Miracle-dz/UniFAR-FTUs huggingface dataset:
The Regulation of Dendritic Spine Plasticity by EphB and N-methyl-D-aspartate Receptors Through Spatial Control Over Cofilin Activity in Mature Hippocampal Neurons

Dendritic spines are the post-synaptic sites of most excitatory synapses in the brain, and changes in their morphology are implicated in synaptic plasticity and long-term memory. F-actin dynamics are thought to be a basis for both the formation of dendritic spines during development and their structural plasticity (Ethell and Pasquale, 2005; Pontrello and Ethell, 2009). We have shown that the F-actin-severing protein cofilin, which is regulated by phosphorylation, can induce remodeling of mature dendritic spines in hippocampal neurons (Shi et al ., 2009). We also demonstrate that b-Arrestins play an important role in spatial control over cofilin activity in dendritic spines, which underlies NMDA-mediated dendritic spine remodeling. Cofilin activity in dendritic spines is regulated through CaMKII-mediated suppression of cofilin activity by phosphorylation, and calcineurin-dependent cofilin activation through its dephosphorylation. In addition, while the EphB receptor promotes spine stabilization through cofilin inactivation, the NMDA receptor prevents EphB-mediated cofilin inactivation through calcineurin. NMDAR activation also promotes the translocation of cofilin to dendritic spines, an event that requires cofilin dephosphorylation and is also dependent on b-Arrestins, which have recently been shown to scaffold cofilin with its regulators, LIM kinase and slingshot phosphatase (Zoudilova et al ., 2010). Our studies demonstrate that cofilin clustering in the spines is affected in both b-Arrestin1- and b-Arrestin2- deficient neurons under normal synaptic activity, and a constitutively-active cofilin S3A mutant fails to translocate to spines in response to NMDA in b-Arrestin2 KO neurons. Moreover, while wt neurons display dendritic spine remodeling in response to NMDA or with over-expression of cofilin S3A , b-Arrestin2-deficient neurons are resistant to both NMDA-induced and cofilin S3A -induced spine remodeling. In contrast, dominant-negative cofilin S3D prevents NMDA-induced dendritic spine remodeling in wt neurons, and also rescues a mature spine phenotype that is lost in b-Arrestin1 KO neurons. In addition, over-expression of b-Arrestin in the KO neurons rescues spine abnormalities. b-Arrestin1-deficient neurons also develop immature spines in vivo , whereas hippocampal neurons lacking b-Arrestin2 develop normal mature spines, but fail to remodel in response to NMDA. Our studies demonstrate novel functions of b-Arrestin1 in the development of mature dendritic spines, and b-Arrestin2 in NMDAR-mediated dendritic spine plasticity through spatial control over cofilin activity.
Absorption and Utilization of Choline and Vitamin B12 in Lactating Dairy Cows using Different Delivery Methods

Improving vitamin B12 absorption is important for optimal performance in dairy cows and for increasing vitamin B12 concentrations in milk for human consumption. However, 80% of a supplement of synthetic vitamin B12, cyanocobalamin (CN-CBL), is degraded in the rumen of dairy cows and only 25% of the amount escaping destruction in the rumen disappears in the small intestine. The objective of this study was to evaluate the efficacy of casein and whey proteins as delivery methods for CN-CBL in solution to increase intestinal absorption of vitamin B12 in cows measuring portal drained viscera (PDV) flux. Four multiparous lactating Holstein cows (236 ± 17 DIM) equipped with a rumen cannula and catheters in the portal vein and a mesenteric artery were used in a randomized cross-over design. They were fed 12 equal meals per day to maintain steady-state. On experimental days, they received a post-ruminal bolus of: 1) CN-CBL alone (0.1g; CA), 2) CN-CBL (0.1g) + casein (10 g; CC) or 3) CN-CBL (0.1g) + whey proteins (10 g; CW). After the bolus, blood samples were taken simultaneously from the 2 catheters every 15 min during the first 2 h and then every 2 h until 24 h post-bolus. Milk yield, DMI, arterial and PDV flux of vitamin B12 were analyzed by the MIXED procedure. Milk yield and DMI were not affected by treatments. Arterial plasma concentrations of vitamin B12 increased when CN-CBL was infused with dairy proteins (average 408 pg/ml, CC and CW) compared with CA (323 pg/ml). On average the PDV net flux of vitamin B12 was positive during the first 45 min after the post-ruminal bolus; the maximal value was already reached 30 49 min after the bolus and decreased rapidly thereafter. The PDV net flux of vitamin B12 during the 24 h period following the bolus of vitamin was greater when the vitamin was given in solution with casein (CC, 4 μg/h) whereas the PDV net flux of vitamin B12 was negative for CA and CW (-25 μg/h and -19 μg/h, respectively). Only 0.74% of the total amount of vitamin B12 infused post-ruminally reached the portal blood within the first 45 min and then there was no further release until 24 h after the bolus. The present results suggest that CN-CBL given with casein increased vitamin B12 absorption as compared to CN-CBL given alone. For practical applications of our findings, development of a casein-based formulation may improve CN-CBL absorption in dairy cows.
Les courbes de croissance chez les oiseaux

