bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Expression of Babesia ovis Secreted Antigen 1 and Evaluation of Its Diagnostic Potential in an Enzyme-Linked Immunosorbent Assay
Authors: Sevinc Ferda , Cao Shinuo , Xuan Xuenan , Sevinc Mutlu , Ceylan Onur
Published: February 2015

In order to identify immunoreactive proteins that are usable for the immunological diagnosis of
Babesia ovis
infections, a phage lambda cDNA expression library was constructed and screened using parasite-specific immune serum. Immunoscreening resulted in the identification of a full-length cDNA clone encoding a secreted protein designated
Babesia ovis
secreted antigen 1 (BoSA1). The full-length BoSA1 cDNA contained a 1,137-bp open reading frame that encoded a protein of 378 amino acids, with a signal peptide and 2 internal repeat domains. The theoretical molecular mass of the mature protein was 42.5 kDa. Recombinant BoSA1 (rBoSA1) protein was expressed in
Escherichia coli
strain DH5α cells as a glutathione
S
-transferase (GST) fusion protein and was purified by affinity chromatography. Purified rBoSA1 was tested for reactivity with sera from animals experimentally or naturally infected with
B. ovis
, in an indirect enzyme-linked immunosorbent assay (ELISA). The results showed that specific antibodies against rBoSA1 were detectable on days 7 and 8 of the experimental infection and were maintained during the sampling period. Additionally, 38 field sera taken from sheep naturally infected with
B. ovis
gave strong positive reactions in the ELISA between day 20 and day 30 of treatment. As a result, the identified recombinant BoSA1 protein seems to be a promising diagnostic antigen that is usable for the development of serological assays for the diagnosis of ovine babesiosis. This is the first report on the molecular cloning, expression, and potential use of a recombinant antigen for the diagnosis of ovine babesiosis.
Challenges in Antigenic Characterization of Circulating Influenza A(H3N2) Viruses during the 2011-2012 Influenza Season: an Ongoing Problem?
Authors: Kossyvakis Athanasios , Pogka Vasiliki , Melidou Aggeliki , Moutousi Afroditi , Gioula Georgia , Kalliaropoulos Antonios , Exindari Maria , Emmanouil Mary , Horefti Elina , Spala Georgia , Meijer Adam , Malisiovas Nikolaos , Mentis Andreas F.
Published: February 2015

Genetic and antigenic characterization of 37 representative influenza A(H3N2) virus strains isolated in Greece during the 2011-2012 winter season was performed to evaluate matching of the viruses with the seasonal influenza vaccine strain A/Perth/16/2009. Hemagglutinin gene sequence analysis revealed that all Greek strains clustered within the Victoria/208 genetic clade. Furthermore, substitutions in the antigenic and glycosylation sites suggested potential antigenic drift. Our hemagglutination inhibition (HI) analysis showed that the Greek viruses were Perth/16-like; however, these viruses were characterized as Victoria/208-like when tested at the United Kingdom WHO Collaborating Centre (CC) with HI assays performed in the presence of oseltamivir, a finding consistent with the genetic characterization data. Variability in the HI test performance experienced by other European laboratories indicated that antigenic analysis of the A(H3N2) virus has limitations and, until its standardization, national influenza reference laboratories should include genetic characterization results for selection of representative viruses for detailed antigenic analysis by the WHO CCs.
Comparative Evaluation of Three Commercial Quantitative Cytomegalovirus Standards by Use of Digital and Real-Time PCR
Authors: Hayden R. T. , Gu Z. , Sam S. S. , Sun Y. , Tang L. , Pounds S. , Caliendo A. M.
Published: February 2015

The recent development of the 1st WHO International Standard for human cytomegalovirus (CMV) and the introduction of commercially produced secondary standards have raised hopes of improved agreement among laboratories performing quantitative PCR for CMV. However, data to evaluate the trueness and uniformity of secondary standards and the consistency of results achieved when these materials are run on various assays are lacking. Three concentrations of each of the three commercially prepared secondary CMV standards were tested in quadruplicate by three real-time and two digital PCR methods. The mean results were compared in a pairwise fashion with nominal values provided by each manufacturer. The agreement of results among all methods for each sample and for like concentrations of each standard was also assessed. The relationship between the nominal values of standards and the measured values varied, depending upon the assay used and the manufacturer of the standards, with the degree of bias ranging from +0.6 to −1.0 log
10
IU/ml. The mean digital PCR result differed significantly among the secondary standards, as did the results of the real-time PCRs, particularly when plotted against nominal log
10
IU values. Commercially available quantitative secondary CMV standards produce variable results when tested by different real-time and digital PCR assays, with various magnitudes of bias compared to nominal values. These findings suggest that the use of such materials may not achieve the intended uniformity among laboratories measuring CMV viral load, as envisioned by adaptation of the WHO standard.
CCCTC-Binding Factor Recruitment to the Early Region of the Human Papillomavirus 18 Genome Regulates Viral Oncogene Expression
Authors: Paris Christian , Pentland Ieisha , Groves Ian , Roberts David C. , Powis Simon J. , Coleman Nicholas , Roberts Sally , Parish Joanna L.
Published: February 2015

Host cell differentiation-dependent regulation of human papillomavirus (HPV) gene expression is required for productive infection. The host cell CCCTC-binding factor (CTCF) functions in genome-wide chromatin organization and gene regulation. We have identified a conserved CTCF binding site in the E2 open reading frame of high-risk HPV types. Using organotypic raft cultures of primary human keratinocytes containing high-risk HPV18 genomes, we show that CTCF recruitment to this conserved site regulates viral gene expression in differentiating epithelia. Mutation of the CTCF binding site increases the expression of the viral oncoproteins E6 and E7 and promotes host cell proliferation. Loss of CTCF binding results in a reduction of a specific alternatively spliced transcript expressed from the early gene region concomitant with an increase in the abundance of unspliced early transcripts. We conclude that high-risk HPV types have evolved to recruit CTCF to the early gene region to control the balance and complexity of splicing events that regulate viral oncoprotein expression.

IMPORTANCE
The establishment and maintenance of HPV infection in undifferentiated basal cells of the squamous epithelia requires the activation of a subset of viral genes, termed early genes. The differentiation of infected cells initiates the expression of the late viral transcripts, allowing completion of the virus life cycle. This tightly controlled balance of differentiation-dependent viral gene expression allows the virus to stimulate cellular proliferation to support viral genome replication with minimal activation of the host immune response, promoting virus productivity. Alternative splicing of viral mRNAs further increases the complexity of viral gene expression. In this study, we show that the essential host cell protein CTCF, which functions in genome-wide chromatin organization and gene regulation, is recruited to the HPV genome and plays an essential role in the regulation of early viral gene expression and transcript processing. These data highlight a novel virus-host interaction important for HPV pathogenicity.
Herpes Simplex Virus 1 Upregulates p35, Alters CDK-5 Localization, and Stimulates CDK-5 Kinase Activity during Acute Infection in Neurons
Authors: Mostafa Heba H. , van Loben Sels Jessica M. , Davido David J.
Published: February 2015

The cyclin-dependent kinase 5 (CDK-5) activating protein, p35, is important for acute herpes simplex virus 1 (HSV-1) replication in mice. This report shows that HSV-1 increases p35 levels, changes the primary localization of CDK-5 from the nucleus to the cytoplasm, and enhances CDK-5 activity during lytic or acute infection. Infected neurons also stained positive for the DNA damage response (DDR) marker γH2AX. We propose that CDK-5 is activated by the DDR to protect infected neurons from apoptosis.
Evidence Supporting a Role for TopBP1 and Brd4 in the Initiation but Not Continuation of Human Papillomavirus 16 E1/E2-Mediated DNA Replication
Authors: Gauson Elaine J. , Donaldson Mary M. , Dornan Edward S. , Wang Xu , Bristol Molly , Bodily Jason M. , Morgan Iain M.
Published: February 2015

To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with host proteins in order to regulate both transcription and replication; TopBP1 and Brd4 are cellular proteins that interact with HPV16 E2. Previous work with E2 mutants demonstrated the Brd4 requirement for the transactivation properties of E2, while TopBP1 is required for DNA replication induced by E2 from the viral origin of replication in association with E1. More-recent studies have also implicated Brd4 in the regulation of DNA replication by E2 and E1. Here, we demonstrate that both TopBP1 and Brd4 are present at the viral origin of replication and that interaction with E2 is required for optimal initiation of DNA replication. Both cellular proteins are present in E1-E2-containing nuclear foci, and the viral origin of replication is required for the efficient formation of these foci. Short hairpin RNA (shRNA) against either TopBP1 or Brd4 destroys the E1-E2 nuclear bodies but has no effect on E1-E2-mediated levels of DNA replication. An E2 mutation in the context of the complete HPV16 genome that compromises Brd4 interaction fails to efficiently establish episomes in primary human keratinocytes. Overall, the results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate DNA replication but are not required for continuing DNA replication, which may be mediated by alternative processes such as rolling circle amplification and/or homologous recombination.

IMPORTANCE
Human papillomavirus 16 (HPV16) is causative in many human cancers, including cervical and head and neck cancers, and is responsible for the annual deaths of hundreds of thousands of people worldwide. The current vaccine will save lives in future generations, but antivirals targeting HPV16 are required for the alleviation of disease burden on the current, and future, generations. Targeting viral DNA replication that is mediated by two viral proteins, E1 and E2, in association with cellular proteins such as TopBP1 and Brd4 would have therapeutic benefits. This report suggests a role for these cellular proteins in the initiation of viral DNA replication by HPV16 E1-E2 but not for continuing replication. This is important if viral replication is to be effectively targeted; we need to understand the viral and cellular proteins required at each phase of viral DNA replication so that it can be effectively disrupted.
Viral DNA Replication-Dependent DNA Damage Response Activation during BK Polyomavirus Infection
Authors: Verhalen Brandy , Justice Joshua L. , Imperiale Michael J. , Jiang Mengxi
Published: February 2015

BK polyomavirus (BKPyV) reactivation is associated with severe human disease in kidney and bone marrow transplant patients. The interplay between viral and host factors that regulates the productive infection process remains poorly understood. We have previously reported that the cellular DNA damage response (DDR) is activated upon lytic BKPyV infection and that its activation is required for optimal viral replication in primary kidney epithelial cells. In this report, we set out to determine what viral components are responsible for activating the two major phosphatidylinositol 3-kinase-like kinases (PI3KKs) involved in the DDR: ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3-related (ATR) kinase. Using a combination of UV treatment, lentivirus transduction, and mutant virus infection experiments, our results demonstrate that neither the input virus nor the expression of large T antigen (TAg) alone is sufficient to trigger the activation of ATM or ATR in our primary culture model. Instead, our data suggest that the activation of both the ATM- and ATR-mediated DDR pathways is linked to viral DNA replication. Intriguingly, a TAg mutant virus that is unable to activate the DDR causes substantial host DNA damage. Our study provides insight into how DDRs are activated by polyomaviruses in primary cells with intact cell cycle checkpoints and how the activation might be linked to the maintenance of host genome stability.

IMPORTANCE
Polyomaviruses are opportunistic pathogens that are associated with several human diseases under immunosuppressed conditions. BK polyomavirus (BKPyV) affects mostly kidney and bone marrow transplant patients. The detailed replication mechanism of these viruses remains to be determined. We have previously reported that BKPyV activates the host DNA damage response (DDR), a response normally used by the host cell to combat genotoxic stress, to aid its own replication. In this study, we identified that the trigger for DDR activation is viral replication. Furthermore, we show that the virus is able to cause host DNA damage in the absence of viral replication and DDR activation. These results suggest an intricate relationship between viral replication, DDR activation, and host genome instability.
Core Principles of Bacterial Autoinducer Systems
Authors: Hense Burkhard A. , Schuster Martin
Published: February 2015

Autoinduction (AI), the response to self-produced chemical signals, is widespread in the bacterial world. This process controls vastly different target functions, such as luminescence, nutrient acquisition, and biofilm formation, in different ways and integrates additional environmental and physiological cues. This diversity raises questions about unifying principles that underlie all AI systems. Here, we suggest that such core principles exist. We argue that the general purpose of AI systems is the homeostatic control of costly cooperative behaviors, including, but not limited to, secreted public goods. First, costly behaviors require preassessment of their efficiency by cheaper AI signals, which we encapsulate in a hybrid “push-pull” model. The “push” factors cell density, diffusion, and spatial clustering determine when a behavior becomes effective. The relative importance of each factor depends on each species' individual ecological context and life history. In turn, “pull” factors, often stress cues that reduce the activation threshold, determine the cellular demand for the target behavior. Second, control is homeostatic because AI systems, either themselves or through accessory mechanisms, not only initiate but also maintain the efficiency of target behaviors. Third, AI-controlled behaviors, even seemingly noncooperative ones, are generally cooperative in nature, when interpreted in the appropriate ecological context. The escape of individual cells from biofilms, for example, may be viewed as an altruistic behavior that increases the fitness of the resident population by reducing starvation stress. The framework proposed here helps appropriately categorize AI-controlled behaviors and allows for a deeper understanding of their ecological and evolutionary functions.
Tracking a big Miocene river across the Continental Divide at Monida Pass, Montana/Idaho
Authors: Sears James W.
Published: February 2015

Exotic Miocene and Pliocene river gravel lies on top of the Continental Divide along the Idaho-Montana border near Monida Pass. The gravel is interlayered with tuffs and basalt flows of the Heise volcanic field, which erupted from the site of the Yellowstone hotspot between 6.62 and 4.45 Ma. The gravel includes pebbles that may have been derived from bedrock outcrops in Nevada and Utah, implying a paleo-river with headwaters to the south of the modern Continental Divide and Snake River Plain. The river may have been a tributary of the pre–ice age Bell River of Canada.

The field trip examines evidence for the tectonic evolution of the Monida Pass area. The course of the Miocene river appears to have been diverted around growing mountain ranges, and then pinched off at Monida Pass on the northern shoulder of the Yellowstone hotspot track.
A slice through time
Authors: Sugden J.C. , Hartshorn A.S. , Dixon J.L. , Montagne C.
Published: February 2015

On this field trip, participants will get their hands dirty while characterizing soils formed on five different rock types: Archean Gneiss, Flathead Sandstone, Wolsey Shale, Meagher Limestone, and Absaroka Volcanics (a basaltic andesite rock). We first recap prior soil survey efforts across the Gallatin National Forest in southwestern Montana and introduce a state factor approach to understanding soils. For over 50 years, Montana State University faculty have explored parts of this lithosequence, using it as a natural laboratory for thousands of students. We continue this tradition with this field guide, emphasizing how the combination of field and laboratory data can enrich our understanding of soil processes. We will observe and measure striking differences in soils; these differences in physical and chemical properties, from textures and colors to pH and elemental composition, are discussed in the context of quantifying the influence of the underlying rock on soil properties. We use these differences to ask whether heterogeneity in soil properties justifies the inference that soil properties are dominated by the underlying lithology. We conclude that the underlying rock strongly influences soil properties, but in variable ways across this lithosequence. This influence is both direct and indirect: chemical weathering of the rock leads to compositional changes in overlying soil, but rock weathering also leads to coarse fragments in the soil profile, which alters soil hydrology.
Polyphase collapse of the Cordilleran hinterland
Authors: Kalakay Thomas J. , Foster David A. , Lonn Jeffrey D.
Published: February 2015

The Anaconda and Bitterroot metamorphic core complexes are located in western Montana, along the eastern edge of the Cordilleran hinterland. This multi-tiered extensional terrain contains exceptional exposures that collectively exhibit a crustal cross section through orogenic continental crust (i.e., middle through upper crust). The core complex footwall rocks consist of Late Cretaceous arc-related plutons and Eocene granitic plutons intruded into deformed and metamorphosed Midproterozoic Belt Supergroup and Paleozoic to Cretaceous shelf-platform strata. Late Cretaceous shear zones and folds dominate footwall structure, representing significant thinning of the stratigraphic section. Eocene detachments, mylonites, and plutonic suites distinctly overprint the Late Cretaceous structures. A stark example of this Eocene overprint is the Anaconda detachment, which resulted in eastward translation of the Late Cretaceous, arc-related Boulder batholith. This field trip will cover a transect through the Anaconda core complex from the Philipsburg valley to Butte, Montana. Field trip participants will examine key locations that clarify the distinction between the timing and structural style of Late Cretaceous crustal thickening and/or collapse features versus those related to Eocene core complex development.
Glacial and Quaternary geology of the northern Yellowstone area, Montana and Wyoming
Authors: Pierce Kenneth L. , Licciardi Joseph M. , Krause Teresa R. , Whitlock Cathy
Published: February 2015

This field guide focuses on the glacial geology and paleoecology beginning in the Paradise Valley and progressing southward into northern Yellowstone National Park. During the last (Pinedale) glaciation, the northern Yellowstone outlet glacier flowed out of Yellowstone Park and down the Yellowstone River Valley into the Paradise Valley. The field trip will traverse the following Pinedale glacial sequence: (1) deposition of the Eightmile terminal moraines and outwash 16.5 ± 1.4 10Be ka in the Paradise Valley; (2) glacial recession of ~8 km and deposition of the Chico moraines and outwash 16.1 ± 1.7 10Be ka; (3) glacial recession of 45 km to near the northern Yellowstone boundary and moraine deposition during the Deckard Flats readjustment 14.2 ± 1.2 10Be ka; and (4) glacial recession of ~37 km and deposition of the Junction Butte moraines 15.2 ± 1.3 10Be ka (this age is a little too old based on the stratigraphic sequence). Yellowstone's northern range of sagebrush-grasslands and bison, elk, wolf, and bear inhabitants is founded on glacial moraines, sub-glacial till, and outwash deposited during the last glaciation. Floods released from glacially dammed lakes and a landslide-dammed lake punctuate this record.

The glacial geologic reconstruction was evaluated by calculation of basal shear stress, and yielded the following values for flow pattern in plan view: strongly converging—1.21 ± 0.12 bars (n = 15); nearly uniform—1.04 ± 0.16 bars (n = 11); and strongly diverging—0.84 ± 0.14 bars (n = 16). Reconstructed mass balance yielded accumulation and ablation each of ~3 km3/yr, with glacial movement near the equilibrium line altitude dominated by basal sliding.

Pollen and charcoal records from three lakes in northern Yellowstone provide information on the postglacial vegetation and fire history. Following glacial retreat, sparsely vegetated landscapes were colonized first by spruce parkland and then by closed subalpine forests. Regional fire activity increased significantly with the development of closed subalpine forests as a result of increased fuel biomass and warmer summers. Warm dry conditions prevailed at low elevations during the early Holocene, as indicated by the presence of steppe and open mixed conifer forest. At the same time, closed subalpine forests with low fire frequency were present at higher elevations, suggesting relatively wet summer conditions. Douglas fir populations expanded throughout northern Yellowstone in the middle Holocene as a result of effectively drier conditions than before, and a decline of mesophytic plant taxa during the late Holocene imply continued drying, even though fire frequency decreased in recent millennia.
A systematic review of the effects of upper body warm-up on performance and injury
Authors: McCrary J Matt , Ackermann Bronwen J , Halaki Mark
Published: February 2015

Purpose

This systematic review was conducted to identify the impact of upper body warm-up on performance and injury prevention outcomes.

Methods

Web of Science, MEDLINE, SPORTDiscus, PsycINFO and Cochrane databases were searched using terms related to upper extremity warm-up. Inclusion criteria were English language randomised controlled trials from peer-reviewed journals in which investigation of upper body warm-up on performance and injury prevention outcomes was a primary aim. Included studies were assessed for methodological quality using the PEDro scale. A wide variety of warm-up modes and outcomes precluded meta-analysis except for one group of studies. The majority of warm-ups were assessed as having ‘positive’, ‘neutral’, ‘negative’ or ‘specific’ effects on outcomes.

Results

Thirty-one studies met the inclusion criteria with 21 rated as having ‘good’ methodological quality. The studies investigated a total of 25 warm-up modes and 43 outcome factors that could be grouped into eight mode and performance outcome categories. No studies of upper body warm-up effects on injury prevention were discovered.

Conclusions

Strong research-based evidence was found for the following: high-load dynamic warm-ups enhance power and strength performance; warm-up swings with a standard weight baseball bat are most effective for enhancing bat speed; short-duration static stretching warm-up has no effect on power outcomes; and passive heating/cooling is a largely ineffective warm-up mode. A clear knowledge gap in upper body warm-up literature is the lack of investigation of injury prevention outcomes.
Bibliometrics of NIHR HTA monographs and their related journal articles
Authors: Royle Pamela , Waugh Norman
Published: February 2015

Objectives

A bibliometric analysis of the UK National Institute for Health Research (NIHR)Health Technology Assessment(HTA) monographs and their related journal articles by: (1) exploring the differences in citations to the HTA monographs in Google Scholar (GS), Scopus and Web of Science (WoS), and (2) comparing Scopus citations to the monographs with their related journal articles.

Setting

A study of 111 HTA monographs published in 2010 and 2011, and their external journal articles.

Main outcome measures

Citations to the monographs in GS, Scopus and WoS, and to their external journal articles in Scopus.

Results

The number of citations varied among the three databases, with GS having the highest and WoS the lowest; however, the citation-based rankings among the databases were highly correlated. Overall, 56% of monographs had a related publication, with the highest proportion for primary research (76%) and lowest for evidence syntheses (43%). There was a large variation in how the monographs were cited, compared to journal articles, resulting in more frequent problems, with unlinked citations in Scopus and WoS. When comparing differences in the number of citations between monograph publications with their related journal articles from the same project, we found that monographs received more citations than their journal articles for evidence syntheses and methodology projects; by contrast, journal articles related to primary research monographs were more highly cited than their monograph.

Conclusions

The numbers of citations to the HTA monographs differed considerably between the databases, but were highly correlated. When a HTA monograph had a journal article from the same study, there were more citations to the journal article for primary research, but more to the monographs for evidence syntheses. Citations to the related journal articles were more reliably recorded than citations to the HTA monographs.
What is the prevalence of MRI-detected inflammation and erosions in small joints in the general population? A collation and analysis of published data
Authors: Mangnus Lukas , Schoones Jan W , van der Helm-van Mil Annette H M
Published: February 2015

Introduction

MRI sensitively depicts erosions, bone marrow edema (BME) and synovitis in rheumatoid arthritis (RA). Recently developed European League Against Rheumatism (EULAR) recommendations stated that MRI is valuable to improve the certainty of a considered diagnosis and to detect structural damage at an early time point. However, these recommendations were mainly based on the data of patients with RA; prevalences of MRI features in the general population were not extensively explored. We reviewed the literature on MRI studies including symptom-free persons to assess the occurrence of MRI features.

Methods

Medical literature databases up to September 2013 were systematically reviewed for symptom-free persons with MRI data on metacarpophalangeal, wrist and metatarsophalangeal joints. Data were extracted and summarised. When allowed because of comparable scanning and scoring protocols, a mean frequency of features was calculated.

Results

Of the 338 articles screened, 31 studies evaluated MRI findings in symptom-free persons (n=516 in total). Both the imaging techniques (<1/≥1 T, with/without contrast enhancement) and the scoring methods (non-validated or RA MRI score (RAMRIS)) varied widely, prohibiting direct comparisons of the results of many studies. 15 studies scored data according to RAMRIS; combining data of similar joint regions showed that erosions (RAMRIS ≥1) were present in 33–52% of symptom-free persons. Similarly, synovitis was present in 27% and BME in 0–16% of symptom-free persons. The prevalence of MRI-detected erosions increased with age.

Conclusions

MRI features, erosions in particular, occur frequently in symptom-free persons. Before MRI can be implemented in the diagnostic process, larger studies should be conducted determining the degree and combination of MRI features that are disease specific.
Glandular trichome diversity on leaves ofLippia origanoidesandLippia stachyoides(Verbenaceae): morphology, histochemistry, and ultrastructure
Authors: Tozin Luiz Ricardo dos Santos , Carvalho Shelly Favorito , Machado Silvia Rodrigues , Rodrigues Tatiane Maria
Published: February 2015

Despite the ecological and medicinal importance of glandular trichomes in Verbenaceae, information on their structure, mainly at the subcellular level, is sparse. We analyzed the morphology and histochemistry of glandular trichomes in Lippia origanoides Kunth and Lippia stachyoides Cham., using conventional methods in anatomy, histochemistry, scanning and transmission electron microscopy, and ultracytochemical techniques. Five morphotypes (I–V) of glandular trichomes were identified in L. origanoides, and four morphotypes (I, III–V) in L. stachyoides. Morphotype I is the most abundant in both species. Lipids were detected in all morphotypes except IV; terpenes in I, II, and V; phenolic compounds in all morphotypes except V; neutral polysaccharides and protein in all morphotypes; mucilage exclusively in IV; alkaloids only in III. Each glandular morphotype showed ultrastructural peculiarities compatible with the chemical compounds produced. An association between glandular morphotype, secretion composition, and ultrastructural features in Lippia species was revealed, suggesting functions specific to each glandular morphotype.
Time-dependent potential barriers and superarrivals
Authors: Karami Hamid , Mousavi S.V.
Published: February 2015

