bluuebunny/crossref_metadata_2025_split huggingface dataset:
From brain noise to syntactic structures: A formal proposal within the oscillatory rhythms perspective
Authors: Grimaldi Mirko 
Published: August 2017

AbstractThe neurobiology investigation of language seems limited by the impossibility to link directly linguistic computations with neural computations. To address this issue, we need to explore the hierarchical interconnections between the investigated fields trying to develop an inter-field theory. Considerable research has realized that event-related fluctuations in rhythmic, oscillatory EEG/MEG activity may provide a new window on the dynamics of functional neuronal networks involved in cognitive processing. Accordingly, this paper aims to outline a formal proposal on neuronal computation and representation of syntactic structures within the oscillatory neuronal dynamics. I briefly present the nature of event-related oscillations and how they work on the base of synchronization and de-synchronization processes. Then, I discuss some theoretical premises assuming that reentrant (hierarchical) properties of synchronized oscillatory rhythms constitute the biological endowment that allow the development of language in humans when exposed to appropriate inputs. The main rhythms involved in language and speech processing are examined: i.e. theta, alpha, beta, and gamma bands. A possible formal representation of the syntactic structures on the base of these oscillatory rhythms is discussed: in this model, the theta-gamma rhythms are cross-frequency coupled into the alpha-gamma-beta and into the gamma-beta-theta rhythms to generate the sentence along reentrant cortico-thalamic pathways through Merge, Label and Move operations. Finally, I present few conclusive remarks within an evolutionary perspective.“…The whole burden of philosophy seems to consist in this, from the phenomena of motions to investigate the forces of nature, and from these forces to demonstrate the other phenomena.”(Newton, 1687/1726)
Protein phosphatase V ensures timely cell cycle remodeling during the mid-blastula transition in Drosophila
Authors: Liu Boyang , Sung Hung-wei , Gregor Ingo , Müller H.-Arno , Großhans Jörg 
Published: August 2017

AbstractCell cycle remodeling from fast nuclear cycles to a generic cell cycle mode is a major feature of the mid-blastula transition (MBT) inDrosophila.Remodeling occurs when Twine/Cdc25 falls below a critical threshold. Timing is based on Twine destabilization induced by zygotic transcription. It is conceivable that appropriate starting levels are also important for timely reaching the threshold. Mechanisms for controlling Twine levels at the onset of MBT are unknown. Here we identify a function of the protein phosphatase V in this mechanism. Twine was increased inPpVmutants, whereas the decay rate was comparable to wildtype.PpVmutants frequently underwent an extra nuclear division. We detected PpV-dependent phosphosites in Twine. Phosphosite mutants contain higher Twine levels and frequently underwent an extra nuclear division, comparable toPpVmutants. Our data support a model that the cell cycle remodeling is controlled by induced destabilization and PpV-d ependent control of Twine levels.
Uncovering Medical Insights from Vast Amounts of Biomedical Data in Clinical Case Reports
Authors: Zhou Yijiang , Liem David A. , Lee Jessica M. , Cao Quan , Bleakley Brian , Caufield J. Harry , Murali Sanjana , Wang Wei , Zhang Li , Bui Alex , Sun Yizhou , Watson Karol E. , Han Jiawei , Ping Peipei 
Published: August 2017

AbstractClinical case reports (CCRs) have a time-honored tradition in serving as an important means of sharing clinical experiences on patients presenting with atypical disease phenotypes or receiving new therapies. However, the huge amount of accumulated case reports are isolated, unstructured, and heterogeneous clinical data, posing a great challenge to clinicians and researchers in mining relevant information through existing indexing tools. In this investigation, in order to render CCRs more findable, accessible, interoperable, and reusable (FAIR) by the biomedical community, we created a resource platform, including the construction of a test dataset consisting of 1000 CCRs spanning 14 disease phenotypes, a standardized metadata template and metrics, and a set of computational tools to automatically retrieve relevant medical information and to analyze all published PubMed clinical case reports with respect to trends in publication journals, citations impact, MeSH Terms, drug use, distributions of patient demographics, and relationships with other case reports and databases. Our standardized metadata template and CCR test dataset may be valuable resources to advance medical science and improve patient care for researchers who are using machine learning approaches with a high-quality dataset to train and validate their algorithms. In the future, our analytical tools may be applied towards other large clinical data sources as well.
Liver physiological T1rho dynamics associated with age and gender
Authors: Wáng Yì Xiáng J , Deng Min , Lin Jiang , Kwok Anthony WL , Liu Eric KW , Chen Weitian 
Published: August 2017

