bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplexed CRISPR-Cas9 based genome editing ofRhodosporidium toruloides
Authors: Otoupal Peter B. , Ito Masakazu , Arkin Adam P. , Magnuson Jon K. , Gladden John M. , Skerker Jeffrey M. 
Published: February 2019

ABSTRACTMicrobial production of biofuels and bioproducts offers a sustainable and economic alternative to petroleum-based fuels and chemicals. The basidiomycete yeastRhodosporidium toruloidesis a promising platform organism for generating bioproducts due to its ability to consume a broad spectrum of carbon sources (including those derived from lignocellulosic biomass) and to naturally accumulate high levels of lipids and carotenoids, two biosynthetic pathways that can be leveraged to produce a wide range of bioproducts. WhileR. toruloideshas great potential, it has a more limited set of tools for genetic engineering relative to more advanced yeast platform organisms such asYarrowia lipolyticaandSaccharomyces cerevisiae.Significant advancements in the past few years have bolsteredR. toruloides’engineering capacity. Here we expand this capacity by demonstrating the first use of CRISPR-Cas9 based gene disruption inR. toruloides.Stably integrating a Cas9 expression cassette into the genome brought about successful targeted disruption of the nativeURA3gene. While editing efficiencies were initially low (0.002%), optimization of the cassette increased efficiencies 364-fold (to 0.6%). Applying these optimized design conditions enabled disruption of another native gene involved in carotenoid biosynthesis,CAR2,with much greater success; editing efficiencies ofCAR2deletion reached roughly 50%. Finally, we demonstrated efficient multiplexed genome editing by disrupting bothCAR2andURA3in a single transformation. Together, our results provide a framework for applying CRISPR-Cas9 toR. toruloidesthat will facilitate rapid and high throughput genome engineering in this industrially relevant organism.IMPORTANCEMicrobial biofuel and bioproduct platforms provide access to clean and renewable carbon sources that are more sustainable and environmentally friendly than petroleum-based carbon sources. Furthermore, they can serve as useful conduits for the synthesis of advanced molecules that are difficult to produce through strictly chemical means.R. toruloideshas emerged as a promising potential host for converting renewable lignocellulosic material into valuable fuels and chemicals. However, engineering efforts to improve the yeast’s production capabilities have been impeded by a lack of advanced tools for genome engineering. While this is rapidly changing, one key tool remains unexplored inR. toruloides; CRISPR-Cas9. The results outlined here demonstrate for the first time how effective multiplexed CRISPR-Cas9 gene disruption provides a framework for other researchers to utilize this revolutionary genome-editing tool effectively inR. toruloides.
TAF1-gene editing impairs Purkinje cell morphology and function
Authors: Janakiraman Udaiyappan , Yu Jie , Moutal Aubin , Batchelor Shelby N. , Annadurai Anandhan , Khanna Rajesh , Nelson Mark A. 
Published: February 2019