This bibliographic review presents, for poultry species, the main mathematical functions used to describe the growth curve : Richards, Gompertz, logistic and Janoschek functions. In a second part, methods commonly used to estimate the parameters of these curves are reported. The influence of species size, ecological factors, sex and selection are studied in a third part. Finally, the available estimations of the genetic parameters of the parameters of the growth curve are presented.
Investigating the role of 53BP1 in regulating gene transcription.

53BP1 is a DNA damage responsive protein that plays a crucial role in checkpoint activation and DNA repair. In addition to its involvement in the cellular response to DNA damage, it has been suggested that 53BP1 can also function to regulate gene expression. 53BP1 was originally identified in a yeast two-hybrid screen for novel modulators of p53 transcriptional activity. Despite this, the role of 53BP1 in transcriptional regulation remains poorly understood. To investigate the effect of 53BP1 on cellular transcription, a microarray approach was utilised to study the gene expression patterns in cells treated with and without 53BP1 siRNA, before and after ionising radiation. Microarray analysis identified numerous genes whose expression was regulated by 53BP1 in the absence and presence of DNA damage. These data suggest that 53BP1 functions as a transcriptional regulator. In support of this, in vitro and in vivo studies have shown that 53BP1 binds to the transcriptional co-activators, CBP and p300. These findings indicate that the binding of 53BP1 to CBP and p300 may be facilitating its role as a regulator of transcription.
Molecular Characterization of Respiratory Bacterial Pathogens in Large and Small Ruminants

Bacterial isolates from different cases of respiratory infections in small and large ruminants were evaluated using bacterial culture and semi-nested PCR and identification was confirmed by DNA sequencing. Universal primers targeting the bacterial 16S rRNA for bacteria were used. Other sets of primers that were specific for Gram-positive bacteria and combinations of primers specific for Gram-negative organisms were used in the second PCR. The amplified PCR products were subjected to DNA sequence analysis. The DNA sequences of the isolated bacteria were aligned with the DNA sequences of bacteria in the GenBank through BLAST. Results confirmed isolation of three Gram-positive and two Gram-negative organisms. Gene sequence studies demonstrated identification of the Gram-positive microorganisms as Staphylococcus sciuri, Staphylococcus sporosarcinae and Bacillus pumilus while the identified Gram-negative organisms were Acinetobacter schindleri and Pseudomonas aeruginosa from ruminants manifesting clinical signs of respiratory infection.
MicroRNAs expression analysis in high grade gliomas

