bluuebunny/crossref_metadata_2025 huggingface dataset:
Does exercise increase or decrease pain? Central mechanisms underlying these two phenomena
Authors: Lima Lucas V. , Abner Thiago S. S. , Sluka Kathleen A.
Published: March 2017

Exercise is an integral part of the rehabilitation of patients suffering a variety of chronic musculoskeletal conditions, such as fibromyalgia, chronic low back pain and myofascial pain. Regular physical activity is recommended for treatment of chronic pain and its effectiveness has been established in clinical trials for people with a variety of pain conditions. However, exercise can also increase pain making participation in rehabilitation challenging for the person with pain. Animal models of exercise‐induced pain have been developed and point to central mechanisms underlying this phenomena, such as increased activation of NMDA receptors in pain‐modulating areas. Meanwhile, a variety of basic science studies testing different exercise protocols, show exercise‐induced analgesia involves activation of central inhibitory pathways. Opioid, serotonin and NMDA mechanisms acting in rostral ventromedial medulla promote analgesia associated with exercise. This review explores and discusses current evidence on central mechanisms underlying exercised‐induced pain and analgesia.

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Potential motivational information encoded within humpback whale non-song vocal sounds
Authors: Dunlop Rebecca A
Published: March 2017

Acoustic signals in terrestrial animals follow motivational-structural rules to inform receivers of the signaler's motivational state, valence and level of arousal. Low-frequency “harsh” signals are produced in aggressive contexts, whereas high-frequency tonal sounds are produced in fearful/appeasement contexts. Using the non-song social call catalogue of humpback whales (Megaptera novaeangliae), this study tested for potential motivational-structural rules within the call catalogue of a baleen whale species. A total of 32 groups within different social contexts (ranging from stable, low arousal groups, such as a female with her calf, to affiliating, higher arousal, groups containing multiple males competing for access to the central female) were visually and acoustically tracked as they migrated southwards along the eastern coast of Australia. Social calls separated into four main cluster types, with signal structures in two categories consistent with “aggressive” signals and, “fearful/appeasement” signals in terrestrial animals. The group's use of signals within these clusters matched their context in that presumed low arousal non-affiliating groups almost exclusively used “low-arousal” signals (a cluster of low frequency unmodulated or upsweep sounds). Affiliating groups used a higher proportion of an intermediate cluster of signal types deemed “higher arousal” signals and groups containing three or more adults used a higher proportion of “aggressive” signal types.
The neural substrates of super memory
Authors: Dzirasa Kafui
Published: March 2017

Specific neural networks support superior memory in world-class memory athletes.
The
N
-Acetylmuramic Acid 6-Phosphate Phosphatase MupP Completes the
Pseudomonas
Peptidoglycan Recycling Pathway Leading to Intrinsic Fosfomycin Resistance
Authors: Borisova Marina , Gisin Jonathan , Mayer Christoph
Published: March 2017

Bacterial cells are encased in and stabilized by a netlike peptidoglycan (PGN) cell wall that undergoes turnover during bacterial growth. PGN turnover fragments are frequently salvaged by the cells via a pathway referred to as PGN recycling. Two different routes for the recycling of the cell wall sugar
N
-acetylmuramic acid (MurNAc) have been recognized in bacteria. In
Escherichia coli
and related enterobacteria, as well as in most Gram-positive bacteria, MurNAc is recovered via a catabolic route requiring a MurNAc 6-phosphate etherase (MurQ in
E. coli
) enzyme. However, many Gram-negative bacteria, including
Pseudomonas
species, lack a MurQ ortholog and use an alternative, anabolic recycling route that bypasses the
de novo
biosynthesis of uridyldiphosphate (UDP)-MurNAc, the first committed precursor of PGN. Bacteria featuring the latter pathway become intrinsically resistant to the antibiotic fosfomycin, which targets the
de novo
biosynthesis of UDP-MurNAc. We report here the identification and characterization of a phosphatase enzyme, named MupP, that had been predicted to complete the anabolic recycling pathway of
Pseudomonas
species but has remained unknown so far. It belongs to the large haloacid dehalogenase family of phosphatases and specifically converts MurNAc 6-phosphate to MurNAc. A Δ
mupP
mutant of
Pseudomonas putida
was highly susceptible to fosfomycin, accumulated large amounts of MurNAc 6-phosphate, and showed lower levels of UDP-MurNAc than wild-type cells, altogether consistent with a role for MupP in the anabolic PGN recycling route and as a determinant of intrinsic resistance to fosfomycin.

