bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs
Authors: Martin Hilary C , Wani Shivangi , Steptoe Anita L , Krishnan Keerthana , Nones Katia , Nourbakhsh Ehsan , Vlassov Alexander , Grimmond Sean M , Cloonan Nicole 
Published: March 2014

Abstract
Background
MicroRNAs (miRNAs) bind to mRNAs and target them for translational inhibition or transcriptional degradation. It is thought that most miRNA-mRNA interactions involve the seed region at the 5′ end of the miRNA. The importance of seed sites is supported by experimental evidence, although there is growing interest in interactions mediated by the central region of the miRNA, termed centered sites. To investigate the prevalence of these interactions, we apply a biotin pull-down method to determine the direct targets of ten human miRNAs, including four isomiRs that share centered sites, but not seeds, with their canonical partner miRNAs.

Results
We confirm that miRNAs and their isomiRs can interact with hundreds of mRNAs, and that imperfect centered sites are common mediators of miRNA-mRNA interactions. We experimentally demonstrate that these sites can repress mRNA activity, typically through translational repression, and are enriched in regions of the transcriptome bound by AGO. Finally, we show that the identification of imperfect centered sites is unlikely to be an artifact of our protocol caused by the biotinylation of the miRNA. However, the fact that there was a slight bias against seed sites in our protocol may have inflated the apparent prevalence of centered site-mediated interactions.

Conclusions
Our results suggest that centered site-mediated interactions are much more frequent than previously thought. This may explain the evolutionary conservation of the central region of miRNAs, and has significant implications for decoding miRNA-regulated genetic networks, and for predicting the functional effect of variants that do not alter protein sequence.
Central Precocious Puberty That Appears to Be Sporadic Caused by Paternally Inherited Mutations in the Imprinted Gene Makorin Ring Finger 3
Authors: Macedo Delanie B. , Abreu Ana Paula , Reis Ana Claudia S. , Montenegro Luciana R. , Dauber Andrew , Beneduzzi Daiane , Cukier Priscilla , Silveira Leticia F. G. , Teles Milena G. , Carroll Rona S. , Junior Gil Guerra , Filho Guilherme Guaragna , Gucev Zoran , Arnhold Ivo J. P. , de Castro Margaret , Moreira Ayrton C. , Martinelli Carlos Eduardo , Hirschhorn Joel N. , Mendonca Berenice B. , Brito Vinicius N. , Antonini Sonir R. , Kaiser Ursula B. , Latronico Ana Claudia 
Published: March 2014

Context:
Loss-of-function mutations in makorin ring finger 3 (MKRN3), an imprinted gene located on the long arm of chromosome 15, have been recognized recently as a cause of familial central precocious puberty (CPP) in humans. MKRN3 has a potential inhibitory effect on GnRH secretion.

Objectives:
The objective of the study was to investigate potential MKRN3 sequence variations as well as copy number and methylation abnormalities of the 15q11 locus in patients with apparently sporadic CPP.

Setting and Participants:
We studied 215 unrelated children (207 girls and eight boys) from three university medical centers with a diagnosis of CPP. All but two of these patients (213 cases) reported no family history of premature sexual development. First-degree relatives of patients with identified MKRN3 variants were included for genetic analysis.

Main Outcome Measures:
All 215 CPP patients were screened for MKRN3 mutations by automatic sequencing. Multiplex ligation-dependent probe amplification was performed in a partially overlapping cohort of 52 patients.

Results:
We identified five novel heterozygous mutations in MKRN3 in eight unrelated girls with CPP. Four were frame shift mutations predicted to encode truncated proteins and one was a missense mutation, which was suggested to be deleterious by in silico analysis. All patients with MKRN3 mutations had classical features of CPP with a median age of onset at 6 years. Copy number and methylation abnormalities at the 15q11 locus were not detected in the patients tested for these abnormalities. Segregation analysis was possible in five of the eight girls with MKRN3 mutations; in all cases, the mutation was inherited on the paternal allele.

