Dynamics of the water environment in a water quantity-quality-soil model of China's Yellow River basin: imbalance and driving factors.

Dynamic assessment of the water environment reflects variations in water resources in a basin under the combined influence of nature and humans and is a prerequisite for rational water management. This study provides an integrated assessment of the water environment in a water quantity-quality-soil model. Using the long-term monthly data from hydrological monitoring stations, the water environment of the Yellow River basin is assessed from the year 2006 to 2019. The kernel density estimation and the Dagum Gini coefficient are used to analyze the spatial and temporal imbalances of the water environment. Geographic detectors are used to extract external driving factors of the unbalanced evolution. The study results reveal that (1) the water environment in the basin shows a fluctuating downward trend, which mainly depends on the organic pollution control indicators, with a contribution of 22.85%. Scores of the water environment in the midstream are lower than those in the upstream and downstream due to the heavy pollutant discharges. (2) The spatial imbalance shows a fluctuating downward trend. Inter-regional variation is the primary source of regional variation in the water environment, with an average contribution of 56.02%. (3) The temporal imbalance of the water environment is on the rise, with a degree of multipolarity. The significant left trailing feature of the kernel density curve suggests that there are areas within the basin where the water environment is extremely poor. (4) For the overall basin and upstream, economic development and technological innovation are the main external driving factors influencing the spatial and temporal imbalances of the water environment. For the midstream and downstream, population density and environmental regulations are the main drivers. The interaction of any two factors has a greater impact than the single one.

Common genetic variation impacts stress response in the brain.

To explain why individuals exposed to identical stressors experience divergent clinical outcomes, we determine how molecular encoding of stress modifies genetic risk for brain disorders. Analysis of post-mortem brain (n=304) revealed 8557 stress-interactive expression quantitative trait loci (eQTLs) that dysregulate expression of 915 eGenes in response to stress, and lie in stress-related transcription factor binding sites. Response to stress is robust across experimental paradigms: up to 50% of stress-interactive eGenes validate in glucocorticoid treated hiPSC-derived neurons (n=39 donors). Stress-interactive eGenes show brain region- and cell type-specificity, and, in post-mortem brain, implicate glial and endothelial mechanisms. Stress dysregulates long-term expression of disorder risk genes in a genotype-dependent manner; stress-interactive transcriptomic imputation uncovered 139 novel genes conferring brain disorder risk only in the context of traumatic stress. Molecular stress-encoding explains individualized responses to traumatic stress; incorporating trauma into genomic studies of brain disorders is likely to improve diagnosis, prognosis, and drug discovery.

Temperature-dependent development and reproduction of Tarsonemus confusus (Acari: Tarsonemidae): an important pest mite of horticulture.

The tarsonemid mite Tarsonemus confusus Ewing has become an economically important pest in orchards in China. This study investigated the temperature-dependent development and reproduction of T. confusus at 15, 20, 25, 30, 33 and 35 °C. Eggs failed to hatch at 35 °C. When temperature increased from 15 to 30 °C, the developmental rate of eggs, larvae and quiescent larvae and that from egg to adulthood of both sexes significantly increased, and the time period required by females to commence oviposition significantly decreased. The lower temperature threshold (T0) for the development of eggs, larvae and quiescent larvae was between 9.3 and 12.0 °C and both sexes required about 60 degree days (DD) to complete a life cycle. Females were expected to start oviposition at 12.9 °C. The number of eggs laid, the number of female offspring produced and the egg hatch rate were significantly higher at 20, 25 and 30 °C than at 15 and 33 °C. Increasing temperature shortened the longevity of both sexes but increased the intrinsic rate of increase (rm) and finite capacity for increase (λ) with significantly shorter generation time (T) and doubling time (DT) within a temperature range of 15-30 °C. The net reproductive rate (R0) was highest at 25 °C. Results of this study may improve our knowledge of fundamental biology and ecology in genus Tarsonemus in general and in T. confusus in particular. Based on the local climate conditions, the applications of these results in predicting the seasonal population dynamics of T. confusus and timing the pest management are discussed.

Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression.

Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute to individual clinical outcomes is unknown. Here, we compared transcriptional responses to hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD (n = 19 hiPSC and n = 20 PBMC donors) and controls (n = 20 hiPSC and n = 20 PBMC donors). In neurons only, we observed diagnosis-specific glucocorticoid-induced changes in gene expression corresponding with PTSD-specific transcriptomic patterns found in human postmortem brains. We observed glucocorticoid hypersensitivity in PTSD neurons, and identified genes that contribute to this PTSD-dependent glucocorticoid response. We find evidence of a coregulated network of transcription factors that mediates glucocorticoid hyper-responsivity in PTSD. These findings suggest that induced neurons represent a platform for examining the molecular mechanisms underlying PTSD, identifying biomarkers of stress response, and conducting drug screening to identify new therapeutics.

Carbon emission of China's power industry: driving factors and emission reduction path.

The low-carbon development of power industry is the key to low-carbon development of the whole society. In order to determine appropriate and feasible emission reduction policies, it is necessary to identify the contribution of different drivers to the change of carbon emissions in China's power sector and to simulate the potential evolution trend of carbon emissions. This paper constructs LMDI model to analyze the driving factors of carbon emission changes in China's power industry from 2000 to 2018 and uses Monte Carlo algorithm to simulate the evolution trend of carbon emission under different scenarios. We can find (1) economic output effect reached 3.817 billion tons from 2000 to 2018, which was the primary factor to increase the carbon emission. Population scale effect reached 251million tons, which had a weak promotion impact on carbon emission. (2) Conversion efficiency effect played a role in restraining carbon emissions, reaching 699 million tons from 2000 to 2018. (3) Emission factor effect and power intensity effect have obvious volatility. The power structure effect showed great volatility before 2013 and mainly played a role in restraining carbon emission after 2013. (4) Under the baseline scenario, the carbon emission of China's power industry shows a growth trend. Under green development scenario and enhanced carbon reduction scenario, the carbon emission shows a trend of first increasing and then decreasing.

Spatial-temporal evolution and driving factors of grey water footprint efficiency in the Yangtze River Economic Belt.

At present, the deterioration of the water ecosystem has constituted a bottleneck for the further development of the Yangtze River Economic Belt (YREB). As a crucial indicator for evaluating the degree of water pollution, grey water footprint (GWF) is of great significance for rationally evaluating the water environment of the YREB. In this study, we calculated the GWF efficiency of the YREB based on the panel data of 9 provinces and 2 cities from 2005 to 2019. On this basis, spatiotemporal methods and Logarithmic Mean Divisia Index (LMDI) model were adopted to analyze the spatial-temporal evolution characteristics and driving factors of GWF efficiency in the YREB. This study drew the following conclusions: (1) the GWF efficiency in the YREB was on an uptrend, with the average annual growth rates of the upstream, midstream and downstream being 17.35 %, 18.31 % and 17.8 % respectively from 2005 to 2019. (2) The GWF efficiency in the YREB showed a weak trend of polarization and the gap between different regions continued to widen. Besides, it was characterized by stability and owned a positive spatial correlation in both geographic distance and economic distance. (3) The improvement of the technology level, water use efficiency, wastewater treatment capacity, economic development level and the reduction in the industrial pollution intensity contributed positively to boosting the GWF efficiency. Meanwhile, the effect of environmental regulation made a significant negative contribution to GWF efficiency. Therefore, in the process of building the YREB, while emphasizing the coordinated development of the economy, all regions should also carry out joint pollution control.

Measurement and driving factors of grey water footprint efficiency in Yangtze River Basin.

Water shortages and poor water quality have become an urgent problem that is constraining the sustainable development of China. Grey water has been found to bring greater stress on the water supply than freshwater consumption, and the grey water footprint (GWF) has received significant attention as a comprehensive indicator to assess wastewater pollution. In this study, we analysed the grey water footprint in the Yangtze River Basin from 2003 to 2017 and established a Logarithmic mean divisia index (LMDI) model to decompose the grey water footprint efficiency into six key factors. Our findings are as follows: (1) The average grey water footprint (AGWF) in the central regions was 40% higher than eastern region and 172% higher than western region; (2) Economic effects and capital deepening effects are the main factors affecting positive changes in grey water footprint efficiency; (3) Based on an analysis of the driving factors of greywater footprint efficiency in each province, we conducted a territorial classification according to the primary driving factors in each province. Our results reflect the spatial distribution characteristics of the influencing factors on the grey water footprint effect in the Yangtze River Basin and will enable the government to formulate relevant policies for each subregion.