Several biomarkers had been proposed as useful parameters to better define the prognosis or to delineate new target therapy strategies for glioblastoma (GBM) patients. MicroRNAs could represent interesting molecules, for their role in tumorigenesis and cancer progression and for their specific tissue expression. Although many studies have tried to identify a specific microRNAs signature for glioblastoma, by now an exhaustive GBM microRNAs profile is far to be well defined. In this work we set up a real-time qPCR, based on LNA primers, to investigate the expression of 19 microRNAs in brain tumors, focusing our attention on GBMs. MiRNAs expression in 30 GBM paired FFPE-Fresh/Frozen samples was firstly analyzed. The good correlation obtained comparing miRNAs results confirmed the feasibility of performing miRNAs analysis starting from FFPE tissues. This leads to many advantages, as a good disposal of archival tumor and normal brain specimens and the possibility to verify the percentage of tumor cells in the analyzed sample. In the second part we compared 3 non-neoplastic brain references to use as control in miRNAs analysis. Normal adjacent the tumor, epileptic specimens and a commercial total RNA were analyzed for miRNAs expression and results showed that different non-neoplastic controls could lead to important discrepancies in GBM miRNAs profiles. Analyzing 50 FFPE GBMs using all 3 non-neoplastic references, we defined a putative GBM miRNAs signature: mir-10b, miR-21 and miR-27a resulted upregulated, while miR-7, miR-9, miR-26a, miR-31, miR-101, miR-137, miR-222 and miR-330 were downregulated. Comparing miRNAs expression among GBM group and gliomas of grade I, II and III, we obtained 3 miRNAs (miR-10b, mir-34a and miR-101) showing a different regulation status between high grade and low grade gliomas. Intriguingly, miR-10b was upregulated in high grade and significantly downregulated in low grade gliomas, suggesting that could be a candidate for a GBM target therapy.
Modulation of exercise-induced gene expression in human skeletal muscle by exercise intensity, training status and short- term endurance training

A single bout of exercise generates a robust, but transient, increase in mRNA abundance for a multitude of genes, which is thought to contribute to the recovery from and adaptation to exercise. Adaptation to exercise training is mediated by the accumulation of pulses of elevated mRNA after individual exercise bout within a training program, leading to longer term increases in protein abundance that culminate in physiological adaptations. Several signalling pathways involving cytoplasmic protein kinases, transcription factors and their coregulators are recognised as regulators by which activation transduces physiological stimuli into transcriptional adaptations. This thesis examined the modulation of gene expression in human skeletal muscle under varying physiological conditions, including divergent exercise intensities, untrained and trained muscle, and short-term endurance training. Compared to low intensity isocaloric exercise (400 kcal, 40%VO2peak), a single bout of high intensity exercise (80% VO2peak) resulted in greater activation of the signalling kinases AMPK and CaMKII, coincident with a larger increase in mRNA abundance of PGC-1α and FOXO1A during recovery. A single bout exercise induced an increase in PGC-1α. FOXO1A, and PDK4 mRNA abundance in both untrained and trained muscle. This may form part of a transcriptional response that contributes to exercise-induced alterations in skeletal muscle metabolism such as glucose sparing and increased fat oxidation during recovery from exercise. Fourteen consecutive days of endurance training resulted in the accumulation of mRNA and corresponding protein for some (ERRα, COXIV), but not all (FOXO1A, PDK4), reportedly acute exercise-responsive genes. This suggests that certain genes are involved in the restoration of homeostasis after acute exercise, whereas others are involved in adaptation to regular exercise. Our results illustrate the well-described phenomenology of skeletal muscle plasticity and suggest that transcript level adjustments underlie modulation of skeletal muscle metabolism and phenotype by regular exercise.
Reply to

mutational status in solid tumors, preliminary texture analysis of computed tomography images showed significant associations with KRAS mutations in colorectal cancer and intrahepatic recurrence after resection for CLM. Given the diverse prognosis among patients undergoing liver resection, a future preoperative prediction of KRAS-mutated tumors using imaging biomarkers would have the potential to identify genetic patterns in a prospective manner, and allow appropriate patient selection for targeted agents and anatomic resection, resulting in improved survival outcome. Radiogenomics has made it possible to extend clinical imaging into genomic imaging and decode tumor phenotypes noninvasively. Notably, radiogenomics is still in its infancy. Standardized imaging protocols with large datasets and multicenter validation are warranted for translation of robust imaging biomarkers into clinical practice. Consequently, genomic-oriented surgical management will empower a step forward in personalized treatment of CLM and radiogenomics may provide a promising paradigm for better surgical decision support.
Use of Bacillus subtilis as biocontrol agent. IV. Salt-stress tolerance induction by Bacillus subtilis FZB24 seed treatment in tropical vegetable field crops, and its mode of action

