In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related ...terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.
Objective The objective of the study was to investigate the effectiveness of preemptive analgesia at pain control in women undergoing total abdominal hysterectomy. Data Sources Eligible studies, ...published through May 31, 2016, were retrieved through Medline, Cochrane Central Register for Controlled Trials, and Cochrane Database of Systematic Reviews. Study Eligibility We included randomized controlled trials with the primary outcome of pain control in women receiving a preemptive medication prior to total abdominal hysterectomy. Comparators were placebo, different doses of the same medication as intervention, or other nonnarcotic or narcotic medication. Study Appraisal and Synthesis Methods Study data were extracted by one reviewer and confirmed by a second reviewer. For each outcome we graded the quality of the evidence. Studies were classified by the type of medication used and by outcome type. Results Eighty-four trials met eligibility, with 69 included. Among nonnarcotic medications, paracetamol, gabapentin, and rofecoxib combined with gabapentin resulted in improvements in pain assessment compared with placebo and other nonnarcotic medications. Patient satisfaction was higher in patients who were given gabapentin combined with paracetamol compared with gabapentin alone. Use of preemptive paracetamol, gabapentin, bupivacaine, and phenothiazine resulted in less narcotic usage than placebo. All narcotics (ketamine, morphine, fentanyl) resulted in improved pain control compared with placebo. Narcotics had a greater reduction in pain assessment scores compared with nonnarcotics, and their use resulted in lower total narcotic usage. Conclusion Preemptive nonnarcotic and narcotic medications prior to abdominal hysterectomy decrease total narcotic requirements and improve patient postoperative pain assessment and satisfaction scores.
Plasmablasts are a highly differentiated, antibody secreting B cell subset whose prevalence correlates with disease activity in Multiple Sclerosis (MS). For most patients experiencing partial ...transverse myelitis (PTM), plasmablasts are elevated in the blood at the first clinical presentation of disease (known as a clinically isolated syndrome or CIS). In this study we found that many of these peripheral plasmablasts are autoreactive and recognize primarily gray matter targets in brain tissue. These plasmablasts express antibodies that over-utilize immunoglobulin heavy chain V-region subgroup 4 (VH4) genes, and the highly mutated VH4+ plasmablast antibodies recognize intracellular antigens of neurons and astrocytes. Most of the autoreactive, highly mutated VH4+ plasmablast antibodies recognize only a portion of cortical neurons, indicating that the response may be specific to neuronal subgroups or layers. Furthermore, CIS-PTM patients with this plasmablast response also exhibit modest reactivity toward neuroantigens in the plasma IgG antibody pool. Taken together, these data indicate that expanded VH4+ peripheral plasmablasts in early MS patients recognize brain gray matter antigens. Peripheral plasmablasts may be participating in the autoimmune response associated with MS, and provide an interesting avenue for investigating the expansion of autoreactive B cells at the time of the first documented clinical event.
The vast, deep, volatile-ice-filled basin informally named Sputnik Planum is central to Pluto's vigorous geological activity. Composed of molecular nitrogen, methane, and carbon monoxide ices, but ...dominated by nitrogen ice, this layer is organized into cells or polygons, typically about 10 to 40 kilometres across, that resemble the surface manifestation of solid-state convection. Here we report, on the basis of available rheological measurements, that solid layers of nitrogen ice with a thickness in excess of about one kilometre should undergo convection for estimated present-day heat-flow conditions on Pluto. More importantly, we show numerically that convective overturn in a several-kilometre-thick layer of solid nitrogen can explain the great lateral width of the cells. The temperature dependence of nitrogen-ice viscosity implies that the ice layer convects in the so-called sluggish lid regime, a unique convective mode not previously definitively observed in the Solar System. Average surface horizontal velocities of a few centimetres a year imply surface transport or renewal times of about 500,000 years, well under the ten-million-year upper-limit crater retention age for Sputnik Planum. Similar convective surface renewal may also occur on other dwarf planets in the Kuiper belt, which may help to explain the high albedos shown by some of these bodies.
