bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the rate-limiting steps in visual phototransduction recovery by bottom-up kinetic modeling
Authors: Invergo Brandon M , Montanucci Ludovica , Koch Karl-Wilhelm , Bertranpetit Jaume , Dell’Orco Daniele
Published: May 2013

Background

Phototransduction in vertebrate photoreceptor cells represents a paradigm of signaling pathways mediated by G-protein-coupled receptors (GPCRs), which share common modules linking the initiation of the cascade to the final response of the cell. In this work, we focused on the recovery phase of the visual photoresponse, which is comprised of several interacting mechanisms.

Results

We employed current biochemical knowledge to investigate the response mechanisms of a comprehensive model of the visual phototransduction pathway. In particular, we have improved the model by implementing a more detailed representation of the recoverin (Rec)-mediated calcium feedback on rhodopsin kinase and including a dynamic arrestin (Arr) oligomerization mechanism. The model was successfully employed to investigate the rate limiting steps in the recovery of the rod photoreceptor cell after illumination. Simulation of experimental conditions in which the expression levels of rhodospin kinase (RK), of the regulator of the G-protein signaling (RGS), of Arr and of Rec were altered individually or in combination revealed severe kinetic constraints to the dynamics of the overall network.

Conclusions

Our simulations confirm that RGS-mediated effector shutdown is the rate-limiting step in the recovery of the photoreceptor and show that the dynamic formation and dissociation of Arr homodimers and homotetramers at different light intensities significantly affect the timing of rhodopsin shutdown. The transition of Arr from its oligomeric storage forms to its monomeric form serves to temper its availability in the functional state. Our results may explain the puzzling evidence that overexpressing RK does not influence the saturation time of rod cells at bright light stimuli. The approach presented here could be extended to the study of other GPCR signaling pathways.
Bacteroides thetaiotaomicron and Faecalibacterium prausnitziiinfluence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent
Authors: Wrzosek Laura , Miquel Sylvie , Noordine Marie-Louise , Bouet Stephan , Chevalier-Curt Marie Joncquel , Robert Véronique , Philippe Catherine , Bridonneau Chantal , Cherbuy Claire , Robbe-Masselot Catherine , Langella Philippe , Thomas Muriel
Published: May 2013

Background

The intestinal mucus layer plays a key role in the maintenance of host-microbiota homeostasis. To document the crosstalk between the host and microbiota, we used gnotobiotic models to study the influence of two major commensal bacteria, Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii, on this intestinal mucus layer. B. thetaiotaomicron is known to use polysaccharides from mucus, but its effect on goblet cells has not been addressed so far. F. prausnitzii is of particular physiological importance because it can be considered as a sensor and a marker of human health. We determined whether B. thetaiotaomicron affected goblet cell differentiation, mucin synthesis and glycosylation in the colonic epithelium. We then investigated how F. prausnitzii influenced the colonic epithelial responses to B. thetaiotaomicron.

Results

B. thetaiotaomicron, an acetate producer, increased goblet cell differentiation, expression of mucus-related genes and the ratio of sialylated to sulfated mucins in mono-associated rats. B. thetaiotaomicron, therefore, stimulates the secretory lineage, favoring mucus production. When B. thetaiotaomicron was associated with F. prausnitzii, an acetate consumer and a butyrate producer, the effects on goblet cells and mucin glycosylation were diminished. F. prausnitzii, by attenuating the effects of B. thetaiotaomicron on mucus, may help the epithelium to maintain appropriate proportions of different cell types of the secretory lineage. Using a mucus-producing cell line, we showed that acetate up-regulated KLF4, a transcription factor involved in goblet cell differentiation.

Conclusions

B. thetaiotaomicron and F. prausnitzii, which are metabolically complementary, modulate, in vivo, the intestinal mucus barrier by modifying goblet cells and mucin glycosylation. Our study reveals the importance of the balance between two main commensal bacteria in maintaining colonic epithelial homeostasis via their respective effects on mucus.
An open-label study of effects of acupuncture on chronic fatigue syndrome and idiopathic chronic fatigue: study protocol for a randomized controlled trial
Authors: Kim Jung-Eun , Hong Kwon-Eui , Kim Hyeong-Jun , Choi Jin-Bong , Baek Yong-Hyeon , Seo Byung-Kwan , Lee Sanghun , Kang Kyung-Won , Lee Min-Hee , Kim Joo-Hee , Lee Seunghoon , Jung So-Young , Jung Hee-Jung , Shin Mi-Suk , Choi Sun-Mi
Published: May 2013

Background

Even though chronic fatigue syndrome and idiopathic chronic fatigue are quite common, there are no clearly known causes. Most treatments are therefore symptomatic in nature, and chronic fatigue syndrome and idiopathic chronic fatigue patients are highly interested in using oriental medicine or complementary and alternative medicine treatment. Acupuncture, one of the major treatments used in oriental medicine, is effective in treating various diseases. This study will attempt to analyze the effectiveness and safety of acupuncture in the treatment of chronic fatigue by comparing the two treatment groups (body acupuncture, Sa-am acupuncture) and the control group (usual care).

