bluuebunny/crossref_metadata_2025 huggingface dataset:
Unifying diagnostic criteria for gestational diabetes mellitus
Authors: Doi Suhail A. R. , Bashir Mohammed , Sheehan Michael T. , Onitilo Adedayo A. , Chivese Tawanda , Ibrahim Ibrahim M. , Beer Stephen F. , Furuya-Kanamori Luis , Abou-Samra Abdul-Badi , McIntyre H. David
Published: July 2021

AIMS

Disagreement about the appropriate criteria for the diagnosis of gestational diabetes mellitus (GDM) persists. This study examines an alternative approach which combines information from all time-points on the glucose tolerance test (GTT) into a single index and expands the GDM spectrum into four categories using data from three geographically and ethnically distinct populations.

METHODS

A retrospective observational study design was used. Data from Wisconsin, USA (723 women) was used in derivation of the criterion and data from Doha, Qatar (1284 women) and Cape Town, South Africa (220 women) for confirmation. Pregnant women without pre-existing diabetes with a GTT done between 23 and 30 weeks gestation were included. A novel index was derived from the GTT termed the weighted average glucose (wAG). This was categorized into four pre-defined groups (henceforth National Priorities Research Program (NPRP) criterion); i) normal gestational glycemia (NGG), ii) impaired gestational glycemia (IGG), iii) GDM and iv) high risk GDM (hGDM).

RESULTS

In the Doha cohort, compared to the NGG group, the odds of large for gestational age babies increased 1.33 fold (P=0.432), 2.86 fold (P<0.001) and 3.35 fold (P<0.001) in the IGG, GDM and hGDM groups respectively. The odds of pregnancy induced hypertension increased 2.10 fold (P=0.024) in GDM & hGDM groups compared to the IGG and NGG groups. In the Cape Town cohort, a third of women in the GDM group and two-thirds in the hGDM group progressed to T2DM at 5 years.

CONCLUSIONS

The NPRP categorization identifies four distinct risk clusters of glycemia in pregnancy which may aid better decision making in routine management, avoid potential over-diagnosis of women at lower risk of complications and assist with diabetes prevention in women at high-risk after an index pregnancy with GDM.
The impact of heat on human physical work capacity; part III: the impact of solar radiation varies with air temperature, humidity, and clothing coverage
Authors: Foster Josh , Smallcombe James W , Hodder Simon , Jay Ollie , Flouris Andreas D , Nybo Lars , Havenith George
Published: July 2021

It is well-known that heat impacts human labour/physical work capacity (PWC), but systematic evaluations of solar radiation (SOLAR) effects and the interaction with air temperature and humidity levels and clothing are lacking, as most lab-studies are conducted in semi-nude subjects without radiation or only in a single climatic condition. Due to the high relevance of SOLAR in various occupations, this study quantified how SOLAR interacts with clothing and other primary environmental factors (air temperature/humidity) of importance to determine PWC in the heat. The data allowed the development of a SOLAR correction factor for predicting PWC in major outdoor industries. Fourteen young adult males (7 wearing a standardised work coverall (0.9 Clo), 7 with shorts and trainers (0.3 Clo) walked for 1-hour at a fixed heart rate of 130 b·min−1, in seven combinations of air temperature (25 to 45°C) and relative humidity (20 or 80%), with and without SOLAR (800 W/m2 from solar lamps). Cumulative energy expenditure in the heat, relative to the work achieved in a cool reference condition, was used to determine PWC%. Skin temperature was the primary determinant of PWC in the heat. In dry climates with exposed skin (0.3 Clo), SOLAR caused PWC to decrease exponentially with rising air temperature, whereas work coveralls (0.9 Clo) negated this effect. In humid conditions, the SOLAR-induced reduction in PWC was consistent and linear across all levels of air temperature, and clothing conditions. WBGT and UTCI based prediction equations of PWC represented SOLAR correctly. For heat indices not intrinsically accounting for SOLAR, correction factors are provided enabling forecasting of heat effects on work productivity.
Temporal Gene Expression in Apical Culms Shows Early Changes in Cell Wall Biosynthesis Genes in Sugarcane
Authors: Hosaka Guilherme Kenichi , Correr Fernando Henrique , Silva Carla Cristina , Sforça Danilo Augusto , Barreto Fernanda Zatti , Almeida Balsalobre Thiago Willian , Pasha Asher , de Souza Anete Pereira , Provart Nicholas James , Carneiro Monalisa Sampaio , Margarido Gabriel Rodrigues Alves
Published: July 2021

