bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of NLRP3 inflammasome in macrophages by mycoplasmal lipoproteins and lipopeptides
Authors: Saeki A. , Sugiyama M. , Hasebe A. , Suzuki T. , Shibata K. 
Published: April 2018

SummaryThe NLRP3 inflammasome, an intracellular sensor consisting of the nucleotide‐binding oligomerization domain‐like receptor family, pyrin domain containing 3 (NLRP3), the adaptor protein apoptosis‐associated speck‐like protein containing a caspase‐recruitment domain (ASC), and procaspase‐1, plays critical roles in host defense against microbial pathogens by inducing production of interleukin‐1β (IL‐1β) and IL‐18. Mycoplasma salivarium and Mycoplasma pneumoniae cells activated murine bone marrow‐derived macrophages (BMMs) to induce production of IL‐1α, IL‐1β, and IL‐18. The IL‐1β production‐inducing activities of these mycoplasmas toward BMMs from Toll‐like receptor 2 (TLR2)‐deficient mice were significantly attenuated compared with those from C57BL/6 mice (B6BMMs). This result suggests the possibility that their lipoproteins as TLR2 agonists are involved in the activity. Lipoproteins of M. salivarium and M. pneumoniae (MsLP and MpLP), and the M. salivarium‐derived lipopeptide FSL‐1 induced IL‐1β production by B6BMMs, but not by BMMs from caspase‐1‐, NLRP3‐ or ASC‐deficient mice. The activities of MsLP and MpLP were not downregulated by the proteinase K treatment, suggesting that the active sites are their N‐terminal lipopeptide moieties. B6BMMs internalized the mycoplasmal N‐terminal lipopeptide FSL‐1 at least 30 min after incubation, FSL‐1‐containing endosomes started to fuse with the lysosomes around 2 hours, and then FSL‐1 translocated into the cytosol from LAMP‐1+ endosomes. The artificial delivery of FSL‐1 into the cytosol of B6BMMs drastically enhanced the IL‐1β production‐inducing activity. FSL‐1 as well as the representative NLRP3 inflammasome activator nigericin induced the NLRP3/ASC speck, but FSL‐1 located in a compartment different from the NLRP3/ASC speck.
Dissociation of frontal‐midline delta‐theta and posterior alpha oscillations: A mobile EEG study
Authors: Liang Mingli , Starrett Michael J. , Ekstrom Arne D. 
Published: April 2018

AbstractNumerous reports have demonstrated low‐frequency oscillations during navigation using invasive recordings in the hippocampus of both rats and human patients. Given evidence, in some cases, of low‐frequency synchronization between midline cortex and hippocampus, it is also possible that low‐frequency movement‐related oscillations manifest in healthy human neocortex. However, this possibility remains largely unexplored, in part due to the difficulties of coupling free ambulation and effective scalp EEG recordings. In the current study, participants freely ambulated on an omnidirectional treadmill and explored an immersive virtual reality city rendered on a head‐mounted display while undergoing simultaneous wireless scalp EEG recordings. We found that frontal‐midline (FM) delta‐theta (2–7.21 Hz) oscillations increased during movement compared to standing still periods, consistent with a role in navigation. In contrast, posterior alpha (8.32–12.76 Hz) oscillations were suppressed in the presence of visual input, independent of movement. Our findings suggest that FM delta‐theta and posterior alpha oscillations arise at independent frequencies, under complementary behavioral conditions, and, at least for FM delta‐theta oscillations, at independent recordings sites. Together, our findings support a double dissociation between movement‐related FM delta‐theta and resting‐related posterior alpha oscillations. Our study thus provides novel evidence that FM delta‐theta oscillations arise, in part, from real‐world ambulation, and are functionally independent from posterior alpha oscillations.
Detecting Multivariate Interactions in Spatial Point Patterns with Gibbs Models and Variable Selection
Authors: Rajala T. , Murrell D. J. , Olhede S. C. 
Published: April 2018

SummaryWe propose a method for detecting significant interactions in very large multivariate spatial point patterns. This methodology thus develops high dimensional data understanding in the point process setting. The method is based on modelling the patterns by using a flexible Gibbs point process model to characterize point-to-point interactions at different spatial scales directly. By using the Gibbs framework significant interactions can also be captured at small scales. Subsequently, the Gibbs point process is fitted by using a pseudolikelihood approximation, and we select significant interactions automatically by using the group lasso penalty with this likelihood approximation. Thus we estimate the multivariate interactions stably even in this setting. We demonstrate the feasibility of the method with a simulation study and show its power by applying it to a large and complex rainforest plant population data set of 83 species.
Protective role of Parkin in skeletal muscle contractile and mitochondrial function
Authors: Gouspillou Gilles , Godin Richard , Piquereau Jérome , Picard Martin , Mofarrahi Mahroo , Mathew Jasmin , Purves‐Smith Fennigje M. , Sgarioto Nicolas , Hepple Russell T. , Burelle Yan , Hussain Sabah N. A. 
Published: April 2018

