bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescent-led sexual and reproductive health and rights research: qualitative evaluation of an innovative participatory action research project in Senegal
Authors: Fortin Geneviève , Vandermorris Ashley , Sall Mohamadou , McKinnon Britt
Published: September 2021

Participatory approaches are increasingly popular in public health, but remain little used to address adolescent health issues. However, adolescent participation in research has enormous potential for identifying solutions to health issues that concern them. In Senegal, a youth-led participatory action research project was implemented to evaluate the potential of the approach to address adolescent sexual and reproductive health and rights issues. A qualitative evaluation was conducted in four Senegalese communities, where teams of adolescents were trained to conduct a research project and identify solutions relevant for their communities. Observations and interviews were carried out during results dissemination meetings in each of the communities. Based on participatory action research principles and expected adolescent participation outcomes, the evaluation of the project demonstrated the potential of the approach to identify relevant solutions, while promoting positive and meaningful adolescent participation. Despite some difficulties, such as community resistance, the youth researchers were able to successfully complete their research project, while developing their confidence and self-esteem. The adolescents were convinced that they could act as agents of positive social change. This project has shown that it is possible and relevant to involve adolescents in research projects, and that this approach has significant potential in global health.
Assessing the validity of dual-minima algorithm for heel-strike and toe-off prediction for the amputee population
Authors: Aftab Zohaib
Published: September 2021

Assessment of gait deficits relies on accurate gait segmentation based on the key gait events of heel strike (HS) and toe-off (TO). Kinematics-based estimation of gait events has shown promise in this regard especially using the leg velocity signal and gyroscopic sensors. However, its validation for the amputee population is not established in the literature. The goal of this study is to assess the accuracy of lower-leg angular velocity signal in determining the TO and HS instants for the amputee population. An open data set containing marker data of 10 subjects with unilateral transfemoral amputation during treadmill walking was used. A rule-based dual-minima algorithm was developed to detect the landmarks in the shank velocity signal indicating TO and HS events. The predictions were compared against the force platform data for 2595 walking cycles from 239 walking trials. Results showed considerable accuracy for the HS with a median error of -1ms. The TO prediction error was larger with the median ranging from 35-84ms. The algorithm consistently predicted the TO earlier than the actual event. Significant differences were found between the prediction accuracy for the sound and prosthetic legs. The prediction accuracy was also affected by the subjects’ mobility level (K-level) but was largely unaffected by gait speed. In conclusion, the leg velocity profile during walking can predict the heel-strike and toe-off events for the transfemoral amputee population with varying degrees of accuracy depending upon the leg side and amputee’s functional ability level.
VaxArray Immunoassay for the Multiplexed Quantification of Poliovirus D-Antigen
Authors: Dawson Erica D. , Taylor Amber W. , Johnson James E. , Hu Tianjing , McCormick Caitlin , Thomas Keely N. , Gao Rachel Y. , Wahid Rahnuma , Mahmood Kutub , Rowlen Kathy L.
Published: September 2021

Next generation poliovirus vaccines are critical to reaching global poliovirus eradication goals. Recent efforts have focused on creating inactivated vaccines using attenuated Sabin strains that maintain patient safety benefits and immunogenicity of conventional inactivated vaccines while increasing manufacturing safety and lowering production costs, and on developing novel oral vaccines using modified Sabin strains that provide critical mucosal immunity but are further attenuated to minimize risk of reversion to neurovirulence. In addition, there is a push to improve the analytical tools for poliovirus vaccine characterization. Conventional and Sabin inactivated poliovirus vaccines typically rely on standard plate-based ELISA as in vitro D-antigen potency assays in combination with WHO international standards as calibrants. While widely utilized, the current D-antigen ELISA assays have a long time to result (up to 72 hours), can suffer from lab-to-lab inconsistency due to non-standardized protocols and reagents, and are inherently singleplex. For D-antigen quantitation, we have developed the VaxArray Polio Assay Kit, a multiplexed, microarray-based immunoassay that uses poliovirus-specific human monoclonal antibodies currently under consideration as standardized reagents for characterizing inactivated Sabin and Salk vaccines. The VaxArray assay can simultaneously quantify all 3 poliovirus serotypes with a time to result of less than 3 hours. Here we demonstrate that the assay has limits of quantification suitable for both bioprocess samples and final vaccines, excellent reproducibility and precision, and improved accuracy over an analogous plate-based ELISA. The assay is suitable for adjuvanted combination vaccines, as common vaccine additives and crude matrices do not interfere with quantification, and is intended as a high throughput, standardized quantitation tool to aid inactivated poliovirus vaccine manufacturers in streamlining vaccine development and manufacturing, aiding the global polio eradication effort.
Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails
Authors: Liu Yusheng , Nie Hu , Sun Rongrong , Wang Jiaqiang , Lu Falong
Published: September 2021

