Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques

AbstractWe analyzed an amino-terminal modification of β-amyloid (Aβ) peptide in brain, using anti-Aβ antibodies that distinguish distinct molecular species. Examination of cortical sections from 28 aged individuals with a wide range in senile plaque density revealed that a molecular species distinct from the standard Aβ is deposited in the brain in a dominant and differential manner. This modified Aβ peptide (AβN3(pE)) starts at the 3rd amino-terminal residue of the standard Aβ, glutamate, converted to pyroglutamate through intramolecular dehydration. Because plaques composed of AβN3(pE) are present in equivalent or greater densities than those composed of standard Aβ bearing the first aminoterminal residue (AβN1) and because deposition of the former species appears to precede deposition of the latter, as confirmed with specimens from Down's syndrome patients, the processes involved in AβN3(pE) production and retention may play an early and critical role in senile plaque formation

Mutations in the stator protein PomA affect switching of rotational direction in bacterial flagellar motor

The flagellar motor rotates bi-directionally in counter-clockwise (CCW) and clockwise (CW) directions. The motor consists of a stator and a rotor. Recent structural studies have revealed that the stator is composed of a pentameric ring of A subunits and a dimer axis of B subunits. Highly conserved charged and neighboring residues of the A subunit interacts with the rotor, generating torque through a gear-like mechanism. The rotational direction is controlled by chemotaxis signaling transmitted to the rotor, with less evidence for the stator being involved. In this study, we report novel mutations that affect the switching of the rotational direction at the putative interaction site of the stator to generate rotational force. Our results highlight an aspect of flagellar motor function that appropriate switching of the interaction states between the stator and rotor is critical for controlling the rotational direction

Effectiveness of Anti-PD-1 Antibody Monotherapy for the Primary Malignant Melanoma of the Esophagus： A Case Report

Primary malignant melanoma of the esophagus（PMME）is extraordinarily rare with a high degree of malignancy and poor prognosis, and a standard therapy remains to be established. The anti-PD-1 antibody nivolumab is a promising agent for various cancers. To our knowledge, this is the first case report of PMME where a complete response was achieved using nivolumab. We report an 80-year-old woman who was diagnosed with PMME with bone metastasis and lymph node metastases. Although dacarbazine combined chemotherapy was performed and continued for six cycles, the primary tumor progressed and liver metastases appeared. The patient then received nivolumab monotherapy. After three cycles, nivolumab monotherapy for PMME resulted in a complete response as shown by positron emission tomography, computed tomography, and esophagogastroduodenoscopy. In our case, nivolumab exerted a curative effect on PMME, thus suggesting that nivolumab can be effective in the treatment of this rare disease

Power generation characteristics of pulse jet rechargeable direct carbon fuel cells at different isooctane fuel supply frequency

INTRODUCTION Our research group previously proposed a new type of a direct carbon fuel cell (DCFC) called a rechargeable direct carbon fuel cell (RDCFC), which uses as fuel the solid-state carbon deposited on the electrode [1~6]. In a typical RDCFC, lower hydrocarbons such as propane are the supplied fuel, and deposition of the solid-state carbon (charging) into the anode is done by pyrolysis. In an RDCFC, this charging method causes several problems, such as low carbon extraction efficiency and batch-type rather than continuous operation. Our research group thus developed a pulse jet RDCFC because a constant power density can be maintained by supplying small amounts of high energy density liquid fuel by a pulse jet while generating electricity and continuous power generation by repeating the charging and power generation at short intervals. In addition, in a pulse jet RDCFC, deterioration of anodes due to carbon is minimized by frequent carbon removal and high energy conversion efficiency by utilizing hydrogen, methane, and other hydrocarbons as well as the solid-state carbon generated by the pyrolysis of liquid fuel. In a pulse jet RDCFC, the frequency at which isooctane fuel is supplied influences the power generation characteristics. When this supply frequency is increased, the power generation characteristics of a pulse jet RDCFC are thought to change to those of a flow-type SOFC. In this study, the effect of a supply frequency of isooctane on power generation characteristics of a pulse jet RDCFC was investigated

Successful treatment of COVID‐19‐related acute respiratory distress syndrome with a rare blood type: A case report

Extracorporeal membrane oxygenation is indispensable for critically severe COVID-19 patients. However, it would be inapplicable to patients with a rare blood type or blood transfusion refusal. In that case, severely conservative fluid management with the sacrifice of renal functions and hydrocortisone therapy should be considered for better oxygenation

Social interaction trajectories and all-cause mortality in older adults: the Otassha study

