Body Mass Index and Pathway Dysregulation in Cancer

Obesity has been a major global problem for more than a decade, associated with many noncommunicable diseases such as cancer. The number of obese people, both adults and children, has risen in every country of the world and the trend will likely to continue. Cancers are caused by dysregulation of various molecular pathways that allow tumour cells to proliferate, survive and migrate. One of the difficulties associated with the treatment of cancers is the identification of the underlying biological pathways that drive tumorigenesis. This research aims to determine whether gene expression signatures exist that are specific to obesity across multiple cancer types, and to investigate whether there are any common pathways being dysregulated in cancers based on these genetic signatures. In this work no genetic signatures differentially expressed genes were found between obese and non-obese patients that were common across multiple cancer types. However, the Akt, epidermal growth factor receptor (EGFR) , transforming growth factor-B (TGFB) and Src pathways may have a role in promoting the tumour progression in patients that are obese. It is likely that there is some complex mechanism underlying the relationship between obesity and cancer. A better understanding of the pathways being dysregulated in cancer cells in obese patients may lead to improved clinical decisions, and contribute towards personalised treatment in the future

Active Gaits Generation of Quadruped Robot Using Pulse-Type Hardware Neuron Models

In this chapter, the authors will propose the active gait generation of a quadruped robot. We developed the quadruped robot system using self-inhibited pulse-type hardware neuron models (P-HNMs) as a solution to elucidate the gait generation method. We feedbacked pressures at the robot system’s each foot to P-HNM and varied the joints’ angular velocity individually. We experimented with making the robot walk from an upright position on a flat floor. As a result of the experiment, we confirmed that the robot system spontaneously generates walk gait and trot gait according to the moving speed. Also, we clarified the process by which the robot actively generates gaits from the upright state. These results suggest that animals may generate gait using a similarly simple method because P-HNM mimics biological neurons’ function. Furthermore, it shows that our robot system can generate gaits adaptively and quite easily

Recessive Spondylocarpotarsal Synostosis Syndrome Due to Compound Heterozygosity for Variants in MYH3

Spondylocarpotarsal synostosis syndrome (SCTS) is characterized by intervertebral fusions and fusion of the carpal and tarsal bones. Biallelic mutations in FLNB cause this condition in some families, whereas monoallelic variants in MYH3, encoding embryonic heavy chain myosin 3, have been implicated in dominantly inherited forms of the disorder. Here, five individuals without FLNB mutations from three families were hypothesized to be affected by recessive SCTS on account of sibling recurrence of the phenotype. Initial whole-exome sequencing (WES) showed that all five were heterozygous for one of two independent splice-site variants in MYH3. Despite evidence indicating that three of the five individuals shared two allelic haplotypes encompassing MYH3, no second variant could be located in the WES datasets. Subsequent genome sequencing of these three individuals demonstrated a variant altering a 5' UTR splice donor site (rs557849165 in MYH3) not represented by exome-capture platforms. When the cohort was expanded to 16 SCTS-affected individuals without FLNB mutations, nine had truncating mutations transmitted by unaffected parents, and six inherited the rs557849165 variant in trans, an observation at odds with the population allele frequency for this variant. The rs557849165 variant disrupts splicing in the 5' UTR but is still permissive of MYH3 translational initiation, albeit with reduced efficiency. Although some MYH3 variants cause dominant SCTS, these data indicate that others (notably truncating variants) do not, except in the context of compound heterozygosity for a second hypomorphic allele. These observations make genetic diagnosis challenging in the context of simplex presentations of the disorder