Conclusions:
We have identified novel inherited MKRN3 defects in children with apparently sporadic CPP, supporting a fundamental role of this peptide in the suppression of the reproductive axis.
Usher protein complexes preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis
Authors: Blanco-Sánchez Bernardo , Clément Aurélie , Fierro Junior Javier , Washbourne Philip , Westerfield Monte 
Published: March 2014

AbstractUsher syndrome (USH), the leading cause of hereditary combined hearing and vision loss, is characterized by sensorineural deafness and progressive retinal degeneration. Mutations in several different genes produce USH, but the proximal cause of sensory cell death remains mysterious. We adapted a proximity ligation assay to analyze associations among three of the USH proteins, Cdh23, Harmonin, and Myo7aa, and the microtubule based transporter Ift88 in zebrafish inner ear mechanosensory hair cells. We found that the proteins are in close enough proximity to form complexes and that these complexes preassemble at the endoplasmic reticulum (ER). Defects in any one of the three USH proteins disrupt formation and trafficking of the complex and result in diminished levels of the other proteins, generalized trafficking defects, and ER stress that triggers apoptosis. ER stress, thus, contributes to sensory hair cell loss and provides a new target to explore for protective therapies for Usher syndrome.
The effect of water temperature and flow on respiration in barnacles: patterns of mass transfer versus kinetic limitation
Authors: Nishizaki Michael T. , Carrington Emily 
Published: March 2014

AbstractIn aquatic systems, physiological processes such as respiration, photosynthesis, and calcification are potentially limited by the exchange of dissolved materials between organisms and their environment. The nature and extent of physiological limitation is, therefore, likely to be dependent on environmental conditions. Here, we assess the metabolic sensitivity of barnacles under a range of water temperatures and velocities, two factors that influence their distribution. Respiration rates increased in response to changes in temperature and flow, with an interaction where flow had less influence on respiration at low temperatures, and a much larger effect at high temperatures. Model analysis suggested that respiration is mass transfer limited under conditions of low velocity (&lt; 7.5 cm s-1) and high temperature (20 to 25°C). In contrast, limitation by uptake reaction kinetics, when the biotic capacity of barnacles to absorb and process oxygen is slower than its physical delivery by mass transport, prevailed at high flows (40 to 150 cm s-1) and low temperatures (5 to 15°C). Moreover, there are intermediate flow-temperature conditions where both mass transfer and kinetic limitation are important. Behavioral monitoring revealed that barnacles fully extend their cirral appendages at low flows and display abbreviated “testing” behaviors at high flows, suggesting some form of mechanical limitation. In low flow-high temperature treatments, however, barnacles displayed distinct “pumping” behaviors that may serve to increase ventilation. Our results suggest that in slow moving waters, respiration may become mass transfer limited as temperatures rise, whereas faster flows may serve to ameliorate the effects of elevated temperatures. Moreover, these results underscore the necessity for approaches that evaluate the combined effects of multiple environmental factors when examining physiological and behavioral performance.
A viral aphrodisiac in the cricket Gryllus texensis
Authors: Adamo Shelley A. , Kovalko Ilya , Easy Russell H. , Stoltz Don 
Published: March 2014

Abstract
We identified the insect iridovirus IIV-6/CrIV as a pathogen of the cricket Gryllus texensis using electron microscopy (EM) and polymerase chain reaction (PCR) analysis. Electron microscopy (EM) showed that the virus attacks the fat body, an organ important for protein production, immune function and lipid storage. During infection the fat body hypertrophied, but egg production withered, leaving the lateral oviducts empty of eggs; the females were effectively sterile. EM of the testis of infected males suggests that the testis was not invaded by the virus, although sperm taken from the spermatophores of infected males showed little or no motility. Nevertheless, males and females continued to mate when infected. In fact, infected males were quicker to court females than uninfected controls. The virus benefits from the continued sexual behaviour of its host; transmission studies show that the virus can be spread through sexual contact. Sickness behaviour, the adaptive reduction of feeding and sexual behaviour that is induced by an activated immune system, is absent in infected crickets. Total hemolymph protein is reduced, as is phenoloxidase activity, suggesting a reduction in immune protein production by the fat body. The evidence suggests that during IIV-6/CrIV infection, the immune signal(s) that induce sickness behaviour are absent. Curtailment of a host's sickness behaviour may be necessary for any pathogen that is spread by host sexual behaviour.
Development of π-Electron Systems Based on [M(dmit)2] (M = Ni and Pd; dmit: 1,3-dithiole-2-thione-4,5-dithiolate) Anion Radicals
Authors: Kato Reizo 
Published: March 2014

