Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus.

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

IL-6 dependent expansion of inflammatory MDSCs (CD11b+ Gr-1+) promote Th-17 mediated immune response during experimental cerebral malaria.

Myeloid derived suppressor cells (MDSCs) are a group of heterogeneous cell populations that can suppress T cell responses. Various aspects of MDSCs in regulating immune responses in several cancer and infectious diseases have been reported till date. But the role and regulation of MDSCs have not been systematically studied in the context of malaria. This study depicts the phenotypic and functional characteristics of splenic MDSCs and how they regulate Th-17 mediated immune response during Experimental Cerebral Malaria (ECM). Flow cytometric analysis reveals that MDSCs in the spleen and bone marrow expand at 8 dpi during ECM. Among subtypes of MDSCs, PMN-MDSCs show significant expansion in the spleen but M-MDSCs remain unaltered. Functional analysis of sorted MDSCs from spleens of Plasmodium berghei ANKA (PbA) infected mice shows suppressive nature of these cells and high production of Nitric oxide (NO). Besides, MDSCs were also found to express various inflammatory markers during ECM suggesting the M1 type phenotype of these cells. In-vivo depletion of MDSCs by the use of Anti Gr-1 increases mice survival but doesn't significantly alter the parasitemia. Previously, it has been reported that Treg/Th-17 balance in the spleen is skewed towards Th-17 during ECM. Depletion of MDSCs was found to regulate Th-17 percentages to homeostatic levels and subvert various inflammatory changes in the spleen. Among different factors, IL-6 was found to play an important role in the expansion of MDSCs and expression of inflammatory markers on MDSCs in a STAT3-dependent manner. These findings provide a unique insight into the role of IL-6 in the expansion of the MDSC population which causes inflammatory changes and increased Th-17 responses during ECM.

Functional networks in non-human primate spinal cord and the effects of injury.

Spontaneous fluctuations of Blood Oxygenation-Level Dependent (BOLD) MRI signal in a resting state have previously been detected and analyzed to describe intrinsic functional networks in the spinal cord of rodents, non-human primates and human subjects. In this study we combined high resolution imaging at high field with data-driven Independent Component Analysis (ICA) to i) delineate fine-scale functional networks within and between segments of the cervical spinal cord of monkeys, and also to ii) characterize the longitudinal effects of a unilateral dorsal column injury on these networks. Seven distinct functional hubs were revealed within each spinal segment, with new hubs detected at bilateral intermediate and gray commissure regions in addition to the bilateral dorsal and ventral horns previously reported. Pair-wise correlations revealed significantly stronger connections between hubs on the dominant hand side. Unilateral dorsal-column injuries disrupted predominantly inter-segmental rather than intra-segmental functional connectivities as revealed by correlation strengths and graph-theory based community structures. The effects of injury on inter-segmental connectivity were evident along the length of the cord both below and above the lesion region. Connectivity strengths recovered over time and there was revival of inter-segmental communities as animals recovered function. BOLD signals of frequency 0.01-0.033 Hz were found to be most affected by injury. The results in this study provide new insights into the intrinsic functional architecture of spinal cord and underscore the potential of functional connectivity measures to characterize changes in networks after an injury and during recovery.

Partial impairment of late-stage autophagic flux in murine splenocytes leads to sqstm1/p62 mediated nrf2-keap1 antioxidant pathway activation and induced proteasome-mediated degradation in malaria.

Splenomegaly, a major symptom in Plasmodium infection, is extensively studied for its immunopathological role in mice malaria model infected with Plasmodium berghei ANKA. The status of autophagic regulation in hosts in malaria pathogenesis remains unreported till date. This study demonstrated the autophagy, proteasomal degradation and NRF2-KEAP1 antioxidant pathway status in the host during Plasmodium infection taking murine spleen as our organ of interest. Initial staining and autophagic gene expression indicate a possibility of autophagic pathway activation. Although the conversion of LC3A to LC3B and lysosome-autophagosome fusion increases, the final degradation step remains incomplete. Resultant upregulation of p62 and its altered phosphorylated status enhances its binding to keap1 causing NRF2 translocation to the nucleus. NRF2 act as transcription factor upregulating p62 level itself leading to an autoinduction loop of p62 expression. Interestingly, enhancement of P62 interaction with proteasome subunit RPT1 indicates a possible role in transporting ubiquitinated cargo to proteasome complex. Ubiquitination level increased with subsequent upregulation of all three modes of proteasomal degradation i.e trypsin-like, caspase-like and especially chymotrypsin-like. Sqstm1/p62 plays a critical central role in regulating autophagy, proteasomal degradation, and NRF2-KEAP1 pathway. The incomplete autophagic flux in the final step may be a key therapeutic target, as autophagic degradation and subsequent pathogenic peptide presentation is of utmost necessity for downstream immune response.

Glioma grading using a machine-learning framework based on optimized features obtained from T1 perfusion MRI and volumes of tumor components.

BACKGROUND: Glioma grading between intermediate grades (Grade II vs. III and Grade III vs. IV) as well as multiclass grades (Grade II vs. III vs. IV) is challenging and needs to be addressed. PURPOSE: To develop an artificial intelligence-based methodology for glioma grading using T1 perfusion parameters and volume of tumor components, and validate the efficacy of the methodology by grading on a cohort of glioma patients. STUDY TYPE: Retrospective. POPULATION: The development set consisted of 53 glioma patients and validation consisted of 13 glioma patients. FIELD STRENGTH/SEQUENCE: Conventional MRI images (2D T1 -W, dual PD-T2 -W, and 3D FLAIR) and 3D T1 perfusion MRI data obtained at 3 T. ASSESSMENT: Enhancing and nonenhancing components of glioma were segmented out and combined to form the region of interest (ROI) for glioma grading. Prominent vessels were removed from the selected ROI. Different T1 perfusion parameters from the ROI were combined with volume of tumor components to form the feature set for glioma grading. Optimization was carried out for selection of the statistic of the T1 perfusion parameters and the features to be used for glioma grading using sequential feature selection and random forest-based feature selection method. An optimized support vector machine (SVM) classifier was used for glioma grading. STATISTICAL TESTS: Mean ± SD, analysis of variance (ANOVA) followed by the Tukey-Kramer test, ROC analysis. RESULTS: Classification error for Grade II vs. III was 3.7%, for Grade III vs. IV was 5.26%, and for Grade II vs. III vs. IV was 9.43% using the proposed methodology. The mean of the values above the 90th percentile value of T1 perfusion parameters provided a maximum area under the curve (AUC) for intermediate grade differentiation. Random forest obtained optimal feature set provided better grading results than other methods using the SVM classifier. DATA CONCLUSION: It was feasible to achieve low classification error for intermediate as well as multiclass glioma grading using an SVM classifier based on optimized features obtained from T1 perfusion MRI and volumes of tumor components. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1295-1306.

Influence of autophagy, apoptosis and their interplay in filaricidal activity of C-cinnamoyl glycosides.

The present work aims to explore the mechanism of action of C-cinnamoyl glycoside as an antifilarial agent against the bovine filarial nematode Setaria cervi. Both apoptosis and autophagy programmed cell death pathways play a significant role in parasitic death. The generation of reactive oxygen species, alteration of the level of antioxidant components and disruption of mitochondrial membrane potential may be the causative factors that drive the parasitic death. Monitoring of autophagic flux via the formation of autophagosome and autophagolysosome was detected via CYTO ID dye. The expression profiling of both apoptotic and autophagic marker proteins strongly support the initial findings of these two cell death processes. The increased interaction of pro-autophagic protein Beclin1 with BCL-2 may promote apoptotic pathway by suppressing anti-apoptotic protein BCL-2 from its function. This in turn partially restrains the autophagic pathway by engaging Beclin1 in the complex. But overall positive increment in autophagic flux was observed. Dynamic interaction and regulative balance of these two critical cellular pathways play a decisive role in controlling disease pathogenesis. Therefore, the present experimental work may prosper the chance for C-cinnamoyl glycosides to become a potential antifilarial therapeutic in the upcoming day after detail in vivo study and proper clinical trial.

Evaluation of B1 inhomogeneity effect on DCE-MRI data analysis of brain tumor patients at 3T.

