bluuebunny/crossref_metadata_2025 huggingface dataset:
EMIL BRUNNER REVISITED: ON THE COGNITIVE SCIENCE OF RELIGION, THEIMAGO DEI, AND REVELATION
Authors: Smedes Taede A.
Published: February 2014

This article aims at a constructive and argumentative engagement between the cognitive science of religion (CSR) and philosophical and theological reflection on theimago Dei. The Swiss theologian Emil Brunner argued that the theological notion that humans were created in the image of God entails that there is a “point of contact” for revelation to occur. This article argues that Brunner's notion resonates quite strongly with the findings of the CSR. The first part will give a short overview of the CSR. The second part deals with Brunner's idea of theimago Deiand the “point of contact.” The third and final part of the article outlines a model of revelation that is in line with Brunner's thought and the CSR. The aim of this article is to show how the naturalistic methodology of the CSR provides a fertile new perspective on several theological issues and thereby enriches theological reflection.
Renal epithelial sodium channel is critical for blood pressure maintenance and sodium balance in the normal late pregnant rat
Authors: West Crystal A. , Han Weiquing , Li Ningjun , Masilamani Shyama M. E.
Published: February 2014

New Findings

What is the central question of this study?

Normal pregnancy is a state marked by avid sodium retention and plasma volume expansion. Increased epithelial sodium channel (ENaC) activity in pregnancy may mediate these changes. We investigated the role of the ENaC using pharmacological and genetic inhibition.

What is the main finding and its importance?

We found that chronic ENaC blockade (systemic and local renal) prevented normal sodium retention in the pregnant rat. Prevention of sodium retention was associated with a decrease in maternal blood pressure and body weight, as well as fetal growth restriction. Taken together, these findings emphasize the importance of increased ENaC activity during pregnancy in maintaining the pregnancy‐mediated changes in sodium balance, volume status and blood pressure.

Normal pregnancy is a state marked by avid sodium retention and plasma volume expansion. Insufficient plasma volume expansion results in the compromised maternal state of intrauterine growth restriction, which afflicts ∼5% of all human pregnancies. We have recently shown that renal epithelial sodium channel (ENaC) activity in vivo in the late pregnant (LP) rat is increased. To determine the importance of the renal versus extrarenal ENaC in sodium retention and blood pressure regulation during pregnancy, we have chronically blocked the ENaC pharmacologically with daily subcutaneous injections of benzamil and genetically using intrarenal transfection of αENaC short hairpin RNA. Compared with untreated LP control animals, LP rats treated with benzamil retain less sodium and have reduced mean arterial blood pressure. Furthermore, LP rats treated with benzamil had lower maternal body weight gain. Intrarenal transfection of αENaC short hairpin RNA versus scrambled small RNA successfully decreased renal αENaC mRNA expression in LP rats. Intrarenal transfection of αENaC short hairpin RNA reduced maternal sodium retention, body weight gain and pup weight. Redundant physiological systems that protect blood pressure and sodium homeostasis were unable to compensate for the loss of ENaC activity in the pregnant rat. These findings demonstrate that the renal ENaC is necessary for maintaining pregnancy‐mediated sodium retention, volume expansion and blood pressure regulation.
Plane Thermal Transpiration of a Rarefied Gas Between Two Walls of Maxwell-Type Boundaries With Different Accommodation Coefficients
Authors: Doi Toshiyuki
Published: February 2014

Plane thermal transpiration of a rarefied gas between two walls of Maxwell-type boundaries with different accommodation coefficients is studied based on the linearized Boltzmann equation for a hard-sphere molecular gas. The Boltzmann equation is solved numerically using a finite difference method, in which the collision integral is evaluated by the numerical kernel method. The detailed numerical data, including the mass and heat flow rates of the gas, are provided over a wide range of the Knudsen number and the entire range of the accommodation coefficients. Unlike in the plane Poiseuille flow, the dependence of the mass flow rate on the accommodation coefficients shows different characteristics depending on the Knudsen number. When the Knudsen number is relatively large, the mass flow rate of the gas increases monotonically with the decrease in either of the accommodation coefficients like in Poiseuille flow. When the Knudsen number is small, in contrast, the mass flow rate does not vary monotonically but exhibits a minimum with the decrease in either of the accommodation coefficients. The mechanism of this phenomenon is discussed based on the flow field of the gas.
An Accurate Jacobi Pseudospectral Algorithm for Parabolic Partial Differential Equations With Nonlocal Boundary Conditions
Authors: Doha E. H. , Bhrawy A. H. , Abdelkawy M. A.
Published: February 2014

A new spectral Jacobi–Gauss–Lobatto collocation (J–GL–C) method is developed and analyzed to solve numerically parabolic partial differential equations (PPDEs) subject to initial and nonlocal boundary conditions. The method depends basically on the fact that an expansion in a series of Jacobi polynomials Jn(θ,ϑ)(x) is assumed, for the function and its space derivatives occurring in the partial differential equation (PDE), the expansion coefficients are then determined by reducing the PDE with its boundary conditions into a system of ordinary differential equations (SODEs) for these coefficients. This system may be solved numerically in a step-by-step manner by using implicit the Runge–Kutta (IRK) method of order four. The proposed method, in contrast to common finite-difference and finite-element methods, has the exponential rate of convergence for the spatial discretizations. Numerical results indicating the high accuracy and effectiveness of this algorithm are presented.
Determination of subband energies and 2DEG characteristics of AlxGa1−xN/GaN heterojunctions using variational method
Authors: Manouchehri Farzin , Valizadeh Pouya , Kabir M. Z.
Published: February 2014

