bluuebunny/crossref_metadata_2025_split huggingface dataset:
Massive introgression drives species radiation at the range limit of Anopheles gambiae
Authors: Vicente José L. , Clarkson Christopher S. , Caputo Beniamino , Gomes Bruno , Pombi Marco , Sousa Carla A. , Antao Tiago , Dinis João , Bottà Giordano , Mancini Emiliano , Petrarca Vincenzo , Mead Daniel , Drury Eleanor , Stalker James , Miles Alistair , Kwiatkowski Dominic P. , Donnelly Martin J. , Rodrigues Amabélia , Torre Alessandra della , Weetman David , Pinto João 
Published: April 2017

AbstractImpacts of introgressive hybridisation may range from genomic erosion and species collapse to rapid adaptation and speciation but opportunities to study these dynamics are rare. We investigated the extent, causes and consequences of a hybrid zone betweenAnopheles coluzziiandAnopheles gambiaein Guinea-Bissau, where high hybridisation rates appear to be stable at least since the 1990s.Anopheles gambiaewas genetically partitioned into inland and coastal subpopulations, separated by a central region dominated byA. coluzzii. Surprisingly, whole genome sequencing revealed that the coastal region harbours a hybrid form characterised by anA. gambiae-like sex chromosome and massive introgression ofA. coluzziiautosomal alleles. Local selection on chromosomal inversions may play a role in this process, suggesting potential for spatiotemporal stability of the coastal hybrid form and providing resilience against introgression of medically-important loci and traits, found to be more prevalent in inlandA. gambiae.
The BMP2 nuclear variant, nBMP2, is expressed in mouse hippocampus and impacts memory
Authors: Cordner Ryan D. , Friend Lindsey N. , Mayo Jaime L. , Badgley Corinne , Wallmann Andrew , Stallings Conrad N. , Young Peter L. , Miles Darla R. , Edwards Jeffrey G. , Bridgewater Laura C. 
Published: April 2017

AbstractThe novel nuclear protein nBMP2 is synthesized from the BMP2 gene by translational initiation at an alternative start codon. We generated a targeted mutant mouse, nBmp2NLStm, in which the nuclear localization signal (NLS) was inactivated to prevent nuclear translocation of nBMP2 while still allowing the normal synthesis and secretion of the BMP2 growth factor. These mice exhibit abnormal muscle function due to defective Ca2+ transport in skeletal muscle. We hypothesized that neurological function, which also depends on intracellular Ca2+ transport, could be affected by the loss of nBMP2. Age-matched nBmp2NLStm and wild type mice were analyzed by immunohistochemistry, behavioral tests, and electrophysiology to assess nBMP2 expression and neurological function. Immunohistochemical staining of the hippocampus detected nBMP2 in the nuclei of CA1 neurons in wild type but not mutant mice, consistent with nBMP2 playing a role in the hippocampus. Mutant mice showed deficits in the novel object recognition task, suggesting hippocampal dysfunction. Electrophysiology experiments showed that long-term potentiation (LTP) in the hippocampus, which is dependent on intracellular Ca2+ transport and is thought to be the cellular equivalent of learning and memory, was impaired. Together, these results suggest that nBMP2 in the hippocampus impacts memory formation.
Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models
Authors: Salman Ahmed M. , Montoya-Díaz Eduardo , West Heather , Lall Amar , Atcheson Erwan , Lopez-Camacho Cesar , Ramesar Jai , Bauza Karolis , Collins Katharine A. , Brod Florian , Reis Fernando , Pappas Leontios , González-Cerón Lilia , Janse Chris J. , Hill Adrian V. S. , Khan Shahid M. , Reyes-Sandoval Arturo 
Published: April 2017

AbstractDevelopment of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation.
Normally lethal amino acid substitutions suppress an ultramutator DNA Polymerase δ variant
Authors: Dennis Daniel G. , McKay-Fleisch Jill , Eitzen Kaila , Dowsett Ian , Kennedy Scott R. , Herr Alan J. 
Published: April 2017