Winter coexistence in herbivorous waterbirds: Niche differentiation in a floodplain, Poyang Lake, China.

The classical niche theory supports the idea that stable coexistence requires ecological differences between closely related species. However, information on waterbirds coexistence in the entirely landlocked freshwater system of Poyang Lake is not well understood, especially when the available biomass of their food in the area decreases. In this study, we tested the ecological segregation mechanisms in the 2015/2016 and 2016/2017 wintering periods among eight herbivorous waterbirds (including the Siberian crane Grus leucogeranus, hooded crane Grus monacha, white-naped crane Grus vipio, common crane Grus grus, greater white-fronted goose Anser albifrons, bean goose Anser fabalis, swan goose Anser cygnoides, and tundra swan Cygnus columbianus) at Poyang Lake. Using field observations and species niche and foraging habitat selection models, we investigated the abundance, distribution, and food sources of these eight waterbird species to quantify and compare their habitat use and ecological niches. Our results showed that niche segregation among the waterbirds, with respect to food types, time, and spatial location, allow them to coexist and use similar resources. The water level gradually receded in the sub-lakes of the Poyang Lake, which could provide food sources and various habitats for wintering herbivorous waterbirds to coexist. We demonstrated that the differences in habitat use could mitigate interspecific competition, which may explain the mechanism whereby waterbirds of Poyang Lake coexist during the wintering period, despite considerable overlap in the dietary niches of herbivorous waterbirds.

Longitudinal genome-wide methylation study of PTSD treatment using prolonged exposure and hydrocortisone.

Epigenetic changes are currently invoked as explanations for both the chronicity and tenacity of post-traumatic stress disorder (PTSD), a heterogeneous condition showing varying, sometimes idiosyncratic responses to treatment. This study evaluated epigenetic markers in the context of a randomized clinical trial of PTSD patients undergoing prolonged-exposure psychotherapy with and without a hydrocortisone augmentation prior to each session. The purpose of the longitudinal epigenome-wide analyses was to identify predictors of recovery (from pretreatment data) or markers associated with symptom change (based on differences between pre- and post-therapy epigenetic changes). The results of these analyses identified the CREB-BDNF signaling pathway, previously linked to startle reaction and fear learning and memory processes, as a convergent marker predicting both symptom change and severity. Several previous-reported resilience markers were also identified (FKBP5, NR3C1, SDK1, and MAD1L1) to associate with PTSD recovery in this study. Especially, the methylation levels of FKBP5 in the gene body region decreased significantly as CAPS score decreased in responders, while no changes occurred in nonresponders. These biomarkers may have future utility in understanding clinical recovery in PTSD and potential applications in predicting treatment effects.

Intergenerational trauma is associated with expression alterations in glucocorticoid- and immune-related genes.

Offspring of trauma survivors are more likely to develop PTSD, mood, and anxiety disorders and demonstrate endocrine and molecular alterations compared to controls. This study reports the association between parental Holocaust exposure and genome-wide gene expression in peripheral blood mononuclear cells (PBMC) from 77 Holocaust survivor offspring and 15 comparison subjects. Forty-two differentially expressed genes (DEGs) were identified in association with parental Holocaust exposure (FDR-adjusted p < 0.05); most of these genes were downregulated and co-expressed in a gene network related to immune cell functions. When both parental Holocaust exposure and maternal age at Holocaust exposure shared DEGs, fold changes were in the opposite direction. Similarly, fold changes of shared DEGs associated with maternal PTSD and paternal PTSD were in opposite directions, while fold changes of shared DEGs associated with both maternal and paternal Holocaust exposure or associated with both maternal and paternal age at Holocaust exposure were in the same direction. Moreover, the DEGs associated with parental Holocaust exposure were enriched for glucocorticoid-regulated genes and immune pathways with some of these genes mediating the effects of parental Holocaust exposure on C-reactive protein. The top gene across all analyses was MMP8, encoding the matrix metalloproteinase 8, which is a regulator of innate immunity. To conclude, this study identified a set of glucocorticoid and immune-related genes in association with parental Holocaust exposure with differential effects based on parental exposure-related factors.

Investigation of esthetic evaluation and its influencing factors for a tunnel portal based on dynamic vision.

With the development of modern cities, roads, and landscapes, it is becoming increasingly important for infrastructure such as tunnels to provide an esthetically pleasing experience. In this respect, it is necessary to conduct studies that consider the esthetic design of tunnel portals using esthetics research. Regarding the esthetic evaluation of tunnel portals, this paper fully considers the dynamic visual effect from the driver's perspective. This study combines the use of Blender, SpeedTree Modeler Cinema, Adobe Photoshop CS6, and other software for secondary development. These programs are connected to the driving simulation platform Euro Truck Simulator 2 (which is equipped with a driving simulator) to construct a set of driving simulation tests that enable the esthetic evaluation of a tunnel portal. The Banlun Tunnel on the Funing-Longliu Expressway in Yunnan Province, China, is used as a case study, and four impact factors that vary significantly in esthetic design are included: the linearity, color, greening and texture of the portal. Using an orthogonal experimental design, the influence of the esthetic degree was simulated and evaluated, and the order of sensitivity to esthetic factors of a headwall tunnel portal was sequentially determined as follows: the portal texture exerts the maximum impact on the beauty degree of the headwall portal, followed by the portal greening and the portal color, while the portal linearity exerts the minimum impact. The results show that the developed driving simulation test system can be used to determine the sensitivity of esthetic factors for a tunnel portal and obtain an optimal collocation of esthetic factors on different levels; hence, it provides feedback for use in designing the optimum esthetic tunnel portal. This test system can be used as a reference when conducting future evaluations and studies on tunnel portal esthetics.

Protein phosphatase 1 regulatory subunit 1A regulates cell cycle progression in Ewing sarcoma.

Ewing sarcoma (ES) is a malignant pediatric bone and soft tissue tumor. Patients with metastatic ES have a dismal outcome which has not been improved in decades. The major challenge in the treatment of metastatic ES is the lack of specific targets and rational combinatorial therapy. We recently found that protein phosphatase 1 regulatory subunit 1A (PPP1R1A) is specifically highly expressed in ES and promotes tumor growth and metastasis in ES. In the current investigation, we show that PPP1R1A regulates ES cell cycle progression in G1/S phase by down-regulating cell cycle inhibitors p21Cip1 and p27Kip1, which leads to retinoblastoma (Rb) protein hyperphosphorylation. In addition, we show that PPP1R1A promotes normal transcription of histone genes during cell cycle progression. Importantly, we demonstrate a synergistic/additive effect of the combinatorial therapy of PPP1R1A and insulin-like growth factor 1 receptor (IGF-1R) inhibition on decreasing ES cell proliferation and migration in vitro and limiting xenograft tumor growth and metastasis in vivo. Taken together, our findings suggest a role of PPP1R1A as an ES specific cell cycle modulator and that simultaneous targeting of PPP1R1A and IGF-1R pathways is a promising specific and effective strategy to treat both primary and metastatic ES.

Correction: Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development.

This Article was originally published without the correct Supplemental Table file (Table S1 was missing). In total, there are seven Supplemental Tables, and six were in the original submission. Furthermore, Fig. 1 was misplaced in the main text; it was embedded in the manuscript file even before the results section. Both issues have now been fixed in the HTML and PDF versions of this Article.

Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development.

