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Background/Objective: Amphibian skin is a valuable source of host defense peptides (HDPs). This study aimed to identify HDPs with novel amino acid sequences from the skin of Rana tagoi yakushimensis and analyze their functions. Methods: cDNAs encoding HDP precursors were cloned and sequenced using RT-PCR and 3′-RACE. The novel HDPs were synthesized to evaluate their antimicrobial activity, antioxidant activity, and cytotoxicity. Antimicrobial activity was evaluated by way of broth microdilution and endotoxin- and β-glucan-binding capacity using an enzyme-linked endotoxin binding assay (ELEBA) and a modified ELEBA, respectively. Results: Nine cDNAs encoding precursors for various HDP families, including temporin, ranatuerin-2, brevinin-1, amurin-9, and a novel yakushimin peptide, were identified. Brevinin-1TYa exhibited antibacterial activity against Staphylococcus aureus, and brevinin-1TYa and amurin-9TYa induced morphological changes in Escherichia coli and S. aureus. Yakushimin-TYa, amurin-9TYa, and brevinin-1TYa showed concentration-dependent antibacterial effects against the plant pathogens Xanthomonas oryzae pv. oryzae and Clavibacter michiganensis subsp. michiganensis. Amurin-9TYa demonstrated strong binding affinity to lipopolysaccharide, lipoteichoic acid, and β-glucan, exhibited antioxidant activity, and lacked cytotoxicity, making it a promising therapeutic candidate. Moreover, brevinin-1TYa showed strong cytotoxicity, whereas yakushimin-TYa exhibited weak cytotoxicity. Conclusions: These findings highlight the potential of these peptides, particularly amurin-9TYa, for future applications as antimicrobial and therapeutic agents. [ABSTRACT FROM AUTHOR]

The present study assessed the growth and fish performance of juvenile red sea bream fed four isonitrogenous (46–48%) and isolipidic (15%) diets containing 45% fishmeal (control) and 15%, 30%, and 45% defatted black soldier fly (BSF) Hermetia illucens meal for 67 days. Subsequent analyses showed that there were no significant differences in the growth parameters, nutrient digestibility, and body composition of fish among all treatments. Although no significant difference was observed in fish growth, low growth was observed when the fish meal was totally replaced with the BSF meal. Higher alpha diversity of intestinal microbiota was observed in fish fed the BSF meal-based diet compared to that of the control. In the treatment groups fed the BSF meal, elevations in the presence of microbial genera that produce digestive enzymes, such as chitinase (Nocardia, Vibrio, Paenibacillus, Photobacterium), lipase (Paenibacillus, Photobacterium), and trypsin-like serine protease (Bacillus, Paenibacillus) and vitamin B group [biotin (Vibrio, Paenibacillus, Bacillus), cobalamin (Pseudomonas, Bacillus, Propionibacterium), and pyridoxin (Photobacterium)], were observed. We also found an increasing trend of bacteria producing antioxidative enzymes, such as superoxide dismutase and catalase (Nocardia, Pseudomonas, Photobacterium) in the BSF groups. These results suggested that the BSF meal could replace 67% of fishmeal without causing a negative impact on growth and lead to beneficial effects on the intestinal microbiota of the red sea bream. [ABSTRACT FROM AUTHOR]

Predicting olfactory perceptions from odorant molecules is challenging due to the complex and potentially discontinuous nature of the perceptual space for smells. In this study, we introduce a deep learning model, Mol-PECO (Molecular Representation by Positional Encoding of Coulomb Matrix), designed to predict olfactory perceptions based on molecular structures and electrostatics. Mol-PECO learns the efficient embedding of molecules by utilizing the Coulomb matrix, which encodes atomic coordinates and charges, as an alternative of the adjacency matrix and its Laplacian eigenfunctions as positional encoding of atoms. With a comprehensive dataset of odor molecules and descriptors, Mol-PECO outperforms traditional machine learning methods using molecular fingerprints and graph neural networks based on adjacency matrices. The learned embeddings by Mol-PECO effectively capture the odor space, enabling global clustering of descriptors and local retrieval of similar odorants. This work contributes to a deeper understanding of the olfactory sense and its mechanisms. [ABSTRACT FROM AUTHOR]

Melanoma of the dog and cat poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current melanoma challenges and controversies. Melanocytic tumors are common in dogs but rare in cats. The history and clinical signs relate to the anatomic site of the melanoma. Oral and subungual malignant melanomas are the most common malignant types in dogs. While many melanocytic tumors are heavily pigmented, making diagnosis relatively straightforward, melanin pigmentation is variable. A validated clinical stage scheme has been defined for canine oral melanoma. For all other locations and for feline melanoma, TNM-based staging applies. Certain histological characteristics have been shown to bear prognostic significance and can thus prove instructive in clinical decision making. Surgical resection using wide margins is currently the mainstay of therapy for the local control of melanomas, regardless of primary location. Radiotherapy forms an integral part of the management of canine oral melanomas, both as a primary and an adjuvant therapy. Adjuvant immunotherapy or chemotherapy is offered to patients at high risk of developing distant metastasis. Location is the major prognostic factor, although it is not completely predictive of local invasiveness and metastatic potential. There are no specific guidelines regarding referral considerations for dogs with melanoma, as this is likely based on a multitude of factors. The ultimate goal is to provide the best options for patients to extend quality of life and survival, either within the primary care or referral hospital setting. [ABSTRACT FROM AUTHOR]

Melanoma of the dog and cat poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current melanoma challenges and controversies. Melanocytic tumors are common in dogs but rare in cats. The history and clinical signs relate to the anatomic site of the melanoma. Oral and subungual malignant melanomas are the most common malignant types in dogs. While many melanocytic tumors are heavily pigmented, making diagnosis relatively straightforward, melanin pigmentation is variable. A validated clinical stage scheme has been defined for canine oral melanoma. For all other locations and for feline melanoma, TNMbased staging applies. Certain histological characteristics have been shown to bear prognostic significance and can thus prove instructive in clinical decision making. Surgical resection using wide margins is currently the mainstay of therapy for the local control of melanomas, regardless of primary location. Radiotherapy forms an integral part of the management of canine oral melanomas, both as a primary and an adjuvant therapy. Adjuvant immunotherapy or chemotherapy is offered to patients at high risk of developing distant metastasis. Location is the major prognostic factor, although it is not completely predictive of local invasiveness and metastatic potential. There are no specific guidelines regarding referral considerations for dogs with melanoma, as this is likely based on a multitude of factors. The ultimate goal is to provide the best options for patients to extend quality of life and survival, either within the primary care or referral hospital setting. [ABSTRACT FROM AUTHOR]

