Hox gene and development of the auditory circuit

Sound vibration is sensed by hair cells in the inner ear. The information is transmitted to the cochlear nucleus in the brainstem via spiral ganglion neurons. The information is further transmitted to higher relaying centers in the brain such as superior olivary complex and inferior colliculus. The connectivity between these components is topographically organized in a frequency-specific manner. It is known that the organization is well-established from the beginning of the circuit development. However, little is still known about the molecular mechanisms underlying the development of connectivity in the auditory circuit. Homeobox transcription factors of the Hox gene family are known for their involvement in early anterior-posterior axis patterning of neuronal progenitors in the hindbrain. Recent evidence indicates that they also play important roles in late aspects of neuronal development and establishment of topographic circuitry. Moreover, a mutation in the HOXA2 gene has been recently shown to be responsible for hearing deficits in humans. By means of spatiotemporally controlled Hoxa2 and Hoxb2 conditional mutations in the mouse we analyzed the involvement of these factors in auditory circuit development and connectivity

Lineage-Specific Duplication and Loss of Pepsinogen Genes in Hominoid Evolution

Fourteen different pepsinogen-A cDNAs and one pepsinogen-C cDNA have been cloned from gastric mucosa of the orangutan, Pongo pygmaeus. Encoded pepsinogens A were classified into two groups, i.e., types A1 and A2, which are different in acidic character. The occurrence of 9 and 5 alleles of A1 and A2 genes (at least 5 and 3 loci), respectively was anticipated. Respective orthologous genes are present in the chimpanzee genome although their copy numbers are much smaller than those of the orangutan genes. Only A1 genes are present in the human probably due to the loss of the A2 gene. Molecular phylogenetic analyses showed that A1 and A2 genes diverged before the speciation of great hominoids. Further reduplications of respective genes occurred several times in the orangutan lineage, with much higher frequencies than those occurred in the chimpanzee and human lineages. The rates of non-synonymous substitutions were higher than those of synonymous ones in the lineage of A2 genes, implying the contribution of the positive selection on the encoded enzymes. Several sites of pepsin moieties were indeed found to be under positive selection, and most of them locate on the surface of the molecule, being involved in the conformational flexibility. Deduced from the known genomic structures of pepsinogen-A genes of primates and other mammals, the duplication/loss were frequent during their evolution. The extreme multiplication in the orangutan might be advantageous for digestion of herbaceous foods due to the increase in the level of enzymes in stomach and the diversification of enzyme specificit

Exophiala dermatitidis infection in non-cystic fibrosis bronchiectasis

SummaryA 54-year-old female presented with an exacerbation of right middle lobe bronchiectasis. A bronchoscopic bronchial washing and repeated trials of sputum culture consistently recovered no other infectious agent except Exophiala dermatitidis. Her illness was improved by administrations of intravenous miconazole and nebulized amphotericin B when sputum cultures yielded no fungi, demonstrating a pathogenic role of the fungi. The present case illustrates E. dermatitidis as a pathogenic agent in non-cystic fibrosis bronchiectasis

Autistic Traits and Brain Activation during Face-to-Face Conversations in Typically Developed Adults

BACKGROUND: Autism spectrum disorders (ASD) are characterized by impaired social interaction and communication, restricted interests, and repetitive behaviours. The severity of these characteristics is posited to lie on a continuum that extends into the general population. Brain substrates underlying ASD have been investigated through functional neuroimaging studies using functional magnetic resonance imaging (fMRI). However, fMRI has methodological constraints for studying brain mechanisms during social interactions (for example, noise, lying on a gantry during the procedure, etc.). In this study, we investigated whether variations in autism spectrum traits are associated with changes in patterns of brain activation in typically developed adults. We used near-infrared spectroscopy (NIRS), a recently developed functional neuroimaging technique that uses near-infrared light, to monitor brain activation in a natural setting that is suitable for studying brain functions during social interactions. METHODOLOGY: We monitored regional cerebral blood volume changes using a 52-channel NIRS apparatus over the prefrontal cortex (PFC) and superior temporal sulcus (STS), 2 areas implicated in social cognition and the pathology of ASD, in 28 typically developed participants (14 male and 14 female) during face-to-face conversations. This task was designed to resemble a realistic social situation. We examined the correlations of these changes with autistic traits assessed using the Autism-Spectrum Quotient (AQ). PRINCIPAL FINDINGS: Both the PFC and STS were significantly activated during face-to-face conversations. AQ scores were negatively correlated with regional cerebral blood volume increases in the left STS during face-to-face conversations, especially in males. CONCLUSIONS: Our results demonstrate successful monitoring of brain function during realistic social interactions by NIRS as well as lesser brain activation in the left STS during face-to-face conversations in typically developed participants with higher levels of autistic traits

Feminizing Wolbachia endosymbiont disrupts maternal sex chromosome inheritance in a butterfly species

Wolbachia is a maternally inherited ubiquitous endosymbiotic bacterium of arthropods that displays a diverse repertoire of host reproductive manipulations. For the first time, we demonstrate that Wolbachia manipulates sex chromosome inheritance in a sexually reproducing insect. Eurema mandarina butterfly females on Tanegashima Island, Japan, are infected with the wFem Wolbachia strain and produce all‐female offspring, while antibiotic treatment results in male offspring. Fluorescence in situ hybridization (FISH) revealed that wFem‐positive and wFem‐negative females have Z0 and WZ sex chromosome sets, respectively, demonstrating the predicted absence of the W chromosome in wFem‐infected lineages. Genomic quantitative polymerase chain reaction (qPCR) analysis showed that wFem‐positive females lay only Z0 eggs that carry a paternal Z, whereas females from lineages that are naturally wFem‐negative lay both WZ and ZZ eggs. In contrast, antibiotic treatment of adult wFem females resulted in the production of Z0 and ZZ eggs, suggesting that this Wolbachia strain can disrupt the maternal inheritance of Z chromosomes. Moreover, most male offspring produced by antibiotic‐treated wFem females had a ZZ karyotype, implying reduced survival of Z0 individuals in the absence of feminizing effects of Wolbachia. Antibiotic treatment of wFem‐infected larvae induced male‐specific splicing of the doublesex (dsx) gene transcript, causing an intersex phenotype. Thus, the absence of the female‐determining W chromosome in Z0 individuals is functionally compensated by Wolbachia‐mediated conversion of sex determination. We discuss how Wolbachia may manipulate the host chromosome inheritance and that Wolbachia may have acquired this coordinated dual mode of reproductive manipulation first by the evolution of female‐determining function and then cytoplasmically induced disruption of sex chromosome inheritance

EMPRESS. XI. SDSS and JWST Search for Local and z~4-5 Extremely Metal-Poor Galaxies (EMPGs): Clustering and Chemical Properties of Local EMPGs

We search for local extremely metal-poor galaxies (EMPGs), selecting photometric candidates by broadband color excess and machine-learning techniques with the SDSS photometric data. After removing stellar contaminants by shallow spectroscopy with Seimei and Nayuta telescopes, we confirm that three candidates are EMPGs with 0.05--0.1 $Z_\odot$ by deep Magellan/MagE spectroscopy for faint {\sc[Oiii]}$\lambda$4363 lines. Using a statistical sample consisting of 105 spectroscopically-confirmed EMPGs taken from our study and the literature, we calculate cross-correlation function (CCF) of the EMPGs and all SDSS galaxies to quantify environments of EMPGs. Comparing another CCF of all SDSS galaxies and comparison SDSS galaxies in the same stellar mass range ($10^{7.0}-10^{8.4} M_\odot$), we find no significant ($>1\sigma$) difference between these two CCFs. We also compare mass-metallicity relations (MZRs) of the EMPGs and those of galaxies at $z\sim$ 0--4 with a steady chemical evolution model and find that the EMPG MZR is comparable with the model prediction on average. These clustering and chemical properties of EMPGs are explained by a scenario of stochastic metal-poor gas accretion on metal-rich galaxies showing metal-poor star formation. Extending the broadband color-excess technique to a high-$z$ EMPG search, we select 17 candidates of $z\sim$ 4--5 EMPGs with the deep ($\simeq30$ mag) near-infrared JWST/NIRCam images obtained by ERO and ERS programs. We find galaxy candidates with negligible {\sc[Oiii]}$\lambda\lambda$4959,5007 emission weaker than the local EMPGs and known high-$z$ galaxies, suggesting that some of these candidates may fall in 0--0.01 $Z_\odot$, which potentially break the lowest metallicity limit known to date

How many times can patients tolerate reoperation?