The rhizobacterium Bacillus subtilis FZB24 registered as biocontrol agent was field tested as a promoter for salt- tolerance to two cultivars of eggplant and pepper in saline soil in the Sinai region (Egypt) under the condition of irrigation with ground saline water. The use of Bacillus subtilis for root bacterization was realized by watering the seedlings with bacterial spore-(preparation-)suspension, titer 10 8 spores/ml. Starting from 8 weeks after transplanting and for 4 weeks, fruit yield (kg/m2), number of fruits/plant, average fruit fresh weight, dry weight percentage and fruit size were evaluated. Compared with the unsaline-irrigated control the yield was reduced in both vegetable crops in all used cultivars, due to irrigating the plants with saline groundwater to more than 90 %. By using Bacillus subtilis FZB24 in the plots irrigated with saline groundwater, the yield increased up to 550 % in eggplants, and up to 430 % in the pepper cultivars, as compared with unbacterized ones. Also in the other plant growth parameters, significant promotions could be found in the bacterized plants in the saline plots. So, the bacterization caused 50 and 25 % reduction in salinity effect on the yield of eggplants and pepper, respectively, and consequently resulted in a remarkable salt-stress tolerance induction, which varied its degree according to the used plant species. To have insight on the mode of actions of the salt stress tolerance-inducing effect of Bacillus subtilis FZB 24, model experiments have been conducted with auxin precursors and IAA in tomato seedlings under controlled, axenic conditions and under salt-stress conditions similar to the field experiment. Up to now, it has been hypothesized for the mode of action of Bacillus subtilis FZB24, which acts as plant growth and health promoter, and stress tolerance inducer, that the given bacterial production of auxin and auxin precursors during root colonization induces a push in the plant auxin synthesis with changing regulation of the appropriate mechanisms. In the model experiments, the pretreatment of seedlings with millimolare amounts of auxin precursors, tryptophan, indole-3-pyruvic acid or indole-3-acetic aldehyde, 75 % growth reduction in untreated seedlings under salt stress could be compensated completely after 1 week. That was not observed to the same degree after preapplication of auxin (IAA). So, the presented model experiment could support the hypothesis of salt-stress tolerance induction in Bacillus subtilis FZB24-treated plants. The results are discussed from the aspect of a general anti-stress effect of Bacillus subtilis FZB24.
Saxifraga banmaensis and S. dingqingensis, two new species of the Saxifragaceae from China

Saxifraga banmaensis J. T. Pan and S. dingqingensis J. T. Pan, two species of the genus Saxifraga (Saxifragaceae) from China, are described and illustrated. Of these, S. banmaensis J. T. Pan is known only from Banma County, Qinghai Province, and related to S. umbellulata Hook. f. & Thoms. (including varieties), but differs by having sepals cartilaginous-mucronulate at apex, and petals linear, not pandurate-oblong to pandurate, base not unguiculate. S. dingqingensis J. T. Pan occurs in Dingqing County, Xizang, and is similar to S. llonakhensis W. W. Smith, but differs by having sepals 3-veined, veins confluent at apex, petals 8-callose, 4–5-veined, base truncate or subauriculate. Both species are endemic to China, and belong to subsect. Rosulares Gornall.
Tocilizumab prevents renal function of a patient with diabetic kidney disease: case report

Abstract Diabetic kidney disease (DKD) is the major cause of end stage renal disease. Despite the best current treatment, it is difficult to stop the progression of DKD. We report a 77-year-old Japanese man in whom rheumatoid arthritis (RA) was diagnosed at the age of 30 years, followed by type 2 diabetes mellitus (T2DM) at age 55. His haemoglobin A1c (HbA1c) was around 7–9%, even after starting insulin therapy. His renal function deteriorated steadily, with the estimated glomerular filtration rate (eGFR) decreasing by 2 mL/min/1.73 m2 per year to reach 29 mL/min/1.73 m2 (consistent with stage IV diabetic kidney disease) at age 69. Because RA was poor controlled with a DAS28-ESR of 4.46, HAQ of 0.375, and SDAI of 8.6, treatment with tocilizumab (an interleukin-6 receptor antibody) was initiated. Thereafter, control of RA improved, but HbA1c stayed in the range of 7–9%. However, eGFR remained around 30 ml/min/1.73 m2 even after 8 years. This case indicates that interleukin-6 might contribute to exacerbation of renal dysfunction, since IL-6 receptor blockade prevented deterioration of renal function in this patient with RA and diabetic kidney disease.
Seven-year Genotype Distribution Among Hepatitis C Patients in a City in the Central Anatolia Region of Turkey

