Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinal Macrophages Synthesize C3 and Activate Complement in AMD and in Models of Focal Retinal Degeneration.

Purpose Complement system dysregulation is strongly linked to the progression of age-related macular degeneration (AMD). Deposition of complement including C3 within the lesions in atrophic AMD is thought to contribute to lesion growth, although the contribution of local cellular sources remains unclear. We investigated the role of retinal microglia and macrophages in complement activation within atrophic lesions, in AMD and in models of focal retinal degeneration. Methods Human AMD donor retinas were labeled for C3 expression via in situ hybridization. Rats were subject to photo-oxidative damage, and lesion expansion was tracked over a 2-month period using optical coherence tomography (OCT). Three strategies were used to determine the contribution of local and systemic C3 in mice: total C3 genetic ablation, local C3 inhibition using intravitreally injected small interfering RNA (siRNA), and depletion of serum C3 using cobra venom factor. Results Retinal C3 was expressed by microglia/macrophages located in the outer retina in AMD eyes. In rodent photo-oxidative damage, C3-expressing microglia/macrophages and complement activation were located in regions of lesion expansion in the outer retina over 2 months. Total genetic ablation of C3 ameliorated degeneration and complement activation in retinas following damage, although systemic depletion of serum complement had no effect. In contrast, local suppression of C3 expression using siRNA inhibited complement activation and deposition, and reduced cell death. Conclusions These findings implicate C3, produced locally by retinal microglia/macrophages, as contributing causally to retinal degeneration. Consequently, this suggests that C3-targeted gene therapy may prove valuable in slowing the progression of AMD.
Strategic value-directed learning and memory in Alzheimer's disease and behavioural-variant frontotemporal dementia.

In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants' memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory.
Survivability of Salmonella typhimurium L1388 and Salmonella enteritidis L1225 under stressful growth conditions

In an earlier study with Salmonella typhimurium L1388 (ST) and Salmonella enteritidis L1225 (SE) isolated from diseased chickens, we found that SE formed more biofilm than ST on abiotic surfaces in a time-dependent manner. Since the ability of salmonellae to survive extreme environment is related to their virulence, the present study examined the survival of Salmonella typhimurium L1388 and Salmonella nteritidis L1225 under the usual stresses that salmonellae encounter during their life cycle. This is with a view to understanding the strains’ stress tolerance that could be used to explain their virulence. Incubation at 37oC for various time periods was done for: i) stationary phase (SP) cells at pH 2.6; ii) log-phase (LP) cells at pH 4.0; log-phase or stationary phase cells in broth containing iii) hydrogen peroxide, iv) sodium chloride and v) ethanol; vi) stationary phase cells in Hank’s balanced salt solution (single strength) containing 10% human serum; and vii) prolong stationary phase cells. Stationary phase cells were also incubated at 52oC for 15 min. Surviving cells at the various incubation times were counted on trypticase soy agar (TSA) after appropriate dilution in saline and overnight incubation at 37oC. Growth iron-poor medium was determined by growing a single bacterial colony in Medium A with shaking at 37oC or 40oC for 24 h. Statistics was done by one-way analysis-of-variance (ANOVA) at P = 0.05. Differences in the survival of ST and SE were insignificant (p>0.05) in acid pH at both pH 4.0 (p = 0.3783) and pH 2.6 (p = 0.4711); at high salinity for log-phase (p = 0.1416) and stationary phase (p = 0.1816) cells; in ethanol (p = 0.5984), human serum (p = 0.8139), prolonged stationary phase (p = 0.3506); and under heat (p = 0.5766). SE was significantly (p<0.05; p = 0.0031) more tolerant to oxidative-killing by hydrogen peroxide. Culturable growth of the ST and SE in an iron-poor medium A revealed insignificant differences at 37oC (p = 0.8381) but marginally significant at 40oC (p = 0.0508). Thus, with the exception of survival in hydrogen peroxide, SE had similar response pattern with ST to the usual stresses that salmonellae encounter during their life cycle, despite the former’s preferential ability to form biofilm on abiotic surfaces. The relationship between the observed enhanced ability of SE to survive in hydrogen peroxide and virulence need to be investigated in subsequent study.
Collagen XVII/laminin-5 activates epithelial-to-mesenchymal transition and is associated with poor prognosis in lung cancer