AbstractTAF1 intellectual disability syndrome is an X-linked disorder caused by loss-of-function mutations in the TAF1 gene. How these mutations cause dysmorphology, hypotonia, intellectual and motor defects is unknown. Mouse models which have embryonically targeted TAF1 have failed, possibly due to TAF1 being essential for viability, preferentially expressed in early brain development, and intolerant of mutation. Novel animal models are valuable tools for understanding neuronal pathology. Here, we report the development and characterization of a novel animal model for TAF1 ID syndrome in which theTAF1gene is deleted in embryonic rats using clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) technology and somatic brain transgenesis mediated by lentiviral transduction. Rat pups, post-natal day 3, were subjected to intracerebroventricular (ICV) injection of either gRNA-control or gRNA-TAF1 vectors. Rats were subjected to a battery of behavioral tests followed by histopathological analyses of brains at post-natal day 14 and day 35.TAF1-edited rats exhibited behavioral deficits at both the neonatal and juvenile stages of development. Deletion of TAF1 lead to a hypoplasia and loss of the Purkinje cells. Abnormal motor symptoms in TAF1-edited rats were associated with irregular cerebellar output caused by changes in the intrinsic activity of the Purkinje cells. Immunostaining revealed a reduction in the expression of the CaV3.1 T-type calcium channel. This animal model provides a powerful new tool for studies of neuronal dysfunction in conditions associated with TAF1 abnormalities and should prove useful for developing therapeutic strategies to treat TAF1 ID syndrome.Significance StatementIntellectual disability (ID) syndrome is an X-linked rare disorder caused by loss-of-function mutations in theTAF1gene. There is no animal model for understanding neuronal pathology and to facilitate development of new therapeutics for this X-linked intellectual disability syndrome. Novel animal models are valuable tools for understanding neuronal pathology and to facilitate development of new therapeutics for diseases. Here we developed a novel animal model for TAF1 ID syndrome in which theTAF1gene is deleted by CRISPR-Cas9 editing and lentiviral transduction. This animal model provides a powerful new tool for studies of neuronal dysfunction associated with TAF1 abnormalities and should prove useful for developing therapeutic strategies to treat TAF1 ID syndrome.
Biogeography and Microscale Diversity Shape the Biosynthetic Potential of Fungus-growing Ant-associated Pseudonocardia
Authors: McDonald Bradon R. , Chevrette Marc G. , Klassen Jonathan L. , Horn Heidi A. , Caldera Eric J. , Wendt-Pienkowski Evelyn , Cafaro Matias J. , Ruzzini Antonio C. , Van Arnam Ethan B. , Weinstock George M. , Gerardo Nicole M. , Poulsen Michael , Suen Garret , Clardy Jon , Currie Cameron R. 
Published: February 2019

AbstractThe geographic and phylogenetic scale of ecologically relevant microbial diversity is still poorly understood. Using a model mutualism, fungus-growing ants and their defensive bacterial associate Pseudonocardia, we analyzed genetic diversity and biosynthetic potential in 46 strains isolated from ant colonies in a 20km transect near Barro Colorado Island in Panama. Despite an average pairwise core genome similarity of greater than 99%, population genomic analysis revealed several distinct bacterial populations matching ant host geographic distribution. We identified both genetic diversity signatures and divergent genes distinct to each lineage. We also identify natural product biosynthesis clusters specific to isolation locations. These geographic patterns were observable despite the populations living in close proximity to each other and provides evidence of ongoing genetic exchange. Our results add to the growing body of literature suggesting that variation in traits of interest can be found at extremely fine phylogenetic scales.
Warming affects predatory faunal impacts upon microbial carbon cycling
Authors: Hunter William Ross , Ogle Neil , O’Connor Nessa 
Published: February 2019

Abstract

Ocean warming and the loss of larger (often predatory) fauna are major threats to seabed (benthic) ecosystem functioning. Yet, we know little about the combined effects of warming and faunal species loss upon the marine carbon cycle.

Using stable isotope pulse‐chase experiments, we tested how faunal species loss affects microbial carbon sequestration and retention in intertidal sediments, under both ambient and predicted future warming conditions (ambient +2°C), using the shore crab Carcinus maenas as a model predator. We traced the fixation and retention of a fixed dose of 13C‐labelled sodium bicarbonate within sediment organic matter and microbial biomass.

Carcinus presence was associated with higher total organic carbon concentration within the mesocosm sediments. Temperature had no significant effect upon sediment total organic carbon concentrations. Temperature and Carcinus presence had no significant effect on polar lipid fatty acid (PLFA) concentrations within the sediment, which is a proxy for microbial biomass.

Carcinus presence increased retention of 13C‐labelled carbon within the sediment organic matter pool under future warming conditions. Retention of the 13C‐label within the microbial PLFAs decreased significantly under future warming conditions.

Changes in the relative abundance of PLFAs revealed increased contribution of microeukaryotes to the microbial community under ambient conditions, in the absence of Carcinus. PLFA profiles revealed significant changes in 13C‐label retention within the bacteria and microeukaryotes, driven by interactions between Carcinus presence and temperature.

Given that temperature is a fundamental control on the metabolic activity of marine organisms (from bacteria to metazoans), we propose that interactions between faunal species loss and ocean warming will have a pronounced effect upon marine carbon budgets.