In vitro transcribed (IVT) mRNA represents a new class of drug in both therapeutics and vaccines. Improving the translation efficiency of IVT mRNA remains a core challenge for mRNA-based applications. Here, using IVT mRNAs with poly(A) tails containing non-A residues which were recently revealed to be widespread in RNA poly(A) tails1,2, we unexpectedly find that non-A residues can effectively promote the mRNA translation. To further support our finding, we provide evidence that non-A residues associated with enhanced mRNA translation efficiency transcriptome-wide in mouse and human cells. Together, our study provides a novel approach to enhance mRNA translation efficiency by inclusion of non-A residues in the mRNA poly(A) tails, holding great potential to promote mRNA-based therapeutics and vaccines.
Frontal cortex activity underlying the production of diverse vocal signals during social communication in marmoset monkeys
Authors: Zhao Lingyun , Wang Xiaoqin
Published: September 2021

Vocal communication is essential for social behaviors in humans and many non-human primates. While the frontal cortex has been shown to play a crucial role in human speech production, its role in vocal production in non-human primates has long been questioned. Recent studies have shown activation in single neurons in the monkey frontal cortex during vocal production in relatively isolated environment. However, little is known about how the frontal cortex is engaged in vocal production in ethologically relevant social context, where different types of vocal signals are produced for various communication purposes. Here we studied single neuron activities and local field potentials (LFP) and in the frontal cortex of marmoset monkeys while the animal engaged in vocal exchanges with other conspecifics in a social environment. Marmosets most frequently produced four types of vocalizations with distinct acoustic structures, three of which were typically not produced in isolation. We found that both single neuron activities and LFP were modulated by the production of each of the four call types. Moreover, the neural modulations in the frontal cortex showed distinct patterns for different call types, suggesting a representation of vocal signal features. In addition, we found that theta-band LFP oscillations were phase-locked to the phrases of twitter calls, which indicates the coordination of temporal structures of vocalizations. Our results suggested important functions of the marmoset frontal cortex in supporting the production of diverse vocalizations in vocal communication.
Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study
Authors: Atabaki-Pasdar Naeimeh , Pomares-Millan Hugo , Koivula Robert W , Tura Andrea , Brown Andrew , Viñuela Ana , Agudelo Leandro , Coral Daniel , van Oort Sabine , Allin Kristine , Chabanova Elizaveta , Cederberg Henna , De Masi Federico , Elders Petra , Tajes Juan Fernandez , Forgie Ian M , Hansen Tue H , Heggie Alison , Jones Angus , Kokkola Tarja , Mahajan Anubha , McDonald Timothy J , McEvoy Donna , Tsirigos Konstantinos , Teare Harriet , Vangipurapu Jagadish , Vestergaard Henrik , Adamski Jerzy , Beulens Joline WJ , Brunak Søren , Dermitzakis Emmanouil , Hansen Torben , Hattersley Andrew T , Laakso Markku , Pedersen Oluf , Ridderstråle Martin , Ruetten Hartmut , Rutters Femke , Schwenk Jochen M , Walker Mark , Giordano Giuseppe N , Ohlsson Mattias , Gupta Ramneek , Mari Andrea , McCarthy Mark I , Thomas E Louise , Bell Jimmy D , Pavo Imre , Pearson Ewan R , Franks Paul W
Published: September 2021

Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.

Measures of glycemia, insulin dynamics, magnetic resonance imaging (MRI)-derived abdominal and liver fat content, serological biomarkers, lifestyle, and anthropometry were obtained in participants from the IMI DIRECT cohorts (n=795 with new onset T2D and 2234 individuals free from diabetes). UK Biobank (n=3641) was used for modelling and replication purposes. Bayesian networks were employed to infer causal pathways, with causal validation using two-sample Mendelian randomization.

Bayesian networks fitted to IMI DIRECT data identified higher basal insulin secretion rate (BasalISR) and MRI-derived excess visceral fat (VAT) accumulation as the features of dysmetabolism most likely to cause liver fat accumulation; the unconditional probability of fatty liver (>5%) increased significantly when conditioning on high levels of BasalISR and VAT (by 23%, 32% respectively; 40% for both). Analyses in UK Biobank yielded comparable results. MR confirmed most causal pathways predicted by the Bayesian networks.

Here, BasalISR had the highest causal effect on fatty liver predisposition, providing mechanistic evidence underpinning the established association of NAFLD and T2D. BasalISR may represent a pragmatic biomarker for NAFLD prediction in clinical practice.
Temporal stability and state-dependence of retrospective self-reports of childhood maltreatment in major depression: a two-year longitudinal analysis of the childhood trauma questionnaire
Authors: Goltermann Janik , Meinert Susanne , Hülsmann Carina , Dohm Katharina , Grotegerd Dominik , Redlich Ronny , Waltemate Lena , Lemke Hannah , Thiel Katharina , Mehler David M. A. , Enneking Verena , Borgers Tiana , Repple Jonathan , Gruber Marius , Winter Nils , Hahn Tim , Brosch Katharina , Meller Tina , Ringwald Kai G. , Schmitt Simon , Stein Frederike , Pfarr Julia-Katharina , Krug Axel , Nenadić Igor , Kircher Tilo , Opel Nils , Dannlowski Udo
Published: September 2021

Background

Retrospective self-reports of childhood maltreatment are widely used in research and clinical practice. However, their validity has been questioned due to potential depressive bias. Yet, systematic investigations of this matter are sparse. Thus, we investigate if and to what extent retrospective maltreatment reports vary in relation to longitudinal changes in depressive symptomatology.

