Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Tyrosine kinase inhibition produces specific alterations in axon guidance in the grasshopper embryo

Tyrosine kinase signaling pathways are essential for process outgrowth and guidance during nervous system development. We have examined the roles of tyrosine kinase activity in programming growth cone guidance decisions in an intact nervous system in which neurons can be individually identified. We applied the tyrosine kinase inhibitors herbimycin A and genistein to whole 40% grasshopper embryos placed in medium, or injected the inhibitors into intact grasshopper eggs. Both inhibitors caused interneuronal axons that normally would grow along the longitudinal connectives to instead leave the central nervous system (CNS) within the segmental nerve root and grow out toward the body wall muscles. In addition, herbimycin A produced pathfinding errors in which many longitudinal axons crossed the CNS midline. To study how this drug affected guidance decisions made by individual growth cones, we dye-filled the pCC interneuron, which normally extends an axon anteriorly along the ipsilateral longitudinal connective. In the presence of herbimycin A, the pCC growth cone was redirected across the anterior commissure. These phenotypes suggest that tyrosine kinase inhibition blocks a signaling mechanism that repels the growth cones of longitudinal connective neurons and prevents them from crossing the midline

放射線エネルギーの違いによる喉頭癌における吸収線量の影響

We investigated the usefulness of Gafchromic MD-55 film (Nuclear Associates, Inc.) for measuring the radiation doses on the radiotherapy of laryngeal cancers. Since larynx has thin wedge-shaped structure in anterior neck adjacent to airway, the radiation doses to the lesion may be diminished because of build-up and build-down. So, the dose has been measured with conventional measuring systems such as thermoluminescent dosimetry (TLD). However, it was not possible to evaluate the dose distribution correctly using TLD, because it is impossible to float a TLD chip in an air cavity. In this study, we employed Gafchromic MD-55 film as a dosimeter, for it can be set on the area of interest and with a measurability of dose range of 3 to 100 Gy, though it has no energy dependency. And this radiometer is composition near the soft tissue of the human body. The dose distributions to larynx were investigated with this film using neck phantom under each radiation beam energy of 4, 6 and 10 MV x-rays. Our neck phantom is made from acrylic resin and simulates a normal larynx on the basis of image information of computed tomography (CT). Moreover we observed secondary build-up and build-down curves in tissue in the vicinity of air cavities, especially at 10 MV x-rays. These findings suggest that patients with TI-T2 glottic cancers with anterior commissure invasion may receive more effective treatment with 4 MV x-rays rather than with 6 MV and 10 MV x-rays.Tl声門癌に対して放射線治療を単独で行うのは確立している方法である｡しかし,頚部は解剖学的に複雑であり,前方に薄いⅤ字形で,喉頭が気道に隣接している構造を持つので,病巣への線量はbuild-upとbuild-downの影響による線量低下が生じることが考えられる｡すなわち,放射線エネルギーの選択が喉頭癌の局所的制御に影響を及ぼすと言える｡この影響は,より高い放射線エネルギーでは,それに伴いより強く起きるということが基礎実験にて報告されている｡また,それらの線量測定は,熱ルミネセンス線量計(TLD)のような従来の測定システムで測定されていた｡しかし,空気空洞へTLD を単体 で浮かせ線量を正確に測定し評価を行うのは困難である｡本研究において,我々は Gafchromic MD-55 film (Nuclear Associates, Inc.)を使用し測定した｡ Gafchromic MD-55 film は,フィルムタイプ線量計でありエネルギー依存性がなく,3～100 Gyを測定可能であり,アクリル製頸部ファントムの空気組織境界面及び,空洞部に線量計を容易に精度良く配置することが可能である｡また,この線量計は人体の軟部組織に近い組成である｡そこで, 4, 6および10MVの各エネルギーでこの線量計を用いてエネルギーの違いによる,頸部ファントムを用いて喉頭の線量評価を行った｡その結果,我々は,特に放射線エネルギー10MVで頸部ファントムにおける,前部組織-組織空洞境界面-空洞部の一連したbuild-upおよびbuild-downを線量計で評価することができた｡これらの研究の結果､前交連浸潤を有するT1-T2に相当する声門癌患者は,放射線エネルギー6MVおよび10MVではなく,4MVを用いることによって,より効果的な放射線治療を行えると推測できる

Development of the early axon scaffold in the rostral brain of the small spotted cat shark (<i>Scyliorhinus canicula</i>) embryo

