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The anatomic organization of evoked potentials in rat parietal cortex: electrically evoked commissural responses.

1. Two 8 x 8 channel microelectrode arrays were positioned over 3.5 x 3.5 mm2 areas in homologous regions of right and left parietal cortex of four rats. Potentials were evoked by delivering epicortical electrical stimulation to each electrode on one hemisphere while mapping the commissural response from the contralateral array. Spatial distributions of the electrically evoked potential (EECP) complex were compared directly with cytochrome oxidase-stained sections of the recorded region. 2. Electrode sites most capable of eliciting a commissural EECP were arranged along a diagonal band extending medially from the rostral to caudal region of each electrode array, approximating the pattern of dysgranular cortex separating primary auditory (Te1) from primary somatosensory (Par1) cortex. Electrode sites in the rostromedial and caudolateral region were ineffectual in eliciting an EECP in either hemisphere. Stimulation sites within secondary visual cortex (Oc2L) also produced strong responses. Only weak responses were elicited from stimulation of Te1 and no EECP could be evoked when stimulating within Par1. 3. When an EECP in the maximally sensitive diagonal region was elicited, its spatial distribution was typically asymmetrical throughout the recording array; the response was largest along a diagonal region also extending medially from the rostral to caudal area of each electrode array. Thus the pattern of EECP in each hemisphere closely matched the pattern of electrically excitable regions in the contralateral hemisphere. 4. The EECP was usually heterogeneous. EECP distributions within the strongly responding diagonal area often formed two regions of maximum amplitude separated by a less active zone. Although responses in Te1 were significantly weaker than those in the adjacent dysgranular cortex, they also revealed a heterogeneous spatial distribution with multiple closely spaced maxima. Only responses in Oc2L appeared consistently homogeneous, with a single maximum representing the EECP. 5. These results provide functional evidence supporting a model of parietal cortex in which there are two basic types of recipient regions, densely granular regions, which are the termination sites of specific thalamocortical fibers, and dysgranular or agranular regions, which receive both ipsilateral and contralateral projections. The functional parceling of rodent parietal cortex on the basis of the spatial and temporal distribution of the epicortical evoked potential complex may be superimposed onto the anatomic parceling into granular and dysgranular zones. Implications for stages of sensory information processing are discussed.

Animals↗

Multi-sampling allows intra-tumoral heterogeneity querying and vulnerability profiling in glioblastoma.

BACKGROUND: Glioblastoma (GBM) remains a devastating cancer with limited treatment options, largely due to its heterogeneity. While supramaximal resection has recently provided survival benefits, therapeutic profiling of different tumor compartments, particularly its infiltrative edge remains largely unexplored. METHODS: Here, we leveraged magnetic resonance imaging (MRI)-guided multi-sampling, collecting 2 cores and 2 margins per case, to query GBM heterogeneity. Whole-exome and RNA-seq with drug testing in two patient-derived 3D models were used to reveal similarities and differences in genomic and transcriptomic makeups, cellular compositions, and drug responses across cores and margins. Bioinformatics interrogations further identified response biomarkers. RESULTS: Mutation analysis showed that oncogenes exhibited a higher degree of spatial heterogeneity than tumor suppressor genes, regardless of MRI status. While the mesenchymal transcriptional subtype with extracellular matrix remodeling, stress response, and immune programs were preferentially enriched in enhancing cores, proneural tumors with neurological processes favored non-enhancing margins. Using a 15-drug GBM-targeted panel, ERK (ulixertinib) and PI3K pathway (paxalisib, CC-115) inhibitors showed preferential efficacy in enhancing cores and non-enhancing margins, respectively. The anti-apoptosis, pan-Bcl2 agent navitoclax and the epigenetic drug trotabresib represented the most effective, tumor-wide monotherapies. Importantly, drug combinations generally outperformed single agents across all regions. CONCLUSIONS: This work demonstrates the regional heterogeneity of therapeutic vulnerabilities in GBM ex vivo, showing various drugs with tumor-wide or MRI-enhancement informed activity. These findings offer preclinical bases of numerous monotherapies and drug combinations for future clinical trial design.