IMPORTANCE
Many Gram-negative bacteria, but not
E. coli
, make use of a cell wall salvage pathway that contributes to the pool of UDP-MurNAc, the first committed precursor of cell wall synthesis in bacteria. This salvage pathway is of particular interest because it confers intrinsic resistance to the antibiotic fosfomycin, which blocks
de novo
UDP-MurNAc biosynthesis. Here we identified and characterized a previously missing enzyme within the salvage pathway, the MurNAc 6-phosphate phosphatase MupP of
P. putida
. MupP, together with the other enzymes of the anabolic recycling pathway, AnmK, AmgK, and MurU, yields UDP-MurNAc, renders bacteria intrinsically resistant to fosfomycin, and thus may serve as a novel drug target for antimicrobial therapy.
Mouse Mammary Tumor Virus Signal Peptide Uses a Novel p97-Dependent and Derlin-Independent Retrotranslocation Mechanism To Escape Proteasomal Degradation
Authors: Byun Hyewon , Das Poulami , Yu Houqing , Aleman Alejandro , Lozano Mary M. , Matouschek Andreas , Dudley Jaquelin P.
Published: March 2017

Multiple pathogens, including viruses and bacteria, manipulate endoplasmic reticulum-associated degradation (ERAD) to avoid the host immune response and promote their replication. The betaretrovirus mouse mammary tumor virus (MMTV) encodes Rem, which is a precursor protein that is cleaved into a 98-amino-acid signal peptide (SP) and a C-terminal protein (Rem-CT). SP uses retrotranslocation for ER membrane extraction and yet avoids ERAD by an unknown mechanism to enter the nucleus and function as a Rev-like protein. To determine how SP escapes ERAD, we used a ubiquitin-activated interaction trap (UBAIT) screen to trap and identify transient protein interactions with SP, including the ERAD-associated p97 ATPase, but not E3 ligases or Derlin proteins linked to retrotranslocation, polyubiquitylation, and proteasomal degradation of extracted proteins. A dominant negative p97 ATPase inhibited both Rem and SP function. Immunoprecipitation experiments indicated that Rem, but not SP, is polyubiquitylated. Using both yeast and mammalian expression systems, linkage of a ubiquitin-like domain (UbL) to SP or Rem induced degradation by the proteasome, whereas SP was stable in the absence of the UbL. ERAD-associated Derlin proteins were not required for SP activity. Together, these results suggested that Rem uses a novel p97-dependent, Derlin-independent retrotranslocation mechanism distinct from other pathogens to avoid SP ubiquitylation and proteasomal degradation.

IMPORTANCE
Bacterial and viral infections produce pathogen-specific proteins that interfere with host functions, including the immune response. Mouse mammary tumor virus (MMTV) is a model system for studies of human complex retroviruses, such as HIV-1, as well as cancer induction. We have shown that MMTV encodes a regulatory protein, Rem, which is cleaved into an N-terminal signal peptide (SP) and a C-terminal protein (Rem-CT) within the endoplasmic reticulum (ER) membrane. SP function requires ER membrane extraction by retrotranslocation, which is part of a protein quality control system known as ER-associated degradation (ERAD) that is essential to cellular health. Through poorly understood mechanisms, certain pathogen-derived proteins are retrotranslocated but not degraded. We demonstrate here that MMTV SP retrotranslocation from the ER membrane avoids degradation through a unique process involving interaction with cellular p97 ATPase and failure to acquire cellular proteasome-targeting sequences.
Plasmodium falciparum Maf1
Confers Survival upon Amino Acid Starvation
Authors: McLean Kyle Jarrod , Jacobs-Lorena Marcelo
Published: March 2017

The target of rapamycin complex 1 (
TORC1
) pathway is a highly conserved signaling pathway across eukaryotes that integrates nutrient and stress signals to regulate the cellular growth rate and the transition into and maintenance of dormancy. The majority of the pathway’s components, including the central
TOR
kinase, have been lost in the apicomplexan lineage, and it is unknown how these organisms detect and respond to nutrient starvation in its absence.
Plasmodium falciparum
encodes a putative ortholog of the RNA polymerase (Pol) III repressor
Maf1
, which has been demonstrated to modulate Pol III transcription in a TOR-dependent manner in a number of organisms. Here, we investigate the role of
P. falciparum Maf1
(
PfMaf1
) in regulating RNA Pol III expression under conditions of nutrient starvation and other stresses. Using a transposon insertion mutant with an altered
Maf1
expression profile, we demonstrated that proper
Maf1
expression is necessary for survival of the dormancy-like state induced by prolonged amino acid starvation and is needed for full recovery from other stresses that slow or stall the parasite cell cycle. This
Maf1
mutant is defective in the downregulation of pre-tRNA synthesis under nutrient-limiting conditions, indicating that the function of
Maf1
as a stress-responsive regulator of structural RNA transcription is conserved in
P. falciparum
. Recent work has demonstrated that parasites carrying artemisinin-resistant
K13
alleles display an enhanced ability to recover from drug-induced growth retardation. We show that one such artemisinin-resistant line displays greater regulation of pre-tRNA expression and higher survival upon prolonged amino acid starvation, suggesting that overlapping,
Pf
Maf1-associated pathways may regulate growth recovery from both artemisinin treatment and amino acid starvation.

