bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-146a suppresses ROCK1 allowing hyperphosphorylation of tau in Alzheimer’s disease
Authors: Wang Gang , Huang Yue , Wang Li-Ling , Zhang Yong-Fang , Xu Jing , Zhou Yi , Lourenco Guinevere F. , Zhang Bei , Wang Ying , Ren Ru-Jing , Halliday Glenda M. , Chen Sheng-Di 
Published: May 2016

AbstractMicroRNA-146a is upregulated in the brains of patients with Alzheimer’s disease (AD). Here, we show that the rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is a target of microRNA-146a in neural cells. Knockdown of ROCK1 mimicked the effects of microRNA-146a overexpression and induced abnormal tau phosphorylation, which was associated with inhibition of phosphorylation of the phosphatase and tensin homolog (PTEN). The ROCK1/PTEN pathway has been implicated in the neuronal hyperphosphorylation of tau that occurs in AD. To determine the function of ROCK1 in AD, brain tissue from 17 donors with low, intermediate or high probability of AD pathology were obtained and analyzed. Data showed that ROCK1 protein levels were reduced and ROCK1 colocalised with hyperphosphorylated tau in early neurofibrillary tangles. Intra-hippocampal delivery of a microRNA-146a specific inhibitor (antagomir) into 5xFAD mice showed enhanced hippocampal levels of ROCK1 protein and repressed tau hyperphosphorylation, partly restoring memory function in the 5xFAD mice. Our in vitro and in vivo results confirm that dysregulation of microRNA-146a biogenesis contributes to tau hyperphosphorylation and AD pathogenesis and inhibition of this microRNA could be a viable novel in vivo therapy for AD.
Composition and aggregation of extracellular polymeric substances (EPS) in hyperhaline and municipal wastewater treatment plants
Authors: Zeng Jie , Gao Jun-Min , Chen You-Peng , Yan Peng , Dong Yang , Shen Yu , Guo Jin-Song , Zeng Ni , Zhang Peng 
Published: May 2016

AbstractAs important constituents of activated sludge flocs, extracellular polymeric substances (EPS) play significant roles in pollutants adsorption, the formation and maintenance of microbial aggregates and the protection of microbes from external environmental stresses. In this work, EPS in activated sludge from a municipal wastewater treatment plant (M-WWTP) with anaerobic/anoxic/oxic (A2/O) process and a hyperhaline wastewater treatment plant (H-WWTP) with anaerobic/oxic (A/O) process were extracted by ultrasound method. The proteins and polysaccharides contents in EPS were determined by using a modified Lowry method and anthrone colorimetry respectively to analyze the detail differences in two types of WWTPs. Fourier transform-infrared spectroscopy and three-dimensional excitation-emission matrix fluorescence spectroscopy demonstrated proteins and polysaccharides were the dominant components of the two types of EPS and the aromatic protein-like substances accounted for a larger proportion in EPS proteins. The results of the aggregation test indicated that EPS were good for the sludge aggregation and the EPS in oxic sludge were more beneficial to sludge aggregation than that in anoxic sludge. Anoxic sludge EPS in H-WWTP showed a negligible effect on sludge aggregation. Comparative study on EPS of different tanks in the M-WWTP and H-WWTP was valuable for understanding the characteristics of EPS isolated from two typical wastewater treatment processes.
Multicolour Multilevel STED nanoscopy of Actin/Spectrin Organization at Synapses
Authors: Sidenstein Sven C. , D’Este Elisa , Böhm Marvin J. , Danzl Johann G. , Belov Vladimir N. , Hell Stefan W. 
Published: May 2016

AbstractSuperresolution fluorescence microscopy of multiple fluorophores still requires development. Here we present simultaneous three-colour stimulated emission depletion (STED) nanoscopy relying on a single STED beam at 620 nm. Toggling the STED beam between two or more power levels (“multilevelSTED”) optimizes resolution and contrast in all colour channels, which are intrinsically co-aligned and well separated. Three-colour recording is demonstrated by imaging the nanoscale cytoskeletal organization in cultured hippocampal neurons. The down to ~35 nm resolution identified periodic actin/betaII spectrin lattices along dendrites and spines; however, at presynaptic and postsynaptic sites, these patterns were found to be absent. Both our multicolour scheme and the 620 nm STED line should be attractive for routine STED microscopy applications.
Abundance and Temperature Dependency of Protein-Protein Interaction Revealed by Interface Structure Analysis and Stability Evolution
Authors: He Yi-Ming , Ma Bin-Guang 
Published: May 2016

AbstractProtein complexes are major forms of protein-protein interactions and implement essential biological functions. The subunit interface in a protein complex is related to its thermostability. Though the roles of interface properties in thermal adaptation have been investigated for protein complexes, the relationship between the interface size and the expression level of the subunits remains unknown. In the present work, we studied this relationship and found a positive correlation in thermophiles rather than mesophiles. Moreover, we found that the protein interaction strength in complexes is not only temperature-dependent but also abundance-dependent. The underlying mechanism for the observed correlation was explored by simulating the evolution of protein interface stability, which highlights the avoidance of misinteraction. Our findings make more complete the picture of the mechanisms for protein complex thermal adaptation and provide new insights into the principles of protein-protein interactions.
Foxa2 and Hif1ab regulate maturation of intestinal goblet cells by modulating agr2 expression in zebrafish embryos
Authors: Lai Yun-Ren , Lu Yu-Fen , Lien Huang-Wei , Huang Chang-Jen , Hwang Sheng-Ping L. 
Published: May 2016

Mammalian anterior gradient 2 (AGR2), an endoplasmic reticulum (ER) protein disulfide-isomerase (PDI), is involved in cancer cell growth and metastasis, asthma and inflammatory bowel disease (IBD). Mice lacking Agr2 exhibit decreased Muc2 protein in intestinal goblet cells, abnormal Paneth cell development, ileitis and colitis. Despite its importance in cancer biology and inflammatory diseases, the mechanisms regulating agr2 expression in the gastrointestinal tract remain unclear. In the present study, we investigated the mechanisms that control agr2 expression in the pharynx and intestine of zebrafish by transient/stable transgenesis, coupled with motif mutation, morpholino knockdown, mRNA rescue and ChIP. A 350 bp DNA sequence with a hypoxia-inducible response element (HRE) and forkhead-response element (FHRE) within a region −4.5 to −4.2 kbp upstream of agr2 directed EGFP expression specifically in the pharynx and intestine. No EGFP expression was detected in the intestinal goblet cells of Tg(HREM:EGFP) or Tg(FHREM:EGFP) embryos with mutated HRE or FHRE, whereas EGFP was expressed in the pharynx of Tg(HREM:EGFP), but not Tg(FHREM:EGFP), embryos. Morpholino knockdown of foxa1 (forkhead box A1) reduced agr2 levels in the pharynx, whereas knockdown of foxa2 or hif1ab decreased intestinal agr2 expression and affected the differentiation and maturation of intestinal goblet cells. These results demonstrate that Foxa1 regulates agr2 expression in the pharynx, whereas both Foxa2 and Hif1ab control agr2 expression in intestinal goblet cells to regulate maturation of these cells.
Mutual coupling reduction between closely spaced microstrip antennas by means of H‐shaped conducting wall
Authors: Park C.‐H. , Son H.‐W. 
Published: May 2016

This Letter presents a novel H‐shaped conducting wall structure that effectively suppresses the mutual coupling between two closely spaced microstrip antennas (MSAs). The wall consists of an H‐shaped copper strip printed on a dielectric substrate, and a row of periodic vias through which the strip is connected to a ground plane. The wall is inserted between the MSAs and surrounds half the periphery of each antenna. Measurements of a prototype show that the high isolation of about 51 dB is achieved between two MSAs separated by the edge‐to‐edge distance of 0.052 λ0 at 5.2 GHz. The proposed structure greatly improves the isolation without causing any significant degradation of the antenna bandwidth, gain, or front‐to‐back ratio, unlike other isolation structures based on resonators or defected ground structures.
Molecular tandem repeat strategy for elucidating mechanical properties of high-strength proteins
Authors: Jung Huihun , Pena-Francesch Abdon , Saadat Alham , Sebastian Aswathy , Kim Dong Hwan , Hamilton Reginald F. , Albert Istvan , Allen Benjamin D. , Demirel Melik C. 
Published: May 2016