A plain language summary is available for this article.
Management of pharmacotherapy‐related problems in acute coronary syndrome: Role of clinical pharmacist in cardiac rehabilitation unit
Authors: Casper Eman Ahmed , El Wakeel Lamiaa Mohamed , Saleh Mohamed Ayman , El‐Hamamsy Manal Hamed 
Published: February 2019

AbstractAcute coronary syndrome (ACS) is one of the leading causes of mortality worldwide and negatively impacts healthcare costs, productivity and quality of life. Polymorbidity and polypharmacy predispose ACS patients to medication discrepancies between cardiologist‐prescribed medication and drug use by the patient, drug‐related problems (DRPs) and inadequate drug adherence. This study aimed to evaluate the impact of clinical pharmacist–provided services on the outcome of ACS patients. This was a prospective, randomized, controlled study on ACS patients participating in a cardiac rehabilitation programme. Forty ACS patients were randomly assigned to either control group, who received standard medical care, or intervention group, who received standard medical care plus clinical pharmacist–provided services. Services included DRP management, clinical assessment and enforcing the patient education and adherence. For both groups, the following were assessed at baseline and after 3 months: DRPs, adherence (assessed by 8‐item Morisky Adherence Questionnaire), patient's knowledge (assessed by Coronary Artery Disease Questionnaire), 36‐Short Form Health Survey (SF‐36), heart rate, systolic and diastolic blood pressure, low‐density lipoprotein (LDL), total cholesterol (TC) and fasting blood glucose (FBG). After 3 months, there was a significant difference between the intervention and control groups in the per cent change of DRPs (median: −100 vs 5.882, P = 0.0001), patient's adherence score (median: 39.13 vs −14.58, P = 0.0001), knowledge score (median: 30.28 vs −5.196, P = 0.0001), SF‐36 scores, heart rate (mean: −10.04 vs 6.791, P = 0.0001), diastolic blood pressure (mean: −17.87 vs 10.45, P = 0.0001), systolic blood pressure (mean: −16.22 vs 4.751, P = 0.0001), LDL (median: −25.73 vs −0.2538, P = 0.0071), TC (median: −14.62 vs 4.123, P = 0.0005) and FBG (median: −11.42 vs 5.422, P = 0.0098). Clinical pharmacists can play an important role as part of a cardiac rehabilitation team through patient education and interventions to minimize DRPs.
Spatial distribution of micrometre‐scale porosity and permeability across the damage zone of a reverse‐reactivated normal fault in a tight sandstone: Insights from the Otway Basin, SE Australia
Authors: Debenham Natalie , Farrell Natalie J. C. , Holford Simon P. , King Rosalind C. , Healy David 
Published: February 2019

AbstractKnowledge of the permeability structure of fault‐bearing reservoir rocks is fundamental for developing robust hydrocarbon exploration and fluid monitoring strategies. Studies often describe the permeability structure of low porosity host rocks that have experienced simple tectonic histories, while investigations of the influence of faults with multiple‐slip histories on the permeability structure of porous clastic rocks are limited. We present results from an integrated petrophysical, microstructural, and mineralogical investigation of the Eumeralla Formation (a tight volcanogenic sandstone) within the hanging wall of the Castle Cove Fault which strikes 30 km NE–SW in the Otway Basin, southeast Australia. This late Jurassic to Cenozoic‐age basin has experienced multiple phases of extension and compression. Core plugs and thin sections oriented relative to the fault plane were sampled from the hanging wall at distances of up to 225 m from the Castle Cove Fault plane. As the fault plane is approached, connected porosities increase by ca. 10% (17% at 225 m to 24% at 0.5 m) and permeabilities increase by two orders of magnitude (from 0.04 mD at 225 m to 1.26 mD at 0.5 m). Backscattered Scanning Electron Microscope analysis shows that microstructural changes due to faulting have enhanced the micrometre‐scale permeability structure of the Eumeralla Formation. These microstructural changes have been attributed to the formation of microfractures and destruction of original pore‐lining chlorite morphology as a result of fault deformation. Complex deformation, that is, formation of macrofractures, variably oriented microfractures, and a hanging wall anticline, associated with normal faulting and subsequent reverse faulting, has significantly influenced the off‐fault fluid flow properties of the protolith. However, despite enhancement of the host rock permeability structure, the Eumeralla Formation at Castle Cove is still considered a tight sandstone. Our study shows that high‐resolution integrated analyses of the host rock are critical for describing the micrometre‐scale permeability structure of reservoir rocks with high porosities, low permeabilities, and abundant clays that have experienced complex deformation.
Does Inattention and Hyperactivity Moderate the Relation Between Speed of Processing and Language Skills?
Authors: Gooch Debbie , Sears Claire , Maydew Harriet , Vamvakas George , Norbury Courtenay F. 
Published: February 2019

