bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically divergent methicillin-resistant Staphylococcus aureus and sec-dependent mastitis of dairy goats in Taiwan
Authors: Chu Chishih , Yu Changyou , Lee Yanhaui , Su Yaochi
Published: March 2012

Background

Widespread in the environment, Staphylococcus spp. infect animals and humans as normal flora or pathogens. By extending our recent report of multi-drug resistant (MDR) S. aureus in dairy goats, this study investigated the staphylococcal infection and characterized the MDR-S. aureus and methicillin-resistant S. aureus (MRSA) isolates collected from goats in 2008 to elucidate the appearance of MRSA in goats and the mastitis associated staphylococcus enterotoxin (SE) types. A total of 555 samples were collected from six goat parts and three environmental sources among four dairy goat farms in southern Taiwan. Coagulase-positive and negative Staphylococcus spp. (CPS and CNS, respectively) were also identified. Furthermore, predominant SE genes of nine enterotoxin genes sea through sej along with antimicrobial resistance and genetic variations were determined.

Results

In total, 137 staphylococcal strains were identified and found predominantly in milk, and in the vagina, anus, and nasal cavity. The most prevalent species was S. lentus, followed by S. aureus, S. epidermidis, and S. xylosus. Enterotoxin genes were not identified in any CNS isolates, however sec and see were identified only in S. aureus associated with mastitis in goat. In compared to the isolates from 2006 to 2007, 27 S. aureus isolates from 2008 were found to be more resistant to ampicillin, cephalothin, oxacillin, oxytetracycline, penicillin G, and tetracycline. Eleven MRSA isolates were identified and belonged to SCCmec type III (nine isolates) as the major type and SCCmec type II (two isolates). These MRSA isolates revealed pulse-field gel electrophoresis (PFGE) pattern A (five isolates), C (one isolate), and D (one isolate) of human isolates. The other two isolates without pulsotypes belonged to ST59.

Conclusion

The prevalence and infection sites of CNS differed from those of CPS. Genetic analyses indicated that genetic divergence, possible zoonotic transfer of MRSA, and the involvement of sec as important virulence factors for of S. aureus that lead to mastitis in goats.
Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation
Authors: Wicki-Stordeur Leigh E , Dzugalo Adrian D , Swansburg Rose M , Suits Jocelyne M , Swayne Leigh Anne
Published: March 2012

Background

Pannexin 1 forms ion and metabolite permeable hexameric channels and is abundantly expressed in the brain. After discovering pannexin 1 expression in postnatal neural stem and progenitor cells we sought to elucidate its functional role in neuronal development.

Results

We detected pannexin 1 in neural stem and progenitor cells in vitro and in vivo. We manipulated pannexin 1 expression and activity in Neuro2a neuroblastoma cells and primary postnatal neurosphere cultures to demonstrate that pannexin 1 regulates neural stem and progenitor cell proliferation likely through the release of adenosine triphosphate (ATP).

Conclusions

Permeable to ATP, a potent autocrine/paracine signaling metabolite, pannexin 1 channels are ideally suited to influence the behavior of neural stem and progenitor cells. Here we demonstrate they play a robust role in the regulation of neural stem and progenitor cell proliferation. Endogenous postnatal neural stem and progenitor cells are crucial for normal brain health, and their numbers decline with age. Furthermore, these special cells are highly responsive to neurological injury and disease, and are gaining attention as putative targets for brain repair. Therefore, understanding the fundamental role of pannexin 1 channels in neural stem and progenitor cells is of critical importance for brain health and disease.
Relevant phosphoproteomic and mass spectrometry: approaches useful in clinical research
Authors: López Elena , Muñoz Sarbelio Rodríguez , Pascual Juan López , Madero Luis
Published: March 2012

Background

“It's not what we do, it's the way that we do it”. Never has this maxim been truer in proteomics than now. Mass Spectrometry‐based proteomics/phosphoproteomics tools are critical to understand the structure and dynamics (spatial and temporal) of signalling that engages and migrates through the entire proteome. Approaches such as affinity purification followed by Mass Spectrometry (MS) have been used to elucidate relevant biological questions disease vs. health. Thousands of proteins interact via physical and chemical association. Moreover, certain proteins can covalently modify other proteins post‐translationally. These post‐translational modifications (PTMs) ultimately give rise to the emergent functions of cells in sequence, space and time.

Findings

Understanding the functions of phosphorylated proteins thus requires one to study proteomes as linked‐systems rather than collections of individual protein molecules. Indeed, the interacting proteome or protein‐network knowledge has recently received much attention, as network‐systems (signalling pathways) are effective snapshots in time, of the proteome as a whole. MS approaches are clearly essential, in spite of the difficulties of some low abundance proteins for future clinical advances.

