Long-insert sequence capture detects high copy numbers in a defence-related beta-glucosidase gene ßglu-1 with large variations in white spruce but not Norway spruce.

Conifers are long-lived and slow-evolving, thus requiring effective defences against their fast-evolving insect natural enemies. The copy number variation (CNV) of two key acetophenone biosynthesis genes Ugt5/Ugt5b and ßglu-1 may provide a plausible mechanism underlying the constitutively variable defence in white spruce (Picea glauca) against its primary defoliator, spruce budworm. This study develops a long-insert sequence capture probe set (Picea_hung_p1.0) for quantifying copy number of ßglu-1-like, Ugt5-like genes and single-copy genes on 38 Norway spruce (Picea abies) and 40 P. glauca individuals from eight and nine provenances across Europe and North America respectively. We developed local assemblies (Piabi_c1.0 and Pigla_c.1.0), full-length transcriptomes (PIAB_v1 and PIGL_v1), and gene models to characterise the diversity of ßglu-1 and Ugt5 genes. We observed very large copy numbers of ßglu-1, with up to 381 copies in a single P. glauca individual. We observed among-provenance CNV of ßglu-1 in P. glauca but not P. abies. Ugt5b was predominantly single-copy in both species. This study generates critical hypotheses for testing the emergence and mechanism of extreme CNV, the dosage effect on phenotype, and the varying copy number of genes with the same pathway. We demonstrate new approaches to overcome experimental challenges in genomic research in conifer defences.

Complementary roles of two classes of defense chemicals in white spruce against spruce budworm.

MAIN CONCLUSION: Monoterpenes and phenolics play distinct roles in defending white spruce trees from insect defoliators. Monoterpenes contribute to the toxicity of the foliage, deterring herbivory, whereas phenolics impede budworm growth. This study demonstrates the complex interplay between monoterpenes and phenolics and their collective influence on the defense strategy of white spruce trees against a common insect defoliator. Long-lived coniferous trees display considerable variations in their defensive chemistry. The impact of these defense phenotype variations on insect herbivores of the same species remains to be thoroughly studied, mainly due to challenges in replicating the comprehensive defense profiles of trees under controlled conditions. This study methodically examined the defensive properties of foliar monoterpenes and phenolics across 80 distinct white spruce families. These families were subsequently grouped into two chemotypes based on their foliar monoterpene concentrations. To understand the separate and combined effects of these classes on tree defenses to the eastern spruce budworm, we conducted feeding experiments using actual defense profiles from representative families. Specifically, we assessed budworm response when exposed to substrates amended with phenolics alone or monoterpenes. Our findings indicate that the ratios and amounts of monoterpenes and phenolics present in the white spruce foliage influence the survival of spruce budworms. Phenotypes associated with complete larval mortality exhibited elevated ratios (ranging from 0.4 to 0.6) and concentrations (ranging from 1143 to 1796 ng mg-1) of monoterpenes. Conversely, families characterized by higher phenolic ratios (ranging from 0.62 to 0.77) and lower monoterpene concentrations (ranging from 419 to 985 ng mg-1) were less lethal to the spruce budworm. Both classes of defense compounds contribute significantly to the overall defensive capabilities of white spruce trees. Monoterpenes appear critical in determining the general toxicity of foliage, while phenolics play a role in slowing budworm development, thereby underscoring their collective importance in white spruce defenses.

Unraveling the multifaceted effects of climatic factors on mountain pine beetle and its interaction with fungal symbionts.

