Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study

IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS

Drosophila Carrying Pex3 or Pex16 Mutations Are Models of Zellweger Syndrome That Reflect Its Symptoms Associated with the Absence of Peroxisomes

The peroxisome biogenesis disorders (PBDs) are currently difficult-to-treat multiple-organ dysfunction disorders that result from the defective biogenesis of peroxisomes. Genes encoding Peroxins, which are required for peroxisome biogenesis or functions, are known causative genes of PBDs. The human peroxin genes PEX3 or PEX16 are required for peroxisomal membrane protein targeting, and their mutations cause Zellweger syndrome, a class of PBDs. Lack of understanding about the pathogenesis of Zellweger syndrome has hindered the development of effective treatments. Here, we developed potential Drosophila models for Zellweger syndrome, in which the Drosophila pex3 or pex16 gene was disrupted. As found in Zellweger syndrome patients, peroxisomes were not observed in the homozygous Drosophila pex3 mutant, which was larval lethal. However, the pex16 homozygote lacking its maternal contribution was viable and still maintained a small number of peroxisome-like granules, even though PEX16 is essential for the biosynthesis of peroxisomes in humans. These results suggest that the requirements for pex3 and pex16 in peroxisome biosynthesis in Drosophila are different, and the role of PEX16 orthologs may have diverged between mammals and Drosophila. The phenotypes of our Zellweger syndrome model flies, such as larval lethality in pex3, and reduced size, shortened longevity, locomotion defects, and abnormal lipid metabolisms in pex16, were reminiscent of symptoms of this disorder, although the Drosophila pex16 mutant does not recapitulate the infant death of Zellweger syndrome. Furthermore, pex16 mutants showed male-specific sterility that resulted from the arrest of spermatocyte maturation. pex16 expressed in somatic cyst cells but not germline cells had an essential role in the maturation of male germline cells, suggesting that peroxisome-dependent signals in somatic cyst cells could contribute to the progression of male germ-cell maturation. These potential Drosophila models for Zellweger syndrome should contribute to our understanding of its pathology

Petrogenesis of isotopically enriched Quaternary magma with adakitic affinity associated with subduction of old lithosphere beneath central Myanmar

ミャンマーの活火山のマグマ生成メカニズムを解明 --今後も噴火する可能性の高い活火山であることが判明--. 京都大学プレスリリース. 2022-03-10.We present a model for the petrogenesis of magma with adakitic affinity in an old subduction zone, which does not involve slab melting and is constrained by new geochronological and geochemical data for Mt. Popa, the largest of three Quaternary volcanoes in central Myanmar (Popa, Monywa and Singu). The edifice is composed of Popa Plateau (0.8–0.6 Ma) with high-K rocks and a stratovolcano ( 40). The distinct K contents indicate that the adakitic magmas cannot be derived from Popa high-K rocks, but they share trace-element signatures and Sr–Nd isotope ratios with medium-K basalts from Monywa volcano. Our estimation of water contents in Popa magma reveals that primary magma for medium-K basalts was generated by partial melting of wedge mantle with normal potential temperature (TP 1330–1340 °C) under wet conditions (H₂O 0.25–0.54 wt%). Its melting was probably induced by asthenospheric upwelling that is recognized by tomographic images. Mafic adakitic magma (Mg# ~ 63, Sr/Y ~ 64) was derived from the medium-K basaltic magma in fractional crystallization of a garnet-bearing assemblage at high pressure, and felsic adakitic rocks (Mg# ~ 45, Sr/Y ~ 50) were produced by assimilation-fractional crystallization processes at mid-crustal depths

Taxonomic overview of Neogene crocodylians in Myanmar

Although Neogene crocodylians were well documented from Indo-Pakistan, few fossils were known from Southeast Asia, precluding the understanding of their evolutionary and biogeographic history. Here, we describe crocodylians from the Neogene Irrawaddy Formation of central Myanmar and evaluate their taxonomic status. Tebingan, SE of Magway (lower Upper Miocene) yields Gavialis and Crocodylus that differ from the previously known species of each genus, and the Gwebin area, SW of Bagan (Upper Pliocene) produces Crocodylus cf. palaeindicus. Taking into account the materials without provenance data, Neogene crocodylians from Myanmar include at least three gavialids and two Crocodylus that are characterized by different craniomandibular and postcranial features. The body length estimates for the gavialines from Tebingan and an unknown locality in central Myanmar are 7.5 m and 8.6 m, respectively, which exceed the maximum size limit of extant Gavialis gangeticus. Together with the previously reported large taxa, gavialids repeatedly evolved large body sizes in the Neogene of Asia. Gavialis from the Miocene of Myanmar is one of the oldest records of the genus, and its unraised orbital rim suggests that the “telescoped” eyes derived later during the genus evolution. Crocodylus cf. palaeindicus from the Pliocene of Myanmar indicates the species range was extended from western India to Myanmar during the Neogene. The absence of Crocodylus siamensis in the Neogene of India and central Myanmar implies the species originated east of central Myanmar

Taxonomic overview of Neogene crocodylians in Myanmar

Although Neogene crocodylians were well documented from Indo-Pakistan, few fossils were known from Southeast Asia, precluding the understanding of their evolutionary and biogeographic history. Here, we describe crocodylians from the Neogene Irrawaddy Formation of central Myanmar and evaluate their taxonomic status. Tebingan, SE of Magway (lower Upper Miocene) yields Gavialis and Crocodylus that differ from the previously known species of each genus, and the Gwebin area, SW of Bagan (Upper Pliocene) produces Crocodylus cf. palaeindicus. Taking into account the materials without provenance data, Neogene crocodylians from Myanmar include at least three gavialids and two Crocodylus that are characterized by different craniomandibular and postcranial features. The body length estimates for the gavialines from Tebingan and an unknown locality in central Myanmar are 7.5 m and 8.6 m, respectively, which exceed the maximum size limit of extant Gavialis gangeticus. Together with the previously reported large taxa, gavialids repeatedly evolved large body sizes in the Neogene of Asia. Gavialis from the Miocene of Myanmar is one of the oldest records of the genus, and its unraised orbital rim suggests that the “telescoped” eyes derived later during the genus evolution. Crocodylus cf. palaeindicus from the Pliocene of Myanmar indicates the species range was extended from western India to Myanmar during the Neogene. The absence of Crocodylus siamensis in the Neogene of India and central Myanmar implies the species originated east of central Myanmar

A Predictive Model for Cancer-Associated Thrombosis in Japanese Cancer Patients: Findings from the J-Khorana Registry

Background Although the close relationship between cancer and venous thromboembolism (VTE) has been identified, risk stratification for VTE in Japanese patients with cancer remains unclear

Wordsworth and Basho: Walking Poets

This exhibition of manuscripts (original and facsimile copies) of William Wordsworth and Matsuo Basho, shown alongside work by contemporary UK and Japanese artists working individually and collaboratively (painters, poets, musicians, sculptors and calligraphers), aims to show that there is much to be gained by comparing and contrasting Eastern (Japanese) and Western (Romantic) views of nature. Working from the original manuscripts of Wordsworth and the romantic poets held by the Wordsworth Trust and both original or facsimile copies of texts by the Haiku master, Matsuo Basho and his contemporaries, the show will emphasize the importance of reflecting upon our emotional response to nature. It will argue for a rebalancing a view of the world that has, since the Enlightenment, placed greater importance on measuring and recording experience, whilst de-valuing our emotional responses to the natural world. The exhibition focuses on two related themes. Related in that they explore the importance of re-developing an embodied relationship to our environment. Firstly, it explores a relationship between the act of walking and creating (art) through the work of two inveterate walker/poets – Wordsworth and Basho. Thomas De Quincey reckoned that Wordsworth “must have traversed a distance of 175,000 to 180,000 English miles - a mode of exertion which, to him, stood in the stead of alcohol and all other stimulants whatsoever to the animal spirits; to which, indeed, he was indebted for a life of unclouded happiness, and we for much of what is most excellent in his writings." Two of the most important experiences related in The Prelude, for instance, found their origins in mountain walks (when overawed by the Ravine of Gondo, the “gloomy Pass” and during a night walk to the top of Snowdon). Basho’s art reached its greatest form during his five-month trip to the Deep North in 1689, during which he wrote his masterpiece The Narrow Road to the Deep North. In this poem/travel book,he recounts the last long walk he completed with his disciple Sora—some 1,200 miles covered over five months beginning in May 1689. Secondly, the exhibition proposes that there is a close relationship to the form and framing of the script used by Wordsworth and Basho and the landscapes (natural and social) in which the texts were written and through which the writers/poets walked. The exhibition will explore the idea developed by writers such as Coleridge and Wordsworth that there is a specific relationship between the word used to describe an object or thing and the object itself – a poetic, embodied relationship. Coleridge believed that ‘words can embody and not just stand for thoughts and things’ … and he ‘puts his faith in words as “living things” – as plants, as live bodies. Indeed, one the artists in the show (calligrapher Ewan Clayton), has a long-standing interest in the calligraphy and writing of the Far East (including the poetry and manuscripts of Basho). In his recent book (The Golden Thread – The Story of Writing), he explores how the ‘experience of sensing movement in the natural world and transferring it into the felt movement of writing is shared across many traditions’ … both East and West. Basho and Wordsworth explored the world by walking through it – and their resulting embodied experiences were mediated by the medium of pen or brush on paper. A series of new essays in an accompanying publication will expand on many of these issues as well as exploring the relationship of the self to the world – reflecting on the similarities and differences between the Romantics’ embodied view of the world and the Japanese (Eastern, Buddhist) view of the self’s ‘emptying-out’. The idea for this exhibition arose, initially from a study produced by the Wordsworth Trust and the Arts Council called Beyond Words: Understanding and Sharing the Meaning of Manuscripts. In it Jeff Cowton, Curator at The Wordsworth Trust, described handwriting as a visual form which can ‘mimic the texture of thought’, revealing valuable clues as to the state of mind of the creator