bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a cell system for siRNA screening of pathogen responses in human and mouse macrophages
Authors: Li Ning , Sun Jing , Benet Zachary L. , Wang Ze , Al-Khodor Souhaila , John Sinu P. , Lin Bin , Sung Myong-Hee , Fraser Iain D. C. 
Published: April 2015

AbstractMacrophages play a critical role in the innate immune response to pathogen infection, but few tools exist for systematic dissection of these responses using modern genome-wide perturbation methods. To develop an assay platform for high-throughput analysis of macrophage activation by pathogenic stimuli, we generated reporter systems in human and mouse macrophages with dynamic readouts for NF-κB and/or TNF-α responses. These reporter cells show responsiveness to a broad range of TLR ligands and to gram-negative bacterial infection. There are significant challenges to the use of RNAi in innate immune cells, including efficient small RNA delivery and non-specific immune responses to dsRNA. To permit the interrogation of the macrophage pathogen response pathways with RNAi, we employed the stably expressed reporter genes to develop efficient siRNA delivery protocols for maximal target gene silencing with minimal activation of the innate macrophage response to nucleic acids. We demonstrate the utility of these macrophage cell systems for siRNA screening of pathogen responses by targeting components of the human and mouse TLR pathways and observe species-specific perturbation of signaling and cytokine responses. Our approach to reporter cell development and siRNA delivery optimization provides an experimental paradigm with significant potential for developing genetic screening platforms in mammalian cells.
RcsAB is a major repressor of Yersinia biofilm development through directly acting on hmsCDE, hmsT and hmsHFRS
Authors: Fang Nan , Yang Huiying , Fang Haihong , Liu Lei , Zhang Yiquan , Wang Li , Han Yanping , Zhou Dongsheng , Yang Ruifu 
Published: April 2015

AbstractBiofilm formation in flea gut is important for flea-borne transmission of Yersinia pestis. There are enhancing factors (HmsHFRS, HmsCDE and HmsT) and inhibiting one (HmsP) for Yersinia pestis biofilm formation. The RcsAB regulatory complex acts as a repressor of Yesinia biofilm formation and adaptive pseudogenization of rcsA promotes Y. pestis to evolve the ability of biofilm formation in fleas. In this study, we constructed a set of isogenic strains of Y. pestis biovar Microtus, namely WT (RscB+ and RcsA-), c-rcsA (RscB+ and RcsA+), ΔrcsB (RscB- and RcsA-) and ΔrcsB/c-rcsA (RscB- and RcsA+). The phenotypic assays confirmed that RcsB alone (but not RcsA alone) had an inhibiting effect on biofilm/c-di-GMP production whereas assistance of RcsA to RcsB greatly enhanced this inhibiting effect. Further gene regulation experiments showed that RcsB in assistance of RcsA tightly bound to corresponding promoter-proximal regions to achieve transcriptional repression of hmsCDE, hmsT and hmsHFRS and, meanwhile, RcsAB positively regulated hmsP most likely in an indirect manner. Data presented here disclose that pseudogenization of rcsA leads to dramatic remodeling of RcsAB-dependent hms gene expression between Y. pestis and its progenitor Y. pseudotuberculosis, enabling potent production of Y. pestis biofilms in fleas.
A cost-effective RNA sequencing protocol for large-scale gene expression studies
Authors: Hou Zhonggang , Jiang Peng , Swanson Scott A. , Elwell Angela L. , Nguyen Bao Kim S. , Bolin Jennifer M. , Stewart Ron , Thomson James A. 
Published: April 2015

AbstractRNA sequencing has increasingly become an indispensable tool for biological research. While sequencing costs have fallen dramatically in recent years, the current cost of RNA sequencing, nonetheless, remains a barrier to even more widespread adoption. Here, we present a simple RNA sequencing protocol with substantially reduced costs. This protocol uses as little as 10 ng of total RNA, allows multiplex sequencing of up to 96 samples per lane and is strand specific. Extensive validation using human embryonic stem cells showed high consistency between technical replicates at various multiplexing levels.
The tumour suppressor CHD5 forms a NuRD-type chromatin remodelling complex
Authors: Kolla Venkatadri , Naraparaju Koumudi , Zhuang Tiangang , Higashi Mayumi , Kolla Sriharsha , Blobel Gerd A. , Brodeur Garrett M. 
Published: April 2015