AbstractPurposeUsing a single breathhold black blood sequence, the current study aims to understand the physiological ranges of liver T1rho relaxation for women and men.Materials and MethodsThis volunteer study was conducted with institutional ethics committee approval, and included 62 females (age mean: 38.9 years; range: 18-75 years) and 34 males (age mean: 44.7 years, range: 24-80 years). MRI was conducted with a 3.0 T scanner, with six spin-lock times of 0, 10, 20, 25, 35, 50msec and a single breathhold of 12 seconds. Six slices were acquired for each examination.ResultsFemale liver T1rho value ranged between 35.07 to 51.97ms, showed an age-dependent decrease with younger women had a higher measurement. Male Liver T1rho values ranged between 34.94 to 43.39 ms, and there was no evidential age-dependence. For females, there was a trend that liver T1rho value could be 4%-5% lower during menstrual phase than nonmenstrual phase. For both females and males, no evidential association was seen between body mass index and liver T1rho.ConclusionLiver T1rho physiological value for males have relatively narrow distribution, while physiological value for females have wider distribution, and decreases with age.Key points1. Liver T1rho shows an age-dependency in women, with young women showing higher measurement. This age-dependency of liver T1rho measurement is not evidential in men. Post-menopausal women have similar liver T1rho value as men.2. Women at menstrual phase may have slight lower liver T1rho measurement.3. No association was noted between body mass index and liver T1rho4. When blood signal suppression sequence is used, in a population of 62 healthy women and 34 healthy men, the highest measured liver T1rho was 52 msec for young women, 44.7 msec for post-menopausal women, and 43.4 msec for men.
A New Mechanism To Identify Cost Savings in NHS Prescribing: Minimising “Price-Per-Unit”
Authors: Croker Richard , Walker Alex J , Bacon Seb , Curtis Helen J , French Lisa , Goldacre Ben 
Published: August 2017

AbstractBackgroundMinimising prescription costs while maintaining quality is a core element of delivering high value healthcare. There are various strategies to achieve savings, but almost no research to date on determining the most effective approach. We describe a new method of identifying potential savings due to large national variations in drug cost, including variation in generic drug cost; and compare these with potential savings from an established method (generic prescribing).MethodsWe used English NHS Digital prescribing data, from October 2015 to September 2016. Potential cost savings were calculated by determining the price-per-unit (e.g. pill, ml) for each drug and dose within each general practice. This was compared against the same cost for the practice at the lowest cost decile, to determine achievable savings. We compared these price-per-unit savings to the savings possible from generic switching; and determined the chemicals with the highest savings nationally. A senior pharmacist manually assessed whether a random sample of savings were practically achievable.ResultsWe identified a theoretical maximum of £410M of savings over 12 months. £273M of these savings were for individual prescribing changes worth over £50 per practice per month; this compares favorably with generic switching, where only £35M of achievable savings were identified. The biggest savings nationally were on glucose blood testing reagents (£12M), fluticasone propionate (£9M) and venlafaxine (£8M). Approximately half of all savings were deemed practically achievable.DiscussionWe have developed a new method to identify and enable large potential cost savings within NHS community prescribing. Given the current pressures on the NHS, it is vital that these potential savings are realised. Our tool enabling doctors to achieve these savings is now launched in pilot form. However savings could potentially be achieved more simply through national policy change.AbbreviationsBNFBritish National FormularyCCGClinical Commissioning GroupGPGeneral PracticeMRModified ReleaseNHSNational Health ServiceNICNet Ingredient CostNP8Non-Part VIII, i.e. drugs not listed in Part VIII of the Drug TariffPPUPrice-Per-Unit
Multi-clonal evolution of MDR/XDRM. tuberculosisin a high prevalence setting in Papua New Guinea over three decades
Authors: Bainomugisa Arnold , Lavu Evelyn , Hiashiri Stenard , Majumdar Suman , Honjepari Alice , Moke Rendi , Dakulala Paison , Hill-Cawthorne Grant A. , Sushil Pandey , Marais Ben J. , Coulter Christopher , Coin Lachlan J. M. 
Published: August 2017

