Strange metal from a frustration-driven charge order instability.

Interparticle interactions are self-conflicting rather than cooperative on particular lattices. When such geometrical frustration occurs, charge ordering (CO) can be destabilized into non-trivial charge states such as the recently observed charge glass (CG). A more extreme case is the frustration-induced quantum melting of the CO that has been theoretically proposed. Here, we report d.c. charge transport and noise spectroscopy measurements for a triangular-lattice organic conductor situated close to the CO or CG. Our experiments demonstrate that these materials can host a strange metal with unusual charge dynamics, which we attribute to frustration-induced fluctuations of the CO or CG. Our results also show that the anomalous charge fluctuations can freeze into an insulating state when uniaxial stress is applied, which reduces the geometrical frustration. The present observations suggest the existence of the frustration-induced quantum melting of charges analogous to spin liquids.

Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis.

OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. DESIGN: To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. RESULTS: SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1ß, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. CONCLUSIONS: Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.

Large Enhancement of Thermoelectric Efficiency Due to a Pressure-Induced Lifshitz Transition in SnSe.

The Lifshitz transition, a change in Fermi surface topology, is likely to greatly influence exotic correlated phenomena in solids, such as high-temperature superconductivity and complex magnetism. However, since the observation of Fermi surfaces is generally difficult in the strongly correlated systems, a direct link between the Lifshitz transition and quantum phenomena has been elusive so far. Here, we report a marked impact of the pressure-induced Lifshitz transition on thermoelectric performance for SnSe, a promising thermoelectric material without a strong electron correlation. By applying pressure up to 1.6 GPa, we have observed a large enhancement of the thermoelectric power factor by more than 100% over a wide temperature range (10-300 K). Furthermore, the high carrier mobility enables the detection of quantum oscillations of resistivity, revealing the emergence of new Fermi pockets at ∼0.86 GPa. The observed thermoelectric properties linked to the multivalley band structure are quantitatively reproduced by first-principles calculations, providing novel insight into designing the SnSe-related materials for potential valleytronic as well as thermoelectric applications.

Endocytosis following dopamine D2 receptor activation is critical for neuronal activity and dendritic spine formation via Rabex-5/PDGFRß signaling in striatopallidal medium spiny neurons.

Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disorders, making those receptors targets for antipsychotic drugs. Here, we report that novel signaling through the intracellularly localized D2R long isoform (D2LR) elicits extracellular signal-regulated kinase (ERK) activation and dendritic spine formation through Rabex-5/platelet-derived growth factor receptor-ß (PDGFRß)-mediated endocytosis in mouse striatum. We found that D2LR directly binds to and activates Rabex-5, promoting early-endosome formation. Endosomes containing D2LR and PDGFRß are then transported to the Golgi apparatus, where those complexes trigger Gαi3-mediated ERK signaling. Loss of intracellular D2LR-mediated ERK activation decreased neuronal activity and dendritic spine density in striatopallidal medium spiny neurons (MSNs). In addition, dendritic spine density in striatopallidal MSNs significantly increased following treatment of striatal slices from wild-type mice with quinpirole, a D2R agonist, but those changes were lacking in D2LR knockout mice. Moreover, intracellular D2LR signaling mediated effects of a typical antipsychotic drug, haloperidol, in inducing catalepsy behavior. Taken together, intracellular D2LR signaling through Rabex-5/PDGFRß is critical for ERK activation, dendritic spine formation and neuronal activity in striatopallidal MSNs of mice.

Evaluation of the fat plane of the pancreatic groove using multidetector CT.