Post-traumatic stress disorder (PTSD) is a condition of stress reactivity, whose clinical manifestations are evident when patients are triggered following exposure to a traumatic event. While baseline differences in gene expression of glucocorticoid signaling and inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) have been associated with PTSD, these alterations do not fully recapitulate the molecular response to physiological triggers, such as stress hormones. Therefore, it is critical to develop new techniques that will capture the dynamic transcriptional response associated with stress-activated conditions relative to baseline conditions. To achieve this goal, cultured PBMCs from combat-exposed veterans with PTSD(+) (n = 10) and without PTSD(-) (n = 10) were incubated with increasing concentrations (vehicle, 2.5 nM, 5 nM, 50 nM) of dexamethasone (DEX). Across diagnosis and dosage, several genes and gene networks were reliable markers of glucocorticoid stimulation (FDR < 5%), including enhanced expression of FKPB5, VIPR1, NR1I3, and apoptosis-related pathways, and reduced expression of NR3C1, STAT1, IRF1, and related inflammatory and cellular stress-responsive pathways. Dose-dependent differential transcriptional changes in several genes were also identified between PTSD+ and PTSD-. Robust changes in expression were observed at 2.5 nM DEX in PTSD- but not PTSD+ participants; whereas, with increasing concentrations (5 nM and 50 nM), several genes were identified to be uniquely up-regulated in PTSD+ but not PTSD- participants. Collectively, these preliminary findings suggest that genome-wide gene expression profiling of DEX-stimulated PBMCs is a promising method for the exploration of the dynamic differential molecular responses to stress hormones in PTSD, and may identify novel markers of altered glucocorticoid signaling and responsivity in PTSD.

Optimizing cold storage of the ectoparasitic mite Pyemotes zhonghuajia (Acari: Pyemotidae), an efficient biological control agent of stem borers.

Pyemotes zhonghuajia Yu, Zhang and He is a newly discovered native ectoparasitic mite that efficiently controls stem borers in China. To provide a steady and sufficient supply, extend adult lifespan and synchronize field augmentative releases of P. zhonghuajia, we determined the optimal cold storage temperature and duration by storing 1-day-old mated females at 8, 10 and 12 °C for 10-90 days with a 10-day interval in the laboratory. We then recorded mite survival during storage and monitored the post-storage reproductive performance of mites at a control temperature of 25 °C. We found that all mites survived at 10 and 12 °C for different durations, but mortality occurred when mites were stored at 8 °C for ≥ 30 days with more than 70% of mites dead when the storage duration prolonged up to 50 days. The proportion of reproductive females was higher at 10 °C but decreased with the prolonged storage duration at all test temperatures. Storage temperature had no significant effect on the pre-reproductive period and offspring sex ratio, whereas prolonged storage induced longer pre-reproductive period and lower proportion of female offspring. The reproductive period increased with increasing storage temperature and with prolonged storage up to 50 and 60 days; however, the longer reproductive period did not directly translate into greater reproductive output. We found that compared with the control, mites stored at 10 °C for up to 30 days did not significantly reduce their survival, proportion of reproductive success and number and sex ratio of offspring, suggesting that 10 °C and ≤ 30 days were the optimal cold storage temperature and duration, respectively, for post-mass production storage before the field augmentative release of P. zhonghuajia.

Regulation of sonic hedgehog expression by integrin ß1 and epidermal growth factor receptor in intestinal epithelium.

We previously found that conditional deletion of integrin ß1 in intestinal epithelium of mice caused early postnatal lethality and intestinal phenotypic changes including excessive proliferation and defective differentiation of intestinal epithelium due to loss of Hedgehog expression. Here, we link these defects to the Hedgehog (Hh) signaling pathway and show that loss of integrin ß1 leads to excessive phosphorylation of MEK-1 and increased expression of ErbB receptors, including the epidermal growth factor receptor (EGFR). We show that increased EGFR signaling attenuates Hh abundance and that an EGFR inhibitor rescues conditional ß1 integrin null pups from postnatal lethality. These studies link the loss of Hh expression in the intestinal epithelium of integrin ß1-deficient mice to excessive EGFR/MAPK signaling, and identify a unique mechanism for crosstalk between stromal and epithelial signaling pathways that is critical for intestinal epithelial differentiation and function.

Deficiency of phospholipase A2 group 7 decreases intestinal polyposis and colon tumorigenesis in Apc(Min/+) mice.