AbstractIn yeast, thepol3-01,L612Mdouble mutant allele, which causes defects in DNA polymerase delta (Pol δ) proofreading (pol3-01) and nucleotide selectivity (pol3-L612M), confers an “ultramutator” phenotype that rapidly drives extinction of haploid and diploid MMR-proficient cells. Here, we investigate antimutator mutations that encode amino acid substitutions in Pol δ that suppress this lethal phenotype. We find that most of the antimutator mutations individually suppress thepol3-01andpol3-L612Mmutator phenotypes. The locations of many of the amino acid substitutions in Pol δ resemble those of previously identified antimutator substitutions; however, two novel mutations encode substitutions (R674G and Q697R) of amino acids in the fingers domain that coordinate the incoming dNTP. These mutations are lethal withoutpol3-L612Mand markedly change the mutation spectra produced by thepol3-01,L612Mmutator allele, suggesting that they alter nucleotide selection to offset thepol3-L612Mmutator phenotype. Consistent with this hypothesis, mutations and drug treatments that perturb dNTP pool levels disproportionately influence the viability ofpol3-L612M,R674Gandpol3-L612M,Q697Rcells. Taken together, our findings suggest that mutation rate can evolve through genetic changes that alter the balance of dNTP binding and dissociation from DNA polymerases.
Neurodevelopmental Changes in Excitatory Synaptic Structure and Function in the Cerebral Cortex of Sanfilippo Syndrome IIIA Mice
Authors: Dwyer Chrissa A. , Scudder Samantha L. , Lin Ying , Dozier Lara E. , Phan Dustin , Allen Nicola J. , Patrick Gentry N. , Esko Jeffrey D. 
Published: April 2017

AbstractSanfilippo syndrome, MPS IIIA-D, results from deficits in lysosomal enzymes that specifically degrade heparan sulfate, a sulfated glycosaminoglycan. The accumulation of heparan sulfate results in neurological symptoms, culminating in extensive neurodegeneration and early death. To study the impact of storage in postnatal neurodevelopment, we examined murine models of MPS IIIA, which lack the enzyme sulfamidase. We show that changes occur in excitatory postsynaptic structure and function in the somatosensory cortex prior to signs of neurodegeneration. These changes coincide with accumulation of heparan sulfate with characteristic non-reducing ends, which is present at birth in the mutant mice. Accumulation of heparan sulfate was also detected in primary cultures of cortical neural cells, especially astrocytes. Accumulation of heparan sulfate in cultured astrocytes corresponded with augmented extracellular heparan sulfate and glypican 4 levels. Heparan sulfate from the cerebral cortex of MPS IIIA mice showed enhanced ability to increase glutamate AMPA receptor subunits at the cell surface of wild type neurons. These data support the idea that abnormalities in heparan sulfate content and distribution contribute to alterations in postsynaptic function. Our findings identify a disease-induced developmental phenotype that temporally overlaps with the onset of behavioral changes in a mouse model of MPS IIIA.
Serum Concentration of HDL Particles Predicts Mortality in Acute Heart Failure Patients
Authors: Potočnjak Ines , Degoricija Vesna , Trbušić Matias , Pregartner Gudrun , Berghold Andrea , Marsche Gunther , Frank Saša 
Published: April 2017

AbstractClinical studies have shown that assessing circulating concentrations of high-density lipoprotein (HDL) particles by nuclear magnetic resonance (NMR) spectroscopy is superior to HDL-cholesterol in predicting cardiovascular risk. We tested the hypothesis that circulating concentrations of HDL particles predict 3-month mortality of patients with acute heart failure (AHF). Out of 152 included patients, 52% were female, additionally the mean patient age was 75.2 ± 10.3 years, and three-month mortality was 27%. Serum lipoprotein profile at admission was determined by NMR spectroscopy. Univariate logistic regression analyses revealed a significant inverse association of total (odds ratio (OR) 0.38 per 1-SD increase, 95% confidence interval (CI) 0.23–0.60, p < 0.001) and small HDL particle concentrations (OR 0.35 per 1-SD increase, 95% CI 0.19–0.60, p < 0.001) with 3-month mortality, whereas concentrations of large HDL particles (p = 0.353) or HDL-cholesterol (p = 0.107) showed no significant association. After adjustment for age, sex, mean arterial pressure, low-density lipoprotein cholesterol, glomerular filtration rate, urea, and N-terminal pro-brain natriuretic peptide, both the total and small HDL particle concentrations remained significantly associated with 3-month mortality. Based on our results, we conclude that total and small HDL particle concentrations strongly and independently predict 3-month mortality in AHF patients.
Auditory Environment Across the Life Span of Cochlear Implant Users: Insights From Data Logging
Authors: Busch Tobias , Vanpoucke Filiep , van Wieringen Astrid 
Published: April 2017