Epithelial-to-mesenchymal transition (EMT) is associated with tumor metastasis and tumorigenesis in lung cancer stem-like cells (CSCs). However, the exact mechanism underlying this is not clear. We used microarray analysis to identify candidate genes responsible for EMT in spheroid and monolayer cultures of lung cancer cells. We found increased expression of a variety of adhesion molecules in CSCs. One of these molecules, Collagen XVII (Col XVII), was demonstrated to be required for maintenance of EMT phenotypes and metastasis ability in lung CSCs. We showed that Col XVII stabilized laminin-5 to activate the FAK/AKT/GSK3β pathway, thereby suppressing Snail ubiquitination-degradation. The function of Col XVII was mainly dependent on shedding by ADAM9 and ADAM10. Patients who underwent surgical resection for lung cancer, and displayed overexpression of both Col XVII and laminin-5, had the worst prognosis of all expression types. Moreover, blockage of the Col XVII/laminin-5 pathway reduced the EMT phenotypes of lung CSCs in vitro and decreased the potential of lung metastasis in vivo. Our findings suggested that targeting Col XVII and laminin-5 could be novel therapeutic strategies for treating lung cancer patients, and warrant further investigation.
Complement fixation test due to the interaction of specific antiplatelet serum and heterologous platelet antigen.

Abstract A complement fixation reaction is described for the detection of platelet antibodies by using antiplatelet rabbit serum and guinea pig platelet antigen. Complete inhibition of hemolysis took place at the serum dilution of 1700. No inhibition of hemolysis was obtained with serum of the same animals before the immunization. This result was obtained by using sera which had been either adsorbed or not adsorbed with sheep red cells and guinea pig kidney extract. Agglutination tests of guinea pig platelets with antiplatelet rabbit serum have shown a positivity in serum dilution as high as 1128. Possible correlations with human pathology and technical developments are discussed.
Pre-harvest factors affecting quality and shelf-life in raspberries and blackberries ( Rubus spp .

Fruit including berries have been demonstrated to exhibit a broad spectrum of benefits including protection against cardiovascular, neurological, and lung diseases, as well as having antioxidant, antimicrobial, anti-inflammatory, antidiabetic and anti-aging properties. These protective effects are reported to be due to their high content of bioactive compounds, such as vitamin C, vitamin E, phenolic acids, ellagitannins, flavonoids and carotenoids. This thesis investigated the effect of preand postharvest factors on the concentrations of bioactive compounds in raspberries and blackberries. The factors studied included genetic variability, organic and synthetic fertilizers, seasonal variation (harvest-to-harvest and annual variation) in greenhouse, high tunnel and open field production, and post-harvest storage. Concentrations of bioactive compounds (anthocyanins, vitamin C, ellagic acid, carotenoids) in the berries, or in the leaves, were quantitatively analysed by high-performance liquid chromatography, and total phenolics were analysed by a spectrophotometric method. Generative parameters (yield, fruit size) investigated for the cultivar difference and organic nitrogen, responded differently to the nitrogen level within cultivars and varied significantly in primocane raspberries. Taste compounds, such as total acidity and different sugars, varied during the season and with nutrient regimes. Time of harvest also affected the ellagic acid content, which was high in early season, and the vitamin C content, which was high in late season in primocane raspberries. Significant changes were also found between different years. Vitamin C decreased significantly with high synthetic N and with low K application, but the application of high N with high K showed positive influence in the level of nutrients and bioactive compounds in blackberries except for ellagic acid. Increased level of organic fertilization (12-17 g N/plant) in primocane raspberries caused only minor changes in the analysed compounds. The post-harvest performance of raspberries regarding the levels of bioactive compounds was less dynamic than in blackberries. In addition, raspberries harvested in late season showed comparatively less changes in sugar content during storage as compared to early harvest, indicating less enzymatic activity in the late season.
A haplotype of the dopamine transporter gene modulates regional homogeneity, gray matter volume, and visual memory in children with attention-deficit/hyperactivity disorder

Abstract Background The dopamine transporter gene (DAT1) and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine whether a DAT1 haplotype affected functional and structural brain alterations in children with ADHD and whether those alterations were associated with visual memory. Method We recruited a total of 37 drug-naïve children with ADHD (17 with the DAT1 rs27048 (C)/rs429699 (T) haplotype and 20 without the CT haplotype) and 37 typically developing children (17 with the CT haplotype and 20 without the CT haplotype). Visual memory was assessed by the pattern recognition memory (PRM) and spatial recognition memory (SRM) tasks. We analyzed functional and structural brain architecture with regional homogeneity (ReHo) and gray matter volume (GMV). Results The CT haplotype was associated with decreased ReHo in the left superior occipital gyrus, cuneus, and precuneus; and decreased GMV in the left superior occipital gyrus, cuneus, and precuneus, and in the right angular gyrus. Significant interactions of ADHD and the CT haplotype were found in the right postcentral gyrus for ReHo and in the right supplementary motor area for GMV. For the ADHD-CT group, we found negative correlations of total correct responses in PRM and SRM and positive correlations of mean latency of correct responses in PRM with the GMV in the left superior occipital gyrus, cuneus, and precuneus. Conclusions Our findings suggest that the DAT1-related GMV alterations in the posterior cortical regions may contribute to visual memory performance in children with ADHD.
The new era of chelation treatments: effectiveness and safety of 10 different regimens for controlling iron overloading in thalassaemia major

