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PubMed2026

Integrated functional genomics and safety assessment of plant-growth-promoting Caryophanales from post-maize-cultivation soils.

This study aimed to evaluate six environmental bacterial strains isolated from post-maize cultivation soils as candidates for agricultural biopreparation development, using an integrated functional genomic and safety assessment framework. Building on experimental validation of plant-growth-promoting activities, the analysis included: plant-growth-promoting traits (PGPT-Pred) using PLABase; carbohydrate-active enzymes (CAZymes) relevant for lignocellulosic crop residue degradation (dbCAN3); secondary metabolite profiles (antiSMASH); and screening for virulence factors and antibiotic resistance genes (ABRicate, BTyper3).All analyzed strains possess 1,449-1,617 predicted PGPT-encoding genes (24.1-35.9% of total genes), which are strongly shaped by taxonomic relatedness, as confirmed by congruence testing against ANI-based genomic divergence. Paenibacillus amylolyticus 5mez and Priestia megaterium 7psych showed distinct functional profiles compared to Bacillus spp., while Bacillus subtilis sensu lato strains were most similar to each other. Genomic predictions suggest involvement in nutrient acquisition (N, P, K, Fe) and stress mitigation. Secondary metabolite analysis revealed high biosynthetic potential, with non-Bacillus species harbouring a large proportion of unknown gene clusters, indicating underexplored metabolite diversity. CAZyme profiling identified P. amylolyticus 5mez as the most enzyme-rich strain, while B. cereus s.s. zielonkawy showed ligninolytic potential despite low overall CAZyme abundance. The safety assessment identified B. cereus s.s. zielonkawy as toxigenic and unsuitable for use. Of the remaining strains, P. amylolyticus 5mez and Pr. megaterium 7psych demonstrated the most favourable safety profiles, exhibiting no detectable virulence factors or antibiotic resistance genes, justifying their priority use in agricultural biopreparations, pending phenotypic validation. Given the high-dimensional, low-sample-size nature of multi-trait datasets in applied microbial genomics, tailored statistical approaches, including noise-reduction-validated PCA and distance-based congruence testing, were applied; their rationale and limitations are discussed.

Soil Microbiology↗

PubMed2002

Functional integration and inference in the brain.

Self-supervised models of how the brain represents and categorises the causes of its sensory input can be divided into two classes: those that minimise the mutual information (i.e. redundancy) among evoked responses and those that minimise the prediction error. Although these models have similar goals, the way they are attained, and the functional architectures employed, can be fundamentally different. This review describes the two classes of models and their implications for the functional anatomy of sensory cortical hierarchies in the brain. We then consider how empirical evidence can be used to disambiguate between architectures that are sufficient for perceptual learning and synthesis. Most models of representational learning require prior assumptions about the distribution of sensory causes. Using the notion of empirical Bayes, we show that these assumptions are not necessary and that priors can be learned in a hierarchical context. Furthermore, we try to show that learning can be implemented in a biologically plausible way. The main point made in this review is that backward connections, mediating internal or generative models of how sensory inputs are caused, are essential if the process generating inputs cannot be inverted. Because these processes are dynamical in nature, sensory inputs correspond to a non-invertible nonlinear convolution of causes. This enforces an explicit parameterisation of generative models (i.e. backward connections) to enable approximate recognition and suggests that feedforward architectures, on their own, are not sufficient. Moreover, nonlinearities in generative models, that induce a dependence on backward connections, require these connections to be modulatory; so that estimated causes in higher cortical levels can interact to predict responses in lower levels. This is important in relation to functional asymmetries in forward and backward connections that have been demonstrated empirically. To ascertain whether backward influences are expressed functionally requires measurements of functional integration among brain systems. This review summarises approaches to integration in terms of effective connectivity and proceeds to address the question posed by the theoretical considerations above. In short, it will be shown that functional neuroimaging can be used to test for interactions between bottom-up and top-down inputs to an area. The conclusion of these studies points toward the prevalence of top-down influences and the plausibility of generative models of sensory brain function.

