bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Florisynthesis of Silver Nano Particles Using Cordia Sebastena Linn
Authors: Ramalingam Arulmathi , Udayaprakash N.K.
Published: September 2019

Synthesis of Silver Nanoparticles [AgNPs] using biological method is widely studied. This mostly involves the extracts of leaves of different plants which resulted in nano/microparticle formation. This was mostly due to the presence of complex phytochemicals. However flower of the plants are found to possess minimal amount of secondary metabolites as well as carotenoid pigments which may serve as a reducing agent. Thus, in this study synthesis of Silver nanoparticles using floral extract of Cordia sebastena and optimization in their synthesis using different pH [5, 7 and 9], concentration of silver nitrate [1mM, 2Mm and 3mM] and floral extract [0.5:10, 1:10 and 1.5:10] was conducted. The characterization of AgNPs was carried using UV-Visible Spectrophotometer, Fourier Transform Infra Red [FTIR] Spectrophotometer and Dynamic Light Scattering [DLS]. Further, the floral extract was screened for the presence of different phytoconstituents. The study showed varied Plasmon resonance ranging from 430 to 470nm. Fourier transform infrared spectrum reveals the presence of phytochemicals which acted as reducing and stabilizing agent. The presence of Alkaloids, flavonoids, Phenols, tannins, cardiac glycosides, terpenoids and pholobatannins were recorded in the extract of the flower of Cordia sebastena. The study confirmed the synthesis of AgNPs with the average particle size of 85.2nm. The optimized condition revealed that the flower extract added with 1: 10 concentration to 2mM silver nitrate at pH9 gives smaller AgNPs.
Experimental analysis of a solar cooker with a parabolic trough enhanced with PCM based thermal storage
Authors: Babu Sasi Kumar S. , Chinna Pandian M.
Published: September 2019

Experiments are conducted on solar cooker using solar energy. Heat collected by a fluid from the Parabolic Trough Collector (PTC) with the manual Tracking Mechanism(TM) is passed through the Storage Tank (ST). A Phase Change Materials (PCM) in the ST products absorbed the heat in the irregular sunlight and is released constantly for cooking purposes. Based on the observation of PTC and ST, a heat transfer analysis of the Solar Cooker (SC) is carried out considering 0.035, 0.045 and 0.065 kg/sec Mass Flow Rate (MFR) of the heat transfer fluid. At 1 pm, themaximum Heat Gain (HG) of PTC receiver at the Rim Angle (RA) of 82° is found to be 2095 W, 13 KW in ST with a medium of Wastage Engine Oils (WEO). The heat output of the WEO found to be 16% more than that of the water. The efficiency of the newly designed the solar cooker is tested at the MFR 0.035, 0.045 and 0.065 kg/sec along with storage medium. The results of the MFR of 0.035 kg/sec are seen as better than 0.045 and 0.065 kg/sec for the water and WEO medium. Hence the energy extracted is greater. The WEO is seen as more stable with smaller energy losses than the water. Stearic acid (SA) is used for PCM materials.
Investigation on Mode I Interlaminar Fracture Toughness of Chemically Treated / Untreated Saw Dust Powder Based Jute Fabric Reinforced Epoxy Composite Structure
Authors: Suthan R. , Jayakumar V. , Madhu S.
Published: September 2019

Nowadays polymer matrix composites are widely used in the areas of automotive, medical, aircraft and aerospace industries. Since, chemically surface modified saw dust with jute fiber reinforced composites play vital role in developing lightweight structural materials in many engineering industries. This study focuses on utilizingchemically surface modified saw dust with jute fiberas reinforcement filler loading malic acid treated and un treated (10 %,20% and 30%) and fiber loading (3-layer jute fiber) in epoxy resin. This composite was fabricated using hand lay-up process. The influence of filler volume fraction and fiber weight fraction on the fracture toughness properties of treated / untreated modified saw dust with jute fiber/filler was studied initially. Test results revealed that the composite 20-volume fraction malic acid treated saw dust with 3-layer jute fiber composite has better fracture properties as compared with other specimens.
Molecular evolution of MHC class II DRB exon 2 in Japanese and Russian raccoon dogs, Nyctereutes procyonoides (Carnivora: Canidae)
Authors: Bartocillo Aye Mee F , Nishita Yoshinori , Abramov Alexei V , Masuda Ryuichi
Published: September 2019

Raccoon dogs, Nyctereutes procyonoides, are native to East Asia, but have been introduced into western Russia and eastern Europe. To determine allelic diversity and elucidate the evolution of major histocompatibility complex (MHC) class II genes in the raccoon dog, we analysed a 237-bp region of DRB exon 2 from 36 individuals of native and introduced populations from Japan and Russia. We detected 23 DRB alleles (Nypr-DRBs), 22 of which were novel. Some alleles were found across the species’ range, while others were geographically restricted. For both native and introduced populations, the ratio of non-synonymous to synonymous substitution rates for codons at predicted antigen-binding sites was significantly greater than 2, indicating that Nypr-DRBs have evolved under positive selection. Mixed effect model evolution analysis and an algorithm to detect recombination showed five positively selected codons and one recombination breakpoint, respectively. Overall, our results suggest that the diversity of MHC class II DRB in N. procyonoides was influenced and maintained by recombination, pathogen-driven positive selection, geographical barriers and the founder effect. A Bayesian phylogenetic tree revealed no evidence of trans-species polymorphism (TSP), but instead showed monophyly for the Nypr-DRB alleles within a larger clade of canid sequences. The lack of TSP may have been due to long-term divergence of raccoon dogs from other canids, or to their having encountered different sets of pathogens due to occupying a different ecological niche.
Treatment Outcome of a Shorter Regimen Containing Clofazimine for Multidrug-resistant Tuberculosis: A Randomized Control Trial in China
Authors: Du Yadong , Qiu Chao , Chen Xiaohong , Wang Jing , Jing Wei , Pan Hongqiu , Chen Wei , Liu Yufeng , Li Chunxiang , Xi Xiu’e , Yin Hongyun , Zeng Jianfeng , Zhang Xia , Xu Tao , Wang Qingfeng , Guo Ru , Wang Jun , Pang Yu , Chu Naihui
Published: September 2019