Conclusion

Clinical proteomics‐MS has come a long way in the past decade in terms of technology/platform development, protein chemistry, and together with bioinformatics and other OMICS tools to identify molecular signatures of diseases based on protein pathways and signalling cascades. Hence, there is great promise for disease diagnosis, prognosis, and prediction of therapeutic outcome on an individualized basis. However, and as a general rule, without correct study design, strategy and implementation of robust analytical methodologies, the efforts, efficiency and expectations to make biomarkers (especially phosphorylated kinases) a useful reality in the near future, can easily be hampered.
The Transcription Factor Encyclopedia
Authors: Yusuf Dimas , Butland Stefanie L , Swanson Magdalena I , Bolotin Eugene , Ticoll Amy , Cheung Warren A , Cindy Zhang Xiao Yu , Dickman Christopher TD , Fulton Debra L , Lim Jonathan S , Schnabl Jake M , Ramos Oscar HP , Vasseur-Cognet Mireille , de Leeuw Charles N , Simpson Elizabeth M , Ryffel Gerhart U , Lam Eric W-F , Kist Ralf , Wilson Miranda SC , Marco-Ferreres Raquel , Brosens Jan J , Beccari Leonardo L , Bovolenta Paola , Benayoun Bérénice A , Monteiro Lara J , Schwenen Helma DC , Grontved Lars , Wederell Elizabeth , Mandrup Susanne , Veitia Reiner A , Chakravarthy Harini , Hoodless Pamela A , Mancarelli M Michela , Torbett Bruce E , Banham Alison H , Reddy Sekhar P , Cullum Rebecca L , Liedtke Michaela , Tschan Mario P , Vaz Michelle , Rizzino Angie , Zannini Mariastella , Frietze Seth , Farnham Peggy J , Eijkelenboom Astrid , Brown Philip J , Laperrière David , Leprince Dominique , de Cristofaro Tiziana , Prince Kelly L , Putker Marrit , del Peso Luis , Camenisch Gieri , Wenger Roland H , Mikula Michal , Rozendaal Marieke , Mader Sylvie , Ostrowski Jerzy , Rhodes Simon J , Van Rechem Capucine , Boulay Gaylor , Olechnowicz Sam WZ , Breslin Mary B , Lan Michael S , Nanan Kyster K , Wegner Michael , Hou Juan , Mullen Rachel D , Colvin Stephanie C , Noy Peter John , Webb Carol F , Witek Matthew E , Ferrell Scott , Daniel Juliet M , Park Jason , Waldman Scott A , Peet Daniel J , Taggart Michael , Jayaraman Padma-Sheela , Karrich Julien J , Blom Bianca , Vesuna Farhad , O'Geen Henriette , Sun Yunfu , Gronostajski Richard M , Woodcroft Mark W , Hough Margaret R , Chen Edwin , Europe-Finner G Nicholas , Karolczak-Bayatti Magdalena , Bailey Jarrod , Hankinson Oliver , Raman Venu , LeBrun David P , Biswal Shyam , Harvey Christopher J , DeBruyne Jason P , Hogenesch John B , Hevner Robert F , Héligon Christophe , Luo Xin M , Blank Marissa Cathleen , Millen Kathleen Joyce , Sharlin David S , Forrest Douglas , Dahlman-Wright Karin , Zhao Chunyan , Mishima Yuriko , Sinha Satrajit , Chakrabarti Rumela , Portales-Casamar Elodie , Sladek Frances M , Bradley Philip H , Wasserman Wyeth W
Published: March 2012

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.
CX3CL1/fractalkine is a novel regulator of normal and malignant human B cell function
Authors: Corcione Anna , Ferretti Elisa , Pistoia Vito
Published: March 2012

Review of the role of the CX3CL1/CX3CR1 axis in the regulation of normal B cells and malignant B cell microenvironment.

CX3CL1, or fractalkine, the unique member of the CX3C chemokine family, exists as a transmembrane glycoprotein, as well as in soluble form, each mediating different biological activities, and is constitutively expressed in many hematopoietic and nonhematopoietic tissues. CX3CR1, the CX3CL1 exclusive receptor, is a classical GPCR, expressed on NK cells, CD14+ monocytes, and some subpopulation of T cells, B cells, and mast cells. A recent paper by our group has demonstrated for the first time that highly purified human B cells from tonsil and peripheral blood expressed CX3CR1 at mRNA and protein levels. In particular, tonsil naïve, GC, and memory B cells expressed CX3CR1, but only GC centrocytes were attracted by soluble CX3CL1, which with its receptor, are also involved in the pathogenesis of several inflammatory disorders, as well as of cancer. Previous studies have shown that CX3CR1 is up-regulated in different types of B cell lymphoma, as well as in B-CLL. Recently, we have demonstrated that the CX3CL1/CX3CR1 axis is involved in the interaction of B-CLL cells with their microenvironment. Taken together, our data delineate a novel role for the CX3CL1/CX3CR1 complex in the biology of normal B cells and B-CLL cells. These topics are the subject of this review article.
The Endemic Paraganglioma Syndrome Type 1: Origin, Spread, and Clinical Expression
Authors: Schiavi Francesca , Demattè Serena , Cecchini Maria Enrica , Taschin Elisa , Bobisse Sara , Del Piano Antonella , Donner Davide , Barbareschi Mattia , Manera Vittorio , Zovato Stefania , Erlic Zoran , Savvoukidis Theodoros , Barollo Susi , Grego Franco , Trabalzini Franco , Amistà Pietro , Grandi Cesare , Branz Fabio , Marroni Fabio , Neumann Hartmut P. H. , Opocher Giuseppe
Published: March 2012

Context:

Anecdotal evidence suggests a high incidence in Trentino, Italy, of head and neck paragangliomas (HNPGL), a rare autosomal dominant disease called paraganglioma type 1 syndrome and caused by germ-line mutations of the SDHD gene.

Objective:

The aim of this study was to investigate the origin, spread, and clinical expression of the disease in this geographic region.

Design, Setting, and Participants:

Trentino natives with HNPGL were recruited for establishing clinical expression of the disease, presence of a founder effect, and age of common ancestor. A large sample of the local population was recruited for determination of mutation prevalence and spread.

