Search Results (37)

Influenza viruses remain a major global public health concern, causing significant morbidity and mortality annually despite widespread vaccination efforts. The limitations of current seasonal vaccines, including strain-specific efficacy and manufacturing delays, have accelerated the development of next-generation candidates aiming for universal protection. This review comprehensively summarizes the recent progress in universal influenza vaccine research. We first outline the key conserved antigenic targets, such as the hemagglutinin (HA) stem, neuraminidase (NA), and matrix proteins (M2e, NP, and M1), which are crucial for eliciting broad cross-reactive immunity. We then delve into advanced antigen design strategies, including immunofocusing, multi-antigen combinations, computationally optimized broadly reactive antigens (COBRA), and nanoparticle-based platforms. Furthermore, we evaluate evolving vaccine delivery systems, from traditional inactivated and live-attenuated vaccines to modern mRNA and viral vector platforms, alongside the critical role of novel adjuvants in enhancing immune responses. The convergence of these disciplines—structural biology, computational design, and nanotechnology—is driving the field toward a transformative goal. We conclude that the successful development of a universal influenza vaccine will likely depend on the strategic integration of these innovative approaches to overcome existing immunological and logistical challenges, ultimately providing durable and broad-spectrum protection against diverse influenza virus strains. Full article

Breast cancer continues to be the leading cancer diagnosis among women worldwide, affecting populations in both industrialized and developing regions. Given the rising number of diagnosed cases each year, there is an urgent need to explore novel compounds with potential anticancer properties. One group of such candidates includes cationic peptides, which have shown promise due to their unique membrane-targeting mechanisms that are difficult for cancer cells to resist. This study presents an initial biophysical assessment of NA-CATH:ATRA-1-ATRA-1, a synthetic peptide modeled after NA-CATH, originally sourced from the venom of the Chinese cobra (Naja atra). The peptide’s interactions with lipid bilayers mimicking cancerous and healthy cell membranes were examined using differential scanning calorimetry and Fourier-transform infrared spectroscopy. Findings revealed a pronounced affinity of NA-CATH:ATRA-1-ATRA-1 for eukaryotic membrane lipids, particularly phosphatidylserine, indicating that its mechanism likely involves electrostatic attraction to negatively charged lipids characteristic of cancer cell membranes. Such biophysical insights are vital for understanding how membrane-active peptides could be harnessed in future cancer therapies. Full article

Special police units like Austria’s EKO Cobra are uniquely trained to manage high-risk operations, including terrorism, amok situations, and hostage crises. This study explores how group dynamics contribute to operational safety and resilience, emphasising the interconnection between risk perception, training, and operational practices. Interviews with current and former EKO Cobra members reveal key risk factors, including overconfidence, insufficient training, inadequate equipment, and the challenges of high-stakes scenarios. Using a structured yet thematically flexible interview analysis approach, the study adopts group dynamics theory as its framework and applies a semi-inductive, semi-deductive qualitative methodology. It examines risk categorisation in ad hoc operations, as well as the interplay between risk perception and training, proposing actionable strategies to enhance safety and preparedness through tailored training programmes. The findings underscore the transformative impact of intensive scenario-based and high-stress training, which enhances situational awareness and reinforces team-based responses through cohesion and effective communication. Group dynamics, including cohesion and effective communication, play a pivotal role in mitigating risks and ensuring operational success. Importantly, this research advocates for continuous, adaptive, and specialised training to address evolving challenges. By linking theoretical frameworks with practical and actionable insights, this study proposes a holistic training approach that promotes both resilience and long-term sustainability in police operations. These findings offer valuable guidance to elite units like EKO Cobra for broader policy frameworks by providing insights that make police operations safer and more effective and resilient. Full article

The composition of Australian snake venoms is the least well-known of any continent. We characterised the venom proteome of the southern death adder Acanthophis antarcticus—one of the world’s most morphologically and ecologically divergent elapids. Using a combined bottom-up proteomic and venom gland transcriptomic approach employing reverse-phase chromatographic and gel electrophoretic fractionation strategies in the bottom-up proteomic workflow, we characterised 92.8% of the venom, comprising twelve different toxin identification hits belonging to seven toxin families. The most abundant protein family was three-finger toxins (3FTxs; 59.8% whole venom), consisting mostly of one long-chain neurotoxin, alpha-elapitoxin-Aa2b making up 59% of the venom and two proteoforms of another long-chain neurotoxin. Phospholipase A₂s (PLA₂s) were the second most abundant, with four different toxins making up 22.5% of the venom. One toxin was similar to two previous non-neurotoxic PLA₂s, making up 16% of the venom. The remaining protein families present were CTL (3.6%), NGF (2.5%), CRiSP (1.8%), LAAO (1.4%), and AChE (0.8%). A. antarcticus is the first Australian elapid characterised that has a 3FTx dominant venom, a composition typical of elapids on other continents, particularly cobras Naja sp. The fact that A. antarcticus has a venom composition similar to cobra venom while having a viper-like ecology illustrates that similar venom expressions can evolve independently of ecology. The predominance of post-synaptic neurotoxins (3FTxs) and pre-synaptic neurotoxins (PLA₂) is consistent with the neurotoxic clinical effects of envenomation in humans. Full article

