bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzyme immunoassay for SARS-CoV-2 antibodies in dried blood spot samples: A minimally-invasive approach to facilitate community- and population-based screening
Authors: McDade Thomas W. , McNally Elizabeth M. , D’Aquila Richard , Mustanski Brian , Miller Aaron , Vaught Lauren A. , Reiser Nina L. , Bogdanovic Elena , Zelikovich Aaron S. , Demonbreun Alexis R.
Published: May 2020

Background

Serological testing for SARS-CoV-2 IgG antibodies is needed to document the community prevalence and distribution of the virus, particularly since many individuals have mild symptoms and cannot access molecular diagnostic testing of naso-pharyngeal swabs. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of capillary whole blood, collected from a simple finger prick and dried on filter paper (dried blood spot, DBS).

Methods

Enzyme linked immunosorbent assay (ELISA) was optimized to detect SARS-CoV-2 IgG antibodies against the receptor-binding domain (RBD) of the spike protein. DBS samples were eluted overnight and transferred to a 96-well plate coated with antigen, and anti-human IgG-HRP was used to generate signal in proportion to bound antibody. DBS samples spiked with anti-SARS IgG antibody, and samples from known positive and negative cases, were compared to evaluate assay performance.

Results

Analysis of samples with known concentrations of anti-SARS IgG produced the expected pattern of dose-response. Optical density (OD) values were significantly elevated for known positive cases in comparison with samples from unexposed individuals.

Discussion

DBS ELISA provides a minimally-invasive alternative to venous blood collection that combines the convenience of sample collection in the home or non-clinical setting with the quantitation of ELISA in the lab. Serological testing for SARS-CoV-2 IgG antibodies in DBS samples should facilitate research across a wide range of community- and population-based settings on seroprevalence, predictors and duration of antibody responses, as well as correlates of protection from reinfection, each of which is critically important for pandemic control.
Definitive Radiation Therapy With Dose Escalation Is Beneficial For Patients With Squamous Cell Cancer Of The Esophagus
Authors: Ghosh-Laskar Sarbani , Mummudi Naveen , Kumar Saurabha , Chandre Mukesh , Mishra Shagun , Tibdewal Anil , Agarwal JP , Patil Vijay , Noronha Vanita , Prabash Kumar , Jiwnani Sabita , Karimundackal George , Pramesh CS , Patil Prachi
Published: May 2020

OBJECTIVE

We report the long term follow-up, toxicity, and outcomes of patients with localized squamous cell carcinoma of the esophagus (ESCC) who underwent definitive chemoradiotherapy (dCRT) at our institute.

MATERIALS AND METHODS

Patients diagnosed with carcinoma post cricoid, upper cervical and thoracic oesophagus and treated with dCRT treated between January 2000 and March 2012 were retrospectively analysed. Data was extracted from the hospital medical records and patient files. Patients deemed inoperable received upfront RT with or without concurrent chemotherapy and patients with borderline resectable and/or bulky disease received neoadjuvant chemotherapy followed by CRT or RT alone. Radiotherapy was delivered in two phases to a maximum dose of 63 Gy in daily fractions of 1.8 Gy using conventional or conformal techniques. Overall survival and progression free survival were defined from date of registration and were calculated by Kaplan-Meier method with comparisons between different subgroup performed using log rank test. All data were analyzed using SPSS Version 22.

RESULTS

Three hundred and fourteen patients with ESCC treated with dCRT were included in this analysis. Median age at presentation was 56 years and median Karnofsky Performance Status (KPS) at presentation was 70. Two-third of patients were treated with conformal technique alone or a combination of conventional and conformal technique. Median dose of radiation delivered was 60 Gy (range 30.6 Gy – 70 Gy). Neoadjuvant chemotherapy was administered in about 35% patients and 57% patients received concurrent chemotherapy. About 82% patients (77%) completed their planned treatment course; 10% patients required hospitalization during treatment due to complications and 7 patients did not complete treatment. Grade 1/2 dermatitis and mucositis was seen in 77% and 71% patients respectively. Grade 3 non-hematological and hematological toxicities were seen infrequently. Complete response at first follow up was observed in 56% of patients. At a median follow up of 56 months, 77 patients were alive with controlled disease. The 1-, 2- and 3-yr OS were 80%, 67% and 62% respectively. Median PFS was 28 months; 1-, 2- and 3-yr PFS were 66%, 52% and 46% respectively. A higher RT dose was found to be a significant predictor for OS and PFS on both uni- and multivariate analysis.

