bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of non-antifungal agrochemicals on the pathogenic fungus Cryptococcus gattii
Authors: Carneiro Hellem Cristina Silva , Ribeiro Noelly Queiroz , Bastos Rafael Wesley , Santos Daniel Assis
Published: February 2019

The chemical control of pests and weeds is employed to improve crop production and the quality of agricultural products. The intensive use of pesticides, however, may cause environmental contamination, thus altering microbial communities. Cryptococcus gattii is an environmental yeast and the causative agent of cryptococcosis in both humans and animals. Up to this day, the effects of agrochemicals on human pathogens living in nature are still widely unknown. In this work, we analyzed the susceptibility of C. gattii to nonfungicide agrochemicals (herbicides and insecticides). Microdilution and drug-combination susceptibility tests were performed for the herbicides flumioxazin (FLX), glyphosate (GLY), isoxaflutole (ISO), pendimethalin (PEND), and also for the insecticide fipronil (FIP). Moreover, these compounds were combined with the clinical antifungals amphotericin B and fluconazole. The MIC values found for the agrochemicals were the following: < 16 μg/ml, for flumioxazin; 128 to 256 μg/ml, for FIP, ISO, and PEND; and >256 μg/ml, for GLY. Synergistic and antagonistic interactions, depending on the strain and concentration tested, were also observed. All strains had undergone adaptation to increasing levels of agrochemicals, in order to select the less susceptible subpopulations. During this process, one C. gattii strain (196 L/03) tolerated high concentrations (50 to 900 μg/ml) of all pesticides assessed. Subsequently, the strain adapted to flumioxazin, isoxaflutole and pendimethalin showed a reduction in the susceptibility to agrochemicals and clinical antifungals, suggesting the occurrence of cross-resistance. Our data point to the risk of exposing C. gattii to agrochemicals existing in the environment, once it might impact the susceptibility of clinical antifungals.
Cassini CIRS and ISS opposition effects of Saturn’s rings – I. C ring narrow or broad surge?
Authors: Déau E , Dones L , Spilker L , Flandes A , Baillié K , Pilorz S , Showalter M , El Moutamid M , Colwell J E
Published: February 2019

We focus on the thermal and optical opposition effects of Saturn’s C ring seen by Cassini CIRS (Composite InfraRed Spectrometer) at 15.7 ${\mu}$m and ISS (Imaging Science Subsystem) at 0.6 ${\mu}$m. The opposition surge is a brightness peak observed at low phase angle (α → 0°). Saturn rings’ opposition surge was recently observed in reflected light and thermal infrared emission by Cassini. There is debate on whether the C ring’s thermal opposition surge width is narrow (≲1°) or broad (≳30°). This surge is important because its width was used to define the scale of ring properties driving the thermal peak. We parametrize the CIRS and ISS phase curves with several morphological models to fit the surge shape. For five of the largest C ring’s plateaus, we find that their thermal surge is 10 times wider than the optical surge and that the thermal surge width (∼4°) is neither narrow, nor broad. We compare radial differences between CIRS and ISS surge morphologies with the optical depth τ (from UVIS, UltraViolet Imaging Spectrograph) and water ice band depth (from VIMS, Visual and Infrared Mapping Spectrometer) profiles. We find that: water ice band depths (microscopic ring signatures) and τ (macroscopic ring signatures) show respectively little and large contrasts between the background and the plateaus. The thermal surge amplitude and τ are correlated, and we found no band depth dependence, contrary to the optical surge amplitude, which shows no correlation with τ. These correlations suggest a macroscopic scale dominance in controlling the C ring’s thermal opposition effect.
Dynamic predictions of long-term kidney graft failure: an information tool promoting patient-centred care
Authors: Fournier Marie-Cécile , Foucher Yohann , Blanche Paul , Legendre Christophe , Girerd Sophie , Ladrière Marc , Morelon Emmanuel , Buron Fanny , Rostaing Lionel , Kamar Nassim , Mourad Georges , Garrigue Valérie , Couvrat-Desvergnes Grégoire , Giral Magali , Dantan Etienne ,   DIVAT Consortium, Blancho Gilles , Branchereau Julien , Cantarovich Diego , Chapelet Agnès , Dantal Jacques , Deltombe Clément , Figueres Lucile , Garandeau Claire , Giral Magali , Gourraud-Vercel Caroline , Hourmant Maryvonne , Karam Georges , Kerleau Clarisse , Meurette Aurélie , Ville Simon , Kandell Christine , Moreau Anne , Renaudin Karine , Cesbron Anne , Delbos Florent , Walencik Alexandre , Devis Anne , Amrouche Lucile , Anglicheau Dany , Aubert Olivier , Bererhi Lynda , Legendre Christophe , Loupy Alexandre , Martinez Frank , Sberro-Soussan Rébecca , Scemla Anne , Tinel Claire , Zuber Julien , Eschwege Pascal , Frimat Luc , Girerd Sophie , Hubert Jacques , Ladriere Marc , Laurain Emmanuelle , Leblanc Louis , Lecoanet Pierre , Lemelle Jean-Louis , Hériot Lyon E , Badet Lionel , Brunet Maria , Buron Fanny , Cahen Rémi , Daoud Sameh , Fournie Coralie , Grégoire Arnaud , Koenig Alice , Lévi Charlène , Morelon Emmanuel , Pouteil-Noble Claire , Rimmelé Thomas , Thaunat Olivier , Delmas Sylvie , Garrigue Valérie , Le Quintrec Moglie , Pernin Vincent , Serre Jean-Emmanuel
Published: February 2019

Background

Informing kidney transplant recipients of their prognosis and disease progression is of primary importance in a patient-centred vision of care. By participating in decisions from the outset, transplant recipients may be more adherent to complex medical regimens due to their enhanced understanding.

Methods

We proposed to include repeated measurements of serum creatinine (SCr), in addition to baseline characteristics, in order to obtain dynamic predictions of the graft failure risk that could be updated continuously during patient follow-up. Adult recipients from the French Données Informatisées et VAlidées en Transplantation (DIVAT) cohort transplanted for the first or second time from a heart-beating or living donor and alive with a functioning graft at 1 year post-transplantation were included.

Results

The model was composed of six baseline parameters, in addition to the SCr evolution. We validated the dynamic predictions by evaluating both discrimination and calibration accuracy. The area under the receiver operating characteristic curve varied from 0.72 to 0.76 for prediction times at 1 and 6 years post-transplantation, respectively, while calibration plots showed correct accuracy. We also provided an online application tool (https://shiny.idbc.fr/DynPG).

Conclusion

We have created a tool that, for the first time in kidney transplantation, predicts graft failure risk both at an individual patient level and dynamically. We believe that this tool would encourage willing patients into participative medicine.
Pulse transit time in pregnancy: a new way to diagnose and classify sleep disordered breathing?
Authors: Link Brittany N , Eid Celine , Bublitz Maggie H , Pengo Martino F , Salameh Myriam , Ludwig Karin S , Millman Richard P , Dworkin Lance , Bourjeily Ghada
Published: February 2019

Study Objectives

There are significant discrepancies between the prevalence of snoring and that of objectively defined sleep disordered breathing among pregnant women, suggesting subtle airflow limitations that may not be captured by conventional scoring. This study examined the performance of pulse transit time, an indirect measure of arterial stiffness and sympathetic activation, in pregnancy.

Methods

Pregnant women with obesity and snoring and a group of controls without symptoms of sleep disordered breathing were recruited in the first trimester. Women underwent a level III in-laboratory sleep monitoring study including an electrocardiogram and pulse oximetry, and pulse transit time was measured. Sleep disordered breathing was defined as an apnea–hypopnea index at least five events per hour of sleep. Statistical analysis was performed using Spearman correlation, Fisher’s exact t-test, and univariate analysis.

Results

Of the 222 women, 38 met criteria for sleep disordered breathing. Pulse transit time drops were very prevalent (95% of participants with snoring had > 5 drops per hour). Median apnea–hypopnea index was 0.7 (interquartile range [IQR]: 2.6) events per hour whereas median pulse transit time drop index was 20.70 (IQR: 35.90) events per hour. Pulse transit time index was significantly higher in snorers with apnea–hypopnea index less than five events per hours and participants with apnea–hypopnea index greater than five events per hour compared to controls. Examination of random epochs with pulse transit time drops showed that 95% of pulse transit time drops were associated with airflow limitation.

Conclusions

Pulse transit time ascertains frequent events of sympathetic activation in at-risk women with and without sleep disordered breathing beyond conventional apneas and hypopneas. Pulse transit time may be an important addition to the identification of clinically significant sleep disordered breathing in pregnant women, and may identify more sleep disordered breathing than apnea–hypopnea index.
Paracoccus sediminilitoris sp. nov., isolated from a tidal flat sediment
Authors: Wei Yuli , Cao Junwei , Yao Huimin , Mao Haiyan , Zhu Kelei , Li Meng , Liu Rulong , Fang Jiasong
Published: February 2019

A novel marine Gram-stain-negative, non-spore-forming, motile, aerobic, coccoid or ovoid bacterium, designated as strain DSL-16T, was isolated from a tidal flat sediment on the East China Sea and characterized phylogenetically and phenotypically. Optimal growth of the strain occurred at 35 °C (range 4–40 °C), at pH 6 (range 5–11) and with 4 % (w/v) NaCl (range 1–14 %). The nearest phylogenetic neighbour was

Paracoccus

seriniphilus

DSM 14827T (98.2 % 16S rRNA gene sequence similarity). The digital DNA–DNA hybridization value between strain DSL-16T and

P. seriniphilus

DSM 14827T was 19.5±2.2 %. The average nucleotide identity value between strain DSL-16T and

P. seriniphilus

DSM 14827T was 83.6 %. The sole respiratory ubiquinone was Q-10. The major polar lipids were phosphatidylmonomethylethanolamine (PME), phosphatidylglycerol (PG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), diphosphatidyglycerol (DPG) and glycolipid (GL). The predominant cellular fatty acids of strain DSL-16T were C18 : 1ω7c, C18 : 0 and 11-methyl C18 : 1ω7c. The G+C content of the genomic DNA was 64.5 mol%. The combined genotypic and phenotypic data indicated that strain DSL-16T represents a novel species of the genus