Methods

Two-year temporal stability of maltreatment reports was assessed via the Childhood Trauma Questionnaire (CTQ). Diagnosis and depressive symptoms were assessed using clinical interview and the Beck Depression Inventory. From two independent cohorts (MACS and MNC) we included a total of n=347 major depressive disorder (MDD) patients, n=419 healthy controls (HC), and a subsample with a lifetime first depressive episode between both assessments (n=27). Analysis plan and hypotheses were preregistered prior to data sighting.

Results

Maltreatment reports were highly stable in HC and MDD patients across both cohorts (ICC=.956; 95%-CI[.949, .963] and ICC=.950; 95%-CI[.933, .963]) and temporal stability did not differ between groups. Stability was lower for cutoff-based maltreatment categorization (K=.551; 95%-CI[.479, .622] and K=.507; 95%-CI[.371, .640]). Baseline maltreatment reports were associated with concurrent and future depression severity. However, longitudinal changes in depression severity predicted variability in CTQ scores only to a small extent across cohorts (b=0.101, p=.009, R2=.021 and b=0.292, p=.320), with the effect being driven by emotional maltreatment subscales.

Conclusions

Findings suggest that the CTQ provides temporally stable self-reports of childhood maltreatment in healthy and depressed populations, and are only marginally biased by depressive symptomatology. Gradual rather than categorical conceptualization of maltreatment is advised for improving psychometric quality.
COVID-19 scenarios for comparing the effectiveness of age-specific vaccination regimes, exemplified for the city of Aschaffenburg (Germany)
Authors: Krebs Tobias , von Jouanne-Diedrich Holger , Moeckel Michael J.
Published: September 2021

Purpose of this report

The purpose of this rapid communication is to illustrate the effectiveness of different vaccination regimes for controlling the number of severe and critical COVID-19 cases in the city of Aschaffenburg, Germany. Our results show that, despite numerous vaccinations in the past, further vaccinations are necessary to immunize the population and to keep the number of severe and critical cases low in the coming months. Considering that not all people can or want to receive vaccination, we compare different age-specific vaccination approaches.

Applied Methods

We use the agent-based epidemiological simulator Covasim for discussing the impact of different vaccination strategies. We calibrate it to reproduce the historical course of the COVID-19 pandemic in the city of Aschaffenburg, Germany; for this, we model and integrate numerous public health interventions imposed on the local population. As for some of the political actions rigorous quantification is currently not available, we fit those unknown (free) model parameters to published data on the measured epidemiological dynamics. Then we calculate the state of immunization of the population, gained through infections and vaccinations, at any time in the past, including models for time-dependent immunity decay that have been made available in Covasim. Finally, we define and compare scenarios of different vaccination regimes, especially with regard to vaccinating adolescents and providing booster vaccinations to the elderly.

Key message

Without further vaccinations, we expect a strong increase in severe and critical cases. In order to restrict their growth our simulations suggest that in all considered cases vaccinations of unvaccinated people is more effective than booster vaccinations for already fully vaccinated people. This applies even to vaccinations of young people who are not themselves at high risk of developing severe or critical illness. We attribute this observation to the fact that immunization of adolescents indirectly protects vulnerable age groups by preventing the spread of the virus more effectively than further immunizing other age groups. This indicates that with the pandemic ongoing, strategies focussed on minimizing individual health risks by vaccinations may no longer coincide with those needed to minimize the number of severe and critical cases.
Health impact and cost of COVID-19 prophylaxis with monoclonal antibodies
Authors: Flaxman Abraham D. , Issema Rodal , Barnabas Ruanne V. , Ross Jennifer M.
Published: September 2021

Background

The COVID-19 pandemic has led to over 600,000 deaths in the United States and continues to disrupt lives even as effective vaccines are available. We aimed to estimate the impact and health system cost of implementing post-exposure prophylaxis against household exposure to COVID-19 with monoclonal antibodies.

Methods

We developed a decision-analytical model analysis of results from a recent randomized controlled trial with complementary data on household demographic structure, vaccine coverage, and COVID-19 confirmed case counts for the representative month of May, 2021. The model population includes individuals of all ages in the United States by sex and race/ethnicity.

Results

In a month of similar intensity to May, 2021, in the USA, a monoclonal antibody post-exposure prophylaxis program reaching 50% of exposed unvaccinated household members aged 50+, would avert 1,813 (1,171 – 2,456) symptomatic infections, 526 (343 - 716) hospitalizations, and 83 (56 - 116) deaths. Assuming the unit cost of administering the intervention was US$ 1,264, this program would save the health system US$ 3,055,202 (−14,034,632 - 18,787,692).