Humans↗

Fluctuating Environments and Phytoplankton Community Structure: A Stochastic Model.

Spatial heterogeneity in organism and resource distributions can generate temporal heterogeneity in resource access for simple organisms like phytoplankton. The role of temporal heterogeneity as a structuring force for simple communities is investigated via models of phytoplankton with contrasting life histories competing for a single fluctuating resource. A stochastic model in which environmental and demographic stochasticity are treated separately is compared with a model with deterministic resource variation to assess the importance of stochasticity. When compared with the deterministic model, the stochastic model allows for coexistence over a wider range of parameter values (or life-history types). The model suggests that demographic stochasticity alone is far more important in increasing the possibility of coexistence than environmental stochasticity alone. However, the combined effects of both types of stochasticity produce the largest likelihood of coexistence. Finally, the influence of relative nutrient levels and nutrient pulse frequency on these results is addressed. We relate our findings to variable environment theory with evidence for both relative nonlinearity and the storage effect acting in this model. We show for the first time that temporal dynamics generated by demographic stochasticity may operate like the storage effect at particular spatial scales.

competition↗

Semiparametric proportional odds models for spatially correlated survival data.

The last decade has witnessed major developments in Geographical Information Systems (GIS) technology resulting in the need for statisticians to develop models that account for spatial clustering and variation. In public health settings, epidemiologists and health-care professionals are interested in discerning spatial patterns in survival data that might exist among the counties. This paper develops a Bayesian hierarchical model for capturing spatial heterogeneity within the framework of proportional odds. This is deemed more appropriate when a substantial percentage of subjects enjoy prolonged survival. We discuss the implementation issues of our models, perform comparisons among competing models and illustrate with data from the SEER (Surveillance Epidemiology and End Results) database of the National Cancer Institute, paying particular attention to the underlying spatial story.

Bayes Theorem↗

Heterogeneity of red blood cell velocity in skeletal muscle decreases with increased flow.

OBJECTIVE: Effective material exchange between blood and tissue depends on the heterogeneity of microvascular flow. The objective was to address inconsistencies between intravital studies regarding this dependency. We tested the hypothesis that heterogeneity of red blood cell velocity (VRBC) in capillary beds varies with the strength of metabolic stimulus and with capillary bed geometry. METHODS: We used videomicroscopy to measure VRBC in a bed of 10-24 capillaries at the surface of extensor digitorum longus (EDL) muscle in anesthetized rats. The coefficient of variation (CV = standard deviation/mean; an index of spatial heterogeneity) was computed in the same bed before and after (i) 1, 2, 4, or 8 Hz supramaximal muscle contraction or (ii) adenosine superfusion (10(-7)-10(-3) M). Beds with or without arteriolar-venular capillary shunts were used. RESULTS: Although control VRBC differed between beds (shunt: 232 microns/s; no shunt: 130 microns/s), the percentage increases in postcontraction VRBC did not (range: 111-326%). In both beds, control CV varied greatly (overall range: 28-117%) and 2-8 Hz muscle contractions reduced CV significantly by 25%. Similar results were obtained for adenosine. In confirmatory experiments using the rat cremaster muscle, contractions (4 Hz) and adenosine (10(-4) M) also reduced CV. Based on all data, CV = 63-0.022 VRBC (r = 0.82, P < 0.001). CONCLUSIONS: The heterogeneity of VRBC decreased with metabolic stress, regardless of capillary bed geometry. We propose that both the large variability in control CV and the relatively shallow dependence of CV on velocity could be responsible for the present inconsistencies between intravital studies.

Analysis of Variance↗

Large-scale genomic correlations in Arabidopsis thaliana relate to chromosomal structure.

