bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep
Authors: Koome Miriam E. , Bennet Laura , Booth Lindsea C. , Davidson Joanne O. , Wassink Guido , Gunn Alistair Jan 
Published: September 2013

New Findings
What is the central question of this study?Can power spectral analysis of fetal heart rate variability provide a reliable, objective estimate of autonomic balance before birth?
What is the main finding and its importance?This study demonstrates that there is a substantial increase in fetal heart rate spectral power over late gestation in chronically instrumented fetal sheep, with changes between sleep states that are consistent with known patterns of autonomic activity. However, parasympathetic blockade with atropine and complete chemical sympathectomy did not support substantial, consistent differences in the frequencies of sympathetic and parasympathetic activity in late gestation, suggesting that this does not provide a reliable index of relative cardiac autonomic activity before birth.
Power spectral analysis of fetal heart rate variability has been proposed to provide a non‐invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0–0.04 Hz), low (0.04–0.15 Hz) and high frequencies (0.15–0.4 Hz), as well as the ratio of low‐ to high‐frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n= 8), 0.7 (n= 7) and 0.8 gestational age (ga; n= 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h−1 for 30 min, n= 6) or 6‐hydroxydopamine (20 mg ml−1 at 2.5 ml h−1 for 3 h; n= 9). Data were analysed by sleep state, defined by low‐voltage–high‐frequency (LV) or high‐voltage–low‐frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P= 0.02). Both atropine (P= 0.05) and 6‐hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late‐gestation fetal sheep.
Characterization of the Bacterial Community of the Chemically Defended Hawaiian Sacoglossan Elysia rufescens
Authors: Davis Jeanette , Fricke W. Florian , Hamann Mark T. , Esquenazi Eduardo , Dorrestein Pieter C. , Hill Russell T. 
Published: September 2013

ABSTRACTSacoglossans are characterized by the ability to sequester functional chloroplasts from their algal diet through a process called kleptoplasty, enabling them to photosynthesize. The bacterial diversity associated with sacoglossans is not well understood. In this study, we coupled traditional cultivation-based methods with 454 pyrosequencing to examine the bacterial communities of the chemically defended Hawaiian sacoglossanElysia rufescensand its secreted mucus.E. rufescenscontains a defense molecule, kahalalide F, that is possibly of bacterial origin and is of interest because of its antifungal and anticancer properties. Our results showed that there is a diverse bacterial assemblage associated withE. rufescensand its mucus, with secreted mucus harboring higher bacterial richness than entire-E. rufescenssamples. The most-abundant bacterial groups affiliated withE. rufescensand its mucus areMycoplasmaspp. andVibriospp., respectively. Our analyses revealed that theVibriospp. that were highly represented in the cultivable assemblage were also abundant in the culture-independent community. Epifluorescence microscopy and matrix-assisted laser desorption–ionization mass spectrometry (MALDI-MS) were utilized to detect the chemical defense molecule kahalalide F on a longitudinal section of the sacoglossan.
Survival of Murine Norovirus, Tulane Virus, and Hepatitis A Virus on Alfalfa Seeds and Sprouts during Storage and Germination
Authors: Wang Qing , Hirneisen Kirsten A. , Markland Sarah M. , Kniel Kalmia E. 
Published: September 2013

ABSTRACT

Human norovirus (huNoV) and hepatitis A virus (HAV) have been involved in several produce-associated outbreaks and identified as major food-borne viral etiologies. In this study, the survival of huNoV surrogates (murine norovirus [MNV] and Tulane virus [TV]) and HAV was investigated on alfalfa seeds during storage and postgermination. Alfalfa seeds were inoculated with MNV, TV, or HAV with titers of 6.46 ± 0.06 log PFU/g, 3.87 ± 0.38 log PFU/g, or 7.01 ± 0.07 log 50% tissue culture infectious doses (TCID
50
)/g, respectively. Inoculated seeds were stored for up to 50 days at 22°C and sampled during that storage period on days 0, 2, 5, 10, and 15. Following storage, virus presence was monitored over a 1-week germination period. Viruses remained infectious after 50 days, with titers of 1.61 ± 0.19 log PFU/g, 0.85 ± 0.21 log PFU/g, and 3.43 ± 0.21 log TCID
50
/g for MNV, TV, and HAV, respectively. HAV demonstrated greater persistence than MNV and TV, without a statistically significant reduction over 20 days (<1 log TCID
50
/g); however, relatively high levels of genomic copies of all viruses persisted over the testing time period. Low titers of viruses were found on sprouts and were located in all tissues as well as in sprout-spent water sampled on days 1, 3, and 6 following seed planting. Results revealed the persistence of viruses in seeds for a prolonged period of time, and perhaps of greater importance these data suggest the ease of which virus may transfer from seeds to sprouts and spent water during germination. These findings highlight the importance of sanitation and prevention procedures before and during germination.
Noninvasive Analysis of Microbiome Dynamics in the Fruit Fly Drosophila melanogaster
Authors: Fink Christine , Staubach Fabian , Kuenzel Sven , Baines John F. , Roeder Thomas 
Published: September 2013