IMPORTANCE
Eukaryote organisms sense changes in their environment and integrate this information through signaling pathways to activate response programs to ensure survival. The
TOR
pathway is a well-studied signaling pathway found throughout eukaryotes that is known to integrate a variety of signals to regulate organismal growth in response to starvation and other stresses. The human malaria parasite
Plasmodium falciparum
appears to have lost the
TOR
pathway over the course of evolution, and it is unclear how the parasite modulates its growth in response to starvation and drug treatment. Here, we show that Maf1, a protein regulated by
TOR
in other eukaryotes, plays an important role in maintaining the parasite’s viability in the face of starvation and other forms of stress. This suggests that
PfMaf1
is a component of a yet-to-be-described nutrient and stress response pathway.
Cause of death and potentially avoidable deaths in Australian adults with intellectual disability using retrospective linked data
Authors: Trollor Julian , Srasuebkul Preeyaporn , Xu Han , Howlett Sophie
Published: March 2017

Objectives

To investigate mortality and its causes in adults over the age of 20 years with intellectual disability (ID).

Design, setting and participants

Retrospective population-based standardised mortality of the ID and Comparison cohorts. The ID cohort comprised 42 204 individuals who registered for disability services with ID as a primary or secondary diagnosis from 2005 to 2011 in New South Wales (NSW). The Comparison cohort was obtained from published deaths in NSW from the Australian Bureau of Statistics (ABS) from 2005 to 2011.

Main outcome measures

We measured and compared Age Standardised Mortality Rate (ASMR), Comparative Mortality Figure (CMF), years of productive life lost (YPLL) and proportion of deaths with potentially avoidable causes in an ID cohort with an NSW general population cohort.

Results

There were 19 362 adults in the ID cohort which experienced 732 (4%) deaths at a median age of 54 years. Age Standardised Mortality Rates increased with age for both cohorts. Overall comparative mortality figure was 1.3, but was substantially higher for the 20–44 (4.0) and 45–64 (2.3) age groups. YPLL was 137/1000 people in the ID cohort and 49 in the comparison cohort. Cause of death in ID cohort was dominated by respiratory, circulatory, neoplasm and nervous system. After recoding deaths previously attributed to the aetiology of the disability, 38% of deaths in the ID cohort and 17% in the comparison cohort were potentially avoidable.

Conclusions

Adults with ID experience premature mortality and over-representation of potentially avoidable deaths. A national system of reporting of deaths in adults with ID is required. Inclusion in health policy and services development and in health promotion programmes is urgently required to address premature deaths and health inequalities for adults with ID.
Comparison of the therapeutic dose of warfarin in HIV-infected and HIV-uninfected patients: a study of clinical practice
Authors: Jackson B S , Mokoena T
Published: March 2017

Background

People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients.

Methods

A prospective and retrospective descriptive study of induction time to therapeutic warfarin dose, as well as of ambulant therapeutic warfarin dose, was performed. HIV-infected and HIV-uninfected patients being treated after deep venous thrombosis with or without pulmonary embolism were compared. Sex and use of antiretroviral drugs (ARVs) were also compared in the groups.

Results

234 patients were entered into the study. Induction time to therapeutic warfarin dose did not differ between the 2 groups. The mean therapeutic dose of warfarin was higher in the HIV-infected than the HIV-uninfected group: 6.06 vs 5.72 mg/day, but this was not statistically significant (p=0.29). There was no difference in therapeutic warfarin dose between ARV-naïve groups—HIV-uninfected and HIV-infected patients not on ARVs.

Conclusions

There appears to be little effect of HIV infection on warfarin dosing. Warfarin therapy should be administered conventionally in HIV-infected patients.
Green shoots of recovery: a realist evaluation of a team to support change in general practice
Authors: Bartlett Maggie , Basten Ruth , McKinley Robert K
Published: March 2017

Objective

A multidisciplinary support team for general practice was established in April 2014 by a local National Health Service (NHS) England management team. This work evaluates the team's effectiveness in supporting and promoting change in its first 2 years, using realist methodology.

Setting

Primary care in one area of England.

Participants

Semistructured interviews were conducted with staff from 14 practices, 3 key senior NHS England personnel and 5 members of the support team. Sampling of practice staff was purposive to include representatives from relevant professional groups.

Intervention

The team worked with practices to identify areas for change, construct action plans and implement them. While there was no specified timescale for the team's work with practices, it was tailored to each.

Primary and secondary outcome measures

In realist evaluations, outcomes are contingent on mechanisms acting in contexts, and both an understanding of how an intervention leads to change in a socially constructed system and the resultant changes are outcomes.

Results

The principal positive mechanisms leading to change were the support team's expertise and its relationships with practice staff. The ‘external view’ provided by the team via its corroborative and normalising effects was an important mechanism for increasing morale in some practice contexts. A powerful negative mechanism was related to perceptions of ‘being seen as a failing practice’ which included expressions of ‘shame’. Outcomes for practices as perceived by their staff were better communication, improvements in patients' access to appointments resulting from better clinical and managerial skill mix, and improvements in workload management.