BACKGROUND: The chromosomes of the plant Arabidopsis thaliana contain various genomic elements, distributed with appreciable spatial heterogeneity. Clustering of and/or correlations between these elements presumably should reflect underlying functional or structural factors. We studied the positional density fluctuations and correlations between genes, indels, single nucleotide polymorphisms (SNPs), retrotransposons, 180 bp tandem repeats, and conserved centromeric sequences (CCSs) in Arabidopsis in order to elucidate any patterns and possible responsible factors for their genomic distributions. RESULTS: The spatial distributions of all these elements obeyed a common pattern: the density profiles of each element within chromosomes exhibited low-frequency fluctuations indicative of regional clustering, and the individual density profiles tended to correlate with each other at large measurement scales. This pattern could be attributed to the influence of major chromosomal structures, such as centromeres. At smaller scales the correlations tended to weaken -- evidence that localized cis-interactions between the different elements had a comparatively minor, if any, influence on their placement. CONCLUSION: The conventional notion that retrotransposon insertion sites are strongly influenced by cis-interactions was not supported by these observations. Moreover, we would propose that large-scale chromosomal structure has a dominant influence on the intrachromosomal distributions of genomic elements, and provides for an additional shared hierarchy of genomic organization within Arabidopsis.

Arabidopsis↗

Heterogeneity of cadmium concentration in soil as a source of uncertainty in plant uptake and its implications for human health risk assessment.

The major route of exposure of humans to the toxic element cadmium (Cd) is via the consumption of vegetables homegrown on Cd contaminated soil. It is well known that soil pH is one of the main soil properties controlling bioavailability of Cd in plants. This is acknowledged in human health risk assessment models that incorporate pH dependant concentration factors (CF=plant Cd/soil Cd). However, variation in spatial heterogeneity of nutrients and heavy metals in soil can have a profound effect on plant performance and uptake of nutrients and heavy metals. Here we show for lettuce (variety Crispino) that variation in plant-scale heterogeneity of Cd in soil affects bioavailability and hence CF by a factor of 2. Plant yield is also significantly affected. This has important implications for both human health risk assessment, as variation in CF affects predicted exposure, and for phytoremediation where an optimal combination of plant yield and contaminant accumulation is required.

Biological Availability↗

Scientist and policy-maker response types and times in suburban watersheds.

Differences between scientist and policy-maker response types and times, or the "how" and "when" of action, constrain effective water resource management in suburbanizing watersheds. Policy-makers are often rushed to find a single policy that can be applied across an entire, homogeneous, geopolitical region, whereas scientists undertake multiyear research projects to appreciate the complex interactions occurring within heterogeneous catchments. As a result, watershed management is often practiced with science and policy out of synch. Meanwhile, development pressures in suburban watersheds create changes in the social and physical fabric and pose a moving target for science and policy. Recent and anticipated advances in the scientific understanding of urbanized catchment hydrology and pollutant transport suggest that management should become increasingly sensitive to spatial heterogeneities in watershed features, such as soil types, terrain slopes, and seasonal watertable profiles. Toward this end, policy-makers should encourage funding scientific research that characterizes the impacts of these watershed heterogeneities within a geopolitical zoning and development framework.

Cities↗

Mouse models of childhood cancer of the nervous system.

Targeted cancer treatments rely on understanding signalling cascades, genetic changes, and compensatory programmes activated during tumorigenesis. Increasingly, pathologists are required to interpret molecular profiles of tumour specimens to target new treatments. This is challenging because cancer is a heterogeneous disease-tumours change over time in individual patients and genetic lesions leading from preneoplasia to malignancy can differ substantially between patients. For childhood tumours of the nervous system, the challenge is even greater, because tumours arise from progenitor cells in a developmental context different from that of the adult, and the cells of origin, neural progenitor cells, show considerable temporal and spatial heterogeneity during development. Thus, the underlying mechanisms regulating normal development of the nervous system also need to be understood. Many important advances have come from model mouse genetic systems. This review will describe several mouse models of childhood tumours of the nervous system, emphasising how understanding the normal developmental processes, combined with mouse models of cancer and the molecular pathology of the human diseases, can provide the information needed to treat cancer more effectively.

