements of the interplanetary medium at heliocentric distances < 0.5 AU. As such, it presents a unique opportunity for observing the innermost heliosphere. It also allows for observations of ICMEs well within 1 AU to study their evolution as they expand and propagate outward, interacting with the solar wind. We catalog ICME events observed by the MESSENGER Magnetometer between 2011 and 2014 and present statistical analyses of ICME properties at Mercury. In addition, using existing data sets of ICMEs at 1 AU, we investigate key ICME property changes from Mercury to 1 AU. We find good agreement with previous studies for the magnetic field strength dependence on distance, and we also find evidence that ICME deceleration continues past the orbit of Mercury. This paper describes the database of ICMEs from MESSENGER orbital observations around Mercury, which is publicly available through the supporting information (Table S1) associated with this manuscript and the Virtual Energetic Particle Observatory. Our ICME database will prove particularly useful for multipoint spacecraft studies of recent ICMEs, as well as for model validation of ICME properties.
Key Points
Comprehensive database of ICMEs from 3.5 years of MESSENGER Magnetometer observations at Mercury
Three lines of evidence for ICME speed decrease past Mercury's orbit to 1 AU
Magnetic field strength‐distance dependence established from Helios data confirmed with MESSENGER
Aims
Alpha‐2 agonists are direct peripheral vasoconstrictors, which achieve these effects by activating vascular smooth muscle alpha‐2 adrenoceptors. The impact of this response during ...dexmedetomidine infusion remains poorly quantified. Our goal was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD, vasoconstriction) effects of a computer‐controlled dexmedetomidine infusion in healthy volunteers.
Methods
After local ethics committee approval, we studied 10 healthy volunteers. To study the peripheral vasoconstrictive effect of dexmedetomidine without concurrent sympatholytic effects, sympathetic fibres were blocked with a brachial plexus block. Volunteers received a dexmedetomidine target‐controlled infusion for 15 min, to a target concentration of 0.3 ng ml–1. Arterial blood samples were collected during and for 60 min after dexmedetomidine infusion for PK analysis. Peripheral vasoconstriction (PD) was assessed using finger photoelectric plethysmography. PK/PD analysis was carried out using nonlinear mixed‐effect models.
Results
We found that the computer‐controlled infusion pump delivered mean concentrations greater than 0.3 ng ml–1 over the 15‐min infusion duration. The peripheral vasoconstrictive effect correlated with dexmedetomidine plasma concentrations during and after the infusion. A three‐compartment model provided a better fit to the data than a two‐compartment model.
Conclusions
We found that dexmedetomidine‐induced vasoconstriction is concentration dependent over time. Dexmedetomidine PK were best estimated by a three‐compartment model with allometric scaling. Our results may contribute to future modelling of dexmedetomidine‐induced haemodynamic effects.