CONCLUSION

Our study highlights that delivery of higher RT doses (≥63□Gy) is feasible in this patient group and that a higher RT dose was associated with significantly better PFS and OS.
Structural alterations in the macaque frontoparietal white matter network after recovery from prefrontal cortex lesions
Authors: Adam Ramina , Schaeffer David J. , Johnston Kevin , Menon Ravi S. , Everling Stefan
Published: May 2020

Unilateral damage to the frontoparietal network typically impairs saccade target selection within the contralesional visual hemifield. Severity of deficits and the degree of recovery have been associated with widespread network dysfunction, yet it is not clear how these behavioural and functional changes relate with the underlying structural white matter pathways. Here, we investigated whether recovery after unilateral prefrontal cortex (PFC) lesions was associated with structural white matter remodeling in the distributed frontoparietal network. Diffusion-weighted MRI was acquired in four macaque monkeys before the lesions and at 2-4 months post-lesion, after recovery of deficits in saccade selection of contralesional targets. Probabilistic tractography was used to reconstruct inter- and intra-hemispheric frontoparietal fiber tracts: bilateral superior longitudinal fasciculus (SLF) and transcallosal fibers connecting bilateral PFC or bilateral posterior parietal cortex (PPC). After behavioural recovery, tract-specific fractional anisotropy in contralesional SLF and transcallosal PPC increased after small lesions and decreased after larger lesions compared to pre-lesion. These findings indicate that remote fiber tracts may provide optimal compensation after small PFC lesions. However, larger lesions may have induced widespread structural damage and hindered compensatory remodeling in the structural frontoparietal network.
Causal roles of frontoparietal cortical areas in feedback control of the limb
Authors: Takei Tomohiko , Lomber Stephen G. , Cook Douglas J. , Scott Stephen H.
Published: May 2020

Goal-directed motor corrections are surprisingly fast and complex, but little is known on how they are generated by the central nervous system. Here we show that temporary cooling of dorsal premotor cortex (PMd) or parietal area 5 (A5) in behaving monkeys caused impairments in corrective responses to mechanical perturbations of the forelimb. Deactivation of PMd impaired both spatial accuracy and response speed, whereas deactivation of A5 impaired spatial accuracy, but not response speed. Simulations based on optimal feedback control demonstrated that ‘deactivation’ of the control policy (reduction of feedback gain) impaired both spatial accuracy and response speed, whereas ‘deactivation’ in state estimation (reduction of Kalman gain) impaired spatial accuracy but not response speed, paralleling the impairments observed from deactivation of PMd and A5, respectively. Furthermore, combined deactivation of both cortical regions led to additive impairments of individual deactivations, whereas reducing the amount of cooling (i.e. milder cooling) to PMd led to impairments in response speed, but not spatial accuracy, both also predicted by the model simulations. These results provide causal support that higher order motor and somatosensory regions beyond primary somatosensory and primary motor cortex are involved in generating goal-directed motor responses. As well, the computational models suggest that the distinct patterns of impairments associated with these cortical regions reflect their unique functional roles in goal-directed feedback control.
An extensive computational approach to inhibit MSP-1 ofP.vivaxelucidates further horizon in the establishment next generation therapeutics against malaria
Authors: Islam Md Ohedul , Palit Parag , Shawon Jakaria , Hasan Md Kamrul , Mahfuz Mustafa , Ahmed Tahmeed , Mondal Dinesh
Published: May 2020

Malaria represents a life-threatening disease caused by the obligate intra-erythrocytic protozoa of thePlasmodiumgenus, exerting a sinister global health burden and accounting for approximately 660,000 deaths annually. Additionally, 219 million new cases are reported each year, most of which result from the growing issue of artemisinin resistance shown by thePlasmodiumparasite. Much of the research done for the purpose of development of therapeutics against malaria has traditionally been focused onPlasmodium falciparum, which is responsible for majority of the cases of mortality due to malaria,Plasmodium vivaxis also known to contribute greatly towards the malaria relate morbidities particularly in vivax endemic areas. In this study, we have used two different computational approaches aimed at establishing newer concepts towards the development of advanced therapeutics against vivax malaria by targeting the surface antigen, merozoite surface protein-1 (MSP-1). In-silico approach involving computational siRNA designing against MSP-1 resulted in a total of four candidate siRNAs being rationally validated following corroboration with a plethora of algorithms. Additionally, molecular docking analysis unraveled a total of three anti-parasitic peptides. These peptides namely: AP02283, AP02285 and AP00101 were found to exhibit considerable binding affinity with MSP-1 ofP.vivax, thus providing an apparent indication of their anti-malarial property and affirming their potency to be used as novel molecules for development of next generation anti-malarials. However, irrespective of the prospective magnitude of these in-silico findings, the results require extensive validation by further rigorous laboratory experiments involving both in-vitro and in-vivo approaches.
A pathway of NADPH diaphorase positivity between central canal and pial surface at anterior fissure in spinal cord: Supra fissure area with hypothesis configuring from dog, rat, monkey and pigeon
Authors: Jia Yunge , Li Yinhua , Hou Wei , Li Fuhong , Sun Haoran , Wu Xianhui , Wen Xiaoxin , Wei Zicun , Rao Chenxu , Xu Ximeng , Masse Sudirman Fakhruddin , Abulikim Kuerbanjiang , Xu Sheng-fei , Du Guang-hui , Tan Huibing
Published: May 2020