Main Outcome Measures:

SDHD genetic testing was offered to first-degree relatives, and clinical surveillance was offered to at-risk carriers. The hypothesis of a founder effect was explored by haplotype analysis, and time to the most recent common ancestor was estimated by decay of haplotype sharing over time.

Results:

A total of 287 of the 540 recruited individuals from 95 kindreds carried the SDHD c.341A>G p.Tyr114Cys mutation. The prevalent phenotype was bilateral or multiple HNPGL, with low prevalence of pheochromocytoma and malignant forms. Penetrance was high. A common ancestor was dated between the 14th and 15th century, with the mutation spreading from the Mocheni Valley, a geographic, cultural and, presumably, a genetic isolate to 1.5% of the region's population.

Conclusions:

A combination of particular demographic, geographical, and historical conditions has resulted in the oldest and largest SDHD founder effect so far characterized and has transformed a rare disease into an endemic disease with major public health implications.
Doing it in reverse: 3′-to-5′ polymerization by the Thg1 superfamily
Authors: Jackman Jane E. , Gott Jonatha M. , Gray Michael W.
Published: March 2012

The tRNAHisguanylyltransferase (Thg1) family of enzymes comprises members from all three domains of life (Eucarya, Bacteria, Archaea). Although the initial activity associated with Thg1 enzymes was a single 3′-to-5′ nucleotide addition reaction that specifies tRNAHisidentity in eukaryotes, the discovery of a generalized base pair–dependent 3′-to-5′ polymerase reaction greatly expanded the scope of Thg1 family–catalyzed reactions to include tRNA repair and editing activities in bacteria, archaea, and organelles. While the identification of the 3′-to-5′ polymerase activity associated with Thg1 enzymes is relatively recent, the roots of this discovery and its likely physiological relevance were described ∼30 yr ago. Here we review recent advances toward understanding diverse Thg1 family enzyme functions and mechanisms. We also discuss possible evolutionary origins of Thg1 family–catalyzed 3′-to-5′ addition activities and their implications for the currently observed phylogenetic distribution of Thg1-related enzymes in biology.
Process Management Impact on Clinical and Experiential Quality: Managing Tensions Between Safe and Patient-Centered Healthcare
Authors: Chandrasekaran Aravind , Senot Claire , Boyer Kenneth K.
Published: March 2012

This research investigates the effect of process management on clinical and experiential quality. Clinical quality measures hospitals' performance on patient safety, i.e., adherence to standards, whereas experiential quality relates to patient centeredness, i.e., responsiveness to the needs and preferences of the patient. Drawing from the organizational learning literature, we argue for a trade-off between clinical and experiential quality as hospitals emphasize process management. We also study how external and internal forces, i.e., state legislation and hospital leadership, influence this relationship. A combination of primary data and secondary data collected at various time intervals is employed to test our hypotheses. Four important implications emerge from this work. First, we find that hospitals' emphasis on process management is associated with an increase in clinical quality but a decrease in experiential quality. Second, we find that state legislation initially reinforces this trade-off but, overtime, facilitates a positive impact of process management on both quality outcomes. Third, a post hoc analysis suggests that a specific type of hospital leadership, namely, patient-centered leadership, helps mitigate the negative association between process management and experiential quality. Finally, our research provides preliminary evidence regarding the relationship between clinical quality and patient satisfaction contingent on experiential quality. Implications for theory and practice are discussed.
Daptomycin Experience in Critical Care Patients: Results from a Registry
Authors: Brown Jack E , Fominaya Cory , Christensen Keith J , McConnell Scott A , Lamp Kenneth C
Published: March 2012

Background:

Vancomycin is often the drug of choice in critically ill patients with gram-positive infections, although circumstances often prevent its use. In these situations, clinicians are frequently left with limited data regarding alternative agents.

Objective:

To describe patients with reported sepsis receiving daptomycin in a critical care unit.

Methods:

This multicenter, noncomparative, noninterventional study identified patients in critical care units, using the Cubicin Outcomes Registry and Experience (CORE) 2005-2009 registry. A descriptive account of patient characteristics, infectious etiology, outcomes at the end of daptomycin therapy, and 30-day mortality is reported. Nonevaluable patients were excluded from the efficacy analysis but included in the safety analysis.

Results:

We identified 128 patients, 98 (77%) of whom were evaluable for efficacy. Patient characteristics for the efficacy population were 55 (56%) males, 30 (31%) aged 66 years or older, 38 (39%) had creatinine clearance less than 30 mL/min, and 27 (28%) were on dialysis. Common underlying diseases included acute or chronic renal failure 44 (45%), hypertension 40 (41%), and diabetes 27 (28%). Seventy-two (73%) patients were bacteremic The most common pathogens found were methicillin-resistant Staphylococcus aureus (32%), vancomycin-resistant Enterococcus faecium (21%), and coagulase-negative staphylococci (20%). Prior to daptomycin, antibiotics were used in 84 (86%) patients, most commonly vancomycin (65/84; 77%). The median (range) initial daptomycin dose was 6 mg/kg (3-10) and duration of 10 days (1-58). Overall success rate was 70% (31% cured; 39% improved). Twelve adverse events possibly related to daptomycin were reported in 9 of 128 (7%) patients in the safety population; 4 of these in 4 (3%) patients were serious. The mortality rate within 30 days of completing daptomycin was 42 of 128 (33%) patients.

Conclusions:

These data provide preliminary results on the use of daptomycin in critically ill patients with complicated conditions. Controlled studies are needed to best evaluate daptomycin use in these patients.
Optimal Alcohol Taxes for Australia
Authors: Fogarty James J.
Published: March 2012

The 2010 Australian government tax review suggested Australia move to a uniform excise tax rate for all alcoholic beverages. Here, a model is presented and calibrated that shows the optimal per litre of pure alcohol (LAL) tax rates for beer, wine, spirits, and ready-to-drink spirits are substantially different to both current alcohol tax rates and the uniform tax rate recommended by the tax review. Specifically, given an individual consumer utility model, the best estimate values of the welfare maximising LAL tax rates are: $37 for beer, $11 for wine, $50 for spirits, and $77 for ready-to-drink spirits. The variation in the optimal tax rate across beverage types flows from differences in the externality costs associated with the consumption of each beverage type, and differences in the proportion of moderate consumption and abusive consumption associated with each beverage type. In addition, it is shown that the optimal tax rates are influenced by the range of costs that are considered to be externality costs, and the relative price responsiveness of abusers and moderate consumers.
The Beads of Translation: Using Beads to Translate mRNA into a Polypeptide Bracelet
Authors: Dunlap Dacey , Patrick Patricia
Published: March 2012

During this activity, by making beaded bracelets that represent the steps of translation, students simulate the creation of an amino acid chain. They are given an mRNA sequence that they translate into a corresponding polypeptide chain (beads). This activity focuses on the events and sites of translation. The activity provides students with a closer look at the process of translation, not focused solely on pairing codons with amino acids. The students move throughout the classroom, which simulates a nucleus, cytoplasm, a ribosome, and the A site, a P site, and an E site of a ribosome.
Streamlined Strategies to Better Visualize Southern Blotting
Authors: Dean Derek M.
Published: March 2012

In this article, I describe an animated slideshow of Southern blotting that I have made freely available to other instructors. My hope is to provide a clear visualization of the logistics behind the technique so that instructors have a solid basis – as well as time freed up – to discuss its applications with students.
Epigenetics: A Fascinating Field with Profound Research, Clinical, & Public Health Implications
Authors: Stein Richard A. , Davis Devra Lee
Published: March 2012

Epigenetics is emerging as one of the most dynamic and vibrant biomedical areas. Multiple lines of evidence confirm that inherited genetic changes alone cannot fully explain all phenotypic characteristics of live organisms, and additional factors, which are not encoded in the DNA sequence, are involved. The contribution of non-genetic factors is perhaps best illustrated by monozygotic twins, which, despite sharing nearly identical DNA sequences, are often discordant for diseases they develop. Even when twins develop the same condition, they may experience different clinical manifestations or clinical onset at different ages. Epigenetic mechanisms explain how a zygote can differentiate into >220 different cell types that form an adult organism and, with rare exceptions, share the same DNA. Increasingly, epigenetic factors emerge, in addition to genetic ones, as important contributors to carcinogenesis. Epigenetic modifications also explain the biological impact of environmental factors, including chemical and dietary compounds, physical agents, pathogens linked to cancer, and social–emotional interactions. Unlike genetic changes, epigenetic changes are reversible, a characteristic that opens unprecedented therapeutic avenues, exemplified by the first epigenetic drugs that were recently approved. Understanding the combined contribution of genetic and epigenetic factors to gene expression will be essential to dissect the biological networks shaping development and disease, and to develop a new array of prophylactic, diagnostic, and therapeutic applications.
Teaching Mitochondrial Genetics & Disease: A GENA Project Curriculum Intervention
Authors: Reardon Ryan A. , Sharer J. Daniel
Published: March 2012

This report describes a novel, inquiry-based learning plan developed as part of the GENA educational outreach project. Focusing on mitochondrial genetics and disease, this interactive approach utilizes pedigree analysis and laboratory techniques to address non-Mendelian inheritance. The plan can be modified to fit a variety of educational goals and is now commercially available.
Using Digital Photography to Supplement Learning of Biotechnology
Authors: Norflus Fran
Published: March 2012

The author used digital photography to supplement learning of biotechnology by students with a variety of learning styles and educational backgrounds. Because one approach would not be sufficient to reach all the students, digital photography was used to explain the techniques and results to the class instead of having to teach each student individually. To analyze the effectiveness of this teaching technique, the students' responses on various examination questions were analyzed.
Using Phylogenetic Analysis to Detect Market Substitution of Atlantic Salmon for Pacific Salmon: An Introductory Biology Laboratory Experiment
Authors: Cline Erica , Gogarten Jennifer
Published: March 2012

We describe a laboratory exercise developed for the cell and molecular biology quarter of a year-long majors’ undergraduate introductory biology sequence. In an analysis of salmon samples collected by students in their local stores and restaurants, DNA sequencing and phylogenetic analysis were used to detect market substitution of Atlantic salmon for Pacific salmon. This allowed students to apply molecular methods such as polymerase chain reaction (PCR) and DNA sequencing to a socially relevant issue.
Determining Annealing Temperatures for Polymerase Chain Reaction
Authors: Porta Angela R. , Enners Edward
Published: March 2012