Methods/design

This study consists of a four-center, three-arm, randomized, controlled, and open-label trial. One hundred and fifty participants are randomly divided into treatment groups A and B and a control group. The treatment groups will receive acupuncture treatments either two or three times per week for a total of 10 sessions over a period of 4 weeks. The control group will not receive acupuncture treatments and will continue their usual care during this period. The primary outcome variable is the Fatigue Severity Scale, which will be utilized 5 weeks after randomization. Secondary outcome variables are the Fatigue Severity Scale at 13 weeks, a short form of the Stress Response Inventory, the Beck Depression Inventory, the Numeric Rating Scale, and the EuroQol-5 Dimension at 5 and 13 weeks after randomization.

Discussion

This study will provide evidence with high external validity on the effectiveness and safety of acupuncture as a treatment for chronic fatigue syndrome and idiopathic chronic fatigue.

Trial registration

Clinical Research Information ServiceKCT0000508
A pharmacist-led system-change smoking cessation intervention for smokers admitted to Australian public hospitals (GIVE UP FOR GOOD): study protocol for a randomised controlled trial
Authors: Thomas Dennis , Abramson Michael J , Bonevski Billie , Taylor Simone , Poole Susan , Weeks Gregory R , Dooley Michael J , George Johnson
Published: May 2013

Background

Intensive smoking cessation interventions initiated during hospitalisation are effective, but currently not widely available. Strategies are needed to integrate smoking cessation treatment into routine inpatient care. Pharmacist-led interventions for smoking cessation are feasible and efficacious in both ambulatory and community pharmacy settings. However, there is a lack of evidence from large scale studies of the effectiveness of pharmacist guided programs initiated during patient hospitalisation in achieving long-term abstinence. This study aims to evaluate the effectiveness of a pharmacist-led system change intervention initiated during hospitalisation in Australian public hospitals.

Methods/design

A multi-centre, randomised controlled trial will be conducted with 12 months follow-up. Smokers, 18 years or older, will be recruited from the wards of three Victorian public hospitals. Participants will be randomly assigned to a usual care or intervention group using a computer generated randomisation list. The intervention group will receive at least three smoking cessation support sessions by a trained pharmacist: the first during the hospital stay, the second on or immediately after discharge and the third within one month post-discharge. All smoking cessation medications will be provided free of charge during the hospital stay and for at least one week after discharge. Participants randomised to usual care will receive the current care routinely provided by the hospital. All measurements at baseline, discharge, one, six and 12 months will be performed by a blinded Research Assistant. The primary outcome measures are carbon monoxide validated 7-day point prevalence abstinence at six and 12 months.

Discussion

This is the first large scale study to develop and test a pharmacist-led system change intervention program initiated during patient hospitalisation. If successful, the program could be considered for wider implementation across other hospitals.

Trial registration

ACTRN12612000368831
A non-invasive biomechanical device and treatment for patients following total hip arthroplasty: results of a 6-month pilot investigation
Authors: Segal Ganit , Bar-Ziv Yaron , Velkes Steven , Benkovich Vadim , Stanger Gilad , Debbi Eytan M , Debi Ronen , Mor Amit , Elbaz Avi
Published: May 2013

Background

The purpose of the study was to examine the effect of a foot-worn biomechanical device on the clinical measurements and gait patterns of patients with total hip arthroplasty (THA).

Methods

Nineteen patients, up to 3 months post-THA, were enrolled to the study. Patients underwent a computerized gait analysis to calculate spatiotemporal parameters and completed the Western Ontario and McMaster Universities osteoarthritis index and the SF-36 health survey. Patients then began therapy with a non-invasive foot-worn biomechanical device coupled with a treatment methodology (AposTherapy). Patients received exercise guidelines and used the device daily during their regular activities at their own environment. Follow-up examinations were conducted after 4, 12, and 26 weeks of therapy. Repeated measures ANOVA was used to evaluate changes over time. The clinical significance of the treatment effect was evaluated by computing the Cohen's effect sizes (ES statistic).

Results

After 26 weeks of therapy, a significant improvement was seen in gait velocity (50.3%), involved step length (22.9%), and involved single limb support (16.5%). Additionally, a significant reduction in pain (85.4%) and improvement in function (81.1%) and quality of life (52.1%) were noted.

Conclusions

Patients following THA demonstrated a significant improvement in gait parameters and in self-assessment evaluations of pain, function, and quality of life. We recommend further RCTs to examine the effect of this therapy compared to other rehabilitation modalities following THA and compared to healthy matched controls.

Trial registration

Clinical trial registration number NCT01266382
Regenerative medicine for the kidney: stem cell prospects & challenges
Authors: Li Yue , Wingert Rebecca A
Published: May 2013

The kidney has key roles in maintaining human health. There is an escalating medical crisis in nephrology as growing numbers of patients suffer from kidney diseases that culminate in organ failure. While dialysis and transplantation provide life‐saving treatments, these therapies are rife with limitations and place significant burdens on patients and healthcare systems. It has become imperative to find alternative ways to treat existing kidney conditions and preemptive means to stave off renal dysfunction. The creation of innovative medical approaches that utilize stem cells has received growing research attention. In this review, we discuss the regenerative and maladaptive cellular responses that occur during acute and chronic kidney disease, the emerging evidence about renal stem cells, and some of the issues that lie ahead in bridging the gap between basic stem cell biology and regenerative medicine for the kidney.
Human amniotic fluid-derived and dental pulp-derived stem cells seeded into collagen scaffold repair critical-size bone defects promoting vascularization
Authors: Maraldi Tullia , Riccio Massimo , Pisciotta Alessandra , Zavatti Manuela , Carnevale Gianluca , Beretti Francesca , La Sala Giovanni B , Motta Antonella , De Pol Anto
Published: May 2013

Introduction

The main aim of this study is to evaluate potential human stem cells, such as dental pulp stem cells and amniotic fluid stem cells, combined with collagen scaffold to reconstruct critical-size cranial bone defects in an animal model.