Background

The emergence of multidrug-resistant tuberculosis (MDR-TB) poses a serious obstacle to global TB control programs.

Methods

We carried out a prospective, randomized, multicenter study in China that was focused on the potential of a shorter regimen containing clofazimine (CFZ) for the treatment of MDR-TB. There were 135 MDR-TB cases that met eligibility requirements and were randomly stratified into either the control group or experimental group. Patients in the control group received an 18-month treatment regimen, whereas patients in the experimental group received a 12-month treatment regimen containing CFZ.

Results

At the completion of the treatment period, the difference in sputum-culture conversion rates between the experimental group and the control group was not significant. Notably, by the end of 3 months of treatment, 68.7% patients receiving the experimental regimen had sputum-culture conversion, as compared with 55.9% of those receiving the control regimen; this was a significant difference, suggesting an early sputum conversion (P = .04). There were 67 adverse events reported in 56 patients in this study, including 32 in the control group and 35 in the experimental group. No significant difference in the overall incidences of adverse events was observed between the 2 groups.

Conclusions

The MDR-TB patients treated with the shorter regimen containing CFZ had a comparable successful outcome rate when compared to those with the standard regimen. The patients assigned to the experimental group achieved more rapid sputum-culture conversion, reflecting superior antimicrobial activity against MDR-TB.

Clinical Trials Registration

Chinese Clinical Trial Registry ChiCTR 1800020391.
Spontaneous Loss-of-Function Dock2 Mutation Alters Murine Colitis Sensitivity and Is a Confounding Variable in Inflammatory Bowel Disease Research
Authors: Peters Diane E , Norris Lauren D , Slusher Barbara S
Published: September 2019

Background

Dextran sodium sulfate (DSS)-induced colitis is the most commonly used mouse model of inflammatory bowel disease (IBD) due to its acute nature, reproducibility, and phenotypic overlap with human disease. Following an unexpected and sharp decline in DSS-induced colitis susceptibility in our commercially acquired C57Bl/6 wild-type mice, we discovered that a spontaneous loss-of-function mutation in dedicator of cytokinesis 2 (Dock2Hsd) was responsible. Presence of this mutation in research colonies has the capacity to broadly impact preclinical IBD studies.

Methods

DSS-colitis was induced in weight-, age-, and gender-matched C57Bl/6NHsd mice. Daily treatment with vehicle or the glutamate carboxypeptidase II (GCPII) inhibitor, 2-PMPA (100 mg/kg IP), was performed and disease activity index was monitored. At termination, colon GCPII activity was measured.

Results

DSS-treated Dock2Hsd mice developed more severe colitis, had significantly increased colon GCPII activity and were more sensitive to pharmacologic inhibition of GCPII.

Conclusions

The Dock2Hsd mutation is a confounding variable of high relevance to the IBD research community. Dock2Hsd mice were distributed as wild-type C57Bl/6 for multiple years and thus it is unknown how prevalent this mutation is in investigator-maintained colonies of C57Bl/6-derived mice. In our research, presence of the Dock2Hsd mutation caused enhanced GCPII colon activity more closely resembling human disease, providing a useful platform for screening GCPII inhibitors for preclinical efficacy. However, unanticipated presence of Dock2Hsd in genetically modified mice used to study IBD pathobiology can confound conclusions. Thus, care must be taken when interpreting studies performed in mice of C57Bl/6 lineage where Dock2 status is unknown.
Understanding Gender Differences in Leadership
Authors: Alan Sule , Ertac Seda , Kubilay Elif , Loranth Gyongyi
Published: September 2019

Using data from a large-scale field experiment, we show that while there is no gender difference in willingness to make risky decisions on behalf of a group in a sample of children, a large gap emerges in a sample of adolescents. The proportion of girls who exhibit leadership willingness drops by 39%, going from childhood to adolescence. We explore the possible factors behind this drop and find that it is largely associated with a dramatic decline in ‘social confidence’, measured by willingness to perform a real effort task in public.
New Non-Bilaterian Transcriptomes Provide Novel Insights into the Evolution of Coral Skeletomes
Authors: Conci Nicola , Wörheide Gert , Vargas Sergio
Published: September 2019