A physics-based model based on the variational method for analyzing the two dimensional electron gas (2DEG) characteristics of polar AlGaN/GaN heterojunctions is developed. The 2DEG carrier concentration, the first and second energy subbands, and the position of the Fermi energy level are calculated for various barrier thicknesses, Al mole fractions, background dopant concentrations, and gate voltages for gated AlGaN/GaN heterojunctions. The results are in good agreement with the data reported based on self-consistent method. Whereas the aforementioned report has dealt with specific values of Al mole fraction, barrier thickness, and unintentional doping level, the present work provides a basis for calculating the 2DEG characteristics for the full range of these parameters. Furthermore, according to the proposed model, the applicability of the triangular approximation of the quantum well in AlGaN/GaN heterojunctions is evaluated.
Engineering the color rendering index of phosphor-free InGaN/(Al)GaN nanowire white light emitting diodes grown by molecular beam epitaxy
Authors: Connie Ashfiqua T. , Nguyen Hieu P. T. , Sadaf Sharif M. , Shih Ishiang , Mi Zetian
Published: February 2014

The functional properties, such as color rendering index (CRI) and correlated color temperature (CCT) of nanowire white light emitting diodes (LEDs), have been studied. The nanowire LEDs can generate broad spectrum white light, and by controlling the growth conditions, it is easy to tailor the spectrum. This is a significant advantage over phosphor converted or nanocrystal based white light sources since it is difficult to modulate the spectrum while maintaining high efficiency using these conventional methods. The authors demonstrated that the InGaN/(Al)GaN dot-in-a-wire heterostructure LEDs can generate high CRI values of 94–98 in both warm and cool white regions. Furthermore, the generated light demonstrates relatively stable CCT, CRI, and Commission Internationale d'Eclairage coordinates at different injection currents.
Evaluation of Active Living Every Day in Adults With Arthritis
Authors: Callahan Leigh F. , Cleveland Rebecca J. , Shreffler Jack , Hootman Jennifer M. , Mielenz Thelma J. , Schoster Britta , Brady Teresa , Schwartz Todd
Published: February 2014

Background:

Adults with arthritis can benefit from participation in physical activity and may be assisted by organized programs. The purpose of this study was to evaluate the effectiveness of a 20-week behavioral lifestyle intervention, Active Living Every Day (ALED), for improvements in primary outcomes (physical activity levels, aerobic endurance, function, symptoms).

Methods:

A 20-week randomized controlled community trial was conducted in 354 adults. Outcomes were assessed at baseline and 20 weeks in the intervention and wait-list control groups. The intervention group was also assessed at 6 and 12 months. Mean outcomes were determined by multilevel regression models in the intervention and control groups at follow-up points.

Results:

At 20 weeks, the intervention group significantly increased participation in physical activity, and improved aerobic endurance, and select measures of function while pain, fatigue and stiffness remained status quo. In the intervention group, significant improvements in physical activity at 20 weeks were maintained at 6 and 12 months, and stiffness decreased.

Conclusions:

ALED appears to improve participation in physical activity, aerobic endurance, and function without exacerbating disease symptoms in adults with arthritis.
Sport Participation and Subjective Well-Being: Instrumental Variable Results From German Survey Data
Authors: Ruseski Jane E. , Humphreys Brad R. , Hallman Kirstin , Wicker Pamela , Breuer Christoph
Published: February 2014

Background:

A major policy goal of many ministries of sport and health is increased participation in sport to promote health. A growing literature is emerging about the benefits of sport participation on happiness. A challenge in establishing a link between sport participation and happiness is controlling for endogeneity of sport participation in the happiness equation.

Methods:

This study seeks to establish causal evidence of a relationship between sport participation and self reported happiness using instrumental variables (IV).

Results:

IV estimates based on data from a 2009 population survey living in Rheinberg, Germany indicate that individuals who participate in sport have higher life happiness. The results suggest a U-shaped relationship between age and self-reported happiness. Higher income is associated with greater self-reported happiness, males are less happy than females, and single individuals are less happy than nonsingles.

Conclusions:

Since the results are IV, this finding is interpreted as a causal relationship between sport participation and subjective well-being (SWB). This broader impact of sport participation on general happiness lends support to the policy priority of many governments to increase sport participation at all levels of the general population.
Effects of Intervention Programs on Child and Adolescent BMI: A Meta-Analysis Study
Authors: Vasques Catarina , Magalhães Pedro , Cortinhas António , Mota Paula , Leitão José , Lopes Vitor Pires
Published: February 2014

Background:

This meta-analysis study aims to assess the efficacy of school-based and after-school intervention programs on the BMIs of child and adolescents, addressing the correlation between some moderating variables.

Methods:

We analyzed 52 studies (N = 28,236) published between 2000–2011.

Results:

The overall effect size was 0.068 (P < .001), school (r = .069) and after-school intervention (r = .065). Programs conducted with children aged between 15–19 years were the most effective (r = .133). Interventions programs with boys and girls show better effect sizes (r = .110) than programs that included just girls (r = .073). There were no significant differences between the programs implemented in school and after-school (P = .770). The effect size was higher in interventions lasting 1 year (r = .095), with physical activity and nutritional education (r = .148), and that included 3–5 sessions of physical activity per week (r = .080). The effect size also increased as the level of parental involvement increased.