BACKGROUND: Dynamic-contrast-enhanced (DCE) MRI data acquired using gradient echo based sequences is affected by errors in flip angle (FA) due to transmit B1 inhomogeneity (B1inh). The purpose of the study was to evaluate the effect of B1inh on quantitative analysis of DCE-MRI data of human brain tumor patients and to evaluate the clinical significance of B1inh correction of perfusion parameters (PPs) on tumor grading. METHODS: An MRI study was conducted on 35 glioma patients at 3T. The patients had histologically confirmed glioma with 23 high-grade (HG) and 12 low-grade (LG). Data for B1-mapping, T1-mapping and DCE-MRI were acquired. Relative B1 maps (B1rel) were generated using the saturated-double-angle method. T1-maps were computed using the variable flip-angle method. Post-processing was performed for conversion of signal-intensity time (S(t)) curve to concentration-time (C(t)) curve followed by tracer kinetic analysis (Ktrans, Ve, Vp, Kep) and first pass analysis (CBV, CBF) using the general tracer-kinetic model. DCE-MRI data was analyzed without and with B1inh correction and errors in PPs were computed. Receiver-operating-characteristic (ROC) analysis was performed on HG and LG patients. Simulations were carried out to understand the effect of B1 inhomogeneity on DCE-MRI data analysis in a systematic way. S(t) curves mimicking those in tumor tissue, were generated and FA errors were introduced followed by error analysis of PPs. Dependence of FA-based errors on the concentration of contrast agent and on the duration of DCE-MRI data was also studied. Simulations were also done to obtain Ktrans of glioma patients at different B1rel values and see whether grading is affected or not. RESULTS: Current study shows that B1rel value higher than nominal results in an overestimation of C(t) curves as well as derived PPs and vice versa. Moreover, at same B1rel values, errors were large for larger values of C(t). Simulation results showed that grade of patients can change because of B1inh. CONCLUSIONS: B1inh in the human brain at 3T-MRI can introduce substantial errors in PPs derived from DCE-MRI data that might affect the accuracy of tumor grading, particularly for border zone cases. These errors can be mitigated using B1inh correction during DCE-MRI data analysis.

Differential modulation of glial cell mediated neuroinflammation in Plasmodium berghei ANKA infection by TGF ß and IL 6.

Modulation of pro-inflammatory and anti-inflammatory axis and orientation of glial cell function towards neuroinflammation, were hallmark signs of cerebral malaria (CM). CM pathogenesis was concerned with the circulating levels of Interleukin 6 (IL 6) and Transforming growth factor ß (TGF ß). Definite roles of these two cytokines in brain related pathology remained largely unexplored. To study the effect of these two cytokines, we have examined changes in morphology and in activation profile of the glial cells after TGF ß and IL 6 neutralization during CM in cortex and cerebellum of the Plasmodium berghei ANKA (PbA) infected male swiss albino mice. PbA infection caused severe inflammation by inducing changes in morphological features as well as in activation profile of the astrocytes and microglia. Similar inflammatory signs were evident in Anti TGF ß treated set. Interestingly in the Anti IL 6 treated set, reduced level of activation of these glial cells corresponds to the reduced level of inflammatory profile. Microglial activation was found to be synchronous with TLR4 engagement. Neuronal death was triggered by neuroinflammatory milieu seen in PbA and PbA+Anti TGF ß treated set. In conclusion, it can be said that IL 6 and TGF ß perform essential role in CM pathogenesis by modulating the level of glial cell induced neuroinflammation.

Role of TGF-ß and IL-6 in dendritic cells, Treg and Th17 mediated immune response during experimental cerebral malaria.

The role of cytokines in Plasmodium infection have been extensively investigated, but pro and anti inflammatory cytokines mediated imbalance during malaria immune-pathogenesis is still unrevealed. Malaria is associated with the circulating levels of Interleukin-6 (IL-6) and transforming growth factor ß (TGF-ß), but association between these two cytokines in immune response remains largely obscured. Using mouse model, we proposed that IL-6 and TGF-ß are involved in immune regulation of dendritic cells (DC), regulatory T cells (Treg), T-helper cells (Th17) during P. berghei ANKA (PbA) infection. Association between the cytokines and the severity of malaria was established with anti-TGF-ß treatment resulting in increased parasitemia and increased immunopathology, whereas; anti-IL-6 treatment delays immunopathology during PbA infection. Further, splenocytes revealed differential alteration of myeloid DC (mDC), plasmocytoid DC (pDC), Treg, Th17 cells following TGF-ß and IL-6 neutralization. Interestingly anti-TGF-ß reduces CD11c+CD8+ DC expression, whereas anti-IL-6 administration causes a profound increase during PbA infection in Swiss mice. We observed down regulation of TGF-ß, IL-10, NFAT, Foxp3, STAT-5 SMAD-3 and upregulation of IL-6, IL-23, IL-17 and STAT-3 in splenocytes during PbA infection. The STAT activity probably plays differential role in induction of Th17 and Treg cells. Interestingly we found increase in STAT-3 and decrease in STAT-5 expression during PbA infection. This pattern of STAT indicates that possibly TGF-ß and IL-6 play a crucial role in differentiation of DCs subsets and Treg/Th17 imbalance during experimental cerebral malaria (ECM).