Significance
Squid have teeth-like structural [squid ring teeth (SRT)] proteins inside their suckers, which have segmented semicrystalline morphology with repetitive amorphous and crystalline domains. These proteins have high elastic modulus and toughness. However, a clear relationship between molecular structure and mechanical properties of this material remains elusive. To investigate the genetic basis of material properties in SRT sequences, we developed a new approach for the design and production of structural proteins. We show that the toughness and flexibility of these synthetic SRT mimics increase as a function of molecular weight, whereas the elastic modulus and yield strength remain unchanged. These results suggest that artificial proteins produced by our approach can help to illuminate the genetic basis of protein material behavior in SRT.
Single-cell twitching chemotaxis in developing biofilms
Authors: Oliveira Nuno M. , Foster Kevin R. , Durham William M. 
Published: May 2016

Significance
Bacterial biofilms affect many aspects of our lives, from causing disease to promoting health and shaping many key processes in the environment. Despite this, surface-attached cells in biofilms are often portrayed as static and sluggish, a stark contrast to the energetic swimming they exhibit in liquid. Here we use microfluidic devices and automated cell tracking to challenge this view: We find that individual cells will actively move toward nutrients within a developing biofilm. This ability not only allows cells to seek out favored positions on a surface but our analyses show that they can regulate their movement with remarkable submicron precision. Our findings suggest we can systematically engineer biofilms by manipulating the movement of the cells from which they are founded.
Cellular folding pathway of a metastable serpin
Authors: Chandrasekhar Kshama , Ke Haiping , Wang Ning , Goodwin Theresa , Gierasch Lila M. , Gershenson Anne , Hebert Daniel N. 
Published: May 2016

Significance
The activity of some proteins requires dramatic conformational movements. The ability to undergo these movements can be enabled by folding of these proteins to constrained higher free energy or metastable states. Metastable proteins are particularly susceptible to misfolding and are therefore associated with a number of pathologies. Here the cellular folding pathway of the serpin antithrombin III (ATIII), which inhibits proteases involved in the coagulation cascade, was determined. ATIII uses a large conformational movement in a mousetrap-like mechanism to bind and distort its target protease, resulting in protease inhibition. This work establishes that folding to an active, cocked state requires early stabilization of the C-terminal region, which is the last sequence translated, explaining how the serpin or mousetrap is set.
Analysis of complex neural circuits with nonlinear multidimensional hidden state models
Authors: Friedman Alexander , Slocum Alanna F. , Tyulmankov Danil , Gibb Leif G. , Altshuler Alex , Ruangwises Suthee , Shi Qinru , Toro Arana Sebastian E. , Beck Dirk W. , Sholes Jacquelyn E. C. , Graybiel Ann M. 
Published: May 2016

Significance
In analyzing complex networks, we are commonly interested in quantifying the influence that the network nodes exert on each other and in decoding the behavior of the network. We present the nonlinear multidimensional hidden state (NMHS) model, which addresses both of these unmet challenges by simultaneously decoding activity from parallel data streams and calculating the interaction strength among them. In NMHS models, each node in a network acts as a stochastic process that can influence the progression of other nodes in the network. We show that our procedure matches or outperforms state-of-the-art techniques in a multitude of scenarios, notably in systems with nonlinear interactions.
Zonal flow generation and its nonlinear dynamics in trapped electron mode turbulence of flat density tokamak plasmas
Authors: Guo Z.B. , Hahm T.S. 
Published: May 2016

Abstract
We investigate zonal flow (ZF) generation in ion temperature gradient driven trapped-electron-mode (ITG-driven TEM) turbulence via modulational instability analysis. We show that the acceleration of a seed ZF is a consequence of the competition of negative radiation pressure (NRP, acting as a driving force) and positive radiation pressure (PRP, acting as a retarding force) of the ITG-driven TEM turbulence. A critical dimensionless ion temperature logarithmic gradient (

R
/

L

T
i

,
c

) normalized to the major radius is obtained by balancing the NRP- and PRP effects. For

R

L

T
i

<

R

L

T
i

,
c

, the NRP effect is dominant and the seed ZF is accelerated. Otherwise, the PRP effect is dominant and the seed ZF is decelerated. In addition, a new nonlinear evolution mechanism of the ZF is also proposed. It is shown that the turbulence energy intensity spectrum gets steepened in k-space due to the ZF shearing, which in turn induces nonlinear growth of the ZF.
Terminating ₂𝐹₁(4)-series perturbed by two integer parameters
Authors: Chu Wenchang 
Published: May 2016

By means of generating functions and the linearization method, we establish analytical formulae for a class of terminating

2

F
1

(
4
)

_2F_1(4)

-series perturbed by two integer parameters. Under the Pfaff transformation, these formulae confirm, unexpectedly, a conjecture about evaluation of the

2

F
1

(
−
3
)

_2F_1(-3)

-series made by Apagodu and Zeilberger (2008).
Absolutely summing operators and atomic decomposition in bi-parameter Hardy spaces
Authors: Müller Paul , Penteker Johanna 
Published: May 2016

For

f
∈

H
p

(

δ
2

)

f \in H^p(\delta ^2)

,

0
>
p
≤
2

0>p\leq 2

, with Haar expansion

f
=
∑

f

I
×
J

h

I
×
J

f=\sum f_{I \times J}h_{I\times J}

we constructively determine the Pietsch measure of the

2
2

-summing multiplication operator
\[

M

f

:

ℓ

∞

→

H
p

(

δ
2

)
,

(

φ

I
×
J

)
↦
∑

φ

I
×
J

f

I
×
J

h

I
×
J

.

\mathcal {M}_f:\ell ^{\infty } \rightarrow H^p(\delta ^2), \quad (\varphi _{I\times J}) \mapsto \sum \varphi _{I\times J}f_{I \times J}h_{I \times J}.

\]
Our method yields a constructive proof of Pisier’s decomposition of

f
∈

H
p

(

δ
2

)

f \in H^p(\delta ^2)

\[

|

f

|

=

|

x

|

1
−
θ

|

y

|

θ

and

‖
x

‖

X
0

1
−
θ

‖
y

‖

H
2

(

δ
2

)

θ

≤
C
‖
f

‖

H
p

(

δ
2

)

,

|f|=|x|^{1-\theta }|y|^{\theta }\quad \quad \text { and }\quad \quad \|x\|_{X_0}^{1-\theta }\|y\|^{\theta }_{H^2(\delta ^2)}\leq C\|f\|_{H^p(\delta ^2)},

\]
where

X
0

X_0

is Pisier’s extrapolation lattice associated to

H
p

(

δ
2

)

H^p(\delta ^2)

and

H
2

(

δ
2

)

H^2(\delta ^2)

. Our construction of the Pietsch measure for the multiplication operator

M

f

\mathcal {M}_f

involves the Haar coefficients of

f
f

and its atomic decomposition. We treated the one-parameter

H
p

H^p

-spaces in Houston Journal Math. 41 (2015), 639–668.
Three-dimensional simulations of rapidly rotating core-collapse supernovae: finding a neutrino-powered explosion aided by non-axisymmetric flows
Authors: Takiwaki Tomoya , Kotake Kei , Suwa Yudai 
Published: May 2016

Abstract
We report results from a series of three-dimensional (3D) rotational core-collapse simulations for 11.2 and 27  M⊙ stars employing neutrino transport scheme by the isotropic diffusion source approximation. By changing the initial strength of rotation systematically, we find a rotation-assisted explosion for the 27 M⊙ progenitor , which fails in the absence of rotation. The unique feature was not captured in previous two-dimensional (2D) self-consistent rotating models because the growing non-axisymmetric instabilities play a key role. In the rapidly rotating case, strong spiral flows generated by the so-called low T/|W| instability enhance the energy transport from the proto-neutron star (PNS) to the gain region, which makes the shock expansion more energetic. The explosion occurs more strongly in the direction perpendicular to the rotational axis, which is different from previous 2D predictions.
Transcranial Doppler to Predict Neurologic Outcome after Mild to Moderate Traumatic Brain Injury
Authors: Bouzat Pierre , Almeras Luc , Manhes Pauline , Sanders Laurence , Levrat Albrice , David Jean-Stephane , Cinotti Raphael , Chabanne Russel , Gloaguen Aurélie , Bobbia Xavier , Thoret Sophie , Oujamaa Lydia , Bosson Jean-Luc , Payen Jean-François ,   for the TBI-TCD Study Investigators
Published: May 2016

Abstract

Background
To assess the performance of transcranial Doppler (TCD) in predicting neurologic worsening after mild to moderate traumatic brain injury.

Methods
The authors conducted a prospective observational study across 17 sites. TCD was performed upon admission in 356 patients (Glasgow Coma Score [GCS], 9 to 15) with mild lesions on cerebral computed tomography scan. Normal TCD was defined as a pulsatility index of less than 1.25 and diastolic blood flow velocity higher than 25 cm/s in the two middle cerebral arteries. The primary endpoint was secondary neurologic deterioration on day 7.

