Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatiotemporal PET Imaging of Dynamic Metabolic Changes After Therapeutic Approaches of Induced Pluripotent Stem Cells, Neuronal Stem Cells, and a Chinese Patent Medicine in Stroke

This study aimed to use spatiotemporal PET imaging to investigate the dynamic metabolic changes after a combined therapeutic approach of induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs), and Chinese patent medicine in a rat model of cerebral ischemia–reperfusion injury. Methods: Cerebral ischemia was established by the middle cerebral artery occlusion approach. Thirty-six male rats were randomly assigned to 1 of the 6 groups: control phosphate-buffered saline (PBS), Chinese patent medicine (Qing-kai-ling [QKL]), induced pluripotent stem cells (iPSCs), combination of iPSCs and QKL, neuronal stem cells (NSCs), and combination of NSCs and QKL. Serial 18F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohistochemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation. Results: Compared with the PBS control group, significantly higher 18F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1–4. Interestingly, the most intensive 18F-FDG accumulation was found in the NSCs + QKL group at week 1 but in the iPSCs + QKL group at week 4. The neurofunctional scores in the 5 treatment groups were significantly higher than that of the PBS group from week 3 to 4. In addition, there was a significant correlation between the PET imaging findings and neurofunctional recovery (P < 0.05) or glucose transporter-1 expression (P < 0.01). Immunohistochemical and immunofluorescence studies found that transplanted iPSCs survived and migrated to the ischemic region and expressed protein markers for cells of interest. Conclusion: Spatiotemporal PET imaging with 18F-FDG demonstrated dynamic metabolic and functional recovery after iPSCs or NSCs combined with QKL in a rat model of cerebral ischemia–reperfusion injury. iPSCs or NSCs combined with Chinese medicine QKL seemed to be a better therapeutic approach than these stem cells used individually.
Effect of Substrate on Release of Myocardial Norepinephrine and Ventricular Arrhythmias Following Reperfusion of the Ischemic Isolated Working Rat Heart

Summary Isolated rat hearts were prelabeled with 3H-norepinephrine (NE), submitted to coronary artery ligation, and perfused through the left atrium with a modified Krebs-Henseleit solution containing 3 mM potassium and four different substrates: 5.5 mM glucose, 5.5 mM glucose plus 0.15 or 0.5 mM palmitate bound to albumin in a molar ratio of 6:1, and 11 mM glucose. The coronary artery ligature was removed after 30 min of perfusion of the ischemic working heart. With all substrates the release of radioactivity in the coronary effluent remained relatively constant during the ischemic period. Reperfusion was associated with a sudden release of radioactivity and of 3H-NE, but the intensity of the efflux was influenced by the nature of the perfusion substrate. The highest release was observed with 5.5 mM glucose and the lowest release in the presence of 0.15 mM palmitate. Intermediate and similar releases were seen with the two other substrates. On reperfusion of the ischemic heart, ventricular arrhythmias (tachycardia and fibrillation) were very marked with 5.5 mM glucose and in the presence of 0.5 mM palmitate. They were significantly delayed in the presence of 0.15 mM palmitate and almost absent with 11 mM glucose. These results do not show a relationship between the amount of NE liberated during the post-ischemic period and the extent of ventricular reperfusion arrhythmias. We conclude that either myocardial NE is not implicated in the genesis of reperfusion arrhythmias or that cardiac vulnerability to the arrhythmogenic effect of NE is influenced by the metabolic state of the myocardium, which is dependent on the nature of the perfusion substrate.
Cellular Immune Response to Diverse Islet Cell Antigens in IDDM

