Consequences of pollen defense compounds for pollinators and antagonists in a pollen-rewarding plant.

Plants produce an array of defensive compounds with toxic or deterrent effects on insect herbivores. Pollen can contain relatively high concentrations of such defense compounds, but the causes and consequences of this enigmatic phenomenon remain mostly unknown. These compounds could potentially protect pollen against antagonists but could also reduce flower attractiveness to pollinators. We combined field observations of the pollen-rewarding Lupinus argenteus with chemical analysis and laboratory assays to test three hypotheses for the presence of pollen defense compounds: (1) these compounds are the result of spillover from adjacent tissues, (2) they protect against pollen thieves, and (3) they act as antimicrobial compounds. We also tested whether pollen defense compounds affect pollinator behavior. We found a positive relationship between alkaloid concentrations in pollen and petals, supporting the idea that pollen defense compounds partly originate from spillover. However, pollen and petals exhibited quantitatively (but not qualitatively) distinct alkaloid profiles, suggesting that plants can adjust pollen alkaloid composition independently from that of adjacent tissues. We found no relationship between pollen alkaloid concentration and the abundance of pollen thieves in Lupinus flowers. However, pollen alkaloids were negatively associated with bacterial abundance. Finally, plants with more alkaloids in their pollen received more pollinator visits, but these visits were shorter, resulting in no change in the overall number of flowers visited. We propose that pollen defense compounds are partly the result of spillover from other tissues, while they also play an antimicrobial role. The absence of negative effects of these compounds on pollinator visitation likely allows their maintenance in pollen at relatively high concentrations. Taken together, our results suggest that pollen alkaloids affect and are mediated by the interplay of multiple interactions.

Acute death as a result of poisoning tropical (Bos taurus indicus) but not temperate (Bos taurus taurus) cattle after oral dosing with Lupinus leucophyllus (velvet lupine).

Due to climate change and increasing summer temperatures, tropical cattle may graze where temperate cattle have grazed, exposing tropical cattle to toxic plants they may be unfamiliar with. This work compared the toxicity of Lupinus leucophyllus (velvet lupine) in temperate and tropical cattle. Orally dosed velvet lupine in tropical cattle caused death. If producers opt to graze tropical cattle, additional care must be taken on rangelands where toxic lupines like velvet lupine grow.

Severus: accurate detection and characterization of somatic structural variation in tumor genomes using long reads.

Most current studies rely on short-read sequencing to detect somatic structural variation (SV) in cancer genomes. Long-read sequencing offers the advantage of better mappability and long-range phasing, which results in substantial improvements in germline SV detection. However, current long-read SV detection methods do not generalize well to the analysis of somatic SVs in tumor genomes with complex rearrangements, heterogeneity, and aneuploidy. Here, we present Severus: a method for the accurate detection of different types of somatic SVs using a phased breakpoint graph approach. To benchmark various short- and long-read SV detection methods, we sequenced five tumor/normal cell line pairs with Illumina, Nanopore, and PacBio sequencing platforms; on this benchmark Severus showed the highest F1 scores (harmonic mean of the precision and recall) as compared to long-read and short-read methods. We then applied Severus to three clinical cases of pediatric cancer, demonstrating concordance with known genetic findings as well as revealing clinically relevant cryptic rearrangements missed by standard genomic panels.

Practical Synthesis of 6-Amino-1-hydroxy-2,1-benzoxaborolane: A Key Intermediate of DNDI-6148.

Visceral leishmaniasis (VL), a parasitic, poverty-linked, neglected disease, is endemic across multiple regions of the world and fatal if untreated. There is an urgent need for a better and more affordable treatment for VL. DNDI-6148 is a promising drug candidate being evaluated for the treatment of VL; however, the current process for producing the key intermediate of DNDI-6148, 6-amino-1-hydroxy-2,1-benzoxaborolane, is expensive and difficult to scale up. Herein, we describe two practical approaches to synthesizing 6-amino-1-hydroxy-2,1-benzoxaborolane from inexpensive and readily available raw materials. Starting with 4-tolunitrile, the first approach is a five-step sequence involving a Hofmann rearrangement, resulting in an overall yield of 40%. The second approach utilizes 2-methyl-5-nitroaniline as the starting material and features borylation of aniline and continuous flow hydrogenation as the key steps, with an overall yield of 46%. Both routes bypass the nitration of 1-hydroxy-2,1-benzoxaborolane, which is challenging and expensive to scale. In particular, the second approach is more practical and scalable because of the mild operating conditions and facile isolation process.

Providing rigor in bee colony strength auditing methods.

The primary method used to audit honey bee (Apis mellifera Linnaeus, 1758 [Hymenoptera: Apidae]) colony strength for almond pollination services, Nasr et al.'s (1990) frame-top cluster count method, is a subjective visual audit that relies on an auditor's spot assessment and may lack rigor and repeatability. We created novel, open-source software for the analysis of frame-top cluster count photographic assessments to improve methodological rigor and repeatability. We evaluated 2 existing visual audit methods, created 3 novel audit method variations, and determined between-method conversion factors using linear modeling. The software has potential applications in apiological research, apiarist and orchardist colony auditing, as well as training future generations of apiarists in auditing techniques. The software enhances the rigor and repeatability of Nasr et al.'s (1990) frame-top cluster count population assessment. In this article, we introduce the novel open-source software and between-method regression equations and review the tested visual assessment methods and their application.

An investigation of the antimicrobial efficacy of a nonwoven CMC PHMB dressing and the ability of the dressing to absorb wound slough.

OBJECTIVE: To conduct an in vitro investigation into the slough absorption and retention attributes of a gelling fiber dressing composed of CMC fibers and PHMB (Dressing A), and to assess its antimicrobial efficacy under compression. MATERIALS AND METHODS: Dressing A is indicated for use with secondary dressings or bandaging, and conditions that replicate this compression element were applied. Dressing A was compared with 5 other dressings. Antimicrobial efficacy testing was conducted over a 7-day challenge period. RESULTS: Dressing A absorbed an average of 33 g/100 cm2 per sample of viscous solution, 28% more than the other dressings tested. A greater than or equal to 6-log reduction of all microorganisms tested was achieved within 168 hours with Dressing A. CONCLUSION: The CMC PHMB gelling fiber dressing is able to absorb and retain viscous solutions (simulated slough). The antimicrobial efficacy of the dressing under compression was demonstrated by total eradication of all microorganisms tested.

Ruminant metabolism of zygacine, the major toxic alkaloid in foothill death camas (Zigadenuspaniculatus).

Death Camas (Zigadenus spp.) are common poisonous plants distributed throughout North America. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. Both cattle and sheep can be poisoned by grazing death camas, however, sheep consume death camas more readily and are most often poisoned. We hypothesized that the presence of enzymes, including esterases present in the rumen, liver, and blood of livestock would metabolize zygacine. The objective of this study was to investigate the metabolism of zygacine in sheep and cattle using in-vitro and in-vivo systems. Results from experiments where zygacine was incubated in rumen culture, plasma, liver S9 fractions, and liver microsomes and from the analysis of rumen and sera from sheep and cattle dosed death camas plant material demonstrated that zygacine is metabolized to zygadenine in the rumen, liver and blood of sheep and cattle. The results from this study indicate that diagnosticians should analyze for zygadenine, and not zygacine, in the rumen and sera for the diagnosis of livestock suspected to have been poisoned by foothill death camas.

Identification and distribution of a fungal endosymbiotic Alternaria species (Alternaria section Undifilum sp.) in Astragalus garbancillo tissues.

Plants belonging to the genera Astragalus, Oxytropis, Ipomoea, Sida, and Swainsona often contain the toxin swainsonine (SW) produced by an associated fungal symbiont. Consumption of SW-containing plants causes a serious neurological disorder in livestock, which can be fatal. In this study, a fungal endophyte, Alternaria section Undifilum, was identified in Astragalus garbancillo seeds, using polymerase chain reaction (PCR) followed by direct sequencing. In seeds, the SW concentrations were about 4 times higher than in other parts of the plant. Furthermore, microscopic examination demonstrated that the fungus mycelium grows inside the petioles and stems, on the outer surface and inside the mesocarp of the fruit, in the mesotesta and endotesta layers of the seed coat, and inside the endosperm of the seeds. Our results support the notion that the SW-producing fungus is vertically transmitted in the host plant A. garbancillo.

Vaccinating humanitarian workers against COVID-19.

Objective: To describe the United Nations' (UN's) coronavirus disease 2019 (COVID-19) vaccination programme and its efforts to vaccinate frontline humanitarian personnel stationed in locations where access to COVID-19 vaccine was limited or absent. Methods: The vaccination programme was structured as a two-level operation: a global vaccine deployment support team and local vaccine deployment teams in each participating country, territory or administrative area. The central group, led by a global vaccine coordinator, oversaw medical, legal, financial, logistical, data, technological and communication aspects. Local vaccine deployment teams were led by coordinators who managed registration, logistics, communication and vaccine administration. The programme used World Health Organization-approved COVID-19 vaccines and developed prioritization criteria for distributing vaccine supplies. The programme ensured that vaccines for the UN personnel were not diverted from the populations they were intended to serve. Findings: The programme successfully formed 120 deployment teams across 152 eligible countries, territories and administrative areas, targeting approximately 673 000 individuals. By April 2023, 72 countries, territories and administrative areas had received over 470 000 doses, of which 337 072 doses were administered. Almost half of the doses administered (167 616) were to individuals in five UN hardship countries. Ninety-five severe adverse events were reported, but none led to any reported medical evacuation, permanent disability or death. Conclusion: The programme demonstrated effective global coordination and local implementation, adapting to diverse contexts and operational challenges. The model can serve as a guide for global actors for future health emergencies, or for deploying health aid at a regional or global scale.

Multiomics Reveals Mechanisms of Alternaria oxytropis Inhibiting Pathogenic Fungi in Oxytropis ochrocephala.

Endophytic fungi can benefit the host plant and increase the plant resistance. Now, there is no in-depth study of how Alternaria oxytropis (A. oxytropis) is enhancing the ability of inhibiting pathogenic fungi in Oxytropis ochrocephala (O. ochrocephala). In this study, the fungal community and metabolites associated with endophyte-infected (EI) and endophyte-free (EF) O. ochrocephala were compared by multiomics. The fungal community indicated that there was more A. oxytropis, less phylum Ascomycota, and less genera Leptosphaeria, Colletotrichum, and Comoclathris in the EI group. As metabolic biomarkers, the levels of swainsonine and apigenin-7-O-glucoside-4-O-rutinoside were significantly increased in the EI group. Through in vitro validation experiments, swainsonine and apigenin-7-O-glucoside-4-O-rutinoside can dramatically suppress the growth of pathogenic fungi Leptosphaeria sclerotioides and Colletotrichum americae-borealis by increasing the level of oxidative stress. This work suggested that O. ochrocephala containing A. oxytropis could increase the resistance to fungal diseases by markedly enhancing the content of metabolites inhibiting pathogenic fungi.

Cecal dilatation in cattle ingesting Megathyrsus maximus (syn. Panicum maximum) cv. Mombaça and cv. Tanzânia.

Nine outbreaks of cecal dilatation are reported in cattle in rotationally-grazed pastures of Megathyrsus maximus during the rainy season with one day grazing and rest intervals of 23-28 days. Clinical signs, observed 6-24 h after entering the pasture, were inappetence, long periods in sternal recumbency, rough hair coat, arched back, tenesmus with difficult defecation, dry stools, reduced ruminal movements, intestinal tympany with right abdominal distention, and decreased milk production. The animals recovered 8-12 h after their removal from the pastures. All pastures were fertilized at 80-120 kg/ha of urea/year. In six farms, in addition to urea, chicken litter (CL) was also added. Water-soluble carbohydrates (WSC), non-fiber carbohydrates (NCF) and starch concentrations in the pastures causing tympany were higher (P < 0.05) than in control pastures. To demonstrate the relationship of the disease with fertilization of the pastures, a pasture of M. maximus was divided into five blocks of 16 m2 and each block subdivided into four plots each, totaling 20 plots. One plot of each block was randomly chosen for 1 of 4 different treatments: 1. fertilized with 8 t/ha of CL; 2. fertilized with 16 t/ha of CL; 3. fertilized with 180 kg/ha urea; 4. control without fertilization. In general, plots fertilized with urea or with CL had higher NFC and starch concentrations (p < 0,05) than the control plots. In another experiment a pasture of M. maximus was divided into 23 paddocks and rotationally grazed. Ten paddocks were fertilized with 180 kg/ha of urea and five fertilized with 8 t/ha of CL. The concentration of NFC and starch were significantly higher (p < 0.05) in the pastures fertilized with urea and with urea plus CL. These results suggest that cecal dilatation may be caused by the high concentrations of NFC and starch in the pastures fertilized with urea and/or poultry litter.

