bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide ChIP-Seq reveals a dramatic shift in the binding of the transcription factor erythroid Kruppel-like factor during erythrocyte differentiation
Authors: Pilon Andre M. , Ajay Subramanian S. , Kumar Swathi Ashok , Steiner Laurie A. , Cherukuri Praveen F. , Wincovitch Stephen , Anderson Stacie M. ,   NISC Comparative Sequencing Center, Mullikin James C. , Gallagher Patrick G. , Hardison Ross C. , Margulies Elliott H. , Bodine David M. 
Published: September 2011

Abstract
Erythropoiesis is dependent on the activity of transcription factors, including the erythroid-specific erythroid Kruppel-like factor (EKLF). ChIP followed by massively parallel sequencing (ChIP-Seq) is a powerful, unbiased method to map trans-factor occupancy. We used ChIP-Seq to study the interactome of EKLF in mouse erythroid progenitor cells and more differentiated erythroblasts. We correlated these results with the nuclear distribution of EKLF, RNA-Seq analysis of the transcriptome, and the occupancy of other erythroid transcription factors. In progenitor cells, EKLF is found predominantly at the periphery of the nucleus, where EKLF primarily occupies the promoter regions of genes and acts as a transcriptional activator. In erythroblasts, EKLF is distributed throughout the nucleus, and erythroblast-specific EKLF occupancy is predominantly in intragenic regions. In progenitor cells, EKLF modulates general cell growth and cell cycle regulatory pathways, whereas in erythroblasts EKLF is associated with repression of these pathways. The EKLF interactome shows very little overlap with the interactomes of GATA1, GATA2, or TAL1, leading to a model in which EKLF directs programs that are independent of those regulated by the GATA factors or TAL1.
A cell factory of Bacillus subtilis engineered for the simple bioconversion of myo-inositol to scyllo-inositol, a potential therapeutic agent for Alzheimer's disease
Authors: Yamaoka Masaru , Osawa Shin , Morinaga Tetsuro , Takenaka Shinji , Yoshida Ken-ichi 
Published: September 2011

Abstract

Background
A stereoisomer of inositol, scyllo-inositol, is known as a promising therapeutic agent for Alzheimer's disease, since it prevents the accumulation of beta-amyloid deposits, a hallmark of the disease. However, this compound is relatively rare in nature, whereas another stereoisomer of inositol, myo-inositol, is abundantly available.

Results

Bacillus subtilis possesses a unique inositol metabolism involving both stereoisomers. We manipulated the inositol metabolism in B. subtilis to permit the possible bioconversion from myo-inositol to scyllo-inositol. Within 48 h of cultivation, the engineered strain was able to convert almost half of 10 g/L myo-inositol to scyllo-inositol that accumulated in the culture medium.

Conclusions
The engineered B. subtilis serves as a prototype of cell factory enabling a novel and inexpensive supply of scyllo-inositol.
c-Myc dependent expression of pro-apoptotic Bim renders HER2-overexpressing breast cancer cells dependent on anti-apoptotic Mcl-1
Authors: Campone Mario , Noël Bélinda , Couriaud Cécile , Grau Morgan , Guillemin Yannis , Gautier Fabien , Gouraud Wilfried , Charbonnel Catherine , Campion Loïc , Jézéquel Pascal , Braun Frédérique , Barré Benjamin , Coqueret Olivier , Barillé-Nion Sophie , Juin Philippe 
Published: September 2011

Abstract

Background
Anti-apoptotic signals induced downstream of HER2 are known to contribute to the resistance to current treatments of breast cancer cells that overexpress this member of the EGFR family. Whether or not some of these signals are also involved in tumor maintenance by counteracting constitutive death signals is much less understood. To address this, we investigated what role anti- and pro-apoptotic Bcl-2 family members, key regulators of cancer cell survival, might play in the viability of HER2 overexpressing breast cancer cells.

Methods
We used cell lines as an in vitro model of HER2-overexpressing cells in order to evaluate how anti-apoptotic Bcl-2, Bcl-xL and Mcl-1, and pro-apoptotic Puma and Bim impact on their survival, and to investigate how the constitutive expression of these proteins is regulated. Expression of the proteins of interest was confirmed using lysates from HER2-overexpressing tumors and through analysis of publicly available RNA expression data.

Results
We show that the depletion of Mcl-1 is sufficient to induce apoptosis in HER2-overexpressing breast cancer cells. This Mcl-1 dependence is due to Bim expression and it directly results from oncogenic signaling, as depletion of the oncoprotein c-Myc, which occupies regions of the Bim promoter as evaluated in ChIP assays, decreases Bim levels and mitigates Mcl-1 dependence. Consistently, a reduction of c-Myc expression by inhibition of mTORC1 activity abrogates occupancy of the Bim promoter by c-Myc, decreases Bim expression and promotes tolerance to Mcl-1 depletion. Western blot analysis confirms that naïve HER2-overexpressing tumors constitutively express detectable levels of Mcl-1 and Bim, while expression data hint on enrichment for Mcl-1 transcripts in these tumors.