Mountain pine beetles (MPBs) pose a substantial threat to North American pine forests, causing extensive tree mortality over large areas. Their tree-killing ability is closely linked to mass aggregation on host trees triggered via pheromones and dependence on their symbiotic fungi. However, the influence of a changing climate on the biology of MPBs and their co-evolved interactions with their fungal symbionts remains uncertain. To investigate this, male and female pairs of beetles were introduced into freshly cut logs from lodgepole pine trees and placed in controlled climate chambers with manipulated environmental conditions, including two levels of CO2 (ambient vs. 1000 ppm), O3 (ambient vs. 100 ppb) and humidity (33% vs. 65%). The beetle-infested logs were left in these chambers for 1 month and then returned to ambient conditions until brood emergence. Emerging broods were collected for further analysis. Additionally, three species of fungal symbionts (Grosmannia clavigera, Ophiostoma montium and Leptographium longiclavatum) were subjected to the same CO2 , O3 and humidity conditions for 5 days. Lower humidity promoted MPB reproduction and fungal growth. Elevated CO2 accelerated larval growth and emergence while improving brood pheromone production. Elevated O3 had a negative impact on MPB reproduction and brood fitness while improving its immune responses to an entomopathogenic fungus (Beauveria bassiana). It also inhibited fungal growth and reproduction, whereas elevated CO2 had varied (positive or negative) effects on fungal growth and ergosterol (proxy to fungal mass) production depending on the fungal species. Together, these findings suggest that climate change can potentially alter the interactions between MPBs and their fungal symbionts, highlighting the importance of understanding how climate change affects forest pests and their symbiotic relationships to develop effective management strategies in the future.

A Pine in Distress: How Infection by Different Pathogenic Fungi Affect Lodgepole Pine Chemical Defenses.

In North America, lodgepole pine is frequently subjected to attacks by various biotic agents that compromise its ability to defend against subsequent attacks by insect herbivores. We investigated whether infections of lodgepole pine by different pathogenic fungal species have varying effects on its defense chemistry. We selected two common pathogens, Atropellis canker, Atropellis piniphila, and western gall rust, Endocronartium harknessii, affecting mature lodgepole pine trees in western Canada. We also included three ophiostomatoid fungi Grosmannia clavigera, Ophiostoma montium, and Leptographium longiclavatum associated with the mountain pine beetle (Dendroctonus ponderosae), because they are commonly used to investigate induced defenses of host trees of bark beetles. We collected phloem samples from lodgepole pines infected with the rust or the canker and healthy lodgepole pines in the same stand. We also inoculated mature lodgepole pines with the three fungal symbionts and collected phloem samples 2 weeks later when the defense chemistry was at its highest level. Different fungal species differentially altered the terpene chemistry of lodgepole pine trees. E. harknessii and the fungal symbionts altered the terpene chemistry in a similar pattern while trees responded to the infection by the A. piniphila differently. Our study highlights the importance of considering specific biotic stress agents in tree susceptibility or resistance to the subsequent attacks by insect herbivores, such as mountain pine beetle.

Beauveria bassiana exhibits strong virulence against Dendroctonus ponderosae in greenhouse and field experiments.

The mountain pine beetle (MPB) has infested over 16 million hectares of pine forests in western Canada, killing over 50% of mature lodgepole pine, Pinus contorta, in British Columbia alone. There are few tools available to manage irruptive bark beetle populations and to mitigate tree mortality. Beauveria bassiana is an entomopathogenic fungus that causes mortality to several bark beetle species. However, the potential for B. bassiana as a biocontrol agent against pine beetle populations is unknown. We selected three strains of B. bassiana from several culture collections and evaluated their conidial stability under cold storage, in planta (greenhouse, and pine bolts) and in natura (forest stand, pine bolts, and live pines) conditions. The stability assays showed that all fungal strains maintained a minimum effective conidial yield through the assay durations (3-12 weeks). In addition, we adapted a biphasic liquid-solid fermentation approach for the large-scale production of conidial biomass, yielding up to a 100-fold increase in production. In greenhouse virulence assays, the mean lethal time of MPBs was reduced to 3-4 days upon treatment with B. bassiana, where high B. bassiana-associated mycosis was also observed. Furthermore, the application of B. bassiana formulation substantially affected the gallery network of MPBs in bolts in the field, resulting in shorter larval galleries and significantly reduced offspring production. Indeed, high titer treatments reduced the mean larvae per gallery to virtually zero. Together these results demonstrate that B. bassiana may be a viable biocontrol tool to reduce mountain pine beetle populations in pine forests in western Canada. KEY POINTS: • Three B. bassiana strains identified to be stable at various test conditions. • Large-scale conidial biomass production using liquid-solid biphasic fermentation. • Reproductive success of D. ponderosae significantly reduced by B. bassiana formulation.

Multiple-trait analyses improved the accuracy of genomic prediction and the power of genome-wide association of productivity and climate change-adaptive traits in lodgepole pine.

BACKGROUND: Genomic prediction (GP) and genome-wide association (GWA) analyses are currently being employed to accelerate breeding cycles and to identify alleles or genomic regions of complex traits in forest trees species. Here, 1490 interior lodgepole pine (Pinus contorta Dougl. ex. Loud. var. latifolia Engelm) trees from four open-pollinated progeny trials were genotyped with 25,099 SNPs, and phenotyped for 15 growth, wood quality, pest resistance, drought tolerance, and defense chemical (monoterpenes) traits. The main objectives of this study were to: (1) identify genetic markers associated with these traits and determine their genetic architecture, and to compare the marker detected by single- (ST) and multiple-trait (MT) GWA models; (2) evaluate and compare the accuracy and control of bias of the genomic predictions for these traits underlying different ST and MT parametric and non-parametric GP methods. GWA, ST and MT analyses were compared using a linear transformation of genomic breeding values from the respective genomic best linear unbiased prediction (GBLUP) model. GP, ST and MT parametric and non-parametric (Reproducing Kernel Hilbert Spaces, RKHS) models were compared in terms of prediction accuracy (PA) and control of bias. RESULTS: MT-GWA analyses identified more significant associations than ST. Some SNPs showed potential pleiotropic effects. Averaging across traits, PA from the studied ST-GP models did not differ significantly from each other, with generally a slight superiority of the RKHS method. MT-GP models showed significantly higher PA (and lower bias) than the ST models, being generally the PA (bias) of the RKHS approach significantly higher (lower) than the GBLUP. CONCLUSIONS: The power of GWA and the accuracy of GP were improved when MT models were used in this lodgepole pine population. Given the number of GP and GWA models fitted and the traits assessed across four progeny trials, this work has produced the most comprehensive empirical genomic study across any lodgepole pine population to date.

Pest defences under weak selection exert a limited influence on the evolution of height growth and drought avoidance in marginal pine populations.

While droughts, intensified by climate change, have been affecting forests worldwide, pest epidemics are a major source of uncertainty for assessing drought impacts on forest trees. Thus far, little information has documented the adaptability and evolvability of traits related to drought and pests simultaneously. We conducted common-garden experiments to investigate how several phenotypic traits (i.e. height growth, drought avoidance based on water-use efficiency inferred from δ13C and pest resistance based on defence traits) interact in five mature lodgepole pine populations established in four progeny trials in western Canada. The relevance of interpopulation variation in climate sensitivity highlighted that seed-source warm populations had greater adaptive capability than cold populations. In test sites, warming generated taller trees with higher δ13C and increased the evolutionary potential of height growth and δ13C across populations. We found, however, no pronounced gradient in defences and their evolutionary potential along populations or test sites. Response to selection was weak in defences across test sites, but high for height growth particularly at warm test sites. Response to the selection of δ13C varied depending on its selective strength relative to height growth. We conclude that warming could promote the adaptability and evolvability of growth response and drought avoidance with a limited evolutionary influence from pest (biotic) pressures.

Plant extract-based synthesis of metallic nanomaterials, their applications, and safety concerns.

Nanotechnology has attracted the attention of researchers from different scientific fields because of the escalated properties of nanomaterials (NMs) compared with the properties of macromolecules. NMs can be prepared through different approaches involving physical and chemical methods. The development of NMs through plant-based green chemistry approaches is more advantageous than other methods from the perspectives of environmental safety, animal, and human health. The biomolecules and metabolites of plants act as reducing and capping agents for the synthesis of metallic green NMs. Plant-based synthesis is a preferred approach as it is not only cost-effective, easy, safe, clean, and eco-friendly but also provides pure NMs in high yield. Since NMs have antimicrobial and antioxidant potential, green NMs synthesized from plants can be used for a variety of biomedical and environmental remediation applications. Past studies have focused mainly on the overall biogenic synthesis of individual or combinations of metallic NMs and their oxides from different biological sources, including microorganisms and biomolecules. Moreover, from the viewpoint of biomedical applications, the literature is mainly focusing on synthetic NMs. Herein, we discuss the extraction of green molecules and recent developments in the synthesis of different plant-based metallic NMs, including silver, gold, platinum, palladium, copper, zinc, iron, and carbon. Apart from the biomedical applications of metallic NMs, including antimicrobial, anticancer, diagnostic, drug delivery, tissue engineering, and regenerative medicine applications, their environmental remediation potential is also discussed. Furthermore, safety concerns and safety regulations pertaining to green NMs are also discussed.

