bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probabilistic Movement Models Show that Postural Control Precedes and Predicts Volitional Motor Control
Authors: Rueckert Elmar , Čamernik Jernej , Peters Jan , Babič Jan 
Published: June 2016

AbstractHuman motor skill learning is driven by the necessity to adapt to new situations. While supportive contacts are essential for many tasks, little is known about their impact on motor learning. To study the effect of contacts an innovative full-body experimental paradigm was established. The task of the subjects was to reach for a distant target while postural stability could only be maintained by establishing an additional supportive hand contact. To examine adaptation, non-trivial postural perturbations of the subjects’ support base were systematically introduced. A novel probabilistic trajectory model approach was employed to analyze the correlation between the motions of both arms and the trunk. We found that subjects adapted to the perturbations by establishing target dependent hand contacts. Moreover, we found that the trunk motion adapted significantly faster than the motion of the arms. However, the most striking finding was that observations of the initial phase of the left arm or trunk motion (100–400 ms) were sufficient to faithfully predict the complete movement of the right arm. Overall, our results suggest that the goal-directed arm movements determine the supportive arm motions and that the motion of heavy body parts adapts faster than the light arms.
Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis
Authors: Ačimovič Jure , Goyal Sandeep , Košir Rok , Goličnik Marko , Perše Martina , Belič Ales , Urlep Žiga , Guengerich F. Peter , Rozman Damjana 
Published: June 2016

AbstractCholesterol synthesis is among the oldest metabolic pathways, consisting of the Bloch and Kandutch-Russell branches. Following lanosterol, sterols of both branches are proposed to be dedicated to cholesterol. We challenge this dogma by mathematical modeling and with experimental evidence. It was not possible to explain the sterol profile of testis in cAMP responsive element modulator tau (Crem τ) knockout mice with mathematical models based on textbook pathways of cholesterol synthesis. Our model differs in the inclusion of virtual sterol metabolizing enzymes branching from the pathway. We tested the hypothesis that enzymes from the cytochrome P450 (CYP) superfamily can participate in the catalysis of non-classical reactions. We show that CYP enzymes can metabolize multiple sterols in vitro, establishing novel branching points of cholesterol synthesis. In conclusion, sterols of cholesterol synthesis can be oxidized further to metabolites not dedicated to production of cholesterol. Additionally, CYP7A1, CYP11A1, CYP27A1, and CYP46A1 are parts of a broader cholesterol synthesis network.
Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65
Authors: Liu Qingshi , Zhang Zhenfeng , Zheng Zhenhua , Zheng Caishang , Liu Yan , Hu Qinxue , Ke Xianliang , Wang Hanzhong 
Published: June 2016

AbstractHuman bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α–mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn’t interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis.
Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway
Authors: Kim Sun-Yong , Tachioka Yuka , Mori Tomoyuki , Hakoshima Toshio 
Published: June 2016

AbstractMOB1 protein is a key regulator of large tumor suppressor 1/2 (LATS1/2) kinases in the Hippo pathway. MOB1 is present in an autoinhibited form and is activated by MST1/2-mediated phosphorylation, although the precise mechanisms responsible for autoinhibition and activation are unknown due to lack of an autoinhibited MOB1 structure. Here, we report on the crystal structure of full-length MOB1B in the autoinhibited form and a complex between the MOB1B core domain and the N-terminal regulation (NTR) domain of LATS1. The structure of full-length MOB1B shows that the N-terminal extension forms a short β-strand, the SN strand, followed by a long conformationally flexible positively-charged linker and α-helix, the Switch helix, which blocks the LATS1 binding surface of MOB1B. The Switch helix is stabilized by β-sheet formation of the SN strand with the S2 strand of the MOB1 core domain. Phosphorylation of Thr12 and Thr35 residues structurally accelerates dissociation of the Switch helix from the LATS1-binding surface by the “pull-the-string” mechanism, thereby enabling LATS1 binding.
Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation
Authors: Chang Jae Won , Jung Seung-Nam , Kim Ju-Hee , Shim Geun-Ae , Park Hee Sung , Liu Lihua , Kim Jin Man , Park Jongsun , Koo Bon Seok 
Published: June 2016

AbstractThe exact regulatory mechanisms of carboxyl-terminal modulator protein (CTMP) and its downstream pathways in cancer have been controversial and are not completely understood. Here, we report a new mechanism of regulation of Akt serine/threonine kinase, one of the most important dysregulated signals in head and neck squamous cell carcinoma (HNSCC) by the CTMP pathway and its clinical implications. We find that HNSCC tumor tissues and cell lines had relatively high levels of CTMP expression. Clinical data indicate that CTMP expression was significantly associated with positive lymph node metastasis (OR = 3.8, P = 0.033) and correlated with poor prognosis in patients with HNSCC. CTMP was also positively correlated with Akt/GSK-3β phosphorylation, Snail up-regulation and E-cadherin down-regulation, which lead to increased proliferation and epithelial-to-mesenchymal transition, suggesting that CTMP expression results in enhanced tumorigenic and metastatic properties of HNSCC cells. Moreover, CTMP suppression restores sensitivity to cisplatin chemotherapy. Intriguingly, all the molecular responses to CTMP regulation are identical regardless of p53 status in HNSCC cells. We conclude that CTMP promotes Akt phosphorylation and functions as an oncogenic driver and prognostic marker in HNSCC irrespective of p53.
Distinct and developmentally regulated activity-dependent plasticity at descending glutamatergic synapses on flexor and extensor motoneurons
Authors: Lenschow Constanze , Cazalets Jean-René , Bertrand Sandrine S. 
Published: June 2016

AbstractActivity-dependent synaptic plasticity (ADSP) is paramount to synaptic processing and maturation. However, identifying the ADSP capabilities of the numerous synapses converging onto spinal motoneurons (MNs) remain elusive. Using spinal cord slices from mice at two developmental stages, 1–4 and 8–12 postnatal days (P1–P4; P8–P12), we found that high-frequency stimulation of presumed reticulospinal neuron axons in the ventrolateral funiculus (VLF) induced either an NMDA receptor-dependent-long-term depression (LTD), a short-term depression (STD) or no synaptic modulation in limb MNs. Our study shows that P1–P4 cervical MNs expressed the same plasticity profiles as P8–P12 lumbar MNs rather than P1–P4 lumbar MNs indicating that ADSP expression at VLF-MN synapses is linked to the rostrocaudal development of spinal motor circuitry. Interestingly, we observed that the ADSP expressed at VLF-MN was related to the functional flexor or extensor MN subtype. Moreover, heterosynaptic plasticity was triggered in MNs by VLF axon tetanisation at neighbouring synapses not directly involved in the plasticity induction. ADSP at VLF-MN synapses specify differential integrative synaptic processing by flexor and extensor MNs and could contribute to the maturation of spinal motor circuits and developmental acquisition of weight-bearing locomotion.
Pathway Analyses Identify Novel Variants in the WNT Signaling Pathway Associated with Tuberculosis in Chinese Population
Authors: Hu Xuejiao , Zhou Juan , Chen Xuerong , Zhou Yanhong , Song Xingbo , Cai Bei , Zhang Jingya , Lu Xiaojun , Ying Binwu 
Published: June 2016

AbstractTuberculosis remains a global public health problem, and its immunopathogenesis is still poorly understood. In this study, 25 single nucleotide polymorphisms (SNPs) in the WNT pathway were evaluated in relation to tuberculosis risk in a Chinese Han discovery set, and 6 candidate susceptible SNPs were further validated in a Chinese Tibetan cohort. Luciferase reporter assay, RT-qPCR and Western blot were used to assess the functionality of the important WNT polymorphisms. Five polymorphisms were associated with tuberculosis susceptibility after Bonferroni correction: SFRP1 rs4736958, CTNNB1 rs9859392, rs9870255 and rs3864004 showed decreased tuberculosis risk; SFRP1 rs7832767 was related to an increased risk (OR = 1.81, 95% CI = 1.30–2.52, p = 0.010). Patients with TT genotype of rs4736958 and rs7832767 correlated with higher CRP concentrations (p = 0.003, <0.001, respectively). Functional assays revealed that mutant alleles of rs9859392 (G), rs9870255 (C) and rs3864004 (A) were associated with significantly decreased transcriptional activity, lower CTNNB1 mRNA expression and p-β-catenin level, which were consistent with their effects of decreasing TB risk. Our results provide evidences that WNT pathway polymorphisms influence tuberculosis susceptibility and host immune response to Mycobacterium tuberculosis, suggesting that these variations may serve as novel markers for identifying the risk of developing tuberculosis.
7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndrome
Authors: Gou-Fàbregas Myriam , Macià Anna , Anerillas Carlos , Vaquero Marta , Jové Mariona , Jain Sanjay , Ribera Joan , Encinas Mario 
Published: June 2016

AbstractSmith-Lemli-Opitz syndrome (SLOS) is a rare disorder of cholesterol synthesis. Affected individuals exhibit growth failure, intellectual disability and a broad spectrum of developmental malformations. Among them, renal agenesis or hypoplasia, decreased innervation of the gut, and ptosis are consistent with impaired Ret signaling. Ret is a receptor tyrosine kinase that achieves full activity when recruited to lipid rafts. Mice mutant for Ret are born with no kidneys and enteric neurons, and display sympathetic nervous system defects causing ptosis. Since cholesterol is a critical component of lipid rafts, here we tested the hypothesis of whether the cause of the above malformations found in SLOS is defective Ret signaling owing to improper lipid raft composition or function. No defects consistent with decreased Ret signaling were found in newborn Dhcr7−/− mice, or in Dhcr7−/− mice lacking one copy of Ret. Although kidneys from Dhcr7−/− mice showed a mild branching defect in vitro, GDNF was able to support survival and downstream signaling of sympathetic neurons. Consistently, GFRα1 correctly partitioned to lipid rafts in brain tissue. Finally, replacement experiments demonstrated that 7-DHC efficiently supports Ret signaling in vitro. Taken together, our findings do not support a role of Ret signaling in the pathogenesis of SLOS.
Hydration Repulsion between Carbohydrate Surfaces Mediated by Temperature and Specific Ions
Authors: Chen Hsieh , Cox Jason R. , Ow Hooisweng , Shi Rena , Panagiotopoulos Athanassios Z. 
Published: June 2016

AbstractStabilizing colloids or nanoparticles in solution involves a fine balance between surface charges, steric repulsion of coating molecules and hydration forces against van der Waals attractions. At high temperature and electrolyte concentrations, the colloidal stability of suspensions usually decreases rapidly. Here, we report a new experimental and simulation discovery that the polysaccharide (dextran) coated nanoparticles show ion-specific colloidal stability at high temperature, where we observed enhanced colloidal stability of nanoparticles in CaCl2 solution but rapid nanoparticle-nanoparticle aggregation in MgCl2 solution. The microscopic mechanism was unveiled in atomistic simulations. The presence of surface bound Ca2+ ions increases the carbohydrate hydration and induces strongly polarized repulsive water structures beyond at least three hydration shells which is farther-reaching than previously assumed. We believe leveraging the binding of strongly hydrated ions to macromolecular surfaces represents a new paradigm in achieving absolute hydration and colloidal stability for a variety of materials, particularly under extreme conditions.
Calibration of pipeline ADC with pruned Volterra kernels
Authors: Centurelli F. , Monsurrò P. , Rosato F. , Ruscio D. , Trifiletti A. 
Published: June 2016

A Volterra model is used to calibrate a pipeline ADC simulated in Cadence Virtuoso using the STMicroelectronics CMOS 45 nm process. The ADC was designed to work at 50 MSps, but it is simulated at up to 125 MSps, proving that calibration using a Volterra model can significantly increase sampling frequency. Equivalent number of bits (ENOB) improves by 1–2.5 bits (6–15 dB) with 37–101 model parameters. The complexity of the calibration algorithm is reduced using different lengths for each Volterra kernels and performing iterative pruning. System identification is performed by least squares techniques with a set of sinusoids at different frequencies spanning the whole Nyquist band. A comparison with simplified Volterra models proposed in the literature shows better performance for the pruned Volterra model with comparable complexity, improving linearity by as much as 1.5 bits more than the other techniques.
Natural Habitat Conditions in a Captive Environment Lead to Spawning of Spotted Gar
Authors: Frenette Bryan D. , Snow Richard 
Published: June 2016

AbstractGars are often spawned by means of hormone injection for aquaculture purposes, but unassisted captive spawning is less common. In May of 2014, Spotted Gars Lepisosteus oculatus spawned while being held in a large research pond at the University of Oklahoma's Aquatic Research Facility. Holding conditions were similar to natural conditions required for these fish to reproduce, and viable offspring were produced. The Spotted Gar is a species of conservation concern at the periphery of its range and can benefit from studies describing aspects of its biology. This description of captive gar spawning may have important implications for both aquaculture and restoration efforts.Received October 28, 2015; accepted March 8, 2016 Published online June 22, 2016
Dualising activation. Responses to unemployment and mental health-related disability retirement in Finland at the turn of the millennium
Authors: Alanko Anna , Outinen Sami 
Published: June 2016

ABSTRACT
‘Activation’, referring to measures that increase the labour supply, has recently been a key concept in discussing employment in the developed countries. This paper analyses the motivations behind activation measures targeted at the unemployed as well as persons disabled due to mental health problems, as expressed through legislation and national policy documents following the 1990s recession in Finland. The analysis points out that the activation measures implemented in Finland at the turn of the millennium have had a tendency to reinforce ‘dualisation’, that is, to polarise citizens as either labour market insiders or outsiders. The analysis shows that activation also involves labels that fix blame on the people themselves for their situation. Hence, the activation measures have increased the risk of exclusion for many of the persons they were supposed to help. The results are discussed in the context of the broader literature on the Nordic welfare and labour market model.
Integrative review of clinical decision support for registered nurses in acute care settings
Authors: Dunn Lopez Karen , Gephart Sheila M , Raszewski Rebecca , Sousa Vanessa , Shehorn Lauren E , Abraham Joanna 
Published: June 2016

Objective: To report on the state of the science of clinical decision support (CDS) for hospital bedside nurses.
Materials and Methods: We performed an integrative review of qualitative and quantitative peer-reviewed original research studies using a structured search of PubMed, Embase, Cumulative Index to Nursing and Applied Health Literature (CINAHL), Scopus, Web of Science, and IEEE Xplore (Institute of Electrical and Electronics Engineers Xplore Digital Library). We included articles that reported on CDS targeting bedside nurses and excluded in stages based on rules for titles, abstracts, and full articles. We extracted research design and methods, CDS purpose, electronic health record integration, usability, and process and patient outcomes.
Results: Our search yielded 3157 articles. After removing duplicates and applying exclusion rules, 28 articles met the inclusion criteria. The majority of studies were single-site, descriptive or qualitative (43%) or quasi-experimental (36%). There was only 1 randomized controlled trial. The purpose of most CDS was to support diagnostic decision-making (36%), guideline adherence (32%), medication management (29%), and situational awareness (25%). All the studies that included process outcomes (7) and usability outcomes (4) and also had analytic procedures to detect changes in outcomes demonstrated statistically significant improvements. Three of 4 studies that included patient outcomes and also had analytic procedures to detect change showed statistically significant improvements. No negative effects of CDS were found on process, usability, or patient outcomes.
Discussion and Conclusions: Clinical support systems targeting bedside nurses have positive effects on outcomes and hold promise for improving care quality; however, this research is lagging behind studies of CDS targeting medical decision-making in both volume and level of evidence.
Significant Differences Between Local Reporting and Central Assessment of Radiographic Complications in a Prospective, Multicenter Study About Locking Plate Fixation of Proximal Humerus Fractures
Authors: Kathrein Susanne , Joeris Alexander , Kralinger Franz , Blauth Michael , Goldhahn Joerg 
Published: June 2016

Objectives:
To compare reporting outcomes of radiographic complications conducted by an independent review board and the responsible on-site study personnel in a multicenter study about locking plate fixation of proximal humeral fractures.