Multiple genes in sugarcane control sucrose accumulation and the biosynthesis of cell wall components; however, it is unclear how these genes are expressed in its apical culms. To better understand this process, we sequenced mRNA from +1 stem internodes collected from four genotypes with different concentrations of soluble solids. Culms were collected at four different time points, ranging from six to 12-month-old plants. Here we show differentially expressed genes related to sucrose metabolism and cell wall biosynthesis, including genes encoding invertases, sucrose synthase and cellulose synthase. Our results showed increased expression of invertases in IN84-58, the genotype with lower sugar and higher fiber content, as well as delayed expression of secondary cell wall-related cellulose synthase for the other genotypes. Interestingly, genes involved with hormone metabolism were differentially expressed across time points in the three genotypes with higher soluble solids content. A similar result was observed for genes controlling maturation and transition to reproductive stages, possibly a result of selection against flowering in sugarcane breeding programs. These results indicate that carbon partitioning in apical culms of contrasting genotypes is mainly associated with differential cell wall biosynthesis, and may include early modifications for subsequent sucrose accumulation. Co-expression network analysis identified transcription factors related to growth and development, showing a probable time shift for carbon partitioning occurred in 10-month-old plants.
Satellitome comparison of two oedipodine grasshoppers highlights the contingent nature of satellite DNA evolution
Authors: Camacho Juan Pedro M. , Cabrero Josefa , López-León María Dolores , Martín-Peciña María , Perfectti Francisco , Garrido-Ramos Manuel A. , Ruiz-Ruano Francisco J.
Published: July 2021

Background

The full catalogue of satellite DNA (satDNA) within a same genome constitutes the satellitome. The Library Hypothesis predicts that satDNA in relative species reflects that in their common ancestor, but the evolutionary mechanisms and pathways of satDNA evolution have never been analyzed for full satellitomes. We compare here the satellitomes of two Oedipodine grasshoppers (Locusta migratoriaandOedaleus decorus) which shared their most recent common ancestor about 22.8 Ma ago.

Results

We found that about one-third of their satDNA families (near 60 in every species) showed sequence homology and were grouped into 12 orthologous superfamilies. The turnover rate of consensus sequences was extremely variable among the 20 orthologous family pairs analyzed in both species. The satDNAs shared by both species showed poor association with sequence signatures and motives frequently argued as functional, except for short inverted repeats allowing short dyad symmetries and non-B DNA conformations. Orthologous satDNAs frequently showed different FISH patterns at both intra- and interspecific levels. We defined indices of homogenization and degeneration and quantified the level of incomplete library sorting between species.

Conclusions

Our analyses revealed that satDNA degenerates through point mutation and homogenizes through partial turnovers caused by massive tandem duplications (the so-called satDNA amplification). Remarkably, satDNA amplification increases homogenization, at intragenomic level, and diversification between species, thus constituting the basis for concerted evolution. We suggest a model of satDNA evolution by means of recursive cycles of amplification and degeneration, leading to mostly contingent evolutionary pathways where concerted evolution emerges promptly after lineages split.
SPOROS: A pipeline to analyze DISE/6mer seed toxicity
Authors: Bartom Elizabeth T. , Kocherginsky Masha , Paudel Bidur , Vaidyanathan Aparajitha , Haluck-Kangas Ashley , Patel Monal , O’Shea Kaitlyn L. , Murmann Andrea E. , Peter Marcus E.
Published: July 2021

micro(mi)RNAs are (18-22nt long) noncoding short (s)RNAs that suppress gene expression by targeting the 3’ untranslated region of target mRNAs. This occurs through the seed sequence located in position 2-7/8 of the miRNA guide strand, once it is loaded into the RNA induced silencing complex (RISC). G-rich 6mer seed sequences can kill cells by targeting C-rich 6mer seed matches located in genes that are critical for cell survival. This results in induction of Death Induced by Survival gene Elimination (DISE), also referred to as 6mer seed toxicity. miRNAs are often quantified in cells by aligning the reads from small (sm)RNA sequencing to the genome. However, the analysis of any smRNA Seq data set for 6mer seed toxicity requires an advanced workflow, solely based on the exact position 2-7 of any sRNA that can enter the RISC. Therefore, we developed SPOROS, an automated pipeline that produces multiple useful outputs to compare 6mer seed toxicity of all cellular sRNAs, regardless of their nature, between different samples. We provide two examples to illustrate the capabilities of SPOROS: Example one involves the analysis of RISC-bound sRNAs in a cancer cell line (either wild-type or two mutant lines unable to produce most miRNAs). Example two is based on a publicly available smRNA Seq data set from postmortem brains (either from normal or Alzheimer’s patients). Our methods are designed to be used to analyze a variety of smRNA Seq data in various normal and disease settings.
Behavioral origin of sound-evoked activity in mouse visual cortex
Authors: Bimbard Célian , Sit Timothy PH , Lebedeva Anna , Reddy Charu B , Harris Kenneth D , Carandini Matteo
Published: July 2021

Sensory cortices can be affected by stimuli of multiple modalities and are thus increasingly thought to be multisensory. For instance, primary visual cortex (V1) is influenced not only by images but also by sounds. Here we show that the activity evoked by sounds in V1 is highly stereotyped across neurons and even across mice. It resembles activity measured elsewhere in the brain and is independent of projections from auditory cortex. Its low-dimensional nature starkly contrasts the high dimensional code that V1 uses to represent images. Furthermore, this sound-evoked activity can be precisely predicted by small body movements that are elicited by each sound and are highly stereotyped across trials and across mice. Thus, neural activity that is apparently multisensory may simply arise from low-dimensional signals associated with changes in internal state and behavior.
A comparative life cycle analysis of electromicrobial production systems
Authors: Abel Anthony J. , Adams Jeremy D. , Clark Douglas S.
Published: July 2021