Dendritic cells subsets mediated immune response during Plasmodium berghei ANKA and Plasmodium yoelii infection.

The roles of dendritic cells (DCs) in mediating immunity against Plasmodium infection have been extensively investigated, but immune response during pathogenesis of malaria is still poorly understood. In the present study, we compared the splenic DCs phenotype and function during P. berghei ANKA (PbA) or P. yoelii (P. yoelii) infection in Swiss mice. We observed that PbA-infected mice developed more myeloid and mature DCs capable of secreting IL-12, while P. yoelii-infected mice had more plasmacytoid and immature DCs secreting higher levels of IL-10. Expression of FoxP3, IL-17, TGF-ß and IL-6 were also different between these two infections. Thus, these results suggest that the phenotypic and functional subsets of splenic DCs are key factors for regulating immune responses to PbA and P. yoelii infections.

Secure hardware IP of GLRT cascade using color interval graph based embedded fingerprint for ECG detector.

This paper presents a security aware design methodology to design secure generalized likelihood ratio test (GLRT) hardware intellectual property (IP) core for electrocardiogram (ECG) detector against IP piracy and fraudulent claim of IP ownership threats. Integrating authentic (secure version) GLRT hardware IP core in the system-on-chip (SoC) of ECG detectors is paramount for reliable operation and estimation of ECG parametric data, such as Q wave, R wave and S wave (QRS) complex detection. A pirated GLRT hardware IP integrated into an ECG detector may result in an unreliable/erratic estimation of ECG parametric data that can be hazardous and fatal for the end patient. The proposed methodology presents an integrated design flow to secure micro GLRT and GLRT cascade hardware IP cores for the ECG detector, using the colored interval graph (CIG) framework based fingerprint biometric, during high level synthesis (HLS). The proposed approach integrates a fingerprint biometric based security constraint generation process for securing the GLRT hardware IP core. This paper also presents a secure register transfer level (RTL) datapath design corresponding to micro GLRT and GLRT cascade hardware IP cores with embedded IP vendor's fingerprint. The proposed secure GLRT hardware IP core embedded with fingerprint biometric achieves superior results in terms of probability of coincidence and tamper tolerance than other security approaches. More explicitly, the proposed approach reports a significantly lower value of probability of coincidence and stronger value for tamper tolerance. Further, the proposed approach incurs zero design cost overhead.

Bio-mimicking DNA fingerprint profiling for HLS watermarking to counter hardware IP piracy.

The multifaceted, multivendor-based global design supply chain induces hardware threats of intellectual property (IP) piracy for modern computing and electronic systems. Current hardware watermarking techniques fall short either in terms of watermark strength (size of covert constraints generated) or number of security layers/variables involved in the security constraints generation process. This paper presents a novel approach for high level synthesis (HLS) watermarking by bio-mimicking DNA fingerprint profiling to counter hardware IP piracy. The proposed approach effectively captures the vital DNA fingerprint profiling phases such as DNA sequencing, DNA fragmentation, fragment replication, DNA ligase, etc. and bio-mimics them to generate a digital watermarking framework. The presented approach has been demonstrated on convolutional layer and JPEG compression-decompression (CODEC) algorithms that are widely used in several medical and machine learning applications. The proposed approach has been thoroughly compared with several state-of-the-art approaches. The proposed approach depicts superior security in the probability of coincidence of up to ~ 104 and tamper tolerance of up to ~ 10368 at 0% overhead as compared to the prior approaches.

Differential Immune Response Patterns Induced by Anionic and Cationic Lipid Adjuvants in Intranasal Anti-Influenza Immunization.

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation.

Estimating nitric oxide (NO) from MDSCs by Griess method.