A general trend observed in animal skeletomes—the proteins occluded in animal skeletons—is the copresence of taxonomically widespread and lineage-specific proteins that actively regulate the biomineralization process. Among cnidarians, the skeletomes of scleractinian corals have been shown to follow this trend. However, distributions and phylogenetic analyses of biomineralization-related genes are often based on only a few species, with other anthozoan calcifiers such as octocorals (soft corals), not being fully considered. We de novo assembled the transcriptomes of four soft-coral species characterized by different calcification strategies (aragonite skeleton vs. calcitic sclerites) and data-mined published nonbilaterian transcriptome resources to construct a taxonomically comprehensive sequence database to map the distribution of scleractinian and octocoral skeletome components. Cnidaria shared no skeletome proteins with Placozoa or Ctenophora, but did share some skeletome proteins with Porifera, such as galaxin-related proteins. Within Scleractinia and Octocorallia, we expanded the distribution for several taxonomically restricted genes such as secreted acidic proteins, scleritin, and carbonic anhydrases, and propose an early, single biomineralization-recruitment event for galaxin sensu stricto. Additionally, we show that the enrichment of acidic residues within skeletogenic proteins did not occur at the Corallimorpharia–Scleractinia transition, but appears to be associated with protein secretion into the organic matrix. Finally, the distribution of octocoral calcification-related proteins appears independent of skeleton mineralogy (i.e., aragonite/calcite) with no differences in the proportion of shared skeletogenic proteins between scleractinians and aragonitic or calcitic octocorals. This points to skeletome homogeneity within but not between groups of calcifying cnidarians, although some proteins such as galaxins and SCRiP-3a could represent instances of commonality.
Maternal seafood consumption during pregnancy and child attention outcomes: a cohort study with gene effect modification by PUFA-related genes
Authors: Julvez Jordi , Fernández-Barrés Sílvia , Gignac Florence , López-Vicente Mónica , Bustamante Mariona , Garcia-Esteban Raquel , Vioque Jesús , Llop Sabrina , Ballester Ferran , Fernández-Somoano Ana , Tardón Adonina , Vrijheid Martine , Tonne Cathryn , Ibarluzea Jesus , Irazabal Amaia , Sebastian-Galles Nuria , Burgaleta Miguel , Romaguera Dora , Sunyer Jordi
Published: September 2019

Background

There is a need to test the fetal programming theoretical framework in nutritional epidemiology. We evaluated whether maternal seafood intake during pregnancy was associated with 8-year-old attention outcomes after adjusting for previous child seafood intake and cognitive function. We also explored effect modification by several single nucleotide polymorphisms (SNPs) related with polyunsaturated fatty acid (PUFA) metabolism.

Methods

Our final analyses included 1644 mother-child pairs from the prospective INMA (INfancia y Medio Ambiente) cohort study (Spain, recruitment between 2003 and 2008). We used food frequency questionnaires to assess prenatal and postnatal seafood consumption of the mother-child pairs. We evaluated attention function of the children through the computer-based Attention Network Test (ANT) and we used the number of omission errors and the hit reaction time standard error (HRT-SE). Parents reported child attention deficit hyperactivity disorder (ADHD) symptoms using the Revised Conners’ Parent Rating Scale Short Form (CPRS-R: S). We measured seven candidate SNPs in a subsample of 845 children. We estimated associations using regression models, adjusting for family characteristics, child seafood intake and cognitive functions at early ages, and to explore SNP effect modifications.

Results

Higher total seafood intake during early pregnancy was associated with a reduction of child ANT omission errors, 5th quintile (median = 854 g/week) vs 1st quintile (median = 195 g/week), incidence risk ratio (IRR) 0.76; 95% CI = 0.61, 0.94. Similar results were observed after adjusting the models for child seafood intake and previous cognitive status. Lean, large and small fatty fish showed similar results, and generally similar but less robust associations were observed with the other attention outcomes. Shellfish and canned tuna showed weaker associations. The association patterns were weaker in late pregnancy and null in child seafood consumption. Child rs1260326 (glucokinase regulator, GCKR) and child/maternal rs2281591 (fatty acid elongase 2, ELOVL2) polymorphisms showed nominal P-value for interactions <0.10 between total seafood intake and ANT outcomes.

Conclusions

After adjusting for previous child cognitive functions and child seafood intake, high pregnancy consumption (total, lean, small and large fatty fish) was independently associated with improvements of some 8-year-old attention outcomes. Genetic effect modification analyses suggest PUFA intake from seafood as a potential biological mechanism of such association.
Locomotion of Ants Walking up Slippery Slopes of Granular Materials
Authors: Humeau A , Piñeirua M , Crassous J , Casas J
Published: September 2019

Many insects encounter locomotory difficulties in walking up sand inclines. This is masterfully exploited by some species for building traps from which prey are rarely able to escape, as the antlion and its deadly pit. The aim of this work is to tear apart the relative roles of granular material properties and slope steepness on the insect leg kinematics, gait patterns, and locomotory stability. For this, we used factorial manipulative experiments with different granular media inclines and the ant Aphaenogaster subterranea. Our results show that its locomotion is similar on granular and solid media, while for granular inclined slopes we observe a loss of stability followed by a gait pattern transition from tripod to metachronal. This implies that neither the discrete nature nor the roughness properties of sand alone are sufficient to explain the struggling of ants on sandy slopes: the interaction between sand properties and slope is key. We define an abnormality index that allows us to quantify the locomotory difficulties of insects walking up a granular incline. The probability of its occurrence reveals the local slipping of the granular media as a consequence of the pressure exerted by the ant’s legs. Our findings can be extended to other models presenting locomotory difficulties for insects, such as slippery walls of urns of pitcher plants. How small arthropods walking on granular and brittle materials solve their unique stability trade-off will require a thorough understanding of the transfer of energy from leg to substrate at the particle level.
The Organismal Form and Function Lab-Course: A New CURE for a Lack of Authentic Research Experiences in Organismal Biology
Authors: Oufiero C E
Published: September 2019