Animals↗

PubMed1983

Functional integrity of isolated rat hepatocytes prepared by whole liver vs biopsy perfusion.

Isolated rat hepatocytes prepared by a newly developed, versatile biopsy perfusion method (HB cells) were compared with hepatocytes prepared by conventional whole liver perfusion (HP cells), immediately after isolation and after 6 h in suspension culture. Thirteen parameters were used to assess the functional integrity of these cells. Both methods produced high yields of metabolically active hepatocytes that were virtually indistinguishable from each other. After 6 h, the average viability of both cell isolates declined approximately 10%, mixed function oxidase activities were decreased approximately 25% at most, and GSH levels were actually increased; other parameters were not significantly changed. The data indicate that HB-cell isolates are at least as viable and metabolically active as HP cells, and, because the biopsy perfusion method can be applied to liver samples from any species, it facilitates comparative studies.

Animals↗

PubMed1984

Functional integrity of T, B, and natural killer cells in homosexual subjects with prodromata and in patients with AIDS.

We have examined the numbers of the total T (T11+) cells, T-helper (T4+) cells, T-suppressor (T8+) cells, NK cells (Leu7+), and the functional integrity of T, B, and NK cells in healthy male heterosexuals and compared the data to those obtained from AIDS patients and male homosexuals at risk. The absolute number of total T (T11+) and T-helper (T4+) cell populations were significantly reduced among most of the asymptomatic homosexual males and even more decreased in the AIDS patients. By contrast, the absolute numbers of T-suppressor cells (T8) remained virtually unaltered in the three study populations. The absolute numbers of circulating natural killer cells were similar in the controls and the homosexual subjects, but significantly reduced in the AIDS patients. Proliferative responses to T-cell mitogen (PHA) and T-cell dependent B-cell mitogen (PWM) were severely impaired in prodromal subjects and more so in the AIDS group. Response to PWM was unrelated to the total number of T-suppressor cells, but was associated with a significant decrease in T-helper cell number. Furthermore, all AIDS patients exhibited a significantly depressed NK-cell activity that could not be normalized by addition of alpha IFN or IL-2 and in most cases correlated with the reduced absolute number of NK (Leu7+) cells as well as T-helper cells (T4) and T4/T8 ratios. Three distinctive subgroups with normal (N-NK), significantly heightened (H-NK), and markedly lowered (L-NK) NK activity could be readily identified among the homosexual male population at risk. The N-NK and L-NK groups displayed marginal to no response to in vitro treatment with alpha IFN and interleukin-2. The NK-cell activity, however, in the H-NK group was moderately to strongly inhibited by inclusion of the two immunomodifiers.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Cellular signal level of cyclic AMP and functional integrity of the small bowel after ischemic preservation: an experimental pilot study in the rat.

The intestinal mucosa is one the tissues most sensitive to ischemia. Anoxia of the gut is known to result in an early impairment of cellular permeability and transcapillary barrier function upon reperfusion. In vitro, an increased permeability of endothelial cell monolayers could be shown to be related to a decrease in cellular content of cyclic AMP (cAMP). Thus, the present study was aimed at investigating the role of the cellular cAMP second messenger signal in the context of intestinal ischemia/reperfusion injury after cold preservation. Segments of the upper jejunum were isolated from Wistar rats with vascular pedicle and flushed with 10 ml of UW preservation solution. The intestinal lumen was rinsed with 10-15 ml of UW solution and the organ was stored immersed in UW solution at 4 degrees C for 4 or 18 h. After 18 h of cold ischemic storage structural and functional integrity of the preparation was tested by perfusion via the vascular system with modified Krebs-Henseleit buffer and the intestinal lumen with saline solution (containing 200 mg % of galactose) for 30 min. In half of the experiments, dibutyryl-cAMP a membrane permeable cAMP analogue, was admixed to the flush solution (2 mM). It was found that tissue levels of cAMP linearily decreased to 34% during 18 h of ischemic preservation in UW. Addition of dibutyryl cAMP significantly improved postischemic recovery of the intestinal preparations by decreasing cellular loss of lactic dehydrogenase (18.2 +/- 4.6 vs. 7.6 +/- 2.6 U/I) and improving intestinal absorbtion of galactose from the luminal circuit (0.18 +/- 0.14 vs. 0.36 +/- 0.14 mg %) after 30 min of oxygenated reperfusion, but was not effective to reduce transcapillary water loss into the gut lumen. It is concluded that the anoxia-related decrease of the cellular cAMP level may represent a codeterminator influencing postischemic recovery of the small bowel and that the control of the cAMP signal of ischemic intestines might improve the quality of cold preservation of the gut prior to transplantation.