The causal role of speed of processing (SOP) in developmental language disorder (DLD) is unclear given that SOP has been implicated in other neurodevelopmental disorders such as attention‐deficit/hyperactivity disorder. This study investigated associations between SOP, language, and inattention/hyperactivity in a U.K. epidemiological cohort (N = 528). Monolingual children from a range of socioeconomic backgrounds were assessed longitudinally; at ages 5–6 (2012/2013) and 7–8 years (2014/2015). Persistent weaknesses in SOP characterized children with DLD but did not predict language longitudinally. Ratings of inattention/hyperactivity moderated the association between SOP and language, indicating that SOP deficits are particularly detrimental for language when coupled with poor attention/hyperactivity. SOP may be a shared risk factor for DLD and inattention/hyperactivity or a general marker of neurodevelopmental disorder.
The Development of Nonsymbolic Probability Judgments in Children
Authors: O'Grady Shaun , Xu Fei 
Published: February 2019

Two experiments were designed to investigate the developmental trajectory of children's probability approximation abilities. In Experiment 1, results revealed 6‐ and 7‐year‐old children's (N = 48) probability judgments improve with age and become more accurate as the distance between two ratios increases. Experiment 2 replicated these findings with 7‐ to 12‐year‐old children (N = 130) while also accounting for the effect of the size and the perceived numerosity of target objects. Older children's performance suggested the correct use of proportions for estimating probability; but in some cases, children relied on heuristic shortcuts. These results suggest that children's nonsymbolic probability judgments show a clear distance effect and that the acuity of probability estimations increases with age.
Associations between maternal age at menarche and anthropometric and metabolic parameters in the adolescent offspring
Authors: Hong Ye , Maessen Sarah E. , Dong Guanping , Huang Ke , Wu Wei , Liang Li , Wang Chun Lin , Chen Xiaochun , Gibbins John D. , Cutfield Wayne S. , Derraik José G.B. , Fu JunFen 
Published: February 2019

SummaryObjectiveWe examined the associations between maternal age at menarche and anthropometry and metabolism in adolescent offspring.MethodsAnthropometric, metabolic and blood pressure data were obtained from 304 girls and 190 boys aged 11‐16 years attending school in Hangzhou (China). Age at menarche for both mothers and daughters was self‐reported. Fasting blood samples were obtained and all participants underwent clinical examinations. Obesity was defined as BMI ≥95th percentile for age and sex.ResultsOlder maternal age at menarche was associated with older age of their daughters at menarche (r = 0.21; P < 0.001). Mother's age at menarche was not associated with anthropometry or metabolism of daughters. However, younger maternal age at menarche was associated with increased hip and waist circumferences, and BMI SDS of their sons. Boys whose mothers were ≤13 years at menarche had an adjusted relative risk of obesity 3‐fold greater than sons of mothers with a later menarcheal onset (2.96; 95% CI 1.49, 5.87). Among daughters, every 1‐year increase in their age at menarche was associated with a 0.34 SDS reduction in BMI. Increasing age at menarche was also associated with reduced waist and hip circumferences (−1.5 and −1.8 cm/y, respectively) and waist‐to‐height ratio (−0.008 per year). Girls in the youngest menarcheal age tertile (8.8‐11.6 years) had diastolic blood pressure 2.2 mm Hg higher than other girls (P = 0.029).ConclusionsYounger maternal age at menarche is associated with increased obesity risk in their sons, but not daughters. However, girls who experience menarche earlier have a less favourable anthropometric profile.
Adaptation of the Mullen Scales of Early Learning for use among infants aged 5‐ to 24‐months in rural Gambia
Authors: Milosavljevic Bosiljka , Vellekoop Perijne , Maris Helen , Halliday Drew , Drammeh Saikou , Sanyang Lamin , Darboe Momodou K. , Elwell Clare , Moore Sophie E. , Lloyd‐Fox Sarah 
Published: February 2019