Eukaryotic gene expression is developmentally regulated, in part by chromatin remodelling, and its dysregulation has been linked to cancer. CHD5 (chromodomain helicase DNA-binding protein 5) is a tumour suppressor gene (TSG) that maps to a region of consistent deletion on 1p36.31 in neuroblastomas (NBs) and other tumour types. CHD5 encodes a protein with chromatin remodelling, helicase and DNA-binding motifs that is preferentially expressed in neural and testicular tissues. CHD5 is highly homologous to CHD3 and CHD4, which are the core subunits of nucleosome remodelling and deacetylation (NuRD) complexes. To determine if CHD5 forms a similar complex, we performed studies on nuclear extracts from NBLS, SY5Y (both with endogenous CHD5 expression), NLF (CHD5 null) and NLF cells stably transfected with CHD5 cDNA (wild-type and V5–histidine-tagged). Immunoprecipitation (IP) was performed with either CHD5 antibody or antibody to V5/histidine-tagged protein. We identified NuRD components both by GST–FOG1 (Friend Of GATA1) pull-down and by IP. We also performed MS/MS analysis to confirm the presence of CHD5 or other protein components of the NuRD complex, as well as to identify other novel proteins. CHD5 was clearly associated with all canonical NuRD components, including metastasis-associated protein (MTA)1/2, GATA zinc finger domain containing 2A (GATAD2A), histone deacetylase (HDAC)1/2, retinoblastoma-binding protein (RBBP)4/7 and methyl DNA-binding domain protein (MBD)2/3, as determined by Western blotting and MS/MS. Our data suggest CHD5 forms a NuRD complex similar to CHD4. However, CHD5–NuRD may also have unique protein associations that confer functional specificity and may contribute to normal development and to tumour suppression in NB and other cancers.
The human sex ratio from conception to birth
Authors: Orzack Steven Hecht , Stubblefield J. William , Akmaev Viatcheslav R. , Colls Pere , Munné Santiago , Scholl Thomas , Steinsaltz David , Zuckerman James E. 
Published: April 2015

SignificanceThe human sex ratio has long interested cell biologists, developmental biologists, demographers, epidemiologists, evolutionary biologists, gynecologists, and statisticians. Nonetheless, the trajectory of the human sex ratio from conception to birth has been poorly characterized. We present the most comprehensive analysis of this trajectory ever done. Our dataset is the largest ever assembled to estimate the sex ratio at conception and is the first, to our knowledge, to include data from 3- to- 6-d-old embryos, induced abortions, chorionic villus sampling, amniocentesis, and fetal deaths and live births. Our results indicate that the sex ratio at conception is unbiased, the proportion of males increases during the first trimester, and total female mortality during pregnancy exceeds total male mortality; these are fundamental insights into early human development.
SOX2 primes the epigenetic landscape in neural precursors enabling proper gene activation during hippocampal neurogenesis
Authors: Amador-Arjona Alejandro , Cimadamore Flavio , Huang Chun-Teng , Wright Rebecca , Lewis Susan , Gage Fred H. , Terskikh Alexey V. 
Published: April 2015

Significance
Sex-determining region Y-related HMG box 2 (SOX2) is a well-established marker of neural stem and progenitor cells, and its function was shown to be required for the self-renewal of these cells. However, the function of SOX2 in neuronal differentiation is poorly understood. Here we described a novel role of SOX2 in neuronal differentiation in which SOX2 binds to bivalently marked promoters of poised proneural genes in neural progenitor cells and limits the activity of polycomb repressive complex 2 and excessive levels of histone H3 Lys 27 trimethylation. We propose a novel function of SOX2 in maintaining a permissive epigenetic state thus enabling proper activation of the neuronal differentiation program under neurogenic cue.
Structural basis for the geometry-driven localization of a small protein
Authors: Gill Richard L. , Castaing Jean-Philippe , Hsin Jen , Tan Irene S. , Wang Xingsheng , Huang Kerwyn Casey , Tian Fang , Ramamurthi Kumaran S. 
Published: April 2015

