Miracle-dz/UniFAR-FTUs huggingface dataset:
Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice

Background:Neonatal exposure to anesthetics that block N-methyl-d-aspartate receptors and/or hyperactivate &ggr;-aminobutyric acid type A receptor has been shown to cause neuronal degeneration in the developing brain, leading to functional deficits later in adulthood. The authors investigated whether exposure of neonatal mice to inhaled sevoflurane causes deficits in social behavior as well as learning disabilities. Methods:Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h. Activated cleaved caspase-3 immunohistochemical staining was used for detection of apoptosis. Cognitive functions were tested by pavlovian conditioned fear test. Social behavior was tested by social recognition and interaction tests. Results:Neonatal exposure to sevoflurane significantly increased the number of apoptotic cells in the brain immediately after anesthesia. It caused persistent learning deficits later in adulthood as evidenced by decreased freezing response in both contextual and cued fear conditioning. The social recognition test demonstrated that mice with neonatal exposure to sevoflurane did not develop social memory. Furthermore, these mice showed decreased interactions with a social target compared with controls in the social interaction test, indicating a social interaction deficit. The authors did not attribute these abnormalities in social behavior to impairments of general interest in novelty or olfactory sensation, because they did not detect significant differences in the test for novel inanimate object interaction or for olfaction. Conclusions:This study shows that exposure of neonatal mice to inhaled sevoflurane could cause not only learning deficits but also abnormal social behaviors resembling autism spectrum disorder.
Functional Assessment of Misdirected Axon Growth After Nerve Repair in the Rat

Age, late repair, loss of nerve tissue, tension, and other factors are now known to influence axon regeneration and the quality of recovery after nerve repair. Many of the factors cannot be controlled by surgery. However, a few important ones depend on surgical technique, and some could be minimized, e.g., suture with tension, scarring due to foreign material, and misdirected axon growth. In this study, the authors tried to assess the functional consequences of misdirected axon growth in the sciatic nerve of the rat. They used a strainless coaptation nerve-repair technique with bioabsorbable plate support (polylactic acid), permitting them to study only the consequences of misdirected axon growth, without tension or suture in the area of nerve repair. Sixty rats were divided into three groups. In Group 1, 20 sciatic nerves were repaired without rotation of the distal nerve stump. In Group 2, 20 sciatic nerves were repaired with a 90-degree rotation of the distal nerve stump. In Group 3, 20 sciatic nerves were repaired with a 180-degree rotation of the distal nerve stump. Functional analyses were performed with the sciatic functional index. The results showed the poor consequences of incorrect nerve-end alignment in nerve repair (p < 0.05). Nerve repair with bioabsorbable plate support is known to allow good stump coaptation, without tension and without foreign material. The authors suggest an adaptation or modification of this technique, which might minimize misdirected axon growth, one of the factors whose effects can be mitigated by surgical technique.
Abnormal centrosome‐centriole cycle in chronic myeloid leukaemia?

Abnormal numbers, structures and functions of centrosomes in chronic myeloid leukaemia (CML) may influence cell proliferation and genomic instability, which are features of the disease. Centrosomes are regulators of mitotic spindle orientation and can act as scaffolds for centrosome‐associated regulators of the cell cycle. This study showed, for the first time, that p210BCR‐ABL1 and p145ABL1 are both centrosome‐associated proteins, as demonstrated by co‐immunoprecipitation with the pericentriolar protein, pericentrin. Furthermore, when CML cells were treated with imatinib there was a 55% and 20% reduction of p210BCR‐ABL1 and p145ABL1 binding to pericentrin, respectively. Cell lines expressing p210BCR‐ABL1 and primary CD34+ cells from CML patients exhibited more numerical and structural centrosomal abnormalities than p210BCR‐ABL1 negative cells. Primary cells from CML blast crisis (BC) patients exhibited a distinctive amorphous staining pattern of pericentrin compared to normal and CML chronic phase (CP) patients, suggesting a possible defect in pericentrin localisation at the centrosomes. Proteins, such as aurora kinases, pericentrin, survivin and separase, regulate centrosome structure and function, cell cycle and mitotic spindle formation. Levels of the protease, separase are abnormally high in CML CP and BC cells in comparison to normal CD34+ cells. The data imply that expression of p210BCR‐ABL1 is associated with abnormalities in the centrosome‐centriole cycle and increased separase expression.
Comparison of the results of 2 targeting methods in Gamma Knife surgery for trigeminal neuralgia.

OBJECT Gamma Knife surgery (GKS) is an effective treatment for intractable trigeminal neuralgia (TN). The authors compared results using two major GKS target points, the dorsal root entry zone and the retrogasserian portion, in a series of patients with intractable TN. METHODS One hundred patients with medically refractory TN underwent GKS between August 1998 and December 2007. Thirty-seven were men, and 63 were women. The median age at GKS was 74 years. With a single isocenter and use of a 4mm collimator, 51 patients received 80 Gy at the proximal trigeminal nerve (posterior group) and 7 patients received 80 Gy, 1 patient received 85 Gy, and 41 patients received 90 Gy at the retrogasserian portion (anterior group). Follow-up was obtained by clinic visits every 3-6 months after GKS. Data on pain control, complications, and pain recurrence were recorded. The relationships between pain control status, complications, recurrence, and the target portions (anterior vs posterior) were analyzed. RESULTS The median duration of follow-up was 30 months (range 3-88 months). Initially, 87 patients achieved pain-free status and 64 achieved complete remission. At the final follow-up visit, 68 patients were still in pain-free status and 42 were in complete remission. Recurrence of facial pain occurred in 15 patients. Forty-one patients developed some degree of trigeminal dysfunction. The rate of initial complete remission was higher in the posterior group than in the anterior group (p = 0.003). More complications were observed in the anterior group than in the posterior group (p = 0.009). CONCLUSIONS The posterior targeting group had better pain control and a lower complication rate. The authors recommend the posterior targeting method and use of 80 Gy for treatment of TN with GKS.
Contribution au projet de génomique structurale du virus d'Epstein-Barr : l'Uracile-ADN glycosylase et les enzymes du métabolisme des acides nucléiques

Le virus d'Epstein-Barr (EBV) est un γ -herpesvirus humain. Il est responsable de maladies telles que la mononucleose-infectieuse et il est associe a de nombreux carcinomes et syndromes immunoproliferatifs. A la difference d'autres herpesvirus tel que herpes-simplex, il n'existe actuellement aucun medicament efficace contre EBV. Le genome d'EBV contient 86 cadres de lecture soit autant de cibles potentielles pour une approche de genomique structurale, permettant le developpement rationnel de nouvelles therapies. La premiere serie de cibles sur laquelle nous avons travaille code pour 23 proteines. De facon inattendue, le principal probleme rencontre lors de ce projet fut la faible expression ainsi que l'insolubilite d'une grande partie des cibles. Parmi les 8 proteines solubles, 5 furent cristallisees a l'issue de quoi, 4 structures furent resolues. La clef de la reussite de ce projet fut un traitement individuel de chaque cible plutot que l'utilisation de protocoles standards. La partie centrale de ce travail porte sur l'Uracile-ADN Glycosylase (UNG). C'est une enzyme de reparation de l'ADN. Il nous fut impossible d'obtenir des cristaux de la proteine seule, mais, grâce a la formation d'un complexe avec une proteine inhibitrice produite par le phage PBS-2, nous obtinmes des cristaux diffractant a 2.3 A. La structure de ce complexe nous permis l'expliquer l'organisation de la « boucle leucine », un domaine du site actif, qui comporte une insertion de 7 residus chez tous les γ-herpesvirus. Malgre cette difference, les constantes catalytiques de l'UNG d'EBV sont proches de celles des autres UNGs ce qui suggere un mecanisme similaire d'interaction avec l'ADN. Le travail sur d'autres cibles et les difficultes qui leur sont inherentes est egalement aborde (notamment l'Alkaline Exonuclease).
A secondary drug resistance mutation of TEM-1 beta-lactamase that suppresses misfolding and aggregation.

In Gram-negative bacteria, TEM-1 beta-lactamase provides the major mechanism of plasmid-mediated beta-lactam resistance. Natural variants of TEM-1 with increased antibiotic resistance have appeared in response to the use of extended-spectrum beta-lactam antibiotics (e.g., ceftazidime) and beta-lactamase inhibitors (e.g., clavulanic acid). Some of the variant enzymes are more efficient at catalyzing beta-lactam hydrolysis, whereas others are more resistant to inhibitors. M182T is a substitution observed in both types of variant TEM-1 beta-lactamases. This mutation is found only in combination with other amino acid substitutions, suggesting that it may correct defects introduced by other mutations that alter the specificity. An engineered core mutation, L76N, which diminishes the periplasmic beta-lactamase activity by 100-fold, was used as a model to understand the mechanism of suppression of the M182T mutation. Biochemical studies of the L76N enzyme alone and in combination with the M182T mutation indicate that the M182T substitution acts at the level of folding but does not affect the thermodynamic stability of TEM-1 beta-lactamase. Thus, the M182T substitution is an example of a naturally occurring mutation that has evolved to alter the folding pathway of a protein and confer a selective advantage during the evolution of drug resistance.
Early history of subplate and interstitial neurons: from Theodor Meynert (1867) to the discovery of the subplate zone (1974)

In this historical review, we trace the early history of research on the fetal subplate zone, subplate neurons and interstitial neurons in the white matter of the adult nervous system. We arrive at several general conclusions. First, a century of research clearly testifies that interstitial neurons, subplate neurons and the subplate zone were first observed and variously described in the human brain – or, in more general terms, in large brains of gyrencephalic mammals, characterized by an abundant white matter and slow and protracted prenatal and postnatal development. Secondly, the subplate zone cannot be meaningfully defined using a single criterion – be it a specific population of cells, fibres or a specific molecular or genetic marker. The subplate zone is a highly dynamic architectonic compartment and its size and cellular composition do not remain constant during development. Thirdly, it is important to make a clear distinction between the subplate zone and the subplate (and interstitial) neurons. The transient existence of the subplate zone (as a specific architectonic compartment of the fetal telencephalic wall) should not be equated with the putative transient existence of subplate neurons. It is clear that in rodents, and to an even greater extent in humans and monkeys, a significant number of subplate cells survive and remain functional throughout life.
Inphase and Quadrature Utilization for Pairing Diversity and Interference Exploitation in Uplink OFDMA

This paper proposes a new pairing cooperative technique to achieve spatial diversity and constructive interference exploitation in uplink orthogonal frequency-division multiple access (OFDMA) systems. The underlying principle is to pair users such that their symbols are combined into a single constellation, according to a predefined rule, so that the same symbol is transmitted by each pair of users so their signals can be coherently summed at the receiver, hence maximizing the received signal power. To achieve such constructive combination of both signal copies, single-dimensional OFDMA is utilized in the inphase and quadrature dimensions. It will be shown that such transmission method not only maximizes the received power but also greatly reduces sensitivity to timing misalignment between the cooperating users. Both time synchronous and asynchronous transmission scenarios will be considered. In the asynchronous case, interference reduction will be applied at the base station to reinstate the pairs' orthogonality and hence minimize co-channel interference. The performance of this technique is evaluated through simulations and mathematical analysis. It will be shown that the results from both models closely match and that the proposed technique provides significant bit-error-rate reductions, particularly at low signal-to-noise ratio, and throughput improvements relative to existing cooperative transmission techniques.
CHARACTER RELEASE FOLLOWING EXTINCTION IN A CARIBBEAN REEF CORAL SPECIES COMPLEX

