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Plasmalogens (Pls) are specialized phospholipids integral to brain health, whose decline due to aging and stress contributes to cognitive impairment and neuroinflammation. This study explores the potential of a novel Pls derivative, KIT-13 (1-O-octadecyl-2-arachidonoyl-sn-glycerol-3-phosphoethanolamine), in mitigating neuroinflammation and enhancing cognition. When administered to mice, KIT-13 exhibited potent memory enhancement attributed to upregulated brain-derived neurotrophic factor (BDNF), a key player in cognitive processes. In vitro experiments with neuronal cells revealed KIT-13’s ability to induce robust cellular signaling, surpassing natural plasmalogens. KIT-13 also promoted neurogenesis and inhibited apoptosis of neuronal-like cells, highlighting its potential in fostering neuronal growth and plasticity. Additionally, KIT-13 treatments reduced pro-inflammatory cytokine expression and attenuated glial activation in the brain. KIT-13’s superior efficacy over natural Pls positions it as a promising therapeutic candidate for neurodegenerative conditions such as Alzheimer’s disease, characterized by cognitive decline and neuroinflammation. This study presents KIT-13 as an innovative approach for addressing cognitive impairment and neuroinflammatory pathologies.

Reactive oxygen species (ROS) play critical roles in metabolism and disease, yet a comprehensive analysis of the cellular response to oxidative stress is lacking. To systematically identify regulators of oxidative stress, we conducted genome-wide Cas9/CRISPR and shRNA screens. This revealed a detailed picture of diverse pathways that control oxidative stress response, ranging from the TCA cycle and DNA repair machineries to iron transport, trafficking, and metabolism. Paradoxically, disrupting the pentose phosphate pathway (PPP) at the level of phosphogluconate dehydrogenase (PGD) protects cells against ROS. This dramatically alters metabolites in the PPP, consistent with rewiring of upper glycolysis to promote antioxidant production. In addition, disruption of peroxisomal import unexpectedly increases resistance to oxidative stress by altering the localization of catalase. Together, these studies provide insights into the roles of peroxisomal matrix import and the PPP in redox biology and represent a rich resource for understanding the cellular response to oxidative stress.

We envisioned that the rumen of Kitasato Yakumo beef cattle would contain unique microorganisms which produce bioactive compounds as their defense response to the external environment. The variety of microorganisms were collected from the feces of Kitasato Yakumo beef cattle. We evaluated the biological activity of the culture broth of the isolated strains, proving the utility of our approach. [ABSTRACT FROM AUTHOR]

In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated as an antifungal active compound from Aspergillus burnettii. However, the antifungal activity of 1 has been revealed in only one fungal species, and the mechanism of action of 1 remains unknown. After the validation of mitochondrial function inhibitory of 1 , we envisioned a new antimalarial drug discovery platform based on mitochondrial function inhibitory activity. We evaluated antimalarial activity and 1 showed antimalarial activity against Plasmodium falciparum FCR3 (chloroquine sensitive) and the K1 strain (chloroquine resistant). Our study revealed the utility of our original screening system based on a multidrug-sensitive yeast and mitochondrial function inhibitory activity for the discovery of new antimalarial drug candidates. [ABSTRACT FROM AUTHOR]

Plasmalogens (Pls) are specialized phospholipids integral to brain health, whose decline due to aging and stress contributes to cognitive impairment and neuroinflammation. This study explores the potential of a novel Pls derivative, KIT-13 (1-O-octadecyl-2-arachidonoyl-sn-glycerol-3-phosphoethanolamine), in mitigating neuroinflammation and enhancing cognition. When administered to mice, KIT-13 exhibited potent memory enhancement attributed to upregulated brain-derived neurotrophic factor (BDNF), a key player in cognitive processes. In vitro experiments with neuronal cells revealed KIT-13’s ability to induce robust cellular signaling, surpassing natural plasmalogens. KIT-13 also promoted neurogenesis and inhibited apoptosis of neuronal-like cells, highlighting its potential in fostering neuronal growth and plasticity. Additionally, KIT-13 treatments reduced pro-inflammatory cytokine expression and attenuated glial activation in the brain. KIT-13’s superior efficacy over natural Pls positions it as a promising therapeutic candidate for neurodegenerative conditions such as Alzheimer’s disease, characterized by cognitive decline and neuroinflammation. This study presents KIT-13 as an innovative approach for addressing cognitive impairment and neuroinflammatory pathologies. [ABSTRACT FROM AUTHOR]