Body Mass Index and Pathway Dysregulation in Cancer

Obesity has been a major global problem for more than a decade, associated with many noncommunicable diseases such as cancer. The number of obese people, both adults and children, has risen in every country of the world and the trend will likely to continue. Cancers are caused by dysregulation of various molecular pathways that allow tumour cells to proliferate, survive and migrate. One of the difficulties associated with the treatment of cancers is the identification of the underlying biological pathways that drive tumorigenesis. This research aims to determine whether gene expression signatures exist that are specific to obesity across multiple cancer types, and to investigate whether there are any common pathways being dysregulated in cancers based on these genetic signatures. In this work no genetic signatures differentially expressed genes were found between obese and non-obese patients that were common across multiple cancer types. However, the Akt, epidermal growth factor receptor (EGFR) , transforming growth factor-B (TGFB) and Src pathways may have a role in promoting the tumour progression in patients that are obese. It is likely that there is some complex mechanism underlying the relationship between obesity and cancer. A better understanding of the pathways being dysregulated in cancer cells in obese patients may lead to improved clinical decisions, and contribute towards personalised treatment in the future

Fabrication of High-Resolution Fine Microneedles Derived from Hydrolyzed Hyaluronic Acid Gels in Vacuum Environment Imprinting Using Water Permeable Mold

Hydrolyzed hyaluronic acid high-resolution fine microneedles of 13 µm in diameter and 24 µm in height were fabricated from hydrolyzed hyaluronic acid gels made in mixtures of water using vacuum environment imprint lithography processes with a water permeable mold. The gas traps of water and volatile solvents in the imprint materials cause transfer failure in the conventional water impermeable molds of quartz and metal. However, the water permeable mold allows the use of 67 wt% dilution water with high solubility to increase the fluidity of the hydrolyzed hyaluronic acid during the patterning of high-resolution fine microneedles for cosmetics and pharmaceuticals. This demonstration sets a new paradigm of functional pure gels for high-resolution nano-patterning applications with various cosmetic and pharmaceutical materials containing dilution water using a water permeable mold

Erratum : Recessive Spondylocarpotarsal Synostosis Syndrome Due to Compound Heterozygosity for Variants in MYH3 (The American Journal of Human Genetics (2018) 102(6) (1115–1125), (S000292971830140X), (10.1016/j.ajhg.2018.04.008))

(The American Journal of Human Genetics 102, 1115–1125; June 7, 2018) In the originally published version of this article, Kathrin Ludwig's name was misspelled in the author list. Her name appears correctly here and in the article online. The authors regret the error

Recessive Spondylocarpotarsal Synostosis Syndrome Due to Compound Heterozygosity for Variants in MYH3

Spondylocarpotarsal synostosis syndrome (SCTS) is characterized by intervertebral fusions and fusion of the carpal and tarsal bones. Biallelic mutations in FLNB cause this condition in some families, whereas monoallelic variants in MYH3, encoding embryonic heavy chain myosin 3, have been implicated in dominantly inherited forms of the disorder. Here, five individuals without FLNB mutations from three families were hypothesized to be affected by recessive SCTS on account of sibling recurrence of the phenotype. Initial whole-exome sequencing (WES) showed that all five were heterozygous for one of two independent splice-site variants in MYH3. Despite evidence indicating that three of the five individuals shared two allelic haplotypes encompassing MYH3, no second variant could be located in the WES datasets. Subsequent genome sequencing of these three individuals demonstrated a variant altering a 5' UTR splice donor site (rs557849165 in MYH3) not represented by exome-capture platforms. When the cohort was expanded to 16 SCTS-affected individuals without FLNB mutations, nine had truncating mutations transmitted by unaffected parents, and six inherited the rs557849165 variant in trans, an observation at odds with the population allele frequency for this variant. The rs557849165 variant disrupts splicing in the 5' UTR but is still permissive of MYH3 translational initiation, albeit with reduced efficiency. Although some MYH3 variants cause dominant SCTS, these data indicate that others (notably truncating variants) do not, except in the context of compound heterozygosity for a second hypomorphic allele. These observations make genetic diagnosis challenging in the context of simplex presentations of the disorder

A Polynesian-specific missense CETP variant alters the lipid profile

Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies