bluuebunny/crossref_metadata_2025 huggingface dataset:
A MiniG Protein Recruitment Assay for the Histamine Receptor Family to Functionally Characterize Histamine Receptor Ligands
Authors: Hoering Carina , Seibel Ulla , Littmann Timo , Graetz Lukas , Strasser Andrea , Bernhardt Guenther
Published: April 2020

In addition to the determination of binding affinities, the functional characterization of biologically active compounds is a prerequisite in drug discovery in order to identify lead structures and to optimize potential scaffolds regarding their mode of action and potency. Therefore, our aim was to develop a high‐throughput screening (HTS) compatible assay procedure yielding functional parameters of histamine receptor ligands at a proximal level avoiding signal amplification.

For this purpose, we applied the NanoLuc split‐luciferase technology
[1] to the histamine receptor subtypes H1, H2, H3 and H4 and the corresponding G protein surrogates miniGq, miniGs and miniGi
[2]. The small fragment of the NanoLuc (NlucC) was fused to the C‐terminus of the respective receptor to retain the integrity of the receptors regarding binding affinities and intracellular signalling, whereas the large fragment of the NanoLuc (NlucN) was N‐terminally fused to the miniG proteins (see fig.
1). Upon activation by a ligand the corresponding miniG protein is recruited to the receptor which then leads to the formation of a functional NanoLuc enzyme enabling the registration of a concentration dependent luminescence signal (see fig.
1).

Compared to reported data, standard ligands for histamine receptors
provide appropriate potencies, intrinsic activities and modes of action.By radioligand saturation binding experiments it could be shown that there was no alteration in the binding affinities of the radioligands due to the minor receptor modification by the C‐terminally fused NlucC. Additionally, this assay principle should be appropriate for HTS assessed by the investigation of the Z′ factor, which was in an excellent range for all histamine receptor subtypes (0.5 < Z′ < 1).

From these results we conclude that the application of the presented methodology is an excellent approach to be implemented in routine and detailed functional characterisation of putative histamine receptor ligands synthesized in our group. Moreover, the assay offers an opportunity to draw conclusions on biased signalling of investigated ligands in combination with the results obtained in β‐arrestin recruitment assays
[3].

Support or Funding Information

This project is funded by the DFG research training group GRK1910.

Schematic illustration of the assay principle.

Two complementing NanoLuc fragments fused to the receptor and the mini G protein form a functional NanoLuc upon activation of the GPCR.

Figure 1
Real Time Direct Detection of β – hydroxybutyrate Production in Perfused Mice Livers Using HP DHA
Authors: Giacalone Anthony Gregory , Ragavan Mukundan , Downes Daniel , McLeod Marc , Carter Alan , Michel Keith , Bankson James A. , Merritt Matthew E.
Published: April 2020

Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH) are increasingly prevalent in the United States. A diagnosis of NAFLD left untreated directly leads to the increase of NASH morbidity which is a result of over‐nutrition, poor diet, lack of exercise, and a sedentary lifestyle. However, NAFLD is typically reversible with a change in lifestyle. NAFLD is a group of common conditions that occur when excess fat accumulates in the liver of those who consume little alcohol. Changes in ketogenesis within the liver has been associated with NAFLD development in high‐fat diet models in mice, and in humans, lower ketogenesis is associated with an increase in hepatic steatosis. Since changes in ketogenesis are associated with different physiological conditions, it would be beneficial if the de novo ketone production can be measured in real‐time.

Here, we report the detection of β‐hydroxybutyrate (BHB) in perfused liver using hyperpolarized [2‐13C] dihydroxyacetone (HP‐DHA) and Magnetic Resonance Spectroscopy (MRS). Dihydroxyacetone (DHA) is avidly taken up by the liver and rapidly phosphorylated into dihydroxyacetone phosphate (DHAP). DHAP is then metabolized into (Fig.
1) phosphoenolpyruvate (PEP), glycerol‐3‐phosphate (G3P) and glucose (in fasted mice), representing glycolysis, fatty acid synthesis, and gluconeogenesis, respectively. HP‐DHA injection does not drive BHB production by a mass action effect. Fasting mice show significantly increased ketone production, but a low alanine and lactate signal are observed as gluconeogenesis is increased. BHB is a compelling indicator of rapid flux of carbon skeletons towards ketones. Metabolism of DHA to BHB requires at least 11 steps with most of the metabolites in fasted mice not being observable. This establishes the interplay between pool size and observable HP MR Signal.

The chemical shift of BHB makes it a prime target for imaging, as it does not overlap with other resonances. While previous research designs have been too complicated for clinical application, this work sets a foundation for a straightforward approach in measuring real‐time ketogenesis even as part of a routine MRI exam. This method, in particular, could serve as a powerful diagnostic tool for NAFLD and its transition to NASH.

Support or Funding Information

NIH R01DK105346

Sum spectra obtained by adding individual transients of the pseudo‐2D NMR acquisition post HP DHA injection. DHA and DHA‐hydrate resonances are not shown. Note dramatically increased BHB intensity in fasting. In the fasted state, 3‐ carbon precursors of glucose (alanine and lactate) show much reduced intensity.

Figure 1
Construct structurally defined Low molecular Heparan Sulfate microarray and its application
Authors: Su Guowei
Published: April 2020

Glycan microarray analysis is a high throughput method to screen the interaction between heparin oligosaccharides and target proteins. It is a powerful tool to investigate the binding between carbohydrates and carbohydrate‐binding proteins. Unlike other screening methods, microarray analysis uses a very small amount of target proteins (10 μg) to screen an entire library of Heparan Sulfate (HS) oligosaccharides. Currently we offers the microarray analysis covering up to 52 structurally defined HS oligosaccharides with a size range from pentasaccharides (5‐mer) to octodecasaccharides (18‐mer) representing many different sulfation types that can be found in nature.

Support or Funding Information

National Heart, Lung and Blood Institute, 1R01HL094463‐05National Institute of General Medical Sciences, 1U01GM1022137‐01, 1R41GM123792US FDA: U19FD004994‐01,NIH SBIR HHSN261201500019C

Symbolic structures of low molecular heparan sulfate synthesized for microarray

Figure 1

Workflow of Printed glycan arrays with fluorescent readout.

Figure 2
Automated Analysis of Microscale Cardiac Contractile Dynamics from Intravital Multiphoton Microscopy in Mouse Ventricle
Authors: Allan-Rahill Nathaniel H. , Small David M. , Lamont Michael R. E. , Djakpa Salomon , Nishimura Nozomi
Published: April 2020

Background

Multiphoton microscopy (MPM) has enabled in vivo time‐lapse imaging of the heart that shows motion of cells within the tissue with micrometer resolution. We developed automated analysis techniques to quantify cellular motion from in vivo cardiac MPM images throughout the cardiac cycle.

Methods

Intravital cardiac MPM was performed on ventilated, male and female, 4–6 month‐old, C57Bl6 mice (n=9). MPM image volumes (100 μm deep) of the beating mouse left ventricle were acquired at 30 frames per second while recording the electrocardiogram and respiratory pressure (Fig.
a). Image volumes were reconstructed by assembling lines acquired nearest to a specified point in the cardio‐respiratory phase space. Bulk‐tissue motion was calculated from the three‐dimensional translational transformation that best aligned images at each point of the cardiac cycle to a reference image at the most stable portion of the cardio‐respiratory phase space (respiratory 50%, cardiac 80%). After bulk‐tissue motion was subtracted, local tissue deformation was extracted via non‐rigid registration of the reconstructed images to the reference image and divergence was calculated from the resulting vector field. Analysis methods were applied to images before and after epinephrine injection (50 μg intramuscular), and following focal sterile injury by laser irradiation (FSI).

Results

Volumes were reconstructed in 50 intervals across the cardiac cycle that show vasculature (intravenous Texas‐red dextran, red) and cardiomyocytes and leukocytes (rhodamine 6G, cyan) moving across the field of view (Fig.
b–c). Automated analysis of bulk‐tissue motion (Fig.
d–e) indicated maximum displacements occurring at 16 % (anterior‐posterior direction), 36 % (superior‐inferior) and 38 % (epi‐endocardial) of the cardiac cycle. The calculated epi‐endocardial motion amplitude correlated with stroke volume (R2=0.35) measured by echocardiography in the same animal one day before MPM imaging. Automated analysis of local tissue deformation indicated a maximum absolute deformation occurring at 10 % of the cardiac cycle (Fig.
f). Comparison to manual feature tracking across the cardiac cycle validated the automated measurements. Rigid and non‐rigid motion analysis techniques were applied to epinephrine stress test and focal sterile injury (FSI) lesion models showing, respectively, increased and decreased bulk‐tissue and local deformation and divergence.

Conclusions

We have shown and applied novel, fast, and accurate techniques for characterizing cardiac motion from in vivo cardiac MPM to study the performance of contractile cells in the heart during health and disease.

Support or Funding Information

American Heart Association (17POST33680127), National Institutes of Health (5R21EB024694‐03), and National Science Foundation (DBI‐1707312).

Figure 1
Examining the link between relaxed predation and bird coloration on islands
Authors: Bliard Louis , Paquet Matthieu , Robert Aloïs , Dufour Paul , Renoult Julien P. , Grégoire Arnaud , Crochet Pierre-André , Covas Rita , Doutrelant Claire
Published: April 2020

Insular ecosystems share analogous ecological conditions, leading to patterns of convergent evolution that are collectively termed as the ‘island syndrome’. In birds, part of this syndrome is a tendency for a duller plumage, possibly as a result of relaxed sexual selection. Despite this global pattern, some insular species display a more colourful plumage than their mainland relatives, but why this occurs has remained unexplained. Here, we examine the hypothesis that these cases of increased plumage coloration on islands could arise through a relaxation of predation pressure. We used comparative analyses to investigate whether average insular richness of raptors of suitable mass influences the plumage colourfulness and brightness across 110 pairs of insular endemic species and their closest mainland relatives. As predicted, we find a likely negative relationship between insular coloration and insular predation while controlling for mainland predation and coloration, suggesting that species were more likely to become more colourful as the number of insular predators decreased. By contrast, plumage brightness was not influenced by predation pressure. Relaxation from predation, together with drift, might thus be a key mechanism of species phenotypic responses to insularity.
Photoreflectance/scattering measurements of spider silks informed by standard optics
Authors: Blamires Sean J. , Little Douglas J. , White Thomas E. , Kane Deb M.
Published: April 2020

