Evolutionary acquisition of promoter-associated non-coding RNA (pancRNA) repertoires diversifies species-dependent gene activation mechanisms in mammals

Diversity of conserved pancRNA expression profile of the five tissues in the five species. Hierarchical clustering and symmetrical heat map of Spearman correlation coefficients of conserved pancRNA (A) and their corresponding mRNA (B) expression profiles. Samples are colored according to the tissues and the species. (PDF 301 kb

Decreased Gray Matter Volume of Right Inferior Parietal Lobule Is Associated With Severity of Mental Disorientation in Patients With Mild Cognitive Impairment

Background: Mental disorientation in time, space, and with respect to people is common in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Recently, a high-resolution functional MRI (fMRI) study revealed that the inferior parietal lobule (IPL) and precuneus are important regions related to mental orientation in healthy individuals. We hypothesized that the IPL and/or precuneus are crucial regions for mental disorientation in patients with amnestic MCI (aMCI). Therefore, our aim was to assess our hypothesis in these patients using voxel-based morphometry (VBM).Methods: Fifteen patients with aMCI participated. The Neurobehavioral Cognitive Status Examination (COGNISTAT) as well as the Mini-Mental State Examination (MMSE) were used to evaluate mental disorientation. Subsequently, we used VBM analysis to identify brain regions that exhibited gray matter (GM) volume loss associated with mental disorientation. Based on our hypothesis, four brain regions (bilateral IPLs and precuneus) were selected as regions of interest (ROIs).Results: We found a significant decreased GM volume in the right IPL, which was correlated with lower orientation scores on the COGNISTAT. In contrast, GM volume in other ROIs did not show a significant positive correlation with mental disorientation. Regarding the MMSE, no significant reduction in GM associated with decline in orientation were observed in any ROI.Conclusion: We found the significant relationship between low GM volume in the right IPL and severity of mental disorientation. Therefore, the right IPL is responsible for mental disorientation in aMCI

Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia

Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia–reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke

Reorganization of Corticospinal Projections after Prominent Recovery of Finger Dexterity from Partial Spinal Cord Injury in Macaque Monkeys

We investigated morphologic changes in the corticospinal tract (CST) to understand the mechanism underlying recovery of hand function after lesion of the CST at the C4/C5 border in seven macaque monkeys. All monkeys exhibited prominent recovery of precision grip success ratio within a few months. The trajectories and terminals of CST from the contralesional (n = 4) and ipsilesional (n = 3) hand area of primary motor cortex (M1) were investigated at 5–29 months after the injury using an anterograde neural tracer, biotinylated dextran amine (BDA). Reorganization of the CST was assessed by counting the number of BDA-labeled axons and bouton-like swellings in the gray and white matters. Rostral to the lesion (at C3), the number of axon collaterals of the descending axons from both contralesional and ipsilesional M1 entering the ipsilesional and contralesional gray matter, respectively, were increased. Caudal to the lesion (at C8), axons originating from the contralesional M1, descending in the preserved gray matter around the lesion, and terminating in ipsilesional Laminae VI/VII and IX were observed. In addition, axons and terminals from the ipsilesional M1 increased in the ipsilesional Lamina IX after recrossing the midline, which were not observed in intact monkeys. Conversely, axons originating from the ipsilesional M1 and directed toward the contralesional Lamina VII decreased. These results suggest that multiple reorganizations of the corticospinal projections to spinal segments both rostral and caudal to the lesion originating from bilateral M1 underlie a prominent recovery in long-term after spinal cord injury

Open-ended Commonsense Reasoning with Unrestricted Answer Scope

Open-ended Commonsense Reasoning is defined as solving a commonsense question without providing 1) a short list of answer candidates and 2) a pre-defined answer scope. Conventional ways of formulating the commonsense question into a question-answering form or utilizing external knowledge to learn retrieval-based methods are less applicable in the open-ended setting due to an inherent challenge. Without pre-defining an answer scope or a few candidates, open-ended commonsense reasoning entails predicting answers by searching over an extremely large searching space. Moreover, most questions require implicit multi-hop reasoning, which presents even more challenges to our problem. In this work, we leverage pre-trained language models to iteratively retrieve reasoning paths on the external knowledge base, which does not require task-specific supervision. The reasoning paths can help to identify the most precise answer to the commonsense question. We conduct experiments on two commonsense benchmark datasets. Compared to other approaches, our proposed method achieves better performance both quantitatively and qualitatively.Comment: Findings of EMNLP 202

