Tissue/Biofluid Specific Molecular Cartography of Leishmania donovani Infected BALB/c Mice: Deciphering Systemic Reprogramming

Pathophysiology of visceral leishmaniasis (VL) is not fully understood and it has been widely accepted that the parasitic components and host immune response both contribute to the perpetuation of the disease. Host alterations during leishmaniasis is a feebly touched area that needs to be explored more to better understand the VL prognosis and diagnosis, which are vital to reduce mortality and post-infection sequelae. To address this, we performed untargeted metabolomics of Leishmania donovani (Ld) infected, uninfected and treated BALB/c mice’s tissues and biofluids to elucidate the host metabolome changes using gas chromatography–mass spectrometry. Univariate and multivariate data treatments provided numerous significant differential hits in several tissues like the brain, liver, spleen and bone marrow. Differential modulations were also observed in serum, urine and fecal samples of Ld-infected mice, which could be further targeted for biomarker and diagnostic validations. Several metabolic pathways were found to be upregulated/downregulated in infected (TCA, glycolysis, fatty acids, purine and pyrimidine, etcetera) and treated (arginine, fumaric acid, orotic acid, choline succinate, etcetera) samples. Results also illustrated several metabolites with different pattern of modulations in control, infected and treated samples as well as in different tissues/biofluids; for e.g. glutamic acid identified in the serum samples of infected mice. Identified metabolites include a range of amino acids, saccharides, energy-related molecules, etcetera. Furthermore, potential biomarkers have been identified in various tissues—arginine and fumaric acid in brain, choline in liver, 9-(10) EpOME in spleen and bone marrow, N-acetyl putrescine in bone marrow, etcetera. Among biofluids, glutamic acid in serum, hydrazine and deoxyribose in urine and 3-Methyl-2-oxo pentanoic acid in feces are some of the potential biomarkers identified. These metabolites could be further looked into for their role in disease complexity or as a prognostic marker. The presented profiling approach allowed us to attain a metabolic portrait of the individual tissue/biofluid modulations during VL in the host and represent a valuable system readout for further studies. Our outcomes provide an improved understanding of perturbations of the host metabolome interface during VL, including identification of many possible potential diagnostic and therapeutic targets.

Neurocognitive Effects of Self-Determined Choice and Emotional Arousal on Time Estimation

Even though effects of emotion and motivation on cognition are well documented, the interaction of all three factors is rarely investigated. Here, we used electroencephalography (EEG) to examine the effects of self-determined choice—as an experimental manipulation of intrinsic motivation - and emotional stimulus content on task preparation and engagement in a temporal production task. Behavioral results indicated a modulation of time processing depending on choice and emotional content. Underlying EEG signals revealed differential modulations by choice on the contingent negative variation (CNV) during task and response preparation and by emotional content on the late positive potential (LPP) in response to the onset of an emotional picture during temporal production. Also, we obtained preliminary evidence for interaction effects of choice and emotional content on the LPP. The feedback-related negativity (FRN) in response to information regarding temporal production success was also affected by interactions of choice and emotional content. These findings indicate that besides separate effects of motivation and emotion, there may be time windows during task engagement in which both factors jointly affect cognitive processing. These results are interpreted as dynamic modulations of attentional resource allocation.

Hematological responses of common carp Cyprinus carpio administered with Neem (Azadirachta indica) leaf extraction

The study investigated the effect of Neem Leaf Extract (NLE)—a herbal product on hematological parameters of common carp, Cyprinus carpio. Common carp fry were fed on diets having different levels of NLE [no NLE (D1), 0.25(D2), 0.5(D3), 1.0(D4), 1.5(D5), 2.0(D6) g/kg in basal diet containing rice bran and mustard] for 180 days in outdoor tanks. The results revealed an increase in TEC, TLC and PCV in groups D2-D6 compared to control (P less than 0.05), but increased PCV was observed only in D2, D3 and D4 groups. Further, increasing trend for Hb content was observed from D2-D6 irrespective of NLE levels. The MCV values decreased with increase in levels of NLE in contrast to MCHC, whereas MCH considerably varied among the treatments. Significantly increased total protein and globulin was also observed while albumin to globulin ratio did not show any response in any of the treatments. Collectively, these observations support the hypothesis that the response of hematological parameters to NLE treatment is regulated via both positive and negative feedback mechanisms, with differential modulations based on the NLE levels. The results imply that NLE can boost the immune system via hematological parameters by increasing TEC, TLC, PCV, Hb at certain levels.

Dorsal and Ventral Attention Systems Underlie Social and Symbolic Cueing

Eye gaze is a powerful cue for orienting attention in space. Studies examining whether gaze and symbolic cues recruit the same neural mechanisms have found mixed results. We tested whether there is a specialized attentional mechanism for social cues. We separately measured BOLD activity during orienting and reorienting attention following predictive gaze and symbolic cues. Results showed that gaze and symbolic cues exerted their influence through the same neural networks but also produced some differential modulations. Dorsal frontoparietal regions in left intraparietal sulcus (IPS) and bilateral MT+/lateral occipital cortex only showed orienting effects for symbolic cues, whereas right posterior IPS showed larger validity effects following gaze cues. Both exceptions may reflect the greater automaticity of gaze cues: Symbolic orienting may require more effort, while disengaging attention during reