Miracle-dz/UniFAR-FTUs huggingface dataset:
JNK regulation of neurogenesis, neuroplasticity and anxiety-related behaviors in mice

8 SAMMANFATTNING (SWEDISH ABSTRACT) . 9 REVIEW OF LITERATURE . 10 1. Introduction to Anxiety disorders . 10 1.1. Anxiety disorders . 10 1.2. Stress and anxiety disorders . 11 1.3. Neurobiology of Anxiety . 13 1.4. Treatments of anxiety disorders . 14 1.5. Modeling anxiety . 16 1.5. 1. Exploratory‐based approach‐avoidance conflict tests . 16 1.5. 2. Other anxiety related tests . 18 1.6. Neuroplasticity changes associated with anxiety disorders . 18 2. Adult neurogenesis . 21 2.1. Role of adult hippocampal neurogenesis in brain . 23 2.3. Factors regulating the adult hippocampal neurogenesis . 24 2.4. Stress and adult hippocampal neurogenesis . 24 2.5. Role of adult hippocampal neurogenesis in anxiety . 26 2.6. Manipulation of neurogenesis in rodents . 27 3. Mitogen activated protein kinases (MAPKs) . 29 3.1. Introduction to MAPK signaling pathways . 29 3.2. MAPK signaling in the central nervous system and implications in anxiety behavior . 31 4. c-JunN-terminal kinase (JNK) pathway . 32 4.1. Physiological functions of JNK signaling in the brain . 33 4.2. Role of JNK in regulating neuronal cytoskeleton . 35 4.2.1. JNK regulates microtubule dynamics via Microtubule associated protein 2 (MAP2) . 37 4.2. 2. JNK regulates actin dynamics via Myristoylated alanine‐rich C‐kinase substrate like protein (MARCKSL1) . 38 4.3. Stress and JNK signaling . 39 4.4. JNK in neuropsychiatric disorders . 40 4.5. The JNK pathway as a therapeutic target . 41 OBJECTIVES . 44 EXPERIMENTAL PROCEDURES . 45 1. Materials . 45 1.1. Plasmids . 45
Single Phase buck-boost derived PV micro-inverter with power decoupling capability

Single Phase micro-inverters have become very popular in grid connected residential PV systems due to their modular structure, plug-and-play attribute and control flexibility. These inverters are geared with power decoupling capability to suppress the reflection of pulsating output power on PV outputs. This paper presents a novel single stage buck-boost derived PV micro-inverter focusing on use of intermediate capacitor for power decoupling. The transformer-less doubly grounded topology ensures removal of common mode ground current issues. The circuit operation and analysis are verified by simulation results.
The timing resolution of scintillation-detector systems: Monte Carlo analysis

Recent advancements in fast scintillating materials and fast photomultiplier tubes (PMTs) have stimulated renewed interest in time-of-flight (TOF) positron emission tomography (PET). It is well known that the improvement in the timing resolution in PET can significantly reduce the noise variance in the reconstructed image resulting in improved image quality. In order to evaluate the timing performance of scintillation detectors used in TOF PET, we use Monte Carlo analysis to model the physical processes (crystal geometry, crystal surface finish, scintillator rise time, scintillator decay time, photoelectron yield, PMT transit time spread, PMT single-electron response, amplifier response and time pick-off method) that can contribute to the timing resolution of scintillation-detector systems. In the Monte Carlo analysis, the photoelectron emissions are modeled by a rate function, which is used to generate the photoelectron time points. The rate function, which is simulated using Geant4, represents the combined intrinsic light emissions of the scintillator and the subsequent light transport through the crystal. The PMT output signal is determined by the superposition of the PMT single-electron response resulting from the photoelectron emissions. The transit time spread and the single-electron gain variation of the PMT are modeled in the analysis. Three practical time pick-off methods are considered in the analysis. Statistically, the best timing resolution is achieved with the first photoelectron timing. The calculated timing resolution suggests that a leading edge discriminator gives better timing performance than a constant fraction discriminator and produces comparable results when a two-threshold or three-threshold discriminator is used. For a typical PMT, the effect of detector noise on the timing resolution is negligible. The calculated timing resolution is found to improve with increasing mean photoelectron yield, decreasing scintillator decay time and decreasing transit time spread. However, only substantial improvement in the timing resolution is obtained with improved transit time spread if the first photoelectron timing is less than the transit time spread. While the calculated timing performance does not seem to be affected by the pixel size of the crystal, it improves for an etched crystal compared to a polished crystal. In addition, the calculated timing resolution degrades with increasing crystal length. These observations can be explained by studying the initial photoelectron rate. Experimental measurements provide reasonably good agreement with the calculated timing resolution. The Monte Carlo analysis developed in this work will allow us to optimize the scintillation detectors for timing and to understand the physical factors limiting their performance.
Musculoskeletal Manifestations in Pediatric Acute Leukemia

