How a Realistic Magnetosphere Alters the Polarizations of Surface, Fast Magnetosonic, and Alfvén Waves.

System-scale magnetohydrodynamic (MHD) waves within Earth's magnetosphere are often understood theoretically using box models. While these have been highly instructive in understanding many fundamental features of the various wave modes present, they neglect the complexities of geospace such as the inhomogeneities and curvilinear geometries present. Here, we show global MHD simulations of resonant waves impulsively excited by a solar wind pressure pulse. Although many aspects of the surface, fast magnetosonic (cavity/waveguide), and Alfvén modes present agree with the box and axially symmetric dipole models, we find some predictions for large-scale waves are significantly altered in a realistic magnetosphere. The radial ordering of fast mode turning points and Alfvén resonant locations may be reversed even with monotonic wave speeds. Additional nodes along field lines that are not present in the displacement/velocity occur in both the perpendicular and compressional components of the magnetic field. Close to the magnetopause, the perpendicular oscillations of the magnetic field have the opposite handedness to the velocity. Finally, widely used detection techniques for standing waves, both across and along the field, can fail to identify their presence. We explain how all these features arise from the MHD equations when accounting for a non-uniform background field and propose modified methods that might be applied to spacecraft observations.

Magnetopause ripples going against the flow form azimuthally stationary surface waves.

Surface waves process the turbulent disturbances which drive dynamics in many space, astrophysical and laboratory plasma systems, with the outer boundary of Earth's magnetosphere, the magnetopause, providing an accessible environment to study them. Like waves on water, magnetopause surface waves are thought to travel in the direction of the driving solar wind, hence a paradigm in global magnetospheric dynamics of tailward propagation has been well-established. Here we show through multi-spacecraft observations, global simulations, and analytic theory that the lowest-frequency impulsively-excited magnetopause surface waves, with standing structure along the terrestrial magnetic field, propagate against the flow outside the boundary. Across a wide local time range (09-15h) the waves' Poynting flux exactly balances the flow's advective effect, leading to no net energy flux and thus stationary structure across the field also. Further down the equatorial flanks, however, advection dominates hence the waves travel downtail, seeding fluctuations at the resonant frequency which subsequently grow in amplitude via the Kelvin-Helmholtz instability and couple to magnetospheric body waves. This global response, contrary to the accepted paradigm, has implications on radiation belt, ionospheric, and auroral dynamics and potential applications to other dynamical systems.

Role of α- and ß-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.

The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and ß-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and ß-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract.

Direct observations of a surface eigenmode of the dayside magnetopause.

The abrupt boundary between a magnetosphere and the surrounding plasma, the magnetopause, has long been known to support surface waves. It was proposed that impulses acting on the boundary might lead to a trapping of these waves on the dayside by the ionosphere, resulting in a standing wave or eigenmode of the magnetopause surface. No direct observational evidence of this has been found to date and searches for indirect evidence have proved inconclusive, leading to speculation that this mechanism might not occur. By using fortuitous multipoint spacecraft observations during a rare isolated fast plasma jet impinging on the boundary, here we show that the resulting magnetopause motion and magnetospheric ultra-low frequency waves at well-defined frequencies are in agreement with and can only be explained by the magnetopause surface eigenmode. We therefore show through direct observations that this mechanism, which should impact upon the magnetospheric system globally, does in fact occur.