Paracoccus

, for which the name

Paracoccus
sediminilitoris sp. nov. is proposed. The type strain is DSL-16T (=KCTC 62644T=MCCC 1K03534T).
Structural redundancy in supracellular actomyosin networks enables robust tissue folding
Authors: Yevick Hannah G. , Miller Pearson W. , Dunkel Jörn , Martin Adam C.
Published: February 2019

Tissue morphogenesis is strikingly reproducible. Yet, how tissues are robustly sculpted, even under challenging conditions, is unknown. Here, we combined network analysis, experimental perturbations, and computational modeling to determine how network connectivity between hundreds of contractile cells on the ventral side of theDrosophilaembryo ensures robust tissue folding. We identified two network properties that mechanically promote robustness. First, redundant supracellular cytoskeletal network paths ensure global connectivity, even with network degradation. By forming many more connections than are required, morphogenesis is not disrupted by local network damage, analogous to the way redundancy guarantees the large-scale function of vasculature and transportation networks. Second, directional stiffening of edges oriented orthogonal to the folding axis promotes furrow formation at lower contractility levels. Structural redundancy and directional network stiffening ensure robust tissue folding with proper orientation.
Maleness-on-the-Y(MoY) orchestrates male sex determination in major agricultural fruit fly pests
Authors: Meccariello Angela , Salvemini Marco , Primo Pasquale , Hall Brantley , Koskinioti Panagiota , Dalíková Martina , Gravina Andrea , Gucciardino Michela Anna , Forlenza Federica , Gregoriou Maria-Eleni , Ippolito Domenica , Monti Simona Maria , Petrella Valeria , Perrotta Maryanna Martina , Schmeing Stephan , Ruggiero Alessia , Scolari Francesca , Giordano Ennio , Tsoumani Konstantina T. , Marec Frantisek , Windbichler Nikolai , Nagaraju Javaregowda , Arunkumar Kallare P. , Bourtzis Kostas , Mathiopoulos Kostas D. , Ragoussis Jiannis , Vitagliano Luigi , Tu Zhijian , Papathanos Philippos Aris , Robinson Mark D. , Saccone Giuseppe
Published: February 2019

In insects, rapidly evolving primary sex-determining signals are transduced by a conserved regulatory module producing sex-specific proteins that direct sex determination and sexual differentiation1-4. In the agricultural pestCeratitis capitata(medfly), a Y-linked maleness factor (M) is thought to repress the autoregulatory splicing oftransformer(Cctra), which is required in XX individuals to establish and maintain female sex determination5,6. Despite previous attempts of isolating Y-linked genes using the medfly whole genome, theMfactor has remained elusive7. Here, we report the identification of a Y-linked gene,Maleness-on the-Y(MoY), and show that it encodes a small novel protein which is both necessary and sufficient for medfly male sex determination. Transient silencing ofMoYin XY individuals leads to the development of fertile females while transient expression ofMoYin XX individuals results in fertile males. Notably, a cross between these sex reverted individuals gives rise to both fertile males and females indicating that a functionalMoYcan be maternally transmitted. In contrast to the diversity ofMfactors found in dipteran species8-11, we discoveredMoYorthologues in seven other Tephritid species spanning ∼111 millions of years of evolution (Mya). We confirmed their male determining function in the olive fly (Bactrocera oleae) and the oriental fruit fly (Bactrocera dorsalis). This unexpected conservation of the primaryMoYsignal in a large number of important agricultural pests12will facilitate the development of transferable genetic control strategies in these species, for example sterile male releases or sex-ratio-distorting gene drives.
Dynamics of cortical degeneration over a decade in Huntington’s Disease
Authors: Johnson E. B. , Ziegler G. , Penny W. , Rees G. , Tabrizi S. J. , Scahill R. I. , Gregory S. ,   the TRACK-HD and TrackOn-HD investigators
Published: February 2019

The neurodegenerative process is typically slowly progressive and complex. While simple models of neurodegeneration suggest that brain changes progress at a near constant rate, previous research shows regional variation within the temporal progression of atrophy, indicating that over the course of neurodegeneration, different regions may undergo changing rates of atrophy. Characterization of long-term dynamic brain changes in neurodegeneration requires both extensive longitudinal MRI datasets and an advanced modeling framework. Until recently, both of these elements were not available. Here, we implement a novel dynamic systems approach to infer patterns of regional progression spatially and temporally in a unique longitudinal dataset with up to seven annual individual brain scans per participant from 49 Huntington’s Disease (HD) gene-carriers. We map participant-and group-level trajectories of cortical atrophy in HD using a decade of data that encompasses motor symptom onset and, for the first time, show that neurodegenerative brain changes exhibit complex temporal dynamics of atrophy with substantial regional variation in progressive cortical atrophy. Some fronto-occipital cortical areas show an almost constant rate of atrophy, while medial-inferior temporal areas undergo only minor change. Interestingly, cortical sensory-motor areas were found to show a noticeable acceleration of atrophy following HD diagnosis. Furthermore, we establish links between individual atrophy and genetic markers of HD (CAG repeat length), as well as showing that cortical motor network changes predict subsequent decline in task-based motor performance, demonstrating face-validity of the model. Our findings highlight the complex pattern of dynamic cortical change occurring in HD that can help to resolve the biological underpinnings of HD progression.
Possible Magneto-Mechanical and Magneto-Thermal Mechanisms of Ion Channel Activation by Iron-Loaded Ferritin in Magnetogenetics
Authors: Barbic Mladen
Published: February 2019

