The challenge of extra-intra craniometry: a computer-assisted three-dimensional approach on the equine skull

Background: The topographical correlations between certain extracranial and intracranial osseous points of interest (POIs), and their age-related changes, are indispensable to know for a diagnostical or surgical access to intracranial structures; however, they are difficult to assess with conventional devices. Materials and methods: In this pilot study, the 3-dimensional coordinates of extra-/intracranial POIs were determined, thus avoiding perspective distortions that used to be intrinsic problems in 2-dimensional morphometry. The data sets were then analysed by creating virtual triangles. The sizes, shapes, and positions of these triangles described the extent and the directions of the age-related shifts of the POIs. A selection of extracranial and intracranial POIs were marked on half skulls of four warmblood horses in two age groups (young: 6 weeks, n = 2; old: 14 and 17 years, n = 2). The x-, y-, and z-coordinates of these POIs were determined with a measurement arm (FaroArm Fusion, FARO Europe®). Direct distances between the POIs as well as their indirect distances on the x-, y-, and z-axis, and angles were calculated. Results: The analysed virtual triangles revealed that some parts of the skull grew in size, but did not change in shape/relative proportions (proportional type of growth, as displayed by POI A and POI B at the Arcus zygomaticus). The same POIs (A and B) remained in a very stable relationship to their closest intracranial POI at the Basis cranii on the longitudinal axis, however, shifted markedly in the dorso-lateral direction. In contrast, a disproportional growth of other parts of the cranium was, for example, related to POI C at the Crista nuchae, which shifted strongly in the caudal direction with age. A topographically stable reference point (so-called anchor point) at the Basis cranii was difficult to determine. Conclusions: Two candidates (one at the Synchondrosis intersphenoidalis, another one at the Synchondrosis sphenooccipitalis) were relatively stable in their positions. However, the epicentre of (neuro-)cranial growth could only be pinpointed to an area between them

Links between topography, wind, deflation, lakes and dust: The case of the Bodélé Depression, Chad

The Bodélé Depression, Chad is the planet's largest single source of dust. Deflation from the Bodélé could be seen as a simple coincidence of two key prerequisites: strong surface winds and a large source of suitable sediment. But here we hypothesise that long term links between topography, winds, deflation and dust ensure the maintenance of the dust source such that these two apparently coincidental key ingredients are connected by land-atmosphere processes with topography acting as the overall controlling agent. We use a variety of observational and numerical techniques, including a regional climate model, to show that: 1) contemporary deflation from the Bodélé is delineated by topography and a surface wind stress maximum; 2) the Tibesti and Ennedi mountains play a key role in the generation of the erosive winds in the form of the Bodélé Low Level Jet (LLJ); 3) enhanced deflation from a stronger Bodélé LLJ during drier phases, for example, the Last Glacial Maximum, was probably sufficient to create the shallow lake in which diatoms lived during wetter phases, such as the Holocene pluvial. Winds may therefore have helped to create the depression in which erodible diatom material accumulated. Instead of a simple coincidence of nature, dust from the world's largest source may result from the operation of long term processes on paleo timescales which have led to ideal conditions for dust generation in the world's largest dust source. Similar processes plausibly operate in other dust hotspots in topographic depressions

Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study

Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS

IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection

Staphylococcus aureus is a common aetiological agent of bacterial brain abscesses. We have previously established that a considerable IL-1 (interleukin-1) response is elicited immediately following S. aureus infection, where the cytokine can exert pleiotropic effects on glial activation and blood–brain barrier permeability. To assess the combined actions of IL-1α and IL-1β during CNS (central nervous system) infection, host defence responses were evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated by enhanced mortality rates and bacterial burdens within the first 24 h following pathogen exposure compared with WT (wild-type) animals. Loss of IL-1RI signalling also dampened the expression of select cytokines and chemokines, concomitant with significant reductions in neutrophil and macrophage infiltrates into the brain. In addition, the opening of astrocyte hemichannels during acute infection was shown to be dependent on IL-1RI activity. Collectively, these results demonstrate that IL-1RI signalling plays a pivotal role in the genesis of immune responses during the acute stage of brain abscess development through S. aureus containment, inflammatory mediator production, peripheral immune cell recruitment, and regulation of astrocyte hemichannel activity. Taken in the context of previous studies with MyD88 (myeloid differentiation primary response gene 88) and TLR2 (Toll-like receptor 2) KO animals, the current report advances our understanding of MyD88-dependent cascades and implicates IL-1RI signalling as a major antimicrobial effector pathway during acute brain-abscess formation