PurposeWe describe the natural auditory environment of people with cochlear implants (CIs), how it changes across the life span, and how it varies between individuals.MethodWe performed a retrospective cross-sectional analysis of Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from 1,501 people with CIs (ages 0–96 years). They covered over 2.4 million hr of implant use and indicated how much time the CI users had spent in various acoustical environments. We investigated exposure to spoken language, noise, music, and quiet, and analyzed variation between age groups, users, and countries.ResultsCI users spent a substantial part of their daily life in noisy environments. As a consequence, most speech was presented in background noise. We found significant differences between age groups for all auditory scenes. Yet even within the same age group and country, variability between individuals was substantial.ConclusionsRegardless of their age, people with CIs face challenging acoustical environments in their daily life. Our results underline the importance of supporting them with assistive listening technology. Moreover, we found large differences between individuals' auditory diets that might contribute to differences in rehabilitation outcomes. Their causes and effects should be investigated further.
Contrecoup Head Injury
Authors: BV Sandeep , Roy Kaushik , Saha Suniti Kumar , Dixit Sourabh , Ghosh Partha , Banga Manpreet Singh 
Published: April 2017

AbstractContrecoup injuries comprise a group of focal brain injuries that occur at areas distant from the point of impact. It has been hypothesized that patients with contrecoup injuries would have a worse outcome because of the diffuse nature of injury. At Nilratan Sircar Medical College, Kolkata, 74 patients presenting with contrecoup injuries over a period of 1 year were prospectively analyzed. Site of primary impact was determined by clinical and CT scan criteria. The age, modes of injury, Glasgow coma scale (GCS), site of injury, pattern of injury, and mortality were analyzed. Delayed presentation of contrecoup injury in patients who deteriorated over time was also noted in imaging. The presence of contrecoup injury implies that the traumatic forces have dissipated into the brain, and from the biomechanisms explained, the brain is likely to have suffered greater damage than the case in coup injury alone. The present study shows that the presence of contrecoup contusions is associated with a poor prognosis across all GCS and age categories.
Fully Endoscopic Minimally Invasive Transrectus Capitis Posterior Muscle Triangle Approach to the Posterolateral Condyle and Jugular Tubercle
Authors: Mingdong Wang , Mathias Roger , Wang Eric , Gardner Paul , Wang Hong , Fernandez-Miranda Juan 
Published: April 2017

Background We evaluated a transrectus capitis posterior muscle triangle approach to the posterolateral foramen magnum, occipital condyles, jugular tubercle, and the fourth ventricle. We also assessed factors that affect the amount of bone removal required.
Objective To evaluate if the proposed approach is as effective as standard open approaches to expose the lateral portion of the foramen magnum.
Methods The proposed minimally invasive fully endoscopic approach was performed in 15 cadaveric specimens using 4-mm (0- and 45-degree) endoscopes.
Results Using a 5-cm straight paramedian incision, the rectus capitis posterior minor and major muscles were partially removed unilaterally, providing a corridor through the muscles to reach the foramen magnum region. After meticulous soft tissue dissection, key anatomical landmarks can be identified such as the greater occipital nerve, the vertebral artery that wraps around the atlanto-occipital joint, and the bony protuberance that heralds the occipital condyle. A suboccipital craniotomy associated with the transcondylar, supracondylar or paracondylar approach is performed depending on the amount of bone removal desired to maximize the surgical view. By doing so, the jugular foramen can be exposed laterally as well as the fourth ventricle medially.
Conclusion The proposed endoscopic approach can provide access through the transrectus capitis posterior muscle triangle leading directly to the occipital condyle. A stepwise approach is critical to gain a surgical corridor to the inferolateral petroclival region and the fourth ventricle.
An Unusual Orthopaedic Disease: Sarcoidosis—A Case Report
Authors: Kemah Bahattin , Özturan Burak , Bilgic Bilge , Özkan Korhan , Akpınar Fuat , Kılıc Bulent 
Published: April 2017

AbstractSarcoidosis is an idiopathic, noncaseating granulomatous disorder with wide systemic involvement. It is encountered widely around the world and it affects both sexes, all the races in all age groups. Lungs, eyes, and skin are the organs most commonly affected. Constitutional features such as weight loss, fatigue, and myalgia are the most common symptoms. Bone involvement, which is very rare, was reported as present in 3 to 13% of effected cases, and it is most commonly seen in hands and feet, compared with long bone involvement, which is extremely rare. We hereby present a case with a diagnosis of sarcoidosis and multiple bone involvement emphasizing the importance of differential diagnosis.
A Method of Locating the Dehiscence during Middle Fossa Approach for Superior Semicircular Canal Dehiscence Surgery
Authors: Beckett Joel , Chung Lawrance , Lagman Carlito , Voth Brittany , Jacky Chen Cheng , Gaonkar Bilwaj , Gopen Quinton , Yang Isaac 
Published: April 2017

Objectives Superior semicircular canal dehiscence (SSCD) results from a defect in the middle cranial fossa floor. One challenge during SSCD repair is the lack of a consistent landmark. This study proposes a reference point above the external auditory canal at the level of the zygoma as the inferior craniectomy edge during surgery.
Design This is a retrospective review of patients with SSCD.
Setting/Participants A total of 72 cases of SSCD in 60 patients were repaired via a middle fossa approach at a single institution.
Main Outcome Measures The distance from the proposed reference point to the dehiscence was statistically analyzed using Shapiro–Wilk's goodness-of-fit test and Student's t-test.
Results Average distance for all patients was 28.84 ± 2.22 mm (range: 22.96–33.43). Average distance for females was 29.08 mm (range: 24.56–33.43) versus 28.26 mm (range: 22.96–32.36) for males. There was no difference in distance by sex (p = 0.174). The distance measurements followed a normal distribution with 95% of the patients between 24.49 and 33.10 mm.
Conclusion This study analyzed a potential reference point during a middle fossa approach for SSCD surgery. The distance from this reference point to the SSCD was found to be consistent and may serve as a readily identifiable landmark in localizing the dehiscence.
Contractile and chiral activities codetermine the helicity of swimming droplet trajectories
Authors: Tjhung Elsen , Cates Michael E. , Marenduzzo Davide 
Published: April 2017

Significance
Active fluids include bacterial suspensions, biological tissues, and the cytoskeleton. They are far from equilibrium because the fluid is continuously stirred by constituent particles themselves. A model droplet of active fluid can show swimming or crawling motilities resembling those in real biological cells despite the simplifications entailed. Here, we consider the effects of microscopic chirality on the motility of these active droplets. We find a rich phase diagram including oscillatory dynamics, run and tumble, and helical swimming with either the same or opposite sign to the microscopic one.
Bisulfite-converted duplexes for the strand-specific detection and quantification of rare mutations
Authors: Mattox Austin K. , Wang Yuxuan , Springer Simeon , Cohen Joshua D. , Yegnasubramanian Srinivasan , Nelson William G. , Kinzler Kenneth W. , Vogelstein Bert , Papadopoulos Nickolas 
Published: April 2017