Methods

We performed two symmetric full-thickness cranial defects on each parietal region of rats and we replenished them with collagen scaffolds with or without stem cells already seeded into and addressed towards osteogenic lineage in vitro. After 4 and 8 weeks, cranial tissue samples were taken for histological and immunofluorescence analysis.

Results

We observed a new bone formation in all of the samples but the most relevant differences in defect correction were shown by stem cell–collagen samples 4 weeks after implant, suggesting a faster regeneration ability of the combined constructs. The presence of human cells in the newly formed bone was confirmed by confocal analysis with an antibody directed to a human mitochondrial protein. Furthermore, human cells were found to be an essential part of new vessel formation in the scaffold.

Conclusion

These data confirmed the strong potential of bioengineered constructs of stem cell–collagen scaffold for correcting large cranial defects in an animal model and highlighting the role of stem cells in neovascularization during skeletal defect reconstruction.
Sex Is an Independent Prognostic Indicator for Survival and Relapse/Progression-Free Survival in Metastasized Stage III to IV Melanoma: A Pooled Analysis of Five European Organisation for Research and Treatment of Cancer Randomized Controlled Trials
Authors: Joosse Arjen , Collette Sandra , Suciu Stefan , Nijsten Tamar , Patel Poulam M. , Keilholz Ulrich , Eggermont Alexander M.M. , Coebergh Jan Willem W. , de Vries Esther
Published: May 2013

Purpose

To study sex differences in survival and progression in patients with stage III or IV metastatic melanoma and to compare our results with published literature.

Patients and Methods

Data were retrieved from three large, randomized, controlled trials of the European Organisation for Research and Treatment of Cancer in patients with stage III and two trials in patients with stage IV melanoma. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for females compared with males, adjusted for different sets of confounders for stage III and stage IV, respectively.

Results

In 2,734 stage III patients, females had a superior 5-year disease-specific survival (DSS) rate compared with males (51.5% v 43.3%), an adjusted HR for DSS of 0.85 (95% CI, 0.76 to 0.95), and an adjusted HR for relapse-free survival of 0.86 (95% CI, 0.77 to 0.95). In 1,306 stage IV patients, females also exhibited an advantage in DSS (2-year survival rate, 14.1% v 19.0%; adjusted HR, 0.81; 95% CI, 0.72 to 0.92) as well as for progression-free survival (adjusted HR, 0.79; 95% CI, 0.70 to 0.88). This female advantage was consistent across pre- and postmenopausal age categories and across different prognostic subgroups. However, the female advantage seems to become smaller in patients with higher metastatic tumor load.

Conclusion

The persistent independent female advantage, even after metastasis to lymph nodes and distant sites, contradicts theories about sex behavioral differences as an explanation for this phenomenon. A biologic sex trait seems to profoundly influence melanoma progression and survival, even in advanced disease.
Barriers to Breast and Colorectal Cancer Survivorship Care: Perceptions of Primary Care Physicians and Medical Oncologists in the United States
Authors: Virgo Katherine S. , Lerro Catherine C. , Klabunde Carrie N. , Earle Craig , Ganz Patricia A.
Published: May 2013

Purpose

High-quality, well-coordinated cancer survivorship care is needed yet barriers remain owing to fragmentation in the United States health care system. This article is a nationwide survey of barriers perceived by primary care physicians (PCPs) and medical oncologists (MOs) regarding breast and colorectal cancer survivorship care beyond 5 years after treatment.

Methods

The Survey of Physician Attitudes Regarding the Care of Cancer Survivors was mailed out in 2009 to a nationally-representative sample (n = 3,596) of US PCPs and MOs. Ten physician-perceived cancer survivorship care barriers/concerns were compared between the two provider types. Using weighted multinomial logistic regression, we modeled each barrier, adjusting for physician demographics, reimbursement, training, and practice characteristics.

Results

We received responses from 2,202 physicians (1,072 PCPs; 1,130 MOs; 65.1% cooperation rate). In adjusted patient-related barriers models, MOs were more likely than PCPs to report patient language barriers (odds ratio, [OR], 1.72; 95% CI, 1.22 to 2.42), insurance restrictions impeding test/treatment use (OR, 1.42; 95% CI, 1.03 to 1.96), and patients requesting more aggressive testing (OR, 4.08; 95% CI, 2.73 to 6.10). In adjusted physician-related barriers models, PCPs were more likely to report inadequate training (OR, 3.06; 95% CI, 2.03 to 4.61) and ordering additional tests/treatments because of malpractice concerns (OR, 1.87; 95% CI, 1.20 to 2.93). MOs were more likely to report uncertainty regarding general preventive care responsibility (often/always: OR, 1.97; 95% CI, 1.13 to 3.43; sometimes: OR, 2.16; 95% CI, 1.60 to 2.93).