A multicenter evaluation of the HeartMate 3 risk score.

BACKGROUND: The Heartmate 3 (HM3) risk score (HM3RS) was derived and validated internally from within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial population and provides 1- and 2-year mortality risk prediction for patients in those before HM3 left ventricular assist device (LVAD) implantation. We aimed to evaluate the HM3RS in nontrial unselected patients, including those not meeting inclusion criteria for MOMENTUM 3 trial enrollment. METHODS: Patients who underwent HM3 LVAD implant at 1 of 7 US centers between 2017 and 2021, with at least 1-year follow-up, were included in this analysis. Patients were retrospectively assessed for their eligibility for the MOMENTUM 3 trial based on study inclusion and exclusion criteria. HM3RS risk discrimination was evaluated using time-dependent receiver operating characteristic curve analysis for 1-year mortality for all patients and further stratified by MOMENTUM 3 trial eligibility. Kaplan-Meier curves were constructed using the HM3RS-based risk categories. RESULTS: Of 521 patients included in the analysis, 266 (51.1%) would have met enrollment criteria for MOMENTUM 3. The 1- and 2-year survival for the total cohort was 85% and 81%, respectively. There was no statistically significant difference in survival between those who met and did not meet enrollment criteria at 1 (87% vs 83%; p = 0.21) and 2 years postimplant (80% vs 78%; p = 0.39). For the total cohort, HM3RS predicted 1-year survival with an area under the curve (AUC) of 0.63 (95% confidence interval [CI]: 0.57-0.69, p < 0.001). HM3RS performed better in the subset of patients meeting enrollment criteria: AUC 0.69 (95% CI:0.61-0.77, p < 0.001) compared to the subset that did not: AUC 0.58 (95% CI: 0.49-0.66, p = 0.078). CONCLUSIONS: In this real-world evidence, multicenter cohort, 1- and 2-year survival after commercial HM3 LVAD implant was excellent, regardless of trial eligibility. The HM3RS provided adequate risk discrimination in "trial-like" patients, but predictive value was reduced in patients who did not meet trial criteria.

The Complete Sequence and Comparative Analysis of Ape Sex Chromosomes.

Apes possess two sex chromosomes-the male-specific Y and the X shared by males and females. The Y chromosome is crucial for male reproduction, with deletions linked to infertility. The X chromosome carries genes vital for reproduction and cognition. Variation in mating patterns and brain function among great apes suggests corresponding differences in their sex chromosome structure and evolution. However, due to their highly repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the state-of-the-art experimental and computational methods developed for the telomere-to-telomere (T2T) human genome, we produced gapless, complete assemblies of the X and Y chromosomes for five great apes (chimpanzee, bonobo, gorilla, Bornean and Sumatran orangutans) and a lesser ape, the siamang gibbon. These assemblies completely resolved ampliconic, palindromic, and satellite sequences, including the entire centromeres, allowing us to untangle the intricacies of ape sex chromosome evolution. We found that, compared to the X, ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements. This divergence on the Y arises from the accumulation of lineage-specific ampliconic regions and palindromes (which are shared more broadly among species on the X) and from the abundance of transposable elements and satellites (which have a lower representation on the X). Our analysis of Y chromosome genes revealed lineage-specific expansions of multi-copy gene families and signatures of purifying selection. In summary, the Y exhibits dynamic evolution, while the X is more stable. Finally, mapping short-read sequencing data from >100 great ape individuals revealed the patterns of diversity and selection on their sex chromosomes, demonstrating the utility of these reference assemblies for studies of great ape evolution. These complete sex chromosome assemblies are expected to further inform conservation genetics of nonhuman apes, all of which are endangered species.

A versatile pumpless multi-channel fluidics system for maintenance and real-time functional assessment of tissue and cells.

To address the needs of the life sciences community and the pharmaceutical industry in pre-clinical drug development to both maintain and continuously assess tissue metabolism and function with simple and rapid systems, we improved on the initial BaroFuse to develop it into a fully functional, pumpless, scalable multi-channel fluidics instrument that continuously measures changes in oxygen consumption and other endpoints in response to test compounds. We and several other laboratories assessed it with a wide range of tissue types including retina, pancreatic islets, liver, and hypothalamus with both aqueous and gaseous test compounds. The setup time was less than an hour for all collaborating groups, and there was close agreement between data obtained from the different laboratories. This easy-to-use system reliably generates real-time metabolic and functional data from tissue and cells in response to test compounds that will address a critical need in basic and applied research.

