Ricin, a highly toxic glycoprotein derived from the seeds of Ricinus communis, poses significant risks in bioterrorism and toxicology due to its rapid absorption and ease of dissemination. Rapid, ultra-sensitive detection is crucial for timely medical intervention and implementing security measures. However, existing methods often lack sufficient sensitivity or require lengthy processing, limiting their utility for trigger-to-treat scenarios. Here, we present an optical modulation biosensing (OMB)-based ricin assay capable of detecting low concentrations of ricin in buffer, plasma, and biological samples. The assay combines magnetic-bead-based target capture with fluorescent signal enhancement, achieving a limit of detection (LoD) of 15 pg/mL in buffer and 62 pg/mL in plasma, with a 4-log dynamic range. Optimized protocols reduced the assay time to 60 min, maintaining an LoD of 114 pg/mL in plasma while preserving accuracy and reproducibility. The assay successfully detected ricin in bronchoalveolar lavage fluid and serum from mice that were intranasally exposed to ricin, with signals persisting up to 48 h post exposure. Its rapid, high-throughput capabilities and simplified workflow make the OMB-based assay a powerful tool for toxicology, forensic analysis, and counter-bioterrorism. This study highlights the OMB platform’s potential as a sensitive and robust diagnostic tool for detecting hazardous biological agents.

Yersinia pestis, the causative agent of plague, remains a significant global health hazard and a potential top-tier biothreat despite modern medical advances. Here, two mRNA constructs encoding different versions of the low-calcium response virulence (LcrV) protective antigen, an essential virulence factor of Y. pestis, are designed and evaluated. Next, the immunogenicity and protective efficacy both independently and in combination is assessed with the previously reported F1-encoding mRNA construct in the well-established mouse model of pneumonic plague. The findings reveal that human Fc-conjugated F1 + LcrV combination mRNA vaccination resulted in significant immune activation and substantial protection against intranasal Y. pestis challenge. Notably, the combined vaccine demonstrates protective efficacy against two highly virulent wild-type Y. pestis strains representing distinct biovars and an atypical, unencapsulated strain. This study represents the first comprehensive evaluation of mRNA constructs encoding innovatively designed versions of LcrV and F1 for pneumonic plague prevention, addressing critical gaps in current vaccination approaches. This study establishes the mRNA-lipid nanoparticle (LNP) platform as a promising tool for addressing bacterial pathogens, including those resistant to antibiotics. By broadening its applicability to diverse threats, this technology represents an innovative approach to tackling some of the most pressing challenges in global health.

Purpose

The dynamic course of sulfur mustard (SM)-induced ocular insult involves an acute phase, which may progress to a chronic phase or a quiescent period, followed by late pathology. Visualizing pathological corneal changes in vivo could enhance understanding of this process and aid treatment development.

Methods

SM burn was induced in the right eyes of three transgenic mouse strains—expressing RFP under the VE-Cadherin promoter (blood vessels and hematopoietic cells), GFP under the keratin 15 promoter (limbal stem cells), and YFP under the Thy-1 promoter (mid-stromal nerve fibers, MSNFs)—by vapor exposure. Cell infiltration, neovascularization (NV), innervation loss, and stem cell (SC) depletion were monitored in vivo by stereomicroscopy for up to 8 weeks. Corneal whole-mounts were used to assess 360° structures, infiltrating cells, and subbasal nerve plexus (SNP) loss. Histology included H&E, Masson-Trichrome, and periodic acid-Schiff staining.

Results

A 35-s exposure caused minor ocular insult with moderate SNP changes, corneal cell infiltration, and reversible SC loss, mostly resolving by 4 weeks. A 120-s exposure caused severe insult with NV, extensive MSNF and SNP loss, marked CD45⁺ and Iba1⁺ infiltration, and irreversible SC depletion. NV, stromal inflammation, edema, epithelial changes, and goblet cells were seen in histology and correlated with fluorescence imaging.