Electromicrobial production (EMP) processes represent an attractive strategy for the capture and conversion of CO2 into carbon-based products. We describe the development and application of comprehensive reactor, process, and life cycle impact models to analyze three major EMP systems relying on formate, H2, and acetate as intermediate molecules. Our results demonstrate that EMP systems can achieve a smaller carbon footprint than traditional bioprocessing strategies provided the electric grid is composed of >~90% renewable energy sources. For each of the three products we consider (biomass, enzymes, and lactic acid), the H2-mediated Knallgas bacteria system achieves the lowest overall global warming potential, indicating that this EMP strategy may be best-suited for industrial efforts based on current technology. We also identify environmental hotspots and process limitations that are key sites for future engineering and research efforts for each EMP system. Our analysis demonstrates the utility of an integrated bioelectrochemical model/life cycle assessment framework in both analyzing and aiding the ecodesign of electromicrobial processes and should help guide the design of working, scalable, and sustainable systems.
Living with high potassium: a balance between nutrient acquisition and stress signaling during K-induced salt stress
Authors: Pantha Pramod , Oh Dong-Ha , Longstreth David , Dassanayake Maheshi
Published: July 2021

High potassium (K) in the growth medium is more toxic to plants than Na at similar concentrations. However, the molecular mechanisms underlying plant responses to K-induced salt stress are virtually unknown.

We examined Arabidopsis thaliana and its extremophyte relative Schrenkiella parvula, using a comparative multi-omics approach to identify cellular processes affected by excess K and understand which deterministic regulatory pathways are active to avoid tissue damage while sustaining growth.

A. thaliana showed limited capacity to curb excess K accumulation and prevent nutrient depletion contrasting to S. parvula which could limit excess K accumulation without restricting nutrient uptake. Facilitated by a targeted transcriptomic response, promoting nitrogen uptake along with other key nutrients and uninterrupted N assimilation into primary metabolites during excess K-stress allowed S. parvula to boost its antioxidant and osmolyte pools concurrently leading to sustained growth. Antithetically, A. thaliana showed transcriptional responses indicative of a poor balance between stress signaling, increased ROS levels, and reduced photosynthesis, subsequently leading to inhibited growth.

The ability to regulate independent nutrient uptake and a coordinated transcriptomic response to avoid non-specific stress signaling are two main deterministic steps towards building stress resilience to excess K+-induced salt stress.
Identifying Site-specific Superoxide and Hydrogen Peroxide Production Rates from the Mitochondrial Electron Transport System Using a Computational Strategy
Authors: Duong Quynh V. , Levitsky Yan , Dessinger Maria J. , Bazil Jason N.
Published: July 2021

Mitochondrial reactive oxygen species (ROS) play important roles in cellular signaling; however, certain pathological conditions such as ischemia/reperfusion (I/R) injury disrupt ROS homeostasis and contribute to cell death. A major impediment to developing therapeutic measures against oxidative stress induced cellular damage is the lack of a quantitative framework to identify the specific sources and regulatory mechanisms of mitochondrial ROS production. We developed a thermodynamically consistent, mass-and-charge balanced, kinetic model of mitochondrial ROS homeostasis focused on redox sites of electron transport chain complexes I, II, and III. The model was calibrated and validated using comprehensive data sets relevant to ROS homeostasis. The model predicts that complex I ROS production dominates other sources under conditions favoring a high membrane potential with elevated NADH and QH2 levels. In general, complex I contributes to significant levels of ROS production under pathological conditions, while complexes II and III are responsible for basal levels of ROS production, especially when QH2 levels are elevated. The model also reveals that hydrogen peroxide production by complex I underlies the non-linear relationship between ROS emission and O2 at low O2 concentrations. Lastly, the model highlights the need to quantify scavenging system activity under different conditions to establish a complete picture of mitochondrial ROS homeostasis. In summary, we describe the individual contributions of the ETS complex redox sites to total ROS emission in mitochondria respiring under various combinations of NADH- and Q-linked respiratory fuels under varying work rates.
RGEN-SEQ FOR HIGHLY SENSITIVE AMPLIFICATION-FREE SCREEN OF OFF-TARGET SITES OF GENE EDITORS
Authors: Kuzin Alexander , Redler Brendan , Onuska Jaya , Slesarev Alexei
Published: July 2021