Conclusion

MOs and PCPs perceive different cancer follow-up care barriers/concerns to be problematic. Resolving inadequate training, malpractice-driven test ordering, and preventive-care responsibility concerns may require continuing education, explicit guidelines, and survivorship care plans. Reviewing care plans with survivors may also reduce patients' requests for unnecessary testing.
Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia
Authors: Schmiegelow Kjeld , Levinsen Mette Frandsen , Attarbaschi Andishe , Baruchel Andre , Devidas Meenakshi , Escherich Gabriele , Gibson Brenda , Heydrich Christiane , Horibe Keizo , Ishida Yasushi , Liang Der-Cherng , Locatelli Franco , Michel Gérard , Pieters Rob , Piette Caroline , Pui Ching-Hon , Raimondi Susana , Silverman Lewis , Stanulla Martin , Stark Batia , Winick Naomi , Valsecchi Maria Grazia
Published: May 2013

Purpose

Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events.

Patients and Methods

We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007.

Results

Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m2per week and mercaptopurine of at least 75 mg/m2per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03).

Conclusion

SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts.
Should a Woman Age 70 to 80 Years Receive Radiation After Breast-Conserving Surgery?
Authors: Hepel Jaroslaw T. , Wazer David E.
Published: May 2013

Case 1: A 72-year-old woman presents with a palpable mass detected during yearly physical examination by her primary care physician. She has controlled hypertension and remains active, playing tennis three times a week. Physical examination reveals a 1.5 cm mass in the upper outer quadrant of the left breast with no palpable axillary lymphadenopathy. Diagnostic imaging reveals a suspicious mass, and core biopsy confirms invasive ductal carcinoma (IDC) that is estrogen receptor moderately positive (60%), progesterone receptor negative and Her2-neu that is not overexpressed. She undergoes a wide local excision and sentinel node biopsy. Pathology reveals a 1.5 cm IDC that is high grade without lymphovascular invasion (LVI). The margins are negative with the closest laterally at 2 mm. One sentinel node is negative for metastasis.

Case 2: A 72-year-old woman presents with an abnormal screening mammogram that shows a small area of architectural distortion in the upper outer quadrant of the left breast ( Fig 1 ). She is a former smoker with mild chronic obstructive pulmonary disease and has mild to moderately symptomatic osteoarthritis managed with a nonsteroidal anti-inflammatory agent. She remains active and independent. Physical examination reveals neither palpable breast mass nor axillary lymphadenopathy. Diagnostic ultrasound confirms a 1.8 cm mass, and core biopsy reveals IDC that is estrogen and progesterone receptor strongly positive (> 90%) and Her2-neu that is not overexpressed. She undergoes a wide local excision and sentinel node biopsy. Pathology reveals a 1.9 cm IDC that is low grade. The margins are widely negative at > 5 mm and there is no LVI. One sentinel node is negative for metastasis.
Sally’s question and a conjecture of shimoda
Authors: Goto Shiro , O’carroll Liam , Planas-Vilanova Francesc
Published: May 2013

In 2007, Shimoda, in connection with a long-standing question of Sally, asked whether a Noetherian local ring, such that all its prime ideals different from the maximal ideal are complete intersections, has Krull dimension at most 2. In this paper, having reduced the conjecture to the case of dimension 3, if the ring is regular and local of dimension 3, we explicitly describe a family of prime ideals of height 2 minimally generated by three elements. Weakening the hypothesis of regularity, we find that, to achieve the same end, we need to add extra hypotheses, such as completeness, infiniteness of the residue field, and the multiplicity of the ring being at most 3. In the second part of the paper, we turn our attention to the category of standard graded algebras. A geometrical approach via a double use of a Bertini theorem, together with a result of Simis, Ulrich, and Vasconcelos, allows us to obtain a definitive answer in this setting. Finally, by adapting work of Miller on prime Bourbaki ideals in local rings, we detail some more technical results concerning the existence in standard graded algebras of homogeneous prime ideals with an (as it were) excessive number of generators.
Induced pluripotent stem cells derived from rabbits exhibit some characteristics of naïve pluripotency
Authors: Osteil Pierre , Tapponnier Yann , Markossian Suzy , Godet Murielle , Schmaltz-Panneau Barbara , Jouneau Luc , Cabau Cédric , Joly Thierry , Blachère Thierry , Gócza Elen , Bernat Agnieszka , Yerle Martine , Acloque Hervé , Hidot Sullivan , Bosze Zsuzsanna , Duranthon Véronique , Savatier Pierre , Afanassieff Marielle
Published: May 2013