Conclusions:

Although of low magnitude (r = .068), the intervention programs had a positive effect in prevention and decreasing obesity in children. This effect seems to be higher in older children’s, involving interventions with physical activity and nutritional education combined, with parent’s participation and with 1-year duration. School or after-school interventions had a similar effect.
Dose-Response of Women’s Health-Related Quality of Life (HRQoL) and Life Satisfaction to Physical Activity
Authors: Eime Rochelle , Harvey Jack , Payne Warren
Published: February 2014

Background:

To examine the dose-response relationship between health related quality of life (HRQoL) and life satisfaction (outcomes) and duration of recreational physical activity (exposure). Further, to explore whether these relationships depend on type of physical activity (PA).

Methods:

793 Australian rural-living women self-reported on duration of recreational PA; HRQoL via SF-36 Mental Component Summary (MCS) and Physical Component Summary (PCS); and a life satisfaction scale. ANOVAs and ANCOVAs investigated differences in outcomes (MCS, PCS, and life satisfaction) between tertiles of exposure to recreational PA, and types of PA (club sport, gymnasium, walking), with adjustment for potential confounders.

Results:

A significant positive dose-response relationship was found between PCS and level of PA. Furthermore, this relationship depended on type of PA, with club-sport participants recording higher PCS than non-club-sport participants in all but the highest tertile of exposure. Life satisfaction and MCS were not significantly related to level of PA.

Conclusion:

Physical health was positively associated with level of recreational PA, with club sport participation contributing greater benefits at low to moderate exposures than participation in gymnasium or walking activities.
Daily Variations in Weather and the Relationship With Physical Activity and Sedentary Time in European 10- to 12-Year-Olds: The ENERGY-Project
Authors: Yildirim Mine , Schoeni Anna , Singh Amika S. , Altenburg Teatske M. , Brug Johannes , De Bourdeaudhuij Ilse , Kovacs Eva , Bringolf-Isler Bettina , Manios Yannis , Chinapaw Mai J.M.
Published: February 2014

Background:

The aim of the study was to examine the association of daily variations in rainfall and temperature with sedentary time (ST) and physical activity (PA) in European children.

Methods:

Children were included from 5 countries (Belgium, Greece, Hungary, the Netherlands, Switzerland) as part of the ENERGY-project. We used cross-sectional data from 722 children aged 10–12 years (47% boys). ST and PA were measured by accelerometers for 6 consecutive days, including weekend days. Weather data were collected from online national weather reports. Multilevel regression models were used for data analyses.

Results:

Maximum temperature was positively associated with light PA (β = 3.1 min/day; 95% CI = 2.4–3.8), moderate-to-vigorous PA (β = 0.6 min/day; 95% CI = 0.4–0.8), and average PA [β = 4.1 counts per minute (cpm); 95% CI = 1.6–6.5, quadratic relationship]. Rainfall was inversely and quadratically associated with light PA (β = –1.3 min/day; 95% CI = –1.9 to –0.6), moderate-to-vigorous PA (β = –0.6 min/day; 95% CI = –0.8 to –0.3), and average PA (β = –1.6 cpm; 95% CI = –2.2 to –0.9). Maximum temperature was not significantly associated with ST (β = –0.2 min/day; 95% CI = –1.0 to 0.6), while rainfall was positively associated with ST (β = 0.9 min/day; 95% CI = 0.6–1.3).

Conclusion:

The current study shows that temperature and rainfall are significantly associated with PA and ST in 10- to 12-year-old European children.
Effects of Metal Ions on Stability and Activity of Hyperthermophilic Pyrolysin and Further Stabilization of This Enzyme by Modification of a Ca
2+
-Binding Site
Authors: Zeng Jing , Gao Xiaowei , Dai Zheng , Tang Bing , Tang Xiao-Feng
Published: February 2014

Pyrolysin is an extracellular subtilase produced by the marine hyperthermophilic archaeon
Pyrococcus furiosus
. This enzyme functions at high temperatures in seawater, but little is known about the effects of metal ions on the properties of pyrolysin. Here, we report that the supplementation of Na
+
, Ca
2+
, or Mg
2+
salts at concentrations similar to those in seawater destabilizes recombinant pyrolysin but leads to an increase in enzyme activity. The destabilizing effect of metal ions on pyrolysin appears to be related to the disturbance of surface electrostatic interactions of the enzyme. In addition, mutational analysis of two predicted high-affinity Ca
2+
-binding sites (Ca1 and Ca2) revealed that the binding of Ca
2+
is important for the stabilization of this enzyme. Interestingly, Asn substitutions at residues Asp818 and Asp820 of the Ca2 site, which is located in the C-terminal extension of pyrolysin, resulted in improvements in both enzyme thermostability and activity without affecting Ca
2+
-binding affinity. These effects were most likely due to the elimination of unfavorable electrostatic repulsion at the Ca2 site. Together, these results suggest that metal ions play important roles in modulating the stability and activity of pyrolysin.
Survival of Airborne MS2 Bacteriophage Generated from Human Saliva, Artificial Saliva, and Cell Culture Medium
Authors: Zuo Zhili , Kuehn Thomas H. , Bekele Aschalew Z. , Mor Sunil K. , Verma Harsha , Goyal Sagar M. , Raynor Peter C. , Pui David Y. H.
Published: February 2014

Laboratory studies of virus aerosols have been criticized for generating airborne viruses from artificial nebulizer suspensions (e.g., cell culture media), which do not mimic the natural release of viruses (e.g., from human saliva). The objectives of this study were to determine the effect of human saliva on the infectivity and survival of airborne virus and to compare it with those of artificial saliva and cell culture medium. A stock of MS2 bacteriophage was diluted in one of three nebulizer suspensions, aerosolized, size selected (100 to 450 nm) using a differential mobility analyzer, and collected onto gelatin filters. Uranine was used as a particle tracer. The resulting particle size distribution was measured using a scanning mobility particle sizer. The amounts of infectious virus, total virus, and fluorescence in the collected samples were determined by infectivity assays, quantitative reverse transcription-PCR (RT-PCR), and spectrofluorometry, respectively. For all nebulizer suspensions, the virus content generally followed a particle volume distribution rather than a number distribution. The survival of airborne MS2 was independent of particle size but was strongly affected by the type of nebulizer suspension. Human saliva was found to be much less protective than cell culture medium (i.e., 3% tryptic soy broth) and artificial saliva. These results indicate the need for caution when extrapolating laboratory results, which often use artificial nebulizer suspensions. To better assess the risk of airborne transmission of viral diseases in real-life situations, the use of natural suspensions such as saliva or respiratory mucus is recommended.
Abundance of Broad Bacterial Taxa in the Sargasso Sea Explained by Environmental Conditions but Not Water Mass
Authors: Sjöstedt Johanna , Martiny Jennifer B. H. , Munk Peter , Riemann Lasse
Published: February 2014

To explore the potential linkage between distribution of marine bacterioplankton groups, environmental conditions, and water mass, we investigated the factors determining the abundance of bacterial taxa across the hydrographically complex Subtropical Convergence Zone in the Sargasso Sea. Based on information from 16S rRNA gene clone libraries from various locations and two depths, abundances of the predominant taxa (eubacteria,
Archaea
,
Alphaproteobacteria
,
Gammaproteobacteria
,
Bacteroidetes
, and the
Roseobacter
, SAR11, and SAR86 clades) were quantified by real-time PCR. In addition, the abundances of
Synechococcus
,
Prochlorococcus
, and picoalgae were determined by flow cytometry. Linear multiple-regression models determining the relative effects of eight environmental variables and of water mass explained 35 to 86% of the variation in abundance of the quantified taxa, even though only one to three variables were significantly related to any particular taxon's abundance. Most of the variation in abundance was explained by depth and chlorophyll
a
. The predominant phototrophs,
Prochlorococcus
and picoalgae, were negatively correlated with phosphate, whereas eubacteria, heterotrophic bacteria, and SAR86 were negatively correlated with nitrite. Water mass showed limited importance for explaining the abundance of the taxonomical groups (significant only for
Roseobacter
, explaining 14% of the variation). The results suggest the potential for predicting the abundance of broad bacterioplankton groups throughout the Sargasso Sea using only a few environmental parameters.
The Lipopeptide Antibiotic Paenibacterin Binds to the Bacterial Outer Membrane and Exerts Bactericidal Activity through Cytoplasmic Membrane Damage
Authors: Huang En , Yousef Ahmed E.
Published: February 2014

Paenibacterin is a broad-spectrum lipopeptide antimicrobial agent produced by
Paenibacillus thiaminolyticus
OSY-SE. The compound consists of a cyclic 13-residue peptide and an N-terminal C
15
fatty acyl chain. The mechanism of action of paenibacterin against
Escherichia coli
and
Staphylococcus aureus
was investigated in this study. The cationic lipopeptide paenibacterin showed a strong affinity for the negatively charged lipopolysaccharides (LPS) from the outer membrane of Gram-negative bacteria. Addition of LPS (100 μg/ml) completely eliminated the antimicrobial activity of paenibacterin against
E. coli
. The electrostatic interaction between paenibacterin and LPS may have displaced the divalent cations on the LPS network and thus facilitated the uptake of antibiotic into Gram-negative cells. Paenibacterin also damaged the bacterial cytoplasmic membrane, as evidenced by the depolarization of membrane potential and leakage of intracellular potassium ions from cells of
E. coli
and
S. aureus
. Therefore, the bactericidal activity of paenibacterin is attributed to disruption of the outer membrane of Gram-negative bacteria and damage of the cytoplasmic membrane of both Gram-negative and Gram-positive bacteria. Despite the evidence of membrane damage, this study does not rule out additional bactericidal mechanisms potentially exerted by paenibacterin.
Synthesis of Flavonoid
O
-Pentosides by Escherichia coli through Engineering of Nucleotide Sugar Pathways and Glycosyltransferase
Authors: Han So Hyun , Kim Bong Gyu , Yoon Jeong A. , Chong Youhoon , Ahn Joong-Hoon
Published: February 2014

