bluuebunny/crossref_metadata_2025 huggingface dataset:
ImmunoStart: preparing patients for immunosuppression
Authors: Martin Charlotte , Muls Vinciane , Brasseur Céline , Meric de Bellefon Laurent , Lam Hoai Xuan-Lan , Vanderhilst Jeroen , Delforge Marc , Di Romana Silvana
Published: December 2021

Objectives

Patients with immune-mediated inflammatory disease (IMID) present an increased risk of infection. Here, we present the concept of a preventive consultation called ImmunoStart and the first results of its implementation in the care pathway of patients with IMID.

Methods

Relevant information about vaccination history, tuberculosis exposure and other infectious risks were collected through blood sampling, complete anamnesis, chest X-ray and Mantoux test. During the ImmunoStart consultation, vaccination schedules, specific treatments and risk considerations were discussed.

Results

Between October 2016 and February 2020, 437 patients were seen at an ImmunoStart consultation, mainly referred by rheumatologists (56%), dermatologists (25%) and gastroenterologists (18%). A total of 421 (96%) patients needed at least one vaccine (a mean of 3.3 vaccines per patient). Live attenuated vaccine was indicated for 45 patients (10%), requiring them to reduce or interrupt their immunosuppressive drug(s). Ninety-two patients (21%) were treated for latent tuberculosis infection.

Conclusion

This preventive consultation provides a centralized and systematic setting for the direct management of patients with IMID in need of vaccination, treatment of latent disease and specific advice regarding their immunomodulating treatments.
Amorphous calcium magnesium phosphate nanocomposites with superior osteogenic activity for bone regeneration
Authors: Jiang Yingying , Tan Shuo , Hu Jianping , Chen Xin , Chen Feng , Yao Qianting , Zhou Zhi , Wang Xiansong , Zhou Zifei , Fan Yunshan , Liu Junjian , Lin Yize , Liu Lijia , He Shisheng
Published: December 2021

The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO43−, when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.
White matter regeneration induced by aligned fibrin nanofiber hydrogel contributes to motor functional recovery in canine T12 spinal cord injury
Authors: Cao Zheng , Man Weitao , Xiong Yuhui , Guo Yi , Yang Shuhui , Liu Dongkang , Zhao He , Yang Yongdong , Yao Shenglian , Li Chuzhong , Zhao Lingyun , Sun Xiaodan , Guo Hua , Wang Guihuai , Wang Xiumei
Published: December 2021

A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.
The chemoprevention of spirulina platensis and garlic against diethylnitrosamine induced liver cancer in rats via amelioration of inflammatory cytokines expression and oxidative stress
Authors: Abouzed Tarek Kamal , Althobaiti Fayez , Omran Alaa Faik , Eldomany Ehab Bedir , El-Shazly Samir Ahmed , Alharthi Fahad , Elkattawy Azza Mansour , Kahilo Khaled Abd Aleim , Dorghamm Doaa Abdallha
Published: December 2021

Natural antioxidant products play a vital role in the treatment and prevention of cancer disease because they have no side effects. This study aimed to compare the chemoprotective effect of Spirulina platensis (SP) and garlic against hepatocellular carcinoma (HCC) in rats. This study was being done by using 60 male Wistar rats and divided into four groups. Group (I): normal group. Group (II): HCC group induced by injection of a single dose of DEN (200 mg/kg/I.P) and after 14 days injected CCl4 (1 mg/kg/I.P) 3 times/week/six weeks. Group (III): HCC group received SP orally at a dose (500 mg/kg). Group (IV): HCC group received garlic (250 mg/kg) orally. The results revealed that the Spirulina and garlic treatment have a significant decrease in Glutamate pyruvate transaminase, Glutamate oxaloacetate transaminase, GGT, LDH, and the Malondialdehyde (MDA) activity, and furthermore, a significant increase in the total protein level, the superoxide dismutase (SOD), and Catalase (CAT) activity nearly to normal activity. Furthermore, the hepatic expression of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase, transforming growth factor-beta (TGF-β1), Heat Shock Protein glycoprotein 96 (HSPgp96), and Glypican 3 (GP3) were down regulated by the Spirulina and garlic treatment in comparison with those in HCC group. All findings reported that the chemoprotective of both Spirulina and garlic that have nearly the same effect may be due to antioxidant activity and inhibition of lipid peroxidation, amelioration of pro-inflammatory cytokine, HSPgp96, and GP3.
A Comparative Study of Children with MIS-C between Admitted to the Pediatric Intensive Care Unit and Pediatric Ward: A One-Year Retrospective Study
Authors: Kıymet Elif , Böncüoğlu Elif , Şahinkaya Şahika , Cem Ela , Çelebi Miray Yılmaz , Düzgöl Mine , Kara Aybüke Akaslan , Arıkan Kamile Ötiken , Vuran Gamze Talay , Yılmazer Murat Muhtar , Sandal Özlem Saraç , Ağın Hasan , Pirinç Neslihan , Bayram Nuri , Devrim İlker
Published: December 2021

Objectives

This descriptive study aimed to compare the clinical and laboratory features of the children with the multisystem inflammatory syndrome in children (MIS-C), requiring pediatric intensive care unit (PICU), admission with the MIS-C patients who did not require PICU admission.