Animals↗

PubMed2002

Functional integration of adult-born neurons.

Over the past decade, it has become clear that neural stem cells in the adult mammalian brain continuously generate new neurons, predominantly in the hippocampus and olfactory bulb. However, the central issue of whether these new neurons participate in functional synaptic circuitry has yet to be resolved. Here, we use virus-based transsynaptic neuronal tracing and c-Fos mapping of odor-induced neuronal activity to demonstrate that neurons generated in the adult functionally integrate into the synaptic circuitry of the brain.

Animals↗

PubMedDate not supplied

Effect of cryopreservation on the structural and functional integrity of cell membranes of sugarcane (Saccharum sp.) embryogenic calluses.

In this paper, we investigated if the differences consistently noted in survival and plantlet production between cryopreserved and non-cryopreserved, control sugarcane embryogenic calluses were related to modifications induced during cryopreservation in the structural and functional integrity of cell membranes. For this, the evolution of electrolyte leakage, lipid peroxidation products and cell membrane protein contents was measured during 5 d after cryopreservation. Differences between control and frozen calluses were observed only during the first 2 (electrolyte leakage) or 3 d (lipid peroxidation products and membrane protein content) after freezing. It was not possible to link these differences with the differences noted in survival and plant production between control and cryopreserved calluses. Additional studies are thus needed to elucidate which biochemical factors, linked to survival and plantlet regeneration, are affected by cryopreservation.

Cell Membrane↗

PubMed1999

The hypoosmotic swelling test performed with coulter counter: a method to assay functional integrity of sperm membrane in rainbow trout.

The hypoosmotic swelling test (HOS) is one of the methods used to evaluate sperm quality in mammals. This test is based on the swelling ability that functional spermatozoa have when submitted to hypoosmotic solutions. Only a slight increase in size is caused in rainbow trout spermatozoa in such conditions and it is not possible to distinguish between reactive cells (cells who were capable to increase in volume) and non-reactive cells (did not increase in volume) under light microscopy. In our approach we have used the coulter counter to verify the effectiveness of the HOS test in this species. Semen was diluted in different hypoosmotic solutions (50, 100, 150, 200, 250 and 320 mosM/kg) and cell volume measured at different times after dilution (30 s, 2, 5, 10, 20, and 30 min). The higher percentage of reactive cells was achieved with the 100 mosM/kg solution and swelling occurred before 30 s. Even with this solution, the small increase in cell size caused the overlapping of volumes from swollen and non-swollen spermatozoa. In order to analyse the data and to choose a parameter suitable for assessing cell reactivity, the test was performed in samples containing known rates of live/dead cells. Two parameters were analysed after swelling: the increase in volume and the percentage of cells over a standard volume (reactive cells). Results showed a high correlation between the percentages of reactive cells and the known rate of live cells (r2 = 0.65). This fact suggests that HOS test could be used to analyse the integrity and functionality of rainbow trout fresh sperm. To study the reliability of this test in cryopreserved sperm, simple linear regressions were made between cell viability determined by Hoechst 33285 dye and the two parameters obtained from coulter counter data. No significant correlation was observed in either case, showing that structural and functional integrity do not correlate after freeze/thaw. Consistently, the HOS test is not a reliable method to evaluate cryopreserved sperm quality in rainbow trout.

Animals↗

PubMedDate not supplied

Some factors controlling morpho-functional integration of the transplanted embryonic brain tissue.

