Miracle-dz/UniFAR-FTUs huggingface dataset:
Lungfish aestivating activities are locked in distinct encephalic γ‐aminobutyric acid type A receptor α subunits

Ammonia in dipnoans plays a crucial role on neuronal homeostasis, especially for those brain areas that maintain torpor and awakening states in equilibrium. In the present study, specific α subunits of the major neuroreceptor inhibitory complex (GABAAR), which predominated during some phases of aestivation of the lungfish Protopterus annectens, turned out to be key adaptive factors of this species. From the isolation, for the first time, of the encoding sequence for GABAAR α1, α4, and α5 subunits in Protopterus annectens, qPCR and in situ hybridization levels of α4 transcript in thalamic (P < 0.001) and mesencephalic (P < 0.01) areas proved to be significantly higher during long aestivating maintenance states. Very evident α5 mRNA levels were detected in diencephalon during short inductive aestivating states, whereas an α4/α1 turnover characterized the arousal state. Contextually, the recovery of physiological activities appeared to be tightly related to an evident up‐regulation of α1 transcripts in telencephalic and cerebellar sites. Surprisingly, TUNEL and amino cupric silver methods corroborated apoptotic and neurodegenerative cellular events, respectively, above all in telencephalon and cerebellum of lungfish exposed to long maintenance aestivating conditions. Overall, these results tend to underlie a novel GABAergic‐related ON/OFF molecular switch operating during aestivation of the lungfish, which might have a bearing on sleeping disorders. © 2011 Wiley‐Liss, Inc.
High podoplanin and low E‐cadherin levels correlate with better prognosis in adenoid cystic carcinoma

As tumour spread is a complicating event for malignant salivary gland tumours, we decided to study factors related to cell adhesion and lymph vessel formation in two of the three most common malignant salivary gland tumours, mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), to clarify the clinical relevance and potential usefulness of these factors. We also included a group of polymorphous adenocarcinoma (PAC) as this tumour, in common with ACC often shows perineural growth, but in contrast to ACC has an overall good prognosis.
Transient Suppression of Ipsilateral Primary Somatosensory Cortex during Tactile Finger Stimulation

The whole human primary somatosensory (SI) cortex is activated by contralateral tactile stimuli, whereas its subarea 2 displays neuronal responses also to ipsilateral stimuli. Here we report on a transient deactivation of area 3b of the ipsilateral SI during long-lasting tactile stimulation. We collected functional magnetic resonance imaging data with a 3 T scanner from 10 healthy adult subjects while tactile pulses were delivered at 1, 4, or 10 Hz in 25 s blocks to three right-hand fingers. In the contralateral SI cortex, activation [positive blood oxygenation level-dependent (BOLD) response] outlasted the stimulus blocks by 20 s, with an average duration of 45 s. In contrast, a transient deactivation (negative BOLD response) occurred in the ipsilateral rolandic cortex with an average duration of 18 s. Additional recordings on 10 subjects confirmed that the deactivation was not limited to the right SI but occurred in the SI cortex ipsilateral to the stimulated hand. Moreover, the primary motor cortex (MI) contained voxels that were phasically deactivated in response to both ipsilateral and contralateral touch. These data indicate that unilateral touch of fingers is associated, in addition to the well known activation of the contralateral SI cortex, with deactivation of the ipsilateral SI cortex and of the MI cortex of both hemispheres. The ipsilateral SI deactivation could result from transcallosal inhibition, whereas intracortical SI–MI connections could be responsible for the MI deactivation. The shorter time course of deactivation than activation would agree with stronger decay of inhibitory than EPSP at the applied stimulus repetition rates.
The role of Homer1c in metabotropic glutamate receptor‐dependent long‐term potentiation