The spinal cord is a cylinder structure in the vertebra and thought a simplified with the gray matter and white matter. Rexed lamination for the gray matter and regional sub-division for whiter matter are completely termed to date. Anterior commissure locates between the central canal and the anterior median fissure. However, some experimental data may still confront with new confined anatomical interpretation. By using NADPH diaphorase [N-d] enzyme histology, we found a vertical oriented neuronal pathway between the central canal and the anterior median fissure in the sacral spinal cord of young adult and aged dog. We used a term “supra fissure area” [SFA] to illustrate the region which consisted of the gray commissure and anterior white commissure. The N-d pathway was notably observable in aged animals. The vertical neurites revealed the cerebrospinal fluid [CSF] contacting neurites between the anterior median fissure and the central canal. We further examined the monkey, rat and pigeon in the region for better understanding of the structure and potential function. The neurodegeneration of N-d dystrophy was detected in the [SFA] in the thoracic spinal cord of the aged monkey. N-d positive fibers were detected in anterior fissure of the rat spinal cord. N-d fibrous structures were also detected in the pigeon spinal cord. These results suggested a new pathway of CSF contacting neurons and the neuronal communications about the central canal.
Heterogeneity of EEG resting-state brain networks in absolute pitch
Authors: Greber Marielle , Klein Carina , Leipold Simon , Sele Silvano , Jäncke Lutz
Published: May 2020

The neural basis of absolute pitch (AP), the ability to effortlessly identify a musical tone without an external reference, is poorly understood. One of the key questions is whether perceptual or cognitive processes underlie the phenomenon as both sensory and higher-order brain regions have been associated with AP. One approach to elucidate the neural underpinnings of a specific expertise is the examination of resting-state networks.

Thus, in this paper, we report a comprehensive functional network analysis of intracranial resting-state EEG data in a large sample of AP musicians (n = 54) and non-AP musicians (n = 51). We adopted two analysis approaches: First, we applied an ROI-based analysis to examine the connectivity between the auditory cortex and the dorsolateral prefrontal cortex (DLPFC) using several established functional connectivity measures. This analysis is a replication of a previous study which reported increased connectivity between these two regions in AP musicians. Second, we performed a whole-brain network-based analysis on the same functional connectivity measures to gain a more complete picture of the brain regions involved in a possibly large-scale network supporting AP ability.

In our sample, the ROI-based analysis did not provide evidence for an AP-specific connectivity increase between the auditory cortex and the DLPFC. In contrast, the whole-brain analysis revealed three networks with increased connectivity in AP musicians comprising nodes in frontal, temporal, subcortical, and occipital areas. Commonalities of the networks were found in both sensory and higher-order brain regions of the perisylvian area. Further research will be needed to confirm these exploratory results.
Microstimulation in the primary visual cortex: activity patterns and their relation to visual responses and evoked saccades
Authors: Oz R. , Edelman-Klapper H. , Nivinsky-Margalit S. , Slovin H.
Published: May 2020

Intra cortical microstimulation (ICMS) in the primary visual cortex (V1) can generate the visual perception of phosphenes and evoke saccades directed to the stimulated location in the retinotopic map. Although ICMS is widely used, little is known about the evoked spatio-temporal patterns of neural activity and their relation to neural responses evoked by visual stimuli or saccade generation. To investigate this, we combined ICMS with Voltage Sensitive Dye Imaging in V1 of behaving monkeys and measured neural activity at high spatial (meso-scale) and temporal resolution. Small visual stimuli and ICMS evoked population activity spreading over few mm that propagated to extrastriate areas. The population responses evoked by ICMS showed faster dynamics and different spatial propagation patterns. Neural activity was higher in trials w/saccades compared with trials w/o saccades. In conclusion, our results uncover the spatio-temporal patterns evoked by ICMS and their relation to visual processing and saccade generation.
PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma
Authors: Vidarsdottir Linda , Azimi Alireza , Sigvaldadottir Ingibjorg , Rahmanto Aldwin Suryo , Petri Andreas , Kauppinen Sakari , Ingvar Christian , Jönsson Göran , Olsson Håkan , Stolt Marianne Frostvik , Tuominen Rainer , Sangfelt Olle , Tamm Katja Pokrovskaja , Hansson Johan , Grandér Dan , Brage Suzanne Egyházi , Johnsson Per
Published: May 2020

Approximately 50% of human cutaneous melanomas carry activating mutations in the serine/threonine protein kinase BRAF. BRAF inhibitors (BRAFi) selectively target the oncogenic BRAFV600E/Kand are effective in approximately 80% of patients carrying the mutation. However, resistance to BRAFi is common and emerges within a median time of 6-7 months of treatment and is prolonged to 11 months when combined with MEK inhibitors. Better characterization of the underlying molecular processes is therefore needed to further improve treatments. Inactivation of the tumor suppressor genePTENhas been suggested to occur during melanomagenesis and drug resistance development. We recently demonstrated that transcription ofPTENis negatively regulated by an antisense RNA from the PTEN pseudogene (PTENP1-AS) and here set out to investigate the impact of this molecular pathway on the resistance to BRAFi and clinical outcome. We used a panel of BRAFi resistant A375 sublines, and observed increased levels of PTENP1-AS associated with reduced expression ofPTEN. Furthermore, this loss ofPTENexpression was correlated to increased recruitment of Enhancer of zeste homolog 2 (EZH2) and formation of the transcriptional repression mark H3K27me3 at thePTENpromoter in the resistant cells. We demonstrated that targeting of PTENP1-AS was able to re-activate the expression ofPTENand sensitize resistant melanoma cells to BRAFi. Finally, we showed that PTENP1-AS is a promising prognostic marker for clinical outcome in melanoma patients as high expression of PTENP1-AS in regional lymph node metastases from stage III melanoma patients correlated with poor survival.
Histopathological Landscape of Molecular Genetics and Clinical Determinants in MDS Patients
Authors: Brück Oscar , Lallukka-Brück Susanna , Hohtari Helena , Ianevski Aleksandr , Ebeling Freja , Kovanen Panu , Kytölä Soili , Aittokallio Tero , Ramos Pedro Marques , Porkka Kimmo , Mustjoki Satu
Published: May 2020