Synopsis

There are many benefits to engaging students in authentic research experiences instead of traditional style lectures and “cookbook” labs. Many Course-based Undergraduate Research Experiences (CUREs) have been developed that provide research experiences to a more inclusive and diverse student body, allow more students to obtain research experiences, and expose students to the scientific process. Most CUREs in the biological sciences focus on cellular and molecular biology, with few being developed in ecology, evolution, and organismal biology. Here, I present a one-semester CURE focused on organismal form and function. The goal of the course was to have students develop their own research questions and hypotheses in relation to invertebrate form and movement, using high-speed cinematography to collect their data. In this paper, I describe the motivation for the course, provide the details of teaching the course, including rubrics for several assignments, the outcomes of the course, caveats, and ways a similar course can be implemented at other institutions. The course was structured to use a scaffolding approach during the first half of the semester to provide the content of form–function relationships and allow students to acquire the laboratory skills to quantify animal movement. The second half of the course focused on student-driven inquiry, with class time dedicated to conducting research. As there is a push to engage more students in research, I hope this course will inspire others to implement similar classes at other universities, providing a network of collaboration on integrative organismal student-driven research.
The Interaction of Compliance and Activation on the Force-Length Operating Range and Force Generating Capacity of Skeletal Muscle: A Computational Study using a Guinea Fowl Musculoskeletal Model
Authors: Cox S M , Easton K L , Lear M Cromie , Marsh R L , Delp S L , Rubenson J
Published: September 2019

Synopsis

A muscle’s performance is influenced by where it operates on its force–length (F–L) curve. Here we explore how activation and tendon compliance interact to influence muscle operating lengths and force-generating capacity. To study this, we built a musculoskeletal model of the lower limb of the guinea fowl and simulated the F–L operating range during fixed-end fixed-posture contractions for 39 actuators under thousands of combinations of activation and posture using three different muscle models: Muscles with non-compliant tendons, muscles with compliant tendons but no activation-dependent shift in optimal fiber length (L0), and muscles with both compliant tendons and activation-dependent shifts in L0. We found that activation-dependent effects altered muscle fiber lengths up to 40% and increased or decreased force capacity by up to 50% during fixed-end contractions. Typically, activation-compliance effects reduce muscle force and are dominated by the effects of tendon compliance at high activations. At low activation, however, activation-dependent shifts in L0 are equally important and can result in relative force changes for low compliance muscles of up to 60%. There are regions of the F–L curve in which muscles are most sensitive to compliance and there are troughs of influence where these factors have little effect. These regions are hard to predict, though, because the magnitude and location of these areas of high and low sensitivity shift with compliance level. In this study we provide a map for when these effects will meaningfully influence force capacity and an example of their contributions to force production during a static task, namely standing.
Have Niche, Will Travel. New Means of Linking Diet and Ecomorphology Reveals Niche Conservatism in Freshwater Cottoid Fishes
Authors: Buser T J , Finnegan D L , Summers A P , Kolmann M A
Published: September 2019

Synopsis

Evolutionary transitions between habitats have been catalysts for some of the most stunning examples of adaptive diversification, with novel niches and new resources providing ecological opportunity for such radiations. In aquatic animals, transitions from saltwater to freshwater habitats are rare, but occur often enough that in the Neotropics for example, marine-derived fishes contribute noticeably to regional ichthyofaunal diversity. Here, we investigate how morphology has evolved in a group of temperate fishes that contain a marine to freshwater transition: the sculpins (Percomorpha; Cottoidea). We devised a novel method for classifying dietary niche and relating functional aspects of prey to their predators. Coupled with functional measurements of the jaw apparatus in cottoids, we explored whether freshwater sculpins have fundamentally changed their niche after invading freshwater (niche lability) or if they retain a niche similar to their marine cousins (niche conservatism). Freshwater sculpins exhibit both phylogeographical and ecological signals of phylogenetic niche conservatism, meaning that regardless of habitat, sculpins fill similar niche roles in either saltwater or freshwater. Rather than competition guiding niche conservatism in freshwater cottoids, we argue that strong intrinsic constraints on morphological and ecological evolution are at play, contra to other studies of diversification in marine-derived freshwater fishes. However, several intertidal and subtidal sculpins as well as several pelagic freshwater species from Lake Baikal show remarkable departures from the typical sculpin bauplan. Our method of prey categorization provides an explicit, quantitative means of classifying dietary niche for macroevolutionary studies, rather than relying on somewhat arbitrary means used in previous literature.
Integrating pharmacogenomics into the electronic health record by implementing genomic indicators
Authors: Caraballo Pedro J , Sutton Joseph A , Giri Jyothsna , Wright Jessica A , Nicholson Wayne T , Kullo Iftikhar J , Parkulo Mark A , Bielinski Suzette J , Moyer Ann M
Published: September 2019