The palette of tools for stimulation and regulation of neural activity is continually expanding. One of the new methods being introduced is magnetogenetics, where mechano-sensitive and thermo-sensitive ion channels are genetically engineered to be closely coupled to the iron-storage protein ferritin. Such genetic constructs could provide a powerful new way of non-invasively activating ion channels in-vivo using external magnetic fields that easily penetrate biological tissue. Initial reports that introduced this new technology have sparked a vigorous debate on the plausibility of physical mechanisms of ion channel activation by means of external magnetic fields. I argue that the initial criticisms leveled against magnetogenetics as being physically implausible were possibly based on the overly simplistic and unnecessarily pessimistic assumptions about the magnetic spin configurations of iron in ferritin protein. Additionally, all the possible magnetic-field-based mechanisms of ion channel activation in magnetogenetics might not have been fully considered. I present and propose several new magneto-mechanical and magneto-thermal mechanisms of ion channel activation by iron-loaded ferritin protein that may elucidate and clarify some of the mysteries that presently challenge our understanding of the reported biological experiments. Finally, I present some additional puzzles that will require further theoretical and experimental investigation.
Impact of Prior Cancer on Outcomes in Nasopharyngeal Carcinoma
Authors: Zhou Huaqiang , Zhang Yaxiong , Liu Jiaqing , Fang Wenfeng , Yang Yunpeng , Hong Shaodong , Chen Gang , Zhao Shen , Shen Jiayi , Xian Wei , Zhang Zhonghan , Chen Xi , Zhao Hongyun , Huang Yan , Zhang Li
Published: February 2019

Background

Prior cancer is a common exclusion criterion in nasopharyngeal carcinoma (NPC) trials. However, whether a prior cancer diagnosis affects trial outcomes is still unknown. We aimed to determine the impact of prior cancer on survival in NPC.

Methods

We identified patients diagnosed with NPC between 2004 and 2009 in the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by chi-squared test and t-test as appropriate. Propensity score-adjusted Kaplan-Meier methods and Cox proportional hazard models were used to evaluate the impact of prior cancer on overall survival (OS).

Results

Among 3,131 eligible NPC patients, 349 (11.15%) patients had a history of prior cancer. The Kaplan-Meier curves did not show a statistically significantly different OS (p=0.19). Subgroup analyses stratified by timing of prior cancer and AJCC TNM stage of index cancer displayed the same tendency, prior cancer didn’t adversely affect OS compared with patients without prior cancer (p>0.05). Furthermore, in propensity score–adjusted COX models analysis, patients with prior cancer had the same/non-inferior OS (hazard ratio [HR] = 1.12, 95% confidence interval= 0.88 to 1.42).

Conclusions

Among patients with nasopharyngeal carcinoma, prior cancer does not convey an adverse effect on clinical outcomes, regardless of the timing of prior cancer and AJCC TNM stage of index cancer. Broader inclusion trial criteria could be adopted in nasopharyngeal carcinoma patients with a history of prior cancer. However, further studies are still needed to confirm.
Multi-allelic APRR2 Gene is Associated with Fruit Pigment Accumulation in Melon and Watermelon
Authors: Oren Elad , Tzuri Galil , Vexler Lea , Dafna Asaf , Meir Ayala , Saar Uzi , Faigenboim Adi , Kenigswald Merav , Portnoy Vitaly , Schaffer Arthur A , Levi Amnon , Buckler Edward S. , Katzir Nurit , Burger Joseph , Tadmor Yaakov , Gur Amit
Published: February 2019

Color and pigment content are important aspects of fruit quality and consumer acceptance of cucurbit crops. Here, we describe the independent mapping and cloning of a common causative APRR2 gene regulating pigment accumulation in melon and watermelon. We initially show that the APRR2 transcription factor is causative for the qualitative difference between dark and light green rind in both crops. Further analyses establish the link between sequence or expression level variations in the CmAPRR2 gene and pigments content in the rind and flesh of mature melon fruits. GWAS of young fruit rind color in a panel composed of 177 diverse melon accessions did not result in any significant association, leading to an earlier assumption that multiple genes are involved in shaping the overall phenotypic variation at this trait. Through resequencing of 25 representative accessions and allelism tests between light rind accessions, we show that multiple independent SNPs in the CmAPRR2 gene are causative for the light rind phenotype. The multi-haplotypic nature of this gene explain the lack of detection power obtained through GBS-based GWAS and confirm the pivotal role of this gene in shaping fruit color variation in melon. This study demonstrates the power of combining bi- and multi-allelic designs with deep sequencing, to resolve lack of power due to high haplotypic diversity and low allele frequencies. Due to its central role and broad effect on pigment accumulation in fruits, the APRR2 gene is an attractive target for carotenoids bio-fortification of cucurbit crops.
BOLD activity during emotion reappraisal positively correlates with dietary self-control success
Authors: Maier Silvia U. , Hare Todd A.
Published: February 2019