We clarified non-radiographic physical parameters associated with the severity of adult spinal deformity (ASD) using community-dwelling adult volunteers. They were subjected to upright entire spine radiographs for standard radiographic parameters and the number of sagittal modifiers of SRS-Schwab ASD classification (Schwab-SM). Clinical evaluations included isometric muscle strength of trunk extensor (TEX), trunk flexor (TFL), quadriceps femoris (QF), gluteus maximus, and iliopsoas; range of motion (ROM) of hip, knee, ankle, and active back extension (BET); SF36 physical component score (PCS), VAS for back and knee pain, and the degree of ambulatory kyphosis (dTIA). Each muscle strength was calibrated by body weight (BW) and expressed as BW ratio. According to our previous study, dTIA ≥ 7.6° was defined as pathological and dTIA ≤ 3.5° as normal. A final total of 409 female volunteers were included, and their demographics were; age 67.0 ± 5.5 years, Schwab-SM 2.1 ± 1.8, TEX 0.90 ± 0.33BW, TFL 0.48 ± 0.15BW, QF 0.45 ± 0.19BW, PCS 33.5 ± 6.5. Subjects were classified as clinical ASD group (cASD, n = 10) with PCS ≤ 27(mean-1SD) and pathological dTIA, robust group (n = 19) with PCS ≥ 40 (mean + 1SD) and normal dTIA, and the rest (non-cASD, n = 338). Statistical analyses showed significant differences in TEX, TFL, QF, knee extension (KEX), and BET between robust and cASD, and the mean values of robust group (TEX ≥ 1.1BW, TFL ≥ 0.5BW, QF ≥ 0.5BW, KEX ≥ 0° and BET ≥ 14 cm) were used as 'ASD-MJ' index. Subjects with fully achieving ASD-MJ goals showed significantly better radiographic and clinical outcomes than those with unmet goals. In conclusion, upon prescribing conservative or physical therapies for ASD patients, modifiable clinical goals should be clarified, and ASD-MJ could be a benchmark. [ABSTRACT FROM AUTHOR]

Internal granular progenitors (IGPs) in the developing cerebellar cortex of ferrets differentiate towards neural and glial lineages. The present study tracked IGPs that proliferated in response to valproic acid (VPA) to determine their fate during cerebellar cortical histogenesis. Ferret kits were used to administer VPA (200 μg/g body weight) on postnatal days 6 and 7. EdU and BrdU were injected on postnatal days 5 and 7, respectively, to label the post-proliferative and proliferating cells when exposed to VPA. At postnatal day 20, when the external granule layer was most expanded, EdU- and BrdU-single-labeled cells were significantly denser in the inner granular layer of VPA-exposed ferrets than in controls. No EdU- or BrdU-labeling was found in Purkinje cells and molecular layer interneurons. Significantly higher percentages of NeuN and Pax6 immunostaining in VPA-exposed ferrets revealed VPA-induced differentiation of IGPs towards granular neurons in BrdU-single-labeled cells. In contrast, both EdU- and BrdU-single-labeled cells exhibited significantly greater percentages of PCNA immunostaining, which appeared in immature Bergman glia, in the internal granular layer of VPA-exposed ferrets. These findings suggest that VPA affects the proliferation of IGPs to induce differentiative division towards granular neurons as well as post-proliferative IGPs toward differentiation into Bergmann glia. [ABSTRACT FROM AUTHOR]

Autophagy is primarily activated by cellular stress, such as starvation or mitochondrial damage. However, stress-independent autophagy is activated by unclear mechanisms in several cell types, such as thymic epithelial cells (TECs). Here we report that the mitochondrial protein, C15ORF48, is a critical inducer of stress-independent autophagy. Mechanistically, C15ORF48 reduces the mitochondrial membrane potential and lowers intracellular ATP levels, thereby activating AMP-activated protein kinase and its downstream Unc-51-like kinase 1. Interestingly, C15ORF48-dependent induction of autophagy upregulates intracellular glutathione levels, promoting cell survival by reducing oxidative stress. Mice deficient in C15orf48 show a reduction in stress-independent autophagy in TECs, but not in typical starvation-induced autophagy in skeletal muscles. Moreover, C15orf48–/– mice develop autoimmunity, which is consistent with the fact that the stress-independent autophagy in TECs is crucial for the thymic self-tolerance. These results suggest that C15ORF48 induces stress-independent autophagy, thereby regulating oxidative stress and self-tolerance. Stress-independent autophagy is less understood than stress-induced autophagy and is important for thymic self-tolerance. Here the authors show that a mitochondrial protein C15ORF48 is important for stress-independent autophagy and alters glutathione metabolism and C15orf48 knockout mice develop autoimmunity and changes to thymic epithelial cells. [ABSTRACT FROM AUTHOR]

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Deep learning (DL) has recently attracted attention for data processing in positron emission tomography (PET). Attenuation correction (AC) without computed tomography (CT) data is one of the interests. Here, we present, to our knowledge, the first attempt to generate an attenuation map of the human head via Sim2Real DL-based tissue composition estimation from model training using only the simulated PET dataset. The DL model accepts a two-dimensional non-attenuation-corrected PET image as input and outputs a four-channel tissue-composition map of soft tissue, bone, cavity, and background. Then, an attenuation map is generated by a linear combination of the tissue composition maps and, finally, used as input for scatter+random estimation and as an initial estimate for attenuation map reconstruction by the maximum likelihood attenuation correction factor (MLACF), i.e., the DL estimate is refined by the MLACF. Preliminary results using clinical brain PET data showed that the proposed DL model tended to estimate anatomical details inaccurately, especially in the neck-side slices. However, it succeeded in estimating overall anatomical structures, and the PET quantitative accuracy with DL-based AC was comparable to that with CT-based AC. Thus, the proposed DL-based approach combined with the MLACF is also a promising CT-less AC approach. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Familial cryptogenic stroke associated with atrial septal defect and patent foramen ovale is rare. The presence of a family history of cryptogenic stroke may lead to the requirement for careful follow‐up for younger family members. [ABSTRACT FROM AUTHOR]