Scattering of a Gaussian wavepacket from rectangular potential barriers with increasing widths or heights is studied numerically. It is seen that during a certain time interval the time-evolving transmission probability increases compared to the corresponding unperturbed cases. In the literature this effect is known as superarrival in transmission probability. We present a trajectory-based explanation for this effect by using the concept of quantum potential energy and computing a selection of Bohmian trajectories. Relevant parameters in superarrivals are determined for the case that the barrier width increases linearly during the dispersion of the wavepacket. Nonlinearity in time perturbation is also considered.
How to strengthen public trust in geosciences
Authors: Solarino Stefano
Published: February 2015

Finding an appropriate way to communicate scientific knowledge has always been a challenge, but lately it has become even more so. In fact a few recent episodes have dramatically weakened the mutual confidence between society and research. This happened within a process that had been slowly leading scientists to communicate science more effectively, and society to being more inclined to learn about natural hazards.

Unfortunately, in some cases the failures or the uncertainty in describing natural phenomena turned out to be very negative for the scientific community. In addition, in a few cases scientists were considered at fault or co-responsible for actions not undertaken to mitigate the risk, and these cases illustrate how the role of science became confused with that of politics.

In this work I analyse what went wrong in the light of geoethics, which studies moral behaviour and the discrimination between right and wrong conduct.

I then try to assess what can be done to recover and possibly instil more confidence in science, again in terms of ethics. In summary, the recent developments of the relationship between science and society suggest a ‘new deal’, in which society has lower expectations as to what science can deliver, and within which there is a scientific community that has been adequately trained to communicate with the public. Additionally, an effort must be made to include uncertainties in communication and to educate citizens in a better understanding of uncertainties as a part of the flow of information.
The role of fluid pressure in contractional systems: examples from the Southern Canadian Rocky Mountains
Authors: Mackay Paul A.
Published: February 2015

Fold and thrust belts are contractional systems created by tectonic plate collisions, creating stress conditions where the maximum principal stress is horizontal and the minimum principal stress is vertical. The stress orientation favours the development of low-angle reverse faults. The trigger mechanism for thrust activation as a recurring seismic event is related to fluctuations in fluid pressure. The fluctuating fluid pressure creates a temporal cycle of elevated and relaxed fluid pressure that shifts the system in and out of failure conditions. The generation of hydrocarbons from organic material is a source of fluids and a means of temporally fluctuating the fluid pressure. In the southern Canadian Rocky Mountains the major detachments follow organic-rich strata that have generated hydrocarbons. The nature of the fluids impacts the size and distributions of faults within the tectonic wedge. The critical taper of the wedge is modified by the presence of high fluid pressure.
Effects of age and unaccustomed resistance exercise on mitochondrial transcript and protein abundance in skeletal muscle of men
Authors: Ogborn Daniel I. , McKay Bryon R. , Crane Justin D. , Safdar Adeel , Akhtar Mahmood , Parise Gianni , Tarnopolsky Mark A.
Published: February 2015

Mitochondrial dysfunction may contribute to age-associated muscle atrophy. Previous data has shown that resistance exercise (RE) increases mitochondrial gene expression and enzyme activity in older adults; however, the acute response to RE has not been well characterized. To characterize the acute mitochondrial response to unaccustomed RE, healthy young (21 ± 3 yr) and older (70 ± 4 yr) men performed a unilateral RE bout for the knee extensors. Muscle biopsies were taken at rest and 3, 24, and 48 h following leg press and knee extension exercise. The expression of the mitochondrial transcriptional regulator proliferator-activated receptor γ coactivator 1-α (PGC-1α) mRNA was increased at 3 h postexercise; however, all other mitochondrial variables decreased over the postexercise period, irrespective of age. ND1, ND4, and citrate synthase (CS) mRNA were all lower at 48 h postexercise, along with specific protein subunits of complex II, III, IV, and ATP synthase. Mitochondrial DNA (mtDNA) copy number decreased by 48 h postexercise, and mtDNA deletions were higher in the older adults and remained unaffected by acute exercise. Elevated mitophagy could not explain the reduction in mitochondrial proteins and DNA, because there was no increase in ubiquitinated voltage-dependent anion channel (VDAC) or its association with PTEN-induced putative kinase 1 (Pink1) or Parkin, and elevated p62 content indicated an impairment or reduction in autophagocytic flux. In conclusion, age did not influence the response of specific mitochondrial transcripts, proteins, and DNA to a bout of RE.
Roles for the sympathetic nervous system, renal nerves, and CNS melanocortin-4 receptor in the elevated blood pressure in hyperandrogenemic female rats
Authors: Maranon Rodrigo , Lima Roberta , Spradley Frank T. , do Carmo Jussara M. , Zhang Howei , Smith Andrew D. , Bui Elizabeth , Thomas R. Lucas , Moulana Mohadetheh , Hall John E. , Granger Joey P. , Reckelhoff Jane F.
Published: February 2015