Conclusions

The support team promoted change within practices leading to signs of the ‘green shoots of recovery’ within the time frame of the evaluation. Such interventions need to be tailored and responsive to practices' needs. The team's expertise and relationships between team members and practice staff are central to success.
The value of museums in the production, sharing, and use of entomological data to document hyperdiversity of the changing North
Authors: Sikes Derek S. , Bowser Matthew , Daly Kathryn , Høye Toke T. , Meierotto Sarah , Mullen Logan , Slowik Jozef , Stockbridge Jill
Published: March 2017

If the current rate of climate change continues, the composition, distribution, and relative population sizes of species in the higher latitudes of the Northern Hemisphere are likely to change considerably. Understanding the magnitude of this change requires a well- documented baseline against which to compare. Although specimen-less observations can help augment such a baseline for the minority of organisms that can be confidently identified in the field or from photographs, the vast majority of species are small-bodied invertebrates, primarily arthropods, that can only be identified from preserved specimens and (or) their tissues. Museum staff archive specimens and make them and their data available for research. This paper describes a number of challenges to the goal of thorough documentation of high-latitude arthropod biodiversity and their potential solutions. Examples are provided from ongoing and recently completed research that demonstrates the value of museum specimens and the sharing of their data via global portals like GBIF.org.
Demand Forecasting and Pricing Decision with the Entry of Store Brand under Various Information Sharing Scenarios
Authors: Zhang Ting , Zhu Xiaowei , Gou Qinglong
Published: March 2017

In this research, we discuss three different approaches to generate demand forecasting and pricing decision for mix of national brand and store brand products in the era of big data. We derive the equilibrium wholesale price and retail price for the national brand products, and the equilibrium retail price for the store brand products based on demand forecast under three different information scenarios, including Noninformation Sharing ([Formula: see text]), Information Sharing ([Formula: see text]), and Retailer Forecasting ([Formula: see text]). We comprehensively discuss how information collection, information sharing, forecast accuracy under era of big data affect firms’ prices and profits. Our numerical experiments illustrate and verify our analytical findings and provide further managerial insights and interpretations.
The molecular dynamics simulation on the mechanical properties of Ni glass with external pressure
Authors: Zhang Chuan-Hui , Wang Ying , Sun Dong-Bai
Published: March 2017

In this paper, rapid quenching of Ni from crystal to metallic glass (MG) at different external pressures is simulated by molecular dynamics. The pair distribution functions (PDFs), mean-square displacement, glass transition temperature ([Formula: see text]) and elastic property are calculated and compared with each other. The split of the second PDF peak means the liquid’s transition to glass state starts as previously reported for other MGs. And the [Formula: see text] ratio rule is found to hold very well in Ni MG and reveals the SPO structural feature in the configurations. Moreover, with high external pressure, [Formula: see text] values are more approximated by density–temperature and enthalpy–temperature curves. At last, the elastic modulus and mechanics modulus of quenching models produced a monotonous effect with increasing external pressure and temperature.
The Lévy noise-induced current reversal phenomenon for self-propelled particles in a two-dimensional potential
Authors: Wang Bing , Qu Zhongwei , Li Xuechao , Ma Jianli
Published: March 2017

Effects of Lévy noise on self-propelled particles in a two-dimensional potential is investigated. The current reversal phenomenon appears in the system. [Formula: see text] ([Formula: see text]-direction average velocity) changes from negative to positive with increasing asymmetry parameter [Formula: see text], and changes from positive to negative with increasing self-propelled velocity [Formula: see text]. [Formula: see text] has a maximum with increasing modulation constant [Formula: see text].
A Digital Linear-Switching Hybrid Power Amplifier for Envelope Tracking Hybrid Supply Modulators
Authors: Salimi Atefeh , Dehghani Rasoul , Nabavi Abdolreza
Published: March 2017

A novel envelope modulator for envelope tracking RF power amplifier (PA) is presented in this paper. The proposed modulator consists of a parallel combination of analog class AB and digitally controlled hybrid PAs. The analog and digital class AB PAs are effective in both reducing the clock frequency and also static power dissipation, thus improving the efficiency of the modulator. On the other hand, lower clock frequencies result in simpler and more power-efficient digital to analog converters required in the architecture. The modulator digital block is evaluated with a 45[Formula: see text]nm CMOS technology. The overall power consumption of the digital block is around 76[Formula: see text]mW at 800[Formula: see text]MHz clock frequency. As an application, the designed digital block is incorporated in a complete envelope modulator architecture. The overall efficiency of the modulator, including the digital block power consumption, is around 80.7% at an average 32[Formula: see text]dBm output power for a 5[Formula: see text]MHz input signal.
Exact Solutions of Fully Nonstationary Random Vibration for Rectangular Kirchhoff Plates Using Discrete Analytical Method
Authors: Yang Dixiong , Chen Guohai , Zhou Jilei
Published: March 2017

This paper proposes the discrete analytical method (DAM) to determine exactly and efficiently the fully nonstationary random responses of rectangular Kirchhoff plates under temporally and spectrally nonstationary acceleration excitation of earthquake ground motions. First, the fully nonstationary power spectral density (PSD) model is suggested by replacing the filtered frequency and damping of Gaussian filtered white-noise model with the time-variant ones. The exact solutions of free vibration of thin plates with two opposite edges simply supported boundary conditions are introduced. Then, the full analytical procedure for random vibration analysis of the plate is established by using a pseudo excitation method (PEM) that can consider all modal auto-correlation and cross-correlation terms. Owing to involving a series of Duhamel time integrals of single degree of freedom systems, it is difficult to fully analytically evaluate the PSD of time-variant responses such as the transverse deflection, velocity, acceleration and stress components. Thus, DAM that combines the PEM with precise integration technique is developed to enhance the computational efficiency. Finally, comparison of the results by the DAM with Monte Carlo simulations and the analytical stationary random vibration analysis demonstrates the high efficiency and accuracy of DAM. Moreover, the fully nonstationary excitation imposes a remarkable effect on the response PSD of rectangular Kirchhoff plates.
Flutter Instability of Cracked Rotating Non-Uniform Beams Subjected to Distributed Follower Force
Authors: Karimi-Nobandegani A. , Fazelzadeh S. A. , Ghavanloo E.
Published: March 2017