The silks of certain orb weaving spiders are emerging as high-quality optical materials. This motivates study of the optical properties of such silk and particularly the comparative optical properties of the silks of different species. Any differences in optical properties may impart biological advantage for a spider species and make the silks interesting for biomimetic prospecting as optical materials. A prior study of the reflectance of spider silks from 18 species reported results for three species of modern orb weaving spiders (
Nephila clavipes, Argiope argentata
and
Micrathena Schreibersi
) as having reduced reflectance in the UV range. (Modern in the context used here means more recently derived.) The reduced UV reflectance was interpreted as an adaptive advantage in making the silks less visible to insects. Herein, a standard, experimental technique for measuring the reflectance spectrum of diffuse surfaces, using commercially available equipment, has been applied to samples of the silks of four modern species of orb weaving spiders:
Phonognatha graeffei
,
Eriophora transmarina
,
Nephila plumipes
and
Argiope keyserlingi
. This is a different technique than used in the previous study. Three of the four silks measured have a reduced signal in the UV. By taking the form of the silks as optical elements into account, it is shown that this is attributable to a combination of wavelength-dependent absorption and scattering by the silks rather than differences in reflectance for the different silks.
Phonognatha graeffei
dragline silk emerges as a very interesting spider silk with a flat ‘reflectance'/scattering spectrum which may indicate it is a low UV absorbing dielectric micro-fibre. Overall the measurement emerges as having the potential to compare the large numbers of silks from different species to prospect for those which have desirable optical properties.
A new member of fossil balaenid (Mysticeti, Cetacea) from the early Pliocene of Hokkaido, Japan
Authors: Tanaka Yoshihiro , Furusawa Hitoshi , Kimura Masaichi
Published: April 2020

The family Balaenidae includes two genus and four extant species. Extinct balaenids are known for at least four genus and 10 species. The oldest known record of members of the Balaenidae is known from the early Miocene, but still need more early members of the family to provide better phylogenetic hypotheses. FCCP 1049 from the lower part of the Chippubetsu Formation, Fukagawa Group (3.5–5.2 Ma, Zanclean, early Pliocene) was preliminary described and identified as
Balaenula
sp. by Furusawa and Kimura in 1982. Later works discussed that FCCP 1049 is different from the genus, and is placed in different clade from
Balaenula astensis
. The result of our phylogenetic analysis places FCCP 1049 basal to
Balaenella brachyrhynus
, and is again separated from
B. astensis.
In this study, FCCP 1049 is re-described and named as
Archaeobalaena dosanko
gen. et sp. nov.
Archaeobalaena dosanko
is distinguishable from other balaenids by having a deep promontorial groove of the pars cochlearis of the periotic.
Archaeobalaena dosanko
can be differentiated from other balaenids, except
Morenocetus parvus
by having a slender zygomatic process, and posteriorly oriented postorbital process in dorsal view.
Archaeobalaena dosanko
adds detailed skull, periotic and bulla morphologies for the earlier balaenids.
Influence of past climate change on phylogeography and demographic history of narwhals,
Monodon monoceros
Authors: Louis Marie , Skovrind Mikkel , Samaniego Castruita Jose Alfredo , Garilao Cristina , Kaschner Kristin , Gopalakrishnan Shyam , Haile James S. , Lydersen Christian , Kovacs Kit M. , Garde Eva , Heide-Jørgensen Mads Peter , Postma Lianne , Ferguson Steven H. , Willerslev Eske , Lorenzen Eline D.
Published: April 2020

The Arctic is warming at an unprecedented rate, with unknown consequences for endemic fauna. However, Earth has experienced severe climatic oscillations in the past, and understanding how species responded to them might provide insight into their resilience to near-future climatic predictions. Little is known about the responses of Arctic marine mammals to past climatic shifts, but narwhals (
Monodon monoceros
) are considered one of the endemic Arctic species most vulnerable to environmental change. Here, we analyse 121 complete mitochondrial genomes from narwhals sampled across their range and use them in combination with species distribution models to elucidate the influence of past and ongoing climatic shifts on their population structure and demographic history. We find low levels of genetic diversity and limited geographic structuring of genetic clades. We show that narwhals experienced a long-term low effective population size, which increased after the Last Glacial Maximum, when the amount of suitable habitat expanded. Similar post-glacial habitat release has been a key driver of population size expansion of other polar marine predators. Our analyses indicate that habitat availability has been critical to the success of narwhals, raising concerns for their fate in an increasingly warming Arctic.
Social interventions can lower COVID-19 deaths in middle-income countries
Authors: Paternina-Caicedo Angel , Choisy Marc , Garcia-Calavaro Christian , España Guido , Rojas-Suarez José , Dueñas Carmelo , Smith Adrian , De la Hoz-Restrepo Fernando
Published: April 2020