Patients and methods

This study was conducted between March 2020 and February 2021 at the University of Health Sciences Dr. Behçet Uz Children’s Hospital, a referral center for pediatric infectious diseases in the Aegean Region of Turkey. All hospitalized patients aged 18 years old or less with MIS-C according to the definition of the universal guidelines were included in the study. Data of the patients with the diagnosis of MIS-C were recorded and collected from the electronic medical records of the hospital. The data included demographic characteristics, presenting signs and symptoms, laboratory findings and clinical data.

Results

A total of 58 patients with MIS-C were included in this study. Thirty-eight (65.5%) patients were male. The median age was 6 years (2 months–16 years). The patients admitted to PICU were 15 (25.9%). The rate of pulmonary involvement was 81.3% (n = 13) in the PICU group. The median procalcitonin, C-reactive protein, erythrocyte sedimentation rate, D-Dimer and ferritin values were significantly higher in the PICU group compared to non-PICU group (p < 0.001, p = 0.02, p < 0.001, p = 0.006 and p = 0.031).

Conclusions

Besides the depressing cardiac functions reported before, the pulmonary involvement and signs of shock are important factors for PICU admission in children with MIS-C.
The evolution of two distinct strategies of moth flight
Authors: Aiello Brett R. , Sikandar Usama Bin , Minoguchi Hajime , Bhinderwala Burhanuddin , Hamilton Chris A. , Kawahara Akito Y. , Sponberg Simon
Published: December 2021

Across insects, wing shape and size have undergone dramatic divergence even in closely related sister groups. However, we do not know how morphology changes in tandem with kinematics to support body weight within available power and how the specific force production patterns are linked to differences in behaviour. Hawkmoths and wild silkmoths are diverse sister families with divergent wing morphology. Using three-dimensional kinematics and quasi-steady aerodynamic modelling, we compare the aerodynamics and the contributions of wing shape, size and kinematics in 10 moth species. We find that wing movement also diverges between the clades and underlies two distinct strategies for flight. Hawkmoths use wing kinematics, especially high frequencies, to enhance force and wing morphologies that reduce power. Silkmoths use wing morphology to enhance force, and slow, high-amplitude wingstrokes to reduce power. Both strategies converge on similar aerodynamic power and can support similar body weight ranges. However, inter-clade within-wingstroke force profiles are quite different and linked to the hovering flight of hawkmoths and the bobbing flight of silkmoths. These two moth groups fly more like other, distantly related insects than they do each other, demonstrating the diversity of flapping flight evolution and a rich bioinspired design space for robotic flappers.
Pathways shaping the mitochondrial inner membrane
Authors: Klecker Till , Westermann Benedikt
Published: December 2021

Mitochondria are complex organelles with two membranes. Their architecture is determined by characteristic folds of the inner membrane, termed cristae. Recent studies in yeast and other organisms led to the identification of four major pathways that cooperate to shape cristae membranes. These include dimer formation of the mitochondrial ATP synthase, assembly of the mitochondrial contact site and cristae organizing system (MICOS), inner membrane remodelling by a dynamin-related GTPase (Mgm1/OPA1), and modulation of the mitochondrial lipid composition. In this review, we describe the function of the evolutionarily conserved machineries involved in mitochondrial cristae biogenesis with a focus on yeast and present current models to explain how their coordinated activities establish mitochondrial membrane architecture.
Expression and function of PDGF-C in development and stem cells
Authors: Tian Yi , Zhan Ying , Jiang Qin , Lu Weisi , Li Xuri
Published: December 2021

Platelet-derived growth factor C (PDGF-C) is a relatively new member of the PDGF family, discovered nearly 20 years after the finding of platelet-derived growth factor A (PDGF-A) and platelet-derived growth factor B (PDGF-B). PDGF-C is generally expressed in most organs and cell types. Studies from the past 20 years have demonstrated critical roles of PDGF-C in numerous biological, physiological and pathological processes, such as development, angiogenesis, tumour growth, tissue remodelling, wound healing, atherosclerosis, fibrosis, stem/progenitor cell regulation and metabolism. Understanding PDGF-C expression and activities thus will be of great importance to various research disciplines. In this review, however, we mainly discuss the expression and functions of PDGF-C and its receptors in development and stem cells.
MYC regulates metabolism through vesicular transfer of glycolytic kinases
Authors: Tsakaneli Alexia , Carregari Victor Corasolla , Morini Martina , Eva Alessandra , Cangemi Giuliana , Chayka Olesya , Makarov Evgeny , Bibbò Sandra , Capone Emily , Sala Gianluca , De Laurenzi Vincenzo , Poon Evon , Chesler Louis , Pieroni Luisa , Larsen Martin R. , Palmisano Giuseppe , Sala Arturo
Published: December 2021