In myelodysplastic syndrome (MDS), bone marrow (BM) histopathology is visually assessed to identify dysplastic cellular morphology, cellularity, and blast excess. Yet, many morphological findings elude the human eye. Here, we extracted visual features of 236 MDS, 87 MDS/MPN, and 10 control BM biopsies with convolutional neural networks. Unsupervised analysis distinguished underlying correlations between tissue composition, leukocyte metrics, and clinical characteristics. We applied morphological features in elastic net-regularized regression models to predict genetic and cytogenetic aberrations, prognosis, and clinical variables. By parallelizing tile, pixel, and leukocyte-level image analysis, we deconvoluted each model to texture and cellular composition to dissect their pathobiological context. Model-based mutation predictions correlated with variant allele frequency and number of affected genes per pathway, demonstrating the models’ ability to identify relevant visual patterns. In summary, this study highlights the potential of deep histopathology in hematology by unveiling the fundamental association of BM morphology with genetic and clinical determinants.
Acute effects of passive listening to Indian musical scale on blood pressure and heart rate variability among healthy young individuals – a randomized controlled trial
Authors: Ubrangala Kirthana Kunikullaya , Vijayadas  , Kunnavil Radhika , Goturu Jaisri , Prakash Vadagenahalli S , Murthy Nandagudi Srinivasa
Published: May 2020

Background

Listening to music is entertaining but also has different health benefits. Music medicine involves passive listening to music, while music therapy involves active music making. Indian music is broadly classified into Hindustani and Carnatic music, each having their own system of musical scales (ragas). Scientific studies of Indian music as an intervention is meagre. Current study determines the effect of passive listening to one melodic scale of Indian music on cardiovascular electrophysiological parameters.

Methods

After informed consent, healthy individuals aged 18 – 30 years, of either gender were recruited and randomly divided into 2 groups (n=34 each). Group A was exposed to passive listening to the music intervention [Hindustani melodic scale elaboration (Bhimpalas raga alaap)], while group B received no intervention except for few natural sounds (played once in every 2 minutes). Blood pressure (BP, systolic – SBP; diastolic – DBP) and Electrocardiogram in lead II were recorded with each condition lasting for 10 minutes (pre, during, post). Heart rate variability (HRV) analysis was done. Data was analysed using SPSS 20.0 version and p<0.05 was considered significant.

Results

Passive listening to the musical scale employed had a unique effect. In group A, the SBP did not change during the intervention but increased insignificantly after the intervention was stopped (P=0.054). The DBP increased in both the groups during intervention and was significant among subjects in group A (P=0.009), with an increase of 1.676 mm Hg (P=0.012) from pre-during and 1.824 mm Hg (P=0.026) from pre-post intervention. On HRV analysis mean NN interval increased and HR reduced in both the groups, but was significant only in group B (P=0.041 and 0.025 respectively). In group A, most of HRV parameters reduced during music intervention, and tended to return towards baseline after intervention, but was statistically significant for Total Power (P=0.031) and Low Frequency (P=0.013) change; while in group B a consistent significant rise in parasympathetic indicators [SDNN, RMSSD, Total power and HF (ms2)] over 30 minutes was observed.

Conclusion

Unique cardiovascular effects were recorded on passive listening to a particular Indian music melodic scale,raga Bhimpalas, wherein, a mild arousal response, was observed. This could be due to attention being paid to the melodic scale as it was an unfamiliar tune or due to certain notes of this melodic scale, that particularly caused an arousal or excitation response. In contrast, the control group had only relaxation response. Exploring electrophysiological effects of different genres, melodic scales and its properties after familiarizing with the music may be illustrative.
Brain activity during facial processing in autism spectrum disorder: an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies
Authors: Costa Cristiano , Cristea Ioana Alina , Bò Elisa Dal , Melloni Caterina , Gentili Claudio
Published: May 2020

Background

Though aberrant face processing is a hallmark of autistic spectrum disorder (ASD), findings on accompanying brain activity are divergent. Therefore, we conducted an activation likelihood estimation (ALE) meta-analysis of studies examining brain activity during face processing.

Methods

We searched PubMed and PsycINFO using combinations of terms as ‘fMRI’, ‘Autism Spectrum Disorder’, ‘Face Perception’. Eligible studies reported on DSM-diagnosed ASD patients, compared to controls (HC), using face stimuli presented in fMRI and reporting whole-brain analysis coordinates. We compared two approaches: “convergence of differences” (primary analysis) using study-level coordinates from ASD vs. HC contrasts, and “differences in convergence” (secondary) pooling coordinates within each group separately, and contrasting the resultant ALE-maps.

Results

Thirty-five studies (655 ASD and 668 HC) were included. Primary analysis identified a cluster in amygdala/parahippocampus where HC showed greater convergence of activation. Secondary analysis yielded no significant results.

Conclusions

Results suggest that ASD dysfunction in face processing relies on structures involved in emotional processing rather than perception. We also demonstrate that the two ALE methodologies lead to divergent results.
Evolution leads to emergence: An analysis of protein interactomes across the tree of life
Authors: Hoel Erik , Klein Brennan , Swain Anshuman , Grebenow Ross , Levin Michael
Published: May 2020

The internal workings of biological systems are notoriously difficult to understand. Due to the prevalence of noise and degeneracy in evolved systems, in many cases the workings of everything from gene regulatory networks to protein-protein interactome networks remain black boxes. One consequence of this black-box nature is that it is unclear at which scale to analyze biological systems to best understand their function. We analyzed the protein interactomes of over 1800 species, containing in total 8,782,166 protein-protein interactions, at different scales. We demonstrate the emergence of higher order ‘macroscales’ in these interactomes and that these biological macroscales are associated with lower noise and degeneracy and therefore lower uncertainty. Moreover, the nodes in the interactomes that make up the macroscale are more resilient compared to nodes that do not participate in the macroscale. These effects are more pronounced in interactomes of Eukaryota, as compared to Prokaryota. This points to plausible evolutionary adaptation for macroscales: biological networks evolve informative macroscales to gain benefits of both being uncertain at lower scales to boost their resilience, and also being ‘certain’ at higher scales to increase their effectiveness at information transmission. Our work explains some of the difficulty in understanding the workings of biological networks, since they are often most informative at a hidden higher scale, and demonstrates the tools to make these informative higher scales explicit.
Homology-directed repair involves multiple strand invasion cycles in fission yeast
Authors: Vines Amanda J. , Cox Kenneth , Leland Bryan A. , King Megan C.
Published: May 2020

Homology-directed repair of DNA double-strand breaks (DSBs) can be a highly faithful pathway. Non-crossover repair dominates in mitotically growing cells, likely through a preference for synthesis-dependent strand annealing (SDSA). While genetic studies highlight a key role for the RecQ helicase BLM/Rqh1 (in human andS. pombecells, respectively) in promoting noncrossover repair, how homology-directed repair mechanism choice is orchestrated in time and space is not well understood. Here, we develop a microscopy-based assay in living fission yeast to determine the dynamics and kinetics of an engineered, site-specific interhomologue repair event. We observe highly efficient homology search and homology-directed repair in this system. Surprisingly, we find that the initial distance between the DSB and the donor sequence does not correlate with the duration of repair. Instead, we observe that repair is likely to involve multiple site-specific and Rad51-dependent co-localization events between the DSB and donor sequence, suggesting that efficient interhomologue repair in fission yeast often involves multiple strand invasion events. By contrast, we find that loss of Rqh1 leads to successful repair through a single strand invasion event, suggesting that multiple strand invasion cycles reflect ongoing SDSA. However, failure to repair is also more likely inrqh1Δcells, which could reflect increased strand invasion at non-homologous sites. This work has implications for the molecular etiology of Bloom syndrome, caused by mutations in BLM and characterized by aberrant sister chromatid crossovers and inefficient repair.
Regulated compartmentalization of enzymes in Golgi by GRASP55 controls cellular glycosphingolipid profile and function
Authors: Pothukuchi Prathyush , Agliarulo Ilenia , Pirozzi Marinella , Rizzo Riccardo , Russo Domenico , Turacchio Gabriele , Nüchel Julian , Yang Jia-Shu , Gehin Charlotte Julie Caroline , Capolupo Laura , Hernandez-Corbacho Maria Jose , Biswas Ansuman , Vanacore Giovanna , Dathan Nina , Nitta Takahiro , Henklein Petra , Thattai Mukund , Inokuchi Jin-Ichi , Hsu Victor W. , Plomann Markus , Obeid Lina M. , Hannun Yusuf A. , Luini Alberto , D’Angelo Giovanni , Parashuraman Seetharaman
Published: May 2020

Glycans are important regulators of cell and organismal physiology. This requires that the glycan biosynthesis be controlled to achieve specific cellular glycan profiles. Glycans are assembled in the Golgi apparatus on secretory cargoes that traverse it. The mechanisms by which the Golgi apparatus ensures cell- and cargo-specific glycosylation remain obscure. We investigated how the Golgi apparatus regulates glycosylation by studying biosynthesis of glycosphingolipids, glycosylated lipids with critical roles in signalling and differentiation. We identified the Golgi matrix protein GRASP55 as a controller of sphingolipid glycosylation by regulating the compartmentalized localization of key sphingolipid biosynthetic enzymes in the Golgi. GRASP55 controls the localization of the enzymes by binding to them and regulating their entry into peri-Golgi vesicles. Impairing GRASP55-enzyme interaction decompartmentalizes these enzymes, changes the substrate flux across competing glycosylation pathways that results in alteration of the cellular glycosphingolipid profile. This GRASP55 regulated pathway of enzyme compartmentalization allows cells to make cell density-dependent adaptations in glycosphingolipid biosynthesis to suit cell growth needs. Thus, the Golgi apparatus controls the cellular glycan (glycosphingolipid) profile by governing competition between biosynthetic reactions through regulated changes in enzyme compartmentalization.
Biodiversity Research and Innovation in Antarctica and the Southern Ocean
Authors: Oldham Paul , Kindness Jasmine
Published: May 2020