Key points
Parkin, an E3 ubiquitin ligase encoded by the Park2 gene, has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are degraded.
The exact physiological significance of Parkin in regulating mitochondrial function and contractility in skeletal muscle remains largely unexplored.
Using Park2−/− mice, we show that Parkin ablation causes a decrease in muscle specific force, a severe decrease in mitochondrial respiration, mitochondrial uncoupling and an increased susceptibility to opening of the permeability transition pore.
These results demonstrate that Parkin plays a protective role in the maintenance of normal mitochondrial and contractile functions in skeletal muscles.
AbstractParkin is an E3 ubiquitin ligase encoded by the Park2 gene. Parkin has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are sequestered in autophagosomes and delivered to lysosomes for degradation. Although Parkin has been mainly studied for its implication in neuronal degeneration in Parkinson disease, its role in other tissues remains largely unknown. In the present study, we investigated the skeletal muscles of Park2 knockout (Park2−/−) mice to test the hypothesis that Parkin plays a physiological role in mitochondrial quality control in normal skeletal muscle, a tissue highly reliant on mitochondrial content and function. We first show that the tibialis anterior (TA) of Park2−/− mice display a slight but significant decrease in its specific force. Park2−/− muscles also show a trend for type IIB fibre hypertrophy without alteration in muscle fibre type proportion. Compared to Park2+/+ muscles, the mitochondrial function of Park2−/− skeletal muscles was significantly impaired, as indicated by the significant decrease in ADP‐stimulated mitochondrial respiratory rates, uncoupling, reduced activities of respiratory chain complexes containing mitochondrial DNA (mtDNA)‐encoded subunits and increased susceptibility to opening of the permeability transition pore. Muscles of Park2−/− mice also displayed a decrease in the content of the mitochondrial pro‐fusion protein Mfn2 and an increase in the pro‐fission protein Drp1 suggesting an increase in mitochondrial fragmentation. Finally, Park2 ablation resulted in an increase in basal autophagic flux in skeletal muscles. Overall, the results of the present study demonstrate that Parkin plays a protective role in the maintenance of normal mitochondrial and contractile functions in normal skeletal muscles.
Enzymatic Synthesis of 6′-Sialyllactose, a Dominant Sialylated Human Milk Oligosaccharide, by a Novel
exo
-α-Sialidase from Bacteroides fragilis NCTC9343
Authors: Guo Longcheng , Chen Xiaodi , Xu Li , Xiao Min , Lu Lili 
Published: April 2018

ABSTRACT

Gut bacteria provide a rich source of glycosidases that can recognize and/or hydrolyze glycans for nutrition. Interestingly, some glycosidases have also been found to catalyze transglycosylation reactions
in vitro
and thus can be used for oligosaccharide synthesis. In this work, six putative and one known
exo
-α-sialidase genes—three from
Bacteroides fragilis
NCTC9343, three from
Clostridium perfringens
ATCC 13124, and one known from
Bifidobacterium bifidum
JCM1254—were subjected to gene cloning and heterogeneous expression in
Escherichia coli
. The recombinant enzymes were purified, characterized for substrate specificity, and screened for transglycosylation activity. A sialidase, named BfGH33C, from
B. fragilis
NCTC9343 was found to possess excellent transglycosylation activity for the synthesis of sialylated human milk oligosaccharide. The native BfGH33C was a homodimer with a molecular weight of 113.6 kDa. The

K
m

and
k
cat
values for 4-methylumbelliferyl
N
-acetyl-α-
d
-neuraminic acid and sialic acid dimer were determined to be 0.06 mM and 283.2 s
−1
, and 0.75 mM and 329.6 s
−1
, respectively. The enzyme was able to transfer sialyl from sialic acid dimer or oligomer to lactose with high efficiency and strict α2-6 regioselectivity. The influences of the initial substrate concentration, pH, temperature, and reaction time on transglycosylation were investigated in detail. Using 40 mM sialic acid dimer (or 40 mg/ml oligomer) and 1 M lactose (pH 6.5) at 50°C for 10 min, BfGH33C could specifically produce 6′-sialyllactose, a dominant sialylated human milk oligosaccharide, at a maximal conversion ratio above 20%. It provides a promising alternative to the current chemical and enzymatic methods for obtaining sialylated oligosaccharides.

IMPORTANCE
Sialylated human milk oligosaccharides are significantly beneficial to the neonate, as they play important roles in supporting resistance to pathogens, gut maturation, immune function, and brain and cognitive development. Therefore, access to the sialylated oligosaccharides has attracted increasing attention both for the study of saccharide functions and for the development of infant formulas that could mimic the nutritional value of human milk. Nevertheless, nine-carbon sialic acids are rather complicated for the traditional chemical modifications, which require multiple protection and deprotection steps to achieve a specific glycosidic bond. Here, the
exo
-α-sialidase BfGH33C synthesized 6′-sialyllactose in a simple step with high transglycosylation activity and strict regioselectivity. Additionally, it could utilize oligosialic acid, which was newly prepared in an easy, economical way to reduce the substrate cost, as a glycosyl donor. All the studies laid a foundation for the practical use of BfGH33C in large-scale synthesis of sialylated oligosaccharides in the future.
Identification of the I38T PA Substitution as a Resistance Marker for Next-Generation Influenza Virus Endonuclease Inhibitors
Authors: Jones Jeremy C. , Kumar Gyanendra , Barman Subrata , Najera Isabel , White Stephen W. , Webby Richard J. , Govorkova Elena A. 
Published: April 2018

ABSTRACT

The clinical severity and annual occurrence of influenza virus epidemics, combined with the availability of just a single class of antivirals to treat infections, underscores the urgent need to develop new anti-influenza drugs. The endonuclease activity within the viral acidic polymerase (PA) protein is an attractive target for drug discovery due to the critical role it plays in viral gene transcription. RO-7 is a next-generation PA endonuclease inhibitor of influenza A and B viruses, but its drug resistance potential is unknown. Through serial passage of influenza A(H1N1) viruses in MDCK cells under selective pressure of RO-7, we identified an I38T substitution within the PA endonuclease domain that conferred
in vitro
resistance to RO-7 (up to a 287-fold change in 50% effective concentration [EC
50
]). I38T emerged between 5 and 10 passages, and when introduced into recombinant influenza A(H1N1) viruses, alone conferred RO-7 resistance (up to an 81-fold change in EC
50
). Cocrystal structures of mutant and wild-type endonuclease domains with RO-7 provided the structural basis of resistance, where a key hydrophobic interaction between RO-7 and the Ile38 side chain is compromised when mutated to the polar threonine. While Ile38 does not have a crucial role in coordinating the endonuclease active site, the switch to threonine does affect the polymerase activity of some viruses and influences RO-7 affinity for the PA
N
target (i.e., the ≈200-residue N-terminal domain of PA). However, the change does not lead to a complete loss of replication activity
in vitro
. Our results predict that RO-7-resistant influenza viruses carrying the I38T substitution may emerge under treatment. This should be taken into consideration for clinical surveillance and in refinement of these drugs.

IMPORTANCE
The effectiveness of antiviral drugs can be severely compromised by the emergence of resistant viruses. Therefore, determination of the mechanisms by which viruses become resistant is critical for drug development and clinical use. RO-7 is a compound that potently inhibits influenza virus replication and belongs to a new class of drugs in late-stage clinical trials for treatment of influenza virus infection. Here we demonstrate that a single amino acid change acquired under prolonged virus exposure to RO-7 renders influenza viruses significantly less susceptible to its inhibitory effects. We have discovered how the mutation can simultaneously interfere with drug activity and still maintain efficient virus replication. These findings have important implications for the development of more effective derivatives of RO-7-like drugs and provide guidance for how to monitor the emergence of resistance.
Impact of age on excess risk of coronary heart disease in patients with familial hypercholesterolaemia
Authors: Mundal Liv J , Igland Jannicke , Veierød Marit B , Holven Kirsten Bjørklund , Ose Leiv , Selmer Randi Marie , Wisloff Torbjorn , Kristiansen Ivar S , Tell Grethe S , Leren Trond P , Retterstøl Kjetil 
Published: April 2018