Amplification of the proto-oncogene
MYCN
is a key molecular aberration in high-risk neuroblastoma and predictive of poor outcome in this childhood malignancy. We investigated the role of MYCN in regulating the protein cargo of extracellular vesicles (EVs) secreted by tumour cells that can be internalized by recipient cells with functional consequences. Using a switchable MYCN system coupled to mass spectrometry analysis, we found that MYCN regulates distinct sets of proteins in the EVs secreted by neuroblastoma cells. EVs produced by MYCN-expressing cells or isolated from neuroblastoma patients induced the Warburg effect, proliferation and c-MYC expression in target cells. Mechanistically, we linked the cancer-promoting activity of EVs to the glycolytic kinase pyruvate kinase M2 (PKM2) that was enriched in EVs secreted by MYC-expressing neuroblastoma cells. Importantly, the glycolytic enzymes PKM2 and hexokinase II were detected in the EVs circulating in the bloodstream of neuroblastoma patients, but not in those of non-cancer children. We conclude that MYC-activated cancers might spread oncogenic signals to remote body locations through EVs.
Frugal manufacturing in smart factories for widespread sustainable development
Authors: Rao Balkrishna C.
Published: December 2021

Manufacturing is a crucial activity of product development that feeds into and is also influenced by the design process. Any material conservation gained during manufacturing directly affects the green credentials of a product. Manufacturing waste can be contrived to approach zero through a recently developed
frugal design approach
that quantifies resource conservation at all stages of development of a product engineered for frugality. Accordingly, this effort presents
frugal manufacturing
(FM), integral to the
frugal design approach
, for utmost reduction of waste while aiming for good surface integrity, better properties, minimal number of processes and low cost. Other than saving on energy and hence emissions, the new concept of FM also goes beyond current
near net shape
technologies, which advocate mainly for zero wastage and suitable properties while using a narrow range of manufacturing processes. Case studies involving
high-speed machining
,
superplastic forming
and
additive manufacturing
of aerospace alloys have been presented that bring out the features and benefits of FM. As such the multipronged objectives of FM should be dovetailed with those of
smart factories
for creating novel technologies that abet widespread sustainable development. Such enhancement of the
smart factories
concept has been argued to support unusual applications such as the fight against pandemics including the current one involving COVID-19.
Uncovering dynamic textual topics that explain crime
Authors: Virtanen Seppo
Published: December 2021

Crime analysis/mapping techniques have been developed and applied for crime detection and prevention to predict where and when crime occurs, leveraging historical crime records over a spatial area and covariates for the spatial domain. Some of these techniques may provide insights for understanding crime and disorder, especially, via interpreting the weights for the spatial covariates based on regression modelling. However, to date, the use of temporal covariates for the time domain has not played a significant role in the analysis. In this work, we collect time-stamped crime-related news articles, infer crime topics or themes based on the collection and associate the topics with the historical numeric crime counts. We provide a proof-of-concept study, where instead of adopting spatial covariates, we focus on temporal (or dynamic) covariates and assess their utility. We present a novel joint model tailored for the crime articles and counts such that the temporal covariates (latent variables, more generally) are inferred based on the data sources. We apply the model for violent crime in London.
Mean and variance of the Eulerian and Lagrangian horizontal velocities induced by nonlinear multi-directional irregular water waves
Authors: Klahn Mathias , Madsen Per A. , Fuhrman David R.
Published: December 2021

In this paper, we study the mean and variance of the Eulerian and Lagrangian fluid velocities as a function of depth below the surface of directionally spread irregular wave fields given by JONSWAP spectra in deep water. We focus on the behaviour of these quantities in the bulk of the water, and using second-order potential flow theory we derive new simple asymptotic approximations for their decay in the limit of large depth below the surface. Specifically, we show that when the depth is greater than about 1.5 peak wavelengths, the variance of the Eulerian velocity decays in proportion to

exp
⁡

(

−

(

135
4

)

1

/

3

(

−

k
p

z

)

2

/

3

)

,

and the mean Lagrangian velocity decays in proportion to

1

(

−

k
p

z

)

1

/

6

exp
⁡

(

−

(

135
4

)

1

/

3

(

−

k
p

z

)

2

/

3

)

.