One hallmark of some autoimmune diseases is the variability of symptoms among individuals. Organs affected by the disease differ between patients, posing a challenge in diagnosing the affected organs. Although numerous studies have investigated the correlation between T cell antigen receptor (TCR) repertoires and the development of infectious and immune diseases, the correlation between TCR repertoires and variations in disease symptoms among individuals remains unclear. This study aimed to investigate the correlation of TCRα and β repertoires in blood T cells with the extent of autoimmune signs that varies among individuals. We sequenced TCRα and β of CD4+CD44highCD62Llow T cells in the blood and stomachs of mice deficient in autoimmune regulator (Aire) (AIRE KO), a mouse model of human autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy. Data analysis revealed that the degree of similarity in TCR sequences between the blood and stomach varied among individual AIRE KO mice and reflected the extent of T cell infiltration in the stomach. We identified a set of TCR sequences whose frequencies in blood might correlate with extent of the stomach manifestations. Our results propose a potential of using TCR repertoires not only for diagnosing disease development but also for diagnosing affected organs in autoimmune diseases. [ABSTRACT FROM AUTHOR]

The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antigens (TSAs), are damaged by these insults and recover thereafter. However, given recent discoveries on the high heterogeneity of mTECs, it remains to be determined whether the frequency and properties of mTEC subsets are restored during thymic recovery from radiation damage. Here we demonstrate that acute total body irradiation with a sublethal dose induces aftereffects on heterogeneity and gene expression of mTECs. Single-cell RNA-sequencing (scRNA-seq) analysis showed that irradiation reduces the frequency of mTECs expressing AIRE, which is a critical regulator of TSA expression, 15 days after irradiation. In contrast, transit-amplifying mTECs (TA-mTECs), which are progenitors of AIRE-expressing mTECs, and Ccl21a-expressing mTECs, were less affected. Interestingly, a detailed analysis of scRNA-seq data suggested that the proportion of a unique mTEC cluster expressing Ccl25 and a high level of TSAs was severely decreased by irradiation. In sum, we propose that the effects of acute irradiation disrupt the heterogeneity and properties of mTECs over an extended period, which potentially leads to an impairment of thymic T cell selection. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) is a natural agonist of toll-like receptor 4 that serves a role in innate immunity. The current study evaluated the LPS-mediated regulation of neurogenesis in the subventricular zone (SVZ) progenitors, that is, the basal radial glia and intermediate progenitors (IPs), in ferrets. Ferret pups were subcutaneously injected with LPS (500 μg/g of body weight) on postnatal days (PDs) 6 and 7. Furthermore, 5-ethynyl-2′-deoxyuridine (EdU) and 5-bromo-2′-deoxyuridine (BrdU) were administered on PDs 5 and 7, respectively, to label the post-proliferative and proliferating cells in the inner SVZ (iSVZ) and outer SVZ (oSVZ). A significantly higher density of BrdU single-labeled proliferating cells was observed in the iSVZ of LPS-exposed ferrets than in controls but not in post-proliferative EdU single-labeled and EdU/BrdU double-labeled self-renewing cells. BrdU single-labeled cells exhibited a lower proportion of Tbr2 immunostaining in LPS-exposed ferrets (22.2%) than in controls (42.6%) and a higher proportion of Ctip2 immunostaining in LPS-exposed ferrets (22.2%) than in controls (8.6%). The present findings revealed that LPS modified the neurogenesis of SVZ progenitors. Neonatal LPS exposure facilitates the proliferation of SVZ progenitors, followed by the differentiation of Tbr2-expressing IPs into Ctip2-expressing immature neurons. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is a rare neoplasm of macrophages or dendritic cells with a poor prognosis in dogs. As the apoptosis inhibitor of macrophage (AIM) is characteristically expressed in canine macrophages, we hypothesised that AIM is involved in the development or progression of HS in dogs. In this study, AIM expression in the tumour region and serum AIM levels in dogs with HS was assessed. Additionally, the effects of AIM overexpression on HS cell viability were investigated using a HS cell line that was selected from five validated HS cell lines. Immunohistochemistry showed that AIM expression was observed in the cytoplasm of the HS cells. CD36, a candidate AIM receptor, was also observed on the cell membrane of HS cells. When the serum AIM level was detected in 36 dogs with HS and 10 healthy dogs via western blot analysis, the AIM levels in the HS dogs were significantly higher than those in the controls. AIM mRNA expression in the 5 HS cell lines varied but was higher than that in the other tumour‐derived lines. Among the five HS cell lines, DH82 originally had lower AIM and the highest CD36 expression. When AIM was overexpressed in DH82, therein cell growth speed and invasion, apoptosis inhibition and phagocytic activity were strongly upregulated. These data suggest that elevated intra‐tumour expression of AIM could induce the progression of HS cells in dogs. Moreover, elevated serum AIM levels in dogs with HS could serve as a biomarker of HS. [ABSTRACT FROM AUTHOR]

Adaptability to changing environments is one of the universal characteristics of living organisms. Because individual modes of adaptation are diverse, a unified understanding of these diverse modes is essential to comprehend adaptation. Adaptations can be categorized from at least two perspectives with respect to information. One is the passivity and activity of adaptation and the other is the type of information transmission. In Darwinian natural selection, organisms are selected among randomly generated traits under which individual organisms are passive in the sense that they do not process any environmental information. On the other hand, organisms can also adapt by sensing their environment and changing their traits. This is an active adaptation in that it makes use of environmental information. In terms of information transfer, adaptation through phenotypic heterogeneity, such as bacterial bet-hedging, is intragenerational in which traits are not passed on to the next generation. In contrast, adaptation through genetic diversity is intergenerational. The theory of population dynamics enables us to unify these various modes of adaptations and their properties can be analyzed qualitatively and quantitatively using techniques from quantitative genetics and information thermodynamics. In addition, such methods can be applied to situations where organisms can learn from past experiences and pass them on from generation to generation. In this work, we introduce the unified theory of biological adaptation based on population dynamics and show its potential applications to evaluate the fitness value of information and to analyze experimental lineage tree data. Finally, we discuss future perspectives for its development. This review article is an extended version of the Japanese article in SEIBUTSU BUTSURI Vol. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) act directly on pathogens and maintain the anti-inflammatory effects and activation of immunocompetent cells. Therefore, the activation of the immune system in poultry via the elevation of endogenous AMPs has been attempted. In this study, we focused on the host defense mechanisms in the bursa of Fabricius (BF) of Japanese quail, cloned the cDNA of cathelicidin (CATH)-1 to -3, and analyzed their expression sites. In situ hybridization experiments revealed the mRNA expression of the CATHs in the interfollicular epithelium surrounding the lumen of the quail BF, which suggests that each CATH may exert its antimicrobial action directly in the BF. The intravenous injection of bacterial lipoteichoic acid and lipopolysaccharide endotoxins into the quail promoted the mRNA expression of CATH-1 and CATH-3 in the BF. The addition of CATH-1 or CATH-2 at the time of the antigen injection into mice resulted in antiserum with high antibody titers. Ad libitum administration of butyrate, a short-chain fatty acid, in the drinking water induced an increase in CATH-2 mRNA expression in the BF under certain conditions. These results may improve the defense mechanisms of quail by stimulating CATH expression in the BF through their diet. [ABSTRACT FROM AUTHOR]

