bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF-κB/STAT3/PI3K signaling crosstalk in iMycEμ B lymphoma
Authors: Han Seong-Su , Yun Hwakyung , Son Dong-Ju , Tompkins Van S. , Peng Liangping , Chung Seung-Tae , Kim Joong-Su , Park Eun-Sung , Janz Siegfried 
Published: April 2010

Abstract

Background
Myc is a well known driver of lymphomagenesis, and Myc-activating chromosomal translocation is the recognized hallmark of Burkitt lymphoma, an aggressive form of non-Hodgkin's lymphoma. We developed a model that mimics this translocation event by inserting a mouse Myc cDNA gene into the immunoglobulin heavy chain locus, just upstream of the intronic Eμ enhancer. These mice, designated iMycEμ, readily develop B-cell lymphoma. To study the mechanism of Myc-induced lymphoma, we analyzed signaling pathways in lymphoblastic B-cell lymphomas (LBLs) from iMycEμ mice, and an LBL-derived cell line, iMycEμ-1.

Results
Nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were constitutively activated in iMycEμ mice, not only in LBLs but also in the splenic B-lymphocytes of young animals months before tumors developed. Moreover, inhibition of either transcription factor in iMycEμ-1 cells suppressed growth and caused apoptosis, and the abrogation of NF-κB activity reduced DNA binding by both STAT3 and Myc, as well as Myc expression. Inhibition of STAT3 signaling eliminated the activity of both NF-κB and Myc, and resulted in a corresponding decrease in the level of Myc. Thus, in iMycEμ-1 cells NF-κB and STAT3 are co-dependent and can both regulate Myc. Consistent with this, NF-κB and phosphorylated STAT3 were physically associated with one another. In addition, LBLs and iMycEμ-1 cells also showed constitutive AKT phosphorylation. Blocking AKT activation by inhibiting PI3K reduced iMycEμ-1 cell proliferation and caused apoptosis, via downregulation of NF-κB and STAT3 activity and a reduction of Myc levels. Co-treatment with NF-κB, STAT3 or/and PI3K inhibitors led to additive inhibition of iMycEμ-1 cell proliferation, suggesting that these signaling pathways converge.

Conclusions
Our findings support the notion that constitutive activation of NF-κB and STAT3 depends on upstream signaling through PI3K, and that this activation is important for cell survival and proliferation, as well as for maintaining the level of Myc. Together, these data implicate crosstalk among NF-κB, STAT3 and PI3K in the development of iMycEμ B-cell lymphomas.
Non-homologous isofunctional enzymes: A systematic analysis of alternative solutions in enzyme evolution
Authors: Omelchenko Marina V , Galperin Michael Y , Wolf Yuri I , Koonin Eugene V 
Published: April 2010

AbstractBackgroundEvolutionarily unrelated proteins that catalyze the same biochemical reactions are often referred to as analogous - as opposed to homologous - enzymes. The existence of numerous alternative, non-homologous enzyme isoforms presents an interesting evolutionary problem; it also complicates genome-based reconstruction of the metabolic pathways in a variety of organisms. In 1998, a systematic search for analogous enzymes resulted in the identification of 105 Enzyme Commission (EC) numbers that included two or more proteins without detectable sequence similarity to each other, including 34 EC nodes where proteins were known (or predicted) to have distinct structural folds, indicating independent evolutionary origins. In the past 12 years, many putative non-homologous isofunctional enzymes were identified in newly sequenced genomes. In addition, efforts in structural genomics resulted in a vastly improved structural coverage of proteomes, providing for definitive assessment of (non)homologous relationships between proteins.ResultsWe report the results of a comprehensive search for non-homologous isofunctional enzymes (NISE) that yielded 185 EC nodes with two or more experimentally characterized - or predicted - structurally unrelated proteins. Of these NISE sets, only 74 were from the original 1998 list. Structural assignments of the NISE show over-representation of proteins with the TIM barrel fold and the nucleotide-binding Rossmann fold. From the functional perspective, the set of NISE is enriched in hydrolases, particularly carbohydrate hydrolases, and in enzymes involved in defense against oxidative stress.ConclusionsThese results indicate that at least some of the non-homologous isofunctional enzymes were recruited relatively recently from enzyme families that are active against related substrates and are sufficiently flexible to accommodate changes in substrate specificity.ReviewersThis article was reviewed by Andrei Osterman, Keith F. Tipton (nominated by Martijn Huynen) and Igor B. Zhulin. For the full reviews, go to the Reviewers' comments section.
Brain perfusion in fibromyalgia patients and its differences between responders and poor responders to gabapentin
Authors: Usui Chie , Hatta Kotaro , Doi Nagafumi , Nakanishi Atsushi , Nakamura Hiroyuki , Nishioka Kusuki , Arai Heii 
Published: April 2010