AIM: To assess the pancreatic groove fat plane in the normal population and compare this with the fat plane in patients with groove pancreatitis or carcinoma using multidetector computed tomography (CT). MATERIAL AND METHODS: The pancreatic groove fat plane was evaluated retrospectively in 460 normal subjects (normal group), and in 25 patients with groove pancreatitis or carcinoma (pathology group) using 5 mm- and 1 mm-thick slices of unenhanced axial multidetector CT images. Two investigators independently assessed the degree of pancreatic groove fat plane visualisation using a four-point scale (grade 1: visualisation of 0-25%, grade 2: 26-50%, grade 3: 51-75%, grade 4: 76-100%). Pancreatic parenchymal condition, age, sex, body mass index, diabetes mellitus, and dyslipidaemia were also evaluated. RESULTS: The interobserver agreement for the visualisation grades was almost perfect (k-value = 0.95). In the normal group, grade 4 visualisation of the pancreatic groove fat plane was more common in those aged >80 years (78.6%) compared with younger age groups. Pancreatic atrophy and fatty infiltration significantly improved fat plane visualisation. In the pathology group, grade 4 visualisation of the pancreatic groove fat plane was not seen in either groove carcinoma or pancreatitis. A cut-off point of ≤50% visualisation of the pancreatic groove fat plane showed 95% sensitivity and 82% specificity for detecting possible abnormalities in older patients (>60 years). The clinical factors investigated were not significantly related to pancreatic groove fat plane visualisation. CONCLUSION: Pancreatic groove fat plane visualisation could be a good predictor for detecting groove abnormalities.

Fifty years of child height and weight in Japan and South Korea: Contrasting secular trend patterns analyzed by SITAR.

Objectives Japanese and South Koreans have traditionally been shorter than Europeans, but have recently become appreciably taller. The aim was to quantify the secular trend patterns in height and weight growth in the two countries over 50 years using the SITAR growth curve model. Methods Data on mean height and weight by sex in 1-year age groups from 1 to 20 years were obtained by decade in South Korea (1965-2005) and Japan (1950-2010). The data were analyzed using SITAR (SuperImposition by Translation And Rotation), which estimates a mean curve and three adjustments-size, timing and intensity-reflecting how the individual surveys differ from the mean. A sensitivity analysis compared results for the Japanese data based on cohort as well as period. Results Growth patterns in the two countries changed dramatically over the study period, affecting not only height and weight but also developmental age, in that the growth period advanced in timing and shrank in duration. SITAR fitted the data well. The trends were larger in South Korea than Japan, and puberty timing in Japan stabilized by 1970. Most of the height increment seen in adults had already accrued by age 1.5 years, whereas the adult weight increment accrued throughout childhood. Conclusions The secular height trend in these countries represents increased growth in the long bones during infancy, so it can be viewed as the inverse of stunting. There are striking country differences in growth pattern, but they are not easily explained by differences in national income, diet or lifestyle.

A rapid method to screen poisoning causative agents in an acute care hospital in Japan.

WHAT IS KNOWN AND OBJECTIVE: A simple, rapid analysis is required to simultaneously analyse medicinal toxicants in emergency medical care. In this regard, the analysis of blood samples by LC-MS/MS equipped with a spin column, involving a rapid, simple pretreatment, has attracted attention. In this study, sample pretreatment using a Monospin C18 column was performed to screen 11 medicinal toxicants in blood samples by LC-MS/MS. METHODS: Serum samples supplemented with 11 medical toxicants-acetaminophen, salicylic acid, nitrazepam, diphenhydramine, bromvalerylurea, phenobarbital, amitriptyline, risperidone, fenitrothion, malathion and methomyl-were pretreated with the Monospin C18 column according to Pretreatment I and Pretreatment II, followed by LC-MS/MS analysis. RESULTS AND DISCUSSION: All toxicants were not detected by a single pretreatment method but were detected by two pretreatment methods. According to Pretreatment I, 10 medicinal toxicants-excluding salicylic acid-were detected. The recovery rates of all medicinal toxicants, except acetaminophen and methomyl, were greater than or equal to 80%. Salicylic acid was detected by Pretreatment II, with a recovery rate of 57.1%. Although the coefficient of variation was less than that reported in previous methods employing SPE, the recovery rates were better possibly because of the simultaneous adsorption of water- and lipid-soluble substances and evaporation by drying. WHAT IS NEW AND CONCLUSION: As LC-MS/MS analysis using Monospin C18 can simultaneously and rapidly screen several medicinal toxicants present in blood samples, it is expected to be highly suitable for clinical settings.

Retroperitoneal leiomyosarcoma: a case report.

Retroperitoneal leiomyosarcoma is a relatively rare and aggressive tumor. Because of its rarity, it is difficult to arrive at a definite diagnosis preoperatively and to design an effective strategy. Here the authors report a case of peritoneal leiomyosarcoma in which diagnosis was difficult because the clinical course resembled that of ovarian cancer. A 77-year-old woman diagnosed with ovarian cancer underwent laparotomy. The excised tumor contained a necrotic polypoid mass that histologically displayed the features of leiomyosarcoma. The patient received adjuvant chemotherapy with a combination of gemcitabine and docetaxel but died two months after surgery owing to the aggressive behavior of the tumor. Because the preoperative diagnosis in this case was ovarian cancer, arriving at a treatment strategy assuming peritoneal leiomyosarcoma was difficult. If complete surgical resection of tumor is not performed, as in the present case, the prognosis can be extremely poor.

Postcomparison of [(18) F]-fluorodeoxyglucose uptake in the brain after short-term bright light exposure and no intervention.

OBJECTIVE: Bright light therapy is widely used as the treatment of choice for seasonal affective disorder. Nonetheless, our understanding of the mechanisms of bright light is limited and it is important to investigate the mechanisms. The purpose of this study is to examine the hypothesis that bright light exposure may increase [(18) F]-fluorodeoxyglucose (FDG) uptake in olfactory bulb and/or hippocampus which may be associated neurogenesis in the human brain. METHOD: A randomized controlled trial comparing 5-day bright light exposure + environmental light (bright light exposure group) with environmental light alone (no intervention group) was performed for 55 participants in a university hospital. The uptake of [(18) F]FDG in olfactory bulb and hippocampus using FDG positron emission tomography was compared between two groups. RESULTS: There was a significant increase of uptake in both right and left olfactory bulb for bright light exposure group vs. no intervention group. After adjustment of log-transformed illuminance, there remained a significant increase of uptake in the right olfactory bulb. CONCLUSION: The present findings suggest a possibility that 5-day bright light exposure may increase [(18) F]FDG in the right olfactory bulb of the human brain, suggesting a possibility of neurogenesis. Further studies are warranted to directly confirm this possibility.

Hyaluronan metabolism in overloaded temporomandibular joint.

This study aimed to examine hyaluronan (HA) metabolism in relation to the onset and progression of temporomandibular joint osteoarthritis (TMJ-OA) induced by mechanical overloading. Two-month-old and 6-month-old C57BL/6N mice were divided into experimental and untreated control groups (n = 5/group). A sliding plate was attached to the maxillary incisors of the experimental mice for 10 days to overload the condylar cartilage in TMJ. In experimental group, profound cartilage degradation was detected in haematoxylin-eosin, Safranin-O-Fast Green-stained sections. It was also shown that the cartilage degradation was greater in older mice in both the control and the experimental groups. The number of HABP-positive cells was decreased by mechanical overloading and with age. The reduction of HA expression was correlated with the progression of cartilage degradation induced by mechanical overloading. The absolute quantification of the mRNA expression related to HA synthesis and HA degradation was also performed in each group. The mRNA expression levels of HA synthase (HAS) 2 and 3 were lower in the experimental group compared with the control group in the younger mice. In contrast, the mRNA expression levels of the HA degradation gene, HYAL2 and KIAA1199, were higher in the experimental group compared with the control group in the older mice. Thus, mechanical overload differently affected the balance of HA degradation and HA synthesis in the older and younger mice, respectively. In conclusion, mechanical overloading affects HA metabolism and it might initiate or amplify the condylar cartilage degradation.

Scaling up nano-milling of poorly water soluble compounds using a rotation/revolution pulverizer.

We previously reported that a rotation/revolution pulverizer (NP-100) could mill a small amount of a drug (0.1 g) into nanoparticles in several minutes. In this investigation, scale up from the milligram to the kilogram scale of the nano-milling process by the rotation/revolution pulverizer was studied. Phenytoin was used as a model drug with low solubility in water. After confirming the improvement of the phenytoin bioavailability by milling to nanoparticles using NP-100, scaling parameters were evaluated using NP-100 and the middle scale model of NP-100 (ARV-3000T). A theoretical equation for the specific collisional energy was adapted for wet milling; this suggested that the relative centrifugal acceleration of revolution (revolution G) and the drug concentration in the suspension were the two most important parameters. The results obtained using NP-100 and ARV-3000T correlated well when these two parameters were identical. These results were applied to the large scale model of NP-100 (ARV-10KT), where 2 kg (1 kg x 2) of phenytoin nanoparticles were obtained in 60 min. The results from PXRD and DSC indicated that the milled phenytoin by ARV-3000T and ARV-10KT maintained its crystallinity. These results suggest nano-milling using a rotation/revolution pulverizer will be widely applicable to the development of nano-medicine.

