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PubMed1978

Kinetics of C-photosynthate translocation in morning glory vines.

The movement of (14)C-photosynthate in morning glory (Ipomea nil Roth, cu. Scarlet O'Hara) vines 2 to 5 meters long was followed by labeling a lone mature leaf with (14)CO(2) and monitoring the arrival rate of tracer at expanding sink leaves on branches along the stem. To a first approximation, the kinetic behavior of the translocation profiles resembled that which would be expected from movement at a single velocity ("plug flow") without tracer loss from the translocation stream. There was no consistent indication of a velocity gradient along the vine length. The profile moved along the vine as a distinct asymmetrical peak which changes shape only slowly. The spatial distribution of tracer along the vine reasonably matched that predicted on the basis of the arrival kinetics at a sink, assuming plug flow with no tracer loss. These observations are in marked contrast to the kinetic behavior of any mechanism describable by diffusion equations.However, a progressive change in profile shape (a symmetrical widening) was observed, indicating a range of translocation velocities. A minimum of at least two factors must have contributed to the observed velocity gradient: the exchange of (14)C between sieve elements and companion cells (demonstrated by microautoradiography) and the range of velocities in the several hundred sieve tubes which carried the translocation stream. Possible effects of these two factors on profile spreading were investigated by means of numerical models. The models are necessarily incomplete, due principally to uncertainties about the exchange rate between sieve elements and companion cells and the degree of functional connectivity between sieve tubes of different conductivities. However, most of the observed profile spreading may be reasonably attributed to the combined effects of those two factors.The mass average velocity of translocation (calculated from the mean times of (14)C arrival at successive sink leaves) was about 75% of the maximum velocity (calculated from the times of initial detection at the same sink leaves), which was usually between 0.6 and 1 cm min(-1). Owing to tracer exchange between sieve elements and companion cells, the mass average velocity of tracer in the sieve tubes was probably closer to 86% of the maximum velocity, a figure which agreed with a predicted velocity distribution based on calculated sieve tube conductivities and the size distribution of functional sieve tubes.

Journal Article↗
PubMed2004

c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15.

c-Cbl associates with the activated EGF receptor before endocytosis. We here reveal that the capacity of c-Cbl to promote receptor internalization depends on its ubiquitin ligase activity, which functionally connects the EGF receptor to Eps15, a mediator of clathrin-coated pit formation. EGF-induced phosphorylation of Eps15, as well as recruitment of Eps15 to the plasma membrane and its co-localization with the EGF receptor in endosomes required the ubiquitin ligase activity of c-Cbl. This suggested that ubiquitin provides a direct or indirect link between the receptor and Eps15. Indeed, EGF-induced redistribution of Eps15 to the plasma membrane and endosomes depended on its ubiquitin-interacting motif. Upon over-expression, the ubiquitin-interacting motif abrogated the capacity of c-Cbl to promote EGF receptor endocytosis and only allowed receptor internalization via a route that lacked Eps15. Our findings disclose a novel function for the c-Cbl ubiquitin ligase and identify ubiquitin as a module that directs the EGF receptor into an endocytic pathway involving Eps15.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Abnormalities in emotion processing within cortical and subcortical regions in criminal psychopaths: evidence from a functional magnetic resonance imaging study using pictures with emotional content.

BACKGROUND: Neurobiology of psychopathy is important for our understanding of current neuropsychiatric questions. Despite a growing interest in biological research in psychopathy, its neural underpinning remains obscure. METHODS: We used functional magnetic resonance imaging to study the influence of affective contents on brain activation in psychopaths. Series containing positive and negative pictures from the International Affective Picture System were shown to six male psychopaths and six male control subjects while 100 whole-brain echo-planar-imaging measurements were acquired. Differences in brain activation were evaluated using BrainVoyager software 4.6. RESULTS: In psychopaths, increased activation through negative contents was found right-sided in prefrontal regions and amygdala. Activation was reduced right-sided in the subgenual cingulate and the temporal gyrus, and left-sided in the dorsal cingulate and the parahippocampal gyrus. Increased activation through positive contents was found left-sided in the orbitofrontal regions. Activation was reduced in right medial frontal and medial temporal regions. CONCLUSIONS: These findings underline the hypotheses that psychopathy is neurobiologically reflected by dysregulation and disturbed functional connectivity of emotion-related brain regions. These findings may be interpreted within a framework including prefrontal regions that provide top-down control to and regulate bottom-up signals from limbic areas. Because of the small sample size, the results of this study have to be regarded as preliminary.

Adult↗
PubMed2004

A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin.

The conserved histone variant H2A.Z functions in euchromatin to antagonize the spread of heterochromatin. The mechanism by which histone H2A is replaced by H2A.Z in the nucleosome is unknown. We identified a complex containing 13 different polypeptides associated with a soluble pool of H2A.Z in Saccharomyces cerevisiae. This complex was designated SWR1-Com in reference to the Swr1p subunit, a Swi2/Snf2-paralog. Swr1p and six other subunits were found only in SWR1-Com, whereas six other subunits were also found in the NuA4 histone acetyltransferase and/or the Ino80 chromatin remodeling complex. H2A.Z and SWR1 were essential for viability of cells lacking the EAF1 component of NuA4, pointing to a close functional connection between these two complexes. Strikingly, chromatin immunoprecipitation analysis of cells lacking Swr1p, the presumed ATPase of the complex, revealed a profound defect in the deposition of H2A.Z at euchromatic regions that flank the silent mating type cassette HMR and at 12 other chromosomal sites tested. Consistent with a specialized role for Swr1p in H2A.Z deposition, the majority of the genome-wide transcriptional defects seen in swr1Delta cells were also found in htz1Delta cells. These studies revealed a novel role for a member of the ATP-dependent chromatin remodeling enzyme family in determining the region-specific histone subunit composition of chromatin in vivo and controlling the epigenetic state of chromatin. Metazoan orthologs of Swr1p (Drosophila Domino; human SRCAP and p400) may have analogous functions.

Adenosine Triphosphatases↗
PubMed2004

Spatio-temporal autoregressive models defined over brain manifolds.

Multivariate Autoregressive time series models (MAR) are an increasingly used tool for exploring functional connectivity in Neuroimaging. They provide the framework for analyzing the Granger Causality of a given brain region on others. In this article, we shall limit our attention to linear MAR models, in which a set of matrices of autoregressive coefficients Ak (k = 1,...,p) describe the dependence of present values of the image on lagged values of its past. Methods for estimating the Ak and determining which elements that are zero are well-known and are the basis for directed measures of influence. However, to date, MAR models are limited in the number of time series they can handle, forcing the a priori selection of a (small) number of voxels or regions of interest for analysis. This ignores the full spatio-temporal nature of functional brain data which are, in fact, collections of time series sampled over an underlying continuous spatial manifold the brain. A fully spatio-temporal MAR model (ST-MAR) is developed within the framework of functional data analysis. For spatial data, each row of a matrix Ak is the influence field of a given voxel. A Bayesian ST-MAR model is specified in which the influence fields for all voxels are required to vary smoothly over space. This requirement is enforced by penalizing the spatial roughness of the influence fields. This roughness is calculated with a discrete version of the spatial Laplacian operator. A massive reduction in dimensionality of computations is achieved via the singular value decomposition, making an interactive exploration of the model feasible. Use of the model is illustrated with an fMRI time series that was gathered concurrently with EEG in order to analyze the origin of resting brain rhythms.

Bayes Theorem↗
PubMed1994

Expression of c-fos protein in rat brain elicited by electrical and chemical stimulation of the hypothalamic paraventricular nucleus.