Here,

k
p

is the peak wave number and

z

is the vertical coordinate measured positively upwards from the still water level. We test the accuracy of the second-order formulation against new fully nonlinear simulations of both short crested and long crested irregular wave fields and find a good match, even when the simulations are known to be affected substantially by third-order effects. To our knowledge, this marks the first fully nonlinear investigation of the Eulerian and Lagrangian velocities below the surface in irregular wave fields.
Does a complex life cycle affect adaptation to environmental change? Genome-informed insights for characterizing selection across complex life cycle
Authors: Albecker Molly A. , Wilkins Laetitia G. E. , Krueger-Hadfield Stacy A. , Bashevkin Samuel M. , Hahn Matthew W. , Hare Matthew P. , Kindsvater Holly K. , Sewell Mary A. , Lotterhos Katie E. , Reitzel Adam M.
Published: December 2021

Complex life cycles, in which discrete life stages of the same organism differ in form or function and often occupy different ecological niches, are common in nature. Because stages share the same genome, selective effects on one stage may have cascading consequences through the entire life cycle. Theoretical and empirical studies have not yet generated clear predictions about how life cycle complexity will influence patterns of adaptation in response to rapidly changing environments or tested theoretical predictions for fitness trade-offs (or lack thereof) across life stages. We discuss complex life cycle evolution and outline three hypotheses—ontogenetic decoupling, antagonistic ontogenetic pleiotropy and synergistic ontogenetic pleiotropy—for how selection may operate on organisms with complex life cycles. We suggest a within-generation experimental design that promises significant insight into composite selection across life cycle stages. As part of this design, we conducted simulations to determine the power needed to detect selection across a life cycle using a population genetic framework. This analysis demonstrated that recently published studies reporting within-generation selection were underpowered to detect small allele frequency changes (approx. 0.1). The power analysis indicates challenging but attainable sampling requirements for many systems, though plants and marine invertebrates with high fecundity are excellent systems for exploring how organisms with complex life cycles may adapt to climate change.
Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of blaKPC-carbapenemase-producing Enterobacterales in a hospital setting
Authors: Stoesser N , George R , Aiken Z , Phan HTT , Lipworth S , Wyllie DH , Quan TP , Mathers AJ , De Maio N , Seale AC , Eyre DW , Vaughan A , Swann J , Peto TEA , Crook DW , Cawthorne J , Dodgson A , Walker AS ,   TRACE Investigators’ Group
Published: December 2021

2.

Healthcare-associated wastewater reservoirs and asymptomatic gastrointestinal patient colonisation by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination. We systematically sampled wastewater sites (n=4488 sampling events; 349 sites) and patients (n=1247) across six wards over 6-12 months in 2016 to better understand blaKPC-associated CPE (KPC-E) diversity within these niches and transmission potential in an endemic healthcare setting. Up to five isolates in KPC-E-positive samples were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based typing approaches were used to characterise antimicrobial resistance genes, insertion sequences, and Tn4401 types/target site sequences. The wider accessory genome was evaluated in a subset of the largest clusters, and those crossing niches.

Wastewater site KPC-E-positivity was substantial (101/349 sites [28.9%] positive); 228/5,601 (4.1%) patients cultured were CPE culture-positive over the same timeframe. At a genomic-level, 13 KPC-E species and 109 strains were identified, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured ≥1 strain. Most diversity was explained by the individual niche, suggesting localised factors are important in selection and spread. Tn4401+target site sequence diversity was greater in wastewater sites (p<0.001), which might favour Tn4401-associated transposition/evolution. Shower/bath and sluice/mop-associated sites were more likely to be KPC-E-positive (Adjusted Odds Ratio [95% CI]: 2.69 [1.44-5.01], p=0.0019 and 2.60 [1.04-6.52], p=0.0410, respectively). Different strains had different transmission and blaKPCdissemination dynamics.

There may be substantial KPC-E colonisation of wastewater sites and patients in KPC-E-endemic healthcare settings. Niche-specific factors (e.g. microbial interactions, selection pressure) likely affect carbapenemase gene persistence and evolution, and different strains and mobile genetic elements with different transmission dynamics influence carbapenemase gene dissemination; these factors should be considered in surveillance and control strategies.
Google Trends as a predictive tool for COVID-19 vaccinations in Italy: a retrospective infodemiological analysis
Authors: Rovetta Alessandro
Published: December 2021

Background

Google Trends is an infoveillance tool widely used by the scientific community to investigate different user behaviors related to COVID-19. However, several limitations regarding its adoption are reported in the literature.

Objective

This brief paper aims to provide an effective and efficient approach to investigating vaccine adherence against COVID-19 via Google Trends.

Methods

Through the cross-correlational analysis of well-targeted hypotheses, we investigate the predictive capacity of web searches related to COVID-19 towards vaccinations in Italy from November 2020 to November 2021. The keyword “vaccine reservation” (VRQ) was chosen as it reflects a real intention of being vaccinated (V). Furthermore, the impact of the second-largest Italian national newspaper on vaccines-related web searches was investigated to evaluate the role of the mass media as a confounding factor.