Abstract The Pleistocene extinction of the widespread organ-pipe Montastraea coral had measurable morphological and ecological effects on surviving lineages of the Montastraea “annularis” species complex. Extinction of the organ-pipe Montastraea occurred after more than 500,000 years of dominance in the shallow-water reef habitat of Barbados. Extinction resulted in a morphological shift of the columnar Montastraea lineage from thick to thin columns in modern reef environments. Pleistocene colonies of the columnar morphotype sympatric with organ-pipe Montastraea showed greater column widths than those in allopatry. We subjected our data to a number of criteria for interpreting the morphological shift as character release following lifting of competitive pressure after extinction. The morphological differences do not appear to be due either to chance or to physical properties of the marine environment. Differential local extinction and recolonization of four members of the species complex did not occur on Barbados, so that the species coexisted and appear to have coevolved between more than 600,000 and 82,000 years ago. The morphological shift is related to coral growth form and growth rate, and thus reflects the acquisition of a primary resource in corals—light. Character release occurred at the same oceanic Caribbean island (Barbados) where environments have fluctuated with similar variance throughout the period of coexistence. Not only has competition among living members of the Montastraea “annularis” species complex been convincingly demonstrated, but trends in relative abundance among fossil members of the species complex strongly suggest that a competitive hierarchy was operating during their Pleistocene coexistence on Barbados. We also observed an ecological analogue to character release on another Caribbean island, Curaçao. The distribution and abundance of living columnar M. annularis s.s. and massive M. faveolata from the leeward reef crest in Curaçao is greater now than in the Pleistocene, when organ-pipe Montastraea dominated this shallow-water reef habitat. Extinction of the faster growing, shallow-water organ-pipe Montastraea resulted in higher abundance of the columnar Montastraea lineage in shallow-water habitats, where it shifted its morphology to one adapted to high light levels. The species extinction released surviving lineages from a competitive network that had resulted in lower rank abundance in the Pleistocene community and enhanced abundance of both columnar M. annularis s.s. and M. faveolata in modern communities. Full validation of our interpretation of character release must await experiments that demonstrate whether phenotypic differences between populations have a genetic basis. However, we believe the results of this study point to the important, yet heretofore neglected, role that biological interactions have played in the evolution of closely related reef coral species. Corresponding Editor: D. Geary
Quality of life 12 months after coronary artery bypass graft surgery.

OBJECTIVE The primary purpose of this study was to assess the relationship between preoperative risk factors, postoperative chronic pain, sleep, and gender on perceptions of quality of life (QoL) in a sample of 123 coronary artery bypass graft (CABG) surgery patients 12 months after surgery. A secondary purpose was to determine whether there is concordance between spousal and patient reporting of QoL after CABG surgery. DESIGN A cross-sectional comparative study. SETTING The study setting included patients living in the community, who had had CABG surgery 12 months earlier at The Alfred hospital, a major metropolitan public acute care center, in Melbourne, Australia. PARTICIPANTS Study participants were 123 adult patients (mean age = 64 years) who had undergone CABG surgery and had participated in a recent clinical trial. These patients were followed up to 12 months. The patient's spouse or next of kin (NoK) was asked questions about their perception of change in the patient's QoL. INSTRUMENTS Results were assessed using The Medical Outcome Study Short Form-36 (SF-36) questionnaire and additional questions given at 12 months after CABG surgery. The Cleveland Clinic Clinical Severity Score (CSS) was used preoperatively as a tool to predict QoL outcome. RESULTS Significant improvements in QoL, as measured by the SF-36, were seen in physical functioning (P <.0001), bodily pain (P =.024), social functioning (P =.011), and role limitations resulting from emotional status (P =.003). Other significant associations (P =.002) were found between poor QoL and patients who reported severe pain or poor quality sleep. Low-risk patients, as identified by the preoperative CSS, were more likely to have improved QoL at 12 months. Alteration in QoL was reported equally by patients and their spouses or NoK. Short-term memory impairment was reported by 41% of spouses or NoK. CONCLUSIONS CABG surgery results in improved QoL for the majority of patients with extensive coronary artery disease. Nevertheless, some patients continue to have severe pain, sleep disturbances, and altered relationship with their spouse or NoK 12 months after surgery.
Comparison of traditional and novel tableting excipients: Physical and compaction properties