Association of rare missense variants in the second intracellular loop of NaV1.7 sodium channels with familial autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder often accompanied by intellectual disability, language impairment and medical co-morbidities. The heritability of autism is high and multiple genes have been implicated as causal. However, most of these genes have been identified in de novo cases. To further the understanding of familial autism, we performed whole-exome sequencing on five families in which second- and third-degree relatives were affected. By focusing on novel and protein-altering variants, we identified a small set of candidate genes. Among these, a novel private missense C1143F variant in the second intracellular loop of the voltage-gated sodium channel NaV1.7, encoded by the SCN9A gene, was identified in one family. Through electrophysiological analysis, we show that NaV1.7C1143F exhibits partial loss-of-function effects, resulting in slower recovery from inactivation and decreased excitability in cultured cortical neurons. Furthermore, for the same intracellular loop of NaV1.7, we found an excess of rare variants in a case-control variant-burden study. Functional analysis of one of these variants, M932L/V991L, also demonstrated reduced firing in cortical neurons. However, although this variant is rare in Caucasians, it is frequent in Latino population, suggesting that genetic background can alter its effects on phenotype. Although the involvement of the SCN1A and SCN2A genes encoding NaV1.1 and NaV1.2 channels in de novo ASD has previously been demonstrated, our study indicates the involvement of inherited SCN9A variants and partial loss-of-function of NaV1.7 channels in the etiology of rare familial ASD.

A new family of bizarre durophagous carnivorous marsupials from Miocene deposits in the Riversleigh World Heritage Area, northwestern Queensland.

A new specimen of the bizarrely specialised Malleodectes mirabilis from middle Miocene deposits in the Riversleigh World Heritage Area provides the first and only information about the molar dentition of this strange group of extinct marsupials. Apart from striking autapomorphies such as the enormous P3, other dental features such as stylar cusp D being larger than B suggest it belongs in the Order Dasyuromorphia. Phylogenetic analysis of 62 craniodental characters places Malleodectes within Dasyuromorphia albeit with weak support and without indication of specific relationships to any of the three established families (Dasyuridae, Myrmecobiidae and Thylacinidae). Accordingly we have allocated Malleodectes to the new family, Malleodectidae. Some features suggest potential links to previously named dasyuromorphians from Riversleigh (e.g., Ganbulanyi) but these are too poorly known to test this possibility. Although the original interpretation of a steeply declining molar row in Malleodectes can be rejected, it continues to seem likely that malleodectids specialised on snails but probably also consumed a wider range of prey items including small vertebrates. Whatever their actual diet, malleodectids appear to have filled a niche in Australia's rainforests that has not been occupied by any other mammal group anywhere in the world from the Miocene onwards.

Enabling dual cellular destinations of polymeric nanoparticles for treatment following partial injury to the central nervous system.

Following neurotrauma, oxidative stress is spread via the astrocytic syncytium and is associated with increased aquaporin 4 (AQP4), inflammatory cell infiltration, loss of neurons and glia and functional deficits. Herein we evaluate multimodal polymeric nanoparticles functionalized with an antibody to an extracellular epitope of AQP4, for targeted delivery of an anti-oxidant as a therapeutic strategy following partial optic nerve transection. Using fluorescence microscopy, spectrophotometry, correlative nanoscale secondary ion mass spectrometry (NanoSIMS) and transmission electron microscopy, in vitro and in vivo, we demonstrate that functionalized nanoparticles are coated with serum proteins such as albumin and enter both macrophages and astrocytes when administered to the site of a partial optic nerve transection in rat. Antibody functionalized nanoparticles synthesized to deliver the antioxidant resveratrol are effective in reducing oxidative damage to DNA, AQP4 immunoreactivity and preserving visual function. Non-functionalized nanoparticles evade macrophages more effectively and are found more diffusely, including in astrocytes, however they do not preserve the optic nerve from oxidative damage or functional loss following injury. Our study highlights the need to comprehensively investigate nanoparticle location, interactions and effects, both in vitro and in vivo, in order to fully understand functional outcomes.

Space magnetometer based on an anisotropic magnetoresistive hybrid sensor.

We report on the design and development of a low resource, dual sensor vector magnetometer for space science applications on very small spacecraft. It is based on a hybrid device combining an orthogonal triad of commercial anisotropic magnetoresistive (AMR) sensors with a totem pole H-Bridge drive on a ceramic substrate. The drive enables AMR operation in the more sensitive flipped mode and this is achieved without the need for current spike transmission down a sensor harness. The magnetometer has sensitivity of better than 3 nT in a 0-10 Hz band and a total mass of 104 g. Three instruments have been launched as part of the TRIO-CINEMA space weather mission, inter-calibration against the International Geomagnetic Reference Field model makes it possible to extract physical signals such as field-aligned current deflections of 20-60 nT within an approximately 45,000 nT ambient field.