ABSTRACT

The diversity and structure of the intestinal microbial community has a strong influence on life history. To understand how hosts and microbes interact, model organisms with comparatively simple microbial communities, such as the fruit fly (
Drosophila melanogaster
), offer key advantages. However, studies of the
Drosophila
microbiome are limited to a single point in time, because flies are typically sacrificed for DNA extraction. In order to test whether noninvasive approaches, such as sampling of fly feces, could be a means to assess fly-associated communities over time on the same cohort of flies, we compared the microbial communities of fly feces, dissected fly intestines, and whole flies across three different
Drosophila
strains. Bacterial species identified in either whole flies or isolated intestines were reproducibly found in feces samples. Although the bacterial communities of feces and intestinal samples were not identical, they shared similarities and obviously the same origin. In contrast to material from whole flies and intestines, feces samples were not compromised by
Wolbachia
spp. infections, which are widespread in laboratory and wild strains. In a proof-of-principle experiment, we showed that simple nutritional interventions, such as a high-fat diet or short-term starvation, had drastic and long-lasting effects on the micobiome. Thus, the analysis of feces can supplement the toolbox for microbiome studies in
Drosophila
, unleashing the full potential of such studies in time course experiments where multiple samples from single populations are obtained during aging, development, or experimental manipulations.
Fatty Alcohols for Wax Esters in Marinobacter aquaeolei VT8: Two Optional Routes in the Wax Biosynthesis Pathway
Authors: Lenneman Eric M. , Ohlert Janet M. , Palani Nagendra P. , Barney Brett M. 
Published: September 2013

ABSTRACT

The biosynthesis of wax esters in bacteria is accomplished by a unique pathway that combines a fatty alcohol and a fatty acyl coenzyme A substrate. Previous
in vitro
enzymatic studies indicated that two different enzymes could be involved in the synthesis of the required fatty alcohol in
Marinobacter aquaeolei
VT8. In this study, we demonstrate through a series of gene deletions and transcriptional analysis that either enzyme is capable of fulfilling the role of providing the fatty alcohol required for wax ester biosynthesis
in vivo
, but evolution has clearly selected one of these, a previously characterized fatty aldehyde reductase, as the preferred enzyme to perform this reaction under typical wax ester-accumulating conditions. These results complement previous
in vitro
studies and provide the first glimpse into the role of each enzyme
in vivo
in the native organism.
Unraveling the Leloir Pathway of Bifidobacterium bifidum: Significance of the Uridylyltransferases
Authors: De Bruyn Frederik , Beauprez Joeri , Maertens Jo , Soetaert Wim , De Mey Marjan 
Published: September 2013