Production of complementary defense metabolites reflects a co-evolutionary arms race between a host plant and a mutualistic bark beetle-fungal complex.

Intra-specific variation in conifers has been extensively studied with respect to defense against herbivores and pathogens. While studies have shown the ability of individual or specific mixtures of compounds to influence insects and microbes, research testing biologically relevant mixtures of defense compounds reflecting intra-specific variation amongst tree populations to enemy complexes is needed. We characterized the variations in lodgepole pine monoterpenes from a progeny trial in western Canada and grouped trees in four clusters using their monoterpene profiles. We then selected 11 representative families across four clusters and amended their entire monoterpene profiles (with the exception of ß-phellandrene) in media to determine how representative families affect the performance of the mountain pine beetle or its fungal symbiont. We placed adult beetles or inoculated fungus on the amended media and measured beetle performance and fungal growth as a proxy to host suitability. We found that different clusters or families differentially influenced beetle or fungal responses. However, monoterpene profiles of trees suitable to the beetle or the fungus were dissimilar. These outcomes reflect a co-evolutionary arms-race between the host and the bark beetle-fungus complex, which has resulted in the production of complementary defense metabolites among different pine populations to enhance tree survival.

Design, Preparation and evaluation of various parameters of controlled release matrices of losartan potassium using polymers combination.

Controlled release formulations are administered once a day and reduce frequency of dose and ensuring patient's compliance. In the current research controlled release matrices of losartan potassium formulated with polymeric combinations of ethocel grade 7 with carbopol 934P NF using different concentrations of polymers. In some polymeric tablets, Co-excipients like CMC, Starch, HPMC was added by replacing of 10% of filler in formulations at 10:5. Tablets were prepared by direct compression method and evaluated for physicochemical characteristics. USP Method-1 (rotating basket method) was used to carry out dissolution study in phosphate buffer pH 6.8. Drug release kinetics determined and comparison of dissolution patterns was done with reference tablets. The polymeric combinations well retarded drug release and drug was released by anamolous non-fickian diffusion mechanism. Dissolution profiles of tested tablets and reference tablets were found not similar. Drug release rate was increased by co-excipients. It was concluded from this research work that this polymeric combination can be used efficiently in designing of controlled release martices.

Role of Vitamin D in reducing number of acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) patients.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by chronic incompletely reversible poor airflow and air trapping and usually this debilitating disorder limits the outside activities of the patients depriving them of sunlight which is a rich source of Vitamin D. The objective of this study was to determine the effect of vitamin D supplementation in reducing number of acute exacerbation in COPD patients. METHODS: This randomized control trial was conducted at East Medical Ward Mayo Hospital Lahore from January to December 2015 as exacerbations of COPD are season dependent. Diagnosis was confirmed by performing Pulmonary Function Tests (PFTs). Basic demographical information was obtained and baseline PFTs of the patient was done. Only Group A patients was treated with oral vitamin D intake of 2000 IU daily for 6 months. Vitamin D level was measured at 0, 2, 4, and 6 months and exacerbation of COPD, FEV1 and FVC was measured weekly. Both the groups were given standard treatment for exacerbation of COPD. Spirometry was repeated at each visit. Blood samples were collected every 2 months for vitamin D. Supplementation was stopped if vitamin D level exceeded 100ng/ml. RESULTS: The mean age of the patients was 46.28±8.83 years, the male to female ratio was 1.8:1. The mean 25(OH) level at baseline was 24.08±2.58 and at 6th month was 29.60±8.74. The mean FVC at baseline was 77.83±5.49 and at 6th month was 91.34±5.52. The exacerbation at baseline was present in all 120(100%) patients and at 6th month was reduced to 4(3.3%). CONCLUSION: Vitamin D supplementation has significant effect in reducing number of acute exacerbation in COPD patients when it is given for prolonged period.