Background: Tumor size is an important prognostic factor in lung cancer in dogs, and the canine lung carcinoma stage classification (CLCSC) recently has been proposed to subdivide tumor sizes. It is unclear if the same classification scheme can be used for small‐breed dogs. Objectives: To investigate whether the tumor size classification of CLCS is prognostic for survival and progression outcomes in small‐breed dogs with surgically resected pulmonary adenocarcinomas (PACs). Animals: Fifty‐two client‐owned small‐breed dogs with PAC. Methods: Single‐center retrospective cohort study conducted between 2005 and 2021. Medical records of dogs weighing <15 kg with surgically resected lung masses histologically diagnosed as PAC were examined. Results: The numbers of dogs with tumor size ≤3 cm, >3 cm to ≤5 cm, >5 cm to ≤7 cm, or >7 cm were 15, 18, 14, and 5, respectively. The median progression‐free interval (PFI) and overall survival time (OST) were 754 and 716 days, respectively. In univariable analysis, clinical signs, lymph node metastasis, margin, and histologic grade were associated with PFI, and age, clinical signs, margin, and lymph node metastasis were associated with OST. Tumor size classification of CLCS was associated with PFI in all categories, and tumor size >7 cm was associated with OST. In multivariable analysis, tumor size >5 cm to ≤7 cm and margin were associated with PFI, and age was associated with OST. Conclusions and Clinical Importance: The tumor size classification of CLCS would be an important prognostic factor in small‐breed dogs with surgically resected PACs. [ABSTRACT FROM AUTHOR]

For patients with perforated diverticulitis, many reports have focused on laparoscopic surgery without primary anastomosis. We performed laparoscopic surgery with primary anastomosis in three patients (two with Hinchey stage III, one with IV), with a median age of 53 years, all female, and no prior medical history. They all were hemodynamically stable. The median operation time was 91 minutes (range: 56–227 minutes) and the median blood loss was 50 mL (range: 0–200 mL). Their post‐operative course was uneventful, and patients commenced oral intake at a median of 5 post‐operative days and were discharged at a median of 12 post‐operative days. This procedure may be an option for Hinchey stages III and IV diverticulitis. [ABSTRACT FROM AUTHOR]

Parechovirus‐A (PeV‐A) causes emerging infection in children, and clinical presentation depends on genotype. The virus has been investigated mainly in developed countries; however, data from developing countries, especially in Asia, are sparse. This study investigated whether PeV‐A circulated in children in Myanmar. This retrospective study evaluated PeV‐A in nasopharyngeal samples from children aged 1 month to 12 years who were hospitalized with acute lower respiratory infection at Yankin Children Hospital, Yangon, Myanmar, during the period from May 2017 to April 2019. Real‐time polymerase chain reaction (PCR) was used to detect PeV‐A, and PCR‐positive samples were used for genotyping and phylogenetic analysis. In total, 11/570 (1.9%) of samples were positive for PeV‐A; 7 were successfully genotyped by sequencing the VP3/VP1 region, as follows: PeV‐A1 (n = 4), PeV‐A5 (n = 1), PeV‐A6 (n = 1), and PeV‐A14 (n = 1). Median age was 10.0 months (interquartile range 4.0–12.0 months), and other respiratory viruses were detected in all cases. Phylogenetic analysis showed that all detected PeV‐A1 strains were in clade 1 A, which was a minor clade worldwide. Four PeV‐A genotypes were detected in Myanmar. The clinical impact of PeV‐A in children should be evaluated in future studies. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients. [ABSTRACT FROM AUTHOR]

Decentralized stochastic control (DSC) is a stochastic optimal control problem consisting of multiple controllers. DSC assumes that each controller is unable to accurately observe the target system and the other controllers. This setup results in two difficulties in DSC; one is that each controller has to memorize the infinite-dimensional observation history, which is not practical, because the memory of the actual controllers is limited. The other is that the reduction of infinite-dimensional sequential Bayesian estimation to finite-dimensional Kalman filter is impossible in general DSC, even for linear-quadratic-Gaussian (LQG) problems. In order to address these issues, we propose an alternative theoretical framework to DSC—memory-limited DSC (ML-DSC). ML-DSC explicitly formulates the finite-dimensional memories of the controllers. Each controller is jointly optimized to compress the infinite-dimensional observation history into the prescribed finite-dimensional memory and to determine the control based on it. Therefore, ML-DSC can be a practical formulation for actual memory-limited controllers. We demonstrate how ML-DSC works in the LQG problem. The conventional DSC cannot be solved except in the special LQG problems where the information the controllers have is independent or partially nested. We show that ML-DSC can be solved in more general LQG problems where the interaction among the controllers is not restricted. [ABSTRACT FROM AUTHOR]

In recent years, 3D data has been widely used in archaeology and in the field of conservation and restoration of cultural properties. Virtual restoration, which reconstructs the original state in virtual space, is one of the promising applications utilizing 3D scanning data. Though many studies of virtual restoration have been conducted, it is still challenging to restore the cultural properties that consist of multiple deformable components because it is not feasible to identify the original shape uniquely. As a solution to such a problem, we proposed a non-rigid 3D shape assembly method for virtually restoring wooden ships that are composed of multiple timbers. The deformed timber can be well represented by ruled surface. We proposed a free-form deformation method with a ruled surface and an assembly method to align the deformable components mutually. The method employs a bottom-up approach that does not require reference data for target objects. The proposed framework narrows down the searching space for optimization using the physical constraints of wooden materials, and it can also obtain optimal solutions. We also showed an experimental result, where we virtually restored King Khufu's first solar boat. The boat was originally constructed by assembling several timbers. The boat was reconstructed as a real object and is currently exhibited at a museum. However, unfortunately, the entire shape of the boat is slightly distorted. We applied the proposed method using archaeological knowledge and then showed the virtual restoration results using the acquired 3D data of the boat's components. [ABSTRACT FROM AUTHOR]