Background: In children, acute leukemia (AL) at presentation can mimic several orthopaedic pathologies, so that a variable delay of the correct diagnosis is often reported. Methods: To define more clearly the clinical and radiological musculoskeletal manifestations of leukemia in children, 122 affected children referred from 1984 to 1999 to our Pediatric Onco-Hematologic Clinic were retrospectively reviewed. Average age at diagnosis was 6.6 years (from 7 months to 17 years). Seventy-three (60%) were boys and adolescent boys, 49 (40%) were girls and adolescent girls. One hundred two (83.6%) had acute lymphoblastic leukemia, 20 (16.4%) had acute myeloid leukemia. The mean follow-up was 8.2 years for the 104 survivors and 2.5 years for the 18 nonsurvivors. The &khgr;2 test was used to perform the statistical analyses. Results: At presentation, complaints related to the musculoskeletal system were frequent (38.3%), including pain (34.4%), functional impairment (22.9%), limping (12.3%), swelling (10.6%), and joint effusion (5.7%). At presentation, 40.2% of children had at least 1 radiographic abnormality. In order, they were osteolysis (13.1%), metaphyseal bands (9.8%), osteopenia (9%), osteosclerosis (7.4%), permeative pattern (5.7%), pathological fractures (5.7%), periosteal reactions (4.1%), and mixed lysis-sclerosis lesions (2.5%). Different from previous reports, late radiographic lesions were uncommon (5.7%), probably because of milder newer medication protocols. They included avascular necrosis (3.3%), vertebral collapses (1.6%), and osteolysis (0.8%). Conclusions: Both clinical and radiological changes had various and no uniform localization. Poor correlation was found between symptoms and radiological lesions. Survival rates in children with AL were 95.8% at 1 year, 89.6% at 3 years, 85.8% at 5 years, and 83.4% at 10 and at 13 years. Radiographic abnormalities (P = 0.400), type of leukemia (P = 0.291), sex (P = 0.245), and white blood cell count at presentation (P = 0.877) were not prognostic factors. The presence of multiple bone lesions did not affect the survival rate (P=0.632). As early diagnosis significantly decreases morbidity and mortality of AL, the orthopaedist should suspect AL in any child with unexplained persistent skeletal pain or radiographic alterations. Accurate history, general physical examination, and complete blood cell count tests should address the suspicion, which is confirmed by a peripheral and/or iliac crest bone marrow biopsy. Level of Evidence: Retrospective comparative study III.
Leucine Supplementation Improves Skeletal Muscle Regeneration after Cryolesion in Rats

This study was undertaken in order to provide further insight into the role of leucine supplementation in the skeletal muscle regeneration process, focusing on myofiber size and strength recovery. Young (2-month-old) rats were subjected or not to leucine supplementation (1.35 g/kg per day) started 3 days prior to cryolesion. Then, soleus muscles were cryolesioned and continued receiving leucine supplementation until 1, 3 and 10 days later. Soleus muscles from leucine-supplemented animals displayed an increase in myofiber size and a reduction in collagen type III expression on post-cryolesion day 10. Leucine was also effective in reducing FOXO3a activation and ubiquitinated protein accumulation in muscles at post-cryolesion days 3 and 10. In addition, leucine supplementation minimized the cryolesion-induced decrease in tetanic strength and increase in fatigue in regenerating muscles at post-cryolesion day 10. These beneficial effects of leucine were not accompanied by activation of any elements of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin signalling pathway in the regenerating muscles. Our results show that leucine improves myofiber size gain and strength recovery in regenerating soleus muscles through attenuation of protein ubiquitination. In addition, leucine might have therapeutic effects for muscle recovery following injury and in some muscle diseases.
Skydive: An interactive data visualization engine