Significance
Despite extensive studies of protein trafficking across length scales of many microns, how proteins correctly localize within the smaller length scales of bacterial cells is still poorly understood. Recently, we proposed that slight membrane curvature, defined by the surface geometry of a bacterium, can drive the localization of certain shape-sensing proteins. Here, we developed an assay to quantify membrane curvature recognition by the small bacterial protein SpoVM and used NMR to determine the structural basis of curvature recognition. NMR and molecular dynamics simulations suggested a model wherein unusually deep membrane insertion allows the protein to sense subtle acyl chain packing differences between differently curved membranes, a distinct curvature-sensing mechanism from those used by proteins that sense high membrane curvature.
Environmental tipping points significantly affect the cost−benefit assessment of climate policies
Authors: Cai Yongyang , Judd Kenneth L. , Lenton Timothy M. , Lontzek Thomas S. , Narita Daiju 
Published: April 2015

SignificanceMost current cost−benefit analyses of climate change suggest global climate policy should be relatively weak. However, relatively few studies account for the market or nonmarket impacts of passing environmental tipping points that cause abrupt and irreversible damages. We use a stochastic dynamic model of the climate and economy to quantify the effect of tipping points on climate change policy. We show that environmental tipping points can profoundly alter cost−benefit analysis, justifying a much more stringent climate policy, which takes the form of a higher immediate price on carbon.
A Field-Based Nursery for Headstarting Lobsters to Improve Postrelease Survival for Potential Stock Enhancement in Long Island Sound, Connecticut
Authors: Mercaldo-Allen Renee , Goldberg Ronald , Kuropat Catherine A , Clark Paul , Alix Robert , Schreiner Werner , Roy John 
Published: April 2015

Abstract
Early benthic stage American lobsters Homarus americanus were held in a pilot nursery system in Long Island Sound (LIS), Connecticut, to test field grow out as a step toward potential stock enhancement. A larger size upon release may increase the probability of survival. Lobsters were placed individually in perforated plastic mesh cylindrical “habitats,” and each habitat was housed in an outer protective sleeve with a larger mesh size. During June 2013, 24 lobsters were transferred to each of three wire mesh cages and deployed southwest of Charles Island in Milford, Connecticut (N = 3). The only source of nutrition was naturally occurring organisms. Cages were retrieved monthly, and lobsters were photographed to measure changes in carapace length (CL). After 11 months in the field, lobsters increased 92% in mean size from 6.0- to 11.6-mm CL, with 70.8% overall survival. Headstarting of early benthic stage lobsters shows promise as a tool for possible future stock enhancement in LIS.
Understanding Social Resilience in the Maine Lobster Industry
Authors: Henry Anna M. , Johnson Teresa R. 
Published: April 2015

Abstract
The Maine lobster Homarus americanus fishery is considered one of the most successful fisheries in the world due in part to its unique comanagement system, the conservation ethic of the harvesters, and the ability of the industry to respond to crises and solve collective-action problems. However, recent threats raise the question whether the industry will be able to respond to future threats as successfully as it has to ones in the past or whether it is now less resilient and can no longer adequately respond to threats. Through ethnographic research and oral histories with fishermen, we examined the current level of social resilience in the lobster fishery. We concentrated on recent threats to the industry and the ways in which it has responded to them, focusing on three situations: a price drop beginning in 2008, a recovery in 2010–2011, and a second collapse of prices in 2012. In addition, we considered other environmental and regulatory concerns identified by fishermen. We found that the industry is not responding effectively to recent threats and identified factors that might explain the level of social resilience in the fishery.
Received August 20, 2013; accepted October 29, 2014
Bayesian analysis of a flow meter calibration problem
Authors: Kok G J P , van der Veen A M H , Harris P M , Smith I M , Elster C 
Published: April 2015

Abstract
A turbine flow meter indicates the volume of fluid flowing through the device per unit of time. Such a flow meter is commonly calibrated at a few known flow rates over its measurement range. A calibration curve relating the pulse factor of the meter to the flow rate is then fitted to calibration data using an ordinary least squares approach. This approach does not consider prior knowledge that may exist about the flow meter or the calibration procedure. A Bayesian analysis enables prior knowledge to be taken into account. A Bayesian inference results in a posterior distribution for the unknown parameters of the calibration curve that may be seen as the most comprehensive uncertainty information about these unknowns. This paper investigates for a flow meter calibration problem the effects of appreciating prior knowledge on values of the calibration curve and their associated uncertainties. It presents the results of a Bayesian analysis and compares them to those obtained by an ordinary least squares approach.
Tauberian conditions, Muckenhoupt weights, and differentiation properties of weighted bases
Authors: Hagelstein Paul , Luque Teresa , Parissis Ioannis 
Published: April 2015