The frequency of resection for the recurrence of colorectal cancer has not been investigated in previous studies. Likewise, the related postoperative complications and the limit for indicating surgical resection has not been reported. Herein, we reported the complications of a highly frequent surgical approach for rectal cancer recurrence, i.e., exceeding three reoperations, based on our clinical experience. We included 15 cases exceeding two operations for the local recurrence of colorectal cancer from 2014 to 2019. We examined the postoperative complications classified as Clavien–Dindo IIIb. The positive rates of the complications were 0 (0.0%), 0 (0.0%), 2 (13.3%), 3 (37.5%), and 0 (0.0%) for the primary, 1st recurrent, 2nd recurrent, 3rd recurrent, and 4th recurrent operation group (p = 0.027), respectively. It is important to exercise caution in handling cases exceeding two reoperations (exceeding three reoperations including the primary operation)

最小IT学習で作成できる、看護学習のためのホームページ作成システムの開発

IT学習に多くの時間を割けない看護系学生が、基礎的なIT学習のみで実用的なhtml文書を作成できるシステムを開発した。html文書による情報表現はOSや特定のアプリケーションによらない、簡便で優れた手段である。しかし看護学生が自ら実用的なhtml文書を作成することは簡単ではない。そこで我々は、使用者が僅か8種類のタグを覚えるだけで実用的なホームページを作成できるシステムを開発した。それは文字色、サイズ、表作成、メール、リンク、正式タグの埋め込みなどである。学生はhtml文書の作成に多くの時間を割く必要がないので、本来の看護学の学習や研究のための情報収集に専念することができる。このシステムの実行プログムのサイズは僅か300キロバイト程度で小さく、新旧PCで無償で利用できる。本システムを利用した、学習ノートとして利用できるhtml文書、研究成果の発表のためのhtml文書などの作成方法について述べる。We developed a homepage creating system that requires only fundamental Information Technology learning to use. This system is designed for nursing students who can not spare much time to learn information technology. Information description by HTML document is a good expression means that is independent from any specific OS and application. However, it is not so easy for nursing students by themselves to create a practical HTML document. We developed a system by which students can make practical web-pages by learning about eight tags. The tags are related to font color, font size, table creation, mail, link, and embedding of standard tags. Students do not need consume much time in learning HTML documentation, and therefore they can dedicate themselves to their essential study and research of nursing theory and practice. Size of this system is as small as approximately 300KB and can run in old and new PCs at free. Here we will explain about (1) HTML documents that can be used as studying notes, (2) HTML documents for presenting research achievement, (3) methods to create these HTML documents by the system

Clinical practice guideline for drug-induced kidney injury in Japan 2016: digest version

Approximately one in eight adults has chronic kidney disease (CKD) in Japan, and the prevalence rate is expected to rise steeply due to the aging of the population in this country. In patients with CKD, quite a few medications require the dosage reduction or discontinuation because of their reduced urinary excretion and the increased risk of further renal impairment. Therefore, CKD patients are often treated by insufficient amounts of the medications, even though they may suffer from various complications. Moreover, it is empirically known that drug-induced kidney injury (DKI) accelerates the progression of renal failure, while it is not superficially ranked as a primary cause of kidney disease.In this context, the early detection, prevention, and treatment of DKI are very important issue in preventing the progression of CKD and the development of renal failure. However, there are no comprehensive and practical guideline on the diagnosis and treatment of DKI for CKD patients and on dosage adjustments for these patients.In response to this need, a clinical practice guideline for DKI was developed with the support of a Health and Labour Science Research Grant from the Ministry of Health, Labour, and Welfare (MHLW) and the Japan Agency for Medical Research and Development (AMED) for Practical Research Project for Renal Diseases, “Early detection and treatment of drug-induced kidney injury that aggravate chronic kidney disease.” This guideline was established by doing a clinical survey on DKIs, evaluating clinicopathological factors, investigating the methods of the early detection of the disease, and analyzing animal models. The present article represents a Committee of Clinical Practice Guideline for DKI. We collected supportive evidence and analyzed data, focusing on several clinical questions that have practical importance