This article examines biodiversity research and innovation in Antarctica and the Southern Ocean based on a review of 150,401 scientific articles and 29,690 patent families for Antarctic species. The paper exploits the growing availability of open access databases, such as the Lens and Microsoft Academic Graph, along with taxonomic data from the Global Biodiversity Information Facility (GBIF) to explore the scientific and patent literature for the Antarctic at scale. The paper identifies the main contours of scientific research in Antarctica before exploring commercially oriented biodiversity research and development in the scientific literature and patent publications. The paper argues that biodiversity is not a free good and must be paid for. Ways forward in debates on commercial research and development in Antarctica can be found through increasing attention to the valuation of ecosystem services, new approaches to natural capital accounting and payment for ecosystem services that would bring the Antarctic, and the Antarctic Treaty System, into the wider fold of work on the economics of biodiversity. Economics based approaches can be criticised for reducing biodiversity to monetary exchange values at the expense of recognition of the wider values of biodiversity and its services. However, approaches grounded in the economics of biodiversity provide a transparent framework for approaching commercial activity in the Antarctic and introducing requirements for investments in the conservation of Antarctic biodiversity by those who seek to profit from it.
Neutralizing Antibodies Isolated by a site-directed Screening have Potent Protection on SARS-CoV-2 Infection
Authors: Liu Xiaoyu , Gao Fang , Gou Liming , Chen Yin , Gu Yayun , Ao Lei , Shen Hongbing , Hu Zhibin , Guo Xiling , Gao Wei
Published: May 2020

Neutralizing antibody is one of the most effective interventions for acute pathogenic infection. Currently, over three million people have been identified for SARS-CoV-2 infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are still lacking. SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 by antibody would cause a directly neutralizing effect against virus. In the current study, we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope for neutralizing antibody screening. We performed site-directed screening by phage display and finally obtained one IgG antibody (4A3) and several domain antibodies. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells. The domain antibody 4A12 was predicted to have the best accessibility to all three ACE2-interfaces on the spike homotrimer. Pseudovirus and authentic SARS-CoV-2 neutralization assays showed that all four antibodies could potently protect host cells from virus infection. Overall, we isolated multiple formats of SARS-CoV-2-neutralizing antibodies via site-directed antibody screening, which could be promising candidate drugs for the prevention and treatment of COVID-19.
Detection of pathogenicLeptospirain the environment and its association with antagonisticPseudomonasspp. and rainy season
Authors: Kumar K. Vinod , Lall Chandan , Raj R. Vimal , Vedhagiri K. , Maile Anwesh , Muruganandam N. , Sunish I. P. , Vijayachari Paluru
Published: May 2020

Typically, humans contract leptospirosis through exposure to soil or water contaminated with the urine of infected animals. Specifically, people working in inundated fields, engaged in aquatic sports, or exposed to contaminated floodwater after periods of heavy rainfall bear the risk of contracting leptospirosis. There is a critical gap in the knowledge of the environmental cycle, transmission, and interaction ofLeptospiraspecies with its environment. A few studies establish the presence of higher concentration of leptospires during the rainy season when compared to the dry season. Therefore, we assessed the abundance of leptospires during the dry and wet months and their interaction with other microbes. The overall detection rate of leptospires in paddy field for the test period was 52 (49.5%). Leptospiral concentration positively correlated with the amount of rainfall (mm) during the sampling when compared to months that received comparatively less rainfall (60% vs. 28.5%, respectively). When observed for the microbial interaction,Leptospirashowed significant negative correlation withPseudomonasand rainfall in the paddy field. Moreover, Pseudomonas negatively correlated with the amount of rainfall. Corroborative results ofin-vitrostudies suggest the antagonistic effect ofPseudomonasspp. on leptospires. The results indicate that seasonal changes influence the diversity of free-living well-adaptive aquatic antagonistic microbe populations and may in turn determine the survival ofLeptospirain the environment. Thus, microbial interaction can be the possible enigma for the fluctuation ofLeptospiracount in rainy and dry seasons in environmental surface water, which needs to be further confirmed. This will pave way for a better understanding of the survival of leptospires and the seasonal trend of exposure to humans.
Coupling metabolic addiction with negative autoregulation to improve strain stability and pathway yield
Authors: Lv Yongkun , Gu Yang , Xu Jingliang , Zhou Jingwen , Xu Peng
Published: May 2020