AbstractAn outbreak of multi-drug resistant tuberculosis has been reported on Daru Island, Papua New Guinea. TheMycobacterium tuberculosisstrains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. We analyzed 100 isolates using whole genome sequencing and found 95 belonged to a single modern Beijing strain cluster. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with virulence potentially enhanced by amycP1mutation. The outbreak cluster demonstrated a high degree of co-resistance between isoniazid and ethionamide (80/95; 84.2%) attributed to aninhApromoter mutation combined withinhAandndhcoding mutations. Multidrug resistance (MDR), observed in 78/95 samples, emerged with the acquisition of a typicalrpoBmutation together with a compensatoryrpoCmutation in the 1980s. There was independent acquisition of fluoroquinolone and aminoglycoside resistance; with evidence of local transmission of extensively-drug resistant (XDR) strains from 2009. These findings underscore the importance of whole-genome sequencing in informing an effective public health response to MDR/XDRM. tuberculosis.
NmeCas9 is an intrinsically high-fidelity genome editing platform
Authors: Amrani Nadia , Gao Xin D. , Liu Pengpeng , Edraki Alireza , Mir Aamir , Ibraheim Raed , Gupta Ankit , Sasaki Kanae E. , Wu Tong , Donohoue Paul D. , Settle Alexander H. , Lied Alexandra M. , McGovern Kyle , Fuller Chris K. , Cameron Peter , Fazzio Thomas G. , Zhu Lihua Julie , Wolfe Scot A. , Sontheimer Erik J. 
Published: August 2017

ABSTRACTBackgroundThe development of CRISPR genome editing has transformed biomedical research. Most applications reported thus far rely upon the Cas9 protein from Streptococcus pyogenes SF370 (SpyCas9). With many RNA guides, wild-type SpyCas9 can induce significant levels of unintended mutations at near-cognate sites, necessitating substantial efforts toward the development of strategies to minimize off-target activity. Although the genome-editing potential of thousands of other Cas9 orthologs remains largely untapped, it is not known how many will require similarly extensive engineering to achieve single-site accuracy within large (e.g. mammalian) genomes. In addition to its off-targeting propensity, SpyCas9 is encoded by a relatively large (~4.2 kb) open reading frame, limiting its utility in applications that require size-restricted delivery strategies such as adeno-associated virus vectors. In contrast, some genome-editing-validated Cas9 orthologs (e.g. from Staphylococcus aureus, Campylobacter jejuni, Geobacillus stearothermophilus and Neisseria meningitidis) are considerably smaller and therefore better suited for viral delivery.ResultsHere we show that wild-type NmeCas9, when programmed with guide sequences of natural length (24 nucleotides), exhibits a nearly complete absence of unintended editing in human cells, even when targeting sites that are prone to off-target activity with wildtype SpyCas9. We also validate at least six variant protospacer adjacent motifs (PAMs), in addition to the preferred consensus PAM (5’-N4GATT-3’), for NmeCas9 genome editing in human cells.ConclusionsOur results show that NmeCas9 is a naturally high-fidelity genome editing enzyme and suggest that additional Cas9 orthologs may prove to exhibit similarly high accuracy, even without extensive engineering.
Whole chromosome loss in tetraploid cells confers tumorigenic potential in a mouse allograft model
Authors: Thomas Rozario , Marks Daniel H , Chin Yvette , Benezra Robert 
Published: August 2017