This review outlines the effectiveness and safety of 10 different regimens for controlling iron overloading in thalassaemia major (TM). For each treatment, the strength of the evidence was documented according to the guidelines of the American College of Cardiology and the American Heart Association. Serum ferritin (SF), liver iron concentration (LIC), heart T2* signal, heart damage and survival were used to assess effectiveness. Five chelation regimens out of 10 showed Level A Evidence in controlling iron overloading, as determined by SF levels and LIC. Three out of 10 chelation regimens were able to control heart iron levels, as determined by T2* signals with Level A Evidence. Two chelation regimens were able to improve/reverse heart damage and four increased of survival with Level B Evidence. These advances mean that the current survival of TM patients is now similar to that of thalassaemia intermedia patients.
Single‐molecule nucleosome remodeling by INO80 and effects of histone tails

Genome maintenance and integrity requires continuous alterations of the compaction state of the chromatin structure. Chromatin remodelers, among others the INO80 complex, help organize chromatin by repositioning, reshaping, or evicting nucleosomes. We report on INO80 nucleosome remodeling, assayed by single‐molecule Foerster resonance energy transfer on canonical nucleosomes as well as nucleosomes assembled from tailless histones. Nucleosome repositioning by INO80 is a processively catalyzed reaction. During the initiation of remodeling, probed by the INO80 bound state, the nucleosome reveals structurally heterogeneous states for tailless nucleosomes (in contrast to wild‐type nucleosomes). We, therefore, propose an altered energy landscape for the INO80‐mediated nucleosome sliding reaction in the absence of histone tails.
Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use

Background: Gut dysbiosis associated with the use of proton-pump inhibitors (PPIs) has been found to lead to the occurrence of infectious and inflammatory adverse events. A longitudinal observational cohort study has demonstrated the heightened risk of death associated with PPI use. Summary: We evaluated meta-analyses to determine the association between PPI use and infectious and inflammatory diseases. Meta-analyses showed that PPI use is a potential risk for the development of enteric infections caused by Clostridium difficile, as well as small intestinal bacterial overgrowth, spontaneous bacterial peritonitis, community-acquired pneumonia, hepatic encephalopathy, and adverse outcomes in inflammatory bowel disease. We also examined changes in the composition and function of the gut microbiota with the use of PPIs. PPI use significantly increased the presence of Streptococcaceae and Enterococcaceae, which are risk factors for C. difficile infection, and decreased that of Faecalibacterium, a commensal anti-inflammatory microorganism. Key Message: High-throughput, microbial 16S rRNA gene sequencing has allowed us to investigate the association between the gut microbiome and PPI use. Future prospective comparison studies are necessary to confirm this association, and to develop new strategies to prevent complications of PPI use
Effects of Dietary Protein on Thyroid Axis Activity

Thyroid hormones (TH) are essential for the normal development and function of every vertebrate. The hypothalamic-pituitary-thyroid (HPT) axis is regulated to maintain euthyroid status. One of the most influential environmental factors that determines HPT axis activity is nutrition. Both food availability and substrate diversity affect thyroid hormone economy. The present paper aims to summarize literature data concerning the influence of the amount and the type of protein on thyroid axis activity. This review sheds light on the contribution of a low-protein diet or insufficient intake of essential amino acids to TH abnormalities. We believe that the knowledge of these dependencies could improve the results of nutritional interventions in thyroid axis disorders and enhance the efficiency of animal breeding.
Depressions by dietary phospholipids of soybean and egg yolk origins of hepatic triacylglycerol and fatty acid synthesis in fasted-refed rats.

Effects of various phospholipid preparations from soybean and egg yolk origins on various indices for lipid biosynthesis in the liver were compared in fasted-refed rats. Phospholipid preparations employed were soybean phospholipid mainly consisting of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidic acid (soybean PL), egg phospholipid mainly consisting of phosphatidylcholine and phosphatidylethanolamine (egg PL) and purified phosphatidylcholines from soybean (soybean PC) and egg yolk (egg PC) origins. The diet containing 3% fatty acids as soybean and egg PLs compared to the those containing the same amount of fatty acids as the fat blend simulating fatty acid composition of soybean PL and no fatty acids profoundly decreased hepatic concentration of triacylglycerol and liver microsomal concentration of diacylglycerol. Soybean and egg PCs compared to the fat blend also decreased the concentrations of these lipid components in the liver but with the much less extents. Soybean and egg PLs compared to the fat blend also profoundly decreased the activities of enzymes in fatty acid synthesis and of microsomal glycerol 3-phosphate acyltransferase in the liver. These phospholipid preparations compared to the fat blend also significantly decreased the activity of microsomal diacylglycerol acyltransferase when it was measured with endogenous microsomal diacylglycerol substrate. The purified PCs from soybean and egg yolk origins compared to the fat blend also significantly decreased some of these parameters in lipid biosynthesis in the liver but with the much less extents. (ABSTRACT TRUNCATED AT 250 WORDS)
Chromobacterium violaceum associated with recurrent vaginal discharge among apparently healthy females in Ekpoma, Nigeria