Abstract
Introduction
The aim of the present study was to determine the brain areas associated with fibromyalgia, and whether pretreatment regional cerebral blood flow (rCBF) can predict response to gabapentin treatment.

Methods
A total of 29 women with fibromyalgia and 10 healthy women (without pain) matched for age were finally enrolled in the study. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc-ECD SPECT) was performed in the fibromyalgia patients and controls. A voxel-by-voxel group analysis was performed using Statistic Parametric Mapping 5 (SPM5). After treatment with gabapentin, 16 patients were considered 'responders', with decrease in pain of greater than 50% as evaluated by visual analogue scale (VAS). The remaining 13 patients were considered 'poor responders'.

Results
We observed rCBF abnormalities, compared to control subjects, in fibromyalgia including hypoperfusion in the left culmen and hyperperfusion in the right precentral gyrus, right posterior cingulate, right superior occipital gyrus, right cuneus, left inferior parietal lobule, right middle temporal gyrus, left postcentral gyrus, and left superior parietal lobule. Compared to responders, poor responders exhibited hyperperfusion in the right middle temporal gyrus, left middle frontal gyrus, left superior frontal gyrus, right postcentral gyrus, right precuneus, right cingulate, left middle occipital gyrus, and left declive. The right middle temporal gyrus, left superior frontal gyrus, right precuneus, left middle occipital gyrus, and left declive exhibited high positive likelihood ratios.

Conclusions
The present study revealed brain regions with significant hyperperfusion associated with the default-mode network, in addition to abnormalities in the sensory dimension of pain processing and affective-attentional areas in fibromyalgia patients. Furthermore, hyperperfusion in these areas was strongly predictive of poor response to gabapentin.
A recruitment maneuver increases oxygenation after intubation of hypoxemic intensive care unit patients: a randomized controlled study
Authors: Constantin Jean-Michel , Futier Emmanuel , Cherprenet Anne-Laure , Chanques Gérald , Guerin Renaud , Cayot-Constantin Sophie , Jabaudon Mathieu , Perbet Sebastien , Chartier Christian , Jung Boris , Guelon Dominique , Jaber Samir , Bazin Jean-Etienne 
Published: April 2010

Abstract
Introduction
Tracheal intubation and anaesthesia promotes lung collapse and hypoxemia. In acute lung injury patients, recruitment maneuvers (RMs) increase lung volume and oxygenation, and decrease atelectasis. The aim of this study was to evaluate the efficacy and safety of RMs performed immediately after intubation.

Methods
This randomized controlled study was conducted in two 16-bed medical-surgical intensive care units within the same university hospital. Consecutive patients requiring intubation for acute hypoxemic respiratory failure were included. Patients were randomized to undergo a RM immediately (within 2 minutes) after intubation, consisting of a continuous positive airway pressure (CPAP) of 40 cmH2O over 30 seconds (RM group), or not (control group). Blood gases were sampled and blood samples taken for culture before, within 2 minutes, 5 minutes, and 30 minutes after intubation. Haemodynamic and respiratory parameters were continuously recorded throughout the study. Positive end expiratory pressure (PEEP) was set at 5 cmH2O throughout.

Results
The control (n = 20) and RM (n = 20) groups were similar in terms of age, disease severity, diagnosis at time of admission, and PaO2 obtained under 10-15 L/min oxygen flow immediately before (81 ± 15 vs 83 ± 35 mmHg, P = 0.9), and within 2 minutes after, intubation under 100% FiO2 (81 ± 15 vs 83 ± 35 mmHg, P = 0.9). Five minutes after intubation, PaO2 obtained under 100% FiO2 was significantly higher in the RM group compared with the control group (93 ± 36 vs 236 ± 117 mmHg, P = 0.008). The difference remained significant at 30 minutes with 110 ± 39 and 180 ± 79 mmHg, respectively, for the control and RM groups. No significant difference in haemodynamic conditions was observed between groups at any time. Following tracheal intubation, 15 patients had positive blood cultures, showing microorganisms shared with tracheal aspirates, with no significant difference in the incidence of culture positivity between groups.