Crystallographic texture- and grain boundary density-independent improvement of corrosion resistance in austenitic 316L stainless steel fabricated via laser powder bed fusion

Improvement of corrosion resistance of austenitic 316L stainless steel via laser powder bed fusion (LPBF) is currently a prominent research topic; however, the effects of crystallographic texture and the related grain boundary density on the corrosion resistance of LPBF-fabricated parts have not been elucidated. For biomedical applications, crystallographic texture control from a single crystalline-like to randomly oriented polycrystalline microstructure is highly attractive for optimizing the mechanical properties (particularly the Young's modulus) of implants. An investigation of the impacts of crystallographic planes and grain boundaries exposed to the biological environment on corrosion behavior is necessary. 316L stainless steels with different crystallographic textures and grain boundary densities were successfully fabricated via LPBF. The corrosion resistances of the LPBF-fabricated specimens were comprehensively assessed by anodic polarization, dissolution, and crevice corrosion repassivation tests. The LPBF-fabricated specimens showed extremely high pitting potentials in the physiological saline compared with the commercially available counterparts, and importantly, excellent pitting corrosion resistance was observed irrespective of the crystallographic planes and grain boundary density exposed. Moreover, the LPBF-fabricated specimens did not show metastable pitting corrosion even in an accelerated test using an acid solution. The repassivation behavior of the specimens was not affected by LPBF. Such a drastic improvement in the corrosion resistances of the LPBF-fabricated specimens might be attributed to suppression of inclusion coarsening owing to the rapid cooling rate during solidification in LPBF. By using LPBF, the desired crystallographic texture can be introduced based on the desired mechanical properties without concern for corrosiveness.Tsutsumi Y., Ishimoto T., Oishi T., et al. Crystallographic texture- and grain boundary density-independent improvement of corrosion resistance in austenitic 316L stainless steel fabricated via laser powder bed fusion. Additive Manufacturing, 45, 102066. https://doi.org/10.1016/j.addma.2021.102066

イヌメラノコルチン2ジュヨウタイイデンシ ニ オケル イチエンキタケイ ノ ケンシュカンヒカク ト クンレンノウ トノ カンレンセイ ニ ツイテ

本研究ではイヌのメラノコルチン2受容体(MC2R)遺伝子に存在する一塩基多型(SNPs ; 600G>C, 858G>A)と,「訓練能スコア」との関連性をゴールデンレトリーバー,ラブラドールレトリーバー,ミニチュアシュナウザー,マルチーズ,柴の5犬種,計77個体のゲノムDNAを用いて調査した。77個体のゲノムDNAについて遺伝子型判別を行った結果,ラブラドールレトリーバー,マルチーズ,柴の3犬種において600G>Cの遺伝子型およびアレル頻度に犬種差が認められた。また,600G>C多型によって判別される遺伝子型と訓練能スコアとの間に有意な関連が認められた。The relationships between behavioral trait data \u27obedience score\u27 and the genotype of two polymorphisms (600G>C and 858G>A) in the melanocortin 2 receptor gene (MC2R) were analyzed in 77 dogs of Golden retriever, Labrador retriever, Maltese, Miniature schnauzer and Shiba Inu breeds. From the genotyping of the polymorphism among the 77 dogs, we found inter-breed variations of genotype and of allelic frequency for 600G>C polymorphic region among Labrador retriever, Maltese, and Shiba Inu breeds. Furthermore, a statistical analysis revealed that genotype of 600G>C (G/G, G/C, C/C) was significantly associated with\u27 obedience score\u27