Results

Simple and generic keywords are more likely to identify the actual web interest in COVID-19 vaccines than specific and elaborated keywords. Cross-correlations between VRQ and V were very strong and significant (min r2 = .460, P<.001, lag = 0 weeks; max r2 = .903, P < .001, lag = 6 weeks). Cross-correlations between VRQ and news about COVID-19 vaccines have been markedly lower and characterized by greater lags (min r2 = .190, P=.001, lag = 0 weeks; max r2 = .493, P < .001, lag = -10 weeks). No correlation between news and vaccinations was sought since the lag would have been too high.

Conclusions

This research provides strong evidence in favor of using Google Trends as a surveillance and prediction tool for vaccine adherence against COVID-19 in Italy. These findings prove that the search for suitable keywords is a fundamental step to reduce confounding factors. Additionally, targeting hypotheses helps diminish the likelihood of spurious correlations. It is recommended that Google Trends be leveraged as a complementary infoveillance tool by government agencies to monitor and predict vaccine adherence in this and future crises by following the methods proposed in this manuscript.
The role of Zambia’s expansive Inter-agency Coordinating Committee (ICC) in supporting evidence-based vaccine and health sector programming
Authors: Sakas Zoe , Rodriguez Katie , Hester Kyra A , Darwar Roopa , Dounebaine Bonheur , Ellis Anna S , Rosenblum Simone , Isett Kimberley R , Orenstein Walter , Freeman Matthew C , Kilembe William , Bednarczyk Robert A
Published: December 2021

New vaccines, technologies, and regulations, alongside increased demand for vaccines, all require prioritization and coordination from key players within the vaccine sector. Inter-agency Coordinating Committees (ICC) support decision-making and coordination at the national-level and act as key drivers for sustainable improvements in vaccination programming. We employed a qualitative case study design to investigate critical success factors for the high routine immunization coverage in Zambia from 2000-2018. Qualitative data were collected between October 2019 and February 2020, including key informant interviews (n=66) at the national, provincial, district, and health facility levels. Thematic analysis was applied to understand the role of the Zambian ICC and its impact on the policy environment overtime. Throughout our study period, the Zambian ICC demonstrated the following improvements: 1) expanded membership to include diverse representation; 2) expanded scope and mandate to include maternal and child health in decision-making; and 3) collaboration with the ZITAG through distinct roles. The diverse and expansive membership of the Zambian ICC, along with its ability to foster government commitment and lobby for additional resources, supported improvements in immunization programming. The Zambian ICC holds considerable influence on government agencies and external partners which facilitates procurement of funding, policy decisions, and strategic planning.
Developing an Antiviral Peptides Predictor with Generative Adversarial Network Data Augmentation
Authors: Lin Tzu-Tang , Sun Yi-Yun , Cheng Wei-Chih , Lu I-Hsuan , Chen Shu-Hwa , Lin Chung-Yen
Published: December 2021

Motivation

New antiviral drugs are urgently needed because of emerging viral pathogens’ increasing severity and drug resistance. Antiviral peptides (AVPs) have multiple antiviral properties and are appealing candidates for antiviral drug development. We developed a sequence-based binary classifier to identify whether an unknown short peptide has AVP activity. We collected AVP sequence data from six existing databases. We used a generative adversarial network to augment the number of AVPs in the positive training dataset and allow our deep convolutional neural network model to train on more data.

Results

Our classifier achieved outstanding performance on the testing dataset compared with other state-of-the-art classifiers. We deployed our trained classifier on a user-friendly web server.

Availability and implementation

AI4AVP is freely accessible at http://axp.iis.sinica.edu.tw/AI4AVP/

Contact

cylin@iis.sinica.edu.tw

Supplementary information

Supplementary data is also available.
Heteologous saRNA-Prime, DNA Dual-Antigen-Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies
Authors: Rice Adrian , Verma Mohit , Voigt Emily , Battisti Peter , Beaver Sam , Reed Sierra , Dinkins Kyle , Mody Shivani , Zakin Lise , Tanaka Shiho , Morimoto Brett , Olson C. Anders , Gabitzsch Elizabeth , Safrit Jeffrey T. , Spilman Patricia , Casper Corey , Soon-Shiong Patrick
Published: December 2021