In IDDM, T-cells are postulated to mediate the destruction of pancreatic β-cells. We analyzed peripheral blood mononuclear cell (PBMC) responses to human insulin, glutamate decarboxylase GAD65, tyrosine phosphatase ICA512, glucagon, membrane preparations of RIN cells and human pancreas, and three control antigens (La = nuclear cell antigen, tetanus toxoid, and phytohemagglutinin). A total of 28 patients with newly diagnosed IDDM, 9 antibody-positive (Ab+) first-degree relatives, and 16 healthy control subjects were included. Increased proliferative responses to pancreatic islet cell antigens were observed in diabetic patients and in Ab+ relatives compared with control subjects, whereas T-cell reactivity to nonpancreatic control antigens was similar between the study groups. The highest differences in the magnitude of proliferative responses were seen for ICA512, followed by membrane preparations of RIN cells, GAD65, and human pancreas. Few subjects reacted with insulin or glucagon. Interestingly, Ab+ relatives showed higher T-cell reactivity with respect to stimulation indexes and prevalences than newly diagnosed diabetic patients, and as many as 89% of Ab+ relatives showed proliferation to more than one islet cell antigen preparation in comparison to 43% of newly diagnosed diabetic patients and none of the control subjects. Statistical analysis revealed significant positive correlation of insulin autoantibody levels with the levels of insulin-specific T-cells in Ab+ relatives, but no relation of PBMC responses to age, sex, or HLA-DR haplotypes. Our results demonstrate the simultaneous existence of various autoreactive T-cells specific for islet cell antigens in the prediabetic period. These T-cells may play a significant role in the pathogenesis of the disease.
Ischemic preconditioning protects liver from hepatectomy under hepatic inflow occlusion for hepatocellular carcinoma patients with cirrhosis.

AIM To investigate the protective effect of ischemic preconditioning (IPC) on hepatocellular carcinoma (HCC) patients with cirrhosis undergoing hepatic resection under hepatic inflow occlusion (HIO) and its possible mechanism. METHODS Twenty-nine consecutive patients with resectable 0HCC were randomized into two groups: IPC group: before HIO, IPC with 5 min of ischemia and 5 min of reperfusion was given; control group: no IPC was given. Liver functions, hepatic Caspase-3 activity, and apoptotic cells were compared between these two groups. RESULTS On postoperative days (POD) 1, 3 and 7, the aspartate transaminase (AST) and alanine transaminase (ALT) levels in the IPC group were significantly lower than those in the control group (P<0.05). On POD 3 and 7, the total bilirubin level in the IPC group was significantly lower than that in the control group (P<0.05). On POD 1, the albumin level in the IPC group was higher than that in the control group (P = 0.053). After 1 h of reperfusion, both hepatic Caspase-3 activity and apoptotic sinusoidal endothelial cells in the IPC group were significantly lower than those in the control group (P<0.05). CONCLUSION IPC has a potential protective effect on HCC patients with cirrhosis. Its protective mechanism underlying the suppression of sinusoidal endothelial cell apoptosis is achieved by inhibiting Caspase-3 activity.
Susceptibility of N'Dama and Boran cattle to sequential challenges with tsetse‐transmitted clones of Trypanosoma congolense

Summary The susceptibility of N'Dama cattle (Bos taurus) to four consecutive infections with different tsetse‐transmitted clones of Trypanosoma congolense was compared with that of Borans (Bos indicus). All animals were aged 13 months al the start of the study and had been born and raised free from trypanosomiasis under the same management and nutritional conditions, thereby limiting environmental factors that could have influenced susceptibility. While cattle of both breeds were equally susceptible to the establishment of trypanosome infections, the N'Damas exhibited superior resistance. Despite infection with virulent parasites, the N'Damas gained weight at the same rate as uninfected control animals, they did not develop anaemia to the extent that trypanocidal drug treatment was required, and all made a spontaneous recovery to normal hacmatological values within two to four months. In contrast, all the Borans needed treatment during the course of the four infections because of severe anaemia and showed markedly reduced liveweight gains. These clinical differences in the N'Damas were associated with two repcatable characteristics, namely, the ability to control parasitaemia and to‘resist’ anaemia, processes that did not appear to be linked. Also in contrast to the Borans. the N'Damas were able to mount accelerated haemopoietic responses, resulting in the reduced severity of anaemia following a primary infection. These findings pose the question as to whether the ability to control parasitaemia and to‘resist’ anaemia could be used as criteria for identifying resistant or trypanotolerant cattle.
Activation of transcription initiation from the nac promoter of Klebsiella aerogenes