In this paper, the effect of an open edge crack on the instability of rotating non-uniform beams subjected to uniform distributed tangential compressive load is studied. The local stiffness due to the presence of crack is considered in the global stiffness matrix of the structure using the finite element method. The cracked beam element is modeled as two equal sub-beam elements connected by a massless rotational spring. Based on the fracture mechanics, the strain energy release rate and the stress intensity factors are employed to investigate the stiffness of the rotational spring. Then, the modified shape functions are developed to reflect the crack stiffness in the finite element analysis. To validate the accuracy of the finite element model and results obtained, comparisons have been made between the results obtained and those available in the literature. The effects of several parameters, including the linear and nonlinear thickness variations, angular velocity, crack location and size, on the instability of cracked rotating non-uniform cantilevers are also examined. The results show that the location of crack significantly influences the critical magnitude of the follower force that destabilizes the cantilevers. In addition, geometric non-uniformity reduces the stability of the cracked cantilevers. For the same amount of cantilever mass, different patterns of mass distribution result in different stability diagrams.
Extreme Events, Critical Infrastructures, Human Vulnerability and Strategic Planning: Emerging Research Issues
Authors: Birkmann Joern , Wenzel Friedemann , Greiving Stefan , Garschagen Matthias , Vallée Dirk , Nowak Wolfgang , Welle Torsten , Fina Stefan , Goris Anna , Rilling Benedikt , Fiedrich Frank , Fekete Alexander , Cutter Susan L. , Düzgün Sebnem , Ley Astrid , Friedrich Markus , Kuhlmann Ulrike , Novák Balthasar , Wieprecht Silke , Riegel Christoph , Thieken Annegret , Rhyner Jakob , Ulbrich Uwe , Mitchell James K.
Published: March 2017

The importance of critical infrastructures and strategic planning in the context of extreme events, climate change and urbanization has been underscored recently in international policy frameworks, such as the Sustainable Development Goals (SDGs), the Sendai Framework for Disaster Risk Reduction 2015–2030 (UNISDR (United Nations/International Strategy for Disaster Risk Reduction) 2015), and the new Paris climate agreement (UNFCCC (United Nations — Framework Convention on Climate Change) 2015) as well as the New Urban Agenda (UN-HABITAT 2016). This paper outlines key research challenges in addressing the nexus between extreme weather events, critical infrastructure resilience, human vulnerability and strategic planning. Using a structured expert dialogue approach (particularly based on a roundtable discussion funded by the German National Science Foundation (DFG)), the paper outlines emerging research issues in the context of extreme events, critical infrastructures, human vulnerability and strategic planning, providing perspectives for inter- and transdisciplinary research on this important nexus. The main contribution of the paper is a compilation of identified research gaps and needs from an interdisciplinary perspective including the lack of integration across subjects and mismatches between different concepts and schools of thought.
Novel contrast mixture improves bladder wall contrast for visualizing bladder injury
Authors: Tyagi Pradeep , Janicki Joseph J. , Hitchens T. Kevin , Foley Lesley M. , Kashyap Mahendra , Yoshimura Naoki , Kaufman Jonathan
Published: March 2017

Here, we tested whether combined contrast-enhanced magnetic resonance imaging (CCE-MRI), using a mixture of gadolinium- and iron oxide-based contrast agents, can segment the bladder wall from the bladder lumen. CCE-MRI relies on the differences in particle size and contrast mechanisms of two agents for improved image contrast. Under isoflurane anesthesia, T1-weighted imaging of adult female Sprague-Dawley rat bladder was performed using standard turbospin echo sequences at 7 Tesla, before and after transurethral instillation of 0.3 ml of single-contrast MRI or CCE-MRI composed of 0.4–64 mM of gadolinium chelate (Gd-DTPA/Gadavist) and 5 mM ferumoxytol. Bladder wall contrast was assessed in the control group exposed to saline and in the bladder injury group exposed to 0.5 ml of protamine sulfate (10 mg/ml) for 30 min. CCE-MRI following instillation of 0.4–4 mM Gd-DTPA and 5 mM ferumoxytol mixture achieved segmentation between the bladder lumen and bladder wall. Hyperintensity in the bladder wall combined with hypointensity in the lumen is consistent with the increased diffusion of the dissolved Gd-DTPA and simultaneous localization of the larger nanoparticles of ferumoxytol in the lumen. The normalized hyperintense signal in the bladder wall increased from 0.46 ± 0.07 in control group to 0.73 ± 0.14 in the protamine sulfate-exposed group ( P < 0.0001). CCE-MRI following instillation of contrast mixture identifies bladder wall changes likely associated with bladder injury with improved image contrast.
Urinary DcR2 is a novel biomarker for tubulointerstitial injury in patients with diabetic nephropathy
Authors: Chen Jia , Zhang Wei-Wei , Chen Ke-Hong , Lin Li-Rong , Dai Huan-Zi , Li Kai-Long , Zhang Jian-Guo , Zheng Lu-Quan , Fu Bi-Qiong , He Ya-Ni
Published: March 2017

Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients who were diagnosed by renal biopsy. uDcR2 levels were measured by ELISA, and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2 and renal functional parameters were evaluated. Receiver operating characteristics (ROC) curve analyzed area under the curve (AUC) of uDcR2 for assessing TII. Double staining was undertaken for renal DcR2 with proximal and distal tubular markers; senescent markers p16, p21, and senescence-associated β-galactosidase (SA-β-gal); and fibrotic markers collagen I and IV. We found DcR2 was primarily expressed in renal proximal tubules; uDcR2 levels were elevated per albuminuria stratum and correlated with renal functional parameters in diabetics and were associated with percentage of tubular DcR2 and TII score in DN. The uDcR2 had an AUC of 0.909 for assessing TII in DN by ROC analysis. Almost all tubular DcR2 was coexpressed with p16 and p21, and nearly more than one-half of tubular DcR2 was positive for SA-β-gal, primarily in collagen I- and IV-positive regions of DN. Our results indicate uDcR2 could potentially serve as a novel biomarker for TII and may reflect senescence of renal proximal tubular cells in DN pathogenesis.
Development and long-term integration of MGE-lineage cortical interneurons in the heterochronic environment
Authors: Larimer Phillip , Spatazza Julien , Stryker Michael P. , Alvarez-Buylla Arturo , Hasenstaub Andrea R.
Published: March 2017

Interneuron precursors transplanted into visual cortex induce network plasticity during their heterochronic maturation. Such plasticity can have a significant impact on the function of the animal and is normally present only during a brief critical period in early postnatal development. Elucidating the synaptic and physiological properties of interneuron precursors as they mature is key to understanding how long-term circuit changes are induced by transplants. We studied the development of transplant-derived interneurons and compared it to endogenously developing interneurons (those that are born and develop in the same animal) at parallel developmental time points, using patch-clamp recordings in acute cortical slices. We found that transplant-derived interneurons develop into fast-spiking and non-fast-spiking neurons characteristic of the medial ganglionic eminence (MGE) lineage. Transplant-derived interneurons matured more rapidly than endogenously developing interneurons, as shown by more hyperpolarized membrane potentials, smaller input resistances, and narrower action potentials at a juvenile age. In addition, transplant-derived fast-spiking interneurons have more quickly saturating input-output relationships and lower maximal firing rates in adulthood, indicating a possible divergence in function. Transplant-derived interneurons both form inhibitory synapses onto host excitatory neurons and receive excitatory synapses from host pyramidal cells. Unitary connection properties are similar to those of host interneurons. These transplant-derived interneurons, however, were less densely functionally connected onto host pyramidal cells than were host interneurons and received fewer spontaneous excitatory inputs from host cells. These findings suggest that many physiological characteristics of interneurons are autonomously determined, while some factors impacting their circuit function may be influenced by the environment in which they develop.

NEW & NOTEWORTHY Transplanting embryonic interneurons into older brains induces a period of plasticity in the recipient animal. We find that these interneurons develop typical fast-spiking and non-fast-spiking phenotypes by the end of adolescence. However, the input-output characteristics of transplant-derived neurons diverged from endogenously developing interneurons during adulthood, and they showed lower connection rates to local pyramidal cells at all time points. This suggests a unique and ongoing role of transplant-derived interneurons in host circuits, enabling interneuron transplant therapies.
Contributions of space-clamp errors to apparent time-dependent loss of Mg2+ block induced by NMDA
Authors: Sun Min-Yu , Chisari Mariangela , Eisenman Lawrence N. , Zorumski Charles F. , Mennerick Steven J.
Published: March 2017

N-methyl-d-aspartate receptors (NMDARs) govern synaptic plasticity, development, and neuronal response to insult. Prolonged activation of NMDARs such as during an insult may activate secondary currents or modulate Mg2+ sensitivity, but the conditions under which these occur are not fully defined. We reexamined the effect of prolonged NMDAR activation in juvenile mouse hippocampal slices. NMDA (10 μM) elicited current with the expected negative-slope conductance in the presence of 1.2 mM Mg2+. However, several minutes of continued NMDA exposure elicited additional inward current at −70 mV. A higher concentration of NMDA (100 µM) elicited the current more rapidly. The additional current was not dependent on Ca2+, network activity, or metabotropic NMDAR function and did not persist on agonist removal. Voltage ramps revealed no alteration of either reversal potential or NMDA-elicited conductance between −30 mV and +50 mV. The result was a more linear NMDA current-voltage relationship. The current linearization was also induced in interneurons and in mature dentate granule neurons but not immature dentate granule cells, dissociated cultured hippocampal neurons, or nucleated patches excised from CA1 pyramidal neurons. Comparative simulations of NMDA application to a CA1 pyramidal neuron and to a cultured neuron revealed that linearization can be explained by space-clamp errors arising from gradual recruitment of distal dendritic NMDARs. We conclude that persistent secondary currents do not strongly contribute to NMDAR responses in juvenile mouse hippocampus and careful discernment is needed to exclude contributions of clamp artifacts to apparent secondary currents.