Animals↗

Handling time promotes the coevolution of aggregation in predator-prey systems.

Predators often have type II functional responses and live in environments where their life history traits as well as those of their prey vary from patch to patch. To understand how spatial heterogeneity and predator handling times influence the coevolution of patch preferences and ecological stability, we perform an ecological and evolutionary analysis of a Nicholson-Bailey type model. We prove that coevolutionarily stable prey and searching predators prefer patches that in isolation support higher prey and searching predator densities, respectively. Using this fact, we determine how environmental variation and predator handling times influence the spatial patterns of patch preferences, population abundances and per-capita predation rates. In particular, long predator handling times are shown to result in the coevolution of predator and prey aggregation. An analytic expression characterizing ecological stability of the coevolved populations is derived. This expression implies that contrary to traditional theoretical expectations, predator handling time can stabilize predator-prey interactions through its coevolutionary influence on patch preferences. These results are shown to have important implications for classical biological control.

Animals↗

X-ray microCT study of pyramids of the sea urchin Lytechinus variegatus.

This paper reports results of a novel approach, X-ray microCT, for quantifying stereom structures applied to ossicles of the sea urchin Lytechinus variegatus. MicroCT, a high resolution variant of medical CT (computed tomography), allows noninvasive mapping of microstructure in 3-D with spatial resolution approaching that of optical microscopy. An intact pyramid (two demipyramids, tooth epiphyses, and one tooth) was reconstructed with 17 microm isotropic voxels (volume elements); two individual demipyramids and a pair of epiphyses were studied with 9-13 microm isotropic voxels. The cross-sectional maps of a linear attenuation coefficient produced by the reconstruction algorithm showed that the structure of the ossicles was quite heterogeneous on the scale of tens to hundreds of micrometers. Variations in magnesium content and in minor elemental constitutents could not account for the observed heterogeneities. Spatial resolution was insufficient to resolve the individual elements of the stereom, but the observed values of the linear attenuation coefficient (for the 26 keV effective X-ray energy, a maximum of 7.4 cm(-1) and a minimum of approximately 2 cm(-1) away from obvious voids) could be interpreted in terms of fractions of voxels occupied by mineral (high magnesium calcite). The average volume fraction of mineral determined for a transverse slice of the demipyramid near where it joins an epiphysis was 0.46; for a slice 3.3 mm adoral it was 0.70. Local volume fractions of mineral approached 1, and, away from resolvable voids, considerable portions of the demipyramids had volume fractions of calcite at or below approximately 0.33. MicroCT imaging of a demipyramid before and after infiltration with a high absorptivity fluid (sodium polytungstate) confirmed the determination of the volume fractions of minerals.

Animals↗

Simultaneous analysis of spatio-temporal gene expression for cephamycin biosynthesis in Streptomyces clavuligerus.

Linkage between structural and regulatory genes implies that a direct correlation should exist between the spatio-temporal distribution of their expression. Green fluorescent protein (GFP) and cyan fluorescent protein (CFP) were used as reporters to analyze simultaneously expression of lysine-epsilon-aminotransferase (LAT) and its corresponding genetic regulator, CcaR. The isogenic strain containing lat::gfp and ccaR::cfp in the chromosome produced cephamycin C at levels similar to wild type Streptomyces clavuligerus. Confocal laser scanning microscopy revealed that expression of both LAT and CcaR in liquid culture was temporally dynamic and spatially heterogeneous in S. clavuligerus mycelia. During the early culture stage only a part of the mycelia began to express LAT and CcaR at low levels. As the culture aged, expression levels and the population of mycelia expressing LAT and CcaR increased and were followed late in the growth cycle by a reduction of the mycelia population expressing LAT and CcaR. The approach provides a precise simultaneous temporal-spatial expression profile and corroborates the regulatory linkage between ccaR and lat in S. clavuligerus.

Blotting, Western↗

Density-dependent foraging behaviors in a parasitoid lead to density-dependent parasitism of its host.