Recent advancements in nanotechnology based drug delivery for the management of cardiovascular disease.

Cardiovascular diseases (CVDs) constitute a predominant cause of both global mortality and morbidity. To address the challenges in the early diagnosis and management of CVDs, there is growing interest in the field of nanotechnology and nanomaterials to develop innovative diagnostic and therapeutic approaches. This review focuses on the recent advancements in nanotechnology-based diagnostic techniques, including cardiac immunoassays (CIA), cardiac circulating biomarkers, cardiac exosomal biomarkers, and molecular Imaging (MOI). Moreover, the article delves into the exciting developments in nanoparticles (NPs), biomimetic NPs, nanofibers, nanogels, and nanopatchs for cardiovascular applications. And discuss how these nanoscale technologies can improve the precision, sensitivity, and speed of CVD diagnosis and management. While highlighting their vast potential, we also address the limitations and challenges that must be overcome to harness these innovations successfully. Furthermore, this review focuses on the emerging opportunities for personalized and effective cardiovascular care through the integration of nanotechnology, ultimately aiming to reduce the global burden of CVDs.

Covalent immobilization of human serum albumin on cellulose acetate membrane for scavenging amyloid beta - A stepping extracorporeal strategy for ameliorating Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by interrupted neurocognitive functions and impaired mental development presumably caused by the accumulation of amyloid beta (Aß) in the form of plaques. Targeting Aß has been considered a promising approach for treating AD. In the current study, human serum albumin (HSA), a natural Aß binder, is covalently immobilized onto the surface of a cellulose acetate (CA) membrane to devise an extracorporeal Aß sequester. The immobilization of HSA at 3.06 ± 0.22 µg/mm2 of the CA membrane was found to be active functionally, as evidenced by the esterase-like activity converting p-nitrophenyl acetate into p-nitrophenol. The green fluorescent protein-Aß (GFP-Aß) fusion protein, recombinantly produced as a model ligand, exhibited characteristics of native Aß. These features include the propensity to form aggregates or fibrils and an affinity for HSA with a dissociation constant (KD) of 0.91 µM. The HSA on the CA membrane showed concentration-dependent sequestration of GFP-Aß in the 1-10-µM range. Moreover, it had a greater binding capacity than HSA immobilized on a commercial amine-binding plate. Results suggest that the covalent immobilization of HSA on the CA surface can be used as a potential platform for sequestering Aß to alleviate AD.

Microscopic investigation and pharmacognostic evaluation of leaves of Anemone rupicola Camb.

There is almost no scientific literature available on the phytochemistry and pharmacognosy of this plant so the basic aim of the study is to analyze pharmacognostic features of dried leaves of Anemone rupicola Camb. Morphology was studied by using the features like margins, shape, length, width, surface and so forth. For anatomical examination leaves were preserved in formalin acetic alcohol (FAA) and cutting the thin section of leaves and petiole with razor blade. Macroscopic characters of powdered drug were evaluated through organoleptic method. Qualitative phytochemical analysis was done by adopting the standard procedures. The antimicrobial activity of methanolic extract of Anemone rupicola Camb. was performed by Agar well diffusion method. The powder microscopic study showed epidermal cells, trichomes, various type of tracheids, pitted vessels, and sclerenchymatous fibers. Transverse cutting of leaves and petiole revealed the presence of different cells such as epidermis, palisade parenchyma, spongy parenchyma cells, aerenchyma, collenchyma, trichomes, and vascular bundles. The investigation of phytochemicals in distilled water, methanol and in ethanol solvent indicated the presence of various secondary compounds such as phenols, saponins, glycosides, alkaloids, tannins, cardiac glycosides, terpenoids, coumarins, and flavonoids. The methanolic extract of Anemone rupicola Camb. has potential as an antimicrobial agent. However, further studies are needed to confirm its efficacy and safety. This study can be used as powerful tool for the identification and authentication of this plant. For the purity and quality control these results will be helpful tool. This will also shed light into new areas where researchers can intervene in developing new drugs for future use. RESEARCH HIGHLIGHTS: Morphological Features of the Anemone rupicola Anatomical examination of leaves of Anemeone rupicola Microscopic features of powdered drug of leaves of Anemone rupicola Qualitative Phytochemical analysis of the leaves of Anemone rupicola.

