Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteolysis activation of Cry1Ac and Cry2Ab protoxins by larval midgut juice proteases from Helicoverpa armigera

Proteolytic processing of Bacillus thuringiensis (Bt) Cry protoxins by insect midgut proteases is critical to their insecticidal activities against target insects. Although transgenic Bt cotton expressing Cry1Ac and Cry2Ab proteins have been widely used for control of the cotton bollworm (Helicoverpa armigera) in the field, the proteolytic cleavage sites in the two protoxins targeted by H. armigera midgut proteases are still not clear. In this study, the proteolysis of Cry1Ac and Cry2Ab protoxins by midgut juice prepared from midgut tissue of H. armigera larvae was investigated. Cleavage of Cry1Ac protoxin by midgut proteases formed a major protein fragment of ~65 kDa, and N-terminal sequencing revealed that cleavage occurred at Arg28 in the fore-end of helix α-1 in domain I of Cry1Ac. Cleavage of Cry2Ab protoxin by midgut juice proteases produced a major protein fragment of ~50 kDa, and the cleavage occurred at Arg139 between helices α-3 and α-4 in domain I of Cry2Ab. The amino acids Arg28 of Cry1Ac and Arg139 of Cry2Ab were predicted as putative trypsin cleavage sites. Bioassay data showed that the toxicities (LC50s) of Cry1Ac and Cry2Ab protoxins were equivalent to those of their respective midgut juice-activated toxins in the susceptible SCD strain of H. armigera. Identification of the exact sites of N-terminal activation of Cry1Ac and Cry2Ab protoxins will provide a basis for a better understanding of the mode of action and resistance mechanisms based on aberrant activation of these protoxins in H. armigera.
Static, Dynamic, and Cognitive Fit of Exosystems for the Human Operator

Objective To define static, dynamic, and cognitive fit and their interactions as they pertain to exosystems and to document open research needs in using these fit characteristics to inform exosystem design. Background Initial exosystem sizing and fit evaluations are currently based on scalar anthropometric dimensions and subjective assessments. As fit depends on ongoing interactions related to task setting and user, attempts to tailor equipment have limitations when optimizing for this limited fit definition. Method A targeted literature review was conducted to inform a conceptual framework defining three characteristics of exosystem fit: static, dynamic, and cognitive. Details are provided on the importance of differentiating fit characteristics for developing exosystems. Results Static fit considers alignment between human and equipment and requires understanding anthropometric characteristics of target users and geometric equipment features. Dynamic fit assesses how the human and equipment move and interact with each other, with a focus on the relative alignment between the two systems. Cognitive fit considers the stages of human-information processing, including somatosensation, executive function, and motor selection. Human cognitive capabilities should remain available to process task- and stimulus-related information in the presence of an exosystem. Dynamic and cognitive fit are operationalized in a task-specific manner, while static fit can be considered for predefined postures. Conclusion A deeper understanding of how an exosystem fits an individual is needed to ensure good human–system performance. Development of methods for evaluating different fit characteristics is necessary. Application Methods are presented to inform exosystem evaluation across physical and cognitive characteristics.
Evaluation of the CareStart™ glucose-6-phosphate dehydrogenase (G6PD) rapid diagnostic test in the field settings and assessment of perceived risk from primaquine at the community level in Cambodia

Background Primaquine is an approved radical cure treatment for Plasmodium vivax malaria but treatment can result in life-threatening hemolysis if given to a glucose-6-phosphate dehydrogenase deficient (G6PDd) patient. There is a need for reliable point-of-care G6PD diagnostic tests. Objectives To evaluate the performance of the CareStart™ rapid diagnostic test (RDT) in the hands of healthcare workers (HCWs) and village malaria workers (VMWs) in field settings, and to better understand user perceptions about the risks and benefits of PQ treatment guided by RDT results. Methods This study enrolled 105 HCWs and VMWs, herein referred to as trainees, who tested 1,543 healthy adult male volunteers from 84 villages in Cambodia. The trainees were instructed on G6PD screening, primaquine case management, and completed pre and post-training questionnaires. Each trainee tested up to 16 volunteers in the field under observation by the study staff. Results Out of 1,542 evaluable G6PD volunteers, 251 (16.28%) had quantitative enzymatic activity less than 30% of an adjusted male median (8.30 U/g Hb). There was no significant difference in test sensitivity in detecting G6PDd between trainees (97.21%), expert study staff in the field (98.01%), and in a laboratory setting (95.62%) (p = 0.229); however, test specificity was different for trainees (96.62%), expert study staff in the field (98.14%), and experts in the laboratory (98.99%) (p < 0.001). Negative predictive values were not statistically different for trainees, expert staff, and laboratory testing: 99.44%, 99.61%, and 99.15%, respectively. Knowledge scores increased significantly post-training, with 98.7% willing to prescribe primaquine for P.vivax malaria, an improvement from 40.6% pre-training (p < 0.001). Conclusion This study demonstrated ability of medical staff with different background to accurately use CareStart™ RDT to identify G6PDd in male patients, which may enable safer prescribing of primaquine; however, pharmacovigilance is required to address possible G6PDd misclassifications.
Brain activation during non-habitual speech production: Revisiting the effects of simulated disfluencies in fluent speakers

Over the past decades, brain imaging studies in fluently speaking participants have greatly advanced our knowledge of the brain areas involved in speech production. In addition, complementary information has been provided by investigations of brain activation patterns associated with disordered speech. In the present study we specifically aimed to revisit and expand an earlier study by De Nil and colleagues, by investigating the effects of simulating disfluencies on the brain activation patterns of fluent speakers during overt and covert speech production. In contrast to the De Nil et al. study, the current findings show that the production of voluntary, self-generated disfluencies by fluent speakers resulted in increased recruitment and activation of brain areas involved in speech production. These areas show substantial overlap with the neural networks involved in motor sequence learning in general, and learning of speech production, in particular. The implications of these findings for the interpretation of brain imaging studies on disordered and non-habitual speech production are discussed.
Advancing Diabetes-Related Equity Through Diabetes Self-Management Education and Training: Existing Coverage Requirements and Considerations for Increased Participation

Supplemental Digital Content is Available in the Text. America is in the grips of a diabetes epidemic. Underserved communities disproportionately bear the burden of diabetes and associated harms. Diabetes self-management education and training (DSME/T) may help address the epidemic. By empowering patients to manage their diabetes, DSME/T improves health outcomes and reduces medical expenditures. However, participation in DSME/T remains low. Insurance coverage offers 1 approach for increasing participation in DSME/T. The impact of DSME/T insurance coverage on advancing diabetes-related health equity depends on which types of insurers must cover DSME/T and the characteristics of such coverage. We conducted a legal survey of DSME/T coverage requirements for private insurers, Medicaid programs, and Medicare, finding that substantial differences exist. Although 43 states require that private insurers cover DSME/T, only 30 states require such coverage for most or all Medicaid beneficiaries. Public health professionals and decision makers may find this analysis helpful in understanding and evaluating patterns and gaps in DSME/T coverage.
Isotope Depletion Mass Spectrometry (ID-MS) for accurate mass determination and improved top-down sequence coverage of intact proteins.

Top-down mass spectrometry (MS) is an increasingly important technique for protein characterization. However, in many biological MS experiments, the practicality of applying top-down methodologies is still limited at higher molecular mass. In large part this is due to detrimental effect resulting from the partitioning of the mass spectral signal into an increasing number of isotopic peaks as molecular mass increases. Reducing the isotopologue distribution of proteins via depletion of heavy stable isotopes was first reported over twenty years ago (Marshall, Senko, Li, Li, Dillon, Guan, and Logan. Protein Molecular Mass to 1 Da by 13C, 15N Double-Depletion and FT-ICR Mass Spectrometry, J. Am. Chem. Soc. 1997, 119, 433-434) and has been demonstrated for several small proteins. Here we extend this approach, introducing a new highly efficient method for the production of recombinant proteins depleted in 13C and 15N and demonstrating its advantages for top-down analysis of larger proteins (up to ~50 kDa). FT-ICR MS of isotopically depleted proteins reveal dramatically reduced isotope distributions with the monoisotopic signal observed up to 50 kDa. In top-down fragmentation experiments, the reduced spectral complexity alleviates fragment-ion signal overlap; the presence of monoisotopic signals allows assignment with higher mass accuracy; and the dramatic increase in signal-to-noise ratio (up to 7-fold) permits vastly reduced acquisition times. These compounding benefits allow the assignment of ~3-fold more fragment ions than comparable analyses of proteins with natural isotopic abundances. Finally, we demonstrate greatly increased sequence coverage in time-limited top-down experiments - highlighting advantages for top-down LC-MS/MS workflows and top-down proteomics.
The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