Riboswitches are structural RNA elements that are generally located in the 5' untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a ...riboswitch triggers a signal to the downstream expression platform. A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time. Here we use femtosecond X-ray free electron laser (XFEL) pulses to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro- and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of 'mix-and-inject' time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.
The morphology of roots and root systems influences the efficiency by which plants acquire nutrients and water, anchor themselves and provide stability to the surrounding soil. Plant genotype and the ...biotic and abiotic environment significantly influence root morphology, growth and ultimately crop yield. The challenge for researchers interested in phenotyping root systems is, therefore, not just to measure roots and link their phenotype to the plant genotype, but also to understand how the growth of roots is influenced by their environment. This review discusses progress in quantifying root system parameters (e.g. in terms of size, shape and dynamics) using imaging and image analysis technologies and also discusses their potential for providing a better understanding of root:soil interactions. Significant progress has been made in image acquisition techniques, however trade‐offs exist between sample throughput, sample size, image resolution and information gained. All of these factors impact on downstream image analysis processes. While there have been significant advances in computation power, limitations still exist in statistical processes involved in image analysis. Utilizing and combining different imaging systems, integrating measurements and image analysis where possible, and amalgamating data will allow researchers to gain a better understanding of root:soil interactions.
This article reviews the progress made in phenotyping roots using imaging and image analysis and looks forward to the potential of using the developed techniques to understand the integral interactions of roots and their rhizosphere. While discussing the utility of different techniques it also discusses the potential of combining phenotyping methods to gain a greater understanding of the dynamic processes involved in root rhizosphere interactions. Since roots are highly responsive to both the biotic and abiotic elements of the soil environment increasing our understanding of root rhizosphere interactions is a necessary step in truly understanding root function and efficiency, in varied and variable, environments.
Tropical tree height-diameter (H:D) relationships may vary by forest type and region making large-scale estimates of above-ground biomass subject to bias if they ignore these differences in stem ...allometry. We have therefore developed a new global tropical forest database consisting of 39 955 concurrent H and D measurements encompassing 283 sites in 22 tropical countries. Utilising this database, our objectives were: 1. to determine if H:D relationships differ by geographic region and forest type (wet to dry forests, including zones of tension where forest and savanna overlap). 2. to ascertain if the H:D relationship is modulated by climate and/or forest structural characteristics (e.g. stand-level basal area, A). 3. to develop H:D allometric equations and evaluate biases to reduce error in future local-to-global estimates of tropical forest biomass. Annual precipitation coefficient of variation (PV), dry season length (SD), and mean annual air temperature (TA) emerged as key drivers of variation in H:D relationships at the pantropical and region scales. Vegetation structure also played a role with trees in forests of a high A being, on average, taller at any given D. After the effects of environment and forest structure are taken into account, two main regional groups can be identified. Forests in Asia, Africa and the Guyana Shield all have, on average, similar H:D relationships, but with trees in the forests of much of the Amazon Basin and tropical Australia typically being shorter at any given D than their counterparts elsewhere. The region-environment-structure model with the lowest Akaike's information criterion and lowest deviation estimated stand-level H across all plots to within amedian −2.7 to 0.9% of the true value. Some of the plot-to-plot variability in H:D relationships not accounted for by this model could be attributed to variations in soil physical conditions. Other things being equal, trees tend to be more slender in the absence of soil physical constraints, especially at smaller D. Pantropical and continental-level models provided less robust estimates of H, especially when the roles of climate and stand structure in modulating H:D allometry were not simultaneously taken into account.