The nac gene of Klebsiella aerogenes encodes a bifunctional transcription factor that activates or represses the expression of several operons under conditions of nitrogen limitation. In experiments with purified components, transcription from the nac promoter was initiated by sigma 54 RNA polymerase and was activated by the phosphorylated form of nitrogen regulator I (NRI) (NtrC). The activation of the nac promoter required a higher concentration of NRI approximately P than did the activation of the Escherichia coli glnAp2 promoter, and both the promoter and upstream enhancer element contributed to this difference. The nac promoter had a lower affinity for sigma 54 RNA polymerase than did glnAp2, and uninitiated competitor-resistant transcription complexes formed at the nac promoter decayed to competitor-sensitive complexes at a greater rate than did similar complexes formed at the glnAp2 promoter. The nac enhancer, consisting of a single high-affinity NRI-binding site and an adjacent site with low affinity for NRI, was less efficient in stimulating transcription than was the glnA enhancer, which consists of two adjacent high-affinity NRI-binding sites. When these binding sites were exchanged, transcription from the nac promoter was increased and transcription from the glnAp2 promoter was decreased at low concentrations of NRI approximately P. Another indication of the difference in the efficiency of these enhancers is that although activation of a nac promoter construct containing the glnA enhancer was relatively insensitive to subtle alterations in the position of these sites relative to the position of the promoter, activation of the natural nac promoter or a nac promoter construct containing only a single high-affinity NRI approximately P binding site was strongly affected by subtle alterations in the position of the NRI approximately P binding site(s), indicating a face-of-the-helix dependency for activation.
Born in blood : the lost secrets of freemasonry

Its mysterious symbols and rituals had been used in secret for centuries before Freemasonry revealed itself in London in 1717. Once known, Freemasonry spread throughout the world and attracted kings, emperors, and statesmen to take its sacred oaths. It also attracted great revolutionaries such as George Washington and Sam Houston in America, Juarez in Mexico, Garibaldi in Italy, and Bolivar in South America. It was outlawed over the centuries by Hitler, Mussolini, and the Ayatollah Khomeini. But where had this powerful organization come from? What was it doing in those secret centuries before it rose from underground more than 270 years ago? And why was Freemasonry attacked with such intense hatred by the Roman Catholic church? This amazing detective story answers those questions and proves that the Knights Templar in Britain, fleeing arrest and torture by pope and king, formed a secret society of mutual protection that came to be called Freemasonry. Based on years of meticulous research, this book solves the last remaining mysteries of the Masons_their secret words, symbols, and allegories whose true meanings had been lost in antiquity. With a richly drawn background of the bloody battles, the opportunistic kings and scheming popes, the tortures and religious persecution throughout the Middle Ages, it is an important book that may require that we take a new look at the history of events leading to the Protestant Reformation.
First mutation in the βA2-crystallin encoding gene is associated with small lenses and age-related cataracts.

PURPOSE A new mouse mutant with small lenses was identified within a mutagenesis screen. The aim of the study was to determine its molecular and morphologic characterization. METHODS The offspring of paternally N-ethyl-N-nitrosourea (ENU)-treated C57BL/6J mice were analyzed for eye-size parameters by noninvasive in vivo laser interference biometry. RESULTS A new mutant characterized by a clear, but significantly smaller lens without any changes for cornea thickness, anterior chamber depth, or aqueous humor size, was identified. The smaller size of the lens was more pronounced in the homozygous mutants, which were fully fertile and viable. The mutation was mapped to chromosome 1 between the markers D1Mit251 and D1Mit253. Using a positional candidate approach, the βA2-crystallin encoding gene Cryba2 was sequenced; a T→C exchange at cDNA position 139 led to a p.S47P amino-acid alteration. The eyes of newborn homozygous mutants showed no gross changes. At the age of three weeks, some clefts appeared at the cornea, but the lens and retina appeared without major changes. At the age of 25 weeks, the lenses of the heterozygous mutants develop a subcapsular cortical cataract, but the lenses of homozygous mutants were completely opaque. CONCLUSIONS These findings demonstrate the first mutation in the Cryba2 gene. In contrast to the closely linked Cryg gene cluster, no congenital cataract mutation could be attributed to the Cryba2 gene. Therefore, the human CRYBA2 gene should be considered as a strong candidate gene for age-related cataracts, and the slightly smaller size of the lens might be recognized as an early biomarker for age-related cataracts.
Functional Switch from Facilitation to Inhibition in the Control of Glutamate Release by Metabotropic Glutamate Receptors*

