3D global and regional patterns of human fetal subplate growth determined in utero

The waiting period of subplate evolution is a critical phase for the proper formation of neural connections in the brain. During this time, which corresponds to 15 to 24 postconceptual weeks (PCW) in the human fetus, thalamocortical and cortico-cortical afferents wait in and are in part guided by molecules embedded in the extracellular matrix of the subplate. Recent advances in fetal MRI techniques now allow us to study the developing brain anatomy in 3D from in utero imaging. We describe a reliable segmentation protocol to delineate the boundaries of the subplate from T2-W MRI. The reliability of the protocol was evaluated in terms of intra-rater reproducibility on a subset of the subjects. We also present the first 3D quantitative analyses of temporal changes in subplate volume, thickness, and contrast from 18 to 24 PCW. Our analysis shows that firstly, global subplate volume increases in proportion with the supratentorial volume; the subplate remained approximately one-third of supratentorial volume. Secondly, we found both global and regional growth in subplate thickness and a linear increase in the median and maximum subplate thickness through the waiting period. Furthermore, we found that posterior regions—specifically the occipital pole, ventral occipito-temporal region, and planum temporale—of the developing brain underwent the most statistically significant increases in subplate thickness. During this period, the thickest region was the developing somatosensory/motor cortex. The subplate growth patterns reported here may be used as a baseline for comparison to abnormal fetal brain development

DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly

AbstractWnt ligands regulate heart morphogenesis but the underlying mechanisms remain unclear. Two Formin-related proteins, DAAM1 and 2, were previously found to bind the Wnt effector Disheveled. Here, since DAAM1 and 2 nucleate actin and mediate Wnt-induced cytoskeletal changes, a floxed-allele of Daam1 was used to disrupt its function specifically in the myocardium and investigate Wnt-associated pathways. Homozygous Daam1 conditional knockout (CKO) mice were viable but had misshapen hearts and poor cardiac function. The defects in Daam1 CKO mice were observed by mid-gestation and were associated with a loss of protrusions from cardiomyocytes invading the outflow tract. Further, these mice exhibited noncompaction cardiomyopathy (NCM) and deranged cardiomyocyte polarity. Interestingly, Daam1 CKO mice that were also homozygous for an insertion disrupting Daam2 (DKO) had stronger NCM, severely reduced cardiac function, disrupted sarcomere structure, and increased myocardial proliferation, suggesting that DAAM1 and DAAM2 have redundant functions. While RhoA was unaffected in the hearts of Daam1/2 DKO mice, AKT activity was lower than in controls, raising the issue of whether DAAM1/2 are only mediating Wnt signaling. Daam1-floxed mice were thus bred to Wnt5a null mice to identify genetic interactions. The hearts of Daam1 CKO mice that were also heterozygous for the null allele of Wnt5a had stronger NCM and more severe loss of cardiac function than Daam1 CKO mice, consistent with DAAM1 and Wnt5a acting in a common pathway. However, deleting Daam1 further disrupted Wnt5a homozygous-null hearts, suggesting that DAAM1 also has Wnt5a-independent roles in cardiac development

Pressure dependent electronic properties of MgO polymorphs: A first-principles study of Compton profiles and autocorrelation functions

The first-principles periodic linear combination of atomic orbitals method within the framework of density functional theory implemented in the CRYSTAL06 code has been applied to explore effect of pressure on the Compton profiles and autocorrelation functions of MgO. Calculations are performed for the B1, B2, B3, B4, B8_1 and h-MgO polymorphs of MgO to compute lattice constants and bulk moduli. The isothermal enthalpy calculations predict that B4 to B8_1, h-MgO to B8_1, B3 to B2, B4 to B2 and h-MgO to B2 transitions take place at 2, 9, 37, 42 and 64 GPa respectively. The high pressure transitions B8_1 to B2 and B1 to B2 are found to occur at 340 and 410 GPa respectively. The pressure dependent changes are observed largely in the valence electrons Compton profiles whereas core profiles are almost independent of the pressure in all MgO polymorphs. Increase in pressure results in broadening of the valence Compton profiles. The principal maxima in the second derivative of Compton profiles shifts towards high momentum side in all structures. Reorganization of momentum density in the B1 to B2 structural phase transition is seen in the first and second derivatives before and after the transition pressure. Features of the autocorrelation functions shift towards lower r side with increment in pressure.Comment: 19 pages, 8 figures, accepted for publication in Journal of Materials Scienc

Universal phase transitions of B1 structured stoichiometric transition-metal carbides

The high-pressure phase transitions of B1-structured stoichiometric transition metal carbides (TMCs, TM=Ti, Zr, Hf, V, Nb, and Ta) were systematically investigated using ab initio calculations. These carbides underwent universal phase transitions along two novel phase-transition routes, namely, B1\rightarrowdistorted TlI (TlI')\rightarrowTlI and/or B1\rightarrowdistorted TiB (TiB')\rightarrowTiB, when subjected to pressures. The two routes can coexist possibly because of the tiny enthalpy differences between the new phases under corresponding pressures. Four new phases result from atomic slips of the B1-structured parent phases under pressure. After completely releasing the pressure, taking TiC as a representative of TMCs, only its new TlI'-type phase is mechanically and dynamically stable, and may be recovered.Comment: [email protected]

Genome structure and chromosome segregation in triploid interspecific plantain bananas (AAB) and breeding accessions (AAAB)