Group I metabotropic glutamate receptors (mGluR1/5) play a role in synaptic plasticity and they demonstrate direct interactions with the neuronal Homer1c protein. We have previously shown that Homer1c can restore the plasticity deficits in Homer1 knockout mice (H1‐KO). Here, we investigated the role of Homer1c in mGluR‐dependent synaptic plasticity in wild‐type mice, H1‐KO, and H1‐KO mice overexpressing Homer1c (KO+H1c). We used a form of plasticity induced by activation of mGluR1/5 that transforms short‐term potentiaion (STP) induced by a subthreshold theta burst stimulation into long‐term potentiation (LTP). We have shown that although acute hippocampal slices from wild‐type animals can induce LTP using this stimulation protocol, H1‐KO only show STP. Gene delivery of Homer1c into the hippocampus of H1‐KO mice rescued LTP to wild‐type levels. This form of synaptic plasticity was dependent on mGluR5 but not mGluR1 activation both in wild‐type mice and in KO+H1c. mGluR1/5‐dependent LTP was blocked with inhibitors of the MEK‐ERK and PI3K‐mTOR pathways in KO+H1c mice. Moreover, blocking Homer1c–mGluR5 interactions prevented the maintenance of LTP in acute hippocampal slices from KO+H1c. These data indicate that Homer1c–mGluR5 interactions are necessary for mGluR‐dependent LTP, and that mGluR1/5‐dependent LTP involves PI3K and ERK activation. © 2013 Wiley Periodicals, Inc.
Nucleotide sequence of the gene for the vitamin B12 receptor protein in the outer membrane of Escherichia coli

The nucleotide sequence of a 2220-base-pair fragment containing the btuB gene of Escherichia coli was determined. There was a single open reading frame which was translated into a 614-amino-acid polypeptide, the first 20 amino acids of which comprised a typical leader sequence. The putative mature or processed form had a molecular weight (66,400) and a composition in close agreement with that determined for the purified receptor. The distribution of amino acids in the receptor protein was similar to that of other outer membrane proteins, showing a fairly even distribution of charged residues and the absence of extensive hydrophobic stretches. The btuB451 mutation appears to alter the receptor to eliminate its ability to function in vitamin B12 uptake without affecting its ligand binding properties. The sequence of the DNA from this mutant was determined and revealed a leucine-to-proline (C-to-T transition) change in the eighth amino acid of the mature form.
Optimization of CD4/gp120 Inhibitors by Thermodynamic‐Guided Alanine‐Scanning Mutagenesis

As protein/protein interactions usually trigger signalling processes, inhibitors of those interactions must preclude protein binding without eliciting the signalling process themselves. To accomplish those goals, small molecules need to target those protein residues that contribute the most to binding (binding hotspots) without disturbing those residues that initiate signalling processes (allosteric hotspots). The availability of a blueprint identifying binding and allosteric hotspots will significantly aid inhibitor design and optimization. In this study, we show that in some situations the blueprint can be constructed by combining the standard technique of alanine‐scanning mutagenesis with isothermal titration calorimetry (ITC). We demonstrate the approach by developing the combined binding and allosteric hotspots blueprint for CD4/gp120, the initial interaction leading to HIV‐1 cell infection. A major finding of these studies is that not all binding hotspots are allosteric hotspots opening the possibility for the rational design of inhibitors and antagonist or agonist modulators.
Social isolation‐induced increase in NMDA receptors in the hippocampus exacerbates emotional dysregulation in mice

Epidemiological studies have shown that early life adverse events have long‐term effects on the susceptibility to subsequent stress exposure in adolescence, but the precise mechanism is unclear. In the present study, mice on postnatal day 21–28 were randomly assigned to either a group or isolated cages for 8 weeks. The socially isolated (SI) mice exhibited a higher level of spontaneous locomotor activity, a longer duration of immobility in the forced swimming test (FST), significantly less prepulse inhibition (PPI) and an increase in aggressive (but not attack) behavior. However, acute stress markedly exacerbated the attack counts of the SI mice but did not affect the group housing (GH) mice. SI mice exhibited higher synaptosomal NR2A and NR2B levels in the hippocampus as compared to the GH mice. Whole‐cell patch clamp recordings of CA1 neurons in hippocampal slices showed that the SI mice exhibited a higher input‐output relationship of NMDAR‐EPSCs as compared to the GH mice. Application of the NR2B‐specific antagonist ifenprodil produced a greater attenuating effect on NMDAR‐EPSCs in slices from the SI mice. NMDAR EPSCs recorded from the SI mice had a slower deactivation kinetic. MK‐801, CPP and ifenprodil, the NMDA antagonists, reversed acute stress‐induced exaggeration of aggressive and depressive behaviors. Furthermore, acute stress‐induced exacerbation of attack behavior in the SI mice was abolished after the knockdown of NR2B expression. These results suggest that social isolation‐induced increased expression of NMDA receptors in the hippocampus involves stress exacerbation of aggressive behaviors. Amelioration of aggressive behaviors by NMDA antagonists may open a new avenue for the treatment of psychopathologies that involve outbursts of emotional aggression in neglected children. © 2014 Wiley Periodicals, Inc.
Behavior of transplanted bone marrow-derived mesenchymal stem cells in periodontal defects.