Not much is known about the molecular and functional features of pluripotent stem cells (PSCs) in rabbits. To address this, we derived and characterized 2 types of rabbit PSCs from the same breed of New Zealand White rabbits: 4 lines of embryonic stem cells (rbESCs), and 3 lines of induced PSCs (rbiPSCs) that were obtained by reprogramming adult skin fibroblasts. All cell lines required fibroblast growth factor 2 for their growth and proliferation. All rbESC lines showed molecular and functional properties typically associated with primed pluripotency. The cell cycle of rbESCs had a prolonged G1 phase and a DNA damage checkpoint before entry into the S phase, which are the 2 features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naïve pluripotency, including resistance to single-cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naïve pluripotency-specific genes, as defined in rodents. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass (ICM) than rbESCs. Furthermore, rbiPSCs were capable of colonizing the ICM after aggregation with morulas. Therefore, we propose that rbiPSCs self-renew in an intermediate state between naïve and primed pluripotency, which represents a key step toward the generation of bona fide naïve PSC lines in rabbits.
Control of Sty1 MAPK activity through stabilisation of the Pyp2 MAPK phosphatase
Authors: Kowalczyk Katarzyna M. , Hartmuth Sonya , Perera David , Stansfield Peter , Petersen Janni
Published: May 2013

In all eukaryotes tight control of mitogen-activated protein kinase (MAPK) activity plays an important role in modulating intracellular signalling in response to changing environments. The fission yeast MAPK Sty1 (also known as Spc1 or Phh1) is highly activated in response to a variety of external stresses. To avoid segregation of damaged organelles or chromosomes, strong Sty1 activation transiently blocks mitosis and cell division until such stresses have been dealt with. MAPK phosphatases dephosphorylate Sty1 to reduce kinase activity. Therefore, tight control of MAPK phosphatases is central for stress adaptation and for cell division to resume. In contrast to Pyp1, the fission yeast Pyp2 MAPK phosphatase is under environmental control. Pyp2 has a unique sequence (the linker region) between the catalytic domain and the amino-terminal MAPK binding site. Here we show that the Pyp2 linker region is a destabilisation domain. Furthermore, the linker region is highly phosphorylated to increase Pyp2 protein stability and this phosphorylation is Sty1 dependent. Our data suggests that Sty1 activation promotes Pyp2 phosphorylation to increase the stability of the phosphatase. This MAPK-dependent Pyp2 stabilisation allows cells to attenuate MAPK signalling and resume cell division, once stresses have been dealt with.
Cell cycle–dependent transcription factors control the expression of yeast telomerase RNA
Authors: Dionne Isabelle , Larose Stéphanie , Dandjinou Alain T. , Abou Elela Sherif , Wellinger Raymund J.
Published: May 2013

Telomerase is a specialized ribonucleoprotein that adds repeated DNA sequences to the ends of eukaryotic chromosomes to preserve genome integrity. Some secondary structure features of the telomerase RNA are very well conserved, and it serves as a central scaffold for the binding of associated proteins. The Saccharomyces cerevisiae telomerase RNA, TLC1, is found in very low copy number in the cell and is the limiting component of the known telomerase holoenzyme constituents. The reasons for this low abundance are unclear, but given that the RNA is very stable, transcriptional control mechanisms must be extremely important. Here we define the sequences forming the TLC1 promoter and identify the elements required for its low expression level, including enhancer and repressor elements. Within an enhancer element, we found consensus sites for Mbp1/Swi4 association, and chromatin immunoprecipitation (ChIP) assays confirmed the binding of Mbp1 and Swi4 to these sites of the TLC1 promoter. Furthermore, the enhancer element conferred cell cycle–dependent regulation to a reporter gene, and mutations in the Mbp1/Swi4 binding sites affected the levels of telomerase RNA and telomere length. Finally, ChIP experiments using a TLC1 RNA-binding protein as target showed cell cycle–dependent transcription of the TLC1 gene. These results indicate that the budding yeast TLC1 RNA is transcribed in a cell cycle–dependent fashion late in G1 and may be part of the S phase–regulated group of genes involved in DNA replication.
Crystal structure of 2-(4-methylphenyl)-2-oxo-1-(phenyliodonio)-1-(triphenylarsonio)ethanid tetrafluoroborate solved from X-ray powder data
Authors: Mironov Andrei V. , Chernyshev Vladimir V. , Matveeva Elena D. , Podrugina Tatyana A. , Alferova Vera A. , Gleiter Rolf , Zefirov Nikolai S.
Published: May 2013

The crystal structure of 2-(4-methylphenyl)-2-oxo-1-(phenyliodonio)-1-(triphenylarsonio)ethanid tetrafluoroborate, C33H27AsIO+BF4
–, was solved and refined from laboratory X-ray powder diffraction data in combination with a DFT calculation (CoK
α1, a=24.427(2) Å, b = 13.3412(18) Å, c=22.399(2) Å, β = 119.49(2)°, S.G. C2/c, R
p/R
wp = 0.030/0.039). The main features of the C33H27AsIO+BF4
– structure are similar to those reported previously for arsenium and phosphorous organic compounds. The distinctive features are short I … O and I … F (2.743(19) and 2.916(17) Å, respectively) intermolecular contacts, also observed previously in the same type of compound, refined from single crystal data.
When it Takes a Network: Creating Strategy and Agility through Wargaming
Authors: Franken Arnoud , Thomsett Harry
Published: May 2013

