A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

THE RESPONSE OF SKIN MICROCIRCULATION TO HYPERTHERMIC STRESS IN TUMOR PATIENTS

Hyperthermia and its effect on tissues are topics of great interest to scientists working in the area of radiation biology and medicine, It has been shown by many workers, that blood now in malignant tissue displays a different response to heating than that in normal tissue. Initially, the blood flow in tumour tissue is greater than that in normal tissue, and when heat is applied there is an increase in blood flow. The extent of the increase in now with increasing temperature is greater in normal tissue than in tumour tissue. In our laboratory we studied the effect of temperature on skin blood flow. The skin overlying tumour tissue was compared with skin with no underlying abnormality in cancer patients, and with the skin in healthy control subjects. The instrument used was a Laser Doppler Perfusion Monitor, Pf3 (Perimed, Stockholm, Sweden). We found that the skin overlying tumour tissue showed higher basal perfusion than the skin at the contralateral site with no underlying abnormality. The skin above tumour tissue showed a reduced perfusion response to an increase in temperature (vascular sluggishness) compared to skin at the contralateral site and skin in healthy controls. The reduction in thermal response depends on the size of the tumour

APPLICATION OF PLASMA VISCOSITY TO ASSESS THE STATUS OF CANCER-PATIENTS

Cancer is a disease which leads to different systemic changes particularly observed in blood. Plasma viscosity is one of the ways of evaluating such changes. A study of plasma viscosity in oral cancers indicated the status of the disease. In cancer at advanced stage (stage IV), it showed non-Newtonian behaviour. Very high viscosity of plasma at low shear was seen in the patients having poor prognosis

HEMORHEOLOGICAL PROFILES IN CANCER-PATIENTS

This study was undertaken to assess the hemorheological changes due to the presence of malignancy in human subjects and to find the usefulness of the hemorheological changes for the diagnosis and prognosis of malignancy and metastasis. 55 (40 males and 15 females) freshly detected head and neck cancer patients, of age group 30-70 years, were considered for this study. Head and neck cancers are a group of cancers having similar characteristics, hence analysed together. Parameters studied include whole blood viscosity (WBV), plasma viscosity (PV), red cell aggregation (RCA), red cell rigidity (RG), hematocrit (HCT), and concentrations of cholesterol (CHOL), total protein (PRTN), albumin (ALBN), triglyceride (TRG) and fibrinogen (FIBRN) in plasma. 80 (55 males and 25 females) blood samples from age and sex matched normal controls were also analysed for comparison. Cases were divided into two groups. One with moderate whole blood viscosity (Group-I) while the other with high whole blood viscosity (Group-II). The results show that there is significant increase in RCA, PV, RG and FIBRN in cancer patients. It was very interesting to note that in spite of significant elevation of whole blood viscosity in Group-II cases, the hematocrit values were within the normal range. Since HCT is the main factor influencing whole blood viscosity, we suspect the role of some other factor(s) in elevating the WBV. It is likely that tumour cells or their products are present in the blood causing increased WBV. It is also observed that patients with high whole blood viscosity were having the disease at a higher stage (Stage IV)