Abstract

Sensitive detection of off-target sites produced by gene editing nucleases is crucial for developing reliable gene therapy platforms. Although several biochemical assays for the characterization of nuclease off-target effects have been recently published, they still leave plenty of room for improvement. Here we describe a sensitive, PCR-free next-generation sequencing method (RGEN-seq) for unbiased detection of double-stranded breaks generated by RNA-guided CRISPR-Cas9 endonuclease. The method is extremely simple, and it is on a par or even supersedes in sensitivity existing assays without reliance on amplification steps. The latter saves time, simplifies workflow, and removes genomic coverage bias and gaps associated with PCR and/or other enrichment procedures. RGEN-seq is fully compatible with existing off-target detection software; moreover, the unbiased nature of RGEN-seq offers a robust foundation for relating assigned DNA cleavage scores to propensity for off-target mutations in cells. A detailed comparison of RGEN-seq with other off-target detection methods is provided using a previously characterized set of guide RNAs.
An Automated SNP-Based Approach for Contaminant Identification in Biparental Polyploid Populations of Tropical Forage Grasses
Authors: Martins Felipe Bitencourt , Moraes Aline da Costa Lima , Aono Alexandre Hild , Ferreira Rebecca Caroline Ulbricht , Chiari Lucimara , Simeão Rosangela Maria , Barrios Sanzio Carvalho Lima , Santos Mateus Figueiredo , Jank Liana , do Valle Cacilda Borges , Vigna Bianca Baccili Zanotto , de Souza Anete Pereira
Published: July 2021

Artificial hybridization plays a fundamental role in plant breeding programs since it generates new genotypic combinations that can result in desirable phenotypes. Depending on the species and mode of reproduction, controlled crosses may be challenging, and contaminating individuals can be introduced accidentally. In this context, the identification of such contaminants is important to avoid compromising further selection cycles, as well as genetic and genomic studies. The main objective of this work was to propose an automated multivariate methodology for the detection and classification of putative contaminants, including apomictic clones, self-fertilized individuals, half-siblings and full contaminants, in biparental polyploid progenies of tropical forage grasses. We established a pipeline to identify contaminants in genotyping-by-sequencing (GBS) data encoded as allele dosages of single nucleotide polymorphism (SNP) markers by integrating principal component analysis (PCA), genotypic analysis (GA) measures based on Mendelian segregation and clustering analysis (CA). The combination of these methods allowed the correct identification of all contaminants in all simulated progenies and the detection of putative contaminants in three real progenies of tropical forage grasses, providing an easy and promising methodology for the identification of contaminants in biparental progenies of tetraploid and hexaploid species. The proposed pipeline was made available through the polyCID Shiny app and can be easily coupled with traditional genetic approaches, such as linkage map construction, thereby increasing the efficiency of breeding programs.
Knockdown of astrocytic monocarboxylate transporter 4 (MCT4) in the motor cortex leads to loss of dendritic spines and a deficit in motor learning
Authors: Lundquist Adam J. , Llewellyn George N. , Kishi Susan H. , Jakowec Nicolaus A. , Cannon Paula M. , Petzinger Giselle M. , Jakowec Michael W.
Published: July 2021

Monocarboxylate transporters (MCTs) shuttle molecules, including L-lactate, involved in metabolism and cell signaling of the central nervous system. Astrocyte-specific MCT4 is a key component of the astrocyte-neuron lactate shuttle (ANLS) and is important for neuroplasticity and learning of the hippocampus. However, the importance of astrocyte-specific MCT4 in neuroplasticity of the M1 primary motor cortex remains unknown. In this study, we investigated astrocyte-specific MCT4 in motor learning and neuroplasticity of the M1 primary motor cortex using a cell-type specific shRNA knockdown of MCT4. Knockdown of astrocyte-specific MCT4 resulted in impaired motor performance and learning on the accelerating rotarod. In addition, MCT4 knockdown was associated with a reduction of neuronal dendritic spine density and spine width and decreased protein expression of PSD95 and Arc. Using near-infrared-conjugated 2-deoxyglucose uptake as a surrogate marker for neuronal activity, MCT4 knockdown was also associated with decreased neuronal activity in the M1 primary motor cortex and associated motor regions including the dorsal striatum and ventral thalamus. Our study supports a potential role for astrocyte-specific MCT4 and the ANLS in the neuroplasticity of the M1 primary motor cortex. Targeting MCT4 may serve to enhance neuroplasticity and motor repair in several neurological disorders, including Parkinson’s disease and stroke.
Phenogenomic characterization of a newly domesticated and novel species from the genus Verrucosispora
Authors: Kennedy Sarah , Atkinson Celine , Tomlinson Brooke , Hammond Lauren , Eswara Prahathees J. , Baker Bill J , Shaw Lindsey N.
Published: July 2021