Conclusions
Recruitment maneuver following intubation in hypoxemic patients improved short-term oxygenation, and was not associated with increased adverse effects.

Trial registration
NCT01014299
Group cognitive–behavioural therapy for anxiety and depression
Authors: Whitfield Graeme 
Published: April 2010

SummaryCognitive–behavioural therapy (CBT) is a psychological treatment approach that can be delivered not only on a one-to-one basis but also to groups and in self-help formats. However, the evidence base supporting individual CBT is more extensive than the research regarding group CBT. This is likely to influence the choice of services that develop in the Improving Access to Psychological Therapies (IAPT) programme for the treatment of depression and anxiety disorders in primary care in England. This article outlines the different forms that group CBT takes, the way in which it may benefit people and the current evidence base supporting its use for anxiety and depression. It also outlines the advantages of group or individual CBT and describes those patients who appear to be best suited to a specific delivery.
Effect of early intervention on 5-year outcome in non-affective psychosis
Authors: Gafoor Rafael , Nitsch Dorothea , McCrone Paul , Craig Tom K. J. , Garety Philippa A. , Power Paddy , McGuire Philip 
Published: April 2010

BackgroundEarly specialised care may improve short-term outcome in first-episode non-affective psychosis, but it is unclear if these benefits endure.AimsTo assess the long-term effect of early intervention in psychosis.MethodIndividuals with first-episode psychosis were randomised to specialised care or care as usual (trial number: ISRCTN73679874). Outcome after 5 years was assessed by case-note review.ResultsThere were no significant differences in the admission rate (coefficient 0.096, 95% CI −0.550 to 0.742, P = 0.770) or the mean number of bed days (coefficient 6.344, 95% CI −46 to 58.7, P = 0.810).ConclusionsThese findings that specialist intervention did not markedly improved outcome at 5 years accord with those from a larger OPUS study. The sample size of this study was small and these results should be generalised with caution. More research is needed.
Cost-effectiveness of psychotherapy for cluster B personality disorders
Authors: Soeteman Djøra I. , Verheul Roel , Delimon Jos , Meerman Anke M. M. A. , van den Eijnden Ellen , Rossum Bert V. , Ziegler Uli , Thunnissen Moniek , Busschbach Jan J. V. , Kim Jane J. 
Published: April 2010

BackgroundRecommendations on current clinical guidelines are informed by limited economic evidence.AimsA formal economic evaluation of three modalities of psychotherapy for patients with cluster B personality disorders.MethodA probabilistic decision-analytic model to assess the cost-effectiveness of out-patient, day hospital and in-patient psychotherapy over 5 years in terms of cost per recovered patient-year and cost per quality-adjusted life-year (QALY). Analyses were conducted from both societal and payer perspectives.ResultsFrom the societal perspective, the most cost-effective choice switched from out-patient to day hospital psychotherapy at a threshold of €12 274 per recovered patient-year; and from day hospital to in-patient psychotherapy at €113 298. In terms of cost per QALY, the optimal strategy changed at €56 325 and €286 493 per QALY respectively. From the payer perspective, the switch points were at €9895 and €155 797 per recovered patient-year, and €43 427 and €561 188 per QALY.ConclusionsOut-patient psychotherapy and day hospital psychotherapy are the optimal treatments for patients with cluster B personality disorders in terms of cost per recovered patient-year and cost per QALY.
Drosophilafly straight by fixating objects in the face of expanding optic flow
Authors: Reiser Michael B. , Dickinson Michael H. 
Published: April 2010