Abstract
Molecular conductors based on [M(dmit)2] (M = Ni and Pd) present a variety of π electron systems that pave the way for a higher stage of solid-state science. Supramolecular interactions between [Ni(dmit)2] anion and halogen-containing cations provide bilayer systems that are characterized by coexistence of two crystallographically independent anion layers with different molecular arrangements and contrasting (for example, metal/insulator and ferromagnetic/antiferromagnetic) properties. In [Pd(dmit)2] salts in the Mott insulating state, a small energy difference between HOMO and LUMO coupled with strong dimerization affords HOMO–LUMO band inversion. The dimer units [Pd(dmit)2]2− form a triangular lattice, and interplay of strong electron correlation and spin frustration generates a wide variety of magnetic/charge states including antiferromagnetic long-range order, quantum spin liquid, charge order, and valence bond order, depending on counter cations. The cation dependence is attributed to a systematic arch-shaped molecular distortion that tunes the anisotropy of interdimer transfer integrals. This means that the [Pd(dmit)2] molecular skeleton is sufficiently flexible within the crystal field, and molecular degrees of freedom play an important role in fine tuning of the electronic state.
Guest effect on spin-crossover frameworks
Authors: Cirera Jordi 
Published: March 2014

AbstractMetal-organic frameworks (MOFs) represent a novel class of materials that are the subject of intense research efforts due to their potential technological applications. Although major efforts are being pursued in improving their adsorption properties, the use of open shell metal centers can add magnetic properties to the frameworks, thus making them suitable targets for the design of multifunctional materials. In this review, we present a summary of the recent advances in the field of spin-crossover frameworks (SCOFs), with emphasis on the guest effect over the magnetic properties of the MOF material. This review is organized as follows: First, an introduction to metal-organic frameworks and the spin-crossover phenomenon is presented. Second, we discuss previously reported SCOFs and examine how chemical modifications of the framework and the host/guest interactions affect their physical properties. Finally, an outlook on future applications of SCOFs is discussed.
Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method
Authors: Raabe Andreas , Beck Jürgen , Schucht Philippe , Seidel Kathleen 
Published: March 2014

Object
The authors developed a new mapping technique to overcome the temporal and spatial limitations of classic subcortical mapping of the corticospinal tract (CST). The feasibility and safety of continuous (0.4–2 Hz) and dynamic (at the site of and synchronized with tissue resection) subcortical motor mapping was evaluated.

Methods
The authors prospectively studied 69 patients who underwent tumor surgery adjacent to the CST (< 1 cm using diffusion tensor imaging and fiber tracking) with simultaneous subcortical monopolar motor mapping (short train, interstimulus interval 4 msec, pulse duration 500 μsec) and a new acoustic motor evoked potential alarm. Continuous (temporal coverage) and dynamic (spatial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device, with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months.

Results
All procedures were technically successful. There was a 1:1 correlation of motor thresholds for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (24 patients, 74 stimulation points; r2 = 0.98, p < 0.001). The lowest individual motor thresholds were as follows: > 20 mA, 7 patients; 11–20 mA, 13 patients; 6–10 mA, 8 patients; 4–5 mA, 17 patients; and 1–3 mA, 24 patients. At 3 months, 2 patients (3%) had a persistent postoperative motor deficit, both of which were caused by a vascular injury. No patient had a permanent motor deficit caused by a mechanical injury of the CST.