Background/Objectives: There is a need for effective seasonal influenza virus vaccines that provide broad and long-lasting protection against influenza virus infections. Methods: In this study, next-generation influenza hemagglutinin (HA) and neuraminidase (NA) vaccine candidates designed using the computationally optimized broadly reactive antigen (COBRA) methodology were formulated with the TLR9 agonist, CpG 1018. These adjuvanted COBRA HA/NA vaccines were administered intramuscularly or intranasally to mice with pre-existing anti-influenza immunity or immunologically naïve mice. Results: Mice with pre-existing immune responses to historical influenza virus strains vaccinated intranasal (IN) with COBRA HA/NA vaccines adjuvanted with CpG 1018 had enhanced IgG titers in their bronchoalveolar lavages (BALF) compared to unadjuvanted vaccines. These mice also had increased serum IgG titers that were like antibody titers observed in mice that were vaccinated intramuscularly. Mice that were vaccinated intranasally with this adjuvanted vaccine also had antibodies with significantly higher hemagglutination inhibition activity against a broad range of H1N1 and H3N2 influenza viruses and more HA and NA specific antibody-secreting cells compared to unadjuvanted vaccine. Following the H1N1 influenza virus challenge, pre-immune mice that were vaccinated with the COBRA HA/NA vaccine with CpG 1018 were protected from morbidity and mortality and had no detectable viral lung titers. Conclusions: Overall, CpG 1018 adjuvanted COBRA HA/NA elicited enhanced protective antibodies compared to the unadjuvanted vaccine against several drifted H1N1 and H3N2 influenza viruses in pre-immune mice that were either intramuscularly or intranasally vaccinated with a balanced Th1/Th2 immune response. Full article

Wheat, a cold-tolerant crop, suffers substantial yield and quality losses under heat stress, yet the genetic mechanisms underlying thermotolerance remain understudied. We characterized TaCOBL6A2, a novel COBRA-like gene on wheat chromosome 6A encoding a glycosylphosphatidylinositol (GPI)-anchored protein with a conserved COBRA domain, and performed subcellular localization, tissue-specific expression, and stress response analyses to investigate its function. Functional validation was conducted based on TaCOBL6A2 overexpression in Arabidopsis and transcriptomic profiling. Additionally, a haplotype analysis of wheat varieties was performed to associate genotypes with heat stress phenotypes. The results show that TaCOBL6A2 is localized to the plasma membrane, the cell wall, and the nucleus, with the highest expression in early-stage grains. Its transcription was strongly induced by heat stress, exceeding that in response to cold, salt, or drought. Its overexpression in Arabidopsis enhanced thermotolerance and activated heat shock proteins (HSPs) and oxygen homeostasis pathways. The elite haplotype, Hap1, was associated with improved seedling growth and elevated antioxidant enzyme activity under heat stress. Our findings reveal that TaCOBL6A2 is a key regulator of wheat heat tolerance and could be used as a molecular target for breeding climate-resilient cultivars. Full article

Soybean production in the southern Great Plains (SGP) faces challenges due to yield-limiting factors, including high temperatures and inconsistent precipitation. These conditions can lead to excess vegetative growth, similar to what occurs in crops like cotton. Management strategies utilizing plant growth regulators (PGRs) have been applied to control this excessive growth, yet there is limited information on methods to mitigate vegetative growth in soybeans through modifications to the apical meristem. Field trials conducted in 2022 and 2023 investigated the effects of altering the apical growth using Ascend SL, Compact, Cobra, Cygin Pro, and physical removal, with treatments applied at the V4 and R2 growth stages. This study highlights the significance of customized application strategies to enhance profitability under diverse environmental conditions. Ascend and Cygin Pro demonstrate improving yield stability under adverse climatic conditions. Both applications of Compact produced relatively stable yields across site years, while Cobra and physical removal methods necessitate careful consideration of timing to minimize yield losses. Further research is essential to optimize these management strategies for soybean production in the SGP. Full article