1Istanbul Medeniyet University Göztepe Training and Research Hospital, Medical Microbiology Laboratory, Istanbul, Turkey 2Istanbul Kartal Dr. Lütfi Kırdar Training and Research Hospital, Medical Microbiology Laboratory, Istanbul, Turkey 3Necmettin Erbakan University Meram Faculty of Medicine, Department of Medical Microbiology, Konya, Turkey Seven-year Genotype Distribution Among Hepatitis C Patients in a City in the Central Anatolia Region of Turkey
Bilateral Ruptured Ectopic Pregnancies with Massive Hemo-Peritonium: A Case Report in a Resource-Low Setting in Sub-Saharan Africa

Background: Bilateral ruptured ectopic pregnancy is the rupture of two implanted product of conception outside of the uterine cavity. Bilateral ruptured ectopic pregnancy without an initial induction of ovulation is extremely rare. It’s occurrence with a major life threatening complication such as massive hemo-peritonium worsens the prognosis. Immediate diagnosis and surgical intervention is required. Few cases have been identified. Case report: We report the case of bilateral ruptured ectopic pregnancy with massive hemo-peritonium diagnosed in a 28-year- old female and managed at African Genesis Health Clinic Yaounde. Discussion and Conclusion: prompt diagnosis and surgical intervention is needed to improve the prognosis related to bilateral ruptured ectopic pregnancies with massive hemo-peritonium. Counseling for assisted means of procreation is important.
Investigating susceptibility to bipolar disorder, migraine and epilepsy

Epidemiological and clinical studies demonstrate a high degree of comorbidity between bipolar disorder (BD) and migraine. A relationship between BD and epilepsy is also suggested, with both disorders displaying phenotypically similar symptom profiles. The overall aim of this thesis was to further explore the relationship between BD and the neurological conditions of migraine, and epilepsy, within a large, well-characterised sample of individuals with BD. Data were utilised from the Bipolar Disorder Research Network (BDRN); a large (n>6000) UK sample of individuals with a diagnosis of BD. Lifetime history of migraine and epilepsy were assessed within BDRN using questionnaire and telephone interview methods. Migraine was highly prevalent within the bipolar sample and was found to disproportionately affect those with bipolar II disorder. Bipolar subjects with comorbid migraine experienced a relatively distinct illness profile, with a multivariate model revealing migraine comorbidity to be characterised by an increased risk of suicide attempt and anxiety disorder. Further analysis of the migraine phenotype revealed that observed differences in the clinical presentation of BD associated with migraine were largely associated with the migraine with aura subtype. A high rate of self-reported epilepsy was identified within the bipolar sample and group differences were revealed in the clinical course of the bipolar illness according to the presence of self-reported epilepsy. Multivariate analysis revealed an independent association of a history of suicide attempt with self-reported epilepsy within BD. Findings from this thesis highlight the importance of identifying migraine and epilepsy within BD, and that their recognition and treatment may have a beneficial impact on the course of illness and outcome in BD. This thesis also suggests that these comorbidities may represent a clinically useful subgroup characterised by specific clinical features, and may provide an opportunity for subcategorising for future aetiological studies, potentially facilitating the identification of shared pathophysiological mechanisms.
Approches intégrées du génome et du transcriptome dans les maladies complexes humaines

Cette these a pour objet l'etude du lien genotype-transcriptome et de son influence sur le developpement des maladies multifactorielles. Les apports de ce travail sont a la fois methodologiques et appliques. Nous etudions d'abord le lien genotype-transcriptome en etablissant la liste des eQTL (expression Quantitative Trait Loci) dans le monocyte et nous evaluons l'apport de l'observation des eQTL pour l'interpretation des analyses d'association genome entier (GWAS). Nous proposons ensuite une methode pour l'identification de variants genetiques affectant des modules de genesco-regules que nous appliquons a l'etude des donnees d'expression de monocytes issus d'une large etude populationnelle (GHS). Nous mettons ainsi en evidence plusieurs loci affectant l'expression de modules de genes co-regules, dont plusieurs sont impliques dans la predisposition au diabete de type I. Nous montrons egalement que le processus d'isolation des cellules monocytaires peut engendrer des biais lies a la contamination par des types cellulaires non desires et nous proposons une approche pour controler ce type de biais dans les analyses.