The functional connectivity of the paraventricular nucleus of the hypothalamus (PVN) was studied by assessing the expression of the immediate early gene, c-fos, after unilateral stimulation of this structure in urethane-anesthetized rats. Electrical stimulation for 1 h (10 s on, 10 s off; 15-40 microA at 20 Hz) was accompanied by increases in mean arterial pressure (13-29 mm Hg). In these animals, ipsilateral increases in numbers of neurons with Fos-like immunoreactivity (FLI) were immunohistochemically demonstrated in the insular cortex, lateral septum, medial amygdala, hypothalamus, lateral division of the parabrachial nucleus (PBN) of the pons and the nucleus of the tractus solitarius (NTS) and ventrolateral medulla (VLM). Numbers of cells with FLI were quantitated in five areas known for their roles in autonomic function: arcuate nucleus, ventromedial hypothalamus, lateral PBN, NTS (at three levels) and VLM (caudal and rostral). In each case, stimulation of the PVN led to significant differences in number of neurons with FLI on the side ipsilateral to the stimulation compared to the contralateral side. To eliminate effects associated with stimulation of fibers of passage in the vicinity of the PVN, the results after electrical stimulation were compared to those obtained in animals in which the PVN was chemically stimulated unilaterally with the excitatory amino acid L-glutamate (5 one-minute infusions of 50 nl, 0.5 M glutamate over 1 h). Mean arterial pressure was increased after each injection (7-13 mm Hg), and significant differences in numbers of neurons with FLI between sides were maintained in all five areas except the NTS caudal to, and at, the level of the area postrema. An increase in neurons with FLI in the piriform cortex of all animals including controls may be due to injury-induced activation of target neurons from the PVN. These data illustrate that electrical and chemical stimulation of the PVN leads to simultaneous activation of neurons in many targets. All of the target areas studied receive direct projections from the PVN, although multisynaptic projections may also contribute to activation of target neurons.

Animals↗
PubMed1997

Histone acetyltransferase activity and interaction with ADA2 are critical for GCN5 function in vivo.

Yeast GCN5 is one component of a putative adaptor complex that includes ADA2 and ADA3 and functionally connects DNA-bound transcriptional activators with general transcription factors. GCN5 possesses histone acetyltransferase (HAT) activity, conceptually linking transcriptional activation with enzymatic modification at chromatin. We have identified the minimal catalytic domain within GCN5 necessary to confer HAT activity and have shown that in vivo activity of GCN5 requires this domain. However, complementation of growth and transcriptional activation in gcn5- cells required not only the HAT domain of GCN5, but also interaction with ADA2. The bromodomain in GCN5 was dispensable for HAT activity and for transcriptional activation by strong activators; however, it was required for full complementation in other assays. Fusion of GCN5 to the bacterial lexA DNA binding domain activated transcription in vivo, and required both the HAT domain and the ADA2 interaction domain. These results suggest that both functions of GCN5, HAT activity and interaction with ADA2, are necessary for targeting and acetylation of nucleosomal histones.

Acetyltransferases↗
PubMedDate not supplied

Corticohypothalamic relationships during the development and realization of the conditioned reflex.

The influence of motivational, emotiogenically positive and emotiogenically negative structures of the hypothalamus on the development and realization of conditioned reflexes was investigated in the experiments on dogs, cats, and rats. It was shown that the motivational structures primarily increase excitability of cortical neurons during the development of the conditioned connection, while the emotiogenically negative and emotiogenically positive structures increase the efficiency of synapses. A high degree of correlatedness of the averaged evoked responses to the conditional stimulus in the hypothalamus and new cortex is characteristic for the consolidated conditioned reflex. Direct stimulation of the motivational-alimentary zones of the hypothalamus reproduce food-procuring conditioned reflexes in dogs, while stimulations of the emotiogenically negative zones reproduce defense conditioned reflexes. Stimulation of the emotiogenically positive zones does not reproduce either; however, an intensification of the activity of neurons of the hypothalamus was recorded in rats during the successful accomplishment of the conditioned reaction of avoidance of an aversive stimulus. In cats which are capable of restraining a conditioned motoric reaction for the sake of obtaining a preferred food, the "motivational", long-latency functional connections between neurons of the lateral hypothalamus and the prefrontal cortex predominate. Short-latency "informational" connections predominate in the "impulsive" cats.