The Philippines has a high diversity of venomous snake species, but there is minimal information on their envenomation effects. This is evidenced by the small number of case reports, the poor reporting of envenomation cases, and the absence of specific antivenoms apart from one against the Philippine cobra (Naja philippinensis). This study sought to profile the action of selected Philippine pit viper venoms on blood coagulation and to investigate whether commercially available non-specific antivenoms can provide adequate protection against these venoms. Venom from the pit vipers Trimeresurus flavomaculatus and Trimeresurus mcgregori were subjected to coagulation assays, antivenom cross-neutralization tests, and thromboelastography. Venoms from both species were able to clot human plasma and isolated human fibrinogen. Consistent with pseudo-procoagulant/thrombin-like activity, the resulting fibrin clots were weak and transient, thereby contributing to net anticoagulation through the depletion of fibrinogen levels. Clotting factors fIXa and fXa were also inhibited by the venoms, further contributing to the net anticoagulant activity. Monovalent and polyvalent antivenoms from the Thai Red Cross Society were effective against both venoms, indicating cross-neutralization of venom toxins; the polyvalent antivenom was able to rescue fibrinogen clotting to a greater degree than the monovalent antivenom. Our findings highlight the coagulopathic effects of these pit viper venoms and suggest the utility of procuring the non-specific antivenoms for areas in the Philippines with a high risk for pit viper envenomation. Full article

Global climate change poses a significant threat to wheat (Triticum aestivum L.) production due to rising temperatures. This study aimed to investigate the impact of high temperatures on wheat yield, thousand kernel weight (TKW), colour, and protein composition to inform breeding strategies for heat tolerance. Two field experiments were conducted: one at three locations in Australia (Horsham, (Vic) Narrabri, (NSW) and Merredin, (W.A.)) in 2019, involving two wheat varieties (Berkut (high-heat-tolerant) and Sokoll (medium-heat-tolerant)) sown at normal (TOS1) and late (TOS2) sowing times; and a second experiment at Narrabri in 2019 and 2020, involving three wheat varieties (Cobra (heat-sensitive), Flanker (high-heat-tolerant) and Suntop (medium-heat-tolerant)) sown at normal (TOS1) and late (TOS2) sowing times. There were reductions in yield and TKW under high temperatures (p < 0.05), particularly in late sowing conditions. The glutenin/gliadin ratio decreased, affecting dough strength and elasticity, especially at Merredin. Heat-tolerant varieties like Flanker and Suntop maintained protein quality, with an increase in the glutenin/gliadin ratio, under high temperature. These findings highlight the necessity for breeding heat-tolerant wheat varieties that can sustain both yield and quality. Future research should focus on genetic traits for heat tolerance, advanced molecular techniques, and interdisciplinary approaches to ensure sustainable wheat production in a changing climate. Full article

The increasing complexity of aerial acrobatics missions necessitates ever-higher levels of attitude control precision in fixed-wing unmanned aerial vehicles (UAVs). Traditional control methods, such as feedback linearization and small disturbance derivation linear models, falter in maintaining attitude tracking accuracy, due to the presence of unanticipated disturbances—most notably, wave disturbances during low-altitude maritime flights—and model uncertainties introduced by factors like large-angle maneuvers, intricate aerodynamic characteristics, and fuel consumption. Consequently, these limitations impede the successful execution of intricate maneuvers, such as looping, the split-S, the Immelmann turn, and the Pougatcheff cobra maneuver. In response to these challenges, we propose an integral sliding mode control based on disturbance observer (ISMC-DO) system to achieve robust attitude angle tracking amidst model uncertainties and mitigate the effects of wave disturbances. Additionally, quaternion representations are adopted as a supplement to Euler angles, thereby resolving the singularity issues inherent in the latter. By using the Lyapunov function, the ISMC-DO-based control system is shown to be asymptotically stable. Simulation results further validate that ISMC-DO can achieve high-precision attitude tracking control of the UAV under wave disturbance. Full article

Building on previous studies of racial inequality in higher education, this paper reports the findings of an online survey (N = 407) exploring the extent to which UK university students recognised the existence of racism in wider society and perceived the need for greater racial diversity and inclusion on campus. Utilising the CoBRAS scale developed by Neville and colleagues together with a new Racially Inclusive Attitudes Scale (RIAS) designed by the lead author of this paper, we find that most students reject the notion that we live in a colour-blind society and feel that their university needs to do more to foster racial diversity and inclusion on campus. However, while the rejection of colour-blind narratives was equally strong across students from all ethnic groups, Black students were significantly more likely than students from other ethnic groups to perceive the need for their university to become more racially diverse and inclusive. Full article