Metabolic addiction, an organism that is metabolically addicted with a compound to maintain its growth fitness, is an underexplored area in metabolic engineering. Microbes with heavily engineered pathways or genetic circuits tend to experience metabolic burden leading to degenerated or abortive production phenotype during long-term cultivation or scale-up. A promising solution to combat metabolic instability is to tie up the end-product with an intermediary metabolite that is essential to the growth of the producing host. Here we present a simple strategy to improve both metabolic stability and pathway yield by coupling chemical addiction with negative autoregulatory genetic circuits. Naringenin and lipids compete for the same precursor with inversed pathway yield in oleaginous yeast. Negative autoregulation of the lipogenic pathways, enabled by CRISPRi and fatty acid-inducible promoters, repartitioned malonyl-CoA to favor flavonoid synthesis and increased naringenin production by 74.8%. With flavonoid-sensing hybrid promoters to control leucine synthesis, this flavonoid addiction phenotype confers a selective growth advantage to the naringenin-producing cell. The engineered yeast persisted 90.9% of naringenin titer up to 324 generations. Cells without flavonoid addiction regained growth fitness but lost 94.5% of the naringenin titer after cell passage beyond 300 generations. Metabolic addiction and negative autoregulation may be generalized as basic tools to eliminate metabolic heterogeneity, improve strain stability and pathway yield.
Optimizing mevalonate pathway for squalene production inYarrowia lipolytica
Authors: Liu Huan , Wang Fang , Deng Li , Xu Peng
Published: May 2020

Squalene is the gateway molecule for triterpene-based natural products and steroids-based pharmaceuticals. As a super lubricant, it has been used widely in health care industry due to its skin compatibility and thermostability. Squalene is traditionally sourced from shark-hunting or oil plant extraction, which is cost-prohibitive and not sustainable. Reconstitution of squalene biosynthetic pathway in microbial hosts is considered as a promising alternative for cost-efficient and scalable synthesis of squalene. In this work, we reported the engineering of the oleaginous yeast,Y. lipolytica, as a potential host for squalene production. We systematically identified the bottleneck of the pathway and discovered that the native HMG-CoA reductase led to the highest squalene improvement. With the recycling of NADPH from the mannitol cycle, the engineered strain produced about 180.3 mg/l and 188.2 mg/L squalene from glucose or acetate minimal media, respectively. By optimizing the C/N ratio, controlling the media pH and mitigating the acetyl-CoA flux competition from lipogenesis, the engineered strain produced about 502.7 mg/L squalene in shake flaks, a 28-fold increase compared to the parental strain (17.2 mg/L). We also profiled the metabolic byproducts citric acid and mannitol level and observed that they are reincorporated into cell metabolism at the late stage of fermentation. This work may serve as a baseline to harnessY. lipolyticaas an oleaginous cell factory for production of squalene or terpene-based chemicals.
Regulation of an iron-dependent repressor by tryptophan availability attenuates transcription of the tryptophan salvage genes inChlamydia trachomatis
Authors: Pokorzynski Nick D. , Hatch Nathan D. , Ouellette Scot P. , Carabeo Rey A.
Published: May 2020

Thetrpoperon ofChlamydia trachomatishas a genetic organization that is distinct from other model bacteria. The operon contains thetrpRopen-reading frame (ORF), an intergenic region (IGR), and thetrpBandtrpAORFs. TrpR mediates tryptophan-dependent regulation of the operon from the major promoter upstream oftrpR(PtrpR). We recently reported thattrpBAis additionally regulated by the iron-dependent repressor YtgR via an operator sequence within the IGR upstream of an alternative promoter for TrpR-independenttrpBAexpression (PtrpBA). Here we report that YtgR repression of PtrpBAis also dependent on tryptophan levels via a rare triple-tryptophan motif (WWW) in the N-terminal permease domain of the YtgCR precursor. Tryptophan limitation inhibits translation at the WWW motif and subsequently promotes transcription termination ofytgCRin a Rho-independent manner. This regulatory schematic resembles mechanisms of transcriptional attenuation fortrpoperons described in model bacteria, such ascis-attenuation by TrpL inE. coliortrans-attenuation by TRAP inB. subtilis.YtgR performs an analogous function by sensing both iron and tryptophan levels, with the latter highlighting the unique strategy ofChlamydiato retain atrans-attenuator mechanism for regulating expression of thetrpRBAoperon.
Antagonistic Effects of Intraspecific Cooperation and Interspecific Competition on Thermal Performance
Authors: Tsai Hsiang-Yu , Rubenstein Dustin R. , Chen Bo-Fei , Liu Mark , Chan Shih-Fan , Chen De-Pei , Sun Syuan-Jyun , Yuan Tzu-Neng , Shen Sheng-Feng
Published: May 2020

Understanding how climate-mediated biotic interactions shape thermal niche width is critical in an era of global change. Yet, most previous work on thermal niches has ignored detailed mechanistic information about the relationship between temperature and organismal performance, which can be described by a thermal performance curve. Here, we develop a model that predicts the width of thermal performance curves will be narrower in the presence of interspecific competitors, causing a species’ optimal breeding temperature to diverge from that of a competitor. We test this prediction in the Asian burying beetleNicrophorus nepalensis, confirming that the divergence in actual and optimal breeding temperatures is the result of competition with blowflies. However, we further show that intraspecific cooperation enables beetles to outcompete blowflies by recovering their optimal breeding temperature. Ultimately, linking direct (abiotic factors) and indirect effects (biotic interactions) on niche width will be critical for understanding species-specific responses to climate change.
Sensitivity assessment of SARS-CoV-2 PCR assays developed by WHO referral laboratories
Authors: Etievant Sibyle , Bal Antonin , Escuret Vanessa , Brengel–Pesce Karen , Bouscambert Maude , Cheynet Valérie , Generenaz Laurence , Oriol Guy , Destras Gregory , Billaud Geneviève , Josset Laurence , Frobert Emilie , Morfin Florence , Gaymard Alexandre
Published: May 2020