NEW & NOTEWORTHY We report that upon sustained activation of NMDARs in juvenile mouse hippocampal neurons there is apparent loss of Mg2+ block at negative membrane potentials. However, the phenomenon is explained by loss of dendritic voltage clamp, leading to a linear current-voltage relationship. Our results give a specific example of how spatial voltage errors in voltage-clamp recordings can readily be misinterpreted as biological modulation.
Functional remodeling of subtype-specific markers surrounding implanted neuroprostheses
Authors: Salatino Joseph W. , Winter Bailey M. , Drazin Matthew H. , Purcell Erin K.
Published: March 2017

Microelectrode arrays implanted in the brain are increasingly used for the research and treatment of intractable neurological disease. However, local neuronal loss and glial encapsulation are known to interfere with effective integration and communication between implanted devices and brain tissue, where these observations are typically based on assessments of broad neuronal and astroglial markers. However, both neurons and astrocytes comprise heterogeneous cellular populations that can be further divided into subclasses based on unique functional and morphological characteristics. In this study, we investigated whether or not device insertion causes alterations in specific subtypes of these cells. We assessed the expression of both excitatory and inhibitory markers of neurotransmission (vesicular glutamate and GABA transporters, VGLUT1 and VGAT, respectively) surrounding single-shank Michigan-style microelectrode arrays implanted in the motor cortex of adult rats by use of quantitative immunohistochemistry. We found a pronounced shift from significantly elevated VGLUT1 within the initial days following implantation to relatively heightened VGAT by the end of the 4-wk observation period. Unexpectedly, we observed VGAT positivity in a subset of reactive astrocytes during the first week of implantation, indicating heterogeneity in early-responding encapsulating glial cells. We coupled our VGLUT1 data with the evaluation of a second marker of excitatory neurons (CamKiiα); the results closely paralleled each other and underscored a progression from initially heightened to subsequently weakened excitatory tone in the neural tissue proximal to the implanted electrode interface (within 40 μm). Our results provide new evidence for subtype-specific remodeling surrounding brain implants that inform observations of suboptimal integration and performance.

NEW & NOTEWORTHY We report novel changes in the local expression of excitatory and inhibitory synaptic markers surrounding microelectrode arrays implanted in the motor cortex of rats, where a progressive shift toward increased inhibitory tone was observed over the 4-wk observation period. The result was driven by declining glutamate transporter expression (VGLUT1) in parallel with increasing GABA transporter expression (VGAT) over time, where a reactive VGAT+ astroglial subtype made an unexpected contribution to our findings.
Spatial attention during saccade decisions
Authors: Jonikaitis Donatas , Klapetek Anna , Deubel Heiner
Published: March 2017

Behavioral measures of decision making are usually limited to observations of decision outcomes. In the present study, we made use of the fact that oculomotor and sensory selection are closely linked to track oculomotor decision making before oculomotor responses are made. We asked participants to make a saccadic eye movement to one of two memorized target locations and observed that visual sensitivity increased at both the chosen and the nonchosen saccade target locations, with a clear bias toward the chosen target. The time course of changes in visual sensitivity was related to saccadic latency, with the competition between the chosen and nonchosen targets resolved faster before short-latency saccades. On error trials, we observed an increased competition between the chosen and nonchosen targets. Moreover, oculomotor selection and visual sensitivity were influenced by top-down and bottom-up factors as well as by selection history and predicted the direction of saccades. Our findings demonstrate that saccade decisions have direct visual consequences and show that decision making can be traced in the human oculomotor system well before choices are made. Our results also indicate a strong association between decision making, saccade target selection, and visual sensitivity.

NEW & NOTEWORTHY We show that saccadic decisions can be tracked by measuring spatial attention. Spatial attention is allocated in parallel to the two competing saccade targets, and the time course of spatial attention differs for fast-slow and for correct-erroneous decisions. Saccade decisions take the form of a competition between potential saccade goals, which is associated with spatial attention allocation to those locations.
SK channel inhibition mediates the initiation and amplitude modulation of synchronized burst firing in the spinal cord
Authors: Mahrous Amr A. , Elbasiouny Sherif M.
Published: March 2017

Burst firing in motoneurons represents the basis for generating meaningful movements. Neuromodulators and inhibitory receptor blocker cocktails have been used for years to induce burst firing in vitro; however, the ionic mechanisms in the motoneuron membrane that contribute to burst initiation and amplitude modulation are not fully understood. Small conductance Ca2+-activated potassium (SK) channels regulate excitatory inputs and firing output of motoneurons and interneurons and therefore, are a candidate for mediating bursting behavior. The present study examines the role of SK channels in the generation of synchronized bursting using an in vitro spinal cord preparation from adult mice. Our results show that SK channel inhibition is required for both initiation and amplitude modulation of burst firing. Specifically, administration of the synaptic inhibition blockers strychnine and picrotoxin amplified the spinal circuit excitatory drive but not enough to evoke bursting. However, when SK channels were inhibited using various approaches, the excitatory drive was further amplified, and synchronized bursting was always evoked. Furthermore, graded SK channel inhibition modulated the amplitude of the burst in a dose-dependent manner, which was reversed using SK channel activators. Importantly, modulation of neuronal excitability using multiple approaches failed to mimic the effects of SK modulators, suggesting a specific role for SK channel inhibition in generating bursting. Both NMDA ( N-methyl-d-aspartate) and AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptors were found to drive the synchronized bursts. The blocking of gap junctions did not disturb the burst synchrony. These results demonstrate a novel mechanistic role for SK channels in initiating and modulating burst firing of spinal motoneurons.