Summary paragraph

A novel pandemic coronavirus disease (COVID-19) was first detected in late 2019 in Wuhan (China)1,2. COVID-19 has caused 77 national governments worldwide to impose a lockdown in part or all their countries, as of April 4, 20203. The United States and the United Kingdom estimated the effectiveness of non-pharmaceutical interventions to reduce COVID-19 deaths, but there is less evidence to support choice of control measures in middle-income countries4. We used Colombia, an upper-middle income country, as a case-study to assess the effect of social interventions to suppress or mitigate the COVID-19 pandemic. Here we show that a combination of social distancing interventions, triggered by critical care admissions, can suppress and mitigate the peak of COVID-19, resulting in less critical care use, hospitalizations, and deaths. We found, through a mathematical simulation model, that a one-time social intervention may delay the number of critical care admissions and deaths related to the COVID-19 pandemic. However, a series of social interventions (social and work distance and school closures) over a period of a year can reduce the expected burden of COVID-19, however, these interventions imply long periods of lockdown. Colombia would prevent up to 97% of COVID-19 deaths using these triggered series of interventions during the first year. Our analyses could be used by decision-makers from other middle-income countries with similar demographics and contact patterns to Colombia to reduce COVID-19 critical care admissions and deaths in their jurisdictions.
Effect of emergency declaration for the COVID-19 outbreak in Tokyo, Japan in the first two weeks
Authors: Kurita Junko , Sugawara Tamie , Ohkusa Yasushi
Published: April 2020

Background

Japan’s Prime Minister Abe declared an emergency to control the COVID-19 outbreak on April 7, 2020. He asked almost half of the population of Japan to reduce their personal contacts by 70–80%.

Object

This study estimates the effectiveness of that emergency declaration. Method: We applied a simple susceptible–infected–recovery model to data of patients with symptoms in Tokyo, Japan for January 14 – April 21 as of April 22. We estimate the reproduction number in four periods: R0 before voluntary event cancellation and school closure (VECSC) which was introduced since February 27 to March 19, Rv during the VECSC, Ra after VECSC, and Re after the emergency declaration.

Results

Results suggest that the value of R0 was estimated as 1.267; its range was [1.214, 1.341]. However, Rv was estimated as 2.360 [1.844, 2.623]. Ra was estimated as 2.307 [2.035, 2.794] and Re was 0.462 [0.347, 0.514].

Discussion and Concussion

One must be reminded that these results reflect only those at two weeks after the emergency declaration. The reproduction number probably changed thereafter continuously.
Development and validation of an early warning score (EWAS) for predicting clinical deterioration in patients with coronavirus disease 2019
Authors: Guo Yabing , Liu Yingxia , Lu Jiatao , Fan Rong , Zhang Fuchun , Yin Xueru , Liu Zhihong , Zeng Qinglang , Yuan Jing , Hu Shufang , Wang Qiongya , Liao Baolin , Huang Mingxing , Yin Sichun , Zhang Xilin , Xin Rui , Lin Zhanzhou , Hu Changzheng , Zhao Boliang , He Ridong , Liang Minfeng , Zhang Zheng , Liu Li , Sun Jian , Tang Lu , Deng Lisi , Xia Jinyu , Tang Xiaoping , Liu Lei , Hou Jinlin
Published: April 2020

Background

Since the pandemic outbreak of coronavirus disease 2019 (COVID-19), the health system capacity in highly endemic areas has been overwhelmed. Approaches to efficient management are urgently needed. We aimed to develop and validate a score for early prediction of clinical deterioration of COVID-19 patients.

Methods

In this retrospective multicenter cohort study, we included 1138 mild to moderate COVID-19 patients admitted to 33 hospitals in Guangdong Province from December 27, 2019 to March 4, 2020 (N =818; training cohort), as well as two hospitals in Hubei Province from January 21 to February 22, 2020 (N =320; validation cohort) in the analysis.

Results

The 14-day cumulative incidences of clinical deterioration were 7.9% and 12.1% in the training and validation cohorts, respectively. An Early WArning Score (EWAS) (ranging from 0 to 4.5), comprising of age, underlying chronic disease, neutrophil to lymphocyte ratio, C-reactive protein, and D-dimer levels, was developed (AUROC: 0.857). By applying the EWAS, patients were categorized into low-, medium-, and high risk groups (cut-off values: two and three). The 14-day cumulative incidence of clinical deterioration in the low-risk group was 1.8%, which was significantly lower than the incidence rates in the medium-(14.4%) and high-risk (40.9%) groups (P <.001). The predictability of EWAS was similar in the validation cohort (AUROC =0.781), patients in the low-, medium-, and high-risk groups had 14-day cumulative incidences of 2.6%, 10.0%, and 25.7%, respectively (P <.001).

Conclusion

The EWAS, which is based on five common parameters, can predict COVID-19-related clinical deterioration and may be a useful tool for a rapid triage and establishing a COVID-19 hierarchical management system that will greatly focus clinical management and medical resources to reduce mortality in highly endemic areas.
A nitrogen source-regulated microprotein confers an alternative mechanism of G1/S transcriptional activation in budding yeast
Authors: Tollis Sylvain , Singh Jaspal , Thattikota Yogitha , Palou Roger , Ghazal Ghada , Coulombe-Huntington Jasmin , Tang Xiaojing , Moore Susan , Blake Deborah , Bonneil Eric , Royer Catherine A. , Thibault Pierre , Tyers Mike
Published: April 2020

Commitment to cell division at the end of G1 phase, termed Start in the budding yeastSaccharomyces cerevisiae,is strongly influenced by nutrient availability. To identify new dominant activators of Start that might operate under different nutrient conditions, we screened a genome-wide ORF overexpression library for genes that bypass a Start arrest caused by absence of the G1 cyclin Cln3 and the transcriptional activator Bck2. We recovered a hypothetical geneYLR053c,renamedNRS1for Nitrogen-Responsive Start regulator 1, which encodes a poorly characterized 108 amino acid microprotein. Endogenous Nrs1 was nuclear-localized, restricted to poor nitrogen conditions, induced upon mTORCl inhibition, and cell cycle-regulated with a peak at Start.NRS1interacted genetically withSWI4andSWI6,which encode subunits of the main G1/S transcription factor complex SBF. Correspondingly, Nrs1 physically interacted with Swi4 and Swi6 and was localized to G1/S promoter DNA. Nrs1 exhibited inherent transactivation activity and fusion of Nrs1 to the SBF inhibitor Whi5 was sufficient to suppress other Start defects. Nrs1 appears to be a recently evolved microprotein that rewires the G1/S transcriptional machinery under poor nitrogeny conditions.

Author Summar

Unicellular microorganisms must adapt to ever-changing nutrient conditions and hence must adjust cell growth and proliferation to maximize fitness. In the budding yeastSaccharomyces cerevisiae, commitment to cell division, termed Start, is heavily influenced by nutrient availability. Our understanding of how Start is activated is based mainly on experiments carried out under rich nutrient conditions. To identify potential new Start regulators specific to poor nutrient environments, we screened for genes able to bypass a genetic Start arrest caused by loss of the G1 cyclin Cln3 and the transcriptional activator Bck2. This screen uncoveredYLR053c, which we renamedNRS1for Nitrogen-Responsive Start regulator. Sequence analysis across yeast species indicated that Nrs1 is a recently-evolved microprotein. We showed thatNRS1is nutrient- and cell cycle-regulated, and directly binds the main G1/S transcription factor complex SBF. We demonstrated that Nrs1 has an intrinsic trans-activation activity and provided genetic evidence to suggest that Nrs1 can bypass the requirement for normal Cln3-dependent activation of G1/S transcription. These results uncover a new mechanism of Start activation and illustrate how microproteins can rapidly emerge to rewire fundamental cellular processes.
Neural correlates of cognitive motor signals in primary somatosensory cortex
Authors: Jafari Matiar , Aflalo Tyson NS , Chivukula Srinivas , Kellis Spencer S , Salas Michelle Armenta , Norman Sumner L , Pejsa Kelsie , Liu Charles Y. , Andersen Richard A
Published: April 2020

Classical systems neuroscience positions primary sensory areas as early feed-forward processing stations for refining incoming sensory information. This view may oversimplify their role given extensive bi-directional connectivity with multimodal cortical and subcortical regions. Here we show that single units in human primary somatosensory cortex encode imagined reaches centered on imagined limb positions in a cognitive motor task. This result suggests a broader role of primary somatosensory cortex in cortical function than previously demonstrated.
Interactions between fungal hyaluronic acid and host CD44 promote internalization by recruiting host autophagy proteins to forming phagosomes
Authors: Ding Sheng Li , Pandey Aseem , Feng Xuehuan , Yang Jing , da Costa Luciana Fachini , Mouneimne Roula , Rice-Ficht Allison , Bell Samantha L. , Watson Robert O. , Patrick Kristin , Qin Qing-Ming , Ficht Thomas A. , de Figueiredo Paul
Published: April 2020

Phagocytosis and autophagy play critical roles in immune defense.Cryptococcus neoformans(Cn), a fungal pathogen that causes fatal infection, subverts the host autophagy initiation complex (AIC) and its upstream regulatory proteins, to promote its phagocytosis and intracellular parasitism of host cells. The mechanisms by which the pathogen engages host AIC proteins remain obscure. Here, we show that the recruitment of host AIC proteins to forming phagosomes is dependent upon the activity of CD44, a host cell surface receptor that engages fungal hyaluronic acid (HA). This interaction elevates intracellular Ca2+concentrations and activates CaMKKβ and its downstream target AMPKα, which results in activation of ULK1 and the recruitment of AIC components. Moreover, we demonstrate that HA-coated beads efficiently recruit AIC components to phagosomes. Taken together, these findings show that fungal HA plays a critical role in directing the internalization and productive intracellular membrane trafficking of a fungal pathogen of global importance.

Graphical Abstract

In Brief

Ding et al. reveal that interactions between fungal hyaluronic acid (HA) and host CD44 activate a Ca2+- CaMKKβ-AMPK-ULK1 signaling pathway that recruits autophagy initiation complex components to forming phagosomes to drive fungal internalization.

Highlights

Fungal HA interactions with host cells drive a novel non-canonical, ligand-induced, autophagy pathway in phagocytic cells

Cryptococcus neoformansrecruits host CD44, together with AIC components and regulatory proteins, to forming phagocytic cups to initiate host cell internalization

Fungal HA interactions with CD44 on host cell surfaces elevate intracellular Ca2+concentrations, leading to activation of CaMKKβ

A Ca2+-CaMKKβ-AMPK-ULK1 signaling axis is involved in HA and CD44 induced autophagy protein recruitment during Cn internalization
Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery
Authors: Ahmed Shiek SSJ , Paramasivam Prabu , Raj Kamal , Kumar Vishal , murugesan Ram , Ramakrishnan
Published: April 2020

We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.
Grapevine pruning time affects natural wound colonization by wood-invading fungi
Authors: del Pilar Martínez-Diz María , Eichmeier Ales , Spetik Milan , Bujanda Rebeca , Díaz-Fernández Ángela , Díaz-Losada Emilia , Gramaje David
Published: April 2020

Grapevine pruning wounds made during the dormant season are a port of entry of wood-invading fungi. Timing of pruning may affect the wound susceptibility to these fungi, such as those associated with grapevine trunk diseases (GTDs). This study aimed to determine the effect of pruning time on natural fungal infection in six vineyards in Galicia, Spain, belonging to three Denominations of Origin (D.O) over two growing seasons. Pruning wounds were left unprotected physically and chemically during two periods of three months each, from November to February and from February to May. The diversity and composition of the fungal microbiome that colonized the pruning wounds was identified by ITS2 high-throughput amplicon sequencing (HTAS). A broad range of fungi was able to colonize grapevine pruning wounds at both infection periods. Fungal microbiome composition did not shift as year of sampling. Fungal communities were affected in their diversity and composition by the D.O., whereas the spatial variation (i.e. vineyard within each region) was low. Pruned canes harboured a core community of fungal species, which appeared to be independent of the infection period. Accumulated rainfall over 8 and 11 weeks after pruning positively correlated with the total fungal microbiome and in particular with the GTD fungal genusDiaportheabundances. A strong seasonal effect on GTD fungal infection was detected for most genera, with higher percentages of abundance detected after pruning in February (winter) as compared with that of pruning in November (mid-autumn). In light of the GTD colonization results and given the environmental conditions and the geographical location of this study, early pruning is recommended to reduce the infections caused by GTD fungi during the pruning season in Galicia.
Particle-associated and free-living bacterial communities in an oligotrophic sea are affected by different environmental and anthropogenic factors
Authors: Rosenberg Dalit Roth , Haber Markus , Goldford Joshua , Lalzar Maya , Aharoonovich Dikla , Al-Ashhab Ashraf , Lehahn Yoav , Krom Michael D. , Segrè Daniel , Steindler Laura , Sher Daniel
Published: April 2020

In the oceans and seas, environmental conditions change over multiple temporal and spatial scales. Here, we ask what factors affect the bacterial community structure across time, depth and size fraction during six seasonal cruises (two years) in the ultra-oligotrophic Eastern Mediterranean Sea. The bacterial community varied most between size fractions (free-living vs particle-associated), followed by depth and finally season. The free-living (FL) community was taxonomically richer and more stable than the particle-associated (PA) one, which was characterized by recurrent “blooms” of heterotrophic bacteria such asAlteromonasandRalstonia. The heterotrophic FL and PA communities were also correlated with different environmental parameters: depth and phytoplankton correlated with the FL population, whereas PA bacteria were correlated primarily with season. A significant part of the variability in community structure could not, however, be explained by the measured environmental parameters. The metabolic potential of the PA community, predicted from 16S amplicon data, was enriched in pathways associated with the degradation and utilization of biological macromolecules, as well as plastics, other petroleum products and herbicides. The FL community was enriched in pathways for the metabolism of inositol phosphate, a potential phosphorus source, and of polycyclic aromatic hydrocarbons.

Originality – Significance Statement

Marine microbial populations are complex and dynamic, and the environmental drivers of the structure and function of these communities are mostly unclear. Specifically, marine microbial communities change over time, over depth and between particle-associated and free-living size fractions, yet the relative importance of each of these axes of variability is unclear. Our results highlight fundamentally different population dynamics between free-living and particle-associated marine bacteria: free living populations were more similar between seasons, whereas particle-associated populations were highly variable and exhibited “blooms” of specific clades of heterotrophic bacteria. We also suggest that the environmental conditions often measured as part of oceanographic cruises are not enough to explain most of the variability in microbial population structure. We speculate that organismal interactions and the presence of anthropogenic pollution may be also be important yet under-sampled drivers of oligotrophic marine microbial communities.
Clearing-induced tisssue shrinkage: Novel observation of a thickness size effect
Authors: Vulders R.C.M. , van Hoogenhuizen R.C. , van der Giessen E. , van der Zaag P.J.
Published: April 2020

The use of clearing agents has provided new insights in various fields of medical research (developmental biology, neurology) by enabling examination of tissue architecture in 3D. One of the challenges is that clearing agents induce tissue shrinkage and the shrinkage rates reported in the literature are incoherent. Here, we report that the shrinkage for a widely-used clearing agent decreases significantly with increasing sample size, and report an analytical description.
Crystal structure, Hirshfeld surface analysis and DFT studies of 6-bromo-3-(12-bromododecyl)-2-(4-nitrophenyl)-4H-imidazo[4,5-b]pyridine
Authors: Jabri Zainab , Jarmoni Karim , Hökelek Tuncer , Mague Joel T. , Sabir Safia , Kandri Rodi Youssef , Misbahi Khalid
Published: April 2020

The title compound, C24H30Br2N4O2, consists of a 2-(4-nitrophenyl)-4H-imidazo[4,5-b]pyridine entity with a 12-bromododecyl substituent attached to the pyridine N atom. The middle eight-carbon portion of the side chain is planar to within 0.09 (1) Å and makes a dihedral angle of 21.9 (8)° with the mean plane of the imidazolopyridine moiety, giving the molecule a V-shape. In the crystal, the imidazolopyridine units are associated through slipped π–π stacking interactions together with weak C—HPyr...ONtr and C—HBrmdcyl...ONtr (Pyr = pyridine, Ntr = nitro and Brmdcyl = bromododecyl) hydrogen bonds. The 12-bromododecyl chains overlap with each other between the stacks. The terminal –CH2Br group of the side chain shows disorder over two resolved sites in a 0.902 (3):0.098 (3) ratio. Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are from H...H (48.1%), H...Br/Br...H (15.0%) and H...O/O...H (12.8%) interactions. The optimized molecular structure, using density functional theory at the B3LYP/ 6–311 G(d,p) level, is compared with the experimentally determined structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.
Structure of a push–pull olefin prepared by ynamine hydroboration with a borandiol ester
Authors: Gubler Joël , Chen Peter
Published: April 2020

N-[(Z)-2-(2H-1,3,2-Benzodioxaborol-2-yl)-2-phenylethenyl]-N-(propan-2-yl)aniline, C23H22BNO2, contains a C=C bond that is conjugated with a donor and an acceptor group. An analysis that included similar push–pull olefins revealed that bond lengths in their B—C=C—N core units correlate with the perceived acceptor and donor strength of the groups. The two phenyl groups in the molecule are rotated with respect to the plane that contains the BCCN atoms, and are close enough for significant π-stacking. Definite characterization of the title compound demonstrates, for the first time in a reliable way, that hydroboration of ynamines with borandiol esters is feasible. Compared to olefin hydroboration with borane, the ynamine substrate is activated enough to undergo reaction with the less active hydroboration reagent catecholborane.
The ‘new’ Philippine future “beside” the exodus
Authors: Opiniano Jeremaiah M.
Published: April 2020

Purpose

The purpose of this paper is to review the international migration-and-development story of the Philippines, amongst the leading migrant-origin countries.

Design/methodology/approach

Migration and socio-economic development data are used to depict the migration-and-development conditions of the Philippines.

Findings

The Philippines has mastered the management of overseas migration based on its bureaucracy and policies for the migrant sector. Migration also rose for decades given structural economic constraints. However, the past 10 years of macro-economic growth may have seen migration and remittances helping lift the Philippines' medium-to-long term acceleration. The new Philippine future beside the overseas exodus hinges on two trends: accelerating the economic empowerment of overseas Filipinos and their families to make them better equipped to handle the social costs of migration; and strategizing how to capture a “diasporic dividend” by pushing for more investments from overseas migrants' savings.

Research limitations/implications

This paper may not cover the entirety of the Philippines' migration-and-development phenomenon.

Practical implications

Improving the financial capabilities of overseas Filipinos and their families will lead to their economic empowerment and to hopefully a more resilient handling of the (negative) social consequences of migration.

Social implications

If overseas Filipinos and their families handle their economic resources better, they may be able to conquer the social costs of migration.

Originality/value

This paper employed a population-and-development (PopDev) framework to analyse the migration-and-development conditions of the Philippines.
Artificial intelligence (AI) in strategic marketing decision-making: a research agenda
Authors: Stone Merlin , Aravopoulou Eleni , Ekinci Yuksel , Evans Geraint , Hobbs Matt , Labib Ashraf , Laughlin Paul , Machtynger Jon , Machtynger Liz
Published: April 2020

Purpose

The purpose of this paper is to review literature about the applications of artificial intelligence (AI) in strategic situations and identify the research that is needed in the area of applying AI to strategic marketing decisions.

Design/methodology/approach

The approach was to carry out a literature review and to consult with marketing experts who were invited to contribute to the paper.

Findings

There is little research into applying AI to strategic marketing decision-making. This research is needed, as the frontier of AI application to decision-making is moving in many management areas from operational to strategic. Given the competitive nature of such decisions and the insights from applying AI to defence and similar areas, it is time to focus on applying AI to strategic marketing decisions.

Research limitations/implications

The application of AI to strategic marketing decision-making is known to be taking place, but as it is commercially sensitive, data is not available to the authors.