The concept of bacterial dark matter stems from our inability to culture most microbes and represents a fundamental hole in our knowledge of microbial diversity. Herein we present the domestication of such an organism: a previously uncultured, novel species from the rare-Actinomycetes genus Verrucosispora. Although initial recovery took >4 months, isolation of phenotypically distinct, domesticated generations occurred within weeks. Two isolates were subjected to phenogenomic analyses, revealing domestication correlated with enhanced growth rates in nutrient-rich media, but diminished capacity to metabolize diverse amino acids. This is seemingly mediated by genomic decay through the pseudogenization of amino acids metabolism genes. Conversely, later generational strains had enhanced spore germination rates, potentially through the reversion of a sporulation-associated kinase from pseudogene to true gene status. We observed that our most wild-type isolate had the greatest potential for antibacterial activity, which correlated with extensive mutational attrition of biosynthetic gene clusters in domesticated strains. Comparative analyses revealed wholesale genomic reordering in strains, with widespread SNP, indel and pseudogene mutations observed. We hypothesize that domestication of this previously unculturable organism resulted from the shedding of genomic flexibility required for life in a dynamic marine environment, parsing out genetic redundancy to allow for a newfound cultivable amenability.
Broad-scale variation in human genetic diversity levels is predicted by purifying selection on coding and non-coding elements
Authors: Murphy David , Elyashiv Eyal , Amster Guy , Sella Guy
Published: July 2021

Analyses of genetic variation in many taxa have established that neutral genetic diversity is shaped by natural selection at linked sites. Whether the mode of selection is primarily the fixation of strongly beneficial alleles (selective sweeps) or purifying selection on deleterious mutations (background selection) remains unknown, however. We address this question in humans by fitting a model of the joint effects of selective sweeps and background selection to autosomal polymorphism data from the 1000 Genomes Project. After controlling for variation in mutation rates along the genome, a model of background selection alone explains ∼60% of the variance in diversity levels at the megabase scale. Adding the effects of selective sweeps driven by adaptive substitutions to the model does not improve the fit, and when both modes of selection are considered jointly, selective sweeps are estimated to have had little or no effect on linked neutral diversity. The regions under purifying selection are best predicted by phylogenetic conservation, with ∼80% of the deleterious mutations affecting neutral diversity occurring in non-exonic regions. Thus, background selection is the dominant mode of linked selection in humans, with marked effects on diversity levels throughout autosomes.
A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine
Authors: Löken Line S. , Wasling Helena Backlund , Olausson Håkan , McGlone Francis , Wessberg Johan
Published: July 2021

Numerous microneurography studies in the human peroneal nerve have suggested that CT afferents are lacking in the more distal parts of the limbs. Here we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves, with the most distal receptive fields located on the proximal phalanx of the third finger for the superficial branch of the radial nerve, and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial, radial and peroneal nerves. Moreover, we found that while CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared to C nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, including a lack of responsiveness to heat, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.
Interplay between BALL and CBP maintains H3K27 acetylation on active genes in Drosophila
Authors: Haider Farooq Khan Muhammad , Shaukat Ammad , Umer Zain , Ahmad Hina , Tariq Muhammad
Published: July 2021

CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In Drosophila, CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in Drosophila. Here, we report direct interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.
The role of pro- and antiangiogenic factors in angiogenesis process by Raman spectroscopy
Authors: Kopec M. , Abramczyk H.
Published: July 2021

Raman spectroscopy and Raman imaging are powerful techniques to monitor biochemical composition around blood vessel. The aim of this study was to understand the role of pro- and antiangiogenic factors in angiogenesis process. Raman imaging and Raman single spectrum measurements allow the diagnosis of cancer biochemical changes in blood vessel based on several biomarkers simultaneously. We have demonstrated that Raman imaging combined with statistical methods are useful to monitoring pro- and antiangiogenic factors responsible for angiogenesis process. In this paper Raman markers of proangiogenic and antiangiogenic factors were identified based on their vibrational signatures. Obtained results can help understand how growing tumor create its vascular system.

Graphical Abstract
Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status
Authors: Langton Paul F. , Baumgartner Michael E. , Logeay Remi , Piddini Eugenia
Published: July 2021

Cell competition induces the elimination of less-fit “loser” cells by fitter “winner” cells. In Drosophila, cells heterozygous mutant in ribosome genes, Rp/+, known as Minutes, are eliminated via cell competition by wild-type cells. Rp/+ cells display proteotoxic stress and the oxidative stress response, which drive the loser status. Minute cell competition also relies on the activities of the transcription factors Irbp18 and Xrp1, however how these contribute to the loser status is partially understood. Here, we show that Irbp18 and Xrp1 induce the loser status by promoting proteotoxic stress. We find that Xrp1 is necessary for Rp/+ - induced proteotoxic stress and is sufficient to induce proteotoxic stress in otherwise wild-type cells. Xrp1 is also induced downstream of proteotoxic stress and required for the competitive elimination of cells suffering from proteotoxic stress. Our data suggests that a feed-forward loop between Xrp1, proteotoxic stress, and Nrf2 drives Minute cells to become losers.
Knockout of Anopheles stephensi immune gene LRIM1 by CRISPR-Cas9 reveals its unexpected role in reproduction and vector competence
Authors: Inbar Ehud , Eappen Abraham , Alford Robert T , Reid William , Harrell Robert A , Hosseini Maryam , Chakravarty Sumana , Li Tao , Sim B. Kim Lee , Billingsley Peter F , Hoffman Stephen L
Published: July 2021