Plants produce two flavonoid
O
-pentoses, flavonoid
O
-xyloside and flavonoid
O
-arabinoside. However, analyzing their biological properties is difficult because flavonoids are not naturally produced in sufficient quantities. In this study,
Escherichia coli
was used to synthesize the plant-specific flavonoid
O
-pentosides quercetin 3-
O
-xyloside and quercetin 3-
O
-arabinoside. Two strategies were used. First,
E. coli
was engineered to express components of the biosynthetic pathways for UDP-xylose and UDP-arabinose. For UDP-xylose biosynthesis, two genes,
UXS
(UDP-xylose synthase) from
Arabidopsis thaliana
and
ugd
(UDP-glucose dehydrogenase) from
E. coli
, were overexpressed. In addition, the gene encoding ArnA (UDP-
l
-Ara4N formyltransferase/UDP-GlcA C-4″-decarboxylase), which competes with UXS for UDP-glucuronic acid, was deleted. For UDP-arabinose biosynthesis,
UXE
(UDP-xylose epimerase) was overexpressed. Next, we engineered UDP-dependent glycosyltransferases (UGTs) to ensure specificity for UDP-xylose and UDP-arabinose. The
E. coli
strains thus obtained synthesized approximately 160 mg/liter of quercetin 3-
O
-xyloside and quercetin 3-
O
-arabinoside.
Effect of C-Terminal Protein Tags on Pentitol and
l
-Arabinose Transport by Ambrosiozyma monospora Lat1 and Lat2 Transporters in Saccharomyces cerevisiae
Authors: Londesborough John , Richard Peter , Valkonen Mari , Viljanen Kaarina
Published: February 2014

Functional expression in heterologous hosts is often less successful for integral membrane proteins than for soluble proteins. Here, two
Ambrosiozyma monospora
transporters were successfully expressed in
Saccharomyces cerevisiae
as tagged proteins. Growth of
A. monospora
on
l
-arabinose instead of glucose caused transport activities of
l
-arabinose,
l
-arabitol, and ribitol, measured using
l
-[1-
3
H]arabinose,
l
-[
14
C]arabitol, and [
14
C]ribitol of demonstrated purity.
A. monospora LAT1
and
LAT2
genes were cloned earlier by using their ability to improve the growth of genetically engineered
Saccharomyces cerevisiae
on
l
-arabinose. However, the
l
-arabinose and pentitol transport activities of
S. cerevisiae
carrying
LAT1
or
LAT2
are only slightly greater than those of control strains.
S. cerevisiae
carrying the
LAT1
or
LAT2
gene fused in frame to the genes for green fluorescent protein (GFP) or red fluorescent protein (mCherry) or adenylate kinase (AK) exhibited large (>3-fold for
LAT1
; >20-fold for
LAT2
) increases in transport activities. Lat1-mCherry transported
l
-arabinose with high affinity (

K
m

≈ 0.03 mM) and
l
-arabitol and ribitol with very low affinity (

K
m

≥ 75 mM). The Lat2-GFP, Lat2-mCherry, and Lat2-AK fusion proteins could not transport
l
-arabinose but were high-affinity pentitol transporters (

K
m

s ≈ 0.2 mM). The
l
-arabinose and pentitol transport activities of
A. monospora
could not be completely explained by any combination of the observed properties of tagged Lat1 and Lat2, suggesting either that tagging and expression in a foreign membrane alters the transport kinetics of Lat1 and/or Lat2 or that
A. monospora
contains at least one more
l
-arabinose transporter.
Genetic Validation of Aminoacyl-tRNA Synthetases as Drug Targets in Trypanosoma brucei
Authors: Kalidas Savitha , Cestari Igor , Monnerat Severine , Li Qiong , Regmi Sandesh , Hasle Nicholas , Labaied Mehdi , Parsons Marilyn , Stuart Kenneth , Phillips Margaret A.
Published: February 2014

Human African trypanosomiasis (HAT) is an important public health threat in sub-Saharan Africa. Current drugs are unsatisfactory, and new drugs are being sought. Few validated enzyme targets are available to support drug discovery efforts, so our goal was to obtain essentiality data on genes with proven utility as drug targets. Aminoacyl-tRNA synthetases (aaRSs) are known drug targets for bacterial and fungal pathogens and are required for protein synthesis. Here we survey the essentiality of eight
Trypanosoma brucei
aaRSs by RNA interference (RNAi) gene expression knockdown, covering an enzyme from each major aaRS class: valyl-tRNA synthetase (ValRS) (class Ia), tryptophanyl-tRNA synthetase (TrpRS-1) (class Ib), arginyl-tRNA synthetase (ArgRS) (class Ic), glutamyl-tRNA synthetase (GluRS) (class 1c), threonyl-tRNA synthetase (ThrRS) (class IIa), asparaginyl-tRNA synthetase (AsnRS) (class IIb), and phenylalanyl-tRNA synthetase (α and β) (PheRS) (class IIc). Knockdown of mRNA encoding these enzymes in
T. brucei
mammalian stage parasites showed that all were essential for parasite growth and survival
in vitro
. The reduced expression resulted in growth, morphological, cell cycle, and DNA content abnormalities. ThrRS was characterized in greater detail, showing that the purified recombinant enzyme displayed ThrRS activity and that the protein localized to both the cytosol and mitochondrion. Borrelidin, a known inhibitor of ThrRS, was an inhibitor of
T. brucei
ThrRS and showed antitrypanosomal activity. The data show that aaRSs are essential for
T. brucei
survival and are likely to be excellent targets for drug discovery efforts.
The Entamoeba histolytica Dnmt2 Homolog (Ehmeth) Confers Resistance to Nitrosative Stress
Authors: Hertz Rivi , Tovy Ayala , Kirschenbaum Michael , Geffen Meirav , Nozaki Tomoyoshi , Adir Noam , Ankri Serge
Published: February 2014

