Substantially thinner internal granular layer and reduced molecular layer surface in the cerebellum of the Tc1 mouse model of Down Syndrome - a comprehensive morphometric analysis with active staining contrast-enhanced MRI

Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer

Fully-automated μMRI morphometric phenotyping of the Tc1 mouse model of Down Syndrome

We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from μMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques-superior to single-atlas methods-together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry-advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings

A surface-patterned chip as a strong source of ultracold atoms for quantum technologies

Laser-cooled atoms are central to modern precision measurements. They are also increasingly important as an enabling technology for experimental cavity quantum electrodynamics, quantum information processing and matter–wave interferometry. Although significant progress has been made in miniaturizing atomic metrological devices, these are limited in accuracy by their use of hot atomic ensembles and buffer gases. Advances have also been made in producing portable apparatus that benefits from the advantages of atoms in the microkelvin regime. However, simplifying atomic cooling and loading using microfabrication technology has proved difficult. In this Letter we address this problem, realizing an atom chip that enables the integration of laser cooling and trapping into a compact apparatus. Our source delivers ten thousand times more atoms than previous magneto-optical traps with microfabricated optics and, for the first time, can reach sub-Doppler temperatures. Moreover, the same chip design offers a simple way to form stable optical lattices. These features, combined with simplicity of fabrication and ease of operation, make these new traps a key advance in the development of cold-atom technology for high-accuracy, portable measurement devices

Foot function during gait and parental perceived outcome in older children with symptomatic club foot deformity

Aims To assess if older symptomatic children with club foot deformity differ in perceived disability and foot function during gait, depending on initial treatment with Ponseti or surgery, compared to a control group. Second aim was to investigate correlations between foot function during gait and perceived disability in this population. Methods In all, 73 children with idiopathic club foot were included: 31 children treated with the Ponseti method (mean age 8.3 years; 24 male; 20 bilaterally affected, 13 left and 18 right sides analyzed), and 42 treated with primary surgical correction (mean age 11.6 years; 28 male; 23 bilaterally affected, 18 left and 24 right sides analyzed). Foot function data was collected during walking gait and included Oxford Foot Model kinematics (Foot Profile Score and the range of movement and average position of each part of the foot) and plantar pressure (peak pressure in five areas of the foot). Oxford Ankle Foot Questionnaire, Disease Specific Index for club foot, Paediatric Quality of Life Inventory 4.0 were also collected. The gait data were compared between the two club foot groups and compared to control data. The gait data were also correlated with the data extracted from the questionnaires. Results Our findings suggest that symptomatic children with club foot deformity present with similar degrees of gait deviations and perceived disability regardless of whether they had previously been treated with the Ponseti Method or surgery. The presence of sagittal and coronal plane hindfoot deformity and coronal plane forefoot deformity were associated with higher levels of perceived disability, regardless of their initial treatment. Conclusion This is the first paper to compare outcomes between Ponseti and surgery in a symptomatic older club foot population seeking further treatment. It is also the first paper to correlate foot function during gait and perceived disability to establish a link between deformity and subjective outcomes.</p

Australia's Dengue Risk Driven by Human Adaptation to Climate Change

Current and projected rainfall reduction in southeast Australia has seen the installation of large numbers of government-subsidised and ad hoc domestic water storage containers that could create the possibility of the mosquito Ae. aegypti expanding out of Queensland into southern Australian's urban regions. By assessing the past and current distribution of Ae. aegypti in Australia, we construct distributional models for this dengue vector for our current climate and projected climates for 2030 and 2050. The resulting mosquito distribution maps are compared to published theoretical temperature limits for Ae. aegypti and some differences are identified. Nonetheless, synthesising our mosquito distribution maps with dengue transmission climate limits derived from historical dengue epidemics in Australia suggests that the current proliferation of domestic water storage tanks could easily result in another range expansion of Ae. aegypti along with the associated dengue risk were the virus to be introduced

Fully-Automated mu MRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome

We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from μMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques–superior to single-atlas methods–together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry–advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings

Serum organochlorines and urinary porphyrin pattern in a population highly exposed to hexachlorobenzene

BACKGROUND: Porphyria cutanea tarda (PCT) is caused by hexachlorobenzene (HCB) in several species of laboratory mammals, but the human evidence is contradictory. In a study among adults of a population highly exposed to HCB (Flix, Catalonia, Spain), the prevalence of PCT was not increased. We aimed at analysing the association of individual urinary porphyrins with the serum concentrations of HCB and other organochlorine compounds in this highly exposed population. METHODS: A cross-sectional study on total porphyrins was carried out in 1994 on 604 inhabitants of the general population of Flix, older than 14 years. Of them, 241 subjects (comprising a random sample and the subgroup with the highest exposure) were included for the present study. The porphyrin profile was determined by high-pressure liquid chromatography. Serum concentrations of HCB, as well as common organochlorine compounds, were determined by gas chromatography coupled to electron capture detection. RESULTS: Coproporphyrin I (CPI) and coproporphyrin III (CPIII) were the major porphyrins excreted, while uroporphyrins I and III were only detected in 2% and 36% of the subjects respectively, and heptaporphyrins I and III in 1% and 6%, respectively. CPI and CPIII decreased with increasing HCB concentrations (p < 0.05). This negative association was not explained by age, alcohol, smoking, or other organochlorine compounds. No association was found between uroporphyrin I and III excretion, nor heptaporphyrin excretion, and HCB. CPIII increased with smoking (p < 0.05). CONCLUSION: HCB exposure in this highly exposed population did not increase urinary concentrations of individual porphyrins