PfSPZ Vaccine against malaria is composed of Plasmodium falciparum (Pf) sporozoites (SPZ) manufactured using aseptically reared Anopheles stephensi mosquitoes. Immune response genes of Anopheles mosquitoes such as Leucin-Rich protein (LRIM1), inhibit Plasmodium SPZ development (sporogony) in mosquitoes by supporting melanization and phagocytosis of ookinetes. With the aim of increasing PfSPZ infection intensities, we generated an A. stephensi LRIM1 knockout line , Δaslrim1 , by embryonic genome editing using CRISPR-Cas9. Δaslrim1 mosquitoes had a significantly increased midgut bacterial load and an altered microbiome composition, including elimination of commensal acetic acid bacteria.  The alterations in the microbiome caused increased mosquito mortality and unexpectedly, significantly reduced sporogony. The survival rate of Δaslrim1 and their ability to support PfSPZ development, were partially restored by antibiotic treatment of the mosquitoes, and fully restored to baseline when Δaslrim1 mosquitoes were produced aseptically. Deletion of LRIM1 also affected reproductive capacity: oviposition, fecundity and male fertility were significantly compromised. Attenuation in fecundity was not associated with the altered microbiome. This work demonstrates that LRIM1’s regulation of the microbiome has a major impact on vector competence and longevity of A. stephensi. Additionally, LRIM1 deletion identified an unexpected role for this gene in fecundity and reduction of sperm transfer by males.
Maturational indices of the cognitive control network are associated with inhibitory control in early childhood
Authors: Berger Philipp , Friederici Angela D. , Wiesmann Charlotte Grosse
Published: July 2021

Goal-directed behavior crucially relies on our capacity to suppress impulses and predominant behavioral responses. This ability, called inhibitory control, emerges in early childhood with marked improvements between 3 and 4 years. Here, we ask which brain structures are related to the emergence of this critical ability. Using a multimodal approach, we relate the pronounced behavioral improvements in different facets of 3-and 4-year-olds’ (N = 37, 20 female) inhibitory control to structural indices of maturation in the developing brain assessed with MRI. Our results show that cortical and subcortical structure of core regions in the adult cognitive control network, including the PFC, thalamus, and the inferior parietal cortices, are associated with early inhibitory functioning in preschool children. Probabilistic tractography revealed an association of frontoparietal (i.e., the superior longitudinal fascicle) and thalamocortical connections with early inhibitory control. Notably, these associations to brain structure were distinct for different facets of early inhibitory control, often referred to as motivational (‘hot’) and cognitive (‘cold’) inhibitory control. Our findings thus reveal the structural brain networks and connectivity related to the emergence of this core faculty of human cognition.

Significance Statement

The capacity to suppress impulses and behavioral responses is crucial for goal-directed behavior. This ability, called inhibitory control, develops between the ages of 3 and 4 years. The factors behind this developmental milestone have been debated intensely for decades, however, the brain structure that underlies the emergence of inhibitory control in early childhood is largely unknown. Here, we relate the pronounced behavioral improvements in inhibitory control between 3 and 4 years with structural brain markers of grey matter and white matter maturation. Using a multimodal approach that combines analyses of cortical surface structure, subcortical structures, and white matter connectivity, our results reveal the structural brain networks and connectivity related to this core faculty of human cognition.
Allergy-induced systemic inflammation impairs tendon quality
Authors: Lehner Christine , Spitzer Gabriel , Langthaler Patrick , Jakubecova Dominika , Klein Barbara , Weissenbacher Nadja , Wagner Andrea , Gehwolf Renate , Trinka Eugen , Iglseder Bernhard , Paulweber Bernhard , Aigner Ludwig , Couillard-Després Sebastien , Weiss Richard , Tempfer Herbert , Traweger Andreas
Published: July 2021

Treatment of tendinopathies still present a major challenge, since the aetiology of the disease remains poorly understood. To determine whether the systemic inflammation accompanying predisposing factors including rheumatoid arthritis, diabetes or smoking contributes to the onset of tendinopathy, we studied the effect of a systemic inflammation induced by an allergic episode on tendon properties. To this end, we elicited an allergic response in mice by exposing them to a plant allergen and subsequently analysed both their flexor and Achilles tendons. Biomechanical testing and histological analysis revealed that tendons from allergic mice not only showed a significant reduction of both elastic modulus and tensile stress, but also alterations of the tendon matrix. Moreover, 3D tendon-like constructs treated with sera from allergic mice displayed a matrix-remodelling expression profile and the expression of macrophage-associated markers and matrix metalloproteinase 2 (MMP2) was increased in allergic Achilles tendons. Analysing data from an epidemiologic study comprising data from more than 10.000 persons, we found that persons suffering from an allergic condition appeared to have an increased propensity to develop a tendinopathy.

