bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractLeishmaniaare 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

AbstractNeural 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

AbstractPartial 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

ABSTRACTThe 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

AbstractA 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 StatementA 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

ABSTRACTAnopheles 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

AbstractThe 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

AbstractMost 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.ImportanceMastitis 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

AbstractThis 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.
Integrated reporting, textual risk disclosure and market value
Authors: Elshandidy Tamer , Elmassri Moataz , Elsayed Mohamed 
Published: September 2021

PurposeExploiting 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/approachArchival data are collected and examined using time-series difference design and difference-in-differences design.FindingsThe 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/valueCollectively, 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

PurposeThe 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/approachFirst, 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.FindingsThe 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/implicationsThis 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/valueA 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.