Conclusions

Currently in the United States, health system and public health actors have an opportunity to improve health and reduce costs through COVID-19 post-exposure prophylaxis with monoclonal antibodies.
Bone-Specific Enhancement of Antibody Therapy for Breast Cancer Metastasis to Bone
Authors: Tian Zeru , Yu Chenfei , Zhang Weijie , Wu Kuan-lin , Gupta Ruchi , Xu Zhan , Wu Ling , Chen Yuda , Zhang Xiang H. -F. , Xiao Han
Published: September 2021

Therapeutic antibodies have gone a long way toward realizing their clinical potential and have become very useful for treating a variety of pathologies. Despite the rapid evolution of therapeutic antibodies, their clinical efficacy in treatment of bone tumors has been hampered by the inadequate pharmacokinetics and poor bone tissue accessibility of these large macromolecules. Here, we show that engineering therapeutic antibodies to include bone-homing peptide sequences dramatically enhances their concentration in the bone metastatic niche, resulting in significantly reduced survival and progression of breast cancer bone metastases. To enhance the bone tumor-targeting ability of engineered antibodies, we introduced varying numbers of a bone-homing peptide into permissive internal sites of the anti-HER2 antibody trastuzumab. Compared to the unmodified antibody, the engineered bone-targeting antibodies have similar pharmacokinetics andin vitrocytotoxic activity against HER2-positive cancer cells, but exhibit improved bone tumor distributionin vivo. Accordingly, in xenograft models of breast cancer metastasis to bone sites, engineered antibodies with enhanced bone specificity exhibit increased inhibition of both initial bone metastases and secondary multi-organ metastases from bone lesions. Furthermore, this engineering strategy is also applied to prepare bone-targeting antibody-drug conjugates with enhanced therapeutic efficacy. These results demonstrate that adding bone-specific targeting to antibody therapy results in robust delivery of therapeutic antibodies to the bone tumor niche. This provides a powerful strategy for overcoming inadequate treatment of bone cancer and the development of potentially acquired resistance to therapy.
Breast tumor Insulin-like growth factor receptor regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics
Authors: Obr Alison E. , Chang Yung-Jun , Ciliento Virginia , Lemenze Alexander , Maingrette Krystopher , Bulatowicz Joseph J. , Shang Quan , Gallagher Emily , LeRoith Derek , Wood Teresa L.
Published: September 2021

The acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF-1R) has been considered a target for inhibition in breast cancer, low levels of IGF-1R expression are associated with worse overall patient survival. To determine how reduced IGF-1R impacts tumor phenotype, we used weighted gene correlation network analysis (WGCNA) of METABRIC patient data and identified gene modules specific to cell cycle, adhesion, and immune cell signaling inversely correlated with IGF-1R expression in human breast cancers. Integration of human patient data with data from mouse tumors revealed similar pathways necessary for promoting metastasis in basal-like tumors with reduced signaling or expression of the IGF-1R. Functional analyses revealed the basis for the enhanced metastatic phenotype including alterations in E- and P-cadherins.
Stress conditions promote the mating competency ofLeishmaniapromastigotesin vitromarked by expression of the ancestral gamete fusogen HAP2
Authors: Louradour Isabelle , Ferreira Tiago Rodrigues , Duge Emma , Karunaweera Nadira , Paun Andrea , Sacks David
Published: September 2021

Leishmaniaare protozoan parasites transmitted by the bite of sand fly vectors producing a wide spectrum of diseases in their mammalian hosts. These diverse clinical outcomes are directly associated with parasite strain and species diversity. AlthoughLeishmaniareproduction is mainly clonal, a cryptic sexual cycle capable of producing hybrid genotypes has been inferred from population genetic studies, and directly demonstrated by laboratory crosses. Experimentally, mating competency has been largely confined to promastigotes developing in the sand fly midgut. The ability to hybridize culture promastigotesin vitrohas been limited so far to low efficiency mating between twoL. tropicastrains, L747 and MA37, that mate with high efficiency in flies. Here, we show that exposure of promastigote cultures to DNA damage stress produces a remarkably enhanced efficiency ofin vitrohybridization of theL. tropicastrains, and extends to other species, includingL. donovani, L. infantum, andL. braziliensis, a capacity to generate intra- and interspecific hybrids. Whole genome sequencing and total DNA content analyses indicate that the hybrids are in each case full genome, polyploid hybrids. Single-cell RNA sequencing of the L747 and MA37 parental lines highlights the transcriptome heterogeneity of culture promastigotes and reveals discrete clusters that emerge post-irradiation in which genes potentially involved in genetic exchange are expressed, including the ancestral gamete fusogenHAP2. By generating reporter constructs for HAP2, we could select for mating-competent and mating-incompetent promastigotes. Overall, this work reveals that there are specific populations involved inLeishmaniamating associated with a discernible transcriptomic signature, and that stress facilitatedin vitrohybridization can be a transformative approach to generate large numbers of hybrid genotypes between diverse species and strains.
Awake perception is associated with dedicated neuronal assemblies in cerebral cortex
Authors: Filipchuk Anton , Schwenkgrub Joanna , Destexhe Alain , Bathellier Brice
Published: September 2021