IntroductionThis longitudinal study aimed to identify aging trajectory patterns of social interaction by sex and determine the association between these patterns and all-cause mortality.MethodsParticipants were 4,065 community-dwelling older adults (1849 men) in Japan, aged 65–89 years, who responded twice or more to a mail survey conducted between 2012 and 2020. Social interaction was examined through the frequency of face-to-face and non-face-to-face contact with non-resident family and friends. The aging trajectories of the social interaction scores were identified using group-based trajectory modeling.ResultsTwo groups were identified among both men and women. Among men with high-frequency interaction, a rapid decrease in the frequency of social interaction was observed after 80 years of age. Conversely, among women, the frequency tended to remain the same, even after 80 years of age. The social interaction score among those aged 65 years in the low-frequency group was approximately 4 points for men and 6 points for women. Among men, no decrease was observed; however, it tended to decline after 85 years of age among women. Among men, the factors associated with the low-frequency group were instrumental activities of daily living score, perceived financial status, and social participation, while among women, they were self-rated health and social participation. The adjusted hazard ratio in the low-frequency group for all-cause mortality was 1.72 (95% confidence interval, 1.27–1.72) for men and 1.45 (95% confidence interval, 0.98–2.14) for women.DiscussionIn the low-frequency group, men had a higher risk of all-cause mortality than women. Daily social interaction from mid-age is important to reduce the risk of social isolation and all-cause mortality in later life

Higher Serum Brain-Derived Neurotrophic Factor Levels Are Associated With a Lower Risk of Cognitive Decline: A 2-Year Follow Up Study in Community-Dwelling Older Adults

ObjectiveTo assess the relationship of serum brain-derived neurotrophic factor (BDNF) levels with the subsequent short-term decline in cognitive functioning in community-dwelling older adults.DesignTwo-year prospective, observational study.Setting and ParticipantsThe study included 405 adults aged 65–84 years, initially free of a dementia diagnosis who were living in Tokyo, Japan.MethodsParticipants underwent health assessments at baseline (2011) and follow-up (2013). Serum BDNF levels and scores from the Montreal Cognitive Assessment-Japanese version (MoCA-J) were systematically measured. Logistic regression was used to estimate the odds of cognitive decline between baseline and follow-up assessments in the full MoCA-J scale (operationally defined as a decrease of two or more points), as well as in MoCA-J subscales (decline of one or more points in a specific subscale), as a function of serum BDNF level, adjusting for baseline demographics, prevalent chronic diseases, and baseline cognitive scores.ResultsAmong individuals who performed worse on the full MoCA-J at baseline (i.e., scores in the bottom quartile [≤21], which is consistent with a mild cognitive impairment status), but not among those who performed better (top 3 quartiles), those with highest baseline serum BDNF levels (top quartile) had lower odds of subsequent decline in the full MoCA-J scale than those with lowest (bottom quartile); i.e., odds ratio (OR): 0.10 (95% confidence interval [CI]: 0.02–0.62; p = 0.013). Regarding MoCA-J subscales, adjusted odds of decline in the executive function subscale, but not in the other five subscales, were substantially low among those with highest baseline serum BDNF levels (top quartile), as compared to those with the lowest (bottom quartile), i.e., OR: 0.27 (95% CI:0.13–0.60; p < 0.001).Conclusion and ImplicationsHigher serum BDNF levels were associated with a lower risk of decline in cognitive function in a sample of community-dwelling older Japanese adults. Risk varied across cognitive subdomains and according to baseline cognition. This warrants further research to evaluate the added-value of serum BDNF in health promotion initiatives directed toward cognitive decline prevention in community-dwelling older adults

Induction of apoptotic lesions in liver and lymphoid tissues and modulation of cytokine mRNA expression by acute exposure to deoxynivalenol in piglets

Six 1-month-old piglets were intravenously injected with deoxynivalenol (DON) at the concentration of 1 mg/kg body weight, with three pigs each necropsied at 6 and 24 h post-injection (PI) for investigation of hepatotoxicity and immunotoxicity with special attention to apoptotic changes and cytokine mRNA expression. Histopathological examination of the DON-injected pigs revealed systemic apoptosis of lymphocytes in lymphoid tissues and hepatocytes. Apoptosis of lymphocytes and hepatocytes was confirmed by the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical staining against single-stranded DNA and cleaved caspase-3. The number of TUNEL-positive cells in the thymus and Peyer's patches of the ileum was increased at 24 h PI compared to 6 h PI, but the peak was at 6 h PI in the liver. The mRNA expression of interleukin (IL)-1β, IL-6, IL-18, and tumor necrosis factor (TNF)-α in the spleen, thymus and mesenteric lymph nodes were determined by semi-quantitative RT-PCR, and elevated expression of IL-1β mRNA at 6 h PI and a decrease of IL-18 mRNA at 24 h PI were observed in the spleen. IL-1β and IL-6 mRNA expressions increased significantly at 6 h PI in the thymus, but TNF-α decreased at 6 h PI in the mesenteric lymph nodes. These results show the apoptosis of hepatocytes suggesting the hepatotoxic potential of DON, in addition to an immunotoxic effect on the modulation of proinflammatory cytokine genes in lymphoid organs with extensive apoptosis of lymphocytes induced by acute exposure to DON in pigs