ABSTRACT
We present MeerKAT 1.28 GHz total-intensity, polarization, and spectral-index images covering the giant (projected length l ≈ 1.57 Mpc) X-shaped radio source PKS 2014−55 with an ...unprecedented combination of brightness sensitivity and angular resolution. They show the clear ‘double boomerang’ morphology of hydrodynamical backflows from the straight main jets deflected by the large and oblique hot-gas halo of the host galaxy PGC 064440. The magnetic field orientation in PKS 2014−55 follows the flow lines from the jets through the secondary wings. The radio source is embedded in faint ($T_\mathrm{b} \approx 0.5 \mathrm{\, K}$) cocoons having the uniform brightness temperature and sharp outer edges characteristic of subsonic expansion into the ambient intragroup medium. The position angle of the much smaller (l ∼ 25 kpc) restarted central source is within 5° of the main jets, ruling out models that invoke jet re-orientation or two independent jets. Compression and turbulence in the backflows probably produce the irregular and low polarization bright region behind the apex of each boomerang as well as several features in the flow with bright heads and dark tails.
Neurocysticercosis is the most common helminthic infection of the CNS but its diagnosis remains difficult. Clinical manifestations are nonspecific, most neuroimaging findings are not pathognomonic, ...and some serologic tests have low sensitivity and specificity. The authors provide diagnostic criteria for neurocysticercosis based on objective clinical, imaging, immunologic, and epidemiologic data. These include four categories of criteria stratified on the basis of their diagnostic strength, including the following: 1) absolute--histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion, cystic lesions showing the scolex on CT or MRI, and direct visualization of subretinal parasites by funduscopic examination; 2) major--lesions highly suggestive of neurocysticercosis on neuroimaging studies, positive serum enzyme-linked immunoelectrotransfer blot for the detection of anticysticercal antibodies, resolution of intracranial cystic lesions after therapy with albendazole or praziquantel, and spontaneous resolution of small single enhancing lesions; 3) minor--lesions compatible with neurocysticercosis on neuroimaging studies, clinical manifestations suggestive of neurocysticercosis, positive CSF enzyme-linked immunosorbent assay for detection of anticysticercal antibodies or cysticercal antigens, and cysticercosis outside the CNS; and 4) epidemiologic--evidence of a household contact with Taenia solium infection, individuals coming from or living in an area where cysticercosis is endemic, and history of frequent travel to disease-endemic areas. Interpretation of these criteria permits two degrees of diagnostic certainty: 1) definitive diagnosis, in patients who have one absolute criterion or in those who have two major plus one minor and one epidemiologic criterion; and 2) probable diagnosis, in patients who have one major plus two minor criteria, in those who have one major plus one minor and one epidemiologic criterion, and in those who have three minor plus one epidemiologic criterion.
Abstract
We report on the detection of a large, extended H
i
cloud complex in the Galaxy and Mass Survey G23 field, located at a redshift of
z
∼ 0.03, observed as part of the MeerKAT Habitat of ...Galaxies Survey campaign (a pilot survey to explore the mosaicing capabilities of the MeerKAT telescope). The cloud complex, with a total mass of 10
10.0
M
⊙
, lies in proximity to a large galaxy group with
M
dyn
∼ 10
13.5
M
⊙
. We identify seven H ɪ peak concentrations, interconnected as a tenuous
chain
structure, extending ∼400 kpc from east to west, with the largest (central) concentration containing 10
9.7
M
⊙
in H ɪ gas distributed across 50 kpc. The main source is not detected in ultraviolet, optical, or infrared imaging. The implied gas mass-to-light ratio (
M
H I
/
L
r
) is extreme (>1000) even in comparison to other
dark clouds
. The complex has very little kinematic structure (110 km s
−1
), making it difficult to identify cloud rotation. Assuming pressure support, the total mass of the central concentration is > 10
10.2
M
⊙
, while a lower limit to the dynamical mass in the case of full rotational support is 10
10.4
M
⊙
. If the central concentration is a stable structure, it has to contain some amount of unseen matter, but potentially less than is observed for a typical galaxy. It is, however, not clear whether the structure has any gravitationally stable concentrations. We report a faint UV-optical-infrared source in proximity to one of the smaller concentrations in the gas complex, leading to a possible stellar association. The system nature and origins is enigmatic, potentially being the result of an interaction with or within the galaxy group it appears to be associated with.
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