Empirical studies of spatial heterogeneity in parasitism by insect parasitoids have focused largely on patterns, while the many possible underlying mechanisms have been little studied in the field. We conducted experimental and observational studies on Tachinomyia similis (Diptera: Tachinidae) attacking western tussock moths (Orgyia vetusta; Lepidoptera: Lymantriidae) on lupine bushes at Bodega Bay, Calif., USA. We examined several foraging behaviors that have been hypothesized to create density-dependent variation in parasitism rates, including spatial aggregation of parasitoids to high host density, mutual interference among searching parasitoids and decelerating functional responses of the parasitoid. At the spatial scale of individual bushes, we detected both aggregation to a high density and a decelerating functional response. The resulting spatial pattern of parasitism was best fit by two models; one included an effect of parasitoid aggregation and the other included an effect of aggregation and a decelerating functional response. Most of the variation in parasitism was not correlated with density of O. vetusta.

Animals↗

Heterogeneity of regional cerebral glucose metabolism demonstrated in situ in rat brain by 19F NMR rotating frame zeugmatography: one dimensional chemical shift imaging of normal and gliosarcoma implanted brain.

Using 19-fluorine (19F) as nuclear magnetic resonance (NMR) signal probe and 2-fluoro-2-deoxy-D-glucose (2-FDG) as metabolic probe, one dimensional "imaging" (metabolite mapping) of pathway specific glucose metabolism in the pentose monophosphate shunt (PMS) and aldose reductase sorbitol (ARS) pathways were performed in situ in rat brain utilizing one dimensional rotating frame zeugmatography. Normal brain showed highest PMS activities in the brainstem consonant with known spatially heterogeneous concentration of glucose-6-phosphate dehydrogenase, the rate limiting enzyme for the PMS. The brain harboring sufficiently large gliosarcoma in the cerebrum showed a higher PMS/ARS area ratio indicating higher PMS activities in tumor which was localized by zeugmatography. The present study demonstrated the feasibility of studying regional glucose metabolism in the PMS and ARS utilizing 2-FDG.

Aldehyde Reductase↗

Decoding the spatiotemporal patterns of food spoilage microbial communities: Integrating multi-omics and artificial intelligence to enable precision preservation.

In the global food supply chain, food wastage caused by spoilage has resulted in significant economic losses, food shortages, and environmental pressure. This process is fundamentally driven by the spatiotemporal dynamics of microbial communities. However, traditional research methods struggle to elucidate the complex mechanisms of spatial heterogeneity, interspecies interactions, and functional succession. This limits the development of effective preservation strategies. This review systematically reviews the cutting-edge progress of integrating multi-omics technologies and artificial intelligence (AI) to study food spoilage microbial communities, breaking through this bottleneck. We propose an intelligent theoretical framework that could potentially analyze microbial metabolic activities and predict dynamic shelf life if implemented. The conceptual framework integrates multidimensional data, including spatial metabolomics, temporal metatranscriptomics, single-cell transcriptomics, and longitudinal metagenomics. It can also be combined with AI models, such as graph neural networks. The article elaborates on the principles and applications of spatio-temporal monitoring technologies, such as nano secondary ion mass spectrometry, hyperspectral imaging, and the Internet of Things sensing. Through illustrative cases of typical perishable foods, it also explores how such a multi-omics - AI system might be applied to spoilage warning and precise intervention. Additionally, the article addresses the current challenges in data coverage, model generalization, and federated learning implementation. Then the research further explores emerging areas such as engineered probiotics, edge AI, and microfluidic sensing. These areas are targeted at transforming food preservation from an empirical control approach to a data-driven, precise regulatory framework. This transformation provides theoretical support and technical approaches for developing a smart, sustainable food preservation system.

Multiomics↗

Temporal distributions of red cell supply rate to individual capillaries of resting skeletal muscle, in frog and rat.