SUMMARYFlies, like all animals that depend on vision to navigate through the world, must integrate the optic flow created by self-motion with the images generated by prominent features in their environment. Although much is known about the responses of Drosophila melanogaster to rotating flow fields, their reactions to the more complex patterns of motion that occur as they translate through the world are not well understood. In the present study we explore the interactions between two visual reflexes in Drosophila: object fixation and expansion avoidance. As a fly flies forward, it encounters an expanding visual flow field. However, recent results have demonstrated that Drosophila strongly turn away from patterns of expansion. Given the strength of this reflex, it is difficult to explain how flies make forward progress through a visual landscape. This paradox is partially resolved by the finding reported here that when undergoing flight directed towards a conspicuous object, Drosophila will tolerate a level of expansion that would otherwise induce avoidance. This navigation strategy allows flies to fly straight when orienting towards prominent visual features.
Mutation of theDrosophilavesicular GABA transporter disrupts visual figure detection
Authors: Fei Hao , Chow Dawnis M. , Chen Audrey , Romero-Calderón Rafael , Ong Wei S. , Ackerson Larry C. , Maidment Nigel T. , Simpson Julie H. , Frye Mark A. , Krantz David E. 
Published: April 2010

SUMMARYThe role of gamma amino butyric acid (GABA) release and inhibitory neurotransmission in regulating most behaviors remains unclear. The vesicular GABA transporter (VGAT) is required for the storage of GABA in synaptic vesicles and provides a potentially useful probe for inhibitory circuits. However, specific pharmacologic agents for VGAT are not available, and VGAT knockout mice are embryonically lethal, thus precluding behavioral studies. We have identified the Drosophila ortholog of the vesicular GABA transporter gene (which we refer to as dVGAT), immunocytologically mapped dVGAT protein expression in the larva and adult and characterized a dVGATminos mutant allele. dVGAT is embryonically lethal and we do not detect residual dVGAT expression, suggesting that it is either a strong hypomorph or a null. To investigate the function of VGAT and GABA signaling in adult visual flight behavior, we have selectively rescued the dVGAT mutant during development. We show that reduced GABA release does not compromise the active optomotor control of wide-field pattern motion. Conversely, reduced dVGAT expression disrupts normal object tracking and figure–ground discrimination. These results demonstrate that visual behaviors are segregated by the level of GABA signaling in flies, and more generally establish dVGAT as a model to study the contribution of GABA release to other complex behaviors.
Minimum viewing angle for visually guided ground speed control in bumblebees
Authors: Baird Emily , Kornfeldt Torill , Dacke Marie 
Published: April 2010

SUMMARY
To control flight, flying insects extract information from the pattern of visual motion generated during flight, known as optic flow. To regulate their ground speed, insects such as honeybees and Drosophila hold the rate of optic flow in the axial direction (front-to-back) constant. A consequence of this strategy is that its performance varies with the minimum viewing angle (the deviation from the frontal direction of the longitudinal axis of the insect) at which changes in axial optic flow are detected. The greater this angle, the later changes in the rate of optic flow, caused by changes in the density of the environment, will be detected. The aim of the present study is to examine the mechanisms of ground speed control in bumblebees and to identify the extent of the visual range over which optic flow for ground speed control is measured. Bumblebees were trained to fly through an experimental tunnel consisting of parallel vertical walls. Flights were recorded when (1) the distance between the tunnel walls was either 15 or 30 cm, (2) the visual texture on the tunnel walls provided either strong or weak optic flow cues and (3) the distance between the walls changed abruptly halfway along the tunnel's length. The results reveal that bumblebees regulate ground speed using optic flow cues and that changes in the rate of optic flow are detected at a minimum viewing angle of 23–30 deg., with a visual field that extends to approximately 155 deg. By measuring optic flow over a visual field that has a low minimum viewing angle, bumblebees are able to detect and respond to changes in the proximity of the environment well before they are encountered.
Mast cell population in the frog brain: distribution and influence of thyroid status
Authors: Monteforte Rossella , Pinelli Claudia , Santillo Alessandra , Rastogi Rakesh K. , Polese Gianluca , Baccari Gabriella Chieffi 
Published: April 2010