Conclusions

This study demonstrates the utility of transgenic mice as powerful models for studying SM-induced ocular injury and for developing novel therapeutic strategies.

Pharmaceutical companies are aware of the ongoing effort to satisfy the increasing global demand for therapeutic grade monoclonal antibodies (mAbs), an especially difficult challenge for poor and developing countries. We present a simple, economical, single-step purification approach at neutral pH for polyclonal human IgG (hIgG) that does not require expensive ligands, chromatography columns, polymers, nor membranes. Instead, porous precipitates of commercial, recyclable aromatic [bathophenanthroline:cation] complexes were found to efficiently capture impurity proteins from CHO cells or E. coli lysate while maintaining the majority of the highly concentrated hIgG (5-15 mg/mL) in the supernatant. [(batho)3:Zn2+] complexes were the most promising, resulting in hIgG with purity ≈95%, by SDS-PAGE. This purified hIgG is monomeric (by dynamic light scattering, DLS) and preserves native secondary structure (by far UV circular dichroism spectroscopy, CD). Process yield is >90% (by densitometry) and is maintained after a 100-fold increase in the reaction volume that required only proportional increase in reagents. While Protein A chromatographic columns, the industry gold standard, have limited binding capacity, are costly and require familiarity with column maintenance, we are attempting, by our efforts, to help produce a more efficient, simple and economical purification platform.

Persistent Dry Spells (PDS) during winter in the eastern Mediterranean are crucial to understanding the regional challenges of water resources and mitigating agricultural and economic impacts. Winter dry spells significantly affect ecosystem stability, public health, and socioeconomic conditions in a region susceptible to climate variability. Therefore, extending the forecast horizon of these extreme weather events to subseasonal time scales is a key challenge. With this aim, we examine the covariability of the sea surface temperature of the Indian Ocean and Persistent Dry Spells during winter over the eastern Mediterranean. The positive Indian Ocean Dipole (IOD) phase alters global circulation patterns, notably increasing the geopotential height at 500 hPa and the sea-level pressure over western Russia, eastern Europe, and the eastern Mediterranean during PDS events. Concurrently, the positive IOD phase enhances moisture fluxes and decreases sea level pressure and geopotential height at 500 hPa in the Western Mediterranean, suggesting increased cyclonic activity in that region. This type of activity probably influences the formation of PDS in the eastern Mediterranean through latent heating and the formation of ridges downstream of the cyclones. The baroclinic, subtropical, and polar regimes are large-scale synoptic regimes alternately prevailing during PDS events. Changes due to the DMI phase are not identical under these regimes and sometimes have opposite trends. The baroclinic regime is the most frequent regime during PDS events. Consequently, the average changes in pressure intensity during PDS events strongly resemble those during baroclinic days. Positive DMI case studies exemplify the effect of these large-scale regimes. We provide evidence for a link between the positive phase of IOD in December and the frequency of longer (> 15 days) PDS events. The normalized frequencies of persistent 15-20-day events under the positive dipole mode index (DMI) are ~ 2% higher than the frequency of negative DMI. The frequencies of 6-7 day events are ~20% lower. Finally, we emphasize the sensitivity of persistent dry spells during winter to event definition, the chosen precipitation data source, and threshold definitions for climate indices. These considerations are essential for improving the accuracy of regional weather and climate predictions, further enhancing our understanding of the climatic impacts of IOD and other teleconnection patterns in the eastern Mediterranean and worldwide.