Microvascular red cell (RBC) supply in resting skeletal muscle fluctuates with time and varies from capillary to capillary. Our aim was to quantitate this heterogeneity in two species (frog, rat) with very different oxygen requirements. Video recordings were made of RBC flow in capillaries associated with superficial fibers of frog sartorius and rat gracilis muscles, for periods of 2-10 min. RBC supply rate (cell/s) to individual capillaries was computed as the product of RBC 'content' (measured as lineal density, cells/mm, by a video-densitometric method) and RBC velocity (mm/s, measured by a spatial correlation technique). The videotapes were analyzed at rates of 6 to 15 samples per second. Regression analysis of the mean data showed little or no correlation between RBC content and RBC velocity (r2: frog 0.095, rat 0.002), both parameters contributing equally to variations in RBC supply rate. Temporal distributions of the three supply parameters demonstrate (1) the wide range of values present within each capillary, and (2) the symmetry of the distributions at high mean values versus a pronounced skewness as mean values approached zero. The wide range of mean values of each parameter, found in both species, suggests considerable 'spatial' heterogeneity of RBC supply among capillaries in resting muscle. Temporal heterogeneity of RBC supply rate to individual capillaries increased markedly as either velocity or content (or both) approached zero (overall mean coefficient of variation: frog, 62%; rat, 100%). Both species show remarkably similar rates of convective transport of RBCs per capillary in resting muscle (e.g. mean supply rates 3.2 and 6.2 RBCs/s in frog and rat, respectively).

Animals↗

Spatio-temporal distribution of Plasmodium falciparum and p. Vivax malaria in Thailand.

Malaria incidence data at the district level from 1997 to 2002 and total malaria case data from 1965 to 2002 in Thailand were analyzed to determine the spatial and temporal dynamics of Plasmodium falciparum and P. vivax malaria incidence. Over the 37-year period, there was a 35-fold reduction in the incidence rates of P. falciparum malaria (11.86% in 1965 versus 0.34% in 2002) and a 7-fold reduction in P. vivax malaria (2.89% in 1965 versus 0.40% in 2002). The incidence ratio of P. falciparum to P. vivax malaria was reduced from 4.1 to 0.8 during this period. Malaria incidence rate exhibited the most rapid reduction between 1975 and 1985, coinciding with the introduction of a combination of antifolate drugs (sulfadoxine-pyrimethamine). The distribution maps of P. falciparum and P. vivax malaria incidence rates indicated a high spatial heterogeneity. The Thailand-Myanmar and Thailand-Cambodia border areas, where migration of foreign workers was pronounced, had the highest incidence rates for P. falciparum, P. vivax, and mixed-species infections. Transition probability analysis based on the malaria incidence rate among Thai residents indicated that there was an overall trend of decrease in the number of malaria cases and the number of high incidence districts between 1997 and 2002. High spatial variation in malaria incidence and local human migration patterns suggest that malaria control measures need to be adjusted according to local environmental and demographic settings.

Animals↗

Robustness of gene expression profiling in glioma specimen samplings and derived cell lines.

One of the most promising applications of microarrays is class distinction through gene expression profiling as a diagnostic tool. However, as there is apparent spatial heterogeneity in the morphology of cancer cells within a tumor, it is unclear if tumor sampling can be applied and yield consistent signals. In this report, we examined six brain tumors, four glioblastoma, and two oligodendroglioma biopsies. The six brain tumor tissues from two distinct different classes were dissected in four distinct areas and gene expression was profiled using microarrays. We used hierarchical clustering to compare the variability of gene expression profiles between spatially distinct biopsies of the same tumor as compared to the variability between tumors of the same histologic group. We conclude that, in general, repeat spatially distinct samples are not needed for microarray experiments and the gene expression signatures are robust across the tumor. Predominantly, variation was much greater between samples from different patients than from the multiple samplings of given tumor. Further, we compared biopsy expression profiles to the cell lines derived from those tissues. In general, the tumor cell lines vary greatly from the parental tissues and cluster more strongly with each other than the parental tissue. We select and examine the set of genes altered in expression to allow adaptation to cell culture.

Brain Neoplasms↗