Nitric oxide (NO) has antimicrobial properties against many pathogens due to its reactivity as an S-nitrosylating agent. It inhibits many of the key enzymes that are involved in the metabolism and virulence of the parasiteEntamoeba histolyticathrough S-nitrosylation of essential cysteine residues. Very little information is available on the mechanism of resistance to NO by pathogens in general and by this parasite in particular. Here, we report that exposure of the parasites toS-nitrosoglutathione (GSNO), an NO donor molecule, strongly reduces their viability and protein synthesis. However, the deleterious effects of NO were significantly reduced in trophozoites overexpressing Ehmeth, the cytosine-5 methyltransferase of the Dnmt2 family. Since these trophozoites also exhibited high levels of tRNAAspmethylation, the high levels suggested that Ehmeth-mediated tRNAAspmethylation is part of the resistance mechanism to NO. We previously reported that enolase, another glycolytic enzyme, binds to Ehmeth and inhibits its activity. We observed that the amount of Ehmeth-enolase complex was significantly reduced in GSNO-treatedE. histolytica, which explains the aforementioned increase of tRNA methylation. Specifically, we demonstrated via site-directed mutagenesis that cysteine residues 228 and 229 of Ehmeth are susceptible to S-nitrosylation and are crucial for Ehmeth binding to enolase and for Ehmeth-mediated resistance to NO. These results indicate that Ehmeth has a central role in the response of the parasite to NO, and they contribute to the growing evidence that NO is a regulator of epigenetic mechanisms.
Trypanosome Alternative Oxidase Possesses both an N-Terminal and Internal Mitochondrial Targeting Signal
Authors: Hamilton VaNae , Singha Ujjal K. , Smith Joseph T. , Weems Ebony , Chaudhuri Minu
Published: February 2014

Recognition of mitochondrial targeting signals (MTS) by receptor translocases of outer and inner membranes of mitochondria is one of the prerequisites for import of nucleus-encoded proteins into this organelle. The MTS for a majority of trypanosomatid mitochondrial proteins have not been well defined. Here we analyzed the targeting signal for trypanosome alternative oxidase (TAO), which functions as the sole terminal oxidase in the infective form of
Trypanosoma brucei
. Deleting the first 10 of 24 amino acids predicted to be the classical N-terminal MTS of TAO did not affect its import into mitochondria
in vitro
. Furthermore, ectopically expressed TAO was targeted to mitochondria in both forms of the parasite even after deletion of first 40 amino acid residues. However, deletion of more than 20 amino acid residues from the N terminus reduced the efficiency of import. These data suggest that besides an N-terminal MTS, TAO possesses an internal mitochondrial targeting signal. In addition, both the N-terminal MTS and the mature TAO protein were able to target a cytosolic protein, dihydrofolate reductase (DHFR), to a
T. brucei
mitochondrion. Further analysis identified a cryptic internal MTS of TAO, located within amino acid residues 115 to 146, which was fully capable of targeting DHFR to mitochondria. The internal signal was more efficient than the N-terminal MTS for import of this heterologous protein. Together, these results show that TAO possesses a cleavable N-terminal MTS as well as an internal MTS and that these signals act together for efficient import of TAO into mitochondria.
Dictyostelium discoideum Dgat2 Can Substitute for the Essential Function of Dgat1 in Triglyceride Production but Not in Ether Lipid Synthesis
Authors: Du Xiaoli , Herrfurth Cornelia , Gottlieb Thomas , Kawelke Steffen , Feussner Kristin , Rühling Harald , Feussner Ivo , Maniak Markus
Published: February 2014

Triacylglycerol (TAG), the common energy storage molecule, is formed from diacylglycerol and a coenzyme A-activated fatty acid by the action of an acyl coenzyme A:diacylglycerol acyltransferase (DGAT). In order to conduct this step, most organisms rely on more than one enzyme. The two main candidates in
Dictyostelium discoideum
are Dgat1 and Dgat2. We show, by creating single and double knockout mutants, that the endoplasmic reticulum (ER)-localized Dgat1 enzyme provides the predominant activity, whereas the lipid droplet constituent Dgat2 contributes less activity. This situation may be opposite from what is seen in mammalian cells.
Dictyostelium
Dgat2 is specialized for the synthesis of TAG, as is the mammalian enzyme. In contrast, mammalian DGAT1 is more promiscuous regarding its substrates, producing diacylglycerol, retinyl esters, and waxes in addition to TAG. The
Dictyostelium
Dgat1, however, produces TAG, wax esters, and, most interestingly, also neutral ether lipids, which represent a significant constituent of lipid droplets. Ether lipids had also been found in mammalian lipid droplets, but the role of DGAT1 in their synthesis was unknown. The ability to form TAG through either Dgat1 or Dgat2 activity is essential for
Dictyostelium
to grow on bacteria, its natural food substrate.
The K
C
Channel in the
cbb
3
-Type Respiratory Oxygen Reductase from Rhodobacter capsulatus Is Required for Both Chemical and Pumped Protons
Authors: Yıldız Gülgez Gökçe , Gennis Robert B. , Daldal Fevzi , Öztürk Mehmet
Published: February 2014