Memory-limited partially observable stochastic control (ML-POSC) is the stochastic optimal control problem under incomplete information and memory limitation. To obtain the optimal control function of ML-POSC, a system of the forward Fokker–Planck (FP) equation and the backward Hamilton–Jacobi–Bellman (HJB) equation needs to be solved. In this work, we first show that the system of HJB-FP equations can be interpreted via Pontryagin's minimum principle on the probability density function space. Based on this interpretation, we then propose the forward-backward sweep method (FBSM) for ML-POSC. FBSM is one of the most basic algorithms for Pontryagin's minimum principle, which alternately computes the forward FP equation and the backward HJB equation in ML-POSC. Although the convergence of FBSM is generally not guaranteed in deterministic control and mean-field stochastic control, it is guaranteed in ML-POSC because the coupling of the HJB-FP equations is limited to the optimal control function in ML-POSC. [ABSTRACT FROM AUTHOR]

Hundred and twenty four females with spondylolisthesis were divided into three groups (A group: anterolisthesis; P group: retrolisthesis; and AP group: antero-retrolisthesis), We reviewed their whole-spine radiographs and measured their standard sagittal parameters, including thoracic kyphosis (TK), pelvic incidence (PI), lumbar lordosis (LL), pelvic tilt (PT), and sacral slope (SS). The muscle strengths of the trunk flexor, trunk extensor, iliopsoas, and quadriceps were measured. Health-related quality of life was assessed using the Short Form 36-item Health Survey–physical component summary (SF-36 PCS). PI, SS, and LL-TK of participants in the P group were significantly lower than those in the A and AP groups (PI: P group vs. A group, p < 0.001, P group vs. AP group, p = 0.01), (SS: P group vs. A group, p = 0.001, P group vs. AP group, p = 0.003), (LL-TK: P group vs. A group, p < 0.001, P group vs. AP group, p = 0.049). TK of participants in the P and AP groups was greater than that of those in the A group. (P group vs. A group, p = 0.04, AP group vs. A group, p = 0.0025). The SF-36 PCS score in the P group was lower than that in the A and AP groups. (P group vs. A group, p = 0.004, P group vs. AP group, p = 0.012). The muscle strengths of the trunk flexor and trunk extensor and quadriceps in the P group were lower than those in the A groups. (Trunk flexor: P group vs. A group, p = 0.012), (Trunk extensor: P group vs. A group, p = 0.018), (Quadriceps: P group vs. A group, p = 0.011). In conclusion, female participants with degenerative retrolisthesis had a smaller PI and SS and a larger TK, along with decreased physical function and QoL scores than those with anterolisthesis. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) is a global health care challenge and a major cause of liver disease. To find new therapeutic avenues with a potential to functionally cure chronic Hepatitis B virus (HBV) infection, we performed a focused screen of epigenetic modifiers to identify potential inhibitors of replication or gene expression. From this work we identified isonicotinic acid inhibitors of the histone lysine demethylase 5 (KDM5) with potent anti-HBV activity. To enhance the cellular permeability and liver accumulation of the most potent KDM5 inhibitor identified (GS-080) an ester prodrug was developed (GS-5801) that resulted in improved bioavailability and liver exposure as well as an increased H3K4me3:H3 ratio on chromatin. GS-5801 treatment of HBV-infected primary human hepatocytes reduced the levels of HBV RNA, DNA and antigen. Evaluation of GS-5801 antiviral activity in a humanized mouse model of HBV infection, however, did not result in antiviral efficacy, despite achieving pharmacodynamic levels of H3K4me3:H3 predicted to be efficacious from the in vitro model. Here we discuss potential reasons for the disconnect between in vitro and in vivo efficacy, which highlight the translational difficulties of epigenetic targets for viral diseases. [ABSTRACT FROM AUTHOR]

Control problems with incomplete information and memory limitation appear in many practical situations. Although partially observable stochastic control (POSC) is a conventional theoretical framework that considers the optimal control problem with incomplete information, it cannot consider memory limitation. Furthermore, POSC cannot be solved in practice except in special cases. In order to address these issues, we propose an alternative theoretical framework, memory-limited POSC (ML-POSC). ML-POSC directly considers memory limitation as well as incomplete information, and it can be solved in practice by employing the technique of mean-field control theory. ML-POSC can generalize the linear-quadratic-Gaussian (LQG) problem to include memory limitation. Because estimation and control are not clearly separated in the LQG problem with memory limitation, the Riccati equation is modified to the partially observable Riccati equation, which improves estimation as well as control. Furthermore, we demonstrate the effectiveness of ML-POSC for a non-LQG problem by comparing it with the local LQG approximation. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluates the phantom attenuation correction (PAC) method as an alternative to maximum-likelihood attenuation correction factor (ML-ACF) correction in time-of-flight (TOF) brain positron emission tomography (PET) studies. Methods: In the PAC algorithm, a template emission image λ Ref and a template attenuation coefficient image μ Ref are prepared as a data set based on phantom geometry. Position-aligned attenuation coefficient image μ Acq is derived by aligning μ Ref using parameters that match the template emission image λ Ref to measured emission image λ Acq . Then, attenuation coefficient image μ Acq combined with a headrest image is used for scatter and attenuation correction in the image reconstruction. To evaluate the PAC algorithm as an alternative to ML-ACF, Hoffman 3D brain and cylindrical phantoms were measured to obtain the image quality indexes of contrast and uniformity. These phantoms were also wrapped with a radioactive sheet to obtain attenuation coefficient images using ML-ACF. Emission images were reconstructed with attenuation correction by PAC and ML-ACF, and the results were compared using contrast and uniformity as well as visual assessment. CT attenuation correction (CT-AC) was also applied as a reference. Results: The contrast obtained by ML-ACF was slightly overestimated due to its unique experimental condition for applying ML-ACF in Hoffman 3D brain phantom but the uniformity was almost equivalent among ML-ACF, CT-AC, and PAC. PAC showed reasonable result without overestimation compared to ML-ACF and CT-AC. Conclusions: PAC is an attenuation correction method that can ensure the performance in phantom test, and is considered to be a reasonable alternative to clinically used ML-ACF-based attenuation correction. [ABSTRACT FROM AUTHOR]