SUMMARYIn the developing frog brain, the majority of mast cells (MC) are distributed in the pia mater, and some immature MC are located adjacent to the blood capillaries in and around the neuropil. In the adult brain, MC are more numerous than in pre- and pro-metamorphic tadpoles; they are mainly located within the pia mater and are particularly numerous in the choroid plexuses. Many MC are found within the brain ventricles juxtaposed to the ependymal lining. MC are rarely observed in the brain parenchyma. In the adult brain, MC number is much higher than in the brain of post-metamorphic froglets. In the latter, MC number is nearly 2-fold over that found in the pre-metamorphic brain. Treatment of pre- and pro-metamorphic tadpoles with 3,5,3′-triiodothyronine (T3) and thyroxine (T4) stimulates overall larval development but does not induce a significant change in MC population within the brain. By contrast, treatment with 6-n-propyl-2-thiouracil (PTU) delays larval development and leads to a significant numerical increase of brain MC. In the adult, PTU treatment also has a similar effect whereas hypophysectomy causes a drastic decrease of MC population. The negative effects of hypophysectomy are successfully counteracted by a two-week replacement therapy with homologous pars distalis homogenate. In the adult frog, MC population seems to be refractory to thyroid hormone treatment. The present study on frog brain suggests that pituitary–thyroid axis may be involved in the regulation of MC frequency.
Carotenoid-based coloration predicts resistance to oxidative damage during immune challenge
Authors: Pérez-Rodríguez Lorenzo , Mougeot Francois , Alonso-Alvarez Carlos 
Published: April 2010

SUMMARYMany animal ornaments may have evolved as signals advertising the quality of the bearer. The honesty of the information content of these signals would rely on the costs associated with their expression, these being relatively greater for low-quality than for high-quality individuals. Given the physiological functions of carotenoids, carotenoid-based ornaments could indicate individual immunocompetence, and possibly the ability to mount an immune response at a lower cost. We evaluated whether the red carotenoid-based coloration of male red-legged partridges (Alectoris rufa) predicts the capacity of the individual to counteract the oxidative stress generated by a cell-mediated immune response. Individuals were subcutaneously injected with phytohaemagglutinin (PHA) or phosphate buffer solution (PBS) as a control. We found that eye ring pigmentation predicted the change in the amount of peroxidized lipids (TBARS) in blood after the PHA-induced inflammatory challenge. The degree of pigmentation of this carotenoid-based ornament was also negatively related to individual changes in γ-glutamyl transferase (GGT), another biomarker of oxidative stress involved in antioxidant metabolism (i.e. glutathione recycling). However, changes in circulating carotenoids did not significantly explain changes in lipid peroxidation or GGT levels, suggesting that the higher resistance to oxidative stress of those individuals with more pigmented eye rings was not directly mediated by their greater circulating levels of carotenoids. Our results indicate that carotenoid-based coloration can predict not only immune responsiveness (more coloured males mount greater responses) but also an individual's ability to counter the oxidative stress generated during immune challenge (more coloured males experience less oxidative damage when mounting an immune response).
Parental behavior in pythons is responsive to both the hydric and thermal dynamics of the nest
Authors: Stahlschmidt Zachary , DeNardo Dale F. 
Published: April 2010

SUMMARYParental behavior contributes to the success of a diverse array of taxa, and female-only nest attendance is particularly widespread. Python egg-brooding behavior is an intriguing example of female-only nest attendance because it significantly influences several critical developmental variables, namely embryonic predation, hydration, respiration and temperature. During brooding, females predominately adopt a tightly coiled posture that reduces the exchange of heat, water vapor, O2 and CO2 between the nest and clutch environment, which benefits egg water balance at the cost of respiration. To determine the plasticity of this important behavior, we manipulated nest temperature and humidity while monitoring nest–clutch thermal, hydric and respiratory relationships to test the hypothesis that female Children's pythons (Antaresia childreni) modify their egg-brooding behavior due to an interaction between environmental thermal and hydric conditions. During moderate and high nest humidity treatments (23 and 32 g m−3 H2O, respectively), females spent more time coiling tightly when the nest was cooling than when it was warming, which benefited clutch temperature. However, brooding females in low-humidity nest environments (13 g m−3 H2O) showed a high frequency of tight coiling even when the nest was warming; thus, nest temperature and humidity had an interactive effect on egg-brooding behavior in support of our hypothesis. Our results also suggest that certain egg-brooding behaviors (i.e. postural adjustments) are more energetically costly to females than other behaviors (i.e. tight coiling). In sum, we provide empirical support for the adaptive plasticity of python egg-brooding behavior, which offers insight into the general significance of female-only nest attendance in animals.