Conclusions
This work establishes that, in HER2-overexpressing tumors, it is necessary, and maybe sufficient, to therapeutically impact on the Mcl-1/Bim balance for efficient induction of cancer cell death.
A reaction-diffusion model of the receptor-toxin-antibody interaction
Authors: Skakauskas Vladas , Katauskis Pranas , Skvortsov Alex 
Published: September 2011

Abstract

Background
It was recently shown that the treatment effect of an antibody can be described by a consolidated parameter which includes the reaction rates of the receptor-toxin-antibody kinetics and the relative concentration of reacting species. As a result, any given value of this parameter determines an associated range of antibody kinetic properties and its relative concentration in order to achieve a desirable therapeutic effect. In the current study we generalize the existing kinetic model by explicitly taking into account the diffusion fluxes of the species.

Results
A refined model of receptor-toxin-antibody (RTA) interaction is studied numerically. The protective properties of an antibody against a given toxin are evaluated for a spherical cell placed into a toxin-antibody solution. The selection of parameters for numerical simulation approximately corresponds to the practically relevant values reported in the literature with the significant ranges in variation to allow demonstration of different regimes of intracellular transport.

Conclusions
The proposed refinement of the RTA model may become important for the consistent evaluation of protective potential of an antibody and for the estimation of the time period during which the application of this antibody becomes the most effective. It can be a useful tool for in vitro selection of potential protective antibodies for progression to in vivo evaluation.
Giant right coronary artery aneurysm presenting with non-ST elevation myocardial infarction and severe mitral regurgitation: a case report
Authors: Nazareth Justin , Weinberg Laurence , Fernandes Jon , Peyton Phil , Seevanayagam Sivan 
Published: September 2011

Abstract

Introduction
Coronary artery aneurysms are seen in 1.5-5% of patients presenting for coronary angiography, but giant aneurysms, defined as being greater than 2 cm in diameter, are rare. Given the paucity of cases and limited experience in diagnosis and management of the disease, each case is a learning tool in itself.

Case presentation
We report the rare case of a 78-year-old Caucasian man who presented to a peripheral emergency department with chest pain and was subsequently found to have a giant right coronary artery aneurysm. Following initial investigation and treatment he was referred to our hospital for definitive management.

Conclusion
The case described illustrates one of the varied presentations and subsequent management of an ill-defined and heterogeneous disease process. Given the limited experience with giant aneurysms in the coronary circulation, this case provides valuable insight into the clinical presentation of the disease and gives an example of the management of the most recent such case at our hospital.
Serum Enterolactone and Prognosis of Postmenopausal Breast Cancer
Authors: Buck Katharina , Vrieling Alina , Zaineddin Aida Karina , Becker Susen , Hüsing Anika , Kaaks Rudolf , Linseisen Jakob , Flesch-Janys Dieter , Chang-Claude Jenny 
Published: September 2011

Purpose Lignans—plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties—have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. Patients and Methods We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. Results Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor–negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor–positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). Conclusion Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.
Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience
Authors: Arun Banu , Bayraktar Soley , Liu Diane D. , Gutierrez Barrera Angelica M. , Atchley Deann , Pusztai Lajos , Litton Jennifer Keating , Valero Vicente , Meric-Bernstam Funda , Hortobagyi Gabriel N. , Albarracin Constance 
Published: September 2011

Purpose To compare the pathologic complete response (pCR) rate and relapse-free survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2 mutations. Patients and Methods A total of 317 women who underwent BRCA genetic testing and were treated with NST for breast cancer between 1997 and 2009 were included in the study. The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models were fit to determine the associations between BRCA status, pCR, and survival. Results Fifty-seven (18%) and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2 carriers and 53 (22%) of 237 BRCA noncarriers (P < .001). In the multivariate logistic model, BRCA1 status (odds ratio [OR] = 3.16; 95% CI, 1.55 to 6.42; P = .002), estrogen receptor (ER) negativity (OR = 1.96; 95% CI:1.05 to 3.65; P = .03) and concurrent trastuzumab use (OR = 4.18; 95% CI, 2.04 to 8.57; P < .001) remained as independent significant predictors for a pCR. At a median follow-up of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No significant differences were noted in survival outcomes with respect to BRCA status and type of NST received. However, among BRCA1 carriers, patients who achieved a pCR had better 5-year RFS (P = .001) and OS (P = .01) rates than patients who did not. Conclusion BRCA1 status and ER negativity are independently associated with higher pCR rates in patients with breast cancer. Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast cancers.
Comparative gene expression profiles for highly similar aggressive phenotypes in male and female cichlid fishes (Julidochromis)
Authors: Schumer Molly , Krishnakant Kavita , Renn Suzy C. P. 
Published: September 2011