ABSTRACT

The GNB/LNB (galacto-
N
-biose/lacto-
N
-biose) pathway plays a crucial role in bifidobacteria during growth on human milk or mucin from epithelial cells. It is thought to be the major route for galactose utilization in
Bifidobacterium longum
as it is an energy-saving variant of the Leloir pathway. Both pathways are present in
B. bifidum
, and galactose 1-phosphate (gal1P) is considered to play a key role. Due to its toxic nature, gal1P is further converted into its activated UDP-sugar through the action of poorly characterized uridylyltransferases. In this study, three uridylyltransferases (
galT1
,
galT2
, and
ugpA
) from
Bifidobacterium bifidum
were cloned in an
Escherichia coli
mutant and screened for activity on the key intermediate gal1P. GalT1 and GalT2 showed UDP-glucose-hexose-1-phosphate uridylyltransferase activity (EC 2.7.7.12), whereas UgpA showed promiscuous UTP-hexose-1-phosphate uridylyltransferase activity (EC 2.7.7.10). The activity of UgpA toward glucose 1-phosphate was about 33-fold higher than that toward gal1P. GalT1, as part of the bifidobacterial Leloir pathway, was about 357-fold more active than GalT2, the functional analog in the GNB/LNB pathway. These results suggest that GalT1 plays a more significant role than previously thought and predominates when
B. bifidum
grows on lactose and human milk oligosaccharides. GalT2 activity is required only during growth on substrates with a GNB core such as mucin glycans.
Structural and Functional Characterization of the N Terminus of Schizosaccharomyces pombe Cwf10
Authors: Livesay S. Brent , Collier Scott E. , Bitton Danny A. , Bähler Jürg , Ohi Melanie D. 
Published: September 2013

ABSTRACT

The spliceosome is a dynamic macromolecular machine that catalyzes the removal of introns from pre-mRNA, yielding mature message.
Schizosaccharomyces pombe
Cwf10 (homolog of
Saccharomyces cerevisiae
Snu114 and human U5-116K), an integral member of the U5 snRNP, is a GTPase that has multiple roles within the splicing cycle. Cwf10/Snu114 family members are highly homologous to eukaryotic translation elongation factor EF2, and they contain a conserved N-terminal extension (NTE) to the EF2-like portion, predicted to be an intrinsically unfolded domain. Using
S. pombe
as a model system, we show that the NTE is not essential, but cells lacking this domain are defective in pre-mRNA splicing. Genetic interactions between
cwf10
-Δ
NTE
and other pre-mRNA splicing mutants are consistent with a role for the NTE in spliceosome activation and second-step catalysis. Characterization of Cwf10-NTE by various biophysical techniques shows that in solution the NTE contains regions of both structure and disorder. The first 23 highly conserved amino acids of the NTE are essential for its role in splicing but when overexpressed are not sufficient to restore pre-mRNA splicing to wild-type levels in
cwf10
-Δ
NTE
cells. When the entire NTE is overexpressed in the
cwf10
-Δ
NTE
background, it can complement the truncated Cwf10 protein in
trans
, and it immunoprecipitates a complex similar in composition to the late-stage U5.U2/U6 spliceosome. These data show that the structurally flexible NTE is capable of independently incorporating into the spliceosome and improving splicing function, possibly indicating a role for the NTE in stabilizing conformational rearrangements during a splice cycle.
Mutations on the N-Terminal Edge of the DELSEED Loop in either the α or β Subunit of the Mitochondrial F
1
-ATPase Enhance ATP Hydrolysis in the Absence of the Central γ Rotor
Authors: La Thuy , Clark-Walker George Desmond , Wang Xiaowen , Wilkens Stephan , Chen Xin Jie 
Published: September 2013

ABSTRACT

F
1
-ATPase is a rotary molecular machine with a subunit stoichiometry of α
3
β
3
γ
1
δ
1
ε
1
. It has a robust ATP-hydrolyzing activity due to effective cooperativity between the three catalytic sites. It is believed that the central γ rotor dictates the sequential conformational changes to the catalytic sites in the α
3
β
3
core to achieve cooperativity. However, recent studies of the thermophilic
Bacillus
PS3 F
1
-ATPase have suggested that the α
3
β
3
core can intrinsically undergo unidirectional cooperative catalysis (T. Uchihashi et al., Science 333:755-758, 2011). The mechanism of this γ-independent ATP-hydrolyzing mode is unclear. Here, a unique genetic screen allowed us to identify specific mutations in the α and β subunits that stimulate ATP hydrolysis by the mitochondrial F
1
-ATPase in the absence of γ. We found that the F446I mutation in the α subunit and G419D mutation in the β subunit suppress cell death by the loss of mitochondrial DNA (ρ
o
) in a
Kluyveromyces lactis
mutant lacking γ.
In organello
ATPase assays showed that the mutant but not the wild-type γ-less F
1
complexes retained 21.7 to 44.6% of the native F
1
-ATPase activity. The γ-less F
1
subcomplex was assembled but was structurally and functionally labile
in vitro
. Phe446 in the α subunit and Gly419 in the β subunit are located on the N-terminal edge of the DELSEED loops in both subunits. Mutations in these two sites likely enhance the transmission of catalytically required conformational changes to an adjacent α or β subunit, thereby allowing robust ATP hydrolysis and cell survival under ρ
o
conditions. This work may help our understanding of the structural elements required for ATP hydrolysis by the α
3
β
3
subcomplex.
d
-Alanine Modification of a Protease-Susceptible Outer Membrane Component by the Bordetella pertussis
dra
Locus Promotes Resistance to Antimicrobial Peptides and Polymorphonuclear Leukocyte-Mediated Killing
Authors: Taneja Neetu Kumra , Ganguly Tridib , Bakaletz Lauren O. , Nelson Kimberly J. , Dubey Purnima , Poole Leslie B. , Deora Rajendar 
Published: September 2013