The polymerase chain reaction (PCR) is a common technique used in high school and undergraduate science teaching. Students often do not fully comprehend the underlying principles of the technique and how optimization of the protocol affects the outcome and analysis. In this molecular biology laboratory, students learn the steps of PCR with an emphasis on primer composition and annealing temperature, which they manipulate to test the effect on successful DNA amplification. Students design experiments to test their hypotheses, promoting a discovery-based approach to laboratory teaching and development of critical-thinking and reasoning skills.
Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chornobyl papillary thyroid carcinoma
Authors: Dinets Andrii , Hulchiy Mykola , Sofiadis Anastasios , Ghaderi Mehran , Höög Anders , Larsson Catharina , Zedenius Jan
Published: March 2012

Background

Increased incidence of papillary thyroid carcinoma (PTC) is observed as a consequence of radiation exposure in connection to the Chornobyl nuclear plant accident in 1986. In this study, we report a cohort of adult Ukrainian patients diagnosed with PTC from 2004 to 2008 following exposure at the age of 18 years or younger.

Methods

In total, 70 patients were identified and clinically characterized. The commonBRAF1799T>A mutation was assessed by pyrosequencing, theRET/PTC1andRET/PTC3(NCOA4) rearrangements by RT-PCR, and the expression of Ki-67 (MIB-1 index), BCL2, cyclin A, and cyclin D1 by immunohistochemistry.

Results

In total, 46/70 (66%) cases carried aBRAFmutation and/or aRET/PTCrearrangement. ABRAFmutation was detected in 26 tumors,RET/PTC1in 20 cases, andRET/PTC3in four cases. In four of these cases,BRAFmutation andRET/PTCrearrangement were coexisting. TheBRAFmutation was underrepresented among PTCs with accompanying chronic lymphocytic thyroiditis (CLT) compared with PTCs without this feature (12 vs 44%). MIB-1 proliferation index determined by double staining with leukocyte common antigen was low (mean 0.8%; range 0.05–4.5%). Moreover, increased expression of cyclin A was observed in PTCs with a tumor size >2 cm compared with PTCs ≤2 cm (1.2 vs 0.6%). BCL2 and cyclin D1 showed frequent expression but without associations to clinical characteristics or amplification of theCCND1locus.

Conclusions

Our results suggest that this cohort has frequentBRAFmutation,RET/PTC1rearrangement, and low proliferation index. Furthermore,BRAF1799T>A was underrepresented in PTCs with CLT, and cyclin A expression was associated with increased PTC tumor size.
Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging
Authors: Ghosh Paramita M , Shu Zhen-Ju , Zhu Bing , Lu Zhongding , Ikeno Yuji , Barnes Jeffrey L , Yeh Chih-Ko , Zhang Bin-Xian , Katz Michael S , Kamat Amrita
Published: March 2012

Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic functional and structural impairment and overall metabolic risk. Previous studies noted an association between hepatic steatosis and age in humans and rodents. However, the mechanisms leading to age-associated hepatic fat accumulation remain unknown. Earlier work from our group showed that β-adrenergic receptor (β-AR) levels and β-AR-stimulated adenylyl cyclase activity increase in rat liver during aging. Here we investigated whether age-associated increases in β-AR signaling play a role in augmenting hepatic lipid accumulation. We demonstrate an increase in hepatic lipid content during senescence and a significant correlation between hepatic fat content and stimulation of adenylyl cyclase activity by the β-AR agonist isoproterenol in rat liver. Isoproterenol administration to young and old rodents in vivo increased hepatic lipid accumulation. Furthermore, in vitro overexpression of β1- and β2-AR subtypes in hepatocytes from young rodents increased cellular lipid content, whereas inhibition of β-ARs by receptor subtype-specific inhibitors reduced lipid levels in hepatocytes from senescent animals. Isoproterenol-induced hepatic lipid accumulation in vivo was prevented by the β-AR nonselective blocker propranolol, suggesting a novel therapeutic effect of this class of drugs in hepatic steatosis. Acipimox, which inhibits adipose tissue lipolysis, did not alter isoproterenol-mediated hepatic fat accumulation; thus β-AR responsive hepatic lipid accumulation does not appear to be related primarily to altered lipolysis. These findings suggest that augmented hepatic β-AR signaling during aging may increase lipid accumulation in liver and advocate a possible role for β-adrenergic blockers in preventing or retarding the development of hepatic steatosis.
The effect of oviductal deleted in malignant brain tumor 1 over porcine sperm is mediated by a signal transduction pathway that involves pro-AKAP4 phosphorylation
Authors: Teijeiro Juan Manuel , Marini Patricia Estela
Published: March 2012

The interaction between sperm and oviduct results in the selection of sperm with certain qualities. Porcine oviductal deleted in malignant brain tumor 1, DMBT1 (previously called sperm-binding glycoprotein, SBG), has been proposed to be implicated in sperm selection through acrosome alteration and suppression of motility of a subpopulation of sperm that have begun capacitation prematurely. It producesin vitroacrosome alteration and decrease of motility of boar sperm, concomitant with tyrosine phosphorylation of a 97 kDa sperm protein (p97). We hypothesized that the phosphorylation of p97 may be a link between DMBT1 sensing by a subpopulation of boar sperm and its biological effect. In this work, p97 was identified by mass spectrometry and immunoprecipitation as a porcine homologue of AKAP4. Pro-AKAP4 was localized by immunofluorescence and subcellular fractionation to the periacrosomal membranes and was shown to be tyrosine phosphorylated by DMBT1 regardless of the presence of calcium or bicarbonate, and of cAMP analogs, protein kinase A inhibitors, or a protein kinase C inductor. A processed ∼80 kDa form of AKAP4 was also detected at the tail of boar sperm, which was not tyrosine phosphorylated by DMBT1 under the conditions tested. Immunohistochemistry of testis showed presence of AKAP4 in boar sperm precursor cells. The evidence presented here supports the involvement of AKAP4 in the formation of the fibrous sheath on boar precursor sperm cells and implicates the phosphorylation of pro-AKAP4 as an early step in the signal transduction pathway gated by DMBT1 that leads to sperm selection through acrosome alteration.
Binder of sperm 1 and epididymal sperm binding protein 1 are associated with different bull sperm subpopulations
Authors: D'Amours Olivier , Bordeleau Louis-Jean , Frenette Gilles , Blondin Patrick , Leclerc Pierre , Sullivan Robert
Published: March 2012

Previously, we showed that binder of sperm 1 (BSP1) and epididymal sperm binding protein 1 (ELSPBP1) proteins are more abundant in the immotile bovine sperm subpopulation following cryopreservation. In this study, we investigated the association of BSP1 and ELSPBP1 with sperm in relation to their ability to survive the cryopreservation process. Fresh and cryopreserved semen samples from the same ejaculate collected from nine Holstein bulls were incubated with a fixable viability probe, fixed and permeabilised and then immunolabelled with rabbit anti-BSP1, rabbit anti-ELSPBP1 or rabbit IgG as negative control. Spermatozoa were then incubated with Alexa 488-conjugated secondary antibody and Hoechst 33342. For each sample, 10 000 ‘Hoechst positive’ events were analysed by flow cytometry. Alternatively, sperm populations were obtained by fluorescence-activated cell sorting. In freshly ejaculated live sperm, two distinct BSP1 detection patterns were revealed: a first population where BSP1 is present along the flagellar region (P1 subpopulation) and a second population where BSP1 is localised on both the flagellar and the acrosomal regions (P3 subpopulation). The dead population presented a BSP1 distribution similar to P3 but with a more intense fluorescence signal (P4 subpopulation). In the corresponding cryopreserved samples, all sperm in the P3 subpopulation were dead while only a small proportion of the P1 subpopulation was dead (P2 subpopulation). ELSPBP1 was detected only in dead spermatozoa and in comparable proportions in both freshly ejaculated and cryopreserved semen. These results show that the presence of BSP1 over the acrosomal region characterises spermatozoa sensitive to cryopreservation and that ELSPBP1 characterises spermatozoa that are already dead at ejaculation.
FGF10 inhibits dominant follicle growth and estradiol secretion in vivo in cattle
Authors: Gasperin Bernardo G , Ferreira Rogério , Rovani Monique T , Santos Joabel T , Buratini José , Price Christopher A , Gonçalves Paulo Bayard D
Published: March 2012

Fibroblast growth factors (FGFs) are involved in paracrine control of follicle development. It was previously demonstrated that FGF10 decreases estradiol (E2) secretion in granulosa cell culture and that theca cellFGF10mRNA expression is decreased in healthy follicles from abattoir ovaries. The main objectives of this study were to evaluateFGF10andFGFR2bmRNA expression during follicular developmentin vivo, to evaluate the effect of FGF10 on follicle growth usingBos taurus tauruscows as a model, and to gain more insight into the mechanisms through which FGF10 inhibits steroidogenesis. Messenger RNA encoding bothFGF10andFGFR2b(main FGF10 receptor) was significantly more expressed in subordinate follicles (SFs) than in dominant follicles (DFs). The intrafollicular injection of FGF10 into the largest growing follicle at 7–8 mm in diameter interrupted the DF growth in a dose-dependent manner (11±0.4, 8.3±1 and 5.9±0.3 mm for 0, 0.1, and 1 μg/ml FGF10, respectively, at 72 h after treatment;P<0.05). In a third experiment, follicles were obtained 24 h after FGF10 (1 μg/ml) or PBS treatment through ovariectomy. In theca cells, FGF10 treatment did not affect mRNA encoding steroidogenic enzymes,LHCGRandIGFBPs, but significantly upregulatedFGF10mRNA expression. The expression ofCYP19A1mRNA in granulosa cells was downregulated by FGF10 treatment, which was accompanied by a 50-fold decrease in E2production, and decreased cyclin D2 mRNA. These results have shown thatFGF10and its receptorFGFR2bare more expressed in SFs and provide solidin vivoevidence that FGF10 acts as an important regulator of follicular growth in cattle.
New effects of Roundup on amphibians: Predators reduce herbicide mortality; herbicides induce antipredator morphology
Authors: Relyea Rick A.
Published: March 2012