Extracellular histones play a dual role—antimicrobial and cytotoxic—in host defense. In this study, we evaluated the antimicrobial and cytotoxic activities of histone H3 and identified the responsible molecular regions for these properties. Broth microdilution assays indicated that histone H3 exhibits growth inhibitory activity against not only Gram-negative and -positive bacteria but also fungi. Observations under scanning electron microscopy (SEM) revealed that histone H3 induced morphological abnormalities on the cell surface of a wide range of reference pathogens. MTT assays and SEM observations indicated that histone H3 has strong cytotoxic and cell lytic effects on mammalian normal, immortal, and tumor cell lines. Assays using synthetic peptides corresponding to fragments 1–34 (H3DP1), 35–68 (H3DP2), 69–102 (H3DP3), and 103–135 (H3DP4) of histone H3 molecule demonstrated that its antimicrobial activity and cytotoxicity are elicited by the H3DP2 and H3DP3 protein regions, respectively. Enzyme-linked endotoxin binding assays indicated that histones H3 and H3DP1, H3DP2, and H3DP4, but not H3DP3, exhibited high affinities toward lipopolysaccharide and lipoteichoic acid. Our findings are expected to contribute to the development of new histone H3-based peptide antibiotics that are not cytotoxic. [ABSTRACT FROM AUTHOR]

The repertoire of T cell receptors encodes various types of immunological information. Machine learning is indispensable for decoding such information from repertoire datasets measured by next-generation sequencing (NGS). In particular, the classification of repertoires is the most basic task, which is relevant for a variety of scientific and clinical problems. Supported by the recent appearance of large datasets, efficient but data-expensive methods have been proposed. However, it is unclear whether they can work efficiently when the available sample size is severely restricted as in practical situations. In this study, we demonstrate that their performances can be impaired substantially below critical sample sizes. To complement this drawback, we propose MotifBoost, which exploits the information of short k-mer motifs of TCRs. MotifBoost can perform the classification as efficiently as a deep learning method on large datasets while providing more stable and reliable results on small datasets. We tested MotifBoost on the four small datasets which consist of various conditions such as Cytomegalovirus (CMV), HIV, a-chain, b-chain and it consistently preserved the stability. We also clarify that the robustness of MotifBoost can be attributed to the efficiency of k-mer motifs as representation features of repertoires. Finally, by comparing the predictions of these methods, we show that the whole sequence identity and sequence motifs encode partially different information and that a combination of such complementary information is necessary for further development of repertoire analysis. [ABSTRACT FROM AUTHOR]

Background: The recommended doxorubicin (DOX) dose for small dogs is 1 mg/kg. Recent data suggest that DOX‐induced gastrointestinal (GI) toxicosis can be reduced with maropitant treatment. Objectives: To investigate the incidence of adverse events (AEs) in small‐breed dogs administered a single 25 mg/m2 DOX followed by administration of maropitant (DOX25). The primary aim was to assess myelo‐ and GI toxicoses for 2 weeks after DOX administration. The secondary aim was to compare the incidence and grades of AEs found in the DOX25 group with a historical control group (DOX 1 mg/kg without administration of antiemetic or antidiarrheal medications). Animals: Nineteen small‐breed tumor‐bearing dogs. Methods: A prospective, observational study of tumor‐bearing dogs, weighing 5 to 10 kg, administered a single 25 mg/m2 dose of DOX IV, followed by administration of maropitant for the next 5 days. Results: Inappetence, vomiting, and diarrhea were found in 7/19, 2/19, and 6/19 of the DOX25 dogs, respectively. Neutropenia and thrombocytopenia was 12/19 and 3/19, respectively. Most AEs were grades 1 and 2, except for grades 3 and 4 inappetence and neutropenia in 3 and 4 dogs, respectively. Furthermore, febrile neutropenia occurred in 3/19 dogs in the DOX25 group. All AEs between the DOX25 and historical control groups were not significantly different. Conclusions and Clinical Importance: Vomiting and diarrhea were deemed acceptable with 25 mg/m2 DOX followed by maropitant treatment in 5 to 10 kg dogs; however, additional supportive care might be needed for dogs with inappetence and neutropenia. [ABSTRACT FROM AUTHOR]

To improve the performance of assisted reproductive technology, it is necessary to find an indicator that can identify and select embryos that will be born or be aborted. We searched for indicators of embryo selection by comparing born/abort mouse embryos. We found that asynchronous embryos during the 4–8-cell stage were predisposed to be aborted. In asynchronous mouse embryos, the nuclear translocation of YAP1 in some blastomeres and compaction were delayed, and the number of ICMs was reduced. Hence, it is possible that asynchronous embryos have abnormal differentiation. When the synchrony of human embryos was observed, it was confirmed that embryos that did not reach clinical pregnancy had asynchrony as in mice. This could make synchrony a universal indicator common to all animal species. [ABSTRACT FROM AUTHOR]

To improve the performance of assisted reproductive technology, it is necessary to find an indicator that can identify and select embryos that will be born or be aborted. We searched for indicators of embryo selection by comparing born/abort mouse embryos. We found that asynchronous embryos during the 4–8-cell stage were predisposed to be aborted. In asynchronous mouse embryos, the nuclear translocation of YAP1 in some blastomeres and compaction were delayed, and the number of ICMs was reduced. Hence, it is possible that asynchronous embryos have abnormal differentiation. When the synchrony of human embryos was observed, it was confirmed that embryos that did not reach clinical pregnancy had asynchrony as in mice. This could make synchrony a universal indicator common to all animal species. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate an image reconstruction algorithm, including a new maximum-likelihood attenuation correction factor (ML-ACF) for time of flight (TOF) brain positron emission tomography (PET). Methods: The implemented algorithm combines an ML-ACF method that simultaneously estimates both the emission image and attenuation sinogram from TOF emission data, and a scaling method based on anatomical features. To evaluate the algorithm's quantitative accuracy, three-dimensional brain phantom images were acquired and soft-tissue attenuation coefficients and emission values were analyzed. Results: The heterogeneous distributions of attenuation coefficients in soft tissue, skull, and nasal cavity were sufficiently visualized. The attenuation coefficient of soft tissue remained within 5% of theoretical value. Attenuation-corrected emission showed no lateral differences, and significant differences among soft tissue were within the error range. Conclusion: The ML-ACF-based attenuation correction implemented for TOF brain PET worked well and obtained practical levels of accuracy. [ABSTRACT FROM AUTHOR]