A review of the experimental data of neurotransplantation, obtained in the laboratory during about a decade, is presented in the paper. The interseries comparison of the data allow to make some conclusions on various factors influencing the graft/host morphological and functional integration. The embryonic rat tissue of somatosensory neocortex, septum and hippocampus with and without dentate fascia, were grafted into the acute cavity in the barrel field of the adult rats. In one special series rat hippocampus was transplanted into the cavity in the septum of the adult rabbit. Solid pieces of embryonic tissue or cellular suspensions were used in various series. Survival rate of the grafts, their histological integration with the host brain, responsiveness of the neurons to electrical and sensory stimulation of the host brain, patterns of spontaneous and evoked activity were compared. It is concluded that so-called tissue-specific factors do not play any significant role in control of the graft/host integration. Other factors, such as presence of the natural intragraft targets for the grafted neurons, degree of preservation of the intrinsic tissue organization within the grafts, composition of surfaces of the solid grafts, presence of physiological activity in the pathways innervating the area of the graft placement determine integrated/isolated status of the graft in the host brain. Patterns of the background and evoked activity of the heterotopic grafts to a large extent are determined by the physiological properties of the grafted neurons, preserved in spite of alien tissue surrounding and unusual inputs.

Animals↗

PubMed2001

Functional food ingredients against colorectal cancer. An example project integrating functional genomics, nutrition and health.

Functional Food Ingredients Against Colorectal Cancer is one of the first European Union funded Research Projects at the cross-road of functional genomics [comprising transcriptomics, the measurement of the expression of all messengers RNA (mRNAs) and proteomics, the measurement of expression/state of all proteins], nutrition and human health. The goal of Functional Food Ingredients Against Colorectal Cancer is to develop a colon epithelial cell line-based screening assay for nutrients with presumed anti-colorectal carcinogenic properties. Genes involved in colon carcinogenesis are identified at the RNA and protein level, using a variety of methods (subtractive hybridisation, DNA microarray, proteomics) in combination with models for colorectal cancer development (human biopsies, rat model for colorectal carcinogenesis, colorectal cancer epithelial cell lines). Secondly, colorectal cancer epithelial cell lines are selected, in terms of their capacity to undergo gene/protein expression changes representing different phases in the colorectal carcinogenesis. Thirdly, these cell lines are used to determine the effects of nutrients with presumed anti-carcinogenic properties (e.g. resveratrol, flavonoids) on functional genomics-derived endpoints. Once validated against the effects of these nutrients in in vivo animal models and classical biomarkers for colorectal carcinogenesis, these cell line models combined with functional genomics represent useful tools to study colorectal carcinogenesis and screen for nutrients with anti-carcinogenic properties.

Animals↗

PubMed1989

Asymptotic behavior of a nonlinear functional-integral equation of cell kinetics with unequal division.

A model of cell cycle kinetics is proposed, which includes unequal division of cells, and a nonlinear dependence of the fraction of cells re-entering proliferation on the total number of cells in the cycle. The model is described by a nonlinear functional-integral equation. It is analyzed using the operator semigroup theory combined with classical differential equations approach. A complete description of the asymptotic behavior of the model is provided for a relatively broad class of nonlinearities. The nonnegative solutions either tend to a stable steady state, or to zero. The simplicity of the model makes it an interesting step in the analysis of dynamics of nonlinear structure populations.

Cell Cycle↗

PubMed1998

Verification of the hygienic adequacy of beef carcass cooling processes by microbiological culture and the temperature-function integration technique.