The use of pesticides is important for growing crops and protecting human health by reducing the prevalence of targeted pest species. However, less attention is given to the potential unintended effects on nontarget species, including taxonomic groups that are of current conservation concern. One issue raised in recent years is the potential for pesticides to become more lethal in the presence of predatory cues, a phenomenon observed thus far only in the laboratory. A second issue is whether pesticides can induce unintended trait changes in nontarget species, particularly trait changes that might mimic adaptive responses to natural environmental stressors. Using outdoor mesocosms, I created simple wetland communities containing leaf litter, algae, zooplankton, and three species of tadpoles (wood frogs [Rana sylvatica or Lithobates sylvaticus], leopard frogs [R. pipiens or L. pipiens], and American toads [Bufo americanus or Anaxyrus americanus]). I exposed the communities to a factorial combination of environmentally relevant herbicide concentrations (0, 1, 2, or 3 mg acid equivalents [a.e.]/L of Roundup Original MAX) crossed with three predator‐cue treatments (no predators, adult newts [Notophthalmus viridescens], or larval dragonflies [Anax junius]). Without predator cues, mortality rates from Roundup were consistent with past studies. Combined with cues from the most risky predator (i.e., dragonflies), Roundup became less lethal (in direct contrast to past laboratory studies). This reduction in mortality was likely caused by the herbicide stratifying in the water column and predator cues scaring the tadpoles down to the benthos where herbicide concentrations were lower. Even more striking was the discovery that Roundup induced morphological changes in the tadpoles. In wood frog and leopard frog tadpoles, Roundup induced relatively deeper tails in the same direction and of the same magnitude as the adaptive changes induced by dragonfly cues. To my knowledge, this is the first study to show that a pesticide can induce morphological changes in a vertebrate. Moreover, the data suggest that the herbicide might be activating the tadpoles' developmental pathways used for antipredator responses. Collectively, these discoveries suggest that the world's most widely applied herbicide may have much further‐reaching effects on nontarget species than previous considered.
Divergence in ectomycorrhizal communities with foreign Douglas‐fir populations and implications for assisted migration
Authors: Kranabetter J. M. , Stoehr M. U. , O'Neill G. A.
Published: March 2012

Assisted migration of forest trees has been widely proposed as a climate change adaptation strategy, but moving tree populations to match anticipated future climates may disrupt the geographically based, coevolved association suggested to exist between host trees and ectomycorrhizal fungal (EMF) communities. We explored this issue by examining the consistency of EMF communities among populations of 40 year‐old Douglas‐fir (Pseudotsuga menziesii var. menziesii) trees in a common‐garden field trial using four provenances from contrasting coastal climates in southwestern British Columbia. Considerable variation in EMF community composition within test sites was found, ranging from 0.38 to 0.65 in the mean similarity index, and the divergence in EMF communities from local populations increased with site productivity. Clinal patterns in colonization success were detected for generalist and specialist EMF species on only the two productive test sites. Host population effects were limited to EMF species abundance rather than species loss, as richness per site averaged 15.0 among provenances and did not differ by transfer extent (up to 450 km), while Shannon's diversity index declined slightly. Large differences in colonization rates of specialist fungi, such as Tomentella stuposa and Clavulina cristata, raise the possibility that EMF communities maladapted to soil conditions contributed to the inferior growth of some host populations on productive sites. The results of the study suggest locally based specificity in host–fungal communities is likely a contributing factor in the outcome of provenance trials, and should be a consideration in analyzing seed‐transfer effects and developing strategies for assisted migration.
Ecological effects of nitrogen and sulfur air pollution in the US: what do we know?
Authors: Greaver Tara L , Sullivan Timothy J , Herrick Jeffrey D , Barber Mary C , Baron Jill S , Cosby Bernard J , Deerhake Marion E , Dennis Robin L , Dubois Jean-Jacques B , Goodale Christine L , Herlihy Alan T , Lawrence Gregory B , Liu Lingli , Lynch Jason A , Novak Kristopher J
Published: March 2012

Four decades after the passage of the US Clean Air Act, air‐quality standards are set to protect ecosystems from damage caused by gas‐phase nitrogen (N) and sulfur (S) compounds, but not from the deposition of these air pollutants to land and water. Here, we synthesize recent scientific literature on the ecological effects of N and S air pollution in the US. Deposition of N and S is the main driver of ecosystem acidification and contributes to nutrient enrichment in many natural systems. Although surface‐water acidification has decreased in the US since 1990, it remains a problem in many regions. Perturbations to ecosystems caused by the nutrient effects of N deposition continue to emerge, although gas‐phase concentrations are generally not high enough to cause phytotoxicity. In all, there is overwhelming evidence of a broad range of damaging effects to ecosystems in the US under current air‐quality conditions.
When the river runs dry: human and ecological values of dry riverbeds
Authors: Steward Alisha L , von Schiller Daniel , Tockner Klement , Marshall Jonathan C , Bunn Stuart E
Published: March 2012

Temporary rivers and streams that naturally cease to flow and dry up can be found on every continent. Many other water courses that were once perennial now also have temporary flow regimes due to the effects of water extraction for human use or as a result of changes in land use and climate. The dry beds of these temporary rivers are an integral part of river landscapes. We discuss their importance in human culture and their unique diversity of aquatic, amphibious, and terrestrial biota. We also describe their role as seed and egg banks for aquatic biota, as dispersal corridors and temporal ecotones linking wet and dry phases, and as sites for the storage and processing of organic matter and nutrients. In light of these valuable functions, dry riverbeds need to be fully integrated into river management policies and monitoring programs. We also identify key knowledge gaps and suggest research questions concerning the values of dry riverbeds.
Soft Drink, Software and Softening of Teeth â€“ a Case Report of Tooth Wear in the Mixed Dentition Due to a Combination of Dental Erosion and Attrition
Authors: Gambon D. L , Brand H. S , Nieuw Amerongen A.V
Published: March 2012