Effects of the masticatory demand on the rat mandibular development.

The influence of masticatory loading stimulus on mandibular development is not fully clear. In this paper, experimental alterations in the daily muscle use, caused by a changed diet consistency, were continuously monitored, while adaptations in bone and cartilage were examined. It is hypothesised that decreased muscular loading will result in a decrease in the growth factor expression and mandible growth. Fourteen 21-day-old Wistar strain male rats were randomly divided into two groups and fed on either a hard or soft diet for 14 weeks. An implanted radio-telemetric device recorded continuously muscle activity of the superficial masseter muscle. Chondroblast proliferation in the condylar cartilage was identified by insulin-like growth factor-1 receptor (IGF-1r) immunostaining. Furthermore, an X-ray was taken for cephalometric analysis. In the soft-diet group, the duty time of the superficial masseter muscle at higher activity levels was significantly lower than that in the hard-diet group. This decrease in muscular loading of the jaw system was accompanied by: a significant reduction in (i) articular cartilage thickness, (ii) expression of IGF-1r immunopositive cells and (iii) mandible ramus height. In conclusion, a decrease in masticatory demand during the growth period leads to insufficient mandibular development.

Production of offspring after sperm chromosome screening: an experiment using the mouse model.

STUDY QUESTION: Is it possible to produce offspring after sperm chromosome screening? SUMMARY ANSWER: It is possible to produce zygotes after examining the genome of individual spermatozoa prior to embryo production. WHAT IS KNOWN ALREADY: Chromosomal aberrations in gametes are a major cause of pregnancy loss in women treated with assisted reproductive technology. However, to our knowledge, there are no reports on the successful genomic screening of spermatozoa, although some attempts have been made using the mouse as a model. STUDY DESIGN: To prevent the transmission of chromosomal aberrations from fathers to offspring, we performed sperm chromosome screening (SCS) prior to fertilization using the mouse as a model. The production of offspring after SCS consists of (i) replication of the sperm chromosomes, (ii) analysis of one copy of the replicated sperm chromosomes, (iii) construction of a zygote using another set of chromosomes and (iv) production of a transferable embryo. MATERIALS, SETTING, METHODS: A single spermatozoon of a male mouse, with or without a Robertsonian translocation, was injected into an enucleated oocyte to allow the replication of sperm chromosomes. One of the sister blastomeres of a haploid androgenic 2-cell embryo was used for chromosome analysis. The other blastomere was fused with an unfertilized oocyte, activated and allowed to develop to a blastocyst before transfer to a surrogate mother. MAIN RESULTS AND ROLE OF CHANCE: With high efficiency, we were able to analyze sperm chromosomes in a blastomere from the androgenic 2-cell embryos and culture zygotes, with and without aberrant chromosomes, to the blastocyst stage before embryo transfer. The karyotypes of the offspring faithfully reflected those of the blastomeres used for SCS. LIMITATIONS, REASONS FOR CAUTION: This study was conducted using a mouse model; whether or not the method is applicable to humans is not known. WIDER IMPLICATIONS OF THE FINDINGS: This study has shown that it is possible to produce zygotes without any paternally inherited aberrations by examining the genome of individual spermatozoa prior to embryo production.

New flexible endoscopic full-thickness suturing device: a triple-arm-bar suturing system.