The heme-copper superfamily of proton-pumping respiratory oxygen reductases are classified into three families (A, B, and C families) based on structural and phylogenetic analyses. Most studies have focused on the A family, which includes the eukaryotic mitochondrial cytochrome
c
oxidase as well as many bacterial homologues. Members of the C family, also called the
cbb
3
-type oxygen reductases, are found only in prokaryotes and are of particular interest because of their presence in a number of human pathogens. All of the heme-copper oxygen reductases require proton-conducting channels to convey chemical protons to the active site for water formation and to convey pumped protons across the membrane. Previous work indicated that there is only one proton-conducting input channel (the K
C
channel) present in the
cbb
3
-type oxygen reductases, which, if correct, must be utilized by both chemical protons and pumped protons. In this work, the effects of mutations in the K
C
channel of the
cbb
3
-type oxygen reductase from
Rhodobacter capsulatus
were investigated by expressing the mutants in a strain lacking other respiratory oxygen reductases. Proton pumping was evaluated by using intact cells, and catalytic oxygen reductase activity was measured in isolated membranes. Two mutations, N346M and Y374F, severely reduced catalytic activity, presumably by blocking the chemical protons required at the active site. One mutation, T272A, resulted in a substantially lower proton-pumping stoichiometry but did not inhibit oxygen reductase activity. These are the first experimental data in support of the postulate that pumped protons are taken up from the bacterial cytoplasm through the K
C
channel.
The Flagellar Soluble Protein FliK Determines the Minimal Length of the Hook in Salmonella enterica Serovar Typhimurium
Authors: Uchida Kaoru , Aizawa Shin-Ichi
Published: February 2014

The length of the flagellar hook is controlled by the soluble protein FliK. FliK is structurally divided into two halves with distinct functions; the N-terminal half determines hook length, while the C-terminal half switches the secretion substrate specificity, consequently terminating hook elongation. FliK properly achieves both functions only when it is secreted. In a previous paper, we showed that a temperature-sensitive
flgE
mutant of
Salmonella enterica
serovar Typhimurium, SJW2219, produced basal bodies with short hooks (average length, 25 nm) at 37°C. In this study, we show that the mutant cells grown at 37°C secrete FliK but not flagellin (FliC), indicating that FliK is abortively secreted into the medium when the hook is shorter than 30 nm. In contrast, FliK unfailingly switches the gate modes when the hook is longer than 30 nm. Taking the FliC, FliK, and FlgM secretion patterns into account, we conclude that FliK determines the minimal length of the hook. We will discuss how FliK detects the critical switching point of the secretion gate.
Analysis of the Loss in Heat and Acid Resistance during Germination of Spores of Bacillus Species
Authors: Luu Stephanie , Setlow Peter
Published: February 2014

A major event in the nutrient germination of spores of
Bacillus
species is release of the spores' large depot of dipicolinic acid (DPA). This event is preceded by both commitment, in which spores continue through germination even if germinants are removed, and loss of spore heat resistance. The latter event is puzzling, since spore heat resistance is due largely to core water content, which does not change until DPA is released during germination. We now find that for spores of two
Bacillus
species, the early loss in heat resistance during germination is most likely due to release of committed spores' DPA at temperatures not lethal for dormant spores. Loss in spore acid resistance during germination also paralleled commitment and was also associated with the release of DPA from committed spores at acid concentrations not lethal for dormant spores. These observations plus previous findings that DPA release during germination is preceded by a significant release of spore core cations suggest that there is a significant change in spore inner membrane permeability at commitment. Presumably, this altered membrane cannot retain DPA during heat or acid treatments innocuous for dormant spores, resulting in DPA-less spores that are rapidly killed.
Internal herniation through a defect in the transverse mesocolon
Authors: Alaker Medhat , Mathias Jegadish
Published: February 2014

Internal hernias are rare, constituting 5.8% of all intestinal obstruction cases. Congenital transverse mesocolon hernias in adults are specifically rare. We hereby present a case of an adult female presenting with acute intestinal obstruction. Her CT scan showed classic signs of internal herniations: ‘Whirlpool sign’, crowding of bowel loops in the upper compartment and the absence of caecum from the Right Iliac Fossa. At operation, she was found to have a congenital defect in the transverse mesocolon, through which have herniated the terminal ileum, caecum and the proximal half of the ascending colon. They have furthermore rotated 360° about the axis of the pedicle forming a volvulus. The bowel was viable. The herniated bowel was derotated, and reduced through the defect, the defect was closed with polydioxanone sutures, and the caecum and ascending colon was fixed to the lateral abdominal wall.
Congenital giant male anterior urethral diverticulum with calculi
Authors: Kamal Mir Reza , Jindal Tarun , Sinha Rajan Kumar , Karmakar Dilip
Published: February 2014

Urethral diverticulum is a sac-like outpouching of urethral mucosa. It may be anterior or posterior according to anatomical locations. It is less common in men than in women. It can be congenital or acquired. Anterior urethral diverticula are usually congenital as compared to majority of posterior diverticula which are acquired. The most common aetiologies of male acquired diverticula are stricture, abscess, trauma or post-hypospadias repair. We report a case of congenital giant anterior urethral diverticulum with a calculus which has been managed successfully with surgical excision and repair in two layers.
The LEAF questionnaire: a screening tool for the identification of female athletes at risk for the female athlete triad
Authors: Melin Anna , Tornberg Åsa B , Skouby Sven , Faber Jens , Ritz Christian , Sjödin Anders , Sundgot-Borgen Jorunn
Published: February 2014

Background

Low energy availability (EA) in female athletes with or without an eating disorder (ED) increases the risk of oligomenorrhoea/functional hypothalamic amenorrhoea and impaired bone health, a syndrome called the female athlete triad (Triad). There are validated psychometric instruments developed to detect disordered eating behaviour (DE), but no validated screening tool to detect persistent low EA andTriadconditions, with or without DE/ED, is available.