ABSTRACT

Bordetella pertussis
is the causative agent of pertussis, a highly contagious disease of the human respiratory tract. Despite very high vaccine coverage, pertussis has reemerged as a serious threat in the United States and many developing countries. Thus, it is important to pursue research to discover unknown pathogenic mechanisms of
B. pertussis
. We have investigated a previously uncharacterized locus in
B. pertussis
, the
dra
locus, which is homologous to the
dlt
operons of Gram-positive bacteria. The absence of the
dra
locus resulted in increased sensitivity to the killing action of antimicrobial peptides (AMPs) and human phagocytes. Compared to the wild-type cells, the mutant cells bound higher levels of cationic proteins and peptides, suggesting that
dra
contributes to AMP resistance by decreasing the electronegativity of the cell surface. The presence of
dra
led to the incorporation of
d
-alanine into an outer membrane component that is susceptible to proteinase K cleavage. We conclude that
dra
encodes a virulence-associated determinant and contributes to the immune resistance of
B. pertussis
. With these findings, we have identified a new mechanism of surface modification in
B. pertussis
which may also be relevant in other Gram-negative pathogens.
Porins Increase Copper Susceptibility of Mycobacterium tuberculosis
Authors: Speer Alexander , Rowland Jennifer L. , Haeili Mehri , Niederweis Michael , Wolschendorf Frank 
Published: September 2013

ABSTRACT

Copper resistance mechanisms are crucial for many pathogenic bacteria, including
Mycobacterium tuberculosis
, during infection because the innate immune system utilizes copper ions to kill bacterial intruders. Despite several studies detailing responses of mycobacteria to copper, the pathways by which copper ions cross the mycobacterial cell envelope are unknown. Deletion of porin genes in
Mycobacterium smegmatis
leads to a severe growth defect on trace copper medium but simultaneously increases tolerance for copper at elevated concentrations, indicating that porins mediate copper uptake across the outer membrane. Heterologous expression of the mycobacterial porin gene
mspA
reduced growth of
M. tuberculosis
in the presence of 2.5 μM copper by 40% and completely suppressed growth at 15 μM copper, while wild-type
M. tuberculosis
reached its normal cell density at that copper concentration. Moreover, the polyamine spermine, a known inhibitor of porin activity in Gram-negative bacteria, enhanced tolerance of
M. tuberculosis
for copper, suggesting that copper ions utilize endogenous outer membrane channel proteins of
M. tuberculosis
to gain access to interior cellular compartments. In summary, these findings highlight the outer membrane as the first barrier against copper ions and the role of porins in mediating copper uptake in
M. smegmatis
and
M. tuberculosis
.
Suicide and accidental deaths in children and adolescents in England and Wales, 2001–2010
Authors: Windfuhr Kirsten , While David , Hunt Isabelle M , Shaw Jenny , Appleby Louis , Kapur Nav 
Published: September 2013