Mukaku Kishu (‘MK’), a small sized mandarin, is an important source of seedlessness in citrus breeding. Identification and mapping the gene(s) governing ‘MK’ seedlessness will expedite seedless cultivar development. In this study, two ‘MK’-derived mapping populations- LB8-9 Sugar Belle® (‘SB’) × ‘MK’ (N=97) and Daisy (‘D’) × ‘MK’ (N=68) were genotyped using an Axiom_Citrus56 Array encompassing 58,433 SNP probe sets, and population specific male and female parent linkage maps were constructed. The parental maps of each population were integrated to produce sub-composite maps, which were further merged to develop a consensus linkage map. All the parental maps (except ‘MK_D’) had nine major linkage groups, and contained 930 (‘SB’), 810 (‘MK_SB’), 776 (‘D’) and 707 (‘MK_D’) SNPs. The linkage maps displayed 96.9 (‘MK_D’) to 98.5% (‘SB’) chromosomal synteny with the reference Clementine genome. The consensus map was comprised of 2588 markers including a phenotypic seedless (Fs)-locus and spanned a genetic distance of 1406.84 cM, with an average marker distance of 0.54 cM, which is substantially lower than the reference Clementine map. For the phenotypic Fs-locus, the distribution of seedy and seedless progenies in both ‘SB’ × ‘MK’ (55:42, χ2 = 1.74) and ‘D’ × ‘MK’ populations (33:35, χ2 = 0.06) followed a test cross pattern. The Fs-locus mapped on chromosome 5 with SNP marker ‘AX-160417325’ at 7.4 cM in ‘MK_SB’ map and between two SNP markers ‘AX-160536283’ and ‘AX-160906995’ at a distance of 2.4 and 4.9 cM, respectively in ‘MK_D’ map. The SNPs ‘AX-160417325’ and ‘AX-160536283’ correctly predicted seedlessness of 25-91.9% progenies in this study. Based on the alignment of flanking SNP markers to the Clementine reference genome, the candidate gene for seedlessness hovered in a ~ 6.0 Mb region between 3.97 Mb (AX-160906995) to 10.00 Mb (AX-160536283). This region has 131 genes of which 13 genes (belonging to seven gene families) reportedly express in seed coat or developing embryo. The findings of the study will prove helpful in directing future research for fine mapping this region and eventually underpinning the exact causative gene governing seedlessness in ‘MK’.

Ethanolamine-containing alkenyl ether glycerophospholipids, plasmalogens, are major cell membrane components of mammalian cells that activate membrane protein receptors such as ion transporters and G-protein coupled receptors. However, the mechanism by which plasmalogens modulate receptor function is unknown. Here, we found that exogenously added plasmalogens activate transient receptor potential cation channel subfamily C member 4 (TRPC4) to increase Ca2+ influx, followed by calcium/calmodulin-dependent protein kinase 2-mediated phosphorylation of AMP-activated protein kinase (AMPK). Upon topical application of plasmalogens to the skin of mice, AMPK activation was observed in TRPC4-expressing hair bulbs and hair follicles. Here, TRPC4 was co-localized with the leucine-rich repeat containing G protein-coupled receptor 5, a marker of hair-follicle stem cells, leading to hair growth. Collectively, this study indicates that plasmalogens could function as gate openers for TRPC4, followed by activating AMPK, which likely accelerates hair growth in mice.

Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. The synthesis of plasmalogens is initiated in peroxisomes and completed in the endoplasmic reticulum. Plasmalogens are transported to the post-Golgi compartment, including endosomes and plasma membranes, in a manner dependent on ATP, but not vesicular transport. Plasmalogens are preferentially localized in the inner leaflet of the plasma membrane in a manner dependent on P4-type ATPase ATP8B2, that associates with the CDC50 subunit. Plasmalogen biosynthesis is spatiotemporally regulated by a feedback mechanism that senses the amount of plasmalogens in the inner leaflet of the plasma membrane and controls the stability of fatty acyl-CoA reductase 1 (FAR1), the rate-limiting enzyme for plasmalogen biosynthesis. The physiological consequences of such asymmetric localization and homeostasis of plasmalogens are discussed in this review.

Plasmalogens are a subclass of glycerophospholipid containing vinyl-ether bond at the sn-1 position of glycerol backbone. Ethanolamine-containing plasmalogens (plasmalogens) are major constituents of cellular membranes in mammalian cells and de novo synthesis of plasmalogens largely contributes to the homeostasis of plasmalogens. Plasmalogen biosynthesis is regulated by a feedback mechanism that senses the plasmalogen level in the inner leaflet of the plasma membrane and regulates the stability of fatty acyl-CoA reductase 1 (Far1), a rate-limiting enzyme for plasmalogen biosynthesis. However, the molecular mechanism underlying the localization of plasmalogens in cytoplasmic leaflet of plasma membrane remains unknown. To address this issue, we attempted to identify a potential transporter of plasmalogens from the outer to the inner leaflet of plasma membrane by focusing on phospholipid flippases, type-IV P-type adenosine triphosphatases (P4-ATPase), localized in the plasma membranes. We herein show that knockdown of ATP8B2 belonging to the class-1 P4-ATPase enhances localization of plasmalogens but not phosphatidylethanolamine in the extracellular leaflet and impairs plasmalogen-dependent degradation of Far1. Furthermore, phosphorylation of protein kinase B (AKT) is downregulated by lowering the expression of ATP8B2, which leads to suppression of cell growth. Taken together, these results suggest that enrichment of plasmalogens in the cytoplasmic leaflet of plasma membranes is mediated by ATP8B2 and this asymmetric distribution of plasmalogens is required for sensing plasmalogens as well as phosphorylation of AKT.

Objective: Evaluation of the healing and toxicological effects of Copaifera duckei Dwyer oleoresin (CDO). Materials and Methods: Rodents with skin lesions were divided into nine groups, including daily treatments with 1, 3 and 10% CDO, collagenase, antibiotic ointment and control groups, for 14 days. Results: Treatment with 10% CDO reduced skin edema and hyperplasia, demonstrating anti-inflammatory effect of the oil. Reduction in the wound area was observed, indicating the healing effect of CDO. Histopathological analysis showed increases in angiogenesis and re-epithelialization in animals treated with the highest concentration. On the other hand, no alterations in ulcerations, inflammatory infiltrate, hemorrhage, congestion, degeneration, percentage of collagen fibers, number of cells stained with anti-macrophage migration inhibitory factor, or density of area stained with anti-collagen I and III were found. Toxicogenetic analysis revealed no differences in micronucleus frequencies or in the ratio of polychromatic erythrocytes to total erythrocytes between treated and negative control, demonstrating the absence of genotoxicity and cytotoxicity, respectively. There was no difference in levels of liver enzymes among groups, indicating the absence of hepatotoxicity. Conclusion: Formulations of CDO exerted beneficial effects on the stages of cutaneous wound healing and are promising options for the treatment of wounds.

ABSTRACT The biological behaviour of the tumours vary according to the species in which they occur, its location within the cavity, clinical stage and histopathological nature. Lingual neoplasms are generally uncommon in companion animals. Rhabdomyosarcomas are malignant, solid, aggressive formations with high metastatic potential. The clinical signs are variable and a definitive diagnosis can only be reached through histopathological analysis of biopsy and necropsy specimen. In some cases, immunohistochemical study may be needed to confirm the diagnosis. This paper aims to highlight important points about this uncommon condition in dogs, using a case report of lingual rhabdomyosarcoma, which showed no evidence of metastasis after diagnosis, nor of local recurrence after surgical excision with a wide safety margin. It was concluded that early diagnosis, the correct interpretation of the complementary tests and the appropriate therapeutic approach contributed to improving the quality of life and survival of the patient in question.