International audienceThe cat shark is increasingly used as a model for Chondrichthyes, an evolutionarily important sister group of the bony vertebrates that include teleosts and tetrapods. In the bony vertebrates, the first axon tracts form a highly conserved early axon scaffold. The corresponding structure has not been well characterised in cat shark and will prove a useful model for comparative studies. Using pan-neural markers, the early axon scaffold of the cat shark, Scyliorhinus canicula, was analysed. Like in other vertebrates, the medial longitudinal fascicle was the first axon tract to form from a small cluster of neurones in the ventral brain. Subsequently, additional neuronal clusters and axon tracts emerged which formed an array of longitudinal, transversal, and commissural axons tracts in the Scyliorhinus canicula embryonic brain. The first structures to appear after the medial longitudinal fascicle were the tract of the postoptic commissure, the dorsoventral diencephalic tract, and the descending tract of the mesencephalic nucleus of the trigeminal nerve. These results confirm that the early axon scaffold in the embryonic brain is highly conserved through vertebrate evolution

Marine bivalve geochemistry and shell ultrastructure from modern low pH environments

Abstract. Bivalve shells can provide excellent archives of past environmental change but have not been used to interpret ocean acidification events. We investigated carbon, oxygen and trace element records from different shell layers in the mussels Mytilus galloprovincialis (from the Mediterranean) and M. edulis (from the Wadden Sea) combined with detailed investigations of the shell ultrastructure. Mussels from the harbour of Ischia (Mediterranean, Italy) were transplanted and grown in water with mean pHT 7.3 and mean pHT 8.1 near CO2 vents on the east coast of the island of Ischia. The shells of transplanted mussels were compared with M. edulis collected at pH ~8.2 from Sylt (German Wadden Sea). Most prominently, the shells recorded the shock of transplantation, both in their shell ultrastructure, textural and geochemical record. Shell calcite, precipitated subsequently under acidified seawater responded to the pH gradient by an in part disturbed ultrastructure. Geochemical data from all test sites show a strong metabolic effect that exceeds the influence of the low-pH environment. These field experiments showed that care is needed when interpreting potential ocean acidification signals because various parameters affect shell chemistry and ultrastructure. Besides metabolic processes, seawater pH, factors such as salinity, water temperature, food availability and population density all affect the biogenic carbonate shell archive.</jats:p

Connections of the corpus cerebelli in the green sunfish and the common goldfish

Examination of the connections of the corpus cerebelli in one perciform (Lepomis cyanellus) and one cypriniform teleost (Carassius auratus) reveal that ipsilateral afferent connections in both species arise from an anterior group of nuclei in the diencephalon and mesencephalon, and a posterior group of nuclei in the rhombencephalon. Some nuclei of the anterior group and all those of the posterior group have in addition a weaker, and the medial octavolateralis nucleus a stronger, contralateral component. The inferior olivary nucleus in both species projects solely contralaterally. Nucleus paracommissuralis, the ventral accessory optic nucleus and nucleus isthmi are minute in Carassius compared to Lepomis. The latter species has in addition a bilateral corpopetal projection (ipsilaterally stronger) from the lateral cuneate nucleus. Efferent fibers in both species reach the contralateral nucleus ruber, oculomotor nucleus, nucleus of the medial longitudinal fasciculus, torus semicircularis, ventromedial and ventrolateral thalamic nuclei, optic tectum and superior and inferior reticular formation. An additional weaker ipsilateral terminal field could be observed in all nuclei except in the ventrolateral and ventromedial thalamic nuclei, the dorsal periventricular pretectal nucleus and the optic tectum. Lepomis in addition has a bilateral terminal field in the ventral accessory optic nucleus (contralaterally stronger). In both species, stronger ipsilateral and weaker contralateral terminal fields were present in the torus Iongitudinalis and the valvula cerebelli. The two patterns of corpopetal connections in Lepomis and Carassius were used as models for perciforms and cypriniforms in the analysis of the existing information in the literature on teleosts. While most discrepancies in the literature on percomorphs and ostariophysines could be interpreted consistently, the available information on mormyrids revealed a very different pattern of corpopetal organization: presence of additional connections (from a division of the nucleus preglomerulosus) and absence of otherwise well-established corpopetal connections in teleosts. In a second step, a phyletic analysis of teleostean corpopetal organization revealed that while teleosts share with all other vertebrates a group of corpopetal connections from the rhombencephalon, they evolved many new, more anteriorly located afferent inputs to the corpus cerebelli. Furthermore, electroreceptive mormyrids in addition evolved newly at least one corpopetal connection and lost many others