Visualization provides a powerful means for data analysis. To be most effective, visual analytics tools must support the fluent and flexible use of visualizations at fast rates. This becomes increasingly difficult with the increasing size of real-world datasets. First, large databases make interactivity more difficult as a query across the entire data can be slow. Second, any attempt to show all items from a dataset will overload the visualization, resulting in clutter.
Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin.

The decline in the high incidence of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer-type dementia among the Chamorro population of the western Pacific islands of Guam and Rota, coupled with the absence of demonstrable viral and hereditable factors in this disease, suggests the gradual disappearance of an environmental factor selectively associated with this culture. One candidate is seed of the neurotoxic plant Cycas circinalis L. , a traditional source of food and medicine which has been used less with the Americanization of the Chamorro people after World War II. Macaques were fed the Cycas amino acid beta-N-methylamino-L-alanine, a low-potency convulsant that has excitotoxic activity in mouse brain, which is attenuated by N-methyl-D-aspartate receptor antagonists. These animals developed corticomoto-neuronal dysfunction, parkinsonian features, and behavioral anomalies, with chromatolytic and degenerative changes of motor neurons in cerebral cortex and spinal cord. In concert with existing epidemiological and animal data, these findings support the hypothesis that cycad exposure plays an important role in the etiology of the Guam disease.
Dynamic Characteristics of the Cardiovascular Autonomic Effects during Severe Arterial Hypoxia in the Unanesthetized Rabbit

The reflex autonomic effects due to inhalation of low concentrations of oxygen (Pao2 30 mm Hg) were assessed in unanesthetized rabbits from the differences in responses between groups of normal and autonomically “deefferented” rabbits and those with selective effector block. Changes due to autonomic effects were estimated for heart rate, total and regional (portal, renal, muscle, and cutaneous) peripheral resistance, and the rate of epinephrine secretion. The autonomic effects could be described by an early component having a time course similar to the initial vagal effects, where the maximum change occurred soon after the start of hypoxia and then declined to 37% of this value in 5 minutes, and a late component similar to the neural effects in muscle, starting 5 minutes after the start of hypoxia and rising slowly to 63% of the maximum in 15 minutes. Four autonomic effector patterns involving different combinations of early and late components were distinguished: (1) vasoconstriction in the portal and renal beds followed the time course of the sum of early and late components; (2) inhibition of cutaneous constrictor tone was the mirror image of the above response; (3) the biphasic sympathoadrenal effect on heart rate was the sum of a negative early and positive late component; (4) the neural constrictor effect in muscle and the rate of epinephrine secretion had only a late component. The early effects resulted in reduction in cardiac output and major redistribution of peripheral blood flow, probably due to chemoreceptor stimulation. During the late phase, cardiac output rose and blood flow was redistributed further, probably mainly through baroreceptor mechanisms.
The association between Diabetes mellitus and Depression

Depression occurrence is two to three times higher in people with diabetes mellitus, the majority of the cases remaining under-diagnosed. The purpose of this review was to show the links between depression and diabetes, point out the importance of identifying depression in diabetic patients and identify the possible ways to address both diseases. Possible common pathophysiological mechanisms as stress and inflammation were explained, while emphasis was made on screening for depression in diabetic patients. An important aspect for the diabetic specialist would be the understanding of the common origins of diabetes and depression and the awareness of this quite common comorbidity, in order to improve the outcomes of both diseases. Abbreviations: DALYS = disability adjusted life years, DSM-5 = American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, DM1 = Type 1 diabetes mellitus, DM2 = Type 2 diabetes mellitus, HPA-axis = hypothalamus – pituitary – adrenal axis, SNS = sympathetic nervous system, BDI = Beck Depression Inventory, CES-D = Centre for Epidemiologic Studies Depression Scale, HADS = Hospital Anxiety and Depression Scale, PHQ = Patient Health Questionnaire.
Enhanced Expression of Lp-PLA2 and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaques

Background and Purpose— Circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) has emerged as a novel biomarker for cardiovascular diseases. However, the correlation between the plaque expression of Lp-PLA2 and plaque oxidative stress, inflammation, and stability as well as the clinical presentation remains poorly defined, especially for cerebrovascular disease. Therefore, this study was performed to test the hypothesis that Lp-PLA2 expression is higher in symptomatic than in asymptomatic carotid plaques of patients undergoing carotid endarterectomy. Methods— The expression of Lp-PLA2 in 167 carotid artery plaques was determined by immunoblotting and immunostaining. Plaque oxidative stress, inflammation, and stability were quantified by NAD(P)H oxidase p67phox and MMP-2 immunoblotting, oxidized LDL (oxLDL) immunoreactivity, macrophage and Sirius red collagen staining. Lysophosphatidylcholine 16:0 (lysoPC) concentration was measured in 55 plaques using liquid chromatography tandem mass spectrometry. Results— Lp-PLA2 expression was significantly higher in plaques of symptomatic patients than asymptomatic patients (1.66±0.19 versus 1.14±0.10, P<0.05) and localized mainly to shoulder and necrotic lipid core areas in colocalization with oxLDL and macrophage content. Similarly, Lp-PLA2 expression was related to collagen content, which was lower in plaques from symptomatic patients than in plaques from asymptomatic patients (9.1±2.2 versus 18.5±1.7% of staining/field, P<0.001). LysoPC plaque concentration was significantly higher in plaques of symptomatic than asymptomatic patients (437.0±57.91 versus 228.84±37.00 mmol/L, P<0.05). Conclusions— Symptomatic carotid artery plaques are characterized by increased levels of Lp-PLA2 and its product lysoPC in correlation with markers of tissue oxidative stress, inflammation, and instability. These findings strongly support a role for Lp-PLA2 in the pathophysiology and clinical presentation of cerebrovascular disease.
Upregulation of Toll-like receptor 2 expression in colorectal cancer infected by human cytomegalovirus

The aim of the present study was to investigate the association between Toll-like receptor 2 (TLR2) expression and human cytomegalovirus (HCMV) in colorectal carcinoma by detecting the expression of IE1–72, TLR2, TLR4 and tumor necrosis factor (TNF)-α in colorectal carcinoma and colon adenoma samples, as well as by analyzing the mRNA levels of the proteins in colon cancer cell lines, following HCMV infection. For this study, 56 colorectal cancer and 36 colon adenoma samples were collected, and normal mucosal tissue adjacent to the tumor was used as the control. The expression of the IE1–72, TLR2, TLR4, nuclear factor (NF)-κB and TNF-α protein was detected by immunohistochemistry. Cells from the SW480 human colon carcinoma cell line were infected with HCMV. The expression of IE1–72, TLR2, TLR4, NF-κB and TNF-α mRNA was quantified at different time points prior to and following infection. The positive expression rate of IE1–72 was 44.6% (25/56) in colorectal cancer and 41.7% (15/36) in colon adenoma. These rates were significantly higher when compared with the 12.5% (7/56) observed in the normal tissues adjacent to the cancer tissues (P<0.05). The expression levels of TLR2, TLR4, NF-κB and TNF-α in colorectal cancer and adenoma were also higher than those in the control tissues. Furthermore, the expression of IE1–72 in colorectal cancer tissues was found to correlate with TLR2 and TLR4, and the correlation coefficients were 0.515 and 0.462, respectively. Following the infection of SW480 cells, the mRNA levels of TLR2 and TNF-α increased gradually from 6 h, peaked at 48 h, and then decreased gradually. No significant differences in TLR4 and NF-κB expression were identified. The results of the present study indicated that there is a specific association between HCMV and the occurrence and development of colorectal cancer, which may be facilitated by the TLR2 signaling pathway.
The gingival biotype revisited: transparency of the periodontal probe through the gingival margin as a method to discriminate thin from thick gingiva.