We combined established emotion regulation and dietary choice tasks with fMRI to investigate behavioral and neural associations in self-regulation across the two domains in human participants. We found that increased BOLD activity during the successful reappraisal of positive and negative emotional stimuli was associated with dietary self-control success. This cross-task correlation was present in medial and lateral prefrontal cortex as well as the striatum. In contrast, BOLD activity during the food choice task was not associated with self-reported emotion regulation efficacy. These results suggest that neural processes utilized during the reappraisal of emotional stimuli may also facilitate dietary choices that override palatability in favor of healthfulness. In summary, our findings indicate that the neural systems supporting emotion reappraisal can generalize to other behavioral contexts that require reevaluation of rewarding stimuli and outcomes to promote choices that conform with the current goal.
Patterns of African and Asian admixture in the Afrikaner population of South Africa
Authors: Hollfelder N , Erasmus JC , Hammaren R , Vicente M , Jakobsson M , Greeff JM , Schlebusch CM
Published: February 2019

The Afrikaner population of South Africa are the descendants of European colonists who started to colonize the Cape of Good Hope in the 1600’s. In the early days of the colony, mixed unions between European males and non-European females gave rise to admixed children who later became incorporated into either the Afrikaner or the “Coloured” populations of South Africa. Ancestry, social class, culture, sex ratio and geographic structure affected admixture patterns and caused different ancestry and admixture patterns in Afrikaner and Coloured populations. The Afrikaner population has a predominant European composition, whereas the Coloured population has more diverse ancestries. Genealogical records estimated the non-European contributions into the Afrikaners to 5.5%-7.2%. To investigate the genetic ancestry of the Afrikaner population today (11-13 generations after initial colonization) we genotyped ~5 million genome-wide markers in 77 Afrikaner individuals and compared their genotypes to populations across the world to determine parental source populations and admixture proportions. We found that the majority of Afrikaner ancestry (average 95.3%) came from European populations (specifically northwestern European populations), but that almost all Afrikaners had admixture from non-Europeans. The non-European admixture originated mostly from people who were brought to South Africa as slaves and, to a lesser extent, from local Khoe-San groups. Furthermore, despite a potentially small founding population, there is no sign of a recent bottleneck in the Afrikaner compared to other European populations. Admixture among diverse groups during early colonial times might have counterbalanced the effects of a founding population with a small census size.

SIGNIFICANCE STATEMENT

Afrikaners are a southern African ethnic group primarily descended from colonial settlers (population ~2.8–3.5 million). Genome-wide studies might offer interesting insights into their ancestry, not the least due to South Africa’s history of segregationist laws known as “apartheid”, resulting in an expectation of low levels of admixture with other groups. Originating from a small founder population, their genetic diversity is also interesting. In our genome-wide study of 77 Afrikaners we found their majority ancestry (average 95.3%) came from Europeans, but almost all Afrikaners had admixture from non-Europeans (Africans and Asians). Despite their small founding population, we found no signs of decreased genetic diversity. Admixture among diverse groups during colonial times might have counterbalanced effects of a small founding population.
Transcriptome analysis ofPlasmodium bergheiduring exo-erythrocytic development
Authors: Caldelari Reto , Dogga Sunil , Schmid Marc W. , Franke-Fayard Blandine , Janse Chris J , Soldati-Favre Dominique , Heussler Volker
Published: February 2019

The complex life cycle of malaria parasites requires well-orchestrated stage specific gene expression. In the vertebrate host the parasites grow and multiply by schizogony in two different environments: within erythrocytes and within hepatocytes. Whereas erythrocytic parasites are rather well-studied in this respect, relatively little is known about the exo-erythrocytic stages. In an attempt to fill this gap, we performed genome wide RNA-seq analyses of various exo-erythrocytic stages ofPlasmodium bergheiincluding sporozoites, samples from a time-course of liver stage development and detached cells, which contain infectious merozoites and represent the final step in exo-erythrocytic development. The analysis represents the completion of the transcriptome of the entire life cycle ofP. bergheiparasites with temporal detailed analysis of the liver stage allowing segmentation of the transcriptome across the progression of the life cycle. We have used these RNA-seq data from different developmental stages to cluster genes with similar expression profiles, in order to infer their functions. A comparison with published data of other parasite stages confirmed stage-specific gene expression and revealed numerous genes that are expressed differentially in blood and exo-erythrocytic stages. One of the most exo-erythrocytic stage-specific genes was PBANKA_1003900, which has previously been annotated as a “gametocyte specific protein”. The promoter of this gene drove high GFP expression in exo-erythrocytic stages, confirming its expression profile seen by RNA-seq. The comparative analysis of the genome wide mRNA expression profiles of erythrocytic and different exo-erythrocytic stages improves our understanding of gene regulation ofPlasmodiumparasites and can be used to model exo-erythrocytic stage metabolic networks and identify differences in metabolic processes during schizogony in erythrocytes and hepatocytes.
Genome wide analysis ofGa1-smodifiers in maize
Authors: Hurst Preston , Liang Zhikai , Smith Christine , Yerka Melinda , Sigmon Brandi , Rodriguez Oscar , Schnable James C
Published: February 2019

A one way reproductive barrier exists between most popcorn varieties and dent corn varieties grown in the United States. This barrier is predominantly controlled by thega1locus. Using data from a diverse population of popcorn accessions pollinated by a dent corn tester, we found that the non-reciprocal pollination barrier conferred byga1is more complex than previously described. Individual accessions ranged from 0% to 100% compatible with dent corn pollen. Using conventional genotyping-by-sequencing data from 371 popcorn accessions carryingGa1-s, seven significant modifiers of dent pollen compatibility were identified on five chromosomes. One locus may either be a nonfunctionalga1allele present within popcorn, or second necessary gene for the reproductive barrier in genetic linkage withga1, while the other modifiers are clearly genetically unlinked. The existence ofga1modifiers segregating in a popcorn genetic background may indicate selective pressure to allow gene flow between populations, which should be incorporated into future models of the impact of genetic incompatibility loci on gene flow in natural and agricultural plant populations.
The unique coding sequence ofpmoCABoperon from type Ia methanotrophs simultaneously optimizes transcription and translation
Authors: Villada Juan C. , Duran Maria F. , Lee Patrick K. H.
Published: February 2019

Understanding the interplay between genotype and phenotype is a fundamental goal of functional genomics. Methane oxidation is a microbial phenotype with global-scale significance as part of the carbon biogeochemical cycle, and is a sink for greenhouse gas. Microorganisms that oxidize methane (methanotrophs) are taxonomically diverse and widespread around the globe. Recent reports have suggested that type Ia methanotrophs are the most prevalent methane-oxidizing bacteria in different environments. In methanotrophic bacteria, complete methane oxidation is encoded in four operons (pmoCAB, mmoXYZBCD, mxaFI, andxoxF), but how evolution has shaped these genes to execute methane oxidation remains poorly understood. Here, we used a genomic meta-analysis to investigate the coding sequences that encode methane oxidation. By analyzing isolate and metagenome-assembled genomes from phylogenetically and geographically diverse sources, we detected an anomalous nucleotide composition bias in the coding sequences of particulate methane monooxygenase genes (pmoCAB) from type Ia methanotrophs around the globe. We found that this was a highly conserved sequence that optimizes codon usage in order to maximize translation efficiency and accuracy, while minimizing the synthesis cost of transcripts and proteins. We show that among the seven types of methanotrophs, only type Ia methanotrophs possess a unique coding sequence of thepmoCABoperon that is under positive selection for optimal resource allocation and efficient synthesis of transcripts and proteins in environmental counter gradients with high oxygen and low methane concentrations. This adaptive trait possibly enables type Ia methanotrophs to respond robustly to fluctuating methane availability and explains their global prevalence.
Salicylic acid-driven association of LENRV and NIMIN1/NIMIN2 binding domain regions in the C-terminus of tobacco NPR1 transduces SAR signal
Authors: Neeley David , Konopka Evelyn , Straub Anna , Maier Felix , Pfitzner Artur J. P. , Pfitzner Ursula M.
Published: February 2019

NONEXPRESSOR OF PATHOGENESIS-RELATED (PR) GENES1 (NPR1) is the central regulator of salicylic acid (SA)-induced PR-1 gene expression and systemic acquired resistance (SAR). The mechanism how SA is transduced through NPR1 is discussed controversially. Previously, we showed that Arabidopsis and tobacco (Nt) NPR1 contain two domains in their C-terminal thirds with relevance to SA signaling. SA sensitivity of NPR1 relies on the arginine residue in the LENRV motif, and SA-induced NIM1-INTERACTING (NIMIN, N) proteins bind to a highly conserved sequence termed N1/N2 binding domain (BD).

We demonstrate that LENRV and N1/N2BD regions of tobacco NPR1, separated from each other, interact in yeast, in vitro, in plant and in animal cells. Physical association of LENRV and N1/N2BD parts is enhanced considerably by SA and functional analogs, but not by a non-functional analog. Furthermore, physical association requires R431 and is most effective with intact LENRV and N1/N2BD interfaces.

Association of separated LENRV and N1/N2BD parts by SA reconstitutes a functional NtNPR1 C-terminus, displaying transcription activity and able to interact with TGA transcription factors at two distinct sites.

Tobacco NIMIN proteins can assemble LENRV and N1/N2BD parts into ternary complexes suggesting that NIMINs shape the NPR1 C-terminus to modulate SA signaling.
Duo-activation of PKA and PKG by PDE1 inhibition facilitates proteasomal degradation of misfolded proteins and protects against proteinopathy
Authors: Zhang Hanming , Pan Bo , Rekhter Mark D. , Goldberg Alfred L. , Wang Xuejun
Published: February 2019