Holmium Laser Enucleation of the Prostate

Introduction: Holmium laser enucleation of the prostate (HoLEP) offers superior voiding outcomes to traditional transurethral resection and less morbidity than open simple prostatectomy. Likewise, HoLEP has been determined to result in excellent outcomes regardless of gland size. We present a step-by-step surgical approach to HoLEP describing both the traditional enucleation technique and a modified “top-down” surgical technique. Materials and Methods: In this video, two techniques are presented that were performed by two (A.E.K., J.E.L.) surgeons at our institution. Results: In the examples of the two enucleation techniques mentioned, outcomes are similar with regard to surgical and functional outcomes. Conclusions: HoLEP as a treatment for BPH with associated lower urinary tract symptoms (LUTS) results in excellent patient outcomes and can be offered to patients regardless of prostate volume

Fluid dynamics of aortic root dilation in Marfan syndrome

Aortic root dilation and propensity to dissection are typical manifestations of the Marfan Syndrome (MS), a genetic defect leading to the degeneration of the elastic fibres. Dilation affects the structure of the flow and, in turn, altered flow may play a role in vessel dilation, generation of aneurysms, and dissection. The aim of the present work is the investigation in-vitro of the fluid dynamic modifications occurring as a consequence of the morphological changes typically induced in the aortic root by MS. A mock-loop reproducing the left ventricle outflow tract and the aortic root was used to measure time resolved velocity maps on a longitudinal symmetry plane of the aortic root. Two dilated model aortas, designed to resemble morphological characteristics typically observed in MS patients, have been compared to a reference, healthy geometry. The aortic model was designed to quantitatively reproduce the change of aortic distensibility caused by MS. Results demonstrate that vorticity released from the valve leaflets, and possibly accumulating in the root, plays a fundamental role in redirecting the systolic jet issued from the aortic valve. The altered systolic flow also determines a different residual flow during the diastole.Comment: Accepted versio

Simultaneous reconstruction of the oral commissure, lip and buccal mucosa with microvascular transfer of combined first-second toe web and dorsalis pedis flap

The reconstruction of oral commissure, lip and mucosa defects following tumour resection is a challenging task to the reconstructive surgeon owing to the increasing aesthetic and functional demands. The authors describe a case in which the use of combined first-second toe web with dorsalis pedis flap was transferred and an optimal result was achieved for the oral commissure, lip and buccal mucosa following resection of squamous cell carcinoma and local flap failur

Redundancy and compensation in axon guidance: genetic analysis of the Drosophila Ptp10D/Ptp4E receptor tyrosine phosphatase subfamily

Background: Drosophila has six receptor protein tyrosine phosphatases (RPTPs), five of which are expressed primarily in neurons. Mutations in all five affect axon guidance, either alone or in combination. Highly penetrant CNS and motor axon guidance alterations are usually observed only when specific combinations of two or more RPTPs are removed. Here, we examine the sixth RPTP, Ptp4E, which is broadly expressed. Results: Ptp4E and Ptp10D are closely related Type III RPTPs. Non-drosophilid insect species have only one Type III RPTP, which is closest to Ptp10D. We found that Ptp4E mutants are viable and fertile. We then examined Ptp4E Ptp10D double mutants. These die before the larval stage, and have a mild CNS phenotype in which the outer longitudinal 1D4 bundle is frayed. Ptp10D Ptp69D double mutants have a strong CNS phenotype in which 1D4 axons abnormally cross the midline and the outer and middle longitudinal bundles are fused to the inner bundle. To examine if Ptp4E also exhibits synthetic phenotypes in combination with Ptp69D, we made Ptp4E Ptp69D double mutants and Ptp4E Ptp10D Ptp69D triple mutants. No phenotype was observed in the double mutant. The triple mutant phenotype differs from the Ptp10D Ptp69D phenotype in two ways. First, the longitudinal tracts appear more normal than in the double mutant; two or three bundles are observed, although they are disorganized and fused. Second, axons labelled by the SemaIIB-tMyc marker often cross in the wrong commissure. We also examined motor axon guidance, and found that no phenotypes are observed in any Ptp4E double mutant combination. However, triple mutants in which Ptp4E Ptp10D was combined with Ptp69D or Ptp52F exhibited stronger phenotypes than the corresponding Ptp10D double mutants. Conclusions: Type III RPTPs are required for viability in Drosophila, since Ptp4E Ptp10D double mutants die before the larval stage. Unlike Ptp10D, Ptp4E appears to be a relatively minor player in the control of axon guidance. Strong phenotypes are only observed in triple mutants in which both Type III RPTPs are eliminated together with Ptp69D or Ptp52F. Our results allow us to construct a complete genetic interaction matrix for all six of the RPTPs