Pharmacogenomics (PGx) clinical decision support integrated into the electronic health record (EHR) has the potential to provide relevant knowledge to clinicians to enable individualized care. However, past experience implementing PGx clinical decision support into multiple EHR platforms has identified important clinical, procedural, and technical challenges. Commercial EHRs have been widely criticized for the lack of readiness to implement precision medicine. Herein, we share our experiences and lessons learned implementing new EHR functionality charting PGx phenotypes in a unique repository, genomic indicators, instead of using the problem or allergy list. The Gen-Ind has additional features including a brief description of the clinical impact, a hyperlink to the original laboratory report, and links to additional educational resources. The automatic generation of genomic indicators from interfaced PGx test results facilitates implementation and long-term maintenance of PGx data in the EHR and can be used as criteria for synchronous and asynchronous CDS.
Dietary energy sources during late gestation and lactation of sows: effects on performance, glucolipid metabolism, oxidative status of sows, and their offspring1
Authors: Yang Yunyu , Hu Cheng Jun , Zhao Xichen , Xiao Kaili , Deng Ming , Zhang Lin , Qiu Xinggang , Deng Jinping , Yin Yulong , Tan Chengquan
Published: September 2019

In this study, the effects of maternal energy sources during late gestation and lactation on the performance, glucolipid metabolism, and oxidative status of sows and their offspring were investigated using a total of 75 (2 to 6 of parity) Landrace × Large White sows at day 85 of gestation under 3 different dietary treatments: SO diet (basal diet plus 3.0% and 5.0% soybean oil during late gestation and lactation, respectively), FO diet (basal diet plus 3.0%/5.0% fish oil during late gestation and lactation, respectively), and CS diet (basal diet plus 32%/42% corn starch during late gestation and lactation, respectively). All the 3 groups showed no obvious differences (P > 0.05) in the number of total piglets born, born alive, after cross-fostering, and at weaning, whereas the CS group exhibited a shorter farrowing duration (P < 0.05) and lower stillbirth rate (P < 0.05) when compared with the SO group. In addition, litter weight at birth was significantly higher in the CS group than in the SO or FO group (P < 0.05). Despite no notable differences in the ADG of suckling piglets among dietary treatments (P > 0.05), the CS group had greater feed intake than the SO group during the lactation period (P < 0.05). In neonatal piglets with normal birth weight (NBW, 1.3 to 1.5 kg), the CS group was lower than the SO group in the content of liver glycogen (P < 0.05) and the mRNA abundances of fatty acid synthase, acetyl-CoA carboxylase, fatty acid-binding protein 1, and acyl-CoA oxidase (P < 0.05). Interestingly, compared with the SO group, the FO group had a lower preweaning mortality rate (P < 0.05), but greater liver glycogen pools (P < 0.05) in neonatal piglets with low birth weight (LBW, <1.1 kg). Compared with the CS group, the FO group showed an increase in the plasma malondialdehyde levels (P < 0.05) of sows, as well as an increase of 8-hydroxy-deoxyguanosine (P < 0.05) and a decrease of ferric reducing ability of plasma (P < 0.05) in NBW piglets. Overall, the diet rich in starch decreased the stillbirth rate and increased the litter weight of neonatal piglets, the dietary supplementation with fish oil decreased preweaning mortality rate, and the diet with a low n6:n3 ratio increased the oxidative status of sows and their offspring.
The hRPC62 subunit of human RNA polymerase III displays helicase activity
Authors: Ayoubi Leyla El , Dumay-Odelot Hélène , Chernev Aleksandar , Boissier Fanny , Minvielle-Sébastia Lionel , Urlaub Henning , Fribourg Sébastien , Teichmann Martin
Published: September 2019

In Eukaryotes, tRNAs, 5S RNA and U6 RNA are transcribed by RNA polymerase (Pol) III. Human Pol III is composed of 17 subunits. Three specific Pol III subunits form a stable ternary subcomplex (RPC62-RPC39-RPC32α/β) being involved in pre-initiation complex formation. No paralogues for subunits of this subcomplex subunits have been found in Pols I or II, but hRPC62 was shown to be structurally related to the general Pol II transcription factor hTFIIEα. Here we show that these structural homologies extend to functional similarities. hRPC62 as well as hTFIIEα possess intrinsic ATP-dependent 3′-5′ DNA unwinding activity. The ATPase activities of both proteins are stimulated by single-stranded DNA. Moreover, the eWH domain of hTFIIEα can replace the first eWH (eWH1) domain of hRPC62 in ATPase and DNA unwinding assays. Our results identify intrinsic enzymatic activities in hRPC62 and hTFIIEα.
Altered Plant and Nodule Development and Protein S-Nitrosylation in Lotus japonicus Mutants Deficient in S-Nitrosoglutathione Reductases
Authors: Matamoros Manuel A , Cutrona Maria C , Wienkoop Stefanie , Begara-Morales Juan C , Sandal Niels , Orera Irene , Barroso Juan B , Stougaard Jens , Becana Manuel
Published: September 2019