NEW & NOTEWORTHY This study demonstrates that cholinergic inhibition or direct blockade of small conductance Ca2+-activated potassium (SK) channels facilitates burst firing in spinal motoneurons. The data provide a novel mechanistic explanation for synchronized bursting initiation and amplitude modulation through SK channel inhibition. Evidence also shows that synchronized bursting is driven by NMDA ( N-methyl-d-aspartate) and AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptors and that gap junctions do not mediate motoneuron synchronization in this behavior.
Evolution of Indoor Positioning Technologies: A Survey
Authors: Brena Ramon F. , García-Vázquez Juan Pablo , Galván-Tejada Carlos E. , Muñoz-Rodriguez David , Vargas-Rosales Cesar , Fangmeyer James
Published: March 2017

Indoor positioning systems (IPS) use sensors and communication technologies to locate objects in indoor environments. IPS are attracting scientific and enterprise interest because there is a big market opportunity for applying these technologies. There are many previous surveys on indoor positioning systems; however, most of them lack a solid classification scheme that would structurally map a wide field such as IPS, or omit several key technologies or have a limited perspective; finally, surveys rapidly become obsolete in an area as dynamic as IPS. The goal of this paper is to provide a technological perspective of indoor positioning systems, comprising a wide range of technologies and approaches. Further, we classify the existing approaches in a structure in order to guide the review and discussion of the different approaches. Finally, we present a comparison of indoor positioning approaches and present the evolution and trends that we foresee.
Linear Optical Properties of Zinc Borotellurite Glass Doped with Lanthanum Oxide Nanoparticles for Optoelectronic and Photonic Application
Authors: Mohd Fudzi Faznny , Mohamed Kamari Halimah , Abd Latif Amirah , Muhammad Noorazlan Azlan
Published: March 2017

Enhancing the optical properties of glasses for the sake of optical application in various fields is an ongoing challenge in materials science and technology. Thus, the optical properties of zinc borotellurite glass doped with lanthanum oxide nanoparticles (La2O3 NPs) with the chemical composition of {[(TeO2)0.7(B2O3)0.3]0.7(ZnO)0.3}1−x (La2O3 NPs)x, where x = 0.01, 0.02, 0.03, 0.04, and 0.05 molar fraction, have been investigated. Characterization techniques such as x-ray diffraction, Fourier Transform Infrared Spectroscopy, and Ultraviolet-Visible Spectroscopy are employed to yield the structural properties and optical parameter of the glass. The amorphous nature of the fabricated glasses is confirmed with the presence of a broad hump via XRD diffraction pattern. The decreasing amount of high polarizable nonbridging oxygen as the concentration of La2O3 NPs increases has contributed to the increasing trend of energy band gap in the range of 2.70 to 3.52 eV and decreasing value of refractive index between 2.34 and 2.48. The fabricated glasses that have a higher refractive index than the widely used fiber material, pure silica glass, indicate that zinc borotellurite glass doped with lanthanum nanoparticles is a promising material to be applied as optical fibers.
Satellite Observations of the Seasonal Evolution of Total Precipitable Water Vapour over the Mediterranean Sea
Authors: Palau J. L. , Rovira F. , Sales M. J.
Published: March 2017

This study shows satellite observations and new findings on the time and spatial distribution of the Total Precipitable Water (TPW) column over the Mediterranean Sea throughout the year. Annual evolution and seasonality of the TPW column are shown and compared to the estimated net evaporation over the Mediterranean Sea. Daily spatiotemporal means are in good agreement with previous short-term field campaigns and also corroborate hypothesis and conclusions reached from previous mesoscale modelling studies: (a) from a meteorological point of view, Mediterranean Basin should be considered as two different subbasins (the Western and the Eastern Mediterranean); (b) accumulation processes may affect the radiative balance at regional scale and the summer precipitation regimes. Furthermore, these satellite observations constitute strong empirical evidences that, (a) from late May to early October, contrary to what happens in the Eastern Mediterranean Basin (EMB), there is a net accumulation of TPW on the Western Mediterranean Basin (WMB) that favours the instability of the atmosphere, (b) there is a seasonal anticorrelation between the seasonal variability of the TPW column over the two Mediterranean subbasins, (c) solar radiation can not be the only driver for the annual variability of the TPW column over the Mediterranean Sea, and (d) both previous features are seasonally dependent and, therefore, their effects on the TPW column are attenuated by annual variability.