Revolutionizing Inflammatory Bowel Disease Management: A Comprehensive Narrative Review of Innovative Dietary Strategies and Future Directions.

This comprehensive narrative review delves into the intricate interplay between diet and inflammatory bowel disease (IBD), shedding light on the potential impact of dietary interventions in disease management. By analyzing nutritional interventions, risks, challenges, and future perspectives, this review serves as a vital resource for clinicians, researchers, and patients alike. The amalgamation of evidence underscores the significance of customizing dietary strategies for individual patients, considering disease phenotype and cultural factors. Through an exploration of dietary components' effects on IBD, including exclusive enteral nutrition and omega-3 fatty acids, this review offers pragmatic implementation advice and outlines avenues for further research. Bridging the gap between research findings and clinical applications, the review facilitates informed decision-making and patient-centric care. In the face of escalating IBD prevalence, this review emerges as an indispensable guide for healthcare professionals, empowering them to navigate the complexities of dietary management while enabling patients to actively participate in their care trajectory. Ultimately, this narrative review advances the understanding of diet's pivotal role in IBD management, fostering a more integrated approach to patient care and paving the way for improved research and policy initiatives in the field of inflammatory bowel diseases.

Local read haplotagging enables accurate long-read small variant calling.

Long-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and enabled rapid genetic diagnosis in clinical settings. Rapidly evolving third-generation sequencing platforms like Pacific Biosciences (PacBio) and Oxford nanopore technologies (ONT) are introducing newer platforms and data types. It has been demonstrated that variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve the genotyping accuracy. However, using local haplotype information creates an overhead as variant calling needs to be performed multiple times which ultimately makes it difficult to extend to new data types and platforms as they get introduced. In this work, we have developed a local haplotype approximate method that enables state-of-the-art variant calling performance with multiple sequencing platforms including PacBio Revio system, ONT R10.4 simplex and duplex data. This addition of local haplotype approximation makes DeepVariant a universal variant calling solution for long-read sequencing platforms.

Risk factors, lab parameters, angiographic characteristics and outcomes of coronary artery disease in young South Asian patients: a systematic review.

This systematic review provides a qualitative summary of the risk factors, angiographic characteristics, treatment, and complications of young South Asians with coronary artery disease (CAD). PubMed, Embase, and Google Scholar were searched to identify research articles published between 1 January 2010 and 13 November 2022. Studies in patients aged 18 to 45 years that were conducted in South Asian countries, were published in the English language, and included information on patients' clinical profiles and at least two risk factors for young CAD were included in the review. Smoking, dyslipidemia, high body mass index, increased high-sensitivity C-reactive protein, and hyperhomocysteinemia were observed in high proportions in young patients with CAD. Single-vessel disease was more common than multi-vessel disease in young CAD. The complications of CAD such as arrhythmias, cardiogenic shock, and heart failure were also commonly observed in young patients. Large-scale health promotion activities that curb modifiable risk factors such as smoking, obesity, and a sedentary lifestyle should be conducted in South Asian countries.

A Rare but Aggressive Malignancy: A Case Report of a Gastrointestinal Neuroectodermal Tumor (GNET).

Gastrointestinal neuroectodermal tumors (GNETs) are extremely rare and intriguing malignancies originating from neural crest cells in the digestive tract. The digestive tract's neural crest cells can give rise to incredibly unusual and interesting gastrointestinal neuroectodermal tumors (GNETs). GNETs present considerable hurdles in diagnosis and management because of their rarity and varied expression. In this case report, a 45-year-old male patient is described who had signs of GNET, such as exhaustion, weight loss, and abdominal pain. A 7-cm jejunum tumor and related thickening of the gut wall were discovered using imaging investigations. The diagnosis of malignant GNET was confirmed by surgical resection, and adjuvant treatment was given. A recurring tumor required a second surgical procedure despite an initial disease-free period. The report emphasizes the difficulties involved in the diagnosis, treatment, and long-term effects of GNETs. The rarity of GNETs necessitates the development of standardized treatment protocols as well as additional research to enhance diagnostic precision and explore novel therapeutic approaches for this aggressive malignancy.