Results
Twenty patients (6%) developed secondary neurologic deterioration within the first posttraumatic week. TCD thresholds had 80% sensitivity (95% CI, 56 to 94%) and 79% specificity (95% CI, 74 to 83%) to predict neurologic worsening. The negative predictive values and positive predictive values of TCD were 98% (95% CI, 96 to 100%) and 18% (95% CI, 11to 28%), respectively. In patients with minor traumatic brain injury (GCS, 14 to 15), the sensitivity and specificity of TCD were 91% (95% CI, 59 to 100%) and 80% (95% CI, 75 to 85%), respectively. The area under the receiver operating characteristic curve of a multivariate predictive model including age and GCS was significantly improved with the adjunction of TCD. Patients with abnormal TCD on admission (n = 86 patients) showed a more altered score for the disability rating scale on day 28 compared to those with normal TCD (n = 257 patients).

Conclusions
TCD measurements upon admission may provide additional information about neurologic outcome after mild to moderate traumatic brain injury. This technique could be useful for in-hospital triage in this context. (Anesthesiology 2016; 125:346-54)
The Effect of Vancomycin and Gentamicin Antibiotics on Human Osteoblast Proliferation, Metabolic Function, and Bone Mineralization
Authors: Philp Ashleigh M. , Raja Saroop , Philp Andrew , Newton Ede Matthew P. , Jones Simon W. 
Published: May 2016

Study Design.
The present study investigates the effect of vancomycin and gentamicin antibiotics on primary human osteoblasts. Osteoblasts were incubated with vancomycin, gentamicin, or with povidone-iodine (PVI), at concentrations advocated for wound irrigation. Osteoblast proliferation, metabolic function, and bone mineralization were measured.

Objective.
The aim of the study was to model gentamicin and vancomycin wound irrigation in vitro and to examine the effect on osteoblast viability and cellular function in comparison to 0.35% PVI.

Summary of Background Data.
Vancomycin, gentamicin, and dilute PVI are employed as wound irrigants in spinal surgery to reduce infection. We have, however, recently demonstrated that 0.35% PVI has a detrimental effect on osteoblast cellular function and bone mineralization. Studies to determine the effects of antibiotic wound irrigation solutions on osteoblasts and bone mineralization are therefore warranted.

Methods.
Primary human osteoblasts were exposed for 20 minutes to phosphate buffered saline (PBS) control, vancomycin (35 or 3.5 mmol/L), gentamicin (34 or 3.4 mmol/L), or 0.35% PVI for 3 minutes. Cellular proliferation was measured during 7 days by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Osteoblast metabolic function was determined using a Seahorse XFe24 Bioanalyzer. Mineralized bone nodules were quantified using Alizarin red.

Results.
At concentrations advocated for wound irrigation, both gentamicin (3.4 mmol/L) and vancomycin (3.5 mmol/L) induced a transient 15% to 20% reduction in osteoblast proliferation, which returned to control values within 72 hours. This was in marked contrast to the effect of 0.35% PVI, which resulted in a sustained reduction in osteoblast proliferation of between 40% and 50% during 7 days. Neither gentamicin nor vancomycin at concentrations up to 10× clinical dose had any effect on osteoblast oxygen consumption rate, or significantly affected mineralized bone nodule formation.

Conclusion.
Vancomycin and gentamicin solutions, at concentrations advocated for intrawound application in spinal surgery, have a small but transient effect on osteoblast proliferation, and no effect on either osteoblast metabolic function or bone nodule mineralization.

Level of Evidence: N/A
Low-Grade Malignant Proliferating Tricholemmal Tumor Associated With Occult Ductal Carcinoma In Situ of the Breast
Authors: Lopez Jonathan J. , Chen Beiyun , Ghosh Karthik , Peters Margot S. 
Published: May 2016

Abstract:
Malignant proliferating tricholemmal tumor (MPTT) is a rare adnexal neoplasm most commonly located on the scalp. We a 62-year-old woman who presented to her local physician with a palpable but not visible nodule of the left breast, initially diagnosed as squamous cell carcinoma. Histopathological evaluation of the reexcision specimen incidentally revealed ductal carcinoma in situ. On referral to our institution, the skin biopsy specimen was reviewed and interpreted as a low-grade MPTT. This patient and 2 previously reported cases of MPTT involving breast skin highlight presentation of a rare tumor at an unusual site and the potential for misdiagnosis as squamous cell carcinoma. Reexcision provided the unexpected benefit for our patient of early diagnosis of ductal carcinoma in situ not revealed by imaging.