Aim

The aim of this observational study was to develop and test a screening tool designed to identify female athletes at risk for theTriad.

Methods

Female athletes (n=84) with 18–39 years of age and training ≥5 times/week filled out the Low Energy Availability in Females Questionnaire (LEAF-Q), which comprised questions regarding injuries and gastrointestinal and reproductive function. Reliability and internal consistency were evaluated in a subsample of female dancers and endurance athletes (n=37). Discriminant as well as concurrent validity was evaluated by testing self-reported data against measured current EA, menstrual function and bone health in endurance athletes from sports such as long distance running and triathlon (n=45).

Results

The 25-item LEAF-Q produced an acceptable sensitivity (78%) and specificity (90%) in order to correctly classify current EA and/or reproductive function and/or bone health.

Conclusions

The LEAF-Q is brief and easy to administer, and relevant as a complement to existing validated DE screening instruments, when screening female athletes at risk for theTriad, in order to enable early detection and intervention.
Depression following fracture in women: a study of age-matched cohorts
Authors: Williams Lana J , Berk Michael , Henry Margaret J , Stuart Amanda L , Brennan Sharon L , Jacka Felice N , Pasco Julie A
Published: February 2014

Objectives

High levels of disability, functional impairment and mortality are independently associated with fracture and depression, however the relationship between fracture and depression is uncertain. The aim of this study was to investigate whether fracture is associated with subsequent depressive symptoms in a population-based sample of women.

Design

A study of age-matched fracture versus non-fracture cohorts of women.

Setting

Barwon Statistical Division, southeastern Australia.

Participants

Two samples of women aged ≥35 years were drawn from the Geelong Osteoporosis Study (GOS). The fracture cohort included women with incident fracture identified from radiology reports and the non-fracture cohort were randomly selected from the electoral roll during 1994–1996.

Outcome measure

Symptoms of depression for women with and without fracture during the 12-month period 2000–2001 were identified by self-report questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.

Results

A total of 296 women with fracture (12 hip, 48 vertebral, 91 wrist/forearm, 17 upper arm, 7 pelvis, 11 rib, 62 lower leg and 48 other fractures) and 590 women without fracture were included. Associations between fracture and depression differed between younger (≤65 years) and older (>65 years) women. Age and weight-adjusted odds ratio for depression following fracture among younger women was 0.62 (0.35 to 1.11, p=0.12) and 3.33 (1.24 to 8.98, p=0.02) for older women. Further adjustment for lifestyle factors did not affect the results.

Conclusions

This study demonstrated that differences in mood status exist between older and younger women following fracture and that fracture is associated with increased depression in older women. Assessment of mood status in both the short and long term following fracture in the elderly seems justified, with early detection and treatment likely to result in improved outcomes.
Planning ahead: Improving escalation plans before the weekend
Authors: Zarkali Angeliki , Black Duncan , Smee Elizabeth , Deshraj Anshul , Smallwood Nicholas
Published: February 2014

Handover is the system by which responsibility for patient care is transferred between healthcare professionals. A significant aspect of handover is the existence of an escalation plan for each patient in case of deterioration over the weekend. According to the Royal College of Physicians, all patients should have a clear escalation plan documented in the notes before a weekend, since parent medical teams (Consultant team in charge of care) are best placed to make these decisions. If left to on-call teams, at a time of deterioration over a weekend, they might not have all available information, the patient might be unable to be involved in the decisions, and the family might not be consulted.

With this is mind, we decided to analyse the existing handover process in a medium sized district general hospital, with the aim of improving the process and the documentation of escalation plans . The results from our retrospective analysis of the system in place revealed a significant lack of documentation of escalation plans in the medical notes.

Three sample wards were selected to analyse the current handover system and test proposed measures before hospital-wide implementation. After trialling of a physical handover meeting in addition to the existing intranet system and a proforma for the Friday ward round, the documentation of escalation plans in the patients' notes improved from 9.1% to 41.1%. Based on these results, as well as formal feedback from junior doctors and informal feedback from other staff, the physical handover meeting and Friday ward round proforma will be implemented throughout the Trust.

Our interventions led to an improvement in the documentation of escalation plans in our hospital, thus saving precious time in the event of a patient’s deterioration. This also ensures that families and patients are involved in the decision making process and kept informed, and reduces the burden for the weekend on-call teams.
Saving the NHS one blood test at a time
Authors: Akhtar Waqas , Chung Yooyun
Published: February 2014

As a team of junior doctors our aim has been to save costs in day to day work so that money can be reallocated to improving nursing staff levels on our wards. Stem cell units have regular blood collection schedules in order to monitor organ response to chemotherapy and to look for complications in immunocompromised patients. We set out to reduce the number of biochemical investigations to a minimum that would be clinically indicated. We designed a new blood collection proforma for nursing staff to follow and audited all blood tests taken during a 2 week period before and after its introduction. The number of inappropriate blood tests were recorded as those that were not clinically indicated or not present on the collection schedule. After the introduction of the change the number of inappropriate tests were reduced by 937 over the 2 week period, with a cost saving of £1,478.42. Similar strategies for reducing unnecessary investigations and focusing on tests that will change management could help the NHS cope with a difficult financial future and provide continued safe staffing levels and quality care.