Rational, analytical, directed approaches for strategy creation and execution may work for creating value by conventional, hierarchically structured organizations operating in stable environments. However, when the basis of competition shifts from product features to an experience delivered by a network of independently acting participants in a complex and fast-evolving market environment, approaches based on command and control do not work. For order to emerge from such chaos and to gain more control over success, strategy based on reason alone is not enough to inspire action in others. To understand what it takes to effectively make strategy under such circumstances, this article shows how the UK's Royal Marines, in collaboration with more than a dozen different stakeholder groups, developed a novel adaptation of wargaming to affect strategic change in Afghanistan. It also demonstrates the broad applicability of this strategic approach.
What Drives Exponential Improvements?
Authors: Funk Jeffrey Lee
Published: May 2013

This article illuminates the drivers of exponential improvements in performance and cost and explains why some technologies experience more rapid improvements than others. It shows how exponential improvements in performance and cost are largely driven by two mechanisms: creating materials to better exploit their physical phenomena; and geometric scaling. Improvements in some technologies are directly experienced through these two mechanisms, while improvements in higher-level “systems” are indirectly experienced through improvements in specific “components.” Understanding these drivers can help us better recognize when new technologies might become economically feasible and thus create appropriate policies for promoting improvements.
Amici's East Coast Pizzeria
Authors: Zafar Naeem , Fuchs Jack , Chang Victoria
Published: May 2013

The Amici's East Coast Pizzeria case study presents the history of Amici's East Coast Pizzeria, started by Peter Cooperstein and Mike Forter in 1987. It allows students to evaluate the company's launch in terms of opportunity identification, as well as to evaluate the company's scaling and growth strategy and options: all in the context of an entrepreneurial startup environment.
Customer-Centric Leadership: How to Manage Strategic Customers as Assets in B2B Markets
Authors: Senn Christoph , Thoma Axel , Yip George S.
Published: May 2013

In this age of tough, global competition, companies in business-to-business markets need to rethink the way they manage their customer portfolio and interact with their customers. Customer managers with mainly sales-or relationship-oriented roles cannot leverage their business relationships with customers who seek co-creation. For such co-creation relationships, companies need to install network-oriented managers who systematically create value and reduce risk together with the customer. This article distinguishes three customer asset management perspectives (i.e., sales, relationship, and network) that may be employed by customer managers at the supplier-customer interface. Following an explication of the evolving network perspective, it describes how firms can nurture the network perspective and the corresponding customer manager role in terms of mindset, context, and competence.
Conscious Capitalism Firms: Do They Behave as Their Proponents Say?
Authors: Wang Chong
Published: May 2013

Proponents of the Conscious Capitalism (CC) movement claim that CC firms should demonstrate a lower gross margin, a higher profit margin, a lower SG&A, and a lower marketing expense than their non-CC comparable firms. Using a sample of industry-year-size matched control firms as the CC firms' benchmark, this article shows that empirical evidence largely disagrees with these conjectures. It further shows that in contrast to the implications of the CC movement, CC firms neither demonstrated superior stock performance relative to the S&P 500 in recent years, nor do they respond less to the pressures from the equity market.
High glucose and insulin differentially modulates proliferation in MCF-7 and MDA-MB-231 cells
Authors: Gupta Chanchal , Tikoo Kulbhushan
Published: May 2013

Various preclinical and clinical studies have linked diabetes and breast cancer, but little is known regarding the molecular mechanism involved. This study aimed to investigate the effect of high glucose and insulin in breast cancer cells (MCF-7: non-invasive, hormone dependent, and MDA-MB-231: invasive, hormone independent). In contrast to MCF-7 cells, high glucose augmented proliferation of MDA-MB-231 cells as observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine assays. The high-glucose condition led to increased expression of cyclin D1, de-phosphorylation of p38, and increased phosphorylation of ERK in MDA-MB-231 cells but not in MCF-7 cells. Interestingly, we observed increased phosphorylation of GSK-3β, NF-κB, and ERα only in MCF-7 cells, highlighting their role as potential targets in prevention of progression of breast cancer under a high-glucose and insulin condition. Furthermore, insulin treatment under a high-glucose condition resulted in increased histone H3 phosphorylation and de-acetylation only in MDA-MB-231 cells. Taken together, we provide the first evidence that high glucose and insulin promotes proliferation of MDA-MB-231 cells by differential alteration of GSK-3β, NF-κB, and ERα expression and histone H3 modifications, which may directly or indirectly modulate the expression of genes involved in its proliferation.
Isolation, genetic manipulation, and transplantation of canine spermatogonial stem cells: progress toward transgenesis through the male germ-line
Authors: Harkey Michael A , Asano Atsushi , Zoulas Mary Ellen , Torok-Storb Beverly , Nagashima Jennifer , Travis Alexander
Published: May 2013