BACKGROUND Recently, there have been an increased number of basic and clinical reports indicating the superior potential of bone marrow-derived mesenchymal stem cells (MSCs) for tissue regeneration. In periodontal treatment, previous animal studies indicated that autotransplantation of bone marrow MSCs into experimental periodontal defects enhanced periodontal tissue regeneration. However, mechanisms for periodontal tissue regeneration with MSCs are still unclear. The purpose of this study was to elucidate the behavior of transplanted MSCs in periodontal defects. METHODS Bone marrow MSCs were isolated from beagle dogs, labeled with green fluorescent protein (GFP), and expanded in vitro. The expanded MSCs were mixed with atelocollagen (2% type I collagen) at final concentrations of 2 x 10(7) cells/ml and transplanted into experimental Class III periodontal defects. Localizations of GFP and proliferating cell nuclear antigen (PCNA)-positive cells were evaluated by immunohistochemical analysis. RESULTS Four weeks after transplantation, the periodontal defects were almost regenerated with periodontal tissue. Cementoblasts, osteoblasts, osteocytes, and fibroblasts of the regenerated periodontal tissue were positive with GFP. PCNA-positive cells were present in regenerating connective tissue. CONCLUSION These findings suggest that transplanted mesenchymal stem cells could survive and differentiate into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration.
Edith Penrose's contribution to the resource-based view of strategic management

Edith Penrose's (1959) book, The Theory of the Growth of the Firm, is considered by many scholars in the strategy field to be the seminal work that provided the intellectual foundations for the modern, resource-based theory of the firm. However, the present paper suggests that Penrose's direct or intended contribution to resource-based thinking has been misinterpreted. Penrose never aimed to provide useful strategy prescriptions for managers to create a sustainable stream of rents; rather, she tried to rigorously describe the processes through which firms grow. In her theory, rents were generally assumed not to occur. If they arose this reflected an inefficient macro-level outcome of an otherwise efficient micro-level growth process. Nevertheless, her ideas have undoubtedly stimulated ‘good conversation’ within the strategy field in the spirit of Mahoney and Pandian (1992); their emerging use by some scholars as building blocks in models that show how sustainable competitive advantage and rents can be achieved is undeniable, although such use was never intended by Edith Penrose herself. Copyright © 2002 John Wiley & Sons, Ltd.
Prenatal diagnosis of congenital genu recurvatum following amniocentesis complicated by leakage

Congenital genu recurvatum (CGR) is an extremely rare condition observed at birth. It is associated with, among other malformations, genetic entities such as the Larsen syndrome. When CGR is isolated, orthopedic treatment will usually lead to a good functional prognosis. We report the first case of isolated CGR diagnosed prenatally and suspected to be a consequence of reduced amniotic fluid volume due to leakage following amniocentesis. The etiology and management options for CGR are briefly discussed. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Empirical Analysis of Object-Oriented Design Metrics for Predicting Unit Testing Effort of Classes

In this paper, we investigate empirically the relationship between object-oriented design metrics and testability of classes. We address testability from the point of view of unit testing effort. We collected data from three open source Java software systems for which JUnit test cases exist. To capture the testing effort of classes, we used metrics to quantify the corresponding JUnit test cases. Classes were classified, according to the required unit testing effort, in two categories: high and low. In order to evaluate the relationship between object-oriented design metrics and unit testing effort of classes, we used logistic regression methods. We used the univariate logistic regression analysis to evaluate the individual effect of each metric on the unit testing effort of classes. The multivariate logistic regression analysis was used to explore the combined effect of the metrics. The performance of the prediction models was evaluated using Receiver Operating Characteristic analysis. The results indicate that: 1) complexity, size, cohesion and (to some extent) coupling were found significant predictors of the unit testing effort of classes and 2) multivariate regression models based on object-oriented design metrics are able to accurately predict the unit testing effort of classes.
How Image-Based Social Media Websites Support Social Movements