The functional importance of nitric oxide (NO) in the fields of immunology concerning its antimicrobial, anti-tumoral, anti-inflammatory, and immunosuppressive effects have made it inevitable to study its secretion from various cells. Nitrogen oxide synthase (NOS) is the enzyme responsible for synthesizing NO and its three isoforms function in a cell-dependent manner. NO is oxidized rapidly to Reactive nitrogen oxide species (RNOS) through which the roles of NO are being carried out. One of the major immune cells secreting NO is myeloid-derived suppressor cells (MDSCs). The function of these MDSCs in the suppression of T-cell proliferation as well as T-cell differentiation is found to be dependent on NO secretion. Apart from T-cell suppressive activity, NO is also known to interfere with natural killer (NK) cell functions. A convenient method to estimate NO secretion is by using Griess reagent named after Johann Peter Griess. In this method, NO reacts with the reagents to form a colored azo dye detectable using a microplate reader at a wavelength of 548nm. In this chapter, we summarized the detailed method of estimating NO from MDSCs by the Griess method.

Administration of rIL-33 Restores Altered mDC/pDC Ratio, MDSC Frequency, and Th-17/Treg Ratio during Experimental Cerebral Malaria.

The onset of malaria causes the induction of various inflammatory markers in the host's body, which in turn affect the body's homeostasis and create several cerebral complications. Polarization of myeloid-derived suppressor cells (MDSCs) from the classically activated M1 to alternatively activated M2 phenotype increases the secretion of pro-inflammatory molecules. Treatment with recombinant IL-33 (rIL-33) not only alters this MDSC's polarization but also targets the glycolysis pathway of the metabolism in MDSCs, rendering them less immunosuppressive. Along with that, the Helper T-cells subset 17 (Th17)/T regulatory cells (Tregs) ratio is skewed towards Th17, which increases inflammation by producing more IL-17. However, treating with rIL-33 also helps to restore this ratio, which brings back homeostasis. During malaria infection, there is an upregulation of IL-12 production from dendritic cells along with a distorted myeloid dendritic cells (mDC)/plasmacytoid dendritic cells (pDC) ratio towards mDCs promoting inflammation. Administering rIL-33 will also subvert this IL-12 production and increase the population of pDC in the host's immune system during malaria infection, thus restoring mDC/pDC to homeostasis. Therefore, treatment with rIL-33 to reduce the pro-inflammatory signatures and maintenance of immune homeostasis along with the increase in survivability could be a potential therapeutic approach for cerebral malaria.

Sex-Specific Immune Responses to Seasonal Influenza Vaccination in Diabetic Individuals: Implications for Vaccine Efficacy.

Seasonal influenza vaccination has different implications on the immune response depending on the comorbidities. Diabetes is one such critical disease that increases the patient's susceptibility to influenza and suppresses vaccine efficacy and immunity. The sex of the individuals also plays a definitive role in the immune responses to both the vaccine and the infection. This study aims to understand the efficacy of the seasonal vaccine against influenza in diabetic groups and undergoing immune mechanisms in different sexes (females and males). In this study, we are reporting about a switching of the immune response of the infected and vaccinated diabetic females towards stronger Th1/Th17 responses with suppressed humoral immunity. They show increased cDC1, enhanced proinflammatory activities within T cells, CD8T activation, Th17 proliferation, and the majority of IgG2 antibody subtypes with reduced neutralization potential. Males with diabetes exhibit enhanced humoral Th2-immunity than the nondiabetic group. They exhibit higher cDC2, and DEC205 levels within them with an increase in plasma B lymphocytes, higher IgG1 subtypes in plasma cells, and influenza-hemagglutinin-specific IgG titer with stronger virus neutralization potential. Males with diabetes recovered better than the females as observed from the changes in their body weight. This study highlights the critical immune mechanisms and sex-specific swapping of their preferred immune response pathways against influenza after vaccination during diabetes. We propose a need for a sex-specific customized vaccine regimen to be implemented against influenza for individuals having diabetes to exploit the manifested strength and weakness in their protective immunity.

Identification of synchronous BOLD signal patterns in white matter of primate spinal cord.

Functional MRI studies of the brain have shown that blood-oxygenation-level-dependent (BOLD) signals are robustly detectable not only in gray matter (GM) but also in white matter (WM). Here, we report the detection and characteristics of BOLD signals in WM of spinal cord (SC) of squirrel monkeys. Tactile stimulus-evoked BOLD signal changes were detected in the ascending sensory tracts of SC using a General-Linear Model (GLM) as well as Independent Component Analysis (ICA). ICA of resting state signals identified coherent fluctuations from eight WM hubs which correspond closely with known anatomical locations of SC WM tracts. Resting state analyses showed that the WM hubs exhibited correlated signal fluctuations within and between SC segments in specific patterns that correspond well with the known neurobiological functions of WM tracts in SC. Overall, these findings suggest WM BOLD signals in SC show similar features as GM both at baseline and under stimulus conditions.