We assessed if immune responses are enhanced in CD-1 mice by heterologous vaccination with two different nucleic acid-based COVID-19 vaccines: a next-generation human adenovirus serotype 5 (hAd5)-vectored dual-antigen spike (S) and nucleocapsid (N) vaccine (AdS+N) and a self-amplifying and -adjuvanted S RNA vaccine (SASA S) delivered by a nano-lipid carrier. The AdS+N vaccine encodes S modified with a fusion motif to increase cell-surface expression. The N antigen is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal compartment and increase MHC class I and II stimulation potential. The S sequence in the SASA S vaccine comprises the D614G mutation, two prolines to stabilize S in the prefusion conformation, and 3 glutamines in the furin cleavage region to increase cross-reactivity across variants. CD-1 mice received vaccination by homologous and heterologous prime > boost combinations. Humoral responses to S were the highest with any regimen including the SASA S vaccine, and IgG bound to wild type and Delta (B.1.617.2) variant S1 at similar levels. An AdS+N boost of an SASA S prime particularly enhanced both CD4+ and CD8+ T-cell responses to both wild type and Delta S peptides relative to all other vaccine regimens. Sera from mice receiving SASA S homologous or heterologous vaccination were found to be highly neutralizing of all pseudovirus strains tested: Wuhan, Beta, Delta, and Omicron strain. The findings here support the clinical testing of heterologous vaccination by an SASA S > AdS+N regimen to provide increased protection against emerging SARS-CoV-2 variants.
The developing kidney actively negotiates geometric packing conflicts to avoid defects
Authors: Prahl Louis S. , Viola John M. , Liu Jiageng , Hughes Alex J.
Published: December 2021

The physiological functions of several organs rely on branched tubular networks, but little is known about conflicts in development between building enough tubules for adequate function and geometric constraints imposed by organ size. We show that the mouse embryonic kidney epithelium negotiates a physical packing conflict between tubule tip duplication and limited area at the organ surface. Imaging, computational, and soft material modeling of tubule ‘families’ identifies six geometric packing phases, including two defective ones. Experiments in kidney explants show that a retrograde tension on tubule families is necessary and sufficient for them to avoid defects by switching to a vertical orientation that increases packing density. These results reveal developmental contingencies in response to physical limitations, and create a framework for classifying kidney defects.

One-Sentence Summary

Epithelial branching in the kidney causes a geometric packing conflict that is resolved through internally generated tensions
MaveDB v2: a curated community database with over three million variant effects from multiplexed functional assays
Authors: Rubin Alan F , Min Joseph K , Rollins Nathan J , Da Estelle Y , Esposito Daniel , Harrington Matthew , Stone Jeremy , Bianchi Aisha Haley , Dias Mafalda , Frazer Jonathan , Fu Yunfan , Gallaher Molly , Li Iris , Moscatelli Olivia , Ong Jesslyn YL , Rollins Joshua E , Wakefield Matthew J , “Sunny” Ye Shenyi , Tam Amy , McEwen Abbye E , Starita Lea M , Bryant Vanessa L , Marks Debora S , Fowler Douglas M
Published: December 2021

A central problem in genomics is understanding the effect of individual DNA variants. Multiplexed Assays of Variant Effect (MAVEs) can help address this challenge by measuring all possible single nucleotide variant effects in a gene or regulatory sequence simultaneously. Here we describe MaveDB v2, which has become the database of record for MAVEs. MaveDB now contains a large fraction of published studies, comprising over two hundred datasets and three million variant effect measurements. We created tools and APIs to streamline data submission and access, transforming MaveDB into a hub for the analysis and dissemination of these impactful datasets.
Compositional forecasting of Chinook Salmon Evolutionarily Significant Units in bycatch for Pacific Hake fisheries
Authors: Moran Paul , Tuttle Vanessa J. , Bishop Susan , LaVoy Larrie
Published: December 2021

Bycatch impacts on non-target species present significant management problems in diverse fisheries throughout the world. Despite successful efforts to minimize bycatch in US West Coast Pacific Hake fisheries, these impacts remain a concern, particularly for sensitive populations of Chinook Salmon. NOAA Fisheries needed predictive models to estimate proportions of Chinook Salmon Evolutionarily Significant Units (ESUs) expected in bycatch. We used genetic mixture analysis to estimate ESU proportions from at-sea bycatch between 2008 and 2015. Using latitude as a predictor and applying jackknife cross validation, we found Dirichlet regression more accurately estimated abundant ESUs, whereas multinomial logistic regression performed better with rare ESUs. This targeted, ESU-specific approach showed the spatial distribution of sensitive stocks in bycatch and supported NOAA’s obligations to forecast impacts on listed ESUs. The overarching goal of this continuing work is to maximize sustainable harvest while protecting threatened and endangered Chinook Salmon ESUs.
HARLEY: A Semi-Automated detection of foci in fluorescence images of yeast
Authors: Shabanov Ilya , Buchan J. Ross
Published: December 2021