AIM To detect groups of subjects in a sample of 100 periodontally healthy volunteers with different combinations of morphometric data related to central maxillary incisors and surrounding soft tissues. MATERIAL AND METHODS Four clinical parameters were included in a cluster analysis: crown width/crown length ratio (CW/CL), gingival width (GW), papilla height (PH) and gingival thickness (GT). The latter was based on the transparency of the periodontal probe through the gingival margin while probing the buccal sulcus. Every first volunteer out of 10 was re-examined to evaluate intra-examiner repeatability for all variables. RESULTS High agreement between duplicate recordings was found for all parameters, in particular for GT, pointing to 85% (kappa=0.70; p=0.002). The partitioning method identified three clusters with specific features. Cluster A1 (nine males, 28 females) displayed a slender tooth form (CW/CL=0.79), a GW of 4.92 mm, a PH of 4.29 mm and a thin gingiva (probe visible on one or both incisors in 100% of the subjects). Cluster A2 (29 males, five females) presented similar features (CW/CL=0.77; GW=5.2 mm; PH=4.54 mm), except for GT. These subjects showed a clear thick gingiva (probe concealed on both incisors in 97% of the subjects). The third group (cluster B: 12 males, 17 females) differed substantially from the other clusters in many parameters. These subjects showed a more quadratic tooth form (CW/CL=0.88), a broad zone of keratinized tissue (GW=5.84 mm), low papillae (PH=2.84 mm) and a thick gingiva (probe concealed on both incisors in 83% of the subjects). CONCLUSIONS The present analysis, using a simple and reproducible method for GT assessment, confirmed the existence of gingival biotypes. A clear thin gingiva was found in about one-third of the sample in mainly female subjects with slender teeth, a narrow zone of keratinized tissue and a highly scalloped gingival margin corresponding to the features of the previously introduced "thin-scalloped biotype" (cluster A1). A clear thick gingiva was found in about two-thirds of the sample in mainly male subjects. About half of them showed quadratic teeth, a broad zone of keratinized tissue and a flat gingival margin corresponding to the features of the previously introduced "thick-flat biotype" (cluster B). The other half could not be classified as such. These subjects showed a clear thick gingiva with slender teeth, a narrow zone of keratinized tissue and a high gingival scallop (cluster A2).
A novel statistical approach to identify co-regulatory gene modules

ChlP-chip experiments are performed to determine binding sites for transcription factors (TFs). Conventional TF-gene regulation is generated based on p-value cutoff of the binding sites as well as their distance to nearest genes. Taking into account that binding sites of one ChlP-chip experiment should follow the same specific location distribution, we proposed a statistical model using both location and significance information to weigh target genes. With multiple ChlP-chip experiments and gene expression data, we identified co-regulatory and differentially expressed gene modules with a joint clustering and Metropolis sampling approach. We demonstrated the efficiency of our method on a ChlP-chip data set with 38 breast cancer related TFs.
Pharmacological and Phytochemical Appraisal of Selected Medicinal Plants from Jordan with Claimed Antidiabetic Activities

Plant species have long been regarded as possessing the principal ingredients used in widely disseminated ethnomedical practices. Different surveys showed that medicinal plant species used by the inhabitants of Jordan for the traditional treatment of diabetes are inadequately screened for their therapeutic/preventive potential and phytochemical findings. In this review, traditional herbal medicine pursued indigenously with its methods of preparation and its active constituents are listed. Studies of random screening for selective antidiabetic bioactivity and plausible mechanisms of action of local species, domesticated greens, or wild plants are briefly discussed. Recommended future directives incurring the design and conduct of comprehensive trials are pointed out to validate the usefulness of these active plants or bioactive secondary metabolites either alone or in combination with existing conventional therapies.