Effects of bait age, larval chemical cues and nutrient depletion on colonization by forensically important Calliphorid and Sarcophagid flies.

Species colonization patterns on corpses and the frequency of carrion fly oviposition and larviposition are affected by decomposition stage and previous maggot colonization. This study investigated these effects on meat bait colonization by Victorian Diptera of forensic importance. Bait treatments were: 'aged' (aged for 4 days at 22 °C, allowing some decomposition); 'nutrient-depleted' [aged for 4 days at 22 °C with feeding Calliphora vicina (Robineau-Desvoidy) (Diptera: Calliphoridae) larvae]; 'extract' (fresh bait mixed with liquid formed by feeding C. vicina larvae), and 'fresh' (untreated control bait). Statistical analysis (α = 0.05) revealed that colonization frequency differed significantly among treatments (Welch's F(3,18.83) = 4.66, P < 0.05). Post hoc tests showed that fresh and extract baits were colonized extensively throughout the experiment with no significant difference, whereas the colonization of nutrient-depleted baits was significantly lower. This suggests that larval digestive enzymes, larval excreta and cuticular hydrocarbons have less effect on colonizing Diptera than the nutritional content of meat. The colonization of aged baits did not differ significantly from that of fresh, extract or nutrient-depleted baits. A further experiment testing 'very aged' (aged for 8 days at 28 °C), 'larvae-added' (fresh bait with C. vicina larvae added before placement) and 'fresh' (untreated control) baits revealed that very aged baits were colonized significantly less frequently than either fresh or larvae-added baits (Welch's F(2, 6.17) = 17.40, P < 0.05).

Utilidad de la presencia y el tipo de placa carotídea en la predicción de eventos cardiovasculares en pacientes de riesgo alto / Usefulnes of the Presence and Type of Carotid Plaque to Predict Cardiovascular Events in High-Risk Patients

Introducción La ateromatosis carotídea es una alteración temprana de la aterosclerosis subclínica que puede determinarse en forma rápida, económica, repetible y no invasiva. Su correlación anatómica y su asociación con los factores de riesgo y diferentes manifestaciones de aterosclerosis avanzada se han demostrado claramente. En la actualidad, la ateromatosis carotídea se utiliza con frecuencia creciente para caracterizar al paciente con factores de riesgo y para evaluar resultados terapéuticos mediante la determinación del grosor íntima-media carotídeo y de la presencia y el tipo de placas bulbares, ya que se ha demostrado su valor predictivo independiente para eventos isquémicos tanto coronarios como cerebrovasculares. Objetivos Determinar si la presencia y el tipo de placa carotídea (PC) agregan información para predecir futuros eventos cardiovasculares en pacientes de riesgo alto. Material y métodos Se estudiaron 502 pacientes de riesgo alto (múltiples factores de riesgo o antecedente de evento vascular) mediante la determinación del grosor íntima-media máximo (GIMmáx), la presencia (elevación localizada) y el tipo de PC según apariencia ecográfica (fibrocálcica o fibrolipídica), la reactividad humeral dependiente del endotelio (RDE, valor basal arteria humeral vs. a los 5 min de isquemia braquial). Se consideró anormalidad la presencia y el tipo de PC, el GIMmáx > 1,1 mm y la RDE < 5%. Los puntos finales incluyeron la ocurrencia de eventos vasculares o de muerte. Los marcadores de enfermedad vascular se analizaron junto con factores de riesgo (FR) clásicos (edad, diabetes, hipertensión, dislipidemia, tabaquismo y componentes del síndrome metabólico) por el método de riesgos proporcionales de Cox y curvas de Kaplan-Meier. Resultados Edad media 65,5 ± 8,8 años, 354 hombres, 43 eventos durante un seguimiento promedio de 21 meses. Fueron predictores de eventos la PC (RR 5,6; p < 0,001), la dislipidemia (RR 5,5; p < 0,005), el GIMmáx (RR 3,2; p < 0,005), la edad > 65 años (RR 2,7; p < 0,003), la hipertensión sistólica (RR 2,5; p < 0,025), el C-HDL < 50 mg/dl (RR 2,4; p < 0,01), el síndrome metabólico (RR 2,2; p < 0,02), la trigliceridemia > 130 mg/dl (RR 2,1; p < 0,02). Ajustado por los FR, el predictor más potente resultó la PC (RR 3,13; p < 0,05). Los individuos sin PC presentaron un 2,3% de eventos, con PC fibrolipídica un 8,8% y con PC fibrocálcica un 13,4% (p < 0,001). Conclusiones Marcadores de enfermedad vascular temprana, como la presencia y el tipo de PC y el GIMmáx, agregan información pronóstica independiente a los FR. La RDE no agregó información en este grupo. Una metodología simplificada de estudio no invasivo como la empleada puede ser de utilidad clínica en la evaluación del riesgo de eventos vasculares.