Quantification of cellular structures in fluorescence microscopy data is a key means of understanding cellular function. Unfortunately, numerous cellular structures present unique challenges in their ability to be unbiasedly and accurately detected and quantified. In our studies on stress granules in yeast, users displayed a striking variation of up to 3.7-fold in foci calls and were only able to replicate their results with 62-78% correlation, when requantifying the same images. To facilitate consistent results we developed HARLEY (Human Augmented Recognition of LLPS Ensembles in Yeast), a customizable software for detection and quantification of stress granules in S.cerevisiae. After a brief model training on ~20 cells the detection of foci is fully automated and based on closed loops in intensity contours, constrained only by the a-priori known size of the features of interest. Since no shape is implied, this method is not limited to round features, as is often the case with other algorithms. Candidate features are annotated with a set of geometrical and intensity-based properties to train a kernel Support Vector Machine to recognize features of interest. The trained classifier is then used to create consistent results across datasets. HARLEY is aimed at users without technical expertise, allows for batch processing and is freely available, which should be of broad interest to users focused on analysis of microscopy data in yeast.
Striatal compartmentalization and clustering of different subtypes of astrocytes is altered in the zQ175 Huntington’s disease mouse model
Authors: Brown Taylor G , Thayer Mackenzie , Zarate Nicole , Gomez-Pastor Rocio
Published: December 2021

Huntington’s disease (HD) is a devastating neurodegenerative disease that primarily affects the striatum, a brain region that controls movement and some forms of cognition. Dysfunction and loss of medium spiny neurons of the striatum is accompanied by astrogliosis (increased astrocyte density and pathology). For decades, astrocytes were considered a homogeneous cell type, but recent transcriptomic analyses revealed astrocytes are a heterogeneous population classified into multiple subtypes depending on the expression of different gene markers. Here, we studied whether three different striatal astrocyte subtypes expressing glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), or S100 calcium-binding protein B (S100B) are differentially altered in HD. We conducted a comparative immunofluorescence analysis in the striatum of WT and the heterozygous zQ175 HD mouse model and found that the expression and abundance of GFAP+ and S100B+ astrocytes increased in zQ175 mice, while GS+ astrocytes showed no alteration. We then explored whether there was a differential spatial distribution of any of these subtypes within the striatum. We developed a systematic brain compartmentalization approach and found that while GS+ and S100B+ astrocytes were more homogeneously distributed throughout the striatum in zQ175 mice, GFAP+ astrocytes preferentially accumulated in the dorsomedial and dorsolateral striatum, which are regions associated with goal-directed and habitual behaviors. Additionally, GFAP+ astrocytes in zQ175 mice showed increased clustering, a parameter that indicates increased proximity and that is associated with localized inflammation and/or neurodegeneration. Our data suggest a differential susceptibility in both increased density and striatal compartmentalization of different subtypes of astrocytes in zQ175. These results highlight new potential implications for our understanding of astrocyte pathology in HD.
The decrotonylase FoSir5 facilitates mitochondrial metabolic state switching in conidial germination of Fusarium oxysporum
Authors: Zhang Ning , Song Limin , Xu Yang , Pei Xueyuan , Luisi Ben F. , Liang Wenxing
Published: December 2021

Fusarium oxysporum is one of the most important pathogenic fungi with a broad range of plant and animal hosts. The first key step of its infection cycle is conidial germination, but there is limited information available on the molecular events supporting this process. We show here that germination is accompanied by a sharp decrease in expression of FoSir5, an ortholog of the human lysine deacetylase SIRT5. We observe that FoSir5 decrotonylates a subunit of the fungal pyruvate dehydrogenase complex (FoDLAT) at K148, resulting in inhibition of the activity of the complex in mitochondria. Moreover, FoSir5 decrotonylates histone H3K18, leading to a downregulation of transcripts encoding enzymes of aerobic respiration pathways. Thus, the activity of FoSir5 coordinates regulation in different organelles to steer metabolic flux through respiration. As ATP content is positively related to fungal germination, we propose that FoSir5 negatively modulates conidial germination in F. oxysporum through its metabolic impact. These findings provide insights into the multifaceted roles of decrotonylation, catalysed by FoSir5, that support conidial germination in F. oxysporum.
Normalisation of SARS-CoV-2 concentrations in wastewater: the use of flow, conductivity and CrAssphage
Authors: Langeveld Jeroen , Schilperoort Remy , Heijnen Leo , Elsinga Goffe , Schapendonk Claudia E.M. , Fanoy Ewout , de Schepper Evelien I.T. , Koopmans Marion P. G. , de Graaf Miranda , Medema Gertjan
Published: December 2021

Over the course of the COVID-19 pandemic in 2020-2021, monitoring of SARS-CoV-2 RNA in wastewater has rapidly evolved into a supplementary surveillance instrument for public health. Short term trends (2 weeks) are used as a basis for policy and decision making on measures for dealing with the pandemic. Normalization is required to account for the varying dilution rates of the domestic wastewater, that contains the shedded virus RNA. The dilution rate varies due to runoff, industrial discharges and extraneous waters. Three normalization methods using flow, conductivity and CrAssphage, have been investigated on 9 monitoring locations between Sep 2020 and Aug 2021, rendering 1071 24-hour flow-proportional samples. In addition, 221 stool samples have been analyzed to determine the daily CrAssphage load per person. Results show that flow normalization supported by a quality check using conductivity monitoring is the advocated normalization method in case flow monitoring is or can be made available. Although Crassphage shedding rates per person vary greatly, the CrAssphage loads were very consistent over time and space and direct CrAssphage based normalization can be applied reliably for populations of 5600 and above.
Emergent multilevel selection in a simple spatial model of the evolution of altruism
Authors: Hermsen Rutger
Published: December 2021