SUMMARY
Julidochromis marlieri and Julidochromis transcriptus are two closely related Tanganyikan cichlids that have evolved different behavior and mating strategies since they diverged from their common ancestor. While J. transcriptus follows the ancestral pattern of male dominance, male-biased sexual size dimorphism and territoriality, the pattern is reversed in J. marlieri. In J. marlieri, females show all of these behavioral and morphological characteristics. This raises the question of whether female J. marlieri achieve the dominant phenotype by expressing the same genes as J. transcriptus males or whether novel brain gene expression patterns have evolved to produce a similar behavioral phenotype in the females of J. marlieri. This study used cDNA microarrays to investigate whether female J. marlieri and male J. transcriptus show conserved or divergent patterns of brain gene expression. Analysis of microarray data in both species showed certain gene expression patterns associated with sex role independent of gonadal sex and, to a lesser extent, gene expression patterns associated with sex independent of sex role. In general, these data suggest that while there has been substantial divergence in gene expression patterns between J. transcriptus and J. marlieri, we can detect a highly significant overlap for a core set of genes related to aggression in both species. These results suggest that the proximate mechanisms regulating aggressive behavior in J. transcriptus and J. marlieri may be shared.
Intra-retinal variation of opsin gene expression in the guppy (Poecilia reticulata)
Authors: Rennison Diana J. , Owens Gregory L. , Allison W. Ted , Taylor John S. 
Published: September 2011

SUMMARY
Although behavioural experiments demonstrate that colouration influences mate choice in many species, a complete understanding of this form of signalling requires information about colour vision in the species under investigation. The guppy (Poecilia reticulata) has become a model species for the study of colour-based sexual selection. To investigate the role of opsin gene duplication and divergence in the evolution of colour-based mate choice, we used in situ hybridization to determine where the guppy's nine cone opsins are expressed in the retina. Long wavelength-sensitive (LWS) opsins were more abundant in the dorsal retina than in the ventral retina. One of the middle wavelength-sensitive opsins (RH2-1) exhibited the opposite pattern, while the other middle wavelength-sensitive opsin (RH2-2) and the short wavelength-sensitive opsins (SWS1, SWS2A and SWS2B) were expressed throughout the retina. We also found variation in LWS opsin expression among individuals. These observations suggest that regions of the guppy retina are specialized with respect to wavelength discrimination and/or sensitivity. Intra-retinal variability in opsin expression, which has been observed in several fish species, might be an adaptation to variation in the strength and spectral composition of light entering the eye from above and below. The discovery that opsin expression varies in the guppy retina may motivate new behavioural experiments designed to study its role in mate choice.
Peripheral injury induces long-term sensitization of defensive responses to visual and tactile stimuli in the squid Loligo pealeii, Lesueur 1821
Authors: Crook Robyn J. , Lewis Trevor , Hanlon Roger T. , Walters Edgar T. 
Published: September 2011

SUMMARY
Survivable injuries are a common yet costly experience. The ability to sense and respond to noxious stimuli is an almost universal trait, and prolonged behavioral alterations, including sensitization to touch and other stimuli, may function to ameliorate fitness costs associated with injury. Cephalopods can modify their behavior by learned association with noxious electric shock, but non-associative alterations of behavioral responses after tissue injury have not been studied. The aim of this study was to make the first systematic investigations in any cephalopod of behavioral responses and alterations elicited by explicit, minor injury. By testing responsiveness in the longfin squid, Loligo pealeii, to the approach and contact of an innocuous filament applied to different parts of the body both before and after injury to the distal third of one arm, we show that a cephalopod expresses behavioral alterations persisting for at least 2 days after injury. These alterations parallel forms of nociceptive plasticity in other animals, including general and site-specific sensitization to tactile stimuli. A novel finding is that hyper-responsiveness after injury extends to visual stimuli. Injured squid are more likely to employ crypsis than escape in response to an approaching visual stimulus shortly after injury, but initiate escape earlier and continue escape behaviors for longer when tested from 1 to 48 h after injury. Injury failed to elicit overt wound-directed behavior (e.g. grooming) or change hunting success. Our results show that long-lasting nociceptive sensitization occurs in cephalopods, and suggest that it may function to reduce predation risk after injury.
Regulation of bat echolocation pulse acoustics by striatal dopamine
Authors: Tressler Jedediah , Schwartz Christine , Wellman Paul , Hughes Samuel , Smotherman Michael 
Published: September 2011

