Interactions between Amyloid-β and Hemoglobin: Implications for Amyloid Plaque Formation in Alzheimer's Disease

Accumulation of amyloid-β (Aβ) peptides in the brain is one of the central pathogenic events in Alzheimer's disease (AD). However, why and how Aβ aggregates within the brain of AD patients remains elusive. Previously, we demonstrated hemoglobin (Hb) binds to Aβ and co-localizes with the plaque and vascular amyloid deposits in post-mortem AD brains. In this study, we further characterize the interactions between Hb and Aβ in vitro and in vivo and report the following observations: 1) the binding of Hb to Aβ required iron-containing heme; 2) other heme-containing proteins, such as myoglobin and cytochrome C, also bound to Aβ; 3) hemin-induced cytotoxicity was reduced in neuroblastoma cells by low levels of Aβ; 4) Hb was detected in neurons and glial cells of post-mortem AD brains and was up-regulated in aging and APP/PS1 transgenic mice; 5) microinjection of human Hb into the dorsal hippocampi of the APP/PS1 transgenic mice induced the formation of an envelope-like structure composed of Aβ surrounding the Hb droplets. Our results reveal an enhanced endogenous expression of Hb in aging brain cells, probably serving as a compensatory mechanism against hypoxia. In addition, Aβ binds to Hb and other hemoproteins via the iron-containing heme moiety, thereby reducing Hb/heme/iron-induced cytotoxicity. As some of the brain Hb could be derived from the peripheral circulation due to a compromised blood-brain barrier frequently observed in aged and AD brains, our work also suggests the genesis of some plaques may be a consequence of sustained amyloid accretion at sites of vascular injury

AV-SUPERB: A Multi-Task Evaluation Benchmark for Audio-Visual Representation Models

Audio-visual representation learning aims to develop systems with human-like perception by utilizing correlation between auditory and visual information. However, current models often focus on a limited set of tasks, and generalization abilities of learned representations are unclear. To this end, we propose the AV-SUPERB benchmark that enables general-purpose evaluation of unimodal audio/visual and bimodal fusion representations on 7 datasets covering 5 audio-visual tasks in speech and audio processing. We evaluate 5 recent self-supervised models and show that none of these models generalize to all tasks, emphasizing the need for future study on improving universal model performance. In addition, we show that representations may be improved with intermediate-task fine-tuning and audio event classification with AudioSet serves as a strong intermediate task. We release our benchmark with evaluation code and a model submission platform to encourage further research in audio-visual learning.Comment: Submitted to ICASSP 2024; Evaluation Code: https://github.com/roger-tseng/av-superb Submission Platform: https://av.superbbenchmark.or

A Nanodot Array Modulates Cell Adhesion and Induces an Apoptosis-Like Abnormality in NIH-3T3 Cells

Micro-structures that mimic the extracellular substratum promote cell growth and differentiation, while the cellular reaction to a nanostructure is poorly defined. To evaluate the cellular response to a nanoscaled surface, NIH 3T3 cells were grown on nanodot arrays with dot diameters ranging from 10 to 200 nm. The nanodot arrays were fabricated by AAO processing on TaN-coated wafers. A thin layer of platinum, 5 nm in thickness, was sputtered onto the structure to improve biocompatibility. The cells grew normally on the 10-nm array and on flat surfaces. However, 50-nm, 100-nm, and 200-nm nanodot arrays induced apoptosis-like events. Abnormality was triggered after as few as 24 h of incubation on a 200-nm dot array. For cells grown on the 50-nm array, the abnormality started after 72 h of incubation. The number of filopodia extended from the cell bodies was lower for the abnormal cells. Immunostaining using antibodies against vinculin and actin filament was performed. Both the number of focal adhesions and the amount of cytoskeleton were decreased in cells grown on the 100-nm and 200-nm arrays. Pre-coatings of fibronectin (FN) or type I collagen promoted cellular anchorage and prevented the nanotopography-induced programed cell death. In summary, nanotopography, in the form of nanodot arrays, induced an apoptosis-like abnormality for cultured NIH 3T3 cells. The occurrence of the abnormality was mediated by the formation of focal adhesions

Numerical investigation of aerodynamic droplet breakup in a high temperature gas environment

The Navier-Stokes equations, energy and vapor transport equations coupled with the VOF methodology and a vaporization rate model are numerically solved to predict aerodynamic droplet breakup in a high temperature gas environment. The numerical model accounts for variable properties and uses an adaptive local grid refinement technique on the gas-liquid interface to enhance the accuracy of the computations. The parameters examined include Weber (We) numbers in the range 15-90 and gas phase temperatures in the range 400-1000 K for a volatile n-heptane droplet. Initially isothermal flow conditions are examined in order to assess the effect of Weber (We) and Reynolds (Re) number. The latter was altered by varying the gas phase properties in the aforementioned temperature range. It is verified that the We number is the controlling parameter, while the Re number affects the droplet breakup at low We number conditions. The inclusion of droplet heating and evaporation mechanisms has revealed that heating effects have generally a small impact on the phenomenon due to its short duration except for low We number cases. Droplet deformation enhances heat transfer and droplet evaporation. An improved 0-D model is proposed, able to predict the droplet heating and vaporization of highly deformed droplets

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Mixed Solid-State Fermentation of Okara and Copra Meal by Probiotics with Non-Starch Polysaccharide Enzymes and Its Effects on the Growth Performance and Ileal Microbiota in Broilers

With the global shortage of feed ingredients, the use of agricultural by-products has become an alternative to animal feed. Okara, a by-product of soymilk and tofu processing, is high in nutrients but contains non-starch polysaccharides (NSP) and has a high-water content, which are disadvantages in animal feed. Herein, we mixed okara and copra meal (CM) with probiotics (Lactobacillus species and Clostridium butyricum) and NSP enzymes (NSPases) for solid-state fermentation (SSF) to enhance okara feed value; the optimal parameters of fermented okara and CM (FOCM) and their effects on broiler growth performance and ileal microbiota were investigated. The result showed that FOCM in combination with NSPases and probiotics at 55% of the initial moisture content and 60 h fermentation time at 37 °C were able to degrade NSP and reduce sugar content. After fermentation, the total viable counts, lactic acid, and butyric acid contents in the FOCM were 8.6 log CFU/g, 3.7%, and 17.15%, respectively. During the fifth week of the feeding period and over the whole feeding period, broilers fed with 1.25% and 2.5% FOCM had a better feed conversion ratio (p p Escherichia-Shigella in the ileal content (p < 0.05). Collectively, supplementation of probiotics and enzymes during SSF was found to be effective in enhancing the nutritional value of FOCM. Moreover, dietary supplementation of FOCM improved the broiler feed conversion ratio, gut morphology, and ileal microbiota