ObjectivesTo investigate the impact of narrative verdicts on suicide statistics among 10–19-year-olds; to identify the number and rate of suicide and accidental deaths, particularly in 10–14-year-olds.DesignNational cohort study.SettingEngland and Wales.MethodsMid-year population estimates from the Office for National Statistics (ONS) were used to calculate rates per 100 000 population for suicide (undetermined and suicide verdicts) and accidental deaths (poisoning, hanging) for those aged 10–14 and 15–19. Trends in rates over time (2001–2010) were investigated using Poisson regression. Interaction tests were carried out to determine differences in trends between the two time periods (2001–2005 and 2006–2010).ResultsThere were 1523 suicides (2.25/100 000). Suicide rates were highest in those aged 15–19 years (4.04/100 000) and in males (3.14/100 000). Between 2001 and 2010, rates significantly decreased among those aged 15–19 years (incidence rate-ratio (IRR): 0.95; 95% CI 0.93 to 0.97), with no change in rates of accidental deaths (IRR: 1.01, 95% CI 0.95 to 1.07). However, there was a significant interaction between the two time periods for accidental poisonings (2001–2005: IRR: 0.79 (95% CI 0.69 to 0.91); 2006–2010: IRR: 1.01 (95% CI 0.89 to 1.15), interaction p=0.012) and accidental hangings (2001–2005: IRR: 0.93 (95% CI 0.76 to 1.14); 2006–2010: IRR: 1.25 (95% CI 1.04 to 1.49), interaction=0.01) Undetermined deaths significantly decreased among females aged 15–19 yeras (IRR: 0.93; 95% CI 0.88 to 0.98). There were no significant trends among 10–14-year-olds.ConclusionsRates of suicide are higher among older adolescents and males. There was a significant fall in suicide rates in males aged 15–19 years that was not accounted for by changes in rates of accidental death. The absence of a significant trend in suicide or accidental deaths in those aged 10–14 years may have been the result of small numbers. However, monitoring should continue to identify longitudinal trends in all young people.
Bilateral optic neuropathy in a patient with familial amyloidotic polyneuropathy
Authors: Hamann Steffen , Jensen Peter Koch , Fledelius Hans Callø 
Published: September 2013

Amyloidogenic transthyretin (ATTR)-related familial amyloidotic polyneuropathy (FAP) is an autosomal-dominant hereditary disease characterised by slowly progressive peripheral sensorimotor and autonomic neuropathy and tissue involvement of the heart, kidneys and central nervous system. Secondary glaucoma has been reported following intraocular surgery, but optic nerve involvement unrelated to glaucoma has not previously been described. We reported a male patient in his late 40s when deceased, who previously had a liver transplant in order to reduce the abnormal protein synthesis underlying his FAP ATTR Val30Met mutation. After 11 years of ophthalmic follow-up best-corrected visual acuity was 20/100 in his seeing eye, which further had visual field findings suggestive of optic neuropathy. This was also the diagnosis underlying the preceding insidious full loss of vision in the fellow eye, with colour Doppler imaging to support an ischaemic aetiology. To our knowledge, this is the first report of ischaemic optic neuropathy in this familial amyloid disorder.
The prevalence, variety and impact of wrist problems in elite professional golfers on the European Tour
Authors: Hawkes Roger , O'Connor Phil , Campbell Doug 
Published: September 2013

ObjectivesGolf is a popular sport played by an estimated 57 million people. Previous studies on wrist injuries in elite golfers have been of simple design and have demonstrated such injuries to be frequent, although no studies report the incidence, variety, severity or impact on the activity of wrist injuries in detail. This prospective cross-sectional study assesses these factors in a cohort of elite professional golfers.MethodsEuropean Tour golfers eligible to compete at the 2009 BMW PGA Championship at Wentworth were studied. Study design involved the completion of a structured questionnaire supplemented by interview and examination when required, with performance statistics provided by the European Tour. The severity of injury was assessed by the number of missed tournaments and the amount of time of missed practice.Results128 of 153 eligible golfers, (84%) completed the study with 38 golfers (30%) reporting 43 problems. The majority of injuries (67%) occurred in the leading wrist at the most common location, the ulnar side of the wrist (35%). 87% of all ulnar-sided and 100% of radial-sided problems were in the leading wrist.ConclusionsThere were clear side differences reported by the players with the lead wrist demonstrating much higher injury rates in all areas. The most significant injury, in terms of absence from competition, was extensor carpi ulnaris tendon subluxation. Specific injuries are explained in relation to the biomechanics of the golf swing. Most structural injuries have a specific treatment and rehabilitation plan, which can involve significant periods of time away from the sport, while the management of many of the more minor problems is through alterations in technique or practice regimes, aiming to keep a golfer playing during recovery.