Women with polycystic ovary syndrome (PCOS) have hyperandrogenemia and increased prevalence of risk factors for cardiovascular disease, including elevated blood pressure. We recently characterized a hyperandrogenemic female rat (HAF) model of PCOS [chronic dihydrotestosterone (DHT) beginning at 4 wk of age] that exhibits similar characteristics as women with PCOS. In the present studies we tested the hypotheses that the elevated blood pressure in HAF rats is mediated in part by sympathetic activation, renal nerves, and melanocortin-4 receptor (MC4R) activation. Adrenergic blockade with terazosin and propranolol or renal denervation reduced mean arterial pressure (MAP by telemetry) in HAF rats but not controls. Hypothalamic MC4R expression was higher in HAF rats than controls, and central nervous system MC4R antagonism with SHU-9119 (1 nmol/h icv) reduced MAP in HAF rats. Taking a genetic approach, MC4R null and wild-type (WT) female rats were treated with DHT or placebo from 5 to 16 wk of age. MC4R null rats were obese and had higher MAP than WT control rats, and while DHT increased MAP in WT controls, DHT failed to further increase MAP in MC4R null rats. These data suggest that increases in MAP with chronic hyperandrogenemia in female rats are due, in part, to activation of the sympathetic nervous system, renal nerves, and MC4R and may provide novel insights into the mechanisms responsible for hypertension in women with hyperandrogenemia such as PCOS.
Mitochondrial dysfunction confers albumin-induced NLRP3 inflammasome activation and renal tubular injury
Authors: Zhuang Yibo , Yasinta Marchella , Hu Caiyu , Zhao Min , Ding Guixia , Bai Mi , Yang Lingyun , Ni Jiajia , Wang Rong , Jia Zhanjun , Huang Songming , Zhang Aihua
Published: February 2015

Proteinuria is involved in the development of tubular lesions and in the progressive loss of renal function in chronic kidney diseases via uncertain mechanisms. Growing evidence suggests a pathogenic role of mitochondrial dysfunction in chronic kidney diseases. Therefore, the present study aimed to define the roles of mitochondria in proteinuria-induced renal tubular injury and their underlying mechanisms. Using the albumin-overload mouse model, we observed severe tubular structure damage and striking tubular cell apoptosis. Furthermore, tubular epithelial cells displayed a loss of E-cadherin expression and gained expression of α-smooth muscle actin and vimentin, indicating a cellular phenotypic alteration. Strikingly, these albumin overload-induced abnormalities were robustly blocked by a mitochondrial SOD2 mimic, Mn(III) tetrakis (4-benzoic acid)porphyrin chloride (MnTBAP). In agreement with these results, we observed a marked change in mitochondrial morphology accompanied by mitochondrial cytochrome c release and a copy number reduction of mitochondrial DNA. These alterations were largely reversed by MnTBAP, suggesting a key role for mitochondria-derived oxidative stress in mediating the albumin effect on mitochondrial dysfunction and subsequent tubular injury. Moreover, the NOD-like receptor family, pyrin domain-containing 3 (NLRP3)/caspase-1/cytokine cascade was activated in the kidney by albumin overload and was entirely abolished by MnTBAP. In albumin-treated mouse proximal tubular cells, albumin directly induced ROS production, mitochondrial dysfunction, NLRP3/caspase-1/cytokine cascade activation, cell apoptosis, and cellular phenotypic transition. Similar to our in vivo results, treatment with either MnTBAP or cyclosporin A, a mitochondrial permeability transition pore inhibitor, remarkably attenuated these abnormalities in cells. Taken together, these novel findings demonstrate a potential role for the mitochondrial dysfunction/NLRP3 inflammasome axis in the pathogenesis of proteinuria-induced renal tubular injury.
A mathematical model of the rat nephron: glucose transport
Authors: Weinstein Alan M.
Published: February 2015

Mathematical models of the proximal tubule (PT), loop of Henle (LOH), and distal nephron have been combined to simulate transport by rat renal tubules. The ensemble is composed of 24,000 superficial (SF) nephrons and 12,000 juxtamedullary (JM) nephrons in 5 classes (according to LOH length); all coalesce into 7,200 connecting tubules (CNT). Medullary interstitial solute concentrations are specified. The model equations require that each nephron glomerular filtration rate (GFR) satisfies a tubuloglomerular feedback (TGF) relationship, and each initial hydrostatic pressure yields a common CNT pressure; that common CNT pressure is determined from an overall distal hydraulic resistance to flow. By virtue of the greater GFR for JM nephrons, fluid delivery to SF and JM tubules is comparable. Glucose reabsorption is restricted to the PT, cotransported with one Na in the convoluted tubule (SGLT2), and two Na in the straight tubule (SGLT1). Increasing ambient glucose from 5 to 10 mM increases proximal Na reabsorption and decreases distal delivery. This is mitigated by a TGF-mediated increase in GFR, and may thus be an etiology for TGF-mediated glomerular hyperfiltration. With SGLT2 inhibition by 95%, the model predicts that under normoglycemic conditions about 60% of filtered glucose will still be reabsorbed, so that profound glycosuria is not to be expected. Compared with glucose-driven osmotic diuresis, SGLT2 inhibition provokes greater natriuresis. When hyperglycemia is superimposed on SGLT2 inhibition, the model suggests that natriuresis may be severe, reflecting synergy of a proximal diuretic and osmotic diuresis. In sum, the model captures TGF-mediated diabetic hyperfiltration and predicts glomerular protection with SGLT2 inhibition.
The swan-neck lesion: proximal tubular adaptation to oxidative stress in nephropathic cystinosis
Authors: Galarreta Carolina I. , Forbes Michael S. , Thornhill Barbara A. , Antignac Corinne , Gubler Marie-Claire , Nevo Nathalie , Murphy Michael P. , Chevalier Robert L.
Published: February 2015