To enhance food safety and keeping quality, beef carcasses are cooled immediately after leaving the slaughter floor. Within hazard analysis and critical control point (HACCP) systems, this cooling process needs to be monitored by the industry and verified by regulatory agencies. This study assessed the usefulness of the temperature-function integration technique (TFIT) for the verification of the hygienic adequacy of two cooling processes for beef carcasses at one abattoir. The cooling process passes carcasses through a spray cooler for at least 17 h and a holding cooler for at least 7 h. The TFIT is faster and cheaper than culture methods. For spray cooler 1, the Escherichia coli generations predicted by TFIT for carcass surfaces (pelvic and shank sites) were compared to estimated E. coli counts from 120 surface excision samples (rump, brisket, and sacrum; 5 by 5 by 0.2 cm) before and after cooling. Counts of aerobic bacteria, coliforms, and E. coli were decreased after spray cooler 1 (P < or = 0.001). The number of E. coli generations (with lag) at the pelvic site calculated by TFIT averaged 0.85 +/- 0.19 and 0.15 +/- 0.04 after emerging from spray coolers 1 and 2, respectively. The TFIT (with lag) was considered convenient and appropriate for the inspection service to verify HACCP systems for carcass cooling processes.

Abattoirs↗

PubMed1989

Reversible electropermeabilisation of human and rat blood platelets: evaluation of morphological and functional integrity 'in vitro' and 'in vivo'.

A high-voltage discharge procedure has been developed for permeabilising the plasma membranes of both human and rat blood platelets. The cells can be resealed by incubation at 37 degrees C, show less than 4% loss of lactate dehydrogenase (LDH) implying minimal cell lysis and also have well maintained morphological and functional integrity. The prototype apparatus used at field strengths between 6 and 8 kV/cm produces membrane pores which allow free diffusion of low molecular weight substances such as adenine nucleotides, inositol phosphate and fluorescent dyes. Two properties, namely Ca2+-induced secretion of granule stored 5-hydroxytryptamine (5HT) and inositol 1,4,5-trisphosphate (IP3)-induced release of intracellularly sequestered 45Ca, which are both well expressed immediately after permeabilisation, are essentially abolished after resealing. The efficiency of permeabilisation and resealing can be simply monitored by shifts in 'apparent platelet volume' using a resistive particle counter (Coulter). Permeabilised platelets show a shift in modal volumes from a control range 4-7 fl to 10-15 fl. Resealing restores these modal volumes to the original control range. Encapsulation of the fluorochrome, Lucifer yellow (Mr 550), during permeabilisation revealed that after resealing greater than 85% of rat platelets, and close to 100% human platelets, contained the encapsulated dye. The initial rates and % aggregation responses of both human and rat platelets to collagen, thrombin and the thromboxane A2-mimetic U46619 remained essentially normal after permeabilisation and resealing further illustrating the maintenance of functional competence following treatment. Resealed rat platelets reinfused into the circulation after labelling with [111In]indium oxine gave survival curves similar to those of control platelets. Therefore, this reversible permeabilisation procedure may allow the use of autologous or heterologous platelets as carrier vehicles for the delivery of drugs and other agents 'in vivo'.

Adenine Nucleotides↗

PubMed1997

Achieving functional integration: a continuum case study.

Inova Mount Vernon Hospital, a part of the Inova Health System in northern Virginia, has developed a plan to redesign its joint replacement service to better coordinate patient care across the entire continuum. The redesign incorporates services, such as presurgery therapy and patient education, registration and insurance activities, rehabilitation, and home care, into an existing acute care joint replacement clinical pathway to create a continuum of care. To encourage the provider partners to integrate the joint replacement service, Inova Mount Vernon Hospital developed new types of clinical, economic, and service outcome measurements to view episodes of care from a system perspective. These measurements will be used to assess the success of the functional integration effort.

Continuity of Patient Care↗

PubMed1983

[Segmental contractility--criterion of the integral function of the left ventricle in patients with ischemic heart disease].

The expulsion fraction was examined with reference to qualitative and quantitative parameters of segment contractility of the left-ventricular wall in 68 coronary patients. Segment contractility of the left-ventricular wall can provide the basis for the interpretation of the left-ventricular integrative function in these patients. Its qualitative assessment can characterize the general condition of the myocardium, whereas its quantitative features may contribute to the elucidation of mechanisms involved in compensatory relationships between the damaged and intact myocardium of the left ventricle.

Adult↗

PubMed2025

The Effect of APOE ε4 Allele on Dynamic Local Spontaneous Brain Activity and Functional Integration in Alzheimer's Disease.