Many banana cultivars are triploid interspecific hybrids between M. acuminata (Genome A, 2n=22) and M. balbisiana (Genome B, 2n=22). They included the important group of Plantain cooking bananas classified as AAB that account for almost 20% of the bananas produced worldwide. Previous molecular analysis suggested that this group is genetically homogeneous but diversified phenotypically through somatic variations. To progress on the understanding of chromosome composition and segregation of the breeding material used to improve plantain bananas, we performed several analysis based on Genotyping By Sequencing (GBS) technologies. We analyzed the A/B chromosomes composition of a few plantain cultivars and discovered chromosome segments with AAA composition and one entire chromosome with ABB composition instead of the supposed general 'AAB' composition. We compared the global chromosome structure of A and B genomes through the construction a high density M. balbisiana genetic map and its comparison with the M. acuminata reference sequence assembly. We identified a large reciprocal translocation between a region of 0.6Mb at the beginning of chromosome 1 and a 8 Mb region at the end of chromosome 3. We also identified a large inversion of 9Mb within chromosome 5. We analyzed the A/B chromosomes segregation in a progeny from an 'AAAB' tetraploid breeding accession derived from a plantain. We revealed frequent recombination between A and B all along the genomes with a few exceptions. The exceptions consisted in the absence of recombination recorded in the inverted segment between A and B on chromosome 5 and a reduced recombination rate near the translocated regions on chromosome 1 and 3. We also observed 62% of aneuploids in the progeny involving mainly the three chromosomes that differed in their global structure between A and B genomes. Implication of these results on the origin of plantain banana cultivars and on breeding of allopolyploid bananas will be discussed based on the patterns of recombination revealed

Update on hepatorenal Syndrome: Definition, Pathogenesis, and management

Hepatorenal syndrome (HRS) is acute kidney injury (AKI) that occurs without evidence of structural abnormalities in the kidneys in patients with liver disease. It is thought to be due to splanchnic vasculature dilatation that is associated with intense increase of renal arteries’ tone, leading to renal cortex ischemia and AKI. Nitric oxide, endotoxins, neurohormonal changes, bacterial infection, high serum bilirubin and bile acids are examples for factors contributing to HRS development. Nevertheless, other unknown factors may have role in HRS pathophysiology. Hence, further discussion and research are needed to clearly understand HRS. Plasma volume restoration and vasoconstrictors are the cornerstone of HRS treatment. Others such as octreotide, noradrenaline, infection control, systemic inflammatory response prevention, shunting, and renal replacement therapy are currently used to manage HRS. Liver or combined liver and kidney transplantation is currently the ultimate cure for HRS. This review was written to help in better understanding the pathogenesis, diagnosis, and treatment options for HRS

Consensus Paper: Cerebellum and Emotion

Over the past three decades, insights into the role of the cerebellum in emotional processing have substantially increased. Indeed, methodological refinements in cerebellar lesion studies and major technological advancements in the field of neuroscience are in particular responsible to an exponential growth of knowledge on the topic. It is timely to review the available data and to critically evaluate the current status of the role of the cerebellum in emotion and related domains. The main aim of this article is to present an overview of current facts and ongoing debates relating to clinical, neuroimaging, and neurophysiological findings on the role of the cerebellum in key aspects of emotion. Experts in the field of cerebellar research discuss the range of cerebellar contributions to emotion in nine topics. Topics include the role of the cerebellum in perception and recognition, forwarding and encoding of emotional information, and the experience and regulation of emotional states in relation to motor, cognitive, and social behaviors. In addition, perspectives including cerebellar involvement in emotional learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are briefly discussed. Results of this consensus paper illustrate how theory and empirical research have converged to produce a composite picture of brain topography, physiology, and function that establishes the role of the cerebellum in many aspects of emotional processing

Efficient multi-class fetal brain segmentation in high resolution MRI reconstructions with noisy labels

Segmentation of the developing fetal brain is an important step in quantitative analyses. However, manual segmentation is a very time-consuming task which is prone to error and must be completed by highly specialized indi-viduals. Super-resolution reconstruction of fetal MRI has become standard for processing such data as it improves image quality and resolution. However, dif-ferent pipelines result in slightly different outputs, further complicating the gen-eralization of segmentation methods aiming to segment super-resolution data. Therefore, we propose using transfer learning with noisy multi-class labels to automatically segment high resolution fetal brain MRIs using a single set of seg-mentations created with one reconstruction method and tested for generalizability across other reconstruction methods. Our results show that the network can auto-matically segment fetal brain reconstructions into 7 different tissue types, regard-less of reconstruction method used. Transfer learning offers some advantages when compared to training without pre-initialized weights, but the network trained on clean labels had more accurate segmentations overall. No additional manual segmentations were required. Therefore, the proposed network has the potential to eliminate the need for manual segmentations needed in quantitative analyses of the fetal brain independent of reconstruction method used, offering an unbiased way to quantify normal and pathological neurodevelopment.Comment: Accepted for publication at PIPPI MICCAI 202

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Near-Monodisperse Ni-Cu Bimetallic Nanocrystals of Variable Composition: Controlled Synthesis and Catalytic Activity for H2 Generation

Near-monodisperse Ni{sub 1-x}Cu{sub x} (x = 0.2-0.8) bimetallic nanocrystals were synthesized by a one-pot thermolysis approach in oleylamine/1-octadecene, using metal acetylacetonates as precursors. The nanocrystals form large-area 2D superlattices, and display a catalytic synergistic effect in the hydrolysis of NaBH{sub 4} to generate H{sub 2} at x = 0.5 in a strongly basic medium. The Ni{sub 0.5}Cu{sub 0.5} nanocrystals show the lowest activation energy, and also exhibit the highest H{sub 2} generation rate at 298 K