Neural activity in sensory cortex combines stimulus responses and ongoing activity, but it remains unclear whether they reflect the same underlying dynamics or separate processes. Here we show that during wakefulness, the neuronal assemblies evoked by sounds in the auditory cortex and thalamus are specific to the stimulus and distinct from the assemblies observed in ongoing activity. In contrast, we observed in three different anesthesia, that evoked assemblies are indistinguishable from ongoing assemblies in the cortex. However, they remain distinct in the thalamus. A strong remapping of sensory responses accompanies this dynamical state change produced by anesthesia. Together, these results show that the awake cortex engages dedicated neuronal assemblies in response to sensory inputs, which we suggest is a network correlate of sensory perception.
Patient derived organoids reveal that PI3K/AKT signalling is an escape pathway for radioresistance and a target for therapy in rectal cancer
Authors: Wanigasooriya Kasun , Barros-Silva Joao D. , Tee Louise , El-Asrag Mohammed E. , Stodolna Agata , Pickles Oliver J. , Stockton Joanne , Bryer Claire , Hoare Rachel , Whalley Celina , Tyler Robert , Sillo Tortieju , Yau Christopher , Ismail Tariq , Beggs Andrew D.
Published: September 2021

Partial or total resistance to preoperative chemoradiotherapy occurs in more than half of locally advanced rectal cancer patients. Several novel or repurposed drugs have been trialled to improve cancer cell sensitivity to radiotherapy, with limited success. To understand the mechanisms underlying this resistance and target them effectively, we initially compared treatment-naive transcriptomes of radiation-resistant and radiation-sensitive patient-derived organoids (PDO) to identify biological pathways involved in radiation resistance. Pathway analysis revealed that PI3K/AKT/mTOR and epithelial mesenchymal transition pathway genes were upregulated in radioresistant PDOs. Moreover, single-cell sequencing of pre & post-irradiation PDOs showed mTORC1 upregulation, which was confirmed by a genome-wide CRSIPR-Cas9 knockout screen using irradiated colorectal cancer (CRC) cell lines. Based on these findings, we evaluated cancer cell viability in vitro when treated with radiation in combination with dual PI3K/mTOR inhibitors apitolisib or dactolisib. Significant AKT phosphorylation was detected in HCT116 cells two hours post-irradiation (p=0.027). Dual PI3K/mTOR inhibitors radiosensitised HCT116 and radiation-resistant PDO lines. The PI3K/AKT/mTOR pathway upregulation contributes to radioresistance and its pharmacological inhibition leads to significant radiosensitisation in an organoid model of CRC and is a target for clinical trials.
Mena regulates the LINC complex to control actin–nuclear lamina associations, trans-nuclear membrane signalling and cancer gene expression
Authors: Li Mow Chee Frederic , Beernaert Bruno , Loftus Alexander , Kumar Yatendra , Griffith Billie G. C. , Wills Jimi C. , Wheeler Ann P. , Armstrong J. Douglas , Parsons Maddy , Leigh Irene M. , Proby Charlotte M. , von Kriegsheim Alex , Bickmore Wendy A. , Frame Margaret C. , Byron Adam
Published: September 2021

Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes (IACs), play key roles in cancer progression and metastasis. We investigated systems-level changes in the integrin adhesome during metastatic progression of a patient-derived cutaneous squamous cell carcinoma (cSCC), and found that the actin regulatory protein Mena is enriched in IACs in metastatic cSCC cells. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope of metastatic cells. Moreover, Mena potentiates the interactions of nesprin-2 with the actin cytoskeleton and the nuclear lamina. CRISPR-mediated Mena depletion causes altered nuclear morphology, reduces tyrosine phosphorylation of the nuclear membrane protein emerin and downregulates expression of the immunomodulatory gene PTX3 via the recruitment of its enhancer to the nuclear periphery. We have uncovered an unexpected novel role for Mena at the nuclear membrane, where it controls the LINC complex, nuclear architecture, chromatin repositioning and cancer gene expression. This is the first description of an adhesion protein regulating gene transcription via direct signalling across the nuclear envelope.

Abstract Figure
Sexual morph specialisation in a trioecious nematode balances opposing selective forces
Authors: Adams Sally , Pathak Prachi , Kittelman Maike , Jones Alun R.C. , Mallon Eamonn B. , Pires-daSilva Andre
Published: September 2021

The coexistence of different mating strategies, whereby a species can reproduce both by selfing and outcrossing, is an evolutionary enigma that has long intrigued biologists (Darwin, 1877). Theory predicts only two stable mating states : outcrossing with strong inbreeding depression or selfing with weak inbreeding depression. As these two mating strategies are subject to opposing selective forces, mixed breeding systems are thought to be a rare transitory state, yet they have been found to persist even after multiple speciation events. We hypothesise that if each mating strategy plays a distinctive role during the species life history, opposing selective pressures could be balanced, permitting the stable co-existence of selfing and outcrossing sexual morphs. In this scenario, we would expect each sexual morph to be specialised in their respective roles. Here we show, using a combination of behavioural, physiological and gene expression studies, that the selfing (hermaphrodite) and outcrossing (female) sexual morphs of the trioecious nematode Auanema freiburgensis have distinct adaptations optimised for their different roles during the life cycle. A. freiburgensis hermaphrodites are produced under stressful conditions, are specialised for dispersal to new habitat patches and exhibit metabolic and intestinal changes that enable them to meet the energetic cost of dispersal and reproduction. In contrast, A. freiburgensis females are produced in favourable conditions, facilitate rapid population growth and compensate for the lack of reproductive assurance by reallocating resources from intestinal development to robust mate-finding behaviour. The specialisation of each mating system for their role in the life cycle could balance opposing selective forces allowing the stable maintenance of both outcrossing and selfing mating systems in A. freiburgensis.
A terrain treadmill to study animal locomotion through large obstacles
Authors: Othayoth Ratan , Strebel Blake , Han Yuanfeng , Francois Evains , Li Chen
Published: September 2021