Background Carotid atheromatosis is an early manifestation of subclinical atherosclerosis that can be determined in a rapid, economic, repeatable and non-invasive fashion. The anatomic correlation and its association with risk factors and different manifestations of advanced atherosclerosis have been clearly demonstrated. The determination of the intima-media thickness and the presence and type of plaques in the carotid bulb are used to assess carotid atheromatosis in patients with risk factors and to evaluate response to treatment, as this method has an independent predictive value for ischemic coronary and cerebrovascular ischemic events. Objectives To determine whether the presence and type of carotid plaques (CPs) add any information to predict future cardiovascular events in high-risk patients. Material and Methods A total of 502 high-risk patients (with multiple risk factors or history of vascular event) underwent ultrasound evaluation of maximum intima-media thickness (IMTmax), presence (localized protrusion of the vessel wall) and type of (fibrocalcific plaque or fibrolipid plaque) CP, flow mediated dilation of the brachial artery (FMD, brachial artery diameter recorded at baseline and after 5 minutes of brachial ischemia). The following variables were considered abnormal: presence and type of CP, IMTmax >1.1 and FMD <5%. Endpoints included vascular events or mortality. Markers of vascular disease and traditional risk factors (RFs) (age, diabetes, hypertension, dyslipemia, smoking habits and components of the metabolic syndrome) were analyzed together using Cox proportional-hazards regression model and Kaplan-Meier curves. Results Mean age was 65.5±8.8 years and 354 were men; 43 events occurred during an average follow-up of 21 months. The presence of CP (RR 5,6; p <0.001), dyslipemia (RR 5.5; p <0.005), IMTmax (RR 3.2; p <0.005), age > 65 years (RR 2.7; p <0.003), systolic hypertension (RR 2.5; p <0.025), HDL-C <50 mg/dl (RR 2.4; p <0.01), metabolic syndrome (RR 2.2; p <0.02), and triglyceride levels >130 mg/dl (RR 2.1; p <0.02) were predictors of events. After adjusting for RFs, PC was the most powerful predictor (RR 3.13; p <0.05). The incidence of events was 2.3% in the absence of CP, 8.8% with fibrolipid plaque, and 13.4% with fibrocalcific plaque p <0.001). Conclusions The presence and type of CP anf IMTmax are markers of early vascular disease providing prognostic information independent of RFs. FMD did not provide additional information in this group. This simple, non-invasive method may be clinically useful in the evaluation of the risk of vascular events.

Crystallization and preliminary structure determination of the membrane-bound complex cytochrome c nitrite reductase from Desulfovibrio vulgaris Hildenborough.