Animals↗
PubMed2000

Retinal ganglion cells regenerating through the peripheral nerve graft retain their electroretinographic responses and mediate light-induced behavior.

To assess the light-induced electrical activity of rodent retinal ganglion cells (RGCs) regenerating into a peripheral nerve (PN) graft we used non-invasive recording of electroretinographic responses to the contrast-reversal of sinusoidal gratings (p-ERG). On comparing the retinas that received a PN graft and retinas with only optic nerve (ON) transection, p-ERG responses were present in grafted retinas as late as 20 months after the surgery while they completely disappeared in non-transplanted controls within 4 months of ON transection. Next, the ability of regenerating RGCs to form functional connections with their targets in the superior colliculus (SC) was tested by a light-escape task. While the bilaterally blinded animals did not improve during the test, unilaterally grafted animals (with the contralateral eye blinded) reached 26% success in the last quartile of the light-escape task. This performance was significantly better than that of blind animals (ANOVA and Student-Newman-Keuls test; p<0.05), but did not reach the level of intact rats (87%). The transplanted rats, therefore, were capable of light perception, but at a sub-normal ability. In addition, we were also able to correlate the amplitude of the p-ERG response with the visual behavioral performance for each transplanted animal. This finding indicates that there is a direct link between the RGC electrophysiological activity and the functional capacity of the regenerated visual pathway. In conclusion, the above results indicate that (a) PN grafts help to preserve the normal electroretinographic activity of injured and regenerating RGCs (b) the regenerated visual pathway is functional and capable of mediating simple visual behavior and that (c) there is a correlation between the light-evoked RGC electrical activity and visual behavior and, finally, that (d) the effect of PN graft on the electrophysiological and functional restoration of the visual pathway is long-lasting or even permanent.

Animals↗
PubMed2003

Hippocampal long-term potentiation attenuated by lesions in the marginal division of neostriatum.

The marginal division (MrD) is a spindled-neurons consisted zone at the caudal border of the neostriatum in the mammalian brain and has been verified as contributing to associative learning and declarative memory in the rat and human with behavior and functional magnetic resonance imaging methods. It was proved to have functional connections with the limbic system. Whether the MrD has influence on the hippocampal long-term potentiation (LTP) was investigated in this study. LTP was induced from the dentate gyrus (DG) in the hippocampus by high-frequency stimulation (HFS) to the perforant path (PP). The amplitude of the population spike (PS) and the slope of the excitatory postsynaptic potential (EPSP) increased significantly to form LTP in the DG of the hippocampus after HFS of PP in normal and saline-injected control groups of rats. Lesions introduced in the MrD reduced significantly both the amplitude of PS and the slope of the EPSP following HFS of the PP. The results indicated that lesions in the MrD could attenuate LTP formation in the hippocampus. Our data suggest that the MrD might very possibly have excitatory functional influence on the hippocampus and therefore might influence the function of the hippocampus.

Animals↗
PubMed2003

Evidence that the bed nucleus of the stria terminalis contributes to the modulation of hypophysiotropic corticotropin-releasing factor cell responses to systemic interleukin-1beta.