Resistant rice cultivars are an alternative of insecticide control for one of the major rice pests: the brown planthopper, Nilaparvatalugens (Hemiptera: Delphacidae). However, N.lugens has obtained virulence to resistant rice cultivars as same as insecticide resistance. The monitoring of virulence to differential cultivars is important for detections of the breakdown of resistance genes 'BPH' owned by the cultivars. We conducted long-term virulence monitoring (2001–2019) of differential cultivars in N. lugens immigrant populations in Japan. The virulence to the cultivars IR26 (BPH1), Mudgo (BPH1), and ASD7 (BPH2) was higher than that to other differential cultivars. The virulence to Babawee (BPH4) was lower than that to IR26, Mudgo, and ASD7, but it fluctuated over the immigrant years. The virulence to Kanto-PL7 (BPH3), Rathu Heenati (BPH3, BPH17) and Balamawee (BPH27, Three QTLs) was lower than that to other differential cultivars. The immigrant populations have therefore not developed virulence to three differential cultivars. These results suggest that N. lugens continued to develop virulence to differential cultivars that possess BPH1 and BPH2 after the breakdown. However, our results indicate that N.lugens could not break through the efficacy of differential cultivars possessing multiple BPH resistance genes. [ABSTRACT FROM AUTHOR]

Subthreshold depression (StD) is a depressive state that does not fulfil the criteria for major depressive disorder (MDD); however, StD has a risk for progression to MDD, and early intervention is therefore needed. Recently, a method for extracting neural extracellular vesicles (NEVs) excreted from neural cells of the brain from blood has been established, and microRNAs (miRNAs) encapsulated in NEVs are attracting interest because of their potential correlation to the pathogenesis of psychiatric disorders. However, miRNAs closely related to StD are still unknown. Therefore, to try to identify miRNAs closely related to the degree of StD, we examined the correlations between expression levels of some candidate miRNAs in NEVs and Patient Health Questionnaire-9 (PHQ-9) scores in subjects. Total RNAs in NEVs were extracted from serum of young adult males who had PHQ-9 scores of less than 10 (n = 9). Expression levels of eight miRNAs that were previously reported to be depression-associated miRNAs (let-7a-5p, miR-17-5p, miR-26b-5p, miR-34a-5p, miR-132-3p, miR-182-5p, miR-212-3p, and miR-1202) were measured using real-time PCR. Two of the eight miRNAs (miR-17-5p and miR-26b-5p) were stably detected. The relative expression levels of miR-17-5p showed a significant positive correlation with PHQ-9 scores (r = 0.85, p < 0.01), while those of miR-26b-5p showed no significance. Although a larger-scale analysis is needed due to the small number of subjects, these findings suggest that miR-17-5p in NEVs is a potential biomarker for StD. [ABSTRACT FROM AUTHOR]

High capacity transmission with a data rate over 10.66 Pb/s is demonstrated in a 13 km, 38-core-3-mode few-mode multi-core fiber. This was achieved with a single optical comb source to generate 368 × 24.5 GBaud 64- or 256-quadrature-amplitude-modulated signals in a 25 GHz wavelength channel grid in combination with a few-mode multi-core fiber with high uniformity amongst cores. We investigated essential transmission channel characteristics and found that mode-dependent loss strongly decreases the achievable data rates in some cores, while we did not observe a correlation between varying impulse response spread and data rate. We further did not find an influence of the (radial) position of a core within the cladding on the data rate. Finally, we explored the potential of multi-span transmission over the same fiber with transmission distances up to 65 km, showing a strong performance penalty from prototype components with sub-optimal transmission properties. [ABSTRACT FROM AUTHOR]

Histiocytic proliferative diseases are rare in cats, and their pathogenesis is poorly understood. In the present study, 25 cases of histiocytic sarcoma (HS) and 6 of feline progressive histiocytosis (FPH) were examined, and survival times were recorded in 19 cases. The immunophenotypes of tumor cells in these cases as well as of nonneoplastic feline histiocytes were characterized using formalin-fixed, paraffin-embedded tissues. An FPH cell line (AS-FPH01) and xenotransplant mouse model of FPH were also established. The median survival time of HS (150 days) was significantly shorter than that of FPH (470 days). Immunohistochemically, nonneoplastic histiocytes were immunopositive for various combinations of Iba-1, HLA-DR, E-cadherin, CD204, CD163, CD208, and MAC387. By immunohistochemistry, dermal interstitial dendritic cells (iDCs) and macrophages were CD204+/E-cadherin−, while epidermal Langerhans cells (LCs) were CD204−/E-cadherin+. Neoplastic cells of 4 FPH and 18 HS were CD204+/E-cadherin− (iDC/macrophage immunophenotype), while 2 FPH and 2 HS were CD204−/E-cadherin+ (LC immunophenotype), and 5 HS were CD204+/E-cadherin+ (LC-like cell immunophenotype). Furthermore, immunohistochemical and western blot analyses of AS-FPH01 cells derived from E-cadherin-negative FPH revealed that cultured cells were immunopositive for both CD204 and E-cadherin in vitro and in vivo. These results indicate that the neoplastic cells of feline HS and FPH were variably positive for iDC/macrophage and LC markers, and their immunophenotype changed in different microenvironments. The novel cell line established in the present study may serve as an experimental model of FPH that will enable further molecular and therapeutic studies on this disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the intra- and inter-observer reliabilities of the newly developed i-Scolioroller for scoliosis screening, and to determine the optimal i-Scolioroller measurement cutoff values for identifying adolescent scoliosis with a Cobb angle ≥ 20°. Methods: The i-Scolioroller displays the right- and left-side maximum inclination angle (Rmax, Lmax) during the forward bending test (FBT), as well as the angle of trunk inclination (ATI, i.e., whether the Rmax or Lmax is greater). Sum-ATI is defined as the sum of Rmax and Lmax. Intra-class correlation coefficients (ICC) of the ATI and sum-ATI measurements were calculated to analyze the intra- and inter-observer reliabilities for 10 plaster torsos in FBT positions obtained from patients with idiopathic scoliosis. The optimal cutoff values for scoliosis were determined using receiver operating characteristic (ROC) analysis of i-Scolioroller measurements versus Cobb angles obtained from the upright whole-spine radiographs of 112 adolescent outpatients. Results: The intra-observer ICCs for the ATI/sum-ATI for 3 observers were 0.851/0.856, 0.786/0.900, and 0.772/0.796, respectively, while the corresponding inter-observer ICCs for all participants were 0.733/0.745. On ROC analysis, an ATI of 8° was the optimal cutoff value for scoliosis (sensitivity and specificity: 79.2% and 70.0%, respectively). The optimal cutoff value for sum-ATI was 11° (sensitivity and specificity: 86.1% and 82.5%, respectively). The areas under the ROC curves were 0.859 for ATI and 0.908 for sum-ATI. Conclusion: The optimal cutoff values for identifying scoliosis using the i-Scolioroller were a combination of 11° for the sum-ATI and 8° for the ATI. [ABSTRACT FROM AUTHOR]