The cytochrome c nitrite reductase (cNiR) isolated from Desulfovibrio vulgaris Hildenborough is a membrane-bound complex formed of NrfA and NrfH subunits. The catalytic subunit NrfA is a soluble pentahaem cytochrome c that forms a physiological dimer of about 120 kDa. The electron-donor subunit NrfH is a membrane-anchored tetrahaem cytochrome c of about 18 kDa molecular weight and belongs to the NapC/NirT family of quinol dehydrogenases, for which no structures are known. Crystals of the native cNiR membrane complex, solubilized with dodecylmaltoside detergent (DDM), were obtained using PEG 4K as precipitant. Anomalous diffraction data were measured at the Swiss Light Source to 2.3 A resolution. Crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 79.5, b = 256.7, c = 578.2 A. Molecular-replacement and MAD methods were combined to solve the structure. The data presented reveal that D. vulgaris cNiR contains one NrfH subunit per NrfA dimer.

Comparative study of ortho- and meta-nitrated inhibitors of catechol-O-methyltransferase: interactions with the active site and regioselectivity of O-methylation.

In this work, we present a comparative case study of "ortho-" and "meta-nitrated" catecholic inhibitors of catechol-O-methyltransferase (COMT), with regard to their interaction with the catalytic site of the enzyme and the in vitro regioselective formation of their mono-O-methyl ether metabolites. In particular, the effects of altering the attachment position of the inhibitors' side-chain substituent, within the classic nitrocatechol pharmacophore, were investigated. For this purpose, we compared two simple regioisomeric nitrocatechol-type inhibitors of COMT, BIA 3-228 and BIA 8-176, which contain the benzoyl substituent attached at the meta and ortho positions, respectively, relative to the nitro group. The two compounds were slowly O-methylated by COMT in vitro, but the particular substitution pattern of each compound was shown to have a profound impact on the regioselectivity of their O-methylation. To provide a plausible interpretation of these results, a comprehensive analysis of the protein-inhibitor interactions and of the relative chemical susceptibility to O-methylation of the catechol hydroxyl groups was performed by means of docking simulations and ab initio molecular orbital calculations. The major structural and chemical factors that determine the enzyme regioselectivity of O-methylation were identified, and the X-ray structure of the complex of COMT with S-adenosyl-l-methionine and BIA 8-176 is herein disclosed. This is the first reported structure of the soluble form of COMT complexed with a nitrocatecholic inhibitor having a bulky substituent group in adjacent position (ortho) to the nitro group. Structural and dynamic aspects of this complex are analyzed and discussed, in the context of the present study.

Fly pupae and puparia as potential contaminants of forensic entomology samples from sites of body discovery.

Fly pupae and puparia may contaminate forensic entomology samples at death scenes if they have originated not from human remains but from animal carcasses or other decomposing organic material. These contaminants may erroneously lengthen post-mortem interval estimates if no pupae or puparia are genuinely associated with the body. Three forensic entomology case studies are presented, in which contamination either occurred or was suspected. In the first case, blow fly puparia collected near the body were detected as contaminants because the species was inactive both when the body was found and when the deceased was last sighted reliably. The second case illustrates that contamination may be suspected at particularly squalid death scenes because of the likely presence of carcasses or organic material. The third case involves the presence at the body discovery site of numerous potentially contaminating animal carcasses. Soil samples were taken along transects to show that pupae and puparia were clustered around their probable sources.

A test of worker policing theory in an advanced eusocial wasp, Vespula rufa.

Mutual policing is an important mechanism for maintaining social harmony in group-living organisms. In some ants, bees, and wasps, workers police male eggs laid by other workers in order to maintain the reproductive primacy of the queen. Kin selection theory predicts that multiple mating by the queen is one factor that can selectively favor worker policing. This is because when the queen is mated to multiple males, workers are more closely related to queen's sons than to the sons of other workers. Here we provide an additional test of worker policing theory in Vespinae wasps. We show that the yellowjacket Vespula rufa is characterized by low mating frequency, and that a significant percentage of the males are workers' sons. This supports theoretical predictions for paternities below 2, and contrasts with other Vespula species, in which paternities are higher and few or no adult males are worker produced, probably due to worker policing, which has been shown in one species, Vespula vulgaris. Behavioral observations support the hypothesis that V. rufa has much reduced worker policing compared to other Vespula. In addition, a significant proportion of worker-laid eggs were policed by the queen.