A major challenge to understanding locomotion in complex 3-D terrain with large obstacles is to create tools for controlled, systematic lab experiments. Existing terrain arenas only allow observations at small spatiotemporal scales (∼10 body length, ∼10 stride cycles). Here, we create a terrain treadmill to enable high-resolution observations of animal locomotion through large obstacles over large spatiotemporal scales. An animal moves through modular obstacles on an inner sphere, while a rigidly-attached, concentric, transparent outer sphere rotated with the opposite velocity via closed-loop feedback to keep the animal on top. During sustained locomotion, a discoid cockroach moved through pillar obstacles for 25 minutes (≈ 2500 strides) over 67 m (≈ 1500 body lengths), and was contained within a radius of 4 cm (0.9 body length) for 83% of the duration, even at speeds of up to 10 body length/s. The treadmill enabled observation of diverse locomotor behaviors and quantification of animal-obstacle interaction.

Summary Statement

A device keeps a small animal on top of a sphere while it traverses obstacles, creating a “terrain treadmill” to study locomotion over a long time and distance at high-resolution.
Novel genome assemblies and Evolutionary Dynamics of North American Anopheles mosquitoes
Authors: Henderson Cory A. , Kemirembe Karen , McKeand Sage , Bergey Christina , Rasgon Jason L.
Published: September 2021

Anopheles mosquitoes are the principal vectors for malaria and lymphatic filariasis, and evidence for arboviral transmission under laboratory and natural contexts has been demonstrated. Vector management approaches require an understanding of the ecological, epidemiological, and biological context of the species in question, and increased interest in gene drive systems for vector control applications has resulted in an increased need for genome assemblies from understudied mosquito species. While the genomes for many Anopheles species have been sequenced, North American Anopheles taxa have been neglected. In this study we present novel genome assemblies for the North American species An. crucians, An. freeborni, An. albimanus, and An. quadrimaculatus, and examine the evolutionary relationship between these species. We identified 790 shared single copy orthologs between the newly sequenced genomes and created a phylogeny using 673 of the orthologs, identifying 525 orthologs with evidence for positive selection on at least one branch of the phylogeny. Gene ontology terms such as calcium ion signaling, histone binding, and protein acetylation were identified as being biased in the set of selected genes. These novel genome sequences will be useful in developing our understanding of the diverse biological traits that drive vectorial capacity in anophelines.
Alternate patterns of temperature variation bring about very different disease outcomes at different mean temperatures
Authors: Kunze Charlotte , Luijckx Pepijn , Jackson Andrew L. , Donohue Ian
Published: September 2021

The dynamics of host-parasite interactions are highly temperature-dependent and may be modified by increasing frequency and intensity of climate-driven heat events. Here, we show that altered patterns of temperature variance lead to an almost order-of-magnitude shift in thermal performance of host and pathogen life history traits over and above the effects of mean temperature and, moreover, that different temperature regimes affect these traits differently. We found that diurnal fluctuations of ±3°C lowered infection rates and reduced spore burden compared to constant temperatures in our focal host Daphnia magna exposed to the microsporidium parasite Ordospora colligata. In contrast, a three-day heatwave (+6°C) did not affect infection rates, but increased spore burden (relative to constant temperatures with the same mean) at 16°C, while reducing burden at higher temperatures. We conclude that changing patterns of climate variation, superimposed on shifts in mean temperatures due to global warming, may have profound and unanticipated effects on disease dynamics.
Towards discrimination of mammary pathogenic Escherichia coli (MPEC) in cattle based on possession of different iron acquisition systems
Authors: Rahmani Hamideh Kalateh , Tabar Gholamreza Hashemi , Badouei Mahdi Askari , Khoramian Babak
Published: September 2021