Significance
The detection of rare mutations in clinical samples is essential to the screening, diagnosis, and treatment of cancer. Although next-generation sequencing has greatly enhanced the sensitivity of detecting mutations, the relatively high error rate of these platforms limits their overall clinical utility. The elimination of sequencing artifacts could facilitate the detection of early-stage cancers and provide improved treatment recommendations tailored to the genetic profile of a tumor. Here, we report the development of BiSeqS, a bisulfite conversion-based sequencing approach that allows for the strand-specific detection and quantification of rare mutations. We demonstrate that BiSeqS eliminates nearly all sequencing artifacts in three common types of mutations and thereby considerably increases the signal-to-noise ratio for diagnostic analyses.
Neurophysiological dynamics of phrase-structure building during sentence processing
Authors: Nelson Matthew J. , El Karoui Imen , Giber Kristof , Yang Xiaofang , Cohen Laurent , Koopman Hilda , Cash Sydney S. , Naccache Lionel , Hale John T. , Pallier Christophe , Dehaene Stanislas 
Published: April 2017

Significance
According to most linguists, the syntactic structure of sentences involves a tree-like hierarchy of nested phrases, as in the sentence [happy linguists] [draw [a diagram]]. Here, we searched for the neural implementation of this hypothetical construct. Epileptic patients volunteered to perform a language task while implanted with intracranial electrodes for clinical purposes. While patients read sentences one word at a time, neural activation in left-hemisphere language areas increased with each successive word but decreased suddenly whenever words could be merged into a phrase. This may be the neural footprint of “merge,” a fundamental tree-building operation that has been hypothesized to allow for the recursive properties of human language.
Integrin extension enables ultrasensitive regulation by cytoskeletal force
Authors: Li Jing , Springer Timothy A. 
Published: April 2017

Significance
There are competing conceptual models of integrin activation. Recent measurements of conformational equilibria and intrinsic affinities of integrins on the cell surface enable quantitative evaluation of these models. We show that among these models, only the combination of adaptor binding and cytoskeletal force provides ultrasensitive regulation of integrin activation and occurs in a range of force experienced by most ligand-bound integrins. Switch-like activation by force relies on the large change in length in integrin extension and explains why integrins extend and why their domain organization is so conserved.
On the treatment, control and elimination of ovine footrot: a comparative review.
Authors: Clifton R. , Green L. E. 
Published: April 2017

Abstract
Ovine footrot is detrimental to sheep health, welfare and production worldwide. Strategies for management of footrot have varied between countries and regions due to differences in climate, production systems and proportion of positive flocks. Recent research from Great Britain, where >90% flocks have footrot has highlighted that treatment of individual lame sheep within 3 days with parenteral and topical antibiotics, and without foot trimming, results in rapid recovery. This benefits both animal welfare and productivity. Recent evidence indicates that foot trimming into sensitive tissue during routine foot trimming is associated with higher prevalence of lameness, and careful routine foot trimming is not associated with lower prevalence of lameness, rendering this practice void for control of footrot. Fifty percent of farmers in England are now no longer practising routine foot trimming. The lowest prevalence of footrot without elimination is achieved by treatment of sheep with footrot within 3 days of onset of lameness, separation of lame sheep until recovered and rapid footbathing of a flock when an outbreak of interdigital dermatitis occurs. Vaccination and selection of breeding replacements from non-lame ewes contribute to further reducing the prevalence of lameness. Improving control of footrot has occurred between 2004 and 2013: the global mean prevalence of lameness in sheep has halved from 10 to 5%. Flock elimination of footrot has been successful in flocks across the world through treatment of diseased sheep, culling all non-respondents and persistently lame sheep, targeted vaccination (including mono and bivalent vaccines) and regular footbathing of healthy sheep in periods of non-transmission until no further disease is detected, even in a period of disease transmission. This has been most successful when initiated when climatic conditions are regularly unfavourable to transmission of footrot and where the percentage of flocks with footrot is low and flock level biosecurity can be maintained to prevent re-introduction of footrot to a naïve flock. Both control and elimination strategies are successful to reduce the global burden of footrot. Success is dependent on choosing the correct strategy for the flock given climate, biosecurity and force of infection and commitment to the programme.