Graphical abstract
Accurately positioning functional residues with robotics-inspired computational protein design
Authors: Krivacic Cody , Kundert Kale , Pan Xingjie , Pache Roland A. , Liu Lin , Conchúir Shane O , Jeliazkov Jeliazko R. , Gray Jeffrey J. , Thompson Michael C. , Fraser James S. , Kortemme Tanja
Published: July 2021

Accurate positioning of functional residues is critical for the design of new protein functions, but has remained difficult because of the prevalence of irregular local geometries in active sites. Here we introduce two computational methods that build local protein geometries from sequence with atomic accuracy: fragment kinematic closure (FKIC) and loophash kinematic closure (LHKIC). FKIC and LHKIC integrate two approaches: robotics-inspired kinematics of protein backbones and insertion of peptide fragments, and show up to 140-fold improvements in native-like predictions over either approach alone. We then integrate these methods into a new design protocol, pull-into-place (PIP), to position functionally important sidechains via design of new structured loop conformations. We validate PIP by remodeling a sizeable active site region in an enzyme and confirming the engineered new conformations of two designs with crystal structures. The described methods can be applied broadly to the design of many new protein geometries and functions.
Why amyloid fibrils have a limited width
Authors: Boyer David R. , Mynhier Nikos A. , Sawaya Michael R.
Published: July 2021

Amyloid fibrils can grow indefinitely long by adding protein chains to the tips of the fibril through β-sheet hydrogen bonding; however, they do not grow laterally beyond ∼10-20 nm. This prevents amyloid fibrils from growing into two-dimensional or three-dimensional arrays. The forces that restrict lateral association of β-sheets in amyloid fibrils are not immediately apparent. We hypothesize that it is the helical symmetry of amyloid fibrils that imposes the limit on fibril width by incurring an increasing separation between helically related molecules as a function of radial distance from the helical axis. The unavoidable consequence is that backbone hydrogen bonds that connect symmetrically related layers of the fibril become weaker towards the edge of the fibril, ultimately becoming too weak to remain ordered. To test our hypothesis, we examined 57 available cryo-EM amyloid fibril structures for trends in interstrand distance and β-sheet hydrogen bonding as a function of radial distance from the helical axis. We find that all fibril structures display an increase in interstrand distance as a function of radius and that most fibril structures have a discernible increase in β-sheet hydrogen bond distances as a function of radius. In addition, we identify a high resolution cryo-EM structure that does not follow our predicted hydrogen bonding trends and perform real space refinement with hydrogen bond distance and angle restraints to restore predicted hydrogen bond trends. This highlights the potential to use our analysis to ensure realistic hydrogen bonding in amyloid fibrils when atomic resolution cryo-EM maps are not available.

Significance Statement

The number of amyloid fibril structures determined has exploded in recent years due to advances in structural biology techniques. However, we are still at the beginning stages of understanding amyloid fibril assembly. One important property that is critical to fibril formation and mechanical properties is the fibril width. Despite the diversity of fibril folds discovered, all amyloid fibrils are constrained to a width of 10-20 nm. Here, we use simple geometry and structural analysis to identify that the limited width of amyloid fibrils arises from the helical twist of β-sheets in amyloid fibrils. Our findings provide important considerations for the accurate modeling of hydrogen bonds in amyloid fibrils as well as for the possible prediction and design of amyloid-based nanomaterials.
Firm performance implications of supply chain integration, agility and innovation in agri-businesses: evidence from an emergent economy
Authors: Aggrey George Augustus Benjamin , Kusi Lawrence Yaw , Afum Ebenezer , Osei-Ahenkan Victoria Yaa , Norman Christine , Boateng Kenneth Boateng , Amponsah Owusu Joseph
Published: July 2021

Purpose

This study empirically examines the effect of supply chain integration (SCI) on financial performance (FP) and controls for the mediating effects of supply chain agility (SCA), supply chain (SC) innovation and operational performance (OP).

Design/methodology/approach

Through a causal research design, structured questionnaires were used for primary data collection from 217 commercial poultry farms (CPFs) operating in the Bono Region of Ghana. Structural equation modeling was reflectively configured to test the formulated hypotheses.

Findings

SCI causes a statistically significant moderate positive variance in OP in terms of cost-effectiveness, order fulfillment rate, operating cycle, inventory turns, business process innovation. SCI is an insignificant weak positive predictor of FP (growth in revenue, profit, return on investment, sales growth) of CPFs operating in Ghana. Furthermore, OP significantly and positively mediates the predictive relationship between SCI and FP. Again, SC innovation significantly mediates the predictive relationship between SCI and OP. However, SCA fails to significantly mediate the predictive relationship between SCI and OP.

Research limitations/implications

Focal firms' characteristics were ignored, although they may determine how SCI affects OP and FP in the presence of SCA and SC innovation.