No current treatment is intended to target cardiac proteotoxicity or can reduce mortality of heart failure with preserved ejection fraction (HFpEF), a prevalent form of heart failure (HF). Selective degradation of misfolded proteins by the ubiquitin-proteasome system (UPS) is vital to the cell. Proteasome impairment is recently implicated in HF genesis. Activation of the cGMP-protein kinase G (PKG) or the cAMP-protein kinase A (PKA) pathways facilitates proteasome functioning. Phosphodiesterase 1 (PDE1) hydrolyzes both cyclic nucleotides and accounts for the majority of PDE activities in human myocardium. Here we report the preclinical therapeutic efficacy and a new mechanism of action of PDE1 inhibition (IC86430) for cardiac proteinopathy caused by Arg120Gly missense mutant αB-crystallin (CryABR120G). In mice expressing GFPdgn, an inverse reporter of UPS proteolytic activity, IC86430 treatment increased myocardial 26S proteasome activities and substantially decreased GFPdgn protein levels. Myocardial PDE1A expression was highly upregulated in CryABR120Gmice. HFpEF was detected in CryABR120Gmice at 4 months; IC86430 treatment initiated at this stage markedly attenuated HFpEF, substantially delayed mouse premature death, increased myocardial levels of Ser14-phosphorylated Rpn6, and reduced the steady state level of the misfolded CryAB species in these mice. In cultured cardiomyocytes, IC86430 treatment increased proteasome activities and accelerated proteasomal degradation of GFPu and CryABR120Gin a PKA- and PKG- dependent manner. We conclude that PDE1 inhibition induces PKA- and PKG-mediated promotion of proteasomal degradation of misfolded proteins in cardiomyocytes and effectively treats HFpEF caused by CryABR120G; hence, PDE1 inhibition represents a potentially new therapeutic strategy for HFpEF and heart disease with increased proteotoxic stress.

One Sentence Summary

PDE1 inhibition enhances proteasomal degradation of misfolded proteins in a PKA and PKG dependent manner and protects against cardiac proteinopathy and heart failure with preserved ejection fraction.
Integrative analysis of Hydra head regeneration reveals activation of distal enhancer-like elements
Authors: Murad Rabi , Macias-Muñoz Aide , Wong Ashley , Ma Xinyi , Mortazavi Ali
Published: February 2019

The cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. Cnidarians and bilaterians diverged about 600 millions years ago but the gene contents of species of both phyla are surprisingly similar despite divergent morphologies and functions. While little is known about the role ofcis-regulatory elements in cnidarians, understanding gene regulatory mechanisms in cnidarians can potentially shed light on metazoan evolution. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-hour head regeneration and 72-hour budding time-courses. In order to understand the regulatory elements controlling hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of organism. We used histone modification ChIP-seq to identify 9998 candidate proximal promoter and 3018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.
Pathogenic potential of Hic1 expressing cardiac stromal progenitors
Authors: Soliman H , Paylor B , Scott W , Lemos DR , Chang CK , Arostegui M , Low M , Lee C , Fiore D , Braghetta P , Pospichalova V , Barkauskas CE , Korinek V , Rampazzo A , MacLeod K , Underhill TM , Rossi FM
Published: February 2019

The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are still poorly understood. Here, we identify heart-resident PDGFRa+Sca-1+cells as cardiac Fibro/Adipogenic Progenitors (cFAPs) and show that they respond to ischemic damage by generating fibrogenic cells. Pharmacological blockade of this differentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardial infarction (MI) remodeling and leads to improvements in heart function. In the undamaged heart, activation of cFAPs through lineage-specific deletion of the quiescence factor Hic1 reveals additional pathogenic potential, causing fibro-fatty infiltration of the myocardium and driving major pathological features of Arrhythmogenic Cardiomyopathy (AC).

Highlights

A subpopulation of PDGFRa+, Sca-1+cells, previously considered to be a sub-type of cardiac fibroblasts, are multipotent mesenchymal progenitors,

Cardiac damage triggers the differentiation of PDGFRa+Sca-1+cells into Sca-1-cells expressing a fibrogenic transcriptional programme,

Blockade of the cFAP-to-fibroblast transition by Nilotinib ameliorated cardiac dysfunction post-MI and modulated cardiac remodelling.

Studies performed on a model of experimentally-induced AC confirmed that cFAPs are a source of both cardiac fibroblasts and adipocytesin vivo.

Conversely, in the undamaged heart, activation of cFAPs by means of lineage-specific deletion of transcription factor Hic1, resulted in fibro/fatty cardiac degeneration and pathological alterations reminiscent of AC. Collectively, our findings show that a proportion of what are commonly termed “fibroblasts” are actually multipotent mesenchymal progenitors that contribute to different forms of cardiac degeneration depending on the damage setting.
Diethyl 4-(1H-indol-3-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Authors: Lee Ji Hye , Koh Dongsoo
Published: February 2019

In the title compound, C21H24N2O4, the 1,4-dihydropyridine ring adopts a very flattened boat conformation, with the 3-pyridine substituent in an axial orientation. The pyridine ring is almost orthogonally twisted relative to the 1,4-dihydropyridine skeleton by 85.97 (2)°. In the crystal, pairs of N—H...O hydrogen bonds form inversion dimers enclosing R
2
2(16) rings. Pairs of intermolecular N—H...O hydrogen bonds link the dimers into chains along [100].
A critical appraisal of the international factors in “One Country, Two Systems” and democratization in Hong Kong
Authors: Chan Kenneth Ka Lok , Chong King Man Eric
Published: February 2019

Purpose

The purpose of this paper is to present an analytical framework to examine the impact of international factors on “One Country, Two Systems” in general and Hong Kong’s democratization in particular.

Design/methodology/approach

The paper has adopted a behavioral approach to identify the agents, mechanisms and observable facets of external–internal interactions.