Theories on the evolutionary origins of altruistic behavior have a long history and have become a canonical part of the theory of evolution. Nevertheless, the mechanisms that allow altruism to appear and persist are still incompletely understood. It is well known, however, that the spatial structure of populations is an important determinant. In both theoretical and experimental studies, much attention has been devoted to populations that are subdivided into discrete groups. Such studies typically imposed the structure and dynamics of the groups by hand. Here, we instead present a simple individual-based model in which altruistic organisms spontaneously self-organize into spatially separated colonies that themselves reproduce by binary fission and hence behave as Darwinian entities in their own right. Using software to automatically track the rise and fall of colonies, we are able to apply formal theory on multilevel selection and thus quantify the within- and among-group dynamics. This reveals that individual colonies inevitably succumb to defectors in a within-colony “tragedy of the commons”. Even so, altruism persists in the population because more altruistic colonies reproduce more frequently and drive less altruistic ones to extinction. Evidently, the colonies promote the selection of altruism but in turn depend on altruism for their existence; the selection of altruism hence involves a kind of evolutionary bootstrapping. The emergence of the colonies also depends crucially on the length scales of motility, altruism, and competition. This reconfirms the general relevance of these scales for social evolution, but also stresses that their impact can only be understood fully in the light of the emergent eco-evolutionary spatial patterns. The results also suggest that emergent spatial population patterns can function as a starting point for transitions of individuality.
Spatiotemporal NF-κB dynamics encodes the position, amplitude and duration of local immune inputs
Authors: Son Minjun , Frank Tino , Holst-Hansen Thomas , Wang Andrew , Junkin Michael , Kashaf Sara S , Trusina Ala , Tay Savaş
Published: December 2021

Infected cells communicate through secreted signaling molecules like cytokines, which inform nearby cells about the type, severity and location of pathogens. How differences in cytokine secretion affect inflammatory signaling over space and time, and how responding cells decode information from propagating cytokine signals are not understood. By computationally and experimentally studying NF-κB dynamics in co-cultures of signal sending cells (macrophages) and receiving cells (fibroblasts), we found that cytokine signals are transmitted by wave-like propagation of NF-κB activity and create well-defined cellular activation zones in a responding cell population. Remarkably, NF-κB dynamics in responding cells can simultaneously encode information about cytokine dose, duration, and distance to the cytokine source. Spatially-resolved transcriptional analysis revealed that responding cells transmit local cytokine information to distance specific pro-inflammatory gene expression patterns, creating “gene expression zones” in the population. Despite single-cell variability, the size and duration of the signaling zone is tightly controlled by the macrophage cytokine secretion profile. Our results highlight how macrophages tune their cytokine secretion dynamics to control signal transmission distance, and how NF-κB interprets these signals to coordinate inflammatory response in space and time.
Euler method can outperform more complex ODE solvers in the numerical implementation of the Izhikevich artificial Spiking Neuron Model given the allocated FLOPS
Authors: de Alteriis Giuseppe , Cataldo Enrico , Mazzoni Alberto , Oddo Calogero Maria
Published: December 2021

The Izhikevich artificial spiking neuron model is among the most employed models in neuromorphic engineering and computational neuroscience, due to the affordable computational effort to discretize it and its biological plausibility. It has been adopted also for applications with limited computational resources in embedded systems. It is important therefore to realize a compromise between error and computational expense to solve numerically the model’s equations. Here we investigate the effects of discretization and we study the solver that realizes the best compromise between accuracy and computational cost, given an available amount of Floating Point Operations per Second (FLOPS). We considered three fixed-step solvers for Ordinary Differential Equations (ODE), commonly used in computational neuroscience: Euler method, the Runge-Kutta 2 method and the Runge-Kutta 4 method. To quantify the error produced by the solvers, we used the Victor Purpura spike train Distance from an ideal solution of the ODE. Counterintuitively, we found that simple methods such as Euler and Runge Kutta 2 can outperform more complex ones (i.e. Runge Kutta 4) in the numerical solution of the Izhikevich model if the same FLOPS are allocated in the comparison. Moreover, we quantified the neuron rest time (with input under threshold resulting in no output spikes) necessary for the numerical solution to converge to the ideal solution and therefore to cancel the error accumulated during the spike train; in this analysis we found that the required rest time is independent from the firing rate and the spike train duration. Our results can generalize in a straightforward manner to other spiking neuron models and provide a systematic analysis of fixed step neural ODE solvers towards an accuracy-computational cost tradeoff.