We present a study of the microphysics, mesoscale and synoptic conditions of a rare radiation-fog and low-level clouds event (hereafter, FC event), and build numerical tools to forecast it. The FC event developed in the south-eastern Mediterranean region during January 3-6, 2021. The FC formed during nighttime from south to coastal areas and dissipated at morning hours leaving low-clouds only. The synoptic conditions were dominated by Red Sea Troughs at the surface without cyclonic upper air circulation, suitable for radiation fog development. The following methods were combined to analyze the event and to evaluate the feasibility of accurately numerical forecasting it: 1. in-situ measurements consisting of Forward Scattering Spectrometer Probe FSSP-100, surface meteorological stations and radiosoundings, 2. satellite-retrieved IR and visible imagery [by the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) instrument (https://www.eumetsat.int/seviri) on-board of Meteosat Second Generation (MSG) satellites], 3. high resolution (1-km grid size) Weather Research and Forecast model (WRF) with Real-Time Four-Dimensional Data Assimilation (RTFDDA) model forecasts, 4. post-processing of the model forecasts with simple and machine learning (ML) algorithms. The micro-physical analysis involved measurements of droplet size distribution and visibility range, allowing the calculation of liquid-water content and effective diameter of droplets. The measured visibility range was 90 m. The droplet diameter main mode was 1-2 micrometers, followed by another one around 6 micrometers. Typical liquid-water content values were 0.01-0.025 g/m3. These measurements were in agreement with the classification of the satellite imagery as “small drops fog/low-clouds”. FC forecasting by numerical-weather-prediction models is still challenging, as microphysics parameterizations are too crude. Therefore, we developed two post-processing algorithms based on basic model-forecast variables: wind speed, dew-point temperature and relative humidity at 1000 and 975 hPa vertical levels. The first post-processing algorithm identified FC based on a combination of thresholds of the aforementioned model variables (“Thresholds Algorithm”, TA). It was verified against satellite imagery and independent in-situ observations. The second is a Gradient Boosted Tree (GBT) ML post-processing algorithm in which the aforementioned model variables served as features and satellite imagery as label in the training process. Verification of the GBT algorithm was performed by cross-validation against satellite imagery and against independent in-situ observations, too. Both, the TA and GBT algorithms proved useful to identify FC areas. The GBT algorithm over-performed the TA algorithm during early morning hours, though it overestimates FC areas during the late morning. The combination of the GBT algorithm and TA is able to remove this inaccuracy providing an optimal strategy to post-process model forecasts. While the satellite imagery cannot distinguish between surface fog and low-level clouds, the post-processed model, does show differences between the two analyzed vertical levels, providing the possibility of determining the vertical extent and level of the phenomenon whether fog or low-level clouds.

There is an urgent need today for interface management with recognition layers composed of short receptor molecules, with excellent specificity and affinity toward a target molecule, for a wide range of sensing applications. The current work demonstrates a specific detection of a G-type nerve agent, which is based on a nucleophilic substitution reaction between the surface-bound 4-amino-2-((dimethylamino)methyl)phenol (amino-2-DMAMP) receptors and the diethyl chlorophosphate (DCP) simulant. The specificity and affinity of 2-DMAMP toward DCP are demonstrated with ³¹P-nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS/MS). The specificity of the proposed recognition layer is utilized and demonstrated through the design and realization of an electronic chemosensor using the meta-nanochannel field-effect transistor (MNC FET). The SiO₂ sensing area of the MNC FET is functionalized with amino-2-DMAMP receptors using amine-based chemistry, and the response toward DCP is quantified. An excellent specificity is demonstrated, coupled with a limit of detection of 1 pg/mL, a dynamic range of 8 orders of magnitude, and excellent linearity and sensitivity. The high specificity and affinity of the recognition layer coupled with the high electronic grade of the MNC FET pave the way to specific, label-free, quantitative, low-cost, easy-to-operate, and field-deployable sensors.

Inverse Distance Weighting (IDW) is a common method for spatial interpolation. Still, its accuracy decreases when there is a cluster of measurement stations or when some measuring stations are hidden behind others. This paper introduces Clusters Unifying Through Hiding Interpolation (CUTHI), a simple approach to enhance IDW accuracy. CUTHI calculates a weight for each station that considers its visibility from the interpolation point, reducing the influence of clustered or hidden stations. The method is tested in three cases: elevation data, rainfall measurements, and a mathematical function. Results demonstrate that CUTHI consistently outperforms traditional IDW, especially in areas with clustered measurement stations. CUTHI also treats the bull’s eye problem. This improved accuracy makes CUTHI a valuable tool for various applications requiring precise spatial interpolation.