Practical implications

There are strong implications for all businesses, particularly large businesses in competitive industries, where failure to deploy AI in the face of competition from firms, who have deployed AI to improve their decision-making could be dangerous.

Social implications

The public sector is a very important marketing decision maker. Although in most cases it does not operate competitively, it must make decisions about making different services available to different citizens and identify the risks of not providing services to certain citizens; so, this paper is relevant to the public sector.

Originality/value

To the best of the authors’ knowledge, this is one of the first papers to probe deployment of AI in strategic marketing decision-making.
Electro-quasistatic field-simulation of biological cells using balanced domain-decomposition
Authors: Böhmelt Sebastian , Kielian Nils , Hagel Michael , Stiemer Marcus , Henkel Marvin-Lucas , Clemens Markus
Published: April 2020

Purpose

The purpose of this paper is to present the implementation of a balanced domain decomposition approach for the numerical simulation of large electro-quasistatic (EQS) systems in biology. The numerical scheme is analyzed and first applications are discussed.

Design/methodology/approach

The scheme is based on a finite element discretization of the individual domains obtained by decomposition and a physically consistent inter-domain coupling realized via Robin boundary conditions. The proposed algorithms can efficiently be implemented on a highly parallelized computing grid.

Findings

The feasibility and applicability of the method is proven. Further, a couple of technical details are found that increase the efficiency of the method.

Originality/value

The presented method offers an enhanced geometrical flexibility and extensibility to simulate larger cell systems with higher model resolution compared to other methods presented in the literature. The presented analysis provides an understanding of the balanced coupling scheme for large EQS systems.
Network planning of urban underground logistics system with hub-and-spoke layout: two phase cluster-based approach
Authors: Hu Wanjie , Dong Jianjun , Hwang Bon-Gang , Ren Rui , Chen Zhilong
Published: April 2020

Purpose

Underground logistics system (ULS) is recognized as sustainable alleviator to road-dominated urban logistics infrastructure with various social and environmental benefits. The purpose of this study is to propose effective modeling and optimization method for planning a hub-and-spoke ULS network in urban region.

Design/methodology/approach

Underground freight tunnels and the last-mile ground delivery were organized as a hierarchical network. A mixed-integer programming model (MIP) with minimum system cost was developed. Then a two-phase optimization schema combining Genetic-based fuzzy C-means algorithm (GA-FCM), Depth-first-search FCM (DFS-FCM) algorithm and Dijkstra algorithm (DA), etc. was designed to optimize the location-allocation of ULS facilities and customer clusters. Finally, a real-world simulation was conducted for validation.

Findings

The multistage strategy and hybrid algorithms could efficiently yield hub-and-spoke network configurations at the lowest objective cost. GA-FCM performed better than K-means in customer-node clustering. The combination of DFS-FCM and DA achieved superior network configuration than that of combining K-means and minimum spanning tree technique. The results also provided some management insights: (1) greater scale economies effect in underground freight movement could reduce system budget, (2) changes in transportation cost would not have obvious impact on ULS network layout and (3) over 90% of transportation process in ULS network took place underground, giving remarkable alleviation to road freight traffic.

Research limitations/implications

Demand pairs among customers were not considered due to lacking data. Heterogeneity of facilities capacity parameters was omitted.

Originality/value

This study has used an innovative hybrid optimization technique to address the two-phase network planning of urban ULS. The novel design and solution approaches offer insights for urban ULS development and management.
Key drivers for smart and sustainable practices in the built environment
Authors: Olawumi Timothy O. , Chan Daniel W.M.
Published: April 2020

Purpose

The construction industry has been evolving in recent years through the adoption of smart tools such as building information modeling to reduce the complexity in the construction process and optimize the project's goals. This paper aims to identify and assess the key drivers for the implementation of smart sustainable practices in the construction industry.

Design/methodology/approach

Inferential and descriptive statistical techniques were employed in analyzing the data collected via an international empirical questionnaire survey deployed in soliciting the perceptions of 220 construction professionals across 21 countries. Factor analysis was used to categorize the identified key drivers into their underlying clusters for further discussion. Also, the data were analyzed based on the various groups and regions of the study's respondents.

Findings

The key drivers (KDs) are related to the technical competence of staff as well as knowledge and awareness level within the industry, issues related to organizational and project's strategy and policies, availability of financial resources and development of relevant standards and policies to aid its execution among others. A comparative analysis of the perceptions of the different respondents' groups was undertaken and discussed.

Practical implications

The analysis of the key drivers for the implementation of smart and sustainable practices in the construction industry is expected to aid the decision-making of the relevant stakeholders as well as serve as a consultation instrument for government agencies in their design of localized policies and guidelines to aid smart and sustainable urbanization. The findings revealed the gaps in the implementation of smart and sustainable practices in various climes and organization setups and provided useful and practical strategies for addressing the current hindrances during implementation.

Originality/value

The study has generated valuable insights into the significant drivers that can enhance the implementation of smart and sustainable practices across regions. It is evident that synergy among the relevant stakeholders in the built environment will help accelerate the implementation of smart sustainable practices in the construction industry. The study findings have provided profound contributions to theory and research as well as to industry practice.