ObjectiveThe primary objective was to study the risk of acute myocardial infarction (AMI) and coronary heart disease (CHD) in patients with familial hypercholesterolaemia (FH) and compare with the risk in the general population.MethodsPatients with an FH mutation but without prior AMI (n=3071) and without prior CHD (n=2795) were included in the study sample during 2001–2009. We obtained data on all AMI and CHD hospitalisations in Norway. We defined incident cases as first time hospitalisation or out-of-hospital death due to AMI or CHD. We estimated standardised incidence ratios (SIRs) with 95% CIs with indirect standardisation using incidence rates for the total Norwegian population stratified by sex, calendar year and 1 year age groups as reference rates.ResultsSIRs for AMI (95% CIs) were highest in the age group 25–39 years; 7.5 (3.7 to 14.9) in men and 13.6 (5.1 to 36.2) in women and decreased with age to 0.9 (0.4 to 2.1) in men and 1.8 (0.9 to 3.7) in women aged 70–79 years. Similarly, SIRs for CHD were highest among patients 25–39 years old; 11.1 (7.1–17.5) in men and 17.3 (9.6–31.2) in women and decreased 2.4 (1.4–4.2) in men and 3.2 (1.5–7.2) in women at age 70–79. For all age groups, combined SIRs for CHD were 4.2 (3.6–5.0) in men and 4.7 (3.9–5.7) in women.ConclusionPatients with FH are at severely increased risk of AMI and CHD compared with the general population. The highest excess risk was in the youngest group aged 25–39 years, in both sexes.
Determining the effects of biochar and an arbuscular mycorrhizal inoculant on the growth of fowl mannagrass (Glyceria striata) (Poaceae)
Authors: Moland Sadie , Robicheau Brent M. , Browne Robin , Newell Ruth , Walker Allison K. 
Published: April 2018

Biochar is gaining attention as an organic soil amendment that can increase plant yields and improve soil fertility. We studied the effect of biochar on the growth of fowl mannagrass ( Glyceria striata (Lam.) Hitchc.) (Poaceae), propagated in a greenhouse for future re-introduction into restored wetlands. Three different application rates (10%, 50%, and 75% biochar volume/substrate volume ( v/ v)) of nutrient-charged (i.e., nutrients added) and uncharged biochar were tested with and without a commercial arbuscular mycorrhizal fungal (AMF) inoculant. Aboveground biomass (shoot mass), belowground biomass (root mass), and shoot height of 166 G. striata samples were recorded after 92 d of growth. Using generalized linear models our data indicated a 50% ( v/ v) application rate of nutrient-charged biochar without AMF produces a significantly greater growth response (4.4× greater shoot height and 85× greater shoot mass compared with 0% biochar (AMF negative) control). We propose that the increased G. striata growth may be due to changes in pH, and (or) increased nutrient availability due to the addition of biochar. We recommend an application rate of 50% biochar ( v/ v) charged with nutrients as an advantageous amendment for propagating G. striata.
<i>Triplocania</i> Roesler: a new species, redescriptions, description of the female of <i>Triplocania spinosa</i> Mockford, and revalidation of the original combination of <i>Belicania cervantesi</i> (García Aldrete) (Psocodea: ‘Psocoptera’: Ptiloneuridae)
Authors: Silva Neto Alberto Moreira da , García Aldrete Alfonso Neri , Rafael José Albertino 
Published: April 2018

Triplocania umbrataoides sp. nov., from the Río Tambopata Reserved Zone, in Madre de Dios, Peru, is here described and illustrated. Triplocania magnifica Roesler and the male of Triplocania spinosa Mockford are redescribed and illustrated. The female Triplocania spinosa is here described and illustrated. The original combination of Belicania cervantesi (García Aldrete) is revalidated.
Causes and Temporal Patterns of 30‐Day Readmission Among Older Adults Hospitalized With Heart Failure With Preserved or Reduced Ejection Fraction
Authors: Goyal Parag , Loop Matthew , Chen Ligong , Brown Todd M. , Durant Raegan W. , Safford Monika M. , Levitan Emily B. 
Published: April 2018

Background

It is unknown whether causes and temporal patterns of 30‐day readmission vary between heart failure (HF) with preserved ejection fraction (
HF
p
EF
) and HF with reduced ejection fraction (
HF
r
EF
). We sought to address this question by examining a 5% national sample of Medicare beneficiaries.