Systemic infection activates the hypothalamic-pituitary-adrenal (HPA) axis, and brainstem catecholamine cells have been shown to contribute to this response. However, recent work also suggests an important role for the central amygdala (CeA). Because direct connections between the CeA and the hypothalamic apex of the HPA axis are minimal, the present study investigated whether the bed nucleus of the stria terminalis (BNST) might act as a relay between them. This was done by using an animal model of acute systemic infection involving intravascular delivery of the proinflammatory cytokine interleukin-1beta (IL-1beta, 1 microg/kg). Unilateral ibotenic acid lesions encompassing the ventral BNST significantly reduced both IL-1beta-induced increases in Fos immunoreactivity in corticotropin-releasing factor (CRF) cells of the hypothalamic paraventricular nucleus (PVN) and corresponding increases in adrenocorticotropic hormone (ACTH) secretion. Similar lesions had no effect on CRF cell responses to physical restraint, suggesting that the effects of BNST lesions were not due to a nonspecific effect on stress responses. In further studies, we examined the functional connections between PVN, BNST, and CeA by combining retrograde tracing with mapping of IL-1beta-induced increases in Fos in BNST and CeA cells. In the case of the BNST, these studies showed that systemic IL-1beta administration recruits ventral BNST cells that project directly to the PVN. In the case of the CeA, the results obtained were consistent with an arrangement whereby lateral CeA cells recruited by systemic IL-1beta could regulate the activity of medial CeA cells projecting directly to the BNST. In conclusion, the present findings are consistent with the hypothesis that the BNST acts as a relay between the CeA and PVN, thereby contributing to CeA modulation of hypophysiotropic CRF cell responses to systemic administration of IL-1beta.

Adrenocorticotropic Hormone↗
PubMed2004

Time-ordered fluctuation-dissipation relation for incompressible isotropic turbulence.

The Kraichnan-Wyld perturbation expansion is used to justify the introduction of a renormalized response function connecting two-point covariances at different times. The resulting relationship was specialized by a suitable choice of initial conditions to the form of a fluctuation-dissipation relation (FDR). This was further developed to reconcile the time symmetry of the covariance with the causality of the response by the introduction of time ordering along with a counterterm. This formulation provides a solution to an old problem, that of representing the time dependence of the covariance and response by exponential forms. We show that the derivative (with respect to difference time) of the covariance now vanishes at the origin. This allows one to study the relationships between two-time spectral closures and time-independent theories such as the self-consistent field theory of Edwards or the more recent renormalization group approaches. We also show that the renormalized response function is transitive with respect to intermediate times and report a different Langevin equation model for turbulence. We note the potential value of this time-ordering procedure in all applications of the FDR.

Journal Article↗
PubMed1986

Properties of self-reinnervated motor units of medial gastrocnemius of cat. II. Axotomized motoneurons and time course of recovery.

This study tested the hypothesis that functional connection to muscle is necessary for expression of normal motoneuron electrical properties. Also examined was the time course of self-reinnervation. Properties of individual medial gastrocnemius (MG) motor units were examined following section and reanastomosis of the MG nerve. Stages examined were 3-5 wk (prior to reinnervation, no-re), 5-6 wk (low-re), 9-10 wk (med-re), and 9 mo (long-re, preceding paper) after nerve section. Motor units were classified on the basis of their mechanical response as type fast twitch, fast fatiguing (FF), fast twitch with intermediate fatigue resistance (FI), fast twitch, fatigue resistant (FR), or slow twitch, fatigue resistant (S) (11, 24). Motoneuron electrical properties were measured. Muscle fibers were classified using histochemical methods as type fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow oxidative (SO) (60). Prior to functional reinnervation, MG motoneurons exhibited increased input resistance, decreased rheobase, decreased rheobase/input resistance, and decreased axonal conduction velocity. There was no change in mean afterhyperpolarization (AHP) half-decay time. Normal relationships between motoneuron electrical properties were lost. These data are consistent with dedifferentiation of motoneuron properties following axotomy (35, 47). At 5-6 wk after reanastomosis, motor-unit tensions were small, and motoneuron membrane electrical properties were unchanged from the no-re stage. There were no differences in motoneuron electrical properties between cells that elicited muscle contraction and those that did not. Motor-unit types were first recognizable at the med-re stage. The proportions of fast and slow motor units were similar to normal MG. Within the fast units, there were fewer type-FF units and more type-FI and type-FR units than normal, reflecting a general increase in fatigue resistance at this stage. Neither motoneuron membrane electrical properties nor muscle contractile properties had reached normal values, although both were changed in that direction from the low-re stage. Normal relationships between muscle properties, between motoneuron properties, and between motoneuron and muscle properties were re-established. The correspondence between motor-unit type and motoneuron type was similar to normal or 9 mo reinnervated MG. Muscle-unit tetanic tensions became larger with time after reinnervation. Most of the increase in muscle tension beyond the med-re stage could be accounted for by increase in muscle fiber area. There was an increased proportion of SO muscle fibers observed in the med-re muscles, as at the long-re stage.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Characterization, scaling, and partial representation of neural junctions and coordinated firing patterns by dynamic similarity.