This case report describes a 9-year-old boy with severe tooth wear as a result of drinking a single glass of soft drink per day. This soft drink was consumed over a period of one to two hours, while he was gaming intensively on his computer. As a result, a deep bite, enamel cupping, sensitivity of primary teeth and loss of fillings occurred. Therefore, dentists should be aware that in patients who are gaming intensively, the erosive potential of soft drinks can be potentiated by mechanical forces leading to excessive tooth wear.
Economic Evaluation of a School-based Combined Program with a Targeted Pit and Fissure Sealant and Fluoride Mouth Rinse in Japan
Authors: Sakuma Shihoko , Yoshihara Akihiro , Miyazaki Hideo , Kobayashi Seigo
Published: March 2012

Background:

In Niigata prefecture, Japan, a system has been developed based on a school-based fluoride mouth rinse program as follows; students with caries susceptible teeth are screened in a school dental examination, and encouraged to receive sealant placement in local dental clinics. However, the cost-effectiveness of sealant application in the public health has been questioned. The aim of this study was to estimate of the cost-effectiveness and cost-benefit ratio for a school-based combined program with fluoride mouth rinse and targeted fissure sealant in children residing in non-fluoridated areas in Japan.

Participants:

The analysis was based on comparing an intervention group with two cohorts in the 8-year-old (n=66) and 11-year-old (n=58) participating in the combined program for four and seven years, respectively, with a control group of the same grades (n=43 and n=54 respectively).

Methods:

The study measured mean differences in number of decayed and filled teeth (DFT) between the study groups and a combined program cost per child during study periods. The cost-effectiveness ratio was expressed as an individual annual program cost per DFT averted. In the cost-benefit ratio the mean difference in treatment cost between groups (program benefit) was compared to program cost.

Results:

The mean reduced DFT differences between groups were 1.44 in 8-year-old and 3.17 in 11-year-old children. The cost-effectiveness ratio was ¥ 493 in the 8-year-old and ¥ 202 in the 11-year-old, respectively. The cost-benefit ratio was 1.84 in 8-year-old children and 2.42 in 11-year-old.

Conclusion:

This combined program indicated acceptable cost-effectiveness and cost –benefit ratio.
In Vitro Osteogenic Induction Of Human Gingival Fibroblasts For Bone Regeneration
Authors: Mostafa Nesrine Z , Uludağ Hasan , Varkey Mathew , Dederich Douglas N , Doschak Michael R , El-Bialy Tarek H
Published: March 2012

Background And Objective:

Periodontitis is an inflammatory disease causing bone loss, and is a primary cause of tooth loss. Gingival fibroblasts are readily available with minimal donor site morbidity and may be ideal for tissue engineering efforts in regenerating lost alveolar bone. Dexamethasone (Dex) is commonly employed forin vitroosteogenic induction of a variety of cells, but its effect on human gingival fibroblasts (HGF) is still controversial. Therefore, the aim of our study was to investigate the osteogenic differentiation of HGF following Dex treatment.

Methods:

Cultured HGFs were exposed to osteogenic medium containing a wide range of Dex concentrations (0.01-10 µM). The osteogenic phenotype was assessed based on changes in alkaline phosphatase (ALP) activity, the mRNA expression of selected extracellular matrix proteins critical for mineralization and the extent of extracellular mineralization (Von Kossa staining and Ca-content).

Results:

All assays showed a consistent and maximal osteogenic effect of Dex on HGF at 0.1 and 0.5 µM (weeks 3 and 4), as evidenced by significant osteopontin and osteocalcin expression and mineralization. Longer cultures (week 4) also yielded positive osteogenic effect of Dex at 0.01 µM. Moreover, ALP activity was significantly stimulated at 0.1 and 0.5 µM Dex initially after one week, but ALP was subsequently reduced under Dex. Higher Dex concentrations caused down regulation of osteogenic effects observed at the optimal (0.1-0.5 µM) concentrations.

Conclusion:

Under appropriate osteogenic conditioning, Dex treated HGFs could be a potential source of cells for cell-based therapy for periodontal bone regeneration.
Evaluation of Quantitative EEG by Classification and Regression Trees to Characterize Responders to Antidepressant and Placebo Treatment
Authors: Rabinoff M , Kitchen C.M.R , Cook I.A , Leuchter A.F
Published: March 2012

The study objective was to evaluate the usefulness of Classification and Regression Trees (CART), to classify clinical responders to antidepressant and placebo treatment, utilizing symptom severity and quantitative EEG (QEEG) data. Patients included 51 adults with unipolar depression who completed treatment trials using either fluoxetine, venlafaxine or placebo. Hamilton Depression Rating Scale (HAM-D) and single electrodes data were recorded at baseline, 2, 7, 14, 28 and 56 days. Patients were classified as medication and placebo responders or non-responders. CART analysis of HAM-D scores showed that patients with HAM-D scores lower than 13 by day 7 were more likely to be treatment responders to fluoxetine or venlafaxine compared to non-responders (p=0.001). Youden’s index γ revealed that CART models using QEEG measures were more accurate than HAM-D-based models. For patients given fluoxetine, patients with a decrease at day 2 in θ cordance at AF2 were classified by CART as treatment responders (p=0.02). For those receiving venlafaxine, CART identified a decrease in δ absolute power at day 7 at the PO2 region as characterizing treatment responders (p=0.01). Using all patients receiving medication, CART identified a decrease in δ absolute power at day 2 in the FP1 region as characteristic of nonresponse to medication (p=0.003). Optimal trees from the QEEG CART analysis primarily utilized cordance values, but also incorporated some δ absolute power values. The results of our study suggest that CART may be a useful method for identifying potential outcome predictors in the treatment of major depression.