The dog is recognized as a highly predictive model for preclinical research. Its size, life span, physiology, and genetics more closely match human parameters than do those of the mouse model. Investigations of the genetic basis of disease and of new regenerative treatments have frequently taken advantage of canine models. However, full utility of this model has not been realized because of the lack of easy transgenesis. Blastocyst-mediated transgenic technology developed in mice has been very slow to translate to larger animals, and somatic cell nuclear transfer remains technically challenging, expensive, and low yield. Spermatogonial stem cell (SSC) transplantation, which does not involve manipulation of ova or blastocysts, has proven to be an effective alternative approach for generating transgenic offspring in rodents and in some large animals. Our recent demonstration that canine testis cells can engraft in a host testis, and generate donor-derived sperm, suggests that SSC transplantation may offer a similar avenue to transgenesis in the canine model. Here, we explore the potential of SSC transplantation in dogs as a means of generating canine transgenic models for preclinical models of genetic diseases. Specifically, we i) established markers for identification and tracking canine spermatogonial cells; ii) established methods for enrichment and genetic manipulation of these cells; iii) described their behavior in culture; and iv) demonstrated engraftment of genetically manipulated SSC and production of transgenic sperm. These findings help to set the stage for generation of transgenic canine models via SSC transplantation.
Factors Affecting Caregivers’ Use of Antibiotics Available Without a Prescription in Peru
Authors: Ecker Lucie , Ochoa Theresa J. , Vargas Martha , Del Valle Luis J , Ruiz Joaquim
Published: May 2013

OBJECTIVE:

To determine factors that affect caregivers’ decisions about antibiotic use in children in settings where antibiotics are available without prescription.

METHODS:

In a house-to-house survey, 1200 caregivers in 3 periurban districts of Lima, Peru, were asked about antibiotic use in young children.

RESULTS:

In this sample, 87.2% of children aged <5 years had received an antibiotic drug in their lives; 70.3% had received antibiotics before 1 year of age, and 98.8% of those had been prescribed by a physician. Given hypothetical cases of common cold and nondysenteric diarrhea, caregivers would seek medical advice in 76.4% and 87.1%, respectively, and 84.6% of caregivers said they respected medical decisions even if an antibiotic was not prescribed. Caregivers with high school–level education accepted 80% more medical decisions of not using an antibiotic and used fewer pharmacist-recommended antibiotics. For each additional year of life, the risk of self-medicated antibiotic use and the use of pharmacist-recommended antibiotics increased in 30%. (OR: 1.3, 95% CI: 1.1–1.4, P = .001 and OR: 1.3, 95% CI: 1.2–1.5, P < .001, respectively). Caregivers respected a medical decision of not prescribing an antibiotic 5 times more when physicians had explained the reason for their advice (OR: 5.0, 95% CI: 3.2–7.8, P < .001).

CONCLUSIONS:

Prescribed antibiotic use in these young children is common. Even if they are available without prescription, caregivers usually comply with medical advice and follow physicians’ recommendations when antibiotics are not prescribed. Improving physician prescribing habits could reduce irrational antibiotic use, decreasing future caregiver-driven misuse.
Irritant Contact Dermatitis From a Black Henna Tattoo Without Sensitization to Para-phenylendiamine
Authors: Kind Fabiola , Hofmeier Kathrin Scherer , Bircher Andreas J.
Published: May 2013

Allergic contact dermatitis from nonpermanent black henna tattoos has been frequently reported, particularly in children. Contamination or adulteration of the dyes with para-phenylendiamine has been identified as major cause of active sensitization and elicitation of severe allergic contact dermatitis. Sequelae include permanent sensitization, hyper- or hypopigmentation, scarring, keloids, and hypertrichosis. We report a rare case of irritant dermatitis to an unknown ingredient in a black henna tattoo with consecutive hypopigmentation. Sensitization to para-phenylendiamine and other para-compounds was excluded by patch test evaluation. This is relevant for future exposure to consumer products such as hair dyes or in occupational settings. Generally, black henna tattoos, particularly if done with dyes of unknown composition, should be strongly discouraged.
Race and Acute Abdominal Pain in a Pediatric Emergency Department
Authors: Caperell Kerry , Pitetti Raymond , Cross Keith P.
Published: May 2013

OBJECTIVE:

To investigate the demographic and clinical factors of children who present to the pediatric emergency department (ED) with abdominal pain and their outcomes.

METHODS:

A review of the electronic medical record of patients 1 to 18 years old, who presented to the Children’s Hospital of Pittsburgh ED with a complaint of abdominal pain over the course of 2 years, was conducted. Demographic and clinical characteristics, as well as visit outcomes, were reviewed. Subjects were grouped by age, race, and gender. Results of evaluation, treatment, and clinical outcomes were compared between groups by using multivariate analysis and recursive partitioning.

RESULTS:

There were 9424 patient visits during the study period that met inclusion and exclusion criteria. Female gender comprised 61% of African American children compared with 52% of white children. Insurance was characterized as private for 75% of white and 37% of African American children. A diagnosis of appendicitis was present in 1.9% of African American children and 5.1% of white children. Older children were more likely to be admitted and have an operation associated with their ED visit. Appendicitis was uncommon in younger children. Constipation was commonly diagnosed. Multivariate analysis by diagnosis as well as recursive partitioning analysis did not reflect any racial differences in evaluation, treatment, or outcome.