Detection and characterization of resting state functional networks in squirrel monkey brain.

Resting-state fMRI based on analyzing BOLD signals is widely used to derive functional networks in the brain and how they alter during disease or injury conditions. Resting-state networks can also be used to study brain functional connectomes across species, which provides insights into brain evolution. The squirrel monkey (SM) is a non-human primate (NHP) that is widely used as a preclinical model for experimental manipulations to understand the organization and functioning of the brain. We derived resting-state networks from the whole brain of anesthetized SMs using Independent Component Analysis of BOLD acquisitions. We detected 15 anatomically constrained resting-state networks localized in the cortical and subcortical regions as well as in the white-matter. Networks encompassing visual, somatosensory, executive control, sensorimotor, salience and default mode regions, and subcortical networks including the Hippocampus-Amygdala, thalamus, basal-ganglia and brainstem region correspond well with previously detected networks in humans and NHPs. The connectivity pattern between the networks also agrees well with previously reported seed-based resting-state connectivity of SM brain. This study demonstrates that SMs share remarkable homologous network organization with humans and other NHPs, thereby providing strong support for their suitability as a translational animal model for research and additional insight into brain evolution across species.

Differentiation of Pilocytic Astrocytoma from Glioblastoma using a Machine-Learning framework based upon quantitative T1 perfusion MRI.

BACKGROUND AND PURPOSE: Differentiation of pilocytic astrocytoma (PA) from glioblastoma is difficult using conventional MRI parameters. The purpose of this study was to differentiate these two similar in appearance tumors using quantitative T1 perfusion MRI parameters combined under a machine learning framework. MATERIALS AND METHODS: This retrospective study included age/sex and location matched 26 PA and 33 glioblastoma patients with tumor histopathological characterization performed using WHO 2016 classification. Multi-parametric MRI data were acquired at 3 T scanner and included T1 perfusion and DWI data along with conventional MRI images. Analysis of T1 perfusion data using a leaky-tracer-kinetic-model, first-pass-model and piecewise-linear-model resulted in multiple quantitative parameters. ADC maps were also computed from DWI data. Tumors were segmented into sub-components such as enhancing and non-enhancing regions, edema and necrotic/cystic regions using T1 perfusion parameters. Enhancing and non-enhancing regions were combined and used as an ROI. A support-vector-machine classifier was developed for the classification of PA versus glioblastoma using T1 perfusion MRI parameters/features. The feature set was optimized using a random-forest based algorithm. Classification was also performed between the two tumor types using the ADC parameter. RESULTS: T1 perfusion parameter values were significantly different between the two groups. The combination of T1 perfusion parameters classified tumors more accurately with a cross validated error of 9.80% against that of ADC's 17.65% error. CONCLUSION: The approach of using quantitative T1 perfusion parameters based upon a support-vector-machine classifier reliably differentiated PA from glioblastoma and performed better classification than ADC.

Administration of soluble gp130Fc disrupts M-1 macrophage polarization, dendritic cell activation, MDSC expansion and Th-17 induction during experimental cerebral malaria.

Regulatory effect of IL-6 on various immune cells plays a crucial role during experimental cerebral malaria pathogenesis. IL-6 neutralization can restore distorted ratios of myeloid dendritic cells and plasmacytoid dendritic cells as well as the balance between Th-17 and T-regulatory cells. IL-6 can also influence immune cells through classical and trans IL-6 signalling pathways. As trans IL-6 signalling is reportedly involved during malaria pathogenesis, we focused on studying the effects of trans IL-6 signalling blockade on various immune cell populations and how they regulate ECM progression. Results show that administration of sgp130Fc recombinant chimera protein lowers the parasitemia, increases the survivability of Plasmodium berghei ANKA infected mice, and restores the distorted ratios of M1/M2 macrophage, mDC/pDC, and Th-17/Treg. IL-6 trans signalling blockade has been found to affect both expansion of myeloid derived suppressor cells (MDSCs) and expression of inflammatory markers on them during Plasmodium berghei ANKA infection indicating that trans IL-6 signalling might regulate various immune cells and their function during ECM. In this work for the first time, we delineate the effect of sgp130Fc administration on influencing the immunological changes within the host secondary lymphoid organ during ECM induced by Plasmodium berghei ANKA infection.