This paper presents a dynamic-similarity-based system for mathematically characterizing the functional connectivity and information flow of neural junctions. This approach allows for quantitative comparison of operations of neural junctions across systems, and an interpretation of their connectivity parameters in terms of the flow of multiunit firing patterns. The paper further uses this characterization to show how to rationally construct reduced operational models of neural junctions. Both uniformly proportional scaling and partial fragmentary representations are developed. The uniformly scaled models are better adapted to overall capacities and broader theoretical conceptualizations; the partial representations are better adapted to direct comparison with microelectrode experimentation. The characterization of information flow is based on coordinated multiunit patterns such as synfire chains or sequential configurations. The system can be applied to component parts of large composite networks including junctions with topographical patchiness and other irregularities. The characterization should be of use to anatomists, physiologists, modelers, and theorists. The theory predicts that the necessity for cooperative confluence of synaptic potentials in sending and receiving sequential configurations across topographically constrained projection fields requires the existence of functional 'pattern modules' within the topographical synaptology of the junction.

Animals↗
PubMed2026

Clinical efficacy and brain mechanism characteristics of guide chi and regulate spirit tuina therapy in the treatment of post-stroke walking dysfunction: A randomized controlled trial based on fNIRS.

BACKGROUND: This study aims to preliminarily evaluate the role of Guide Chi and Regulate Spirit(GCRS) Tuina in enhancing walking function in post-stroke patients with walking dysfunction; secondly, by using functional near-infrared spectroscopy (fNIRS), it investigates the effect of GCRS Tuina on the restoration of brain function in this patient population. METHODS: Participants in the control group received 4-week rehabilitation treatment, while those in the Combined Tuina Group (CTG) additionally received GCRS Tuina therapy for another 4 weeks on this basis. Functional Ambulation Category (FAC), Fugl - Meyer Assessment Scale for Lower Extremity Motor Function (FMA - LE), and Modified Barthel Index (MBI) were evaluated at the baseline and after 4 treatment weeks. A gait and motion analysis system was used to measure step length, stride, walking speed, and step frequency. FNIRS was used to measure the resting-state functional connectivity(FC) strength, as well as the &#x3b2; - value and HbO2 concentration mean during the walking task. RESULTS: A total of 60 participants completed the randomized, and 53 completed the trial and entered the statistical analysis. Compared with the Single Rehabilitation Group(SRG), the CTG group had higher FAC, FMA-LE, and MBI scores after 4 weeks. After the treatment course, the standardized step length, stride, walking speed, and step frequency of the CTG were higher than SRG. At the Region of Interest(ROI) level, the CTG exhibited 13 inter-ROI FC strengths that were higher than SRG, and the differences could survive the FDR correction (PFDR<0.05). Under the walking task, the CTG group had higher &#x3b2; values in 18 channels and higher Oxyhemoglobin(HbO2) concentrations in 19 channels than the SRG (PFDR <0.05). CONCLUSION: GCRS Tuina therapy can significantly improve patients' walking function, enhance lower limb motor ability and daily living ability. It can improve walking efficiency. Tuina can significantly increase the FC and enhance the activation levels and HbO2 concentrations. The stimulation of Tuina may help reconstruct the brain's motor control network, restore impaired motor function, promote the occurrence of neural plasticity, strengthen the neural circuits in the cognitive-motor-sensory cortex to improve walking function. TRIAL REGISTRATION: This study has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR2024000654).