We have investigated the role of metabotropic glutamate receptors linked to phosphoinositide hydrolysis in the control of glutamate release in cerebrocortical nerve terminals. The activation of these receptors with the agonist 3,5-dihydroxyphenylglycine enhanced intrasynaptosomal diacylglycerol and facilitated both the depolarization-induced increase in the cytosolic free Ca2+ concentration and the release of glutamate. However, 5 min after receptor activation, a second stimulation of the pathway with the agonist failed to produce diacylglycerol and to facilitate glutamate release. Interestingly, during the period in which the diacylglycerol response was desensitized, a strong agonist-induced inhibition of Ca2+entry and glutamate release was observed. This change in the presynaptic effects of 3,5-dihydroxyphenylglycine is reversible since 30 min after the first stimulation, the agonist-induced inhibition of release disappeared, whereas both the production of diacylglycerol and the facilitation of glutamate release were recovered. The tonic elevation of the extracellular glutamate concentration from basal levels (0.8 μm) up to 5 μm also produced the switch from facilitation to inhibition in the receptor response. The existence of this activity-dependent switch in the presynaptic control of glutamate release suggests that release facilitation is limited to conditions under which an appropriate clearance of synaptic glutamate exists, probably to prevent the neurotoxic accumulation of glutamate in the synapse.
Recovering from spousal bereavement in later life: does volunteer participation play a role?

OBJECTIVES Volunteering is an important component of social life but may be interrupted by life events. This research investigated how widowhood influences subsequent volunteer participation as well as the potential moderating effect volunteer participation may have in coping with the death of a spouse. METHODS Analysis of three waves (1986-1994) of longitudinal data from the Americans' Changing Lives study tested (a) the effect of widowhood on volunteer participation, (b) the influence of the timing since becoming widowed on volunteering and personal well-being, and (c) the interaction effects of volunteering and widowhood on personal well-being. A cross-sectional time-series design is used to test relationships with people aged 50 years and older at baseline. RESULTS Compared with their continually married counterparts, people who experienced spousal loss reported greater likelihood of pursuing volunteer roles, not immediately but a few years after the death of their spouse. Volunteer roles adopted after spousal loss protected against depressive symptoms, and increases in volunteer hours enhanced self-efficacy. DISCUSSION These patterns highlight the compensatory function of volunteer participation that helps to offset the negative impact of widowhood on well-being in later life.
Increased Coherence of Circadian Rhythms in Mature Fibroblast Cultures

Circadian transcriptional rhythms in confluent NIH 3T3 and PER2::LUCIFERASE fibroblast cultures become more coherent as they mature. This enhanced coherence correlated with increased culture density, while inhibition of the cell cycle increased coherence in immature cultures. Mature cultures may therefore express more coherent rhythms for longer because of their reduced rate of cell division. The authors conclude that mature fibroblast cultures will be of great utility for high-throughput pharmacological and mutational circadian screening.
Optimization of Rosmarinic Acid Production by Lavandula vera MM Plant Cell Suspension in a Laboratory Bioreactor