Let

B

\mathfrak {B}

be a homothecy invariant collection of convex sets in

R

n

\mathbb {R}^{n}

. Given a measure

μ
\mu

, the associated weighted geometric maximal operator

M

B

,
μ

M_{\mathfrak {B}, \mu }

is defined by

M

B

,
μ

f
(
x
)
:=

sup

x
∈
B
∈

B

1

μ
(
B
)

∫

B

|

f

|

d
μ
.

\begin{align*} M_{\mathfrak {B}, \mu }f(x) := \sup _{x \in B \in \mathfrak {B}}\frac {1}{\mu (B)}\int _{B}|f|d\mu . \end{align*}

It is shown that, provided

μ
\mu

satisfies an appropriate doubling condition with respect to

B

\mathfrak {B}

and

ν
\nu

is an arbitrary locally finite measure, the maximal operator

M

B

,
μ

M_{\mathfrak {B}, \mu }

is bounded on

L

p

(
ν
)

L^{p}(\nu )

for sufficiently large

p
p

if and only if it satisfies a Tauberian condition of the form

ν

(

{

x
∈

R

n

:

M

B

,
μ

(

1

E

)
(
x
)
>

1
2

}

)

≤

c

μ
,
ν

ν
(
E
)
.

\begin{align*} \nu \big (\big \{x \in \mathbb {R}^{n} : M_{\mathfrak {B}, \mu }(\textbf {1}_E)(x) > \frac {1}{2} \big \}\big ) \leq c_{\mu , \nu }\nu (E). \end{align*}

As a consequence of this result we provide an alternative characterization of the class of Muckenhoupt weights

A

∞
,

B

A_{\infty , \mathfrak {B}}

for homothecy invariant Muckenhoupt bases

B

\mathfrak {B}

consisting of convex sets. Moreover, it is immediately seen that the strong maximal function

M

R

,
μ

M_{\mathfrak {R}, \mu }

, defined with respect to a product-doubling measure

μ
\mu

, is bounded on

L

p

(
ν
)

L^{p}(\nu )

for some

p
>
1

p > 1

if and only if

ν

(

{

x
∈

R

n

:

M

R

,
μ

(

1

E

)
(
x
)
>

1
2

}

)

≤

c

μ
,
ν

ν
(
E
)

\begin{align*} \nu \big (\big \{x \in \mathbb {R}^{n} : M_{\mathfrak {R}, \mu }(\textbf {1}_E)(x) > \frac {1}{2}\big \}\big ) \leq c_{\mu , \nu }\nu (E)\; \end{align*}

holds for all

ν
\nu

-measurable sets

E
E

in

R

n

\mathbb {R}^{n}

. In addition, we discuss applications in differentiation theory, in particular proving that a

μ
\mu

-weighted homothecy invariant basis of convex sets satisfying appropriate doubling and Tauberian conditions must differentiate

L

∞

(
ν
)

L^{\infty }(\nu )

.
Photosphere, thermalization surface and spectra of black hole accretion flows under electron scattering
Authors: Masuda Takao , Fukue Jun 
Published: April 2015

Abstract
We examine the expected spectra of black hole accretion flows, which are assumed to be steady and spherically symmetric, considering the separation of the apparent photosphere and thermalization surface under electron scattering. Although the flow itself is spherical, the apparent shape of the photosphere is not spherical, since the density distribution gradually decreases with radius. Furthermore, due to electron scattering, the thermalization surface decouples with the photosphere, and is located deep inside the photosphere for scattering-dominated flows. Since the shape of the thermalization surface is also aspherical, the temperature there is not uniform, which causes a strong limb-darkening effect, and we may observe a non-blackbody spectrum with multi-color-type.
Relationship between extreme ultraviolet microflares and small-scale magnetic fields in the quiet Sun
Authors: Jiang Fayu , Zhang Jun , Yang Shuhong 
Published: April 2015