Humans↗
PubMedDate not supplied

A neural network model of chemotaxis predicts functions of synaptic connections in the nematode Caenorhabditis elegans.

The anatomical connectivity of the nervous system of the nematode Caenorhabditis elegans has been almost completely described, but determination of the neurophysiological basis of behavior in this system is just beginning. Here we used an optimization algorithm to search for patterns of connectivity sufficient to compute the sensorimotor transformation underlying C. elegans chemotaxis, a simple form of spatial orientation behavior in which turning probability is modulated by the rate of change of chemical concentration. Optimization produced differentiator networks capable of simulating chemotaxis. A surprising feature of these networks was inhibitory feedback connections on all neurons. Further analysis showed that feedback regulates the latency between sensory input and behavior. Common patterns of connectivity between the model and biological networks suggest new functions for previously identified connections in the C. elegans nervous system.

Action Potentials↗
PubMed2026

GiGCN: a network-based framework for uncovering synthetic lethal and viable genetic interactions.

Genetic interactions (GIs) underpin the functional connectivity of genes and pathways, and are important for dissecting genotype-phenotype relationships and identifying therapeutic targets for diseases. However, the scale of the human genome restricts systematic experimental interrogation of GIs. Existing computational tools focus on predicting synthetic lethality (SL) and synthetic viability (SV), the two primary forms of GIs, yet their accuracy and biological interpretability are compromised by inadequate modeling of the molecular mechanisms behind positive and negative interactions, as well as the limitation of negative samples. To overcome these challenges, we developed Genetic Interaction Graph Convolutional Network (GiGCN), a signed network modeling framework for the joint identification of gene pairs with SL and SV. We built a high-confidence signed genetic network by integrating verified GIs, and non-interacting gene pairs, together with gene semantic similarity derived from biological processes. By leveraging disentangled subspace decomposition, this framework separately models distinct functional dimensions within gene networks, enabling robust representation of context-dependent regulatory relationships and accurate discrimination of SL and SV events. Benchmark experiments demonstrate that GiGCN outperforms state-of-the-art approaches (area under receiver operating-characteristic curve: 0.978, and area under precision-recall curve: 0.944). Further analyses reveal biologically meaningful insights, including known and novel SL interactions centered on the oncogene MYC Proto-Oncogene (MYC), as well as SV interactions linked to autophagy and mitophagy pathways. This study provides a robust and interpretable network-based strategy for systematically exploring GIs. The GiGCN framework not only improves the precision of SL and SV prediction, but also offers mechanistic insights into gene functional relationships, thereby supporting the discovery of actionable therapeutic targets for cancer and other human diseases.

Humans↗
PubMed2002

Upregulation of EphA receptor expression in the injured adult rat spinal cord.

After spinal cord injury (SCI), the inability of supraspinal neurons to regenerate or reform functional connections is likely due to proteins in the surrounding microenvironment restricting regeneration. EphAs are a family of receptor tyrosine kinases that are involved in axonal guidance during development. These receptors and their ligands, the Ephrins, act via repulsive mechanisms to guide growing axons towards their appropriate targets and allow for the correct developmental connections to be made. In the present study, we investigated whether EphA receptor expression changed after a thoracic contusion SCI. Our results indicate that several EphA molecules are upregulated after SCI. Using semiquantitative RT-PCR to investigate mRNA expression after SCI, we found that EphA3, A4, and A7 mRNAs were upregulated. EphA3, A4, A6, and A8 receptor immunoreactivity increased in the ventrolateral white matter (VWM) at the injury epicenter. EphA7 had the highest level of immunoreactivity in both control and injured rat spinal cord. EphA receptor expression in the white matter originated from glial cells as coexpression in both astrocytes and oligodendrocytes was observed. In contrast, gray matter expression was localized to neurons of the ventral gray matter (motor neurons) and dorsal horn. After SCI, specific EphA receptor subtypes are upregulated and these increases may create an environment that is unfavorable for neurite outgrowth and functional regeneration.

Animals↗