The Internet has disrupted the traditional progression of social movements. We explore common characteristics of image-based activism on Instagram by qualitatively analyzing 300 Instagram posts from three social movements: Black Lives Matter, the battle against defunding Planned Parenthood, and the backlash against the Indiana Religious Freedom Restoration Act. We found that common types of images emerged among the three social movements, indicating a possible underlying pattern in social movement content posted on Instagram. Users also engage in workarounds to leverage Instagram toward a collective goal, going beyond the features offered by the platform to communicate their message. These findings have implications for future work studying social movement theories online.
Performance characteristics of two automated solid-phase red cell adherence systems for pretransfusion antibody screening: a cautionary tale

Abstract Our institution has implemented two instruments, the Galileo and the Echo, that use different solid-phase red cell adherence assays for antibody screening in pretransfusion compatibility testing. During the initial implementation of these two instruments, we noticed very different problems: falsely positive results on the Galileo, and falsely negative results and lack of reproducibility on the Echo. Comparison of falsely positive antibody screen results from approximately equivalent numbers of samples run on the Galileo and samples tested by standard manual tube technique using low-ionic-strength saline enhancement showed a false-positive rate of 1.4 percent on the Galileo (defined as a positive screen with a negative panel). Testing using the Echo identified four cases of falsely negative antibody screens, (defined as a negative screen on a patient sample subsequently shown to be positive by the same method). In addition, we note a lack of reproducibility on the Echo, which emphasizes the importance of replicate testing during validation of automated antibody screening platforms. Immunohematology2012;28:137–9.
Serum holotranscobalamine, vitamin B12, folic acid and homocysteine levels in alopecia areata patients

Alopecia areata has been associated with many autoimmune diseases. There is a common belief that the prevalance of pernicious anemia is increased in patients with alopecia areata. In this study, we sought to investigate vitamin B12, folate and homocysteine metabolism in alopecia areata. We measured holotranscobalamine (holoTC), vitamin B12, folate and homocysteine levels in 75 patients with alopecia areata and 54 controls. We did not find any significant differences in these parameters between these groups. We think that alopecia areata may not be associated with vitamin B12 deficiency. The co-occurence of pernicious anemia and alopecia areata in rare autoimmune syndromes, may not justify routine measurements of these parameters in alopecia areata patients.
Post-craniotomy intracranial infection in patients with brain tumors: a retrospective analysis of 5723 consecutive patients

Abstract Aim: To determine the risk factors for and the incidence, outcomes, and causative pathogens of post-craniotomy intracranial infection (PCII) in patients with brain tumors. Methods: A retrospective study was performed of 5723 patients with brain tumors who were surgically treated between January 2012 and December 2013 in Beijing Tiantan Hospital. The patients’ demographics, pathohistological diagnoses, surgical procedures, postoperative variables, causative pathogens, and outcomes were evaluated. Results: The overall incidence of PCII was 6.8%, and 82.1% of all cases were diagnosed within two weeks after the craniotomy. Postoperative administration of antibiotics reduced the incidence of PCII. Independent risk factors included clean-contaminated craniotomy, prolonged operation (> 7 h), external cerebrospinal fluid (CSF) drainage/monitoring device placement, and postoperative CSF leakage. Patients ≤ 45 years old were more susceptible to infection. Compared with supratentorial tumors, tumors located in the infratentorial or intraventricular regions were more vulnerable to PCII. Gram-positive bacteria were the most common causative pathogens isolated from the CSF samples, accounting for 82.0% of the PCII cases. Conclusions: Risk factors for PCII can be identified early in the perioperative period. These findings raise the possibility of improving the clinical outcomes of patients with brain tumors who undergo craniotomy.
Pathomorphological study of Kupffer cells in hepatocellular carcinoma and hyperplastic nodular lesions in the liver