Anti-microbial resistance (AMR) is one of the greatest threats to global health. The continual battle between the emergence of AMR and the development of drugs will be extremely difficult to stop as long as traditional anti-biotic approaches are taken. In order to overcome this impasse, we here focused on the type III secretion system (T3SS), which is highly conserved in many Gram-negative pathogenic bacteria. The T3SS is known to be indispensable in establishing disease processes but not essential for pathogen survival. Therefore, T3SS inhibitors may be innovative anti-infective agents that could dramatically reduce the evolutionary selective pressure on strains resistant to treatment. Based on this concept, we previously identified a polyketide natural product, aurodox (AD), as a specific T3SS inhibitor using our original screening system. However, despite its promise as a unique anti-infective drug of AD, the molecular target of AD has remained unclear. In this paper, using an innovative chemistry and genetic biology-based approach, we show that AD binds to adenylosuccinate synthase (PurA), which suppresses the production of the secreted proteins from T3SS, resulting in the expression of bacterial virulence both in vitro and in vivo experiments. Our findings illuminate the potential of PurA as a target of anti-infective drugs and vaccination and could open a avenue for application of PurA in the regulation of T3SS. [ABSTRACT FROM AUTHOR]

ABSTRACT: Canine hip dysplasia (CHD) is a common condition observed in the surgical clinics for small animals. Among the surgical techniques for management of CHD, triple pelvic osteotomy and sacroiliac wedge promote acetabular lateral axial rotation (ventroversion), increasing acetabular coverage and joint stability. The present study aimed to evaluate radiographically, by measuring the Norberg angle (NA) and the acetabular coverage percentage (ACP), the acetabular ventroversion induced by the sacroiliac wedge technique, with or without pelvic osteotomies; we also checked the feasibility of wedges made of polyamide with an angulation of 20° and 30°. The software used to measure NA and ACP was AutoCAD® 2009. Pelves from 10 canine corpses were evaluated radiographically at four time-points: M0 (Control Group), M1 (wedges of 20° and 30°), M2 and M3 (wedges associated with bilateral pubis and ischium osteotomies, respectively). There was no significant increase in the acetabular ventroversion at M1, M2, and M3. The polyamide sacroiliac wedge technique proved to be feasible, stable, and easy to apply. Further, the software proved to be efficient and easy to use for NA and ACP measurements. In the present study, even in the cases of non-dysplasic adult canine corpses, it was concluded that the sacroiliac wedge technique does not require to be accompanied by pubis and ischial osteotomies because they did not significantly increase the NA and ACP.

Abstract GNSS-A (combination of Global Navigation Satellite System and Acoustic ranging) observations have provided important geophysical results, typically based on static GNSS-Acoustic positioning methods. Recently, continuous GNSS-Acoustic observations using a moored buoy have been attempted. Precise kinematic GNSS-Acoustic positioning is essential for these approaches. In this study, we developed a new kinematic GNSS-A positioning method using the extended Kalman filter (EKF). As for the observation model, parameters expressing underwater sound speed structure [nadir total delay (NTD) and underwater delay gradients] are defined in a similar manner to the satellite geodetic positioning. We then investigated the performance of the new method using both the synthetic and observational data. We also investigated the utility of a GNSS-Acoustic array geometry composed of multi-angled transponders for detection of vertical displacements. The synthetic tests successfully demonstrated that (1) the EKF-based GNSS-Acoustic positioning method can resolve the GNSS-Acoustic array displacements, as well as NTDs and underwater delay gradients, more precisely than those estimated by the conventional kinematic positioning methods and (2) precise detection of vertical displacements can be achieved using multi-angled transponders and EKF-based GNSS-Acoustic positioning. Analyses of the observational data also demonstrated superior performance of the EKF-based GNSS-Acoustic positioning method, when assuming a laterally stratified sound speed structure. Further, we found three superior aspects to the EKF-based array positioning method when using observational data: (1) robustness of the solutions when some transponders fail to respond, (2) precise detection for an abrupt vertical displacement, and (3) applicability to real-time positioning when sampling interval of the acoustic ranging is shorter than 30 min. The precision of the detection of abrupt steps, such as those caused by coseismic slips, is ~ 5 cm (1σ) using this method, an improvement on the precision of ~ 10 cm of conventional methods. Using the observational data, the underwater delay gradients and the horizontal array displacements could not be accurately solved even using the new method. This suggests that short-wavelength spatial heterogeneity exists in the actual ocean sound speed structure, which cannot be approximated using a simple horizontally graded sound speed structure.