BACKGROUND AND STUDY AIM: A reliable full-thickness suturing device is necessary for pure natural orifice transluminal endoscopic surgery (NOTES). The present study focused on assessing the reliability of a new suturing device. METHODS: A total of 60 single sutures were tested to close 5-cm incisions in 8-cm square pieces of resected swine stomach. Each incision was sutured by an over-the-scope clip (OTSC; n = 20), a single hand-sewn stitch (n = 20), or a single triple-arm-bar suturing system (TBSS) stitch. The maximum pulling force durability (MPD) of each suture was tested. To assess the reliability of the TBSS for endoscopic full-thickness resection (EFTR), 60 EFTRs of 50 mm diameter were performed on excised swine stomachs. After EFTR, full-thickness sutures were made using 3-stitch OTSCs (n = 20), 10-stitch hand-sewn sutures (n = 20), or 10-stitch TBSS sutures (n = 20). Outcomes were the MPD test for both single stitch and multiple stitch applications and the suturing time for single-stitch sutures. RESULTS: In the single-stitch MPD tests, there were significant differences between OTSCs and hand-sewn sutures (P = 0.0002) and between OTSCs and TBSS sutures (P = 0.0001), but no significant difference between hand-sewn and TBSS sutures. The multiple-stitch sutures revealed significant differences between OTSCs and hand-sewn sutures (P = 0.0039), and between OTSCs and TBSS sutures (P = 0.013). There was no significant difference between hand-sewn and TBSS sutures. There were significant differences in suture times between OTSC, hand-sewn sutures, and TBSS sutures (P < 0.05). CONCLUSIONS: Both single-stitch and multiple-stitch sutures using TBSS have similar strength to hand-sewn sutures. TBSS is a reliable suturing device.

Aberrant activation of the intrarenal renin-angiotensin system in the developing kidneys of type 2 diabetic rats.

We have previously reported that intrarenal angiotensin II (Ang II) levels are increased long before diabetes becomes apparent in obese Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of type 2 diabetes. In this study, we examined the changes in intrarenal renin-angiotensin system (RAS) activity in the developing kidneys of OLETF rats. Ang II contents and mRNA levels of RAS components were measured in male OLETF and control Long-Evans Tokushima (LETO) rats at postnatal days (PND) 1, 5, and 15, and at 4-30 weeks of age. In both LETO and OLETF rats, kidney Ang II levels peaked at PND 1, then decreased during the pre- and post-weaning periods. However, Ang II levels and gene expression of RAS components, including angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE), were not significantly different between LETO and OLETF rats. Intrarenal Ang IIcontents further decreased during puberty (from 7 to 11 weeks of age) in LETO rats, bur not in OLETF rats. At 11 weeks of age, kidney Ang II levels, urinary AGT excretion, and mRNA levels of AGT and renin were higher in OLETF rats than in LETO rats, while blood glucose levels were not significantly different between these groups of rats. These data indicate that continued intrarenal expression of Ang II during pubescence contributes to the increases in intrarenal Ang II levels in prediabetic OLETF rats, and is associated with increased intrarenal AGT and renin expression. Inappropriate activation of the intrarenal RAS in the prediabetic stage may facilitate the onset and development of diabetic nephropathy in later life.

Prevalence and epidemiological traits of HIV infections in populations with high-risk behaviours as revealed by genetic analysis of HBV.

The prevalence and epidemiological traits of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) infections in high-risk populations (HRPs) remained unclarified in Japan. We determined the prevalence of HIV, HBV and Treponema pallidum (TP) and the viral genotypes in HRPs who attended primary sexually transmitted infection (STI) clinics in Osaka province during 2006-2011. Of 7898 specimens, 133 (1·7%) were HIV positive, which was significantly higher than the figures reported by Japanese Red Cross (0·0019%) and public health centres (0·27%) in Japan. The frequency of HIV-1 subtype B was 88·7%, followed by CRF01_AE (2·3%) and C (0·8%), which were almost identical to the national trend. HBV seroprevalence was surprisingly high in the HIV-positive group (63·2%), which was significantly higher than that in the HIV-negative group (25·6%). By contrast, there was no statistical correlation between HIV and TP infection. Interestingly, the distinct HBV genotypes Ae and G were prevalent in the HIV-positive population (60·0% and 20·0%, respectively), although both were rarely detected during nationwide surveillance. The transmission of HIV and HBV appeared to occur largely within a closed community early in life. Of note, about one-quarter of HIV-positive cases would have remained untested if health professionals had not motivated individuals to undergo HIV testing. This is the first evidence-based assessment of HIV positivity and HIV/HBV co-infection in HRPs at primary STIs in Japan and the effect of the involvement of health professionals in the diagnosis of HIV infections in asymptomatic carriers. The genotyping of HBV provided valuable information for understanding HIV epidemical traits.