A pathomorphological study was conducted to clarify the localization of Kupffer cells in hepatocellular carcinoma (HCC) tissues and such hyperplastic nodular lesions as adenomatous hyperplasia (AH) and focal nodular hyperplasia (FNH). Materials were surgical specimens of 50 HCCs, 7 AHs, and 13 FNHs. These tissues were immunohistochemically stained with an anti‐human macrophage antibody (anti‐CD68 antibody). Among CD68‐positive cells, short spindle‐shaped cells were considered as Kupffer cells, and Kupffer cell numbers in tumor lesions and surrounding liver tissues of each specimen were comparatively examined. As a result, the number of Kupffer cells in well‐differentiated HCC tissues less than 1 cm in diameter was 27.8 ± 3.3 (mean ± SE/0.25 mm2); in noncancerous tissues, it was 30.2 ± 3.2, showing no statistically significant differences. The number of Kupffer cells in cancerous tissues decreased in comparison with the number in noncancerous tissues, as the tumor size increased and histological grade decreased. In hyperplastic nodular lesions, the number was higher in nodular lesions than in the surrounding liver tissues in 4 of 7 AHs (57.1%) and 6 of 13 FNHs (46.2%). This could explain the reason why enhanced MRI, which utilizes the selective taken‐up mechanism of chondroitin sulfate iron colloid and superparamagnetic iron oxide into the reticuloendothelial system of the liver and spleen, depicts well‐ differentiated HCC and AH at the same signal intensity as in the surrounding liver tissues. Our findings also indicate that there is a limitation in differentiating or diagnosing small HCC and hyperplastic nodular lesions by using enhanced MRI, which utilizes Kupffer cell functions.
Hyperlipidemia in APOE2 transgenic mice is ameliorated by a truncated apoE variant lacking the C-terminal domain Published, JLR Papers in Press, October 16, 2002. DOI 10.1194/jlr.M200313-JLR200

Familial dysbetalipoproteinemia associated with the apolipoprotein E2 (APOE2) genotype is a recessive disorder with low penetrance. We have investigated whether additional expression of full-length APOE3, APOE4, or a truncated variant of APOE4 (APOE4-202) can reduce APOE2- associated hyperlipidemia. This was achieved using adenovirus-mediated gene transfer to mice transgenic for human APOE2 and deficient for endogenous Apoe (APOE2.Apoe−/− mice). The hyperlipidemia of APOE2.Apoe−/− mice was readily aggravated by APOE3 and APOE4 overexpression. Only a very low dose of APOE4 adenovirus was capable of reducing the serum cholesterol and triglyceride (TG) levels. Expression of higher doses of APOE4 was associated with an increased VLDL-TG production rate and the accumulation of TG-rich VLDL in the circulation. In contrast, a high dose of adenovirus carrying APOE4-202 reduced both the cholesterol and TG levels in APOE2.Apoe−/− mice. Despite the absence of the C-terminal lipid-binding domain, APOE4-202 is apparently capable of binding to lipoproteins and mediating hepatic uptake. Moreover, overexpression of APOE4-202 in APOE2.Apoe−/− mice does not aggravate their hypertriglyceridemia. These results extend our previous analyses of APOE4-202 expression in Apoe−/− mice and demonstrate that apoE4-202 functions even in the presence of clearance-defective apoE2. Thus, apoE4-202 is a safe and efficient candidate for future therapeutic applications.
Influence of mineralogy on swelling and consolidation of soils in eastern Saudi Arabia

The mineral calcium sulphate transforms from anhydrite through bassanite to gypsum and then can convert back to bassanite and anhydrite. This transformation of calcium sulphate causes volume change that adds to the poten- tial hazards with indigenous soils containing expansive clay minerals. Heave and settlement are the most important geotechnical problems associated with many argillaceous soils in eastern Saudi Arabia. Mineralogical evolution and engineering behaviour of such soils are governed by local geology and severe climatic and environmental conditions prevalent in the region. Based on laboratory investigations, this paper discusses the influence of mineralogy on swelling and consolidation of expansive clay, calcium sulphate forms, and their mixtures. Mineralogy is investigated using geotechnical index properties and thermal and X-ray diffraction analyses. Swelling and consolidation characteristics are directly determined and are studied in conjunction with microstructural assessment. Results indicate that under the hot and humid climate prevalent in eastern Saudi Arabia, form changes in calcium sulphate can take place in the time frame of engineering importance. The volume-change behaviour of local expansive clay depends on the form and amount of calcium sulphate present in the soil.