CONCLUSIONS:

Constipation is the most common diagnosis in children presenting with abdominal pain. Our data demonstrate that no racial differences exist in the evaluation, treatment, and disposition of children with abdominal pain.
Usefulness of Routine Head Ultrasound Scans Before Surgery for Congenital Heart Disease
Authors: Rios Danielle R. , Welty Stephen E. , Gunn Julia K. , Beca John , Minard Charles G. , Goldsworthy Michelle , Coleman Lee , Hunter Jill V. , Andropoulos Dean B. , Shekerdemian Lara S.
Published: May 2013

OBJECTIVE:

The purpose of this study was to assess the utility of preoperative head ultrasound scan (HUS) in a cohort of newborns also undergoing preoperative MRI as part of a prospective research study of brain injury in infants having surgery for congenital heart disease (CHD).

METHODS:

A total of 167 infants diagnosed with CHD were included in this 3-center study. None of the patients had clinical signs or symptoms of preoperative brain injury, and all patients received both HUS and brain MRI before undergoing surgical intervention. HUS and MRI results were reported by experienced neuroradiologists who were blinded to any specific clinical details of the study participants. The findings of the individual imaging modes were compared to evaluate for the presence of brain injury.

RESULTS:

Preoperative brain injury was present on HUS in 5 infants (3%) and on MRI in 44 infants (26%) (P < .001). Four of the HUS showed intraventricular hemorrhage not seen on MRI, suggesting false-positive results, and the fifth showed periventricular leukomalacia. The predominant MRI abnormality was white matter injury (n = 32). Other findings included infarct (n = 16) and hemorrhage (n = 5).

CONCLUSIONS:

Preoperative brain injury on MRI was present in 26% of infants with CHD, but only 3% had any evidence of brain injury on HUS. Among positive HUS, 80% were false-positive results. Our findings suggest that routine HUS is not indicated in asymptomatic term or near-term neonates undergoing surgery for CHD, and MRI may be a preferable tool when the assessment of these infants is warranted.
Beyond just species: Is Africa the most taxonomically diverse bird continent?
Authors: Lotz Chris N. , Caddick John A. , Forner Monika , Cherry Michael I.
Published: May 2013

We analysed avian diversity in 8 similar-sized regions of Africa, and in an additional 16 regions spread across the world; half of these 24 regions were tropical and the other half were temperate. For each region, counts of species, genus, family and order were recorded rather than only a species count. We assert that this approach gives more accurate insights into diversity patterns, as we show that in relatively species-rich parts of the world species are on average taxonomically more similar to each other than in species-poor areas. Northwestern South America is the world’s most species-rich region for birds, but we show that sub-Saharan Africa has greater diversity at higher taxonomic levels and is thus arguably the richest corner of the world for birds: the Mozambique–Zimbabwe region displays the highest diversity at the order level (with 30 orders), with all other sub-Saharan regions having between 27 and 29 orders each. Northern India is also extremely diverse (surprisingly so for a marginally temperate region) at all taxonomic levels below that of order. We hope that our study might generate further analyses of avian diversity beyond the species level.
Effect of selenium on cadmium-induced oxidative stress and esterase activity in rat organs
Authors: Dzobo Kevin , Naik Yogeshkumar S.
Published: May 2013

Metal toxicity is a threat mainly in the industrialised world where industry discharges many toxic metals into the environment. We investigated the effects of two metals – cadmium and selenium – on the cytosolic antioxidant enzymes and esterases in the liver, kidneys and testes of rats. Male Sprague-Dawley rats (n=28) were divided equally into four groups: control, cadmium, selenium and cadmium/selenium. Salts of the metals were administered intraperitoneally for 15 days. In the liver, cadmium treatment (1.67 mg/kg per day) resulted in a decrease in catalase activity and an increase superoxide dismutase (SOD) activity. Selenium treatment (0.23 mg/kg per day) resulted in increases in glutathione s-transferase, catalase and DT-diaphorase activities. Treatment with both cadmium and selenium resulted in an increase in glutathione peroxidase (GPx) activity. Esterase activities were significantly lower in the presence of cadmium. In the kidney, cadmium treatment caused a decrease in catalase, DT-diaphorase, and SOD activities and selenium supplementation reversed the cadmium-induced decrease in these enzyme activities. Selenium treatment increased catalase and SOD activities in the kidney. In the testis, cadmium treatment decreased GPx and SOD activities, but at the same time increased catalase and DT-diaphorase activities. Esterase activities increased in the presence of selenium in both the kidney and testis. These results suggest that selenium might be toxic to the liver while at the same time play a protective role against cadmium-induced oxidative stress and toxicity in the kidney and testis.
Hydropower converters with head differences below 2·5 m
Authors: Bozhinova Snezhana , Hecht Veronika , Kisliakov Dimitar , Müller Gerald , Schneider Silke
Published: May 2013

Hydropower with very low head (VLH) differences constitutes a largely unused potential source of renewable energy. A literature review of hydropower converters for VLH differences covering the engineering literature from the 1830s onwards was conducted to assess the potential of historic, current and emerging technologies. The results showed that a large number of different interesting technologies were used/developed, and that several novel and promising concepts are currently under development. Technologies emerged for different market segments: water wheels for low flow rates, turbines for large flow volumes. To take account of increased ecological demands and the desire for cost reduction, further improvements of existing technologies and new converter technologies have been developed. Other concepts described in the literature were apparently never applied although they promise development potential. The information gathered allowed for a comparison of available technologies with respect to area of application, performance, ecological impact and cost level.