Cobalt-doped zinc oxide based memristors with nociceptor characteristics for bio-inspired technology.

Neuromorphic computing is a new field of information technology, which is inspired by the biomimetic properties of the memristor as an electronic synapse and neuron. If there are electronic receptors that can transmit exterior impulses to the internal nervous system, then the use of memristors can be expanded to artificial nerves. In this study, a layer type memristor is used to build an artificial nociceptor in a very feasible and straightforward manner. An artificial nociceptor is demonstrated here through the fabrication and characterization of a cobalt-doped zinc oxide (CZO)/Au based memristor. In order to increase threshold switching performance, the surface effects of the CZO layer are eliminated by adding cobalt cobalt-doped zinc oxide (CZO) layer between the P++-Si and Au electrodes. Allodynia, hyperalgesia, threshold, and relaxation are the four distinct nociceptive behaviours that the device displays based on the strength, rate of relapse, and duration of the external stimuli. The electrons that are trapped in or released from the CZO layer's traps are responsible for these nociceptive behaviours. A multipurpose nociceptor performance is produced by this type of CZO-based device, which is crucial for artificial intelligence system applications such as neural integrated devices with nanometer-sized characteristics.

Genomic insights into heart health: Exploring the genetic basis of cardiovascular disease.

Cardiovascular diseases (CVDs) are considered as the leading cause of death worldwide. CVD continues to be a major cause of death and morbidity despite significant improvements in its detection and treatment. Therefore, it is strategically important to be able to precisely characterize an individual's sensitivity to certain illnesses. The discovery of genes linked to cardiovascular illnesses has benefited from linkage analysis and genome-wide association research. The last 20 years have seen significant advancements in the field of molecular genetics, particularly with the development of new tools like genome-wide association studies. In this article we explore the profound impact of genetic variations on disease development, prognosis, and therapeutic responses. And the significance of genetics in cardiovascular risk assessment and the ever-evolving realm of genetic testing, offering insights into the potential for personalized medicine in this domain. Embracing the future of cardiovascular care, the article explores the implications of pharmacogenomics for tailored treatments, the promise of emerging technologies in cardiovascular genetics and therapies, including the transformative influence of nanotechnology. Furthermore, it delves into the exciting frontiers of gene editing, such as CRISPR/Cas9, as a novel approach to combat cardiovascular diseases. And also explore the potential of stem cell therapy and regenerative medicine, providing a holistic view of the dynamic landscape of cardiovascular genomics and its transformative potential for the field of cardiovascular medicine.

Potential role of Citrus bergamia flower essential oil against oral pathogens.

BACKGROUND: Oral bacterial infections are difficult to treat due to emergence of resistance against antibiotic therapy. Essential oils are considered emerging alternate therapy against bacterial infections and biofilms. We investigated Citrus bergemia flower essential oil against oral pathogens. METHODS: The essential oil was analsyed using Gas Chromatography(GC-MS), in silico investigations, antioxidant, antimicrobial, antibiofilm and antiquorum sensing assays. RESULTS: Gas Chromatography analysis confirmed presence of 17 compounds including 1,6-Octadien-3-ol,3,7-dimethyl, 48.17%), l-limonene (22.03%) and p-menth-1-ol, 8-ol (7.31%) as major components. In silico analysis showed compliance of all tested major components with Lipinski's rule, Bioavailability and antimicrobial activity using PASS (prediction of activity spectrum of substances). Molecular docking with transcriptional regulators 3QP5, 5OE3, 4B2O and 3Q3D revealed strong interaction of all tested compounds except 1,6-Octadien-3-ol,3,7-dimethyl. All tested compounds presented significant inhibition of DPPH (2,2-diphenyl-1-picrylhydrazyl) (IC50 0.65 mg/mL), H2O2 (hydrogen peroxide) (63.5%) and high FRAP (ferrous reducing antioxidant power) value (239.01 µg). In antimicrobial screening a significant activity (MIC 0.125 mg/mL) against Bacillus paramycoides and Bacillus chungangensis was observed. Likewise a strong antibiofilm (52.1 - 69.5%) and anti-QS (quorum sensing) (4-16 mm) activity was recorded in a dose dependent manner. CONCLUSION: It was therefore concluded that C. bergemia essential oil posess strong antioxidant, antimicrobial and antibiofilm activities against tested oral pathogens.