AbstractWhole chromosome gains or losses (aneuploidy) are a hallmark of ~70% of human tumors. Modeling the consequences of aneuploidy has relied on perturbing spindle assembly checkpoint (SAC) components but interpretations of these experiments are clouded by the multiple functions of these proteins. Here we used a Cre recombinase-mediated chromosome loss strategy to individually delete mouse chromosomes 9, 10, 12 or 14 in tetraploid immortalized murine embryonic fibroblasts. While the aneuploid cells generally display a growth disadvantagein vitro, they grow significantly better in low adherence sphere-forming conditions and 3 of the 4 lines are transformedin vivo, forming large and invasive tumors in immunocompromised mice. The aneuploid cells display increased chromosomal instability and DNA damage, a mutator phenotype associated with tumorigenesisin vivo.Thus, these studies demonstrate a causative role for whole chromosome loss in tumorigenesis and may shed light on the early consequences of aneuploidy in mammalian cells.
In situgenome editing method suitable for routine generation of germline modified animal models
Authors: Ohtsuka Masato , Miura Hiromi , Arifin Naomi , Nakamura Shingo , Wada Kenta , Gurumurthy Channabasavaiah B. , Sato Masahiro 
Published: August 2017

AbstractAnimal genome engineering experimental procedures involve three major steps: isolation of zygotes from pregnant females; microinjection of zygotes, and; transfer of injected zygotes into recipient females, that have been practiced for over three decades. The laboratory set ups intending to performing these procedures require to have sophisticated equipment as well as highly skilled technical personnel. Because of these reasons, animal transgenesis experiments are typically performed at centralized core facilities in most research organizations. We recently showed that all three steps, of animal transgensis, can be bypassed using a method termed GONAD (Genome-editing viaOviductalNucleicAcidsDelivery), by directly electroporating genome editing components into zygotesin situ. Although our first report demonstrated the genome-editing capability, its efficiency was lower than the standard methods using microinjection. Here we investigated critical parameters of GONAD to make it suitable for creating animal models of large genomic deletions, single nucleotide corrections and long sequence insertions. The efficiency of genome editing in the improved GONAD (i-GONAD) method reached to the levels comparable to traditional microinjection methods. The streamlined parameters, and the simplified experimental steps, in thei-GONAD method makes it suitable for routine genome editing applications performed both at centralized facilities as well as at the laboratories that lack highly skilled personnel and the sophisticated equipment.
Modulation of host learning inAedes aegyptimosquitoes
Authors: Vinauger Clément , Lahondère Chloé , Wolff Gabriella H. , Locke Lauren T. , Liaw Jessica E. , Parrish Jay Z. , Akbari Omar S. , Dickinson Michael H. , Riffell Jeffrey A. 
Published: August 2017

AbstractHow mosquitoes determine which individuals to bite has important epidemiological consequences. This choice is not random; most mosquitoes specialize in one or a few vertebrate host species, and some individuals in a host population are preferred over others. Here we show that aversive olfactory learning contributes to mosquito preference both between and within host species. Combined electrophysiological and behavioural recordings from tethered flying mosquitoes demonstrated that these odours evoke changes in both behaviour and antennal lobe (AL) neuronal responses. Using electrophysiological and behavioural approaches, and CRISPR gene editing, we demonstrate that dopamine plays a critical role in aversive olfactory learning and modulating odour-evoked responses in AL neurons. Collectively, these results provide the first experimental evidence that olfactory learning in mosquitoes can play an epidemiological role.
Tolerance to hypothermic and antinoceptive effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in rats
Authors: Nguyen Jacques D. , Grant Yanabel , Kerr Tony M. , Gutierrez Arnold , Cole Maury , Taffe Michael A. 
Published: August 2017

AbstractRationaleA reduced effect of a given dose of Δ9-tetrahydrocannabinol (THC) emerges with repeated exposure to the drug. This tolerance can vary depending on THC dose, exposure chronicity and the behavioral or physiological measure of interest. A novel THC inhalation system based on e-cigarette technology has been recently shown to produce the hypothermic and antinociceptive effects of THC in rats.ObjectiveTo determine if tolerance to these effects can be produced with repeated vapor inhalation.MethodsGroups of male and female Wistar rats were exposed to 30 minutes of inhalation of the propylene glycol (PG) vehicle or THC (200 mg/mL in PG) two or three times per day for four days. Rectal temperature changes and nociception were assessed after the first exposure on the first and fourth days of repeated inhalation.ResultsFemale, but not male, rats developed tolerance to the hypothermic and antinociceptive effects of THC after four days of twice-daily THC vapor inhalation. Thrice daily inhalation for four days resulted in tolerance in both male and female rats. The plasma THC levels reached after a 30 minute inhalation session did not differ between the male and female rats.ConclusionsRepeated daily THC inhalation induces tolerance in female and male rats, providing further validation of the vapor inhalation method for preclinical studies.AbbreviationsPG, propylene glycol; THC; Δ9tetrahydrocannabinol;
DeepATAC: A deep-learning method to predict regulatory factor binding activity from ATAC-seq signals
Authors: Hiranuma Naozumi , Lundberg Scott , Lee Su-In 
Published: August 2017