Design:
Prospective, multicenter study; setting: 9 level I trauma centers.

Patients:
One hundred fifty patients (age 50–90) with a radiographically confirmed displaced proximal humeral fracture fixed with a locking plate were included in the study.

Intervention:
All radiographic data were reevaluated by an independent review board according to predefined criteria.

Main Outcome Measurements:
Differences in outcomes between the review board and the on-site assessment were analyzed with a paired t test. Interrater agreements between the central review board and on-site assessments were estimated by means of kappa statistics.

Results:
The review board revealed significantly more radiographic complications than the on-site assessment (P = 0.006), except for the complication “head necrosis.” The interrater agreement was slight to moderate in all calculated categories.

Conclusions:
Implementation of a complication review board using predefined criteria is recommended for clinical studies to prevent underreporting of radiographic complications by on-site assessment.
Whole-body vibration improves neuromuscular parameters and functional capacity in osteopenic postmenopausal women
Authors: Dutra Milena C. , de Oliveira Mônica L. , Marin Rosangela V. , Kleine Hellen C.R. , Silva Orivaldo L. , Lazaretti-Castro Marise 
Published: June 2016

Abstract

Objective:
In this longitudinal, paired-control study, we developed special vibration platforms to evaluate the effects of low-intensity vibration on neuromuscular function and functional capacity in osteopenic postmenopausal women.

Methods:
Women in the platform group (PG; n = 62) stood still and barefoot on the platform for 20 minutes, 5 times a week for 12 months. Each platform vibrated with a frequency of 60 Hz, intensity of 0.6g, and amplitude of less than 1 mm. Women in the control group (CG; n = 60) were followed up and instructed not to modify their physical activity during the study. Every 3 months all volunteers were invited to a visit to check for any change in their lifestyle. Assessments were performed at baseline and at 12 months, and included isometric muscle strength in the hip flexors and back extensors, right handgrip strength, dynamic upper limb strength (arm curl test), upper trunk flexibility (reach test [RT]), mobility (timed up and go test), and static balance (unipedal stance test). Statistical analyses were performed using the intention-to-treat strategy.

Results:
Both groups were similar for all variables at baseline. At the end of intervention, the PG was significantly better than CG in all parameters but in the RT. When compared with baseline, after 12 months of vibration the PG presented statistically significant improvements in isometric and dynamic muscle strength in the hip flexors (+36.7%), back extensors (+36.5%), handgrip strength (+4.4%), arm curl test (+22.8%), RT (+9.9%), unipedal stance test (+6.8%), and timed up and go test (−9.2%), whereas the CG showed no significant differences during the same period of time. As such, there were no side effects related to the study procedures during the 12 months of intervention.

Conclusions:
Low-intensity vibration improved balance, motility, and muscle strength in the upper and lower limbs in postmenopausal women.
Three-dimensional printing and pediatric liver disease
Authors: Alkhouri Naim , Zein Nizar N. 
Published: June 2016

Purpose of review
Enthusiastic physicians and medical researchers are investigating the role of three-dimensional printing in medicine. The purpose of the current review is to provide a concise summary of the role of three-dimensional printing technology as it relates to the field of pediatric hepatology and liver transplantation.

Recent findings
Our group and others have recently demonstrated the feasibility of printing three-dimensional livers with identical anatomical and geometrical landmarks to the native liver to facilitate presurgical planning of complex liver surgeries. Medical educators are exploring the use of three-dimensional printed organs in anatomy classes and surgical residencies. Moreover, mini-livers are being developed by regenerative medicine scientist as a way to test new drugs and, eventually, whole livers will be grown in the laboratory to replace organs with end-stage disease solving the organ shortage problem.

Summary
From presurgical planning to medical education to ultimately the bioprinting of whole organs for transplantation, three-dimensional printing will change medicine as we know in the next few years.