Findings

The need for international recognition on the performance of the Hong Kong Special Administrative Region (HKSAR) under Chinese sovereignty has provided external actors with the necessary leverage. Though the impact of the international community has been indirect and limited, the authors have identified two mechanisms – lesson drawing and socialization – whereby the impact of international actors and their actions towards Hong Kong may be subtly felt. Moreover, there are at least three observable facets of external actions which are pertinent to the democracy issue. At the end of day, the external impacts will be determined not by the international actors per se but the balance of power between the domestic actors in Hong Kong.

Originality/value

There is a scholarly consensus that international factors matter to Hong Kong. But there has been a lack of serious investigation as to why and how they matter. The observable facets of external–internal interactions and the mechanisms identified in this work have not only enriched our understanding of the relevance of external factors in Hong Kong affairs, but also provided a sound foundation for future research.
The ties that bind: mutuality of political destiny between Hong Kong and Taiwan
Authors: Wong Wai Kwok Benson
Published: February 2019

Purpose

The purpose of this paper is to explain how post-1997 Hong Kong has been perceived in Taiwan and to critically evaluate the demonstration effects of Hong Kong under the “One Country, Two Systems” policy on cross-strait relations.

Design/methodology/approach

“Today’s Hong Kong, Tomorrow’s Taiwan” has become a dominant discourse in cross-strait relations in recent years. The paper has adopted discourse analysis of selected texts during and after the 2014 Sunflower Movement to elucidate the disapproval of the developments of post-handover Hong Kong and the construction of the Movement’s self-identity.

Findings

It has observed the following arguments which shaped the prevailing perceptions among critics of the “One Country, Two Systems” policy: political infiltration of China in Hong Kong could be extended to Taiwan in the sense that the Beijing authorities would adopt the identical approach to manipulate Taiwan through the cross-strait trading agreements; negative perceptions and images of China and Chinese capitals as a collective aggressor and a threat, raising fear and worries in both Hong Kong and Taiwan; and Kuomintang, as a ruling party at that time under the leadership of President Ma Ying-jeoh, was dismissed by protesters as an incompetent gatekeeper and defender of Taiwan’s interests.

Originality/value

The pervasive sentiments and perceptions about post-1997 Hong Kong has been articulated discursively by the young activists in Taiwan and Hong Kong into a statement – “Today’s Hong Kong, Tomorrow’s Taiwan” – which has brought about a somewhat unexpected bonding effect between Hong Kong and Taiwan through a strong disapproval of “One Country, Two Systems” and the China factor, which has be reproduced, delivered and circulated in both societies since 2014.
Collaboration quality assessment for sustainable supply chains: benchmarking
Authors: Dania Wike Agustin Prima , Xing Ke , Amer Yousef
Published: February 2019

Purpose

The purpose of this paper is to propose an instrument to evaluate the collaboration quality of sustainable supply chains by considering collaboration behaviour and sustainability factors.

Design/methodology/approach

The proposed model integrates Quality Function Deployment (QFD), Fuzzy Analytical Network Process (FANP) and Data Envelopment Analysis (DEA) to assess the efficiency score of each stakeholder involved. A case of a sugar company in Indonesia was analysed as the illustration of the application of the model.

Findings

The integrated QFD-FANP-DEA method enables to incorporate collaboration behaviour and sustainability factors in a single assessment model. The results of the case study showed the benchmarking results associated with the performance variance of stakeholders and the number of samples.

Research limitations/implications

Future research could consider other DEA approaches, extend the research by simulating a different number of scenarios and evaluating the improvement/deterioration, and expand the scope of collaboration.

Practical implications

Each stakeholder will be able to obtain the collaboration assessment results, and the improvements suggested by the model.

Social implications

Smallholders and farmers will be able to increase their benefits by using the existing resources.

Originality/value

This paper provides a methodological contribution by introducing new collaboration quality assessment methods that can accommodate any variance in multi-stakeholders, involve qualitative and quantitative measurements, and benefit all stakeholders.
Green Agrevolution Pvt Ltd: delivering 360° “seed-to-market” solution
Authors: Sinha Aditya , Jha Suresh , Amritesh Amritesh
Published: February 2019

Learning outcomes

The purpose of this paper is to introduce learners to a successful Agri-start-up where they can explore the existing challenges and critical strategic decisions for the firm’s growth.

Case overview/synopsis

Shashank, the CEO and co-founder of an agriculture-based Indian start-up Green Agrevolution Pvt Ltd (GAPL), is planning to reach out to more than one million farmers by 2021-2022, which is more than 20 times of the present volume. His team is presently serving around 42,000 farmers with a home-grown technological platform DeHaat which provides end–to-end services right from seed to the market. Micro-entrepreneurs are selected and groomed to act as local touchpoints for farmers in the respective catchment areas ranging from 3 to 5 km. Shashank has been a recipient of multiple accolades and recognition and is now firmly seated to drive his start-up to the next level of growth and pan-India market penetration. The venture also requires an understanding of segment-specific needs, cropping pattern, using local resources and channelizing the advisory services to occupy a central role in the value chain. There are other impending issues such as low smartphone adoption, low internet access and lack of entrepreneurial mindset among the rural youth. Similar issues were relatively backward states of India with little or no provision of app-based services. Will he be successful to expand on such a high pace in other States with the existing resources and capabilities?

Complexity academic level

Senior undergraduate and Master's level business students

Supplementary materials

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Subject code

CSS 11: Strategy