Nitric oxide (NO) is a crucial signaling molecule that conveys its bioactivity mainly through protein S-nitrosylation. This is a reversible post-translational modification (PTM) that may affect protein function. S-nitrosoglutathione (GSNO) is a cellular NO reservoir and NO donor in protein S-nitrosylation. The enzyme S-nitrosoglutathione reductase (GSNOR) degrades GSNO, thereby regulating indirectly signaling cascades associated with this PTM. Here, the two GSNORs of the legume Lotus japonicus, LjGSNOR1 and LjGSNOR2, have been functionally characterized. The LjGSNOR1 gene is very active in leaves and roots, whereas LjGSNOR2 is highly expressed in nodules. The enzyme activities are regulated in vitro by redox-based PTMs. Reducing conditions and hydrogen sulfide-mediated cysteine persulfidation induced both activities, whereas cysteine oxidation or glutathionylation inhibited them. Ljgsnor1 knockout mutants contained higher levels of S-nitrosothiols. Affinity chromatography and subsequent shotgun proteomics allowed us to identify 19 proteins that are differentially S-nitrosylated in the mutant and the wild-type. These include proteins involved in biotic stress, protein degradation, antioxidant protection and photosynthesis. We propose that, in the mutant plants, deregulated protein S-nitrosylation contributes to developmental alterations, such as growth inhibition, impaired nodulation and delayed flowering and fruiting. Our results highlight the importance of GSNOR function in legume biology.
3,4-Dibromo-7-Azaindole Modulates Arabidopsis Circadian Clock by Inhibiting Casein Kinase 1 Activity
Authors: Ono Azusa , Sato Ayato , Fujimoto Kazuhiro J , Matsuo Hiromi , Yanai Takeshi , Kinoshita Toshinori , Nakamichi Norihito
Published: September 2019

The circadian clock is a timekeeping system for regulation of numerous biological daily rhythms. One characteristic of the circadian clock is that period length remains relatively constant in spite of environmental fluctuations, such as temperature change. Here, using the curated collection of in-house small molecule chemical library (ITbM chemical library), we show that small molecule 3,4-dibromo-7-azaindole (B-AZ) lengthened the circadian period of Arabidopsis thaliana (Arabidopsis). B-AZ has not previously been reported to have any biological and biochemical activities. Target identification can elucidate the mode of action of small molecules, but we were unable to make a molecular probe of B-AZ for target identification. Instead, we performed other analysis, gene expression profiling that potentially reveals mode of action of molecules. Short-term treatment of B-AZ decreased the expression of four dawn- and morning-phased clock-associated genes, CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1), LATE ELONGATED HYPOCOTYL (LHY), PSEUDO-RESPONSE REGULATOR 9 (PRR9) and PRR7. Consistently, amounts of PRR5 and TIMING OF CAB EXPRESSION 1 (TOC1) proteins, transcriptional repressors of CCA1, LHY, PRR9 and PRR7 were increased upon B-AZ treatment. B-AZ inhibited Casein Kinase 1 family (CK1) that phosphorylates PRR5 and TOC1 for targeted degradation. A docking study and molecular dynamics simulation suggested that B-AZ interacts with the ATP-binding pocket of human CK1 delta, whose amino acid sequences are highly similar to those of Arabidopsis CK1. B-AZ-induced period-lengthening effect was attenuated in prr5 toc1 mutants. Collectively, this study provides a novel and simple structure CK1 inhibitor that modulates circadian clock via accumulation of PRR5 and TOC1.
Outcomes of Nonsurgical Treatments for Symptomatic Adult Degenerative Scoliosis: A Systematic Review
Authors: Schoutens Carlijn , Cushman Daniel M , McCormick Zachary L , Conger Aaron , van Royen Barend J , Spiker William R
Published: September 2019

Objective

To evaluate the effectiveness of nonsurgical treatments in symptomatic adult degenerative scoliosis (ADS).

Design

A systematic literature review.

Methods

PubMed, Web of Science, and The Cochrane Library were searched to identify research published since 1988. Randomized controlled trials (RCTs) and observational cohort studies were eligible if they featured symptomatic ADS patients aged ≥50 who received nonsurgical treatment. Minimum follow-up was six weeks, and outcomes of interest were pain, disability, quality of life, and Cobb angle. Evidence quality per intervention was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Results

Six studies were included. Of these, four focused specifically on injections, bracing, or yoga; two involved multiple treatments. One RCT provided evidence for greater effectiveness of transforaminal epidural steroid injection over anesthetic alone in reducing radiating pain and disability. Two single-group retrospective cohort studies lent support for bracing to slow curve progression. One retrospective single-group cohort study suggested an association between yoga and reduced curve progression. Evidence for injections to reduce ADS symptoms was rated as low quality; evidence for bracing and yoga was rated as very low quality. No specific evidence was identified regarding other treatments, including physical therapy and analgesics.

Conclusions

Literature describing the effectiveness of nonoperative treatments in symptomatic ADS is scarce. The quantity and quality of the evidence regarding injections, bracing, and yoga are insufficient to advise for or against the use of these methods to improve outcomes in symptomatic ADS. For these and other nonoperative treatment forms, further research is needed.
Measuring the Welfare Gains from Optimal Incentive Regulation
Authors: Abito Jose Miguel
Published: September 2019

I empirically measure the welfare gains from optimal incentive regulation in the context of electric utilities facing both emissions and rate of return regulation (RORR). I provide evidence that RORR induces lower fuel efficiency, leading to greater coal consumption and higher emissions abatement costs. Replacing RORR with the optimal mechanism of Laffont and Tirole (1986) yields annual welfare gains of $686 million or a 11% reduction in electricity prices. I construct a much simpler two-contract menu that can achieve more than 65% of these welfare gains.
Symmetric and Asymmetric Market Betas and Downside Risk
Authors: Levi Yaron , Welch Ivo
Published: September 2019