The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for sporadic Alzheimer's disease (AD), yet its mechanisms in AD pathology and cognitive decline remain unclear. Using a sliding-time window approach to directly quantify the instantaneous fluctuations of various local metrics based on continuous time series and calculate voxel-wise concordance of these metrics, we explored the impact of APOE ε4 on dynamic local brain activity and functional integration in AD, and its interrelations with plasma biomarkers and cognition. Results showed that APOE ε4 widely affected dALFF, dReHo, dGSCorr, and voxel-wise concordance. For AD patients, APOE ε4 carriers uniquely exhibited correlations between dALFF in the right angular gyrus/supramarginal gyrus and MoCA scores and orientation function, and between voxel-wise concordance in the right caudate nucleus (CAU) and general cognition, attention, language function, orientation function, plasma Aβ42. Critically, APOE ε4-related altered voxel-wise concordance in the right CAU mediated the relationship between plasma Aβ and language cognition in AD. Moreover, the combined model incorporating dynamic metrics, plasma AD biomarkers, and demographic data effectively distinguished AD from NC (AUC = 0.94, sensitivity = 87.69%, specificity = 86.84%). In conclusion, the APOE ε4 allele might play a pivotal role in modulating brain dynamic functional activities in AD, which may contribute to the association between Aβ pathology and cognitive decline. Our findings may provide imaging markers and targets for the diagnosis and treatment of AD.

Humans↗

PubMed2026

Integrated Functional Characterization of Hemileia vastatrix Effector Candidates Reveals Coordinated Immune Suppression, Sequential Deployment and Compartment-Specific Targeting.

Coffee leaf rust, caused by the obligate biotrophic fungus Hemileia vastatrix, remains the most destructive disease of coffee worldwide. Although genomic and transcriptomic studies have identified a large number of candidate effectors, experimental evidence supporting their biological roles during infection remains limited. Here, we integrated functional assays, temporal expression profiling during coffee infection and subcellular localization analyses to investigate the biological properties of 44 H. vastatrix effector candidates (HvECs). Using the Pseudomonas fluorescens EtHAn effector delivery system in Nicotiana benthamiana, 15 HvECs consistently suppressed pattern-triggered immunity (PTI), indicating that immune suppression is a widespread property among the H. vastatrix effector repertoire, as assessed in this heterologous system. Five HvECs also attenuated AvrB-triggered effector-triggered immunity (ETI), and three suppressed both PTI and ETI, suggesting that a subset of HvECs targets conserved regulatory nodes shared by these interconnected immune pathways. Temporal expression profiling revealed sequential deployment of HvECs throughout infection, with distinct subsets predominating during pre-biotrophic development, host penetration or biotrophic colonization, consistent with stage-specific functions during fungal pathogenesis. Subcellular localization analyses further showed that HvECs preferentially accumulated in the nucleus or chloroplasts, compartments known as central hubs of plant immune regulation. This study provides the most comprehensive functional characterization of H. vastatrix effector candidates to date, establishes a biologically informed framework for prioritizing candidates for future identification of avirulence determinants recognized by SH resistance genes, and advances our understanding of how the coffee rust fungus orchestrates immune suppression across time and cellular space during pathogenesis.

Nicotiana↗

PubMed2001

Viral vectors as part of an integrated functional genomics program.

Over the past decade, viral vectors have slowly gained mainstream acceptance in the neuroscience and genetics communities for the in vivo study of gene function [1]. Using stereotactic techniques, it is possible to characterize neuroanatomical relationships through the delivery of neurotropic viral vectors to specific brain regions. More sophisticated studies combine viral vectors with other methods of genetic manipulation such as germline transgenic mice. As more is learned about the properties of different viral vectors, it has become possible to use viral vectors to test hypotheses about the function of genes, through targeted in vivo delivery to the central nervous system (CNS). The effects of gene expression in the brain can be measured on the molecular, biochemical, electrophysiological, morphological, and behavioral levels. We propose that viral vectors should be considered as part of an integrated functional genomics platform in the CNS.

Animals↗