Conclusions
Continuous dynamic mapping was found to be a feasible and ergonomic technique for localizing the exact site of the CST and distance to the motor fibers. The acoustic feedback and the ability to stimulate the tissue continuously and exactly at the site of tissue removal improves the accuracy of mapping, especially at low (< 5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery.
Filum terminale lipomas: imaging prevalence, natural history, and conus position
Authors: Cools Michael J. , Al-Holou Wajd N. , Stetler William R. , Wilson Thomas J. , Muraszko Karin M. , Ibrahim Mohannad , La Marca Frank , Garton Hugh J. L. , Maher Cormac O. 
Published: March 2014

Object
Filum terminale lipomas (FTLs) are being identified with increasing frequency due to the increasing utilization of MRI. Although an FTL may be associated with tethered cord syndrome (TCS), in many cases FTLs are diagnosed incidentally in patients without any symptoms of TCS. The natural history of FTLs is not well defined.

Methods
The authors searched the clinical and imaging records at a single institution over a 14-year interval to identify patients with FTLs. For patients with an FTL, the clinical records were reviewed for indication for imaging, presenting symptoms, perceived need for surgery, and clinical outcome. A natural history analysis was performed using all patients with more than 6 months of clinical follow-up.

Results
A total of 436 patients with FTL were identified. There were 217 males and 219 females. Of these patients, 282 (65%) were adults and 154 (35%) were children. Symptoms of TCS were present in 22 patients (5%). Fifty-two patients underwent surgery for FTL (12%). Sixty-four patients (15%) had a low-lying conus and 21 (5%) had a syrinx. The natural history analysis included 249 patients with a mean follow-up time of 3.5 years. In the follow-up period, only 1 patient developed new symptoms.

Conclusions
Filum terminale lipomas are a common incidental finding on spinal MRI, and most patients present without associated symptoms. The untreated natural history is generally benign for asymptomatic patients.
Metabolism and Antiretroviral Activity of Tenofovir Alafenamide in CD4+ T-Cells and Macrophages from Demographically Diverse Donors
Authors: Bam Rujuta A , Birkus Gabriel , Babusis Darius , Cihlar Tomas , Yant Stephen R 
Published: March 2014

Background Tenofovir alafenamide (TAF) is a novel investigational prodrug of tenofovir (TFV) that permits enhanced delivery of TFV into peripheral blood mono-nuclear cells (PBMCs) and lymphatic tissues. A critical step in the intracellular metabolic activation of TAF is mediated by the lysosomal protease cathepsin A (CatA). Here, we investigated CatA levels together with intracellular metabolism and antiretroviral activity of TAF in primary CD4+ T-lymphocytes (CD4s) and monocyte-derived macrophages (MDMs) isolated from a demographically diverse group of blood donors. Methods CD4s and MDMs were prepared from fresh PBMCs. CatA levels were quantified in cell extracts by monitoring TAF hydrolysis using HPLC. Intracellular TAF metabolites were quantified by HPLC combined with mass spectrometry. Antiviral activities in activated CD4s and MDMs were determined using HIV-1 single-cycle reporter and p24 antigen production assays, respectively. Results The levels of CatA and intracellular TAF metabolites differed minimally in CD4s and MDMs among 13 tested donors. TAF was >600-fold and 80-fold more potent than parent TFV in CD4s and MDMs, respectively, and its relative range of antiviral activity across all tested donors was comparable to that of other HIV-1 reverse transcriptase inhibitors, with mean ±sd (range) EC50 values of 11.0 ±3.4 (6.6–19.9) nM and 9.7 ±4.6 (2.5–15.7) nM in CD4s and MDMs, respectively. Conclusions These results indicate consistent intracellular metabolism and antiretroviral potency of TAF in relevant target cells of HIV-1 infection across multiple donors of variable gender, age and ethnicity, supporting further clinical investigation of TAF.
Organic Semiconductors
Authors: Sariciftci Niyazi Serdar 
Published: March 2014