Our paper explores whether a symmetric plain or an asymmetric down-beta is a better hedging measure (Roy 1952; Markowitz 1959). Unlike Ang, Chen, and Xing (2006) and Lettau, Maggiori, and Weber (2014), we find that the prevailing plain market beta is the better predictor, even for crashes. It also predicts the subsequent down-beta (i.e., beta measured only on days when the stock market had declined) better than down-beta itself. Stocks with higher down-betas ex ante also do not earn higher average rates of return ex post. Thus, down-betas are useful for neither hedging nor risk-pricing purposes.
Effects of Auricular Acupressure Therapy on Stress and Sleep Disturbance of Middle-Aged Women in South Korea
Authors: Cha Nam Hyun , Park Yi Kyun , Sok Sohyune R.
Published: September 2019

This study sought to examine the effect of auricular acupressure therapy on the stress and sleep status of middle-aged women in South Korea. A quasi-experimental pretest/posttest control group design was employed. The study sample consisted of 67 middle-aged women (experimental: 35 samples; control: 32 samples) in Seoul, South Korea. Auricular acupressure therapy including the auricular acupressure needle on the skin paper tape was applied on an ear for 2 weeks, 2 times per week. The acupoints were Gyogam, Sinmun, Bushin, Naebunbi, and Pijilha. For the placebo control group, only the skin paper tape without the auricular acupressure needle was applied on the same acupoints. Measures were a stress scale, cortisol level in blood, and a sleep status scale. The findings showed that there were significant differences on stress (physical: t = 2.170, P < .033; psychological: t = 2.117, P < .037), cortisol level in blood (t = 2.277, P < .025), and sleep status (t = −3.127, P < .004). Health care providers should consider providing auricular acupressure therapy as an alternative method for reducing physical and psychological stress, cortisol level in blood, and sleep disturbance of middle-aged women in South Korea.
2015 Glenn A. Fry Award Lecture: Driving toward a New Vision: Understanding the Role of Vision in Driving
Authors: Wood Joanne M.
Published: September 2019

More than 90% of the sensory information that we use for driving is estimated to be visual. However, there is ongoing debate regarding the extent to which different ocular conditions and types of visual impairment affect driving performance and which visual functions are most important for safe driving. My program of research has sought to address these questions using a range of experimental approaches including measures of real-world driving performance on a closed-circuit driving course and under in-traffic conditions. This article provides a current overview of how visual impairment affects driving ability and safety and also highlights the visual challenges of nighttime driving, including the visibility of vulnerable road users, based on the wider research literature, as well as providing a snapshot of some of my own studies. Emphasis is placed on those studies that are relevant to assessing a patient's visual fitness to drive, as well as providing appropriate advice regarding the impact of common visual impairments on driving ability and safety.
Equivalent Change Enrichment Analysis: Assessing Equivalent and Inverse Change in Biological Pathways between Diverse Experiments
Authors: Thompson Jeffrey A. , Koestler Devin C.
Published: September 2019

In silico functional genomics have become a driving force in the way we interpret and use gene expression data, enabling researchers to understand which biological pathways are likely to be affected by the treatments or conditions being studied. There are many approaches to functional genomics, but a number of popular methods determine if a set of modified genes has a higher than expected overlap with genes known to function as part of a pathway (functional enrichment testing). Recently, researchers have started to apply such analyses in a new way: to ask if the data they are collecting show similar disruptions to biological functions compared to reference data. Examples include studying whether similar pathways are perturbed in smokers vs. users of e-cigarettes, or whether a new mouse model of schizophrenia is justified, based on its similarity in cytokine expression to a previously published model. However, there is a dearth of robust statistical methods for testing hypotheses related to these questions and most researchers resort to ad hoc approaches. In this work, we propose a statistical approach to answering such questions. First, we propose a statistic for measuring the degree of equivalent change in individual genes across different treatments. Using this statistic, we propose applying gene set enrichment analysis to identify pathways enriched in genes that are affected in similar or opposing ways across treatments. We evaluate this approach in comparison to ad hoc methods on a simulated dataset, as well as two biological datasets and show that it provides robust results.
Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation
Authors: Haery Leila , Deverman Benjamin E. , Matho Katherine , Cetin Ali , Woodard Kenton , Cepko Connie , Guerin Karen I. , Rego Meghan A. , Ersing Ina , Bachle Susanna M. , Kamens Joanne , Fan Melina
Published: September 2019

Cell-type-specific expression of molecular tools and sensors is critical to construct circuit diagrams and to investigate the activity and function of neurons within the nervous system. Strategies for targeted manipulation include combinations of classical genetic tools such as Cre/loxP and Flp/FRT, use of cis-regulatory elements, targeted knock-in transgenic mice, and gene delivery by AAV and other viral vectors. The combination of these complex technologies with the goal of precise neuronal targeting is a challenge in the lab. This report will discuss the theoretical and practical aspects of combining current technologies and establish best practices for achieving targeted manipulation of specific cell types. Novel applications and tools, as well as areas for development, will be envisioned and discussed.
A single-cell and single-nucleus RNA-seq toolbox for fresh and frozen human tumors
Authors: Slyper Michal , Porter Caroline B. M. , Ashenberg Orr , Waldman Julia , Drokhlyansky Eugene , Wakiro Isaac , Smillie Christopher , Smith-Rosario Gabriela , Wu Jingyi , Dionne Danielle , Vigneau Sébastien , Jané-Valbuena Judit , Napolitano Sara , Su Mei-Ju , Patel Anand G. , Karlstrom Asa , Gritsch Simon , Nomura Masashi , Waghray Avinash , Gohil Satyen H. , Tsankov Alexander M. , Jerby-Arnon Livnat , Cohen Ofir , Klughammer Johanna , Rosen Yanay , Gould Joshua , Li Bo , Nguyen Lan , Wu Catherine J. , Izar Benjamin , Haq Rizwan , Hodi F. Stephen , Yoon Charles H. , Hata Aaron N. , Baker Suzanne J. , Suvà Mario L. , Bueno Raphael , Stover Elizabeth H. , Matulonis Ursula A. , Clay Michael R. , Dyer Michael A. , Collins Natalie B. , Wagle Nikhil , Rotem Asaf , Johnson Bruce E. , Rozenblatt-Rosen Orit , Regev Aviv
Published: September 2019