Seven hundred and two high vaginal swab samples of apparently healthy adult females with recurrent vaginal discharge were collected and analyzed at Searchlight Medical Diagnostic Centre, Ekpoma between July 2003 and August 2005. Isolation, identification and antibiogram of isolates were done using standard Microbiological techniques. Randomized Block Design and Completely Randomized Design at (α = 0.1) were used to test the statistical significance of results. While occupational distribution of isolates was not statistically significant, age and response of bacterial isolates to antibiotics used were statistically significant. Total number and percentage prevalence of bacteria isolated include: 297(42.4%) Chromobacterium violaceum, 156 (22.2%) Escherichia coli and 139 (19.8%) Staphylococcus aureus. Chromobacterium violaceum was 81.8% sensitive to ofloxacin, and 12.8% to Ceftriazone. Escherichia coli and S. aureus were 70.5% and 71.9% sensitive to sparfloxacin respectively. Though source of infection of C. violaceum in Ekpoma was not very clear, soil and water contamination and other risk factors were hypothesized. A high index of suspicion is required for diagnosis. Surveillance with improved diagnostic facilities can increase awareness among health care providers on this form of infection. Appropriate systemic antimicrobial therapy to halt progression of infection is mandatory, even when the infection appears to be localized.
Individualized estimation of human core body temperature using noninvasive measurements

A rising core body temperature (Tc) during strenuous physical activity is a leading indicator of heat-injury risk. Hence, a system that can estimate Tc in real time and provide early warning of an impending temperature rise may enable proactive interventions to reduce the risk of heat injuries. However, real-time field assessment of Tc requires impractical invasive technologies. To address this problem, we developed a mathematical model that describes the relationships between Tc and noninvasive measurements of an individual’s physical activity, heart rate, and skin temperature, and two environmental variables (ambient temperature and relative humidity). A Kalman filter adapts the model parameters to each individual and provides real-time personalized Tc estimates. Using data from three distinct studies, comprising 166 subjects who performed treadmill and cycle ergometer tasks under different experimental conditions, we assessed model performance via the root mean squared error (RMSE). The individualized model yielded an overall average RMSE of 0.33 (SD = 0.18)°C, allowing us to reach the same conclusions in each study as those obtained using the Tc measurements. Furthermore, for 22 unique subjects whose Tc exceeded 38.5°C, a potential lower Tc limit of clinical relevance, the average RMSE decreased to 0.25 (SD = 0.20)°C. Importantly, these results remained robust in the presence of simulated real-world operational conditions, yielding no more than 16% worse RMSEs when measurements were missing (40%) or laden with added noise. Hence, the individualized model provides a practical means to develop an early warning system for reducing heat-injury risk. NEW & NOTEWORTHY A model that uses an individual’s noninvasive measurements and environmental variables can continually “learn” the individual’s heat-stress response by automatically adapting the model parameters on the fly to provide real-time individualized core body temperature estimates. This individualized model can replace impractical invasive sensors, serving as a practical and effective surrogate for core temperature monitoring.
Generalization without Systematicity: On the Compositional Skills of Sequence-to-Sequence Recurrent Networks

Humans can understand and produce new utterances effortlessly, thanks to their compositional skills. Once a person learns the meaning of a new verb "dax," he or she can immediately understand the meaning of "dax twice" or "sing and dax. " In this paper, we introduce the SCAN domain, consisting of a set of simple compositional navigation commands paired with the corresponding action sequences. We then test the zero-shot generalization capabilities of a variety of recurrent neural networks (RNNs) trained on SCAN with sequence-to-sequence methods. We find that RNNs can make successful zero-shot generalizations when the differences between training and test commands are small, so that they can apply "mix-and-match" strategies to solve the task. However, when generalization requires systematic compositional skills (as in the "dax" example above), RNNs fail spectacularly. We conclude with a proof-of-concept experiment in neural machine translation, suggesting that lack of systematicity might be partially responsible for neural networks' notorious training data thirst.