Antimicrobial drugs administered systemically may cause the emergence and dissemination of antimicrobial resistance among enteric bacteria. To develop logical, research-based recommendations for food animal veterinarians, we must understand how to maximize antimicrobial drug efficacy while minimizing risk of antimicrobial resistance. Our objective is to evaluate the effect of two approved dosing regimens of enrofloxacin (a single high dose or three low doses) on Escherichia coli in cattle. We look specifically at bacteria above and below the epidemiological cutoff (ECOFF), above which the bacteria are likely to have an acquired or mutational resistance to enrofloxacin. We developed a differential equation model for the antimicrobial drug concentrations in plasma and colon, and bacteria populations in the feces. The model was fit to animal data of drug concentrations in the plasma and colon obtained using ultrafiltration probes. Fecal E. coli counts and minimum inhibitory concentrations were measured for the week after receiving the antimicrobial drug. We predict that the antimicrobial susceptibility of the bacteria above the ECOFF pre-treatment strongly affects the composition of the bacteria following treatment. Faster removal of the antimicrobial drugs from the colon throughout the study leads to improved clearance of bacteria above the ECOFF in the low dose regimen. If we assume a fitness cost is associated with bacteria above the ECOFF, the increased fitness costs leads to reduction of bacteria above the ECOFF in the low dose study. These results suggest the initial E. coli susceptibility is a strong indicator of how steers respond to antimicrobial drug treatment.
Paths for colonization or exodus? New insights from the brown bear (Ursus arctos) population of the Cantabrian Mountains

Over the centuries, the geographical distribution of brown bear (Ursus arctos) across the Iberian Peninsula has been decreasing, with the species currently confined to North Iberia. The Cantabrian brown bear population is one of the smallest in Europe and is structured into two subpopulations, positioned along an east-west axis. Given the current critically endangered status of this population, it is essential to have a clear picture of its within-population genetic patterns and processes. We use a set of three molecular markers (mitochondrial DNA, autosomal microsatellites and sex markers) to clarify the genetic origins and assess the migration patterns and gene flow of the Cantabrian brown bear population. Our results reveal the presence of two different mitochondrial (matrilineal) haplotypes in the Cantabrian population, both belonging to European brown bear clade 1a. The two haplotypes are geographically structured between Eastern (haplotype CanE) and Western Cantabrian (haplotype CanW) subpopulations, which is consistent with the genetic structure previously identified using nuclear markers. Additionally, we show that CanE is closer to the historical Pyrenean (Pyr) haplotype than to CanW. Despite strong structuring at the levels of mtDNA and nuclear loci, there is evidence of bidirectional gene flow and admixture among subpopulations. Gene flow is asymmetrical and significantly more intense from the Eastern to the Western Cantabrian subpopulation. In fact, we only detected first generation male migrants from the Eastern to the Western Cantabrian subpopulation. These results suggest more intense migration from the smaller and more vulnerable Eastern Cantabrian subpopulation towards the larger and more stable Western Cantabrian subpopulation. These new insights are relevant for assessments of on-going conservation measures, namely the role of dispersal corridors and enhanced connectivity. We discuss the importance of complementary conservation measures, such as human-wildlife conflict mitigation and habitat improvement, for the conservation of a viable Cantabrian brown bear population.
Host-microbiome intestinal interactions during early life: considerations for atopy and asthma development.

PURPOSE OF REVIEW The body's largest microbial community, the gut microbiome, is in contact with mucosal surfaces populated with epithelial, immune, endocrine and nerve cells, all of which sense and respond to microbial signals. These mutual interactions have led to a functional coevolution between the microbes and human physiology. Examples of coadaptation are anaerobes Bifidobacteria and Bacteroides, which have adjusted their metabolism to dietary components of human milk, and infant immune development, which has evolved to become reliant on the presence of beneficial microbes. Current research suggests that specific composition of the early-life gut microbiome aligns with the maturation of host immunity. Disruptions of natural microbial succession patterns during gut colonization are a consistent feature of immune-mediated diseases, including atopy and asthma. RECENT FINDINGS Here, we catalog recent birth cohorts documenting associations between immune dysregulation and microbial alterations, and summarize the evidence supporting the role of the gut microbiome as an etiological determinant of immune-mediated allergic diseases. SUMMARY Ecological concepts that describe microbial dynamics in the context of the host environment, and a portray of immune and neuroendocrine signaling induced by host-microbiome interactions, have become indispensable in describing the molecular role of early-life microbiome in atopy and asthma susceptibility.
Factors associated with tuberculosis-associated haemophagocytic syndrome: a multicentre case-control study.