Context: Novel tableting excipients are continuously developed and advertised with superior flow and compaction characteristics. Objective: The objective of this study was to compare two traditionally used and two novel tableting excipients with regard to their physical and tableting properties as well as their magnesium stearate sensitivity. Avicel® PH102 (microcrystalline cellulose) was compared to the novel co-processed excipient Prosolv® SMCC90 (silicified microcrystalline cellulose), whereas Anhydrous Emcompress® (anhydrous dicalcium phosphate) was compared to the novel spherically granulated excipient Fujicalin® (anhydrous dicalcium phosphate). Materials and methods: True density, particle size, specific surface area (SSA), flowability, tabletability, and magnesium stearate sensitivity of the excipients was determined. Results and discussion: Due to the silification process (Prosolv®) and the unique manufacturing process (Fujicalin®), the novel excipients showed a comparably larger SSA. Hardest tablets by far could be obtained with Prosolv®, followed by Avicel® and Fujicalin®. Avicel® and Prosolv® were sensitive to magnesium stearate, whereas Fujicalin® and Emcompress® did not show lubricant sensitivity. This confirms the plastic deformation behavior of microcrystalline cellulose and the brittle fracture of anhydrous dicalcium phosphate. Conclusion: Compared to the traditional excipients the investigated novel tableting excipients were advantageous with regard to their SSA and their tableting properties.
Suppression of tumour necrosis factor‐α by Schizonepeta tenuifolia water extract via inhibition of IκBα degradation and Jun N‐terminal kinase/stress‐activated protein kinase activation

Objectives The anti‐inflammatory effects of an aqueous extract of Schizonepeta tenuifolia on lipopolysaccharide (LPS)‐induced tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) in vivo and in vitro have been investigated.
A conserved N‐terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins

The three FET (FUS, EWSR1, and TAF15) family RNA binding proteins are expressed in all tissues and almost all cell types. The disordered N‐terminal parts are always present in FET fusion oncoproteins of sarcomas and leukemia. Mutations in FUS and TAF15 cause aggregation of FET proteins in neurological disorders. Here we used recombinant proteins in pulldown experiments and mass spectrometry to identify major interaction partners of the FET N‐terminal parts. We report that FUS, EWSR1, and TAF15 form homo‐ and heterocomplexes as major binding partners and identify an evolutionarily conserved N‐terminal motif (FETBM1) that is required for this interaction. The binding is RNA and DNA independent and robust up to 1 M of NaCl. The localization of FETBM1 and its target sequences supports a simple model for FET protein aggregation as reported in neurological disorders such as amyotrophic lateral sclerosis, frontotemporal dementia, and essential tremor. The FETBM1 localization also explains the binding of normal full‐length FET proteins to their oncogenic fusion proteins. —Thomsen, C. , Grundevik, P., Elias, P., Ståhlberg, A. , Åman, P., A conserved N‐terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins. FASEB J. 27, 4965–4974 (2013). www.fasebj. org
No advanced retinopathy of prematurity stages 4 or 5 in a large high-risk German cohort

Background Retinopathy of prematurity (ROP) remains a major cause of juvenile blindness. As screening recommendations are refined, decreasing gestational age (GA) and birth weight (BW) constitute an increasing risk for ROP. This retrospective case series reviews the screening results of a very immature cohort in Germany. Methods We conducted ROP screening according to the German guidelines of 1999: all preterm infants with a GA of <32 weeks and/or a BW of <1501 g, or with GA ≥32 weeks and postnatal oxygen treatment for >3 days, were assigned for screening. Dense laser coagulation was performed according to the current treatment criteria. Results All 767 consecutive inborn (patients born at the Department of Neonatology, University Hospital of Cologne, Germany) preterm infants of a tertiary medical centre of maximum care underwent complete screening from 2001 to 2009. The treatment incidence was 7.0%. No preterm infant developed stage 4/5 ROP. Mean GA and BW of untreated/treated preterm infants were 28.4/24.6 weeks and 1109/635 g, respectively. Increasing treatment incidence was associated with lower GA, but not with lower BW in logistic regression analysis. Conclusion In this very immature high-risk cohort, advanced stages 4 and 5 were avoided throughout 9 years of screening. We suggest three factors that contributed to this outcome: (1) strict adherence to current ROP screening and treatment guidelines; (2) prompt and very dense laser coagulation if necessary; and (3) a specialised neonatal intensive care unit with experience of very immature babies.