Bark Beetles Utilize Ophiostomatoid Fungi to Circumvent Host Tree Defenses.

Bark beetles maintain symbiotic associations with a diversity of microbial organisms, including ophiostomatoid fungi. Studies have frequently reported the role of ophiostomatoid fungi in bark beetle biology, but how fungal symbionts interact with host chemical defenses over time is needed. We first investigated how inoculations by three fungal symbionts of mountain pine beetle affect the terpene chemistry of live lodgepole pine trees. We then conducted a complimentary laboratory experiment specifically measuring the host metabolite degradation by fungi and collected the fungal organic volatiles following inoculations with the same fungal species on lodgepole pine logs. In both experiments, we analyzed the infected tissues for their terpene chemistry. Additionally, we conducted an olfactometer assay to determine whether adult beetles respond to the volatile organic chemicals emitted from each of the three fungal species. We found that all fungi upregulated terpenes as early as two weeks after inoculations. Similarly, oxygenated monoterpene concentrations also increased by several folds (only in logs). A large majority of beetles tested showed a strong attraction to two fungal species, whereas the other fungus repelled the beetles. Together this study shows that fungal symbionts can alter host defense chemistry, assist beetles in overcoming metabolite toxicity, and provide possible chemical cues for bark beetle attraction.

Human serum albumin binders: A piggyback ride for long-acting therapeutics.

Human serum albumin (HSA) is the most abundant protein in the blood and has desirable properties as a drug carrier. One of the most promising ways to exploit HSA as a carrier is to append an albumin-binding moiety (ABM) to a drug for in situ HSA binding upon administration. Nature- and library-derived ABMs vary in size, affinity, and epitope, differentially improving the pharmacokinetics of an appended drug. In this review, we evaluate the current state of knowledge regarding various aspects of ABMs and the unique advantages of ABM-mediated drug delivery. Furthermore, we discuss how ABMs can be specifically modulated to maximize potential benefits in clinical development.

Development and evaluation of bioinspired pH-responsive sericin-chitosan-based hydrogel for controlled colonic delivery of PETase: Harnessing PETase-triggered degradation of microplastics.

The gravity of threats posed by microplastic pollution to the environment cannot be overestimated. Being ubiquitous in the living environment, microplastics reach humans through the food chain causing various hazardous effects. Microplastics can be effectively degraded by PETase enzymes. The current study reports, for the first time, a hydrogel-encapsulated, bioinspired colonic delivery of PETase. A free radical polymerization-assisted hydrogel system was synthesized from sericin, chitosan, and acrylic acid using N,N'-methylenebisacrylamide as a crosslinker and ammonium persulfate as an initiator. The hydrogel was characterized with FTIR, PXRD, SEM, and thermal analysis to confirm the development of a stabilized hydrogel system. The hydrogel showed 61 % encapsulation efficiency, maximum swelling, and cumulative PETase release (96 %) at pH 7.4. The mechanism of PETase release exhibited the Higuchi pattern of release with an anomalous transport mechanism. SDS-PAGE analysis confirmed the preservation of the post-release structural integrity of PETase. The released PETase exhibited concentration- and time-dependent degradation of polyethylene terephthalate in vitro. The developed hydrogel system exhibited the intended features of a stimulus-sensitive carrier system that can be efficiently used for the colonic delivery of PETase.