This longitudinal observational study investigated the relationship between changes in spinal sagittal alignment and changes in lower extremity coronal alignment. A total of 58 female volunteers who visited our institution at least twice during the 1992 to 1997 and 2015 to 2019 periods were investigated. We reviewed whole-spine radiographs and lower extremity radiographs and measured standard spinal sagittal parameters including pelvic incidence [PI], lumbar lordosis [LL], pelvic tilt [PT], sacral slope [SS] and sagittal vertical axis [SVA], and coronal lower extremity parameters including femorotibial angle (FTA), hip–knee–ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA) and mechanical lateral distal tibial angle (mLDTA). Lumbar spondylosis and knee osteoarthritis were assessed using the Kellgren–Lawrence (KL) grading system at baseline and at final follow-up. We investigated the correlation between changes in spinal sagittal alignment and lower extremity alignment and changes in lumbar spondylosis. The mean age [standard deviation (SD)] was 48.3 (6.3) years at first visit and 70.2 (6.3) years at final follow-up. There was a correlation between changes in PI-LL and FTA (R = 0.449, P < 0.001) and between PI-LL and HKA (R = 0.412, P = 0.001). There was a correlation between changes in lumbar spondylosis at L3/4 (R = 0.383, P = 0.004) and L4/5 (R = 0.333, P = 0.012) and the knee joints. Changes in lumbar spondylosis at L3/4 and L4/5 were related to changes in KOA. Successful management of ASD must include evaluation of the state of lower extremity alignment, not only in the sagittal phase, but also the coronal phase. [ABSTRACT FROM AUTHOR]

Background: Age-related height loss is a normal physical change that occurs in all individuals over 50 years of age. Although many epidemiological studies on height loss have been conducted worldwide, none have been long-term longitudinal epidemiological studies spanning over 30 years. This study was designed to investigate changes in adult spinal deformity and examine the relationship between adult spinal deformity and height loss.Methods: Fifty-three local healthy subjects (32 men, 21 women) from Furano, Hokkaido, Japan, volunteered for this longitudinal cohort study. Their heights were measured in 1983 and again in 2017. Spino-pelvic parameters were compared between measurements obtained in 1983 and 2017. Individuals with height loss were then divided into two groups, those with degenerative spondylosis and those with degenerative lumbar scoliosis, and different characteristics were compared between the two groups.Results: The mean age of the subjects was 44.4 (31-55) years at baseline and 78.6 (65-89) years at the final follow-up. The mean height was 157.4 cm at baseline and 153.6 cm at the final follow-up, with a mean height loss of 3.8 cm over 34.2 years. All parameters except for thoracic kyphosis were significantly different between measurements taken in 1983 and 2017 (p < 0.05). Height loss in both sexes was related to changes in pelvic parameters including pelvic incidence-lumbar lordosis (R = 0.460 p = 0.008 in men, R = 0.553 p = 0.012 in women), pelvic tilt (R = 0.374 p = 0.035 in men, R = 0.540 p = 0.014 in women), and sagittal vertical axis (R = 0.535 p = 0.002 in men, R = 0.527 p = 0.017 in women). Greater height loss was more commonly seen in women (p = 0.001) and in patients with degenerative lumbar scoliosis (p = 0.02).Conclusions: This longitudinal study revealed that height loss is more commonly observed in women and is associated with adult spinal deformity and degenerative lumbar scoliosis. Height loss is a normal physical change with aging, but excessive height loss is due to spinal kyphosis and scoliosis leading to spinal malalignment. Our findings suggest that height loss might be an early physical symptom for spinal malalignment. [ABSTRACT FROM AUTHOR]

Summary Phenotypic variability in a population of cells can work as the bet-hedging of the cells under an unpredictably changing environment, the typical example of which is the bacterial persistence. To understand the strategy to control such phenomena, it is indispensable to identify the phenotype of each cell and its inheritance. Although recent advancements in microfluidic technology offer us useful lineage data, they are insufficient to directly identify the phenotypes of the cells. An alternative approach is to infer the phenotype from the lineage data by latent-variable estimation. To this end, however, we must resolve the bias problem in the inference from lineage called survivorship bias. In this work, we clarify how the survivorship bias distorts statistical estimations. We then propose a latent-variable estimation algorithm without the survivorship bias from lineage trees based on an expectation–maximization (EM) algorithm, which we call lineage EM algorithm (LEM). LEM provides a statistical method to identify the traits of the cells applicable to various kinds of lineage data. Availability and implementation An implementation of LEM is available at https://github.com/so-nakashima/Lineage-EM-algorithm. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Intracellular reactions are intrinsically stochastic. Nonetheless, cells can reliably respond to the changing environment by sensing their target molecules sensitively and specifically, even with the existence of abundant structurally-similar non-target molecules. The mechanism of how the cells can balance and achieve such different characteristics is not yet fully understood. In this work, we demonstrate that these characteristics can be attained by a ligand-induced stochastic cluster formation of receptors via the noise-induced symmetry breaking, in which the intrinsic stochasticity works to enhance sensitivity and specificity. We also show that the noise-induced cluster formation enables cells to detect the target ligand reliably by compensating the abundant non-target ligands in the environment. The proposed mechanism may lead to a deeper understanding of a biological function of the receptor clustering and provide an alternative candidate for the reliable ligand detection to the kinetic proofreading. [ABSTRACT FROM AUTHOR]

The genome is packaged and organized in an ordered, non-random manner and specific chromatin segments contact nuclear substructures to mediate this organization. Transfer RNA genes (tDNAs) are binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the role of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacks any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromatin architecture or chromosome tethering and mobility. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long-range HML-HMR heterochromatin clustering with concomitant effects on gene silencing. We propose that the tDNAs primarily affect local chromatin structure that result in effects on long-range chromosome architecture. [ABSTRACT FROM AUTHOR]

We demonstrated simultaneous usage of 228 spatial channels (effectively) within a strand of fiber. We fabricated a 13-km 39-core 3-mode fiber and constructed a bi-directional space division multiplexing (SDM) transmission setup by using cascaded spatial multiplexers on both fiber ends. Aggregated intercore crosstalk and return loss of the system were below −35 and above 31 dB, respectively, over the C and L bands. The feasibility of using bi-directional SDM transmission was investigated using 10 GBaud, 37.38-Gb/s dual-polarization QPSK signals at 1550 nm and coherent detection with a 6 × 6 multi-input-multi-output equalizer. Excellent transmission properties were obtained for most spatial channels. [ABSTRACT FROM AUTHOR]