The center of Israel presents a relatively simple vertical topographical cross-section: The eastern Mediterranean coast to the west, Judea and Samaria mountains in the center and the deep and steep Jordan valley to the east. Further to the east of the Jordan valley there is a plateau of the Moab mountains.

This work presents climatological examination of the daytime boundary layer height (BLH a.g.l) variability during non-summer months according to high resolution (3 km) WRF simulations during at least 5 years (2009-2013). Verification against radiosonde measurements at Beit Dagan at the central coastal plain has shown good agreement between predicted and measured variables including the BLH (mean absolute error 200-500 m).

The shape of monthly BLH histograms varies as a function of season and topography. During December-February the monthly BLH median above the mountain peak and its easterly slope is lower than that over the coastal area (0.3-1.2, 0.9-1.5 km), while during the transitional months September, October, May, the situation is reversed (0.9-1.8, 0.6-1.2 km). In order to track the reason behind the reduction of the BLH over the mountain peak during winter, an examination of the BLH variability during the local afternoon, 10-13 UTC, (12-15 LT) during the various months was performed. As a result, 8 test cases with relatively low (<350 m) BLH were isolated mainly during December. Weak pressure gradients and weak (< 5 m/s) easterly flows were found to be responsible for the low BLH. The synoptic pressure during these events is characterized by a ridge from the south in the middle troposphere and central Red Sea Trough or high to the east or to the north of Israel next to the surface. Foehn winds, which locally reduce the humidity and enhance the temperature, flow over the eastern slope of the Jordan valley and the western slope of the mountain. In such cases, the mild synoptic pressure gradients are responsible for the maintenance of the local cooling over the mountain peak. Limited warm air advection to the mountain peak and close to zero sensible heat flux maintain relatively cold air over the mountain peak and its eastern slope. This examination gives insights into the mechanism of shallow winter day time boundary layer events over the mountain peak and serves as a starting point for further research.

Background: Rift Valley fever virus (RVFV) is a zoonotic virus that poses a significant threat to both livestock and human health and has caused outbreaks in endemic regions. In humans, most patients experience a febrile illness; however, in some patients, RVF disease may result in hemorrhagic fever, retinitis, or encephalitis. While several veterinary vaccines are being utilized in endemic countries, currently, there are no licensed RVF vaccines or therapeutics for human use. Neutralizing antibodies specifically targeting vulnerable pathogen epitopes are promising candidates for prophylactic and therapeutic interventions. In the case of RVFV, the surface glycoproteins Gc and Gn, which harbor neutralizing epitopes, represent the primary targets for vaccine and neutralizing antibody development. Methods: We report the implementation of advanced 10x Genomics technology, enabling high-throughput single-cell analysis for the identification of rare and potent antibodies against RVFV. Following the immunization of mice with live attenuated rMP-12-GFP virus and successive Gc/Gn boosts, memory B cell populations (both general and antigen-specific) were sorted from splenocytes by flow cytometry. Deep sequencing of the antibody repertoire at a single-cell resolution, together with bioinformatic analyses, was applied for BCR pair selection based on their abundance and specificity. Results: Twenty-three recombinant monoclonal antibodies (mAbs) were selected and expressed, and their antigen-binding capacities were characterized. About half of them demonstrated specific binding to their cognate antigen with relatively high binding affinities. Conclusions: These antibodies could be used for the future development of efficacious therapeutics, as well as for studying virus-neutralizing mechanisms. The current study, in which the single-cell sequencing approach was implemented for the development of antibodies targeting the RVFV surface proteins Gc and Gn, demonstrates the effective applicability of this technique for antibody discovery purposes.