Platelet-activating factor (PAF) is a naturally occurring phospholipid that mediates diverse effects such as physiological and pathological inflammation, immunosuppression, and cancer. Several lines of evidence support both positive and negative roles for PAF in carcinogenesis. PAF stimulates cell growth, oncogenic transformation, and metastasis, but can also limit proliferation and induce apoptosis. The biological context and microenvironment seem to define whether PAF has pro- or anticarcinogenic effects. To investigate the role of exacerbated PAF signaling in colon cancer, we conducted cell-based and in vivo studies using genetically engineered mice lacking expression of phospholipase A2 group 7 (PLA2G7), an enzyme that specifically metabolizes PAF and structurally related glycerophospholipids. Absence of Pla2g7 robustly decreased intestinal polyposis and colon tumor formation in Apc(Min)(/+) mice, suggesting an antitumorigenic role for PAF in settings characterized by aberrant function of the tumor suppressor Adenomatous polyposis coli (Apc). In colonic epithelial cells, exposure to a PAF analog led to dephosphorylation of Akt at serine-473 and induction of apoptosis. The mechanism of this response involved formation of a complex between ß-arrestin 1 and the Akt phosphatase PHLPP2, and activation of the intrinsic pathway of apoptosis. Our results suggest that strategies based on inhibiting PLA2G7 activity or increasing PAF-mediated signaling hold promise for the treatment of intestinal malignancies that harbor mutations in APC.

Pharmacologic downregulation of c-FLIP(L) restores juxtacrine death receptor-mediated apoptosis in cancer cells in a peritoneal carcinomatosis model.

Metastasis occurs when circulating cancer cells implant in normal secondary tissues. Paradoxically, many cancer cells express death receptors while many normal tissues express the cognate death receptor ligands, suggesting that cancer cells possess mechanisms to inhibit death receptor signaling. Pharmacological restoration of juxtacrine-mediated death receptor signaling could prevent cancer cells from implanting in normal tissues such as the peritoneum. The results showed that BAY 11-7085 significantly inhibited peritoneal carcinomatosis in mice following the introduction of colon and pancreatic cancer cell lines into the intra-abdominal cavity. Treatment with BAY 11-7085 restored juxtacrine death receptor signaling during the adhesion of the cancer cells to mesothelial cells, which line the peritoneum. BAY 11-7085 rapidly inhibited c-FLIP(L) expression in colon and pancreatic cancer cell lines during adhesion to mesothelial cells. Pancreatic cancer cells sorted for high c-FLIP(L) expression formed peritoneal implants much more readily than cells with low c-FLIP(L) expression, and RNAi inhibition of c-FLIP(L) in colon cancer cells dramatically reduced peritoneal implantation. This is a novel demonstration that the restoration of death receptor-mediated apoptotic signaling in cancer cells through the pharmacological inhibition of c-FLIP(L) can inhibit tumor implantation in a clinically relevant model of peritoneal carcinomatosis, a fatal disease. Pharmacological inhibitors of FLIP hold promise as a way to curtail cancer cell colonization of secondary tissues.

Immunoproteomic identification of polyvalent vaccine candidates from Vibrio parahaemolyticus outer membrane proteins.

Bacterium is still a major cause of many infectious diseases and a global threat to human health, aquaculture, and animal feeding. Prevention by vaccination is the most efficient and economical way of fighting bacterial diseases, but one of the persistent challenges to prevent bacterial infections and disease transmissions is the existence of multiple bacterial species, families, and genera and the lack of efficient polyvalent vaccines against them. The information on candidate immunogens for polyvalent vaccine development is elusive, as well. For the development of broad cross-protective vaccines, we have employed heterogeneous antiserum-based immunoproteomics approaches to identify antigenically similar outer membrane (OM) proteins that could be used as potential polyvalent vaccine candidates against Vibrio parahaemolyticus , V. alginolyticus , V. fluvialis , Aeromonas hydrophila , and A. sobria infections. VPA1435, VP0764, VPA1186, VP1061, and VP2850 could be recognized by at least three antisera and demonstrated significantly passive and active immune protection against V. parahaemolyticus infection in a crucian carp model. VP1061 and VP2850 induced higher immune and protective abilities than the other three OM proteins. Furthermore, the abilities of VP1061 and VP2850 in the generation of broad cross-protective immune reaction against the infections of V. alginolyticus , A. hydrophila , and Pseudomonas fluorescens were also investigated in fish and mouse models. Our results suggested that VP1061 and VP2850 could potentially be used as polyvalent vaccine candidates for the development of novel polyvalent vaccines against V. parahaemolyticus and other Gram-negative pathogens. On the basis of these results, characteristics of OM proteins as polyvalent vaccine candidates have been addressed.