AbstractInfants in low‐resource settings are at heightened risk for compromised cognitive development due to a multitude of environmental insults in their surroundings. However, the onset of adverse outcomes and trajectory of cognitive development in these settings is not well understood. The aims of the present study were to adapt the Mullen Scales of Early Learning (MSEL) for use with infants in a rural area of The Gambia, to examine cognitive development in the first 24‐months of life and to assess the association between cognitive performance and physical growth. In Phase 1 of this study, the adapted MSEL was tested on 52 infants aged 9‐ to 24‐months (some of whom were tested longitudinally at two time points). Further optimization and training were undertaken and Phase 2 of the study was conducted, where the original measures were administered to 119 newly recruited infants aged 5‐ to 24‐months. Infant length, weight and head circumference were measured concurrently in both phases. Participants from both phases were split into age categories of 5–9 m (N = 32), 10–14 m (N = 92), 15–19 m (N = 53) and 20–24 m (N = 43) and performance was compared across age groups. From the ages of 10–14 m, Gambian infants obtained lower MSEL scores than US norms. Performance decreased with age and was lowest in the 20–24 m old group. Differential onsets of reduced performance were observed in the individual MSEL domains, with declines in visual perception and motor performance detected as early as at 10–14 months, while reduced language scores became evident after 15–19 months of age. Performance on the MSEL was significantly associated with measures of growth.
Digestibility of common native starches with reference to starch granule size, shape and surface features towards guidelines for starch‐containing food products
Authors: Corgneau Magda , Gaiani Claire , Petit Jeremy , Nikolova Yoana , Banon Sylvie , Ritié‐Pertusa Léa , Le Doan Thanh Lam , Scher Joël 
Published: February 2019

SummaryInfluence of diverse botanical sources (wheat, maize, waxy maize, cassava, potato, rice or waxy rice) on in vitro native starch digestibility has been investigated. Physicochemical properties (chemical composition, particles size and shape, surface features) of starch granules were determined with a view to explaining digestibility differences between samples. Rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS) contents were measured according to Englyst method. Potato starch was shown to be composed of large rounded granules having smooth surfaces, which explains its slow enzymatic breakdown. Potato starch displayed the highest RS (86%) content and the lowest RDS content (9.9%). Since RS positively influences health and SDS may result in cell, tissue and/or organ damages, potato starch is an ideal starch nutrient. Conversely, waxy rice starch was rich in amylopectin and displayed small diameters and angular shapes, which are both known to facilitate enzymatic starch hydrolysis. It exhibited a near‐zero RS content (0.9%) and a high RDS fraction (60%). According to this study, potato starch exhibited the best nutrient profile, followed up in this order by cassava, waxy maize, wheat, maize and waxy rice starches.
Interfacial structures of spinel crystals with borosilicate nuclear waste glasses from molecular dynamics simulations
Authors: Sun Wei , Du Jincheng 
Published: February 2019

AbstractSpinel crystal formation presents a critical issue and glass formulation in nuclear waste glass processing. In this paper, the interfacial structures of the model borosilicate nuclear waste glasses, the international simple glass (ISG), with two types of spinel crystals, namely the MgAl2O4 and NiFe2O4, were studied using classical molecular dynamics simulations with effective partial charge potentials and recently developed composition‐dependent boron‐related parameters. The simulation results revealed the structural features of the borosilicate nuclear waste glasses and their interfaces with the two types of spinel crystals. It was found that there exist notable structural changes of glasses close to the interfacial region, affected by the adjacent crystal structures, terms of preferential segregation and ordering of cations, as well as ctaion coordination numbers. Specifically, the fraction of fourfold coordinated boron (B3) in glass near the interface decreases as compared to the bulk glass. In addition, the amount of fourfold coordinated Al decreases while fivefold Al increases in the glass region close to the glass‐crystal interface, which suggests indication of initial stage of crystal growth as Al adopts higher (sixfold) coordination like in the crystal as compared to majority of fourfold coordination in the glass. These interfacial structure changes obtained from MD simulations provide evidence of the influence of the precipitated crystals on the surrounding melt and glass and the initial stage of crystal growth.