SUMMARY
The ability to control the bandwidth, amplitude and duration of echolocation pulses is a crucial aspect of echolocation performance but few details are known about the neural mechanisms underlying the control of these voice parameters in any mammal. The basal ganglia (BG) are a suite of forebrain nuclei centrally involved in sensory-motor control and are characterized by their dependence on dopamine. We hypothesized that pharmacological manipulation of brain dopamine levels could reveal how BG circuits might influence the acoustic structure of bat echolocation pulses. A single intraperitoneal injection of a low dose (5 mg kg–1) of the neurotoxin 1-methyl-4-phenylpyridine (MPTP), which selectively targets dopamine-producing cells of the substantia nigra, produced a rapid degradation in pulse acoustic structure and eliminated the bat's ability to make compensatory changes in pulse amplitude in response to background noise, i.e. the Lombard response. However, high-performance liquid chromatography (HPLC) measurements of striatal dopamine concentrations revealed that the main effect of MPTP was a fourfold increase rather than the predicted decrease in striatal dopamine levels. After first using autoradiographic methods to confirm the presence and location of D1- and D2-type dopamine receptors in the bat striatum, systemic injections of receptor subtype-specific agonists showed that MPTP's effects on pulse acoustics were mimicked by a D2-type dopamine receptor agonist (Quinpirole) but not by a D1-type dopamine receptor agonist (SKF82958). The results suggest that BG circuits have the capacity to influence echolocation pulse acoustics, particularly via D2-type dopamine receptor-mediated pathways, and may therefore represent an important mechanism for vocal control in bats.
Symmorphosis and the insect respiratory system: allometric variation
Authors: Snelling Edward P. , Seymour Roger S. , Runciman Sue , Matthews Philip G. D. , White Craig R. 
Published: September 2011

SUMMARYTaylor and Weibel's theory of symmorphosis predicts that structures of the respiratory system are matched to maximum functional requirements with minimal excess capacity. We tested this hypothesis in the respiratory system of the migratory locust, Locusta migratoria, by comparing the aerobic capacity of the jumping muscles with the morphology of the oxygen cascade in the hopping legs using an intraspecific allometric analysis of different body mass (Mb) at selected juvenile life stages. The maximum oxygen consumption rate of the hopping muscle during jumping exercise scales as Mb1.02±0.02, which parallels the scaling of mitochondrial volume in the hopping muscle, Mb1.02±0.08, and the total surface area of inner mitochondrial membrane, Mb0.99±0.10. Likewise, at the oxygen supply end of the insect respiratory system, there is congruence between the aerobic capacity of the hopping muscle and the total volume of tracheoles in the hopping muscle, Mb0.99±0.16, the total inner surface area of the tracheoles, Mb0.99±0.16, and the anatomical radial diffusing capacity of the tracheoles, Mb0.99±0.18. Therefore, the principles of symmorphosis are upheld at each step of the oxygen cascade in the respiratory system of the migratory locust.
Spectral and duration sensitivity to light-at-night in ‘blind’ and sighted rodent species
Authors: Zubidat Abed E. , Nelson Randy J. , Haim Abraham 
Published: September 2011

SUMMARYLight-at-night (LAN) has become a defining feature of human and animal ecosystems and may possibly compromise human and animal physiology and health. Spectral and acclimation duration (AD) sensitivity were compared between social voles (Microtus socialis) and ‘blind’ mole rats (Spalax ehrenbergi) in four increasing ADs (0, 1, 7 and 21 days) to LAN (1×30 min, 293 μW cm–2) of three different monochromatic lights [blue (479 nm), yellow (586 nm) and red (697 nm)]. Animals were sampled for urine and oxygen consumption (VO2) promptly after each LAN-AD. Urine samples were analyzed for production rate, urinary 6-sulfatoxymelatonin and urinary metabolites of adrenalin and cortisol. Overall, the blue light elicited the greatest effects on the biological markers of M. socialis, whereas similar effects were detected for S. ehrenbergi in response to red light. The increasing LAN-AD resulted in a dose-dependent decrement of all markers tested, except of stress hormones, which showed a direct positive correlation with LAN-AD. Our results suggest that: (1) photoperiod is an important cue for entraining physiological functions in the ‘blind’ S. ehrenbergi, which is essentially characterized by red-shifted sensitivity compared with the blue-shifted sensitivity detected for the sighted counterpart species, and (2) there is a strong association between LAN of the appropriate wavelength and adrenal endocrine responses, suggesting that LAN is a potential environmental stressor.