AbstractDetermining the binding locations ofregulatory factors, such as transcription factors and histone modifications, is essential to both basic biology research and many clinical applications. Obtaining such genome-wide location maps directly is often invasive and resource-intensive, so it is common to impute binding locations from DNA sequence or measures of chromatin accessibility. We introduce DeepATAC, a deep-learning approach for imputing binding locations that uses both DNA sequence and chromatin accessibility as measured by ATAC-seq. DeepATAC significantly outperforms current approaches such as FIMO motif predictions overlapped with ATAC-seq peaks, and models based only on DNA sequence, such as DeepSEA. Visualizing the input importances for the DeepATAC model reveals DNA sequence motifs and ATAC-seq signal patterns that are important for predicting binding events. The Keras implementation and analysis pipelines of DeepATAC are available athttps://github.com/hiranumn/deepatac.
Geobacter sulfurreducensextracellular multiheme cytochrome PgcA facilitates respiration to Fe(III) oxides but not electrodes
Authors: Zacharoff Lori , Morrone Dana , Bond Daniel R. 
Published: August 2017

AbstractExtracellular cytochromes are hypothesized to facilitate the final steps of electron transfer between the outer membrane of the metal-reducing bacteriumGeobacter sulfurreducensand solid-phase electron acceptors such as metal oxides and electrode surfaces during the course of respiration. The trihemec-type cytochrome PgcA exists in the extracellular space ofG. sulfurreducens, and is one of many multihemec-type cytochromes known to be loosely bound to the bacterial outer surface. Deletion ofpgcAusing a markerless method resulted in mutants unable to transfer electrons to Fe(III) and Mn(IV) oxides; yet the same mutants maintained the ability to respire electrode surfaces and soluble Fe(III) citrate. When expressed and purified fromShewanella oneidensis, PgcA demonstrated a primarily alpha helical structure, three bound hemes, and was processed into a shorter 41 kDa form lacking the lipodomain. Purified PgcA bound Fe(III) oxides, but not magnetite, and when PgcA was added to cell suspensions ofG. sulfurreducens,PgcA accelerated Fe(III) reduction similar to addition of FMN. Addition of soluble PgcA to ∆pgcAmutants also restored Fe(III) reduction. This report highlights a distinction between proteins involved in extracellular electron transfer to metal oxides and poised electrodes, and suggests a specific role for PgcA in facilitating electron transfer at mineral surfaces.
Mouse MRI shows brain areas larger in males emerge earlier than those larger in females
Authors: Qiu Lily R. , Fernandes Darren J. , Szulc Kamila U. , Dazai Jun , Nieman Brian J. , Turnbull Daniel H. , Palmert Mark R. , Lerch Jason P. 
Published: August 2017

2AbstractSex differences exist in behaviours, disease and neuropsychiatric disorders. Sexual dimorphisms however, have yet to be studied across the whole brain and across a comprehensive time course of postnatal development. We used manganese-enhanced MRI (MEMRI) to longitudinally image male and female C57BL/6J mice across 9 time points, beginning at postnatal day 3. We recapitulated findings on canonically dimorphic areas, demonstrating the ability of MEMRI to study neuroanatomical sex differences. We discovered, upon whole-brain volume correction, that neuroanatomical regions larger in males develop early in life, while regions larger in females develop in peripubertal life. Furthermore, we found groups of areas with shared sexually dimorphic developmental trajectories that reflect behavioural and functional networks, and expression of genes involved with sex processes. Our results demonstrate the ability of MEMRI to reveal comprehensive developmental differences between male and female brains, which will improve our understanding of sex-specific predispositions to various neuropsychiatric disorders.