Devices such as organic light emitting diodes (OLED), flat panel displays, organic field effect transistors (OFET), organic photovoltaic elements (OPV), organic photodetector arrays (OPDA) are entering the market. Liquid crystal based optoelectronic devices are commonly used today in display technology and in spatial light modulators. Other applications such as OLED's are commercially introduced in home electronics and mobile phones. The technological advantages of this class of materials consist among others: i) tunability of the electronic bandgap by chemical synthesis, ii) processability of the materials in a large scale (large area devices), iii) reduction of production costs by roll‐to‐roll production (typical for polymeric “plastic materials”). Thus, the advantages of the chemical industrial production schemes such as dye industry or plastic industry and the properties of semiconductors are combined in the organic semiconductor technology.This article reviews organic semiconductor devices in general by discussing the electronic properties of molecular crystals and polymers with extended π‐electrons. The analogy will be illustrated between valence band (VB), conduction band (CB) picture in semiconductor physics and π, π*bands in organic chemistry, respectively. Transport properties and photophysical effects will be explained briefly. Examples of devices and their operations will be reviewed. A visit to photonic devices using molecular semiconductors will close the article.
Firearm and Toolmark Opinion Evidence: Admissibility of Opinions After
Daubert
and the
NAS
Reports
Authors: DesPortes Betty Layne 
Published: March 2014

Abstract

Firearm and toolmark opinion evidence—in particular firearm identification testimony—has been admitted in courts in the United States for over a century, but the milestones of
Daubert
and the “
NAS
Reports” mark changes in the legal landscape concerning the admission of certain firearm and toolmark opinion evidence. The seminal event of the 1993 United States Supreme Court opinion in
Daubert v. Merrell Dow Pharmaceuticals
led to challenges to the admission of firearm and toolmark opinion evidence, but more challenges resulted from the publication of two reports by the National Academy of Sciences in 2008 and 2009. In 2008, the National Academy of Sciences published “
Ballistic Imaging
”, which questioned the fundamental assumptions of uniqueness and reproducibility underlying firearm identification evidence. The 2009 publication of the National Academy of Sciences Report
Strengthening Forensic Science in the United States: A Path Forward
further sparked challenges to the admission of firearm and toolmark opinion testimony and identification conclusions offered by experts. Published so closely in time, it is difficult to separate the legal impact of the two reports and for purposes of this article the two reports will be considered together. In this article, the “post‐
Daubert
” and “post‐
NAS
Reports” decisions concerning the admission of firearm and toolmark opinion evidence are discussed with a focus on cases involving firearm identification evidence.

As with other areas of forensic science, neither
Daubert
nor the
NAS
Reports resulted in the widespread exclusion of firearm and toolmark opinion evidence but the legal landscape has been altered with some courts limiting opinions of certainty and with broader recognition of the reliance on the subjective findings of examiners in firearm identification evidence.
Tribocharging and the Triboelectric Series
Authors: Gooding Diana M. , Kaufman George K. 
Published: March 2014

Abstract

Tribocharging is a process in which materials contact one another, rub, and then separate, each with a resulting charge distribution. This process is familiar and applied extensively in processes such as electrophotography and energy harvesting, but it is not completely understood. The triboelectric series is a qualitative or semiquantitative ordering of materials according to their tendency to develop a positive or negative net charge when tribocharged against other materials. It is remarkable that, despite differences in surface preparation, modes of contact among materials, and laboratory conditions, triboelectric series generated by different groups remain largely consistent with each other. This article examines a variety of triboelectric series, discrepancies among them, and the competing possible mechanisms behind tribocharging, which appear to include electron transfer, ion transfer, H
+
and OH
–
partitioning, bond dissociation, chemical changes, and material transfer. Combinations of these mechanisms may occur simultaneously but at different rates, which may help to explain some of the inconsistencies among different triboelectric series.