Cystinosis is an inherited disorder resulting from a mutation in the CTNS gene, causing progressive proximal tubular cell flattening, the so-called swan-neck lesion (SNL), and eventual renal failure. To determine the role of oxidative stress in cystinosis, histologic sections of kidneys from C57BL/6 Ctns−/−and wild-type mice were examined by immunohistochemistry and morphometry from 1 wk to 20 mo of age. Additional mice were treated from 1 to 6 mo with vehicle or mitoquinone (MitoQ), an antioxidant targeted to mitochondria. The leading edge of the SNL lost mitochondria and superoxide production, and became surrounded by a thickened tubular basement membrane. Progression of the SNL as determined by staining with lectin from Lotus tetragonolobus accelerated after 3 mo, but was delayed by treatment with MitoQ (38 ± 4% vs. 28 ± 1%, P < 0.01). Through 9 mo, glomeruli had retained renin staining and intact macula densa, whereas SNL expressed transgelin, an actin-binding protein, but neither kidney injury molecule-1 (KIM-1) nor cell death was observed. After 9 mo, clusters of proximal tubules exhibited localized oxidative stress (4-hydroxynonenal binding), expressed KIM-1, and underwent apoptosis, leading to the formation of atubular glomeruli and accumulation of interstitial collagen. We conclude that nephron integrity is initially maintained in the Ctns−/−mouse by adaptive flattening of cells of the SNL through loss of mitochondria, upregulation of transgelin, and thickened basement membrane. This adaptation ultimately fails in adulthood, with proximal tubular disruption, formation of atubular glomeruli, and renal failure. Antioxidant treatment targeted to mitochondria delays initiation of the SNL, and may provide therapeutic benefit in children with cystinosis.
Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome
Authors: Wang Weidong , Luo Renfei , Lin Yu , Wang Feifei , Zheng Peili , Levi Moshe , Yang Tianxin , Li Chunling
Published: February 2015

Ureteral obstruction is associated with reduced expression of renal aquaporins (AQPs), urinary concentrating defects, and an enhanced inflammatory response, in which the renin-angiotensin system (RAS) may play an important role. We evaluated whether RAS blockade by a direct renin inhibitor, aliskiren, would prevent the decreased renal protein expression of AQPs in a unilateral ureteral obstruction (UUO) model and what potential mechanisms may be involved. UUO was performed for 3 days (3UUO) and 7 days (7UUO) in C57BL/6 mice with or without aliskiren injection. In 3UUO and 7UUO mice, aliskiren abolished the reduction of AQP2 protein expression but not AQP1, AQP3, and AQP4. mRNA levels of renal AQP2 and vasopressin type 2 receptor were decreased in obstructed kidneys of 7UUO mice, which were prevented by aliskiren treatment. Aliskiren treatment was also associated with a reduced inflammatory response in obstructed kidneys of UUO mice. Aliskiren significantly decreased mRNA levels of several proinflammatory factors, such as transforming growth factor-β and tumor necrosis factor-α, seen in obstructed kidneys of UUO mice. Interestingly, mRNA and protein levels of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome components apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, and IL-1β were dramatically increased in obstructed kidneys of 7UUO mice, which were significantly suppressed by aliskiren. In primary cultured inner medullary collecting duct cells, IL-1β significantly decreased AQP2 expression. In conclusions, RAS blockade with the direct renin inhibitor aliskiren increased water channel AQP2 expression in obstructed kidneys of UUO mice, at least partially by preventing NLRP3 inflammasome activation in association with ureteral obstruction.
Decoding thalamic afferent input using microcircuit spiking activity
Authors: Sederberg Audrey J. , Palmer Stephanie E. , MacLean Jason N.
Published: February 2015

A behavioral response appropriate to a sensory stimulus depends on the collective activity of thousands of interconnected neurons. The majority of cortical connections arise from neighboring neurons, and thus understanding the cortical code requires characterizing information representation at the scale of the cortical microcircuit. Using two-photon calcium imaging, we densely sampled the thalamically evoked response of hundreds of neurons spanning multiple layers and columns in thalamocortical slices of mouse somatosensory cortex. We then used a biologically plausible decoder to characterize the representation of two distinct thalamic inputs, at the level of the microcircuit, to reveal those aspects of the activity pattern that are likely relevant to downstream neurons. Our data suggest a sparse code, distributed across lamina, in which a small population of cells carries stimulus-relevant information. Furthermore, we find that, within this subset of neurons, decoder performance improves when noise correlations are taken into account.