The all‐round effect of dissolved oxygen concentration, agitation speed, and temperature on the rosmarinic acid production by Lavandula veraMM cell suspension was studied in a 3‐L laboratory bioreactor by means of the modified Simplex method. Polynomial regression models were elaborated for description of the process of rosmarinic acid production (Y) in the bioreactor as a consequence of the variation of the dissolved oxygen (X1) concentration between 10% and 50%; agitation (X2) between 100 and 400 rpm; and temperature (X3) between 22 and 30 °C. The optimization made it possible to establish the optimal conditions for the biosynthesis of rosmarinic acid by L. veraMM: dissolved oxygen (X1*), 50% of air saturation; agitation (X2*), 400 rpm; and temperature (X3*), 29.9 °C, where maximal yield (Ymax) of 3489.4 mg/L of rosmarinic acid was achieved (2 times higher compared with the shake‐flasks cultivation).
Simple Magnetic Swallowing Detection System

A magnetic swallowing-detection system that can detect swallowing sounds and measure the distance between two magnetic coils was developed to detect the swallowing function non-invasively. The coils were set on both sides of the thyroid cartilage, and the distance between them changes in accordance with the movement of the thyroid cartilage. Swallowing sounds were detected by a piezoelectric microphone attached to the neck. The coils and microphone were installed in a holding unit that can be positioned at the front of the neck. The system was simultaneously used with videofluorography (VF) to measure nine healthy subjects while they swallowed liquid barium. To evaluate the correlation between the swallowing event detected by the magnetic swallowing-detection system and the swallowing event obtained from VF, two-dimensional positions of the hyoid bone in each VF image were detected. Based on the detection results, the swallowing starting time that was detected by the magnetic swallowing-detection system coincided with that determined from VF, namely, 38±172 ms. The coincidence among the peak time point of VF, that of the distance between the magnetic coils, and that of the swallowing sound appeared to have an intraclass correlation coefficient of 0.9. Correlation between the peak time points of the VF tracking waveforms, the peak time points of distance between the magnetic coils, and the peak timing of the swallowing sound had an intraclass correlation coefficient of 0.9. It can be concluded that the magnetic swallowing-detection system can detect swallowing movements simply and non-invasively without x-ray exposure.
Cigarette Smoke-induced Ca2+ Release Leads to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Dysfunction*

Background: COPD is the 4th leading cause of death worldwide, yet little is known about its pathogenesis. Results: Exposure to cigarette smoke elevated intracellular Ca2+ levels, which triggered CFTR internalization/inhibition. Conclusion: Cigarette smoke-induced Ca2+ release and CFTR inhibition may be involved in COPD pathogenesis. Significance: Our data provide novel information regarding the underlying mechanism of cigarette smoke-induced lung injury. Chronic obstructive pulmonary disease affects 64 million people and is currently the fourth leading cause of death worldwide. Chronic obstructive pulmonary disease includes both emphysema and chronic bronchitis, and in the case of chronic bronchitis represents an inflammatory response of the airways that is associated with mucus hypersecretion and obstruction of small airways. Recently, it has emerged that exposure to cigarette smoke (CS) leads to an inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel, causing airway surface liquid dehydration, which may play a role in the development of chronic bronchitis. CS rapidly clears CFTR from the plasma membrane and causes it to be deposited into aggresome-like compartments. However, little is known about the mechanism(s) responsible for the internalization of CFTR following CS exposure. Our studies revealed that CS triggered a rise in cytoplasmic Ca2+ that may have emanated from lysosomes. Furthermore, chelation of cytoplasmic Ca2+, but not inhibition of protein kinases/phosphatases, prevented CS-induced CFTR internalization. The macrolide antibiotic bafilomycin A1 inhibited CS-induced Ca2+ release and prevented CFTR clearance from the plasma membrane, further linking cytoplasmic Ca2+ and CFTR internalization. We hypothesize that CS-induced Ca2+ release prevents normal sorting/degradation of CFTR and causes internalized CFTR to reroute to aggresomes. Our data provide mechanistic insight into the potentially deleterious effects of CS on airway epithelia and outline a hitherto unrecognized signaling event triggered by CS that may affect the long term transition of the lung into a hyper-inflammatory/dehydrated environment.