Most efforts to elucidate virulence mechanisms of mammary pathogenic Escherichia coli (MPEC), causative agent of bovine clinical mastitis, have been failed but some recent studies introduced iron acquisition systems as major role players in pathogenicity. Here, we investigated the different iron uptake systems genotypes and assessed how they relate to virulence potential of MPEC. In total, 217 E. coli isolates (MPEC= 157, fecal isolates= 60) were screened for the presence of nine genes related to iron acquisition (iroN, iutA, fecA, fyuA, sitA, irp2, iucD, chuA and tonB) and phylogenetic groups were also determined. Next, bacterial growth potential and survival in raw and UHT milk which are representative for crucial steps in mastitis development were evaluated. In addition, the mineral consumption of E. coli cultured in milk were measured. The results showed that MPEC strains considerably tend to possess fecA (93%, p= 0.000) and belong to phylogenetic group A (42%, p= 0.042). The fecA+ strains from both mastitis and fecal E. coli had a significant (p= 0.000) growth potential in raw and UHT milk. Interestingly, for the first time, it was shown that fecA+ isolates consumed less amounts of iron and other metal ions. Overall, it seems that the uptake systems related to fecA contributes to overcoming harsh conditions of milk and genetic lineages could also affect pathogenicity of MPEC. These findings could lead us to define MPEC with more clarity based on genotypes or growth potential in milk and possibly promote novel solutions to control mastitis more effectively in future.

Importance

Mastitis is one of the most costly concerns in bovine medicine and the main cause of antibiotic use in dairy herds’ worldwide. As a rule of thumb, it was believed that extraintestinal pathogenic E. coli expands iron acquisition virulence arsenal to enhance pathogenic potential in the environments of the host outside the intestines. The present study indicated that the long believed idea of possession of diverse mineral acquisition systems and siderophores in all ExPEC groups could be a fairy tale. Along with recent studies, the present research showed that the fec operon could be the minimal necessary factor to overcome the harsh conditions of milk with limiting mineral concentrations. Obviously, the fecA+ isolates were fast-growing and consumed less amounts of minerals. It seems that the fec locus and its related metabolic pathways could be the potential targets for diagnostic, preventive, and therapeutic purposes.
Impact of charge patches on tumor disposition and biodistribution of therapeutic antibodies
Authors: Stüber Jakob C. , Rechberger Karin F. , Miladinović Saša M. , Pöschinger Thomas , Zimmermann Tamara , Villenave Remi , Eigenmann Miro J. , Kraft Thomas E. , Shah Dhaval K. , Kettenberger Hubert , Richter Wolfgang F.
Published: September 2021

This study explores the impact of antibody surface charge on tissue distribution into various tissues including tumor. Tumor-bearing mice were dosed intravenously with a mixture comprising three antibodies engineered to carry negative charge patches, a balanced charge distribution, or positive patches, respectively. Tissue levels were analyzed with a specific LC-MS/MS method. In addition, the antibody mix was administered to non-tumor bearing mice. Muscle and skin interstitial fluid were obtained by centrifugation and analyzed by LC-MS/MS. An in-vitro endothelium model was explored for its feasibility to mimic the observed distribution differences. A balanced charge distribution was optimal in terms of total tumor exposure, while in other tissues negatively charged and balanced charged antibodies gave similar results. In contrast, positive charge patches generally result in increased serum clearance but markedly enhance tumor and organ uptake, leading to higher tissue-to-serum ratios. The uptake and availability in the interstitial space were confirmed by specific assessment of antibody levels in the interstitial fluid of muscle and skin, with similar charge impact as in total tissue. The in vitro model was able to differentiate the transport propensity of this series of antibody variants. In summary, our results show the differential effects of charge patches on an antibody surface on biodistribution and tumor uptake. These insights may help in the design of molecules with biodistribution properties tailored to their purpose and an optimized safety profile.
Ex Vivo Brain Preparation to Analyze Vocal Pathways of Xenopus Frogs
Authors: Yamaguchi Ayako
Published: September 2021

Understanding the neural basis of behavior is a challenging task for technical reasons. Most methods of recording neural activity require animals to be immobilized, but neural activity associated with most behavior cannot be recorded from an anesthetized, immobilized animal. Using amphibians, however, there has been some success in developing in vitro brain preparations that can be used for electrophysiological and anatomical studies. Here, we describe an ex vivo frog brain preparation from which fictive vocalizations (the neural activity that would have produced vocalizations had the brain been attached to the muscle) can be elicited repeatedly. When serotonin is applied to the isolated brains of male and female African clawed frogs, Xenopus laevis, laryngeal nerve activity that is a facsimile of those that underlie sex-specific vocalizations in vivo can be readily recorded. Recently, this preparation was successfully used in other species within the genus including Xenopus tropicalis and Xenopus victorianus. This preparation allows a variety of techniques to be applied including extracellular and intracellular electrophysiological recordings and calcium imaging during vocal production, surgical and pharmacological manipulation of neurons to evaluate their impact on motor output, and tract tracing of the neural circuitry. Thus, the preparation is a powerful tool with which to understand the basic principles that govern the production of coherent and robust motor programs in vertebrates.
Integrated reporting, textual risk disclosure and market value
Authors: Elshandidy Tamer , Elmassri Moataz , Elsayed Mohamed
Published: September 2021

Purpose

Exploiting the mandatory provision of integrated reporting in South Africa, this paper aims to investigate whether this regulatory switch from the conventional annual report is associated with differences in the level of textual risk disclosure (TRD). This paper also examines the economic usefulness of this regulatory change by observing the impact of TRD on the complying firms’ market values.

Design/methodology/approach

Archival data are collected and examined using time-series difference design and difference-in-differences design.