Leptospirosis, a global zoonotic disease caused by Leptospira spp., presents high morbidity and mortality risks, especially in tropical regions like Thailand. Military personnel deployed in endemic areas, such as during the Cobra Gold Joint exercise, face heightened exposure. This study assessed Leptospira’s prevalence in rodents and environmental reservoirs at military training sites from 2017 to 2022. A surveillance program was conducted at Engineering Civil Assistance Program (ENCAP) training sites using real-time PCR, dark-field microscopy, and 16S rRNA gene sequencing to detect Leptospira in rodents and environmental samples. Results showed a 1.3% infection rate in rodents (15 of 1161), while Leptospira was detected in 10.2% of water samples (42 of 413) and 23.1% of soil samples (30 of 130). Diverse Leptospira interrogans strains circulated among rodents, and three groups of naturally circulating Leptospira strains were detected in environmental reservoirs. These findings underscore Leptospira’s survival and transmission potential within exercise sites, informing Force Health Protection (FHP) decisions. By integrating pre-exercise data on primary hosts and environmental reservoirs with historical local outbreak records and research on risk factors, this study identifies key areas for public health intervention and potential mitigation strategies. Full article

Barley (Hordeum vulgare L.), a diverse cereal crop, exhibits remarkable versatility in its applications, ranging from food and fodder to industrial uses. The content of cellulose in barley is significantly influenced by the COBRA genes, which encode the plant glycosylphosphatidylinositol (GPI)-anchored protein (GAP) that plays a pivotal role in the deposition of cellulose within the cell wall. The COBL (COBRA-Like) gene family has been discovered across numerous species, yet the specific members of this family in barley remain undetermined. In this study, we discovered 13 COBL genes within the barley genome using bioinformatics methods, subcellular localization, and protein structure analysis, finding that most of the barley COBL proteins have a signal peptide structure and are localized on the plasma membrane. Simultaneously, we constructed a phylogenetic tree and undertook a comprehensive analysis of the evolutionary relationships. Other characteristics of HvCOBL family members, including intraspecific collinearity, gene structure, conserved motifs, and cis-acting elements, were thoroughly characterized in detail. The assessment of HvCOBL gene expression in barley under various hormone treatments was conducted through qRT-PCR analysis, revealing jasmonic acid (JA) as the predominant hormonal regulator of HvCOBL gene expression. In summary, this study comprehensively identified and analyzed the barley COBL gene family, aiming to provide basic information for exploring the members of the HvCOBL gene family and to propose directions for further research. Full article

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is still very limited when compared to that of other Elapidae snakes like cobras, kraits, and mambas. In this study, two previously described 3FTx from the venom of M. corallinus, NXH1 (3SOC1_MICCO), and NXH8 (3NO48_MICCO) were characterized. Using in silico, in vitro, and ex vivo experiments, the biological activities of these toxins were predicted and evaluated. The results showed that only NXH8 was capable of binding to skeletal muscle cells and modulating the activity of nAChRs in nerve–diaphragm preparations. These effects were antagonized by anti-rNXH8 or antielapidic sera. Sequence analysis revealed that the NXH1 toxin possesses eight cysteine residues and four disulfide bonds, while the NXH8 toxin has a primary structure similar to that of non-conventional 3FTx, with an additional disulfide bond on the first loop. These findings add more information related to the structural diversity present within the 3FTx class, while expanding our understanding of the mechanisms of the toxicity of this coralsnake venom and opening new perspectives for developing more effective therapeutic interventions. Full article

Toll-like receptor 4 (TLR4) is a crucial inflammatory signaling pathway that can serve as a potential treatment target for various disorders. A number of inhibitors have been developed for the TLR4 pathway, and although no inhibitors have been approved for clinical use, most have been screened against the TLR4-MD2 conformation. The venom gland is the organ of venomous snakes that secretes substances that are toxic to other animals. The level of gene transcription in venom glands is different from that in other tissues, includes a large number of biologically active ingredients, and is an important natural resource for the development of new drugs. We constructed a T7 phage display library using the cobra (Naja atra) venom gland from the Guangdong Snake Breeding Plant and performed three rounds of screening with TLR4 as the target, randomly selecting monoclonal phage spots for PCR followed by Sanger sequencing. The obtained sequences were subjected to length analysis, molecular docking, solubility prediction, and stability prediction, and a peptide containing 39 amino acids (NA39) was finally screened out. The BLAST results indicated that NA39 was a sequence in RPL19 (Ribosomal Protein L19). After peptide synthesis, the binding ability of NA39 to TLR4 was verified by the surface plasmon resonance (SPR) technique. In this study, a new peptide that can specifically bind TLR4 was successfully screened from the cobra venom gland cDNA library, further demonstrating the effectiveness of phage display technology in the field of drug discovery. Full article