Methods and Results

We included individuals who experienced a hospitalization for
HF
p
EF
or
HF
r
EF
between 2007 and 2013. We identified causes of 30‐day readmission based on primary discharge diagnosis and further classified causes of readmission as
HF
‐related, non–
HF
cardiovascular‐related, and non–cardiovascular‐related. We calculated the cumulative incidence of these classifications for
HF
p
EF
and
HF
r
EF
in a competing risks model and calculated subdistribution hazard ratios of these classifications by comparing those with
HF
p
EF
and those with
HF
r
EF
. Among 60 640 Medicare beneficiaries, we identified 13 785 unique older adults hospitalized with
HF
p
EF
and 15 205 who were hospitalized with
HF
r
EF
. Noncardiovascular diagnoses represented the most common causes of 30‐day readmission (
HF
p
EF
: 59%;
HF
r
EF
: 47%), a pattern that was observed for each week of the 30‐day study period for both
HF
p
EF
and
HF
rEF participants. In comparing readmission diagnoses in an adjusted model, non–cardiovascular‐related diagnoses were more common and
HF
‐related diagnoses were less common in
HF
pEF participants.

Conclusions

Non–cardiovascular‐related diagnoses represented the most common causes of 30‐day readmission following
HF
hospitalization for each week of the 30‐day postdischarge period.
HF
diagnoses were less common among those with
HF
p
EF
compared with
HF
r
EF
. Future interventions aimed at reducing 30‐day readmissions following an
HF
hospitalization would benefit from an increased focus on noncardiovascular comorbidity and interventions that target
HF
p
EF
and
HF
r
EF
separately.
Eddy Lifetime, Number, and Diffusivity and the Suppression of Eddy Kinetic Energy in Midwinter
Authors: Schemm Sebastian , Schneider Tapio 
Published: April 2018

Abstract
The wintertime evolution of the North Pacific storm track appears to challenge classical theories of baroclinic instability, which predict deeper extratropical cyclones when baroclinicity is highest. Although the surface baroclinicity peaks during midwinter, and the jet is strongest, eddy kinetic energy (EKE) and baroclinic conversion rates have a midwinter minimum over the North Pacific. This study investigates how the reduction in EKE translates into a reduction in eddy potential vorticity (PV) and heat fluxes via changes in eddy diffusivity. Additionally, it augments previous observations of the midwinter storm-track evolution in both hemispheres using climatologies of tracked surface cyclones. In the North Pacific, the number of surface cyclones is highest during midwinter, while the mean EKE per cyclone and the eddy lifetime are reduced. The midwinter reduction in upper-level eddy activity hence is not associated with a reduction in surface cyclone numbers. North Pacific eddy diffusivities exhibit a midwinter reduction at upper levels, where the Lagrangian decorrelation time is shortest (consistent with reduced eddy lifetimes) and the meridional parcel velocity variance is reduced (consistent with reduced EKE). The resulting midwinter reduction in North Pacific eddy diffusivities translates into an eddy PV flux suppression. In contrast, in the North Atlantic, a milder reduction in the decorrelation time is offset by a maximum in velocity variance, preventing a midwinter diffusivity minimum. The results suggest that a focus on causes of the wintertime evolution of Lagrangian decorrelation times and parcel velocity variance will be fruitful for understanding causes of seasonal storm-track variations.
A Correction for the Thermal Mass–Induced Errors of CTD Tags Mounted on Marine Mammals
Authors: Mensah Vigan , Roquet Fabien , Siegelman-Charbit Lia , Picard Baptiste , Pauthenet Etienne , Guinet Christophe 
Published: April 2018

AbstractThe effect of thermal mass on the salinity estimate from conductivity–temperature–depth (CTD) tags sensor mounted on marine mammals is documented, and a correction scheme is proposed to mitigate its impact. The algorithm developed here allows for a direct correction of the salinity data, rather than a correction of the sample’s conductivity and temperature. The amplitude of the thermal mass–induced error on salinity and its correction are evaluated via comparison between data from CTD tags and from Sea-Bird Scientific CTD used as a reference. Thermal mass error on salinity appears to be generally O(10−2) g kg−1, it may reach O(10−1) g kg−1, and it tends to increase together with the magnitude of the cumulated temperature gradient (THP) within the water column. The correction we propose yields an error decrease of up to ~60% if correction coefficients specific to a certain tag or environment are calculated, and up to 50% if a default value for the coefficients is provided. The correction with the default coefficients was also evaluated using over 22 000 in situ dive data from five tags deployed in the Southern Ocean and is found to yield significant and systematic improvements on the salinity data, including for profiles whose THP was weak and the error small. The correction proposed here yields substantial improvements in the density estimates, although a thermal mass–induced error in temperature measurements exists for very large THP and has yet to be corrected.