SETTING: Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.OBJECTIVE: To assess the risk factors associated with HS in patients with TB.DESIGN: We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS-) associated HS.RESULTS: Twenty-one patients with TB/HS+ (24% women, median age, 37 years [IQR 30-48]) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS-), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%; P < 0.001) and to present with disseminated TB (80% vs. 12%; P < 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%; P < 0.001) and a higher risk of death (38% vs. 7%; P = 0.005). CONCLUSION: TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.
Transactivation of Sus1 and Sus2 by Opaque2 is an essential supplement to sucrose synthase‐mediated endosperm filling in maize

Summary The endosperm‐specific transcription factor Opaque2 (O2) acts as a central regulator for endosperm filling, but its functions have not been fully defined. Regular o2 mutants exhibit a non‐vitreous phenotype, so we used its vitreous variety Quality Protein Maize to create EMS‐mutagenesis mutants for screening o2 enhancers (oen). A mutant (oen1) restored non‐vitreousness and produced a large cavity in the seed due to severely depleted endosperm filling. When oen1 was introgressed into inbred W64A with a normal O2 gene, the seeds appeared vitreous but had a shrunken crown. oen1 was determined to encode Shrunken1 (Sh1), a sucrose synthase (SUS, EC 2.4.1.13). Maize contains three SUS‐encoding genes (Sh1, Sus1, and Sus2) with Sh1 contributing predominantly to the endosperm. We determined SUS activity and found a major and minor reduction in oen1 and o2, respectively. In o2;oen1-1, SUS activity was further decreased. We found all Sus gene promoters contain at least one O2 binding element that can be specifically recognized and be transactivated by O2. Sus1 and Sus2 promoters had a much stronger O2 transactivation than Sh1, consistent with their transcript reduction in o2 endosperm. Although sus1 and sus2 alone or in combination had no perceptible phenotype, either of them could dramatically enhance seed opacity and cavity in sh1, indicating that transactivation of Sus1 and Sus2 by O2 supplements SUS‐mediated endosperm filling in maize. Our findings demonstrate that O2 transcriptionally regulates the metabolic source entry for protein and starch synthesis during endosperm filling.
Dietary management of blood glucose in medical critically ill patients with overweight/obesity.

PURPOSE OF REVIEW As the obesity epidemic continues, there is a greater proportion of patients with overweight, obesity, and other forms of adiposity-based chronic disease that require intensive care. Nutrition therapy in the ICU is a vital part of critical care but can be challenging in this setting because of the increased risk of stress hyperglycemia and adverse impact of obesity- and diabetes-related complications. RECENT FINDINGS Current guidelines favor early nutritional therapy with a hypocaloric, high-protein diet in patients with overweight/obesity. More aggressive protein intake may be useful in those with greater severity of overweight/obesity with an upper limit of 3 g/kg ideal body weight per day. Although there is no specific recommendation, choosing enteral formulas with higher fat content and slower digesting carbohydrates may assist with glucose control. Supplementation with immunonutrients is recommended, given their known benefits in obesity and in reducing inflammation, but must be done in an individualized manner. SUMMARY Aggressive nutritional therapy is crucial in patients with overweight/obesity to support ongoing metabolic demands. Although a hypocaloric high-protein feeding strategy is a starting point, nutritional therapy should be approached in an individualized manner taking into account age, weight and BMI, basal metabolism, nutrition status, complications, and comorbidities.
In hospital but not forgotten: an exploration into children and young people’s narratives about their experiences of hospitalisation and hospital school

Today, increasing numbers of children and young people (CYPs) live with chronic health conditions. A fact reflected in recent UK legislation which highlights the necessity of supporting these CYPs to fully access education. This study explores the experiences and perspectives of children and young people with chronic conditions (CYPCCs) regarding hospitalisation and hospital school. A narrative methodology was selected to explore the experiences of five hospitalised CYPCCs (aged 12 to 16 years) in addition to the meanings they ascribed to these experiences. Findings contribute important insights into CYPCCs' experiences of hospitalisation in relation to the following family, personal growth, health-related identity, relationships, coping, unpredictability and uncertainty and medical intervention and physical pain. This research makes a unique contribution to the field, in relation to the substantive topic (how CYPCCs perceive educational experiences in hospital settings) and the original application of a narrative research methodology. I argue the necessity for professionals to recognise CYPCCs as a potentially vulnerable group. Ethical issues concerning access to hospitalised CYPCCs for research purposes are highlighted and the value of narrative research with CYPs is endorsed. Implications for professional practice and research are discussed which seek to improve the educational opportunities, experiences and outcomes for CYPCCs.