Single cell genomics is essential to chart the complex tumor ecosystem. While single cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated from fresh tumor tissues, single nucleus RNA-Seq (snRNA-Seq) is needed to profile frozen or hard-to-dissociate tumors. Each strategy requires modifications to fit the unique characteristics of different tissue and tumor types, posing a barrier to adoption. Here, we developed a systematic toolbox for profiling fresh and frozen clinical tumor samples using scRNA-Seq and snRNA-Seq, respectively. We tested eight tumor types of varying tissue and sample characteristics (resection, biopsy, ascites, and orthotopic patient-derived xenograft): lung cancer, metastatic breast cancer, ovarian cancer, melanoma, neuroblastoma, pediatric sarcoma, glioblastoma, pediatric high-grade glioma, and chronic lymphocytic leukemia. Analyzing 212,498 cells and nuclei from 39 clinical samples, we evaluated protocols by cell quality, recovery rate, and cellular composition. We optimized protocols for fresh tissue dissociation for different tumor types using a decision tree to account for the technical and biological variation between clinical samples. We established methods for nucleus isolation from OCT embedded and fresh-frozen tissues, with an optimization matrix varying mechanical force, buffer, and detergent. scRNA-Seq and snRNA-Seq from matched samples recovered the same cell types and intrinsic expression profiles, but at different proportions. Our work provides direct guidance across a broad range of tumors, including criteria for testing and selecting methods from the toolbox for other tumors, thus paving the way for charting tumor atlases.
Generation and characterisation of an estrogen receptor-positive GEMM-derivedPten p53null transplantable breast tumour model for therapeutic testing
Authors: Davies E.J. , Morgan H. , Tornillo G. , Chabbert C.D. , Kendrick H. , Adhesmaki M.J. , Luke S. , Barry S.T. , Smalley M.J.
Published: September 2019

Assessing the signalling pathway dependencies of tumours that arise autochthonously in genetically engineered mouse models (GEMMs) of breast cancer is particularly challenging due to the high degree of intra- and inter-tumour heterogeneity, as well as the long latency of tumour development in such models. Use of transplantable tumour lines derived from autochthonous tumours (‘Mouse Derived Xenografts’ or MDXs) is one possible solution and has been used successfully in models of BRCA1-associated triple negative breast cancer. However, their potential in ER+ breast cancer models has not been addressed. Here, we assess the utility of orthotopic transplantable tumour lines derived from an autochthonous ER+Blg-cre Ptenfl/flp53fl/flbreast cancer model. We show that initial tumour implantation and early passage results in the development of lines of progeny with heterogeneous histopathological phenotypes which is coincident with an accumulation of, or selection for,de novomutations. Importantly, these lines also display different dependencies on the key pathways that drive tumourigenesis, which can lead to inherent resistance to treatment with pharmacological agents targeting these pathways and makes them important models to test strategies to overcome such resistance.
Severity of Early Life Stress Moderates the Effect of Fine Particle Air Pollution on Adolescent Brain Development
Authors: Miller Jonas G. , Dennis Emily L. , Jo Booil , Gotlib Ian H.
Published: September 2019

Air pollution is currently the greatest environmental threat to public health, but we know little about its effects on adolescent brain development. In this context, exposure to air pollution co-occurs, and could interact, with social factors that also affect brain development, such as early life stress (ELS). Here, we show that severity of ELS moderates the association between fine particle air pollution (particulate matter 2.5; PM2.5) and structural brain development. We interviewed adolescents about ELS, used census-tract data to characterize PM2.5 concentrations, and conducted longitudinal tensor-based morphometry to assess regional changes in brain volume over a two-year period. Across various cortical, thalamic, and white matter tract regions, there was a remarkably consistent effect of PM2.5 on volumetric change for adolescents who had experienced less, rather than more, severe ELS. Furthermore, exposure to higher levels of PM2.5 and experiencing moderate to severe ELS were associated with comparable volumetric changes in the brain in adolescence.
Systemic Infection Facilitates Transmission ofPseudomonas aeruginosa
Authors: Bachta Kelly E. R. , Allen Jonathan P. , Cheung Bettina H. , Chiu Cheng-Hsun , Hauser Alan R.
Published: September 2019

Health care-associated infections such asPseudomonas aeruginosa(PA) bacteremia pose a major clinical risk for hospitalized patients, and efforts to limit them are a priority. The fitness pressures accounting for PA virulence factors that facilitate bloodstream infections are unclear, as these infections are presumed to be a “dead-end” and have no impact on transmission. Here, we used a mouse model to show that PA spreads from the bloodstream to the gallbladder, where it replicates to extremely high numbers. Bacteria in the gallbladder then seed the intestines and feces, leading to transmission to uninfected cage-mate mice. The findings demonstrate that the gallbladder is critical for spread of PA from the bloodstream to the feces during bacteremia, a process that promotes transmission.