High-resolution CT findings in Streptococcus milleri pulmonary infection.

AIM: To assess pulmonary high-resolution computed tomography (CT) findings in patients with acute Streptococcus milleri pulmonary infection. MATERIALS AND METHODS: Sixty consecutive patients with acute S. milleri pneumonia who had undergone high-resolution CT chest examinations between January 2004 and March 2010 were retrospectively identified. Twenty-seven patients with concurrent infections were excluded. The final study group comprised 33 patients (25 men, 8 women; aged 20-88 years, mean 63.1 years) with S. milleri infection. The patients' clinical findings were assessed. Parenchymal abnormalities, enlarged lymph nodes, and pleural effusion were evaluated on high-resolution CT. RESULTS: Underlying conditions included malignancy (n = 15), a smoking habit (n = 11), and diabetes mellitus (n = 8). CT images of all patients showed abnormal findings, including ground-glass opacity (n = 24), bronchial wall thickening (n = 23), consolidation (n = 17), and cavities (n = 7). Pleural effusion was found in 18 patients, and complex pleural effusions were found in seven patients. CONCLUSION: Pulmonary infection caused by S. milleri was observed mostly in male patients with underlying conditions such as malignancy or a smoking habit. The CT findings in patients with S. milleri consisted mainly of ground-glass opacity, bronchial wall thickening, pleural effusions, and cavities.

Stress analysis in human temporomandibular joint affected by anterior disc displacement during prolonged clenching.

Parafunctional habits, such as prolonged clenching and bruxism, have been associated with dysfunctional overloading in the temporomandibular joint (TMJ). In this study, stress distributions in the TMJ were analysed during prolonged clenching, using three-dimensional finite element (FE) models of the TMJ with and without disc displacement. The aim of this study was to investigate stress distribution of the cartilaginous tissues in the TMJ with and without disc displacement. Finite element models were developed on the basis of magnetic resonance images from two subjects with and without anterior disc displacement. Condylar movements recorded during a 5-min clenching were used as the loading condition for stress analysis. In the asymptomatic model, the highest von Mises stresses were located in the lateral area (4·91 MPa) of the disc surfaces, and after 5-min clenching, the higher stresses were still located at the lateral area (3·65 MPa). In all the cartilaginous tissues, 30-50% of stress reduction occurred during 5-min clenching. In contrast, the von Mises stress in the cartilaginous tissues of the symptomatic model with disc displacement was markedly lower, compared with the asymptomatic model. However, in the condylar cartilage, stress relaxation during clenching was not recognised. Furthermore, relatively high stresses were observed in the retrodiscal tissues throughout clenching. The present results indicate that disc position could be involved in the stress distribution of the TMJ components during prolonged clenching.

Impact of amino acid 233 in Tax on bovine leukemia virus infection in Japanese Black cattle.

Bovine leukemia virus (BLV) is an economically important pathogen that both causes fatal enzootic bovine leukosis (EBL) and reduces lifetime milk production, reproductive efficiency, carcass weight, and longevity in dairy cows. The virus can be divided into two categories based on the amino acid at position 233 in Tax protein, which activates viral transcription and probably plays crucial roles in leukemogenesis. We recently reported that early-onset EBL in Japanese Black (JB) cattle was frequently caused by L233-Tax-carrying virus. This study examined the impact of BLV infection, the proviral load (PVL), and amino acid 233 in Tax on the outcomes of JB cattle. We measured PVL in cattle enrolled between February 2016 and December 2018, determined the Tax type of the isolates, and performed follow-up until March 2022. The results demonstrated that BLV infection increased the risk of involuntary culling and mortality in JB cattle in a PVL-dependent manner. Infection with L233-Tax-carrying virus increased the likelihood of mortality by 1.6-fold compared with the effects of P233-Tax-carrying virus infection. Intrauterine and perinatal infections were frequently caused by L233-Tax-carrying virus, and these infections were likely to influence the early onset of EBL in JB cattle. Conversely, breeding cows infected with P233-Tax-carrying virus were often eliminated by involuntary culling. These findings indicate that amino acid 233 in Tax has importance in terms of preventing economic loss attributable to EBL in JB cattle.