¹H NMR based metabolomics of CSF and blood serum: a metabolic profile for a transgenic rat model of Huntington disease

AbstractHuntington disease (HD) is a hereditary brain disease. Although the causative gene has been found, the exact mechanisms of the pathogenesis are still unknown. Recent investigations point to metabolic and energetic dysfunctions in HD neurons.Both univariate and multivariate analyses were used to compare proton nuclear magnetic resonance spectra of serum and cerebrospinal fluid (CSF) taken from presymptomatic HD transgenic rats and their wild-type littermates. N-acetylaspartate (NAA), was found to be significantly decreased in the serum of HD rats compared to wild-type littermates. Moreover, in the serum their levels of glutamine, succinic acid, glucose and lactate are significantly increased as well. An increased concentration of lactate and glucose is also found in CSF. There is a 1:1 stoichiometry coupling glucose utilization and glutamate cycling. The observed increase in the glutamine concentration, which indicates a shutdown in the neuronal-glial glutamate-glutamine cycling, results therefore in an increased glucose concentration. The elevated succinic acid concentration might be due to an inhibition of succinate dehydrogenase, an enzyme linked to the mitochondrial respiratory chain and TCA cycle. Moreover, reduced levels of NAA may reflect an impairment of mitochondrial energy production. In addition, the observed difference in lactate supports a deficiency of oxidative energy metabolism in rats transgenic for HD as well.The observed metabolic alterations seem to be more profound in serum than in CSF in presymptomatic rats. All findings suggest that even in presymptomatic rats, a defect in energy metabolism is already apparent. These results support the hypothesis of mitochondrial energy dysfunction in HD

Modulation of BACE1 Activity by Chemically Modified Aptamers

A modified DNA aptamer that binds BACE1, a therapeutic target involved in Alzheimer's disease has been developed. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides incorporating two nucleobase modifications: 5‐chlorouracil and 7‐deazaadenine. The nucleoside analogue 5‐chloro‐2′‐deoxyuridine has already been explored as a replacement for thymidine in a chemically modified genome of a bacterium. Thus, 5‐chlorouracil modification is a good candidate to support genetic transfer in vivo as well as functional activity

Microwave Spin Control of a Tin-Vacancy Qubit in Diamond

The negatively charged tin-vacancy (SnV-) center in diamond is a promising solid-state qubit for applications in quantum networking due to its high quantum efficiency, strong zero phonon emission, and reduced sensitivity to electrical noise. The SnV- has a large spin-orbit coupling, which allows for long spin lifetimes at elevated temperatures, but unfortunately suppresses the magnetic dipole transitions desired for quantum control. Here, by use of a naturally strained center, we overcome this limitation and achieve high-fidelity microwave spin control. We demonstrate a pi-pulse fidelity of up to 99.51+/0.03%$ and a Hahn-echo coherence time of T2echo = 170.0+/-2.8 microseconds, both the highest yet reported for SnV- platform. This performance comes without compromise to optical stability, and is demonstrated at 1.7 Kelvin where ample cooling power is available to mitigate drive induced heating. These results pave the way for SnV- spins to be used as a building block for future quantum technologies

TWO NEW PLOCENE SPECIES OF CYCLOSTEPHANOS (BACILLARIOPHYCEAE) WITH COMMENTS ON THE CLASSIFICATION OF THE FRESHWATER THALASSIOSIRACEAE 1

Two new species of the diatom genus Cyclostephanos Round are described from Pliocene fossil deposits in western North America. Cyclostephanos undatus is distinguished from other Cyclostephanos species by its tangentially undulate valve face; Cyclostephanos fenestratus is distinguished by its extremely shallow alveoli. This paper records previously unreported morphological detail of Cyclostephanos and speculates that structure of the punctum, labiate process and strutted process may enhance diagnosis of the freshwater genera of the Thalassiosiraceae Lebour emend. Hasle. Cyclostephanos undatus is similar to several Cyclotella species, but its external costae are raised and its alveolar morphology is similar to that of Cyclostephanos dubius (Fricke) Round. Cyclostephanos fenestratus is similar in external view to Stephanodiscus Ehrenb. However, the two species described here have flat cribra covering the mantle puncta and the labiate processes appear to lack external tubes, whereas Stephanodiscus species have domed mantle cribra and external tubes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65645/1/j.1529-8817.1986.tb04154.x.pd