Abstract We assessed the positioning accuracy of GNSS-Acoustic (GNSS-A) measurement using a slackly moored buoy. A key feature of real-time buoy-based GNSS-A measurement is that positioning must be performed via single ranging from an arbitrary observation position and encompassing the drifting range of the buoy. In this study, slack-line mooring was employed to resist strong Kuroshio current of up to 5.5 knots in the Nankai Trough. During a year-long sea trial, the buoy drifted within a circle of ~ 4000 m radius, which is much larger than the dimension of a seafloor transponder array. In the sea trial, more than 500 successful regular and on-demand ranging measurements were obtained at various observation positions. The results show that the horizontal positioning accuracy (2σ) of the array for single ranging was 46 cm when the buoy was inside the array and 97 cm when it was outside the array. These accuracies are comparable to those achieved through single ranging in traditional ship-based surveys at the same site. In addition to the distance dependency, we observed directivity in the accuracy, depending on the geometry between an observation point and seafloor transponders. To interpret the accuracy degradation and directivity as a function of observation position, we calculated error ellipses using a dilution-of-precision (DOP) analysis procedure for GNSS-A positioning. The error ellipses clearly illustrate that the variance in array positions is large in the line-of-sight direction from an observation point to the array center. We translated the error ellipses to positioning accuracies using the standard deviation of travel time residuals when an array position is estimated using all pings. The positioning accuracy resulting from the translation corresponded to that obtained using array positions in a buoy observation. The DOP analysis results and their translation into positioning accuracies enabled a detailed assessment of the directional accuracy of GNSS-A positioning at an arbitrary observation position, which is important for real-time measurement of seafloor movement in the event of a huge earthquake.

O crescente avanço da medicina veterinária e desenvolvimento de suas subáreas exigem o aprimoramento de métodos para o avanço das técnicas cirúrgicas e a realização de procedimentos especializados que reduzam complicações no pós-operatório, principalmente na ortopedia veterinária. Diante disso, o incremento das técnicas necessita de conhecimento prévio sobre a composição do tecido ósseo e de suas principais funções. Sabe-se que o tecido ósseo é composto por quatro tipos celulares, os osteoblastos, osteócitos, osteoclastos e células osteoprogenitoras, que são responsáveis pela formação, reparação e remodelagem do tecido. Atualmente, a utilização de enxertos ósseos vem sendo amplamente empregada, pois utilizam o tecido ósseo como a base da técnica, exercendo funções que estimulam a gênese de um novo tecido (tecido ósseo). Estes são de grande valia para o tratamento de fraturas cominutivas, artrodeses, exérese de tumores ósseos, osteomielite, má união e não união óssea e osteotomias corretivas, minimizando as chances de amputação do membro acometido. Uma gama de classificações são encontradas para descrever os tipos de enxertos ósseos e de acordo com sua origem, estes podem ser autógenos, alógenos, xenógenos e alopásticos e quanto a classificação estrutural, podem ser chamados de esponjosos, corticais, corticoesponjosos, dependendo do sítio doador. Cada enxerto possui características e funções distintas que devem ser avaliadas antes do processo de enxertia, para que melhor se adeque ao tipo de paciente. Sendo assim, o intuito do trabalho é descrever sobre os enxertos ósseos e suas aplicações na medicina veterinária.