Originality/value

Empirically, SCI has no direct impact on FP of CPFs but does so indirectly through the mediating role of OP.
Video storytelling ads vs argumentative ads: how hooking viewers enhances consumer engagement
Authors: Coker Kesha K. , Flight Richard L. , Baima Dominic M.
Published: July 2021

Purpose

Digital engagement with advertising remains challenging for marketers. This research examines “being hooked” as the mechanism of narrative transportation associated with digital video storytelling ads. Its purpose is to examine the efficacy of digital video ad format (storytelling vs argumentative) in hooking viewers (i.e. grabbing attention and interest in the ad). This research also presents a conceptual model of the effect of being hooked on digital engagement with advertising.

Design/methodology/approach

This study employs a quasi-experimental research design with a final sample of 273 undergraduate students. It tests the hypothesis that digital video storytelling ads hook viewers more effectively than argumentative ads do. It also tests a conceptual model of the positive effect of being hooked on digital engagement with advertising.

Findings

Digital video storytelling ads hook viewers more effectively than argumentative ads do. SEM analysis shows that being hooked positively impacts intentions to view, share, promote and spread positive word of mouth. Attitude toward the ad partially mediates the relationship between being hooked and intentions to promote and spread positive word of mouth.

Research limitations/implications

Findings are applicable to target audience profiles that match the sample in this study. Despite this and other limitations, findings advance theory on the process underlying digital video storytelling advertising effects on consumer engagement.

Practical implications

Marketers are advised to invest in more digital video storytelling than argumentative ads. In doing so, marketers are more likely to hook viewers on the ad, thereby generating positive digital engagement with advertising.

Originality/value

This research focuses on attention and interest dimensions of narrative transportation as measured by “being hooked.” It also extends past models of narrative transportation by including more representative measures of digital engagement with advertising.
Production planning, monitoring and review: comparison between the practices in an urban rail transit megaproject with the Last Planner System
Authors: Belayutham Sheila , Mohamad Jaafar Rabiatul Nurul Akmar , Ismail Herda Balqis , Che Ibrahim Che Khairil Izam
Published: July 2021

Purpose

Megaprojects are typically very expensive public-centred projects that leave little space for any mismanagement or deficient planning, which could affect the project adversely. The Last Planner™ System (LPS) is a lean construction planning and control tool that functions to reduce waste and increase performance. Given the benefits, the application of the LPS in megaprojects is still scarce, especially in Malaysia. Hence, this study aims to compare the current production planning, monitoring and review practices in a megaproject with the LPS in order to explore the possibilities of adapting the LPS to the current practices.

Design/methodology/approach

This longitudinal case-based study has first explored the current practices implemented in an infrastructure megaproject, which is an urban rapid transit (URT) project, which was then compared to the standard LPS practices. The case study has adopted several research methods such as observation, interview and document review.

Findings

Findings from the study highlight that the current production planning, monitoring and review practices in the URT project mostly differs from the standard LPS practices with only slight similarities found in the major planning phases. The comparative study, which based on five reference points through master, phase, look-ahead, weekly work plan and measure, and learning has resulted in several key elements, representative of the different planning phases, such as collaborative programming, reverse planning, reliability, dependability and continuous learning.

Practical implications

This study provides an alternative perspective to rail planners, as well as other types of project planners in considering the use of the LPS to enhance the quality of planning, monitoring and review in projects. The framework that highlights the core values and key elements for the related planning phases enables project teams with no lean background to partially adapt their current practices to the LPS with minimal disruption.

Originality/value

This study first contributes to the body of knowledge, where limited study was found comparing and contrasting current production planning practices against the LPS, particularly in rail-based megaproject. The results from the comparison are the key elements representing each of the planning phases that was rooted back to the core values (teamwork, involvement and collaboration, communication and transparency, and continuous improvement) necessary to enhance the current practices.
The assessment of the impact of induction spatial effects on magnetic flux measurements of toner‐printed documents to the detection of forged or altered documents
Authors: Polston Carrie , Thompson David , Buzzini Patrick
Published: July 2021

Magnetic flux measurements of toners can aid in the rapid differentiation of toner‐printed specimens in the context of investigations of forgeries or alterations of printed documents. However, some variables that may impact magnetic flux measurements, including hysteresis effects, are not currently well understood. This study assessed the impact of hysteresis and other induction spatial effects on magnetic flux measurements of toners analyzing five toner‐printed samples produced from different devices. The samples were printed with controlled grids of square, rectangular, and elongated rectangular blocks with the same area. Thirty measurements were conducted on each sample, on each grid type. The measurements were repeated in planes of rotation 90°, 180°, and 270° counter to this original position. The values obtained for the square grids were evaluated using one‐way ANOVA to assess the presence and impact of hysteresis effects. The values obtained for the rectangular grids were compared with those obtained for the square grids using a two‐way ANOVA to determine potential induction current orientation effects. The results of both one‐way and two‐way ANOVA were significant withp < 0.05, indicating that both hysteresis effects and induction current spatial effects contribute significantly to variations in magnetic flux measurements. Results confirmed that sensor orientation is an important factor that must be accounted for in method protocols for the measurement of magnetic flux of toners. Controlling these variables is a step forward toward the development of a reliable screening method to be deployed in the context of investigations of document forgeries or alterations.