Social isolation and delayed discovery of bodies in houses: the value of forensic pathology, anthropology, odontology and entomology in the medico-legal investigation.

The bodies of socially isolated people may remain undiscovered in their own houses for prolonged periods. Occasionally the body is in situ for sufficient time to become skeletonised, or partially so. Medico-legal investigation of these cases is complicated by degradation and contamination of evidence. Thus, a multidisciplinary forensic investigation is recommended. The potential contributions of forensic pathology, anthropology, odontology and entomology are outlined here with reference to two cases that occurred in Victoria, Australia, in 2003. Forensic pathologists are often unable to determine the cause of death in skeletonised bodies, however, they may find evidence to support either a natural or unnatural mode of death, and they may describe skeletal pathology or trauma, and identify skeletal features to support radiological identification of the deceased. Anthropologists can provide supplementary evidence of skeletal trauma. Additionally, they can assess age, sex, stature and racial affiliation from skeletal remains. Odontologists can identify individuals through comparison with ante-mortem dental records; however, potential difficulties exist in identifying the treating dentist of a socially isolated person. Odontologists may also examine the teeth and oro-facial skeleton for trauma. Entomologists may estimate minimum death time and/or season of death. Entomological examination of insect remains may also confirm that a body has lain in situ for a considerable period.

Potential contamination of forensic entomology samples collected in the mortuary: a case report.

Carrion insects originating from infested bodies may establish small mortuary populations. Two Victorian Institute of Forensic Medicine cases are presented to illustrate how these insects can potentially contaminate forensic entomology samples collected in the mortuary. The first case proves that bodies can be colonised in the mortuary: when a decomposed body in freezer storage was thawed for a procedure in the main mortuary, it was colonised within five minutes of exposure by the beetle Necrobia rufipes De Geer (Cleridae, Coleoptera). The second case illustrates that immobile juvenile insects can be transferred between bodies, and describes the transfer of an Eristalis sp. (Syrphidae, Diptera) pupa from a decomposed to a fresh body. While the contamination risk is slight, it can be further minimised by checking mortuary-collected samples against those taken from the body discovery site, by mortuary pest control, and by checking previous mortuary admittance records for possible contamination sources.

Crystallization and preliminary X-ray diffraction studies of a catechol-O-methyltransferase/inhibitor complex.

Inhibitors of the enzyme catechol-O-methyltransferase (COMT) are used as co-adjuvants in the therapy of Parkinson's disease. A recombinant form of the soluble cytosolic COMT from rat has been co-crystallized with a new potent inhibitor, BIA 8-176 [(3,4-dihydroxy-2-nitrophenyl)phenylmethanone], by the vapour-diffusion method using PEG 6K as precipitant. Crystals diffract to 1.6 A resolution on a synchrotron-radiation source and belong to the monoclinic space group P2(1), with unit-cell parameters a = 52.77, b = 79.63, c = 61.54 A, beta = 91.14 degrees.

Macroporous silicon electrical sensor for DNA hybridization detection.

Macroporous silicon (pore diameter 1-2 microm) was used in an electrical sensor for real time, label free detection of DNA hybridization. Electrical contacts were made exclusively on the back side of the substrate, which allowed complete exposure of the porous layer to DNA. Hybridization of a DNA probe with its complementary sequence produced a reduction in the impedance and a shift in the phase angle resulting from a change in dielectric constant inside the porous matrix and a modification of the depletion layer width in the crystalline silicon structure. The effect of the DNA charge on the response was corroborated using peptide nucleic acid (PNA), an uncharged analog of DNA. The sensitivity and selectivity of the device were characterized and the sensing properties of the porous layer alone were investigated using self-supporting macroporous silicon membranes.