The sensitivity of SARS-CoV-2 RT-PCR tests developed by Charité (Germany), HKU (Hong-Kong), China CDC (China), US CDC (United-States), and Institut Pasteur, Paris (France) was assessed on SARS-CoV-2 cell culture supernatants and clinical samples. Although all RT-PCR assays performed well for SARS-CoV-2 detection, RdRp Institut Pasteur (IP2, IP4), N China CDC, and N1 US CDC were found to be the most sensitive.
Direct PA-binding by Chm7 is required for nuclear envelope surveillance at herniations
Authors: Thaller David J. , Tong Danqing , Marklew Christopher J. , Borah Sapan , Ciani Barbara , Lusk C. Patrick
Published: May 2020

Mechanisms that control nuclear membrane remodeling are essential to maintain the integrity of the nucleus but remain to be fully defined. Here, we identify a phosphatidic acid (PA)-binding activity in the nuclear envelope-specific ESCRT, Chm7, in budding yeast. PA-binding is mediated through a conserved hydrophobic stretch of amino acids, which confers specific binding to the inner nuclear membrane (INM). This INM-binding is independent but nonetheless required for interaction with the LAP2-emerin-MAN1 (LEM) domain protein, Heh1 (LEM2). Consistent with the functional importance of PA-binding, mutation of this region inhibits recruitment of Chm7 to the INM and abolishes Chm7 function in the context of nuclear envelope herniations or “blebs” that form during defective nuclear pore complex (NPC) biogenesis. In fact, we show that PA accumulates at nuclear envelope herniations. We suggest that local control of PA metabolism is important for ensuring productive nuclear envelope remodeling and that its dysregulation may contribute to pathologies associated with defective NPC assembly.
A fuzzy-regression-PSO based hybrid method for selecting welding conditions in robotic gas metal arc welding
Authors: Rout Amruta , Bbvl Deepak , Biswal Bibhuti B. , Mahanta Golak Bihari
Published: May 2020

Purpose

This paper aims to propose fuzzy-regression-particle swarm optimization (PSO) based hybrid optimization approach for getting maximum weld quality in terms of weld strength and bead depth of penetration.

Design/methodology/approach

The prediction of welding quality to achieve best of it is not possible by any single optimization technique. Therefore, fuzzy technique has been applied to predict the weld quality in terms of weld strength and weld bead geometry in combination with a multi-performance characteristic index (MPCI). Then regression analysis has been applied to develop relation between the MPCI output value and the input welding process parameters. Finally, PSO method has been used to get the optimal welding condition by maximizing the MPCI value.

Findings

The predicted weld quality or the MPCI values in terms of combined weld strength and bead geometry has been found to be highly co-related with the weld process parameters. Therefore, it makes the process easy for setting of weld process parameters for achieving best weld quality, as there is no need to finding the relation for individual weld quality parameter and weld process parameters although they are co-related in a complicated manner.

Originality/value

In this paper, a new hybrid approach for predicting the weld quality in terms of both mechanical properties and weld geometry and optimizing the same has been proposed. As these parameters are highly correlated and dependent on the weld process parameters the proposed approach can effectively analyzing the ambiguity and significance of each process and performance parameter.
Optimal energy management for hybrid-electric aircraft
Authors: Pinto Leite José Pedro Soares , Voskuijl Mark
Published: May 2020

Purpose

In recent years, increased awareness on global warming effects led to a renewed interest in all kinds of green technologies. Among them, some attention has been devoted to hybrid-electric aircraft – aircraft where the propulsion system contains power systems driven by electricity and power systems driven by hydrocarbon-based fuel. Examples of these systems include electric motors and gas turbines, respectively. Despite the fact that several research groups have tried to design such aircraft, in a way, it can actually save fuel with respect to conventional designs, the results hardly approach the required fuel savings to justify a new design. One possible path to improve these designs is to optimize the onboard energy management, in other words, when to use fuel and when to use stored electricity during a mission. The purpose of this paper is to address the topic of energy management applied to hybrid-electric aircraft, including its relevance for the conceptual design of aircraft and present a practical example of optimal energy management.

Design/methodology/approach

To address this problem the dynamic programming (DP) method for optimal control problems was used and, together with an aircraft performance model, an optimal energy management was obtained for a given aircraft flying a given trajectory.

Findings

The results show how the energy onboard a hybrid fuel-battery aircraft can be optimally managed during the mission. The optimal results were compared with non-optimal result, and small differences were found. A large sensitivity of the results to the battery charging efficiency was also found.

Originality/value

The novelty of this work comes from the application of DP for energy management to a variable weight system which includes energy recovery via a propeller.