Abstract
Microflares are small dynamic signatures observed in X-ray and extreme-ultraviolet channels. Because of their impulsive emission enhancements and wide distribution, they are thought to be closely related to coronal heating. By using the high-resolution 171 Å images from the Atmospheric Imaging Assembly and the lines-of-sight magnetograms obtained by the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory, we trace 10794 microflares in a quiet region near the disk center with a field of view of 960″ × 1068″ during 24 hr. The microflares have an occurrence rate of 4.4 × 103 hr−1 extrapolated over the whole Sun. Their average brightness, size, and lifetime are 1.7I0 (of the quiet Sun), 9.6 Mm2, and 3.6 min, respectively. There exists a mutual positive correlation between the microflares’ brightness, area, and lifetime. In general, the microflares distribute uniformly across the solar disk, but form network patterns locally, which are similar to and matched with the magnetic network structures. Typical cases show that the microflares prefer to occur in magnetic cancellation regions of network boundaries. We roughly calculate the upper limit of energy flux supplied by the microflares and find that the result is still a factor of ∼ 15 below the coronal heating requirement.
Suzaku observations of the old pulsar wind nebula candidate HESS J1356−645
Authors: Izawa Masaharu , Dotani Tadayasu , Fujinaga Takahisa , Bamba Aya , Ozaki Masanobu , Hiraga Junko S. 
Published: April 2015

Abstract
A largely extended X-ray emission was discovered around the pulsar PSR  J1357−6429 with the Suzaku deep observations. The pulsar, whose characteristic age is 7.3 kyr, is located within the TeV γ-ray source HESS J1356−645. The extended emission is found to have a 1 σ X-ray size of ∼ 4′, or ∼ 3 pc at 2.4 kpc, with a small offset from the pulsar. Its X-ray spectrum is well reproduced by a simple power-law model with a photon index of $1.70_{-0.06}^{+0.07}$. No significant spatial variation was found for the X-ray photon index as a function of distance from the pulsar. We conclude that the extended emission is associated to the pulsar wind nebula (PWN) of PSR  J1357−6429. This is a new sample of largely extended nebulae around middle-aged pulsars. We discuss the evolution of this PWN according to the relic PWN scenario.
Simple genetic models for autism spectrum disorder
Authors: Mukhopadhyay Swagatam , Wigler Michael , Levy Dan 
Published: April 2015

AbstractTo explore the interplay between new mutation, transmission, and gender bias in genetic disease requires formal quantitative modeling. Autism spectrum disorders offer an ideal case: they are genetic in origin, complex, and show a gender bias. The high reproductive costs of autism ensure that most strongly associated genetic mutations are short-lived, and indeed the disease exhibits both transmitted andde novocomponents. There is a large body of both epidemiologic and genomic data that greatly constrain the genetic mechanisms that may contribute to the disorder. We develop a computational framework that assumes classes of additive variants, each member of a class having equal effect. We restrict our initial exploration to single class models, each having three parameters. Only one model matches epidemiological data. It also independently matches the incidence ofde novomutation in simplex families, the gender bias in unaffected siblings in simplex populations, and rates of mutation in target genes. This model makes strong and as yet not fully tested predictions, namely that females are the primary carriers in cases of genetic transmission, and that the incidence ofde novomutation in target genes for families at high risk for autism are not especially elevated. In its simplicity, this model does not account for MZ twin concordance or the distorted gender bias of high functioning children with ASD, and does not accommodate all the known mechanisms contributing to ASD. We point to the next steps in applying the same computational framework to explore more complex models.Author summaryFor understanding complex genetic diseases one needs both data and molecular/genetic models. In the absence of any model, it is impossible to do more than summarize observations. A good model will be consistent with much or all of the existing data and puts the data in the context of known genetic principles. Ideally the model will make testable predictions. Where the good models fail often shows the directions that require more thought about mechanisms. In this paper we describe a new computational framework that we use to explore a complex genetic disorder with many gene targets, with bothde novoand transmitted variants, and with gender bias. The disorder we consider is autism spectrum disorder (ASD), and our framework rules out some previous models that make unsustainable predictions. We identify a formal model that satisfies diverse epidemiologic and genomic observations. This model makes strong and untested predictions and thereby suggests new studies that would resolve outstanding aspects of autism genetics.