Findings

The authors find that the level of TRD within the mandatory integrated reporting is significantly lower than that of annual reports. The authors find that the impact of TRD in integrated reporting on market value compared to that of annual reports is statistically not different from zero. The authors’ further analyses suggest that corporate governance effectiveness is not a moderating factor to the study results. The results are robust to comparisons with the voluntary adoption of integrated reporting in the UK.

Originality/value

Collectively, the study results suggest that managers’ adherence to the mandatory provision of integrated reporting has significantly decreased the level of (voluntary) TRD they tended to convey within the conventional annual reports, resulting in a trivial impact on market value. These unintended consequences should be of interest to the International Integrated Reporting Council and other bodies interested in integrated reporting.
Evaluation of green building suppliers based on IVPLTS-CBR decision-making method
Authors: Li Peng , Chen Huizhen
Published: September 2021

Purpose

The purpose of this paper is to propose a multi-criteria decision-making model based on the case-based reasoning (CBR) method for interval-valued probabilistic linguistic term set (IVPLTS), which can cluster different categories of building suppliers for targeted management.

Design/methodology/approach

First, a new score function and distance measure for IVPLTS are proposed. Second, a green building supplier evaluation criterion system is constructed from five aspects: operation management, green management, cooperation potential, service level and product information. Finally, the IVPLTS-CBR model is used to evaluate the green building suppliers and groups them into three preset categories.

Findings

The feasibility and validity of the proposed method are verified by comparing with the advanced TOPSIS method and the IVPLTS-based VlseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method. The compared results show that the proposed method is more consistent with the actual situation and has strong theoretical significance and practical value.

Research limitations/implications

This paper presents a new method for clustering construction suppliers. Decision makers can use this method to classify construction suppliers into different categories, so that they can be targeted management. In this way, suppliers can be better guided and motivated to accelerate the green transformation and contribute their share to achieve the strategic goal of carbon neutral and carbon peak as soon as possible.

Originality/value

A new score function and distance measure for IVPLTS are proposed. Besides, a novel IVPLTS-CBR method is applied to rank and cluster building suppliers.
Labour market localisation policies and organizational responses: an analysis of the aims and effects of the Saudi Nitaqat reforms
Authors: Basahal Abdulrahman , Forde Chris , MacKenzie Robert
Published: September 2021

Purpose

The aim of this paper is twofold. First, to understand the degree to which the intended outcomes of Saudi’s Nitaqat labour market policy corresponds to the actual responses from private companies. Second, to investigate how these gaps between policy intentions and actual outcomes have informed recent changes to Nitaqat policy.

Design/methodology/approach

This paper uses a qualitative approach with a case study design and thematic analysis procedures. Data were obtained from the following three sources: semi-structured interviews completed during the early stage of Nitaqat in 2013–2014 with nine policymakers and 44 key stakeholders from six private Saudi companies; policy documents and gray literature on the aims and effects of the Nitaqat program; and available peer-reviewed literature on the subject.

Findings

This paper sets out and analyses the following four main goals of Nitaqat: First, to increase the Saudi national employment rate, second, increase company efficiency, third, improve human resource capabilities, and fourth, increase female labour participation. This paper reveals that although Nitaqat has certainly resulted in a positive change in some of these areas, in other areas, there remain gaps between the intentions and the actual effects of Nitaqat. This paper analyses recent changes to Nitaqat and argues that further changes may be needed to achieve the full goals of Nitaqat.

Originality/value

This paper’s originality lies in its analysis of the aims of labour market policies and organisational responses. It highlights the reasons for disconnections between the policy aims and organisational practices and explores how policymakers react and respond to these implementation gaps.
Systematic review of crisis reactions toward major disease outbreaks: application of the triple helix model in the context of tourism
Authors: Chen Li-Hsin , Munoz Kyrie Eleison , Aye Nandar
Published: September 2021

Purpose

While academia, industry and government have made various efforts to ameliorate the impacts of Covid-19, no study has hitherto used an integrative framework to assess the reactions of all three of these sectors to previous multinational epidemics. Such fragmentation ignores the holistic nature of crisis management. To better understand the impacts of health crises on tourism, this study aims to examine the past literature related to academic, industrial and governmental responses to multinational epidemics through the lens of the triple helix model.

Design/methodology/approach

Based on preferred reporting items for systematic reviews and meta-analyzes and the best-fit approach, this paper conducts a systematic review of the literature published between 2000 and 2020 on five multinational epidemics that had significant impacts on the tourism industry: food and mouth disease, severe acute respiratory syndrome, bird flu (novel influenza A and avian flu), Ebola and middle east respiratory syndrome. Thematic analysis was used to identify major themes in the 63 relevant articles identified.

Findings

No substantial increase was found in the quantity of multinational epidemic-related studies after 2010. Collectively, the 10 identified themes strongly emphasized economic recovery.

Originality/value

No existing tourism-related study examines reactions toward multiple health crises by integrating three important sectors: academia, industry and government. This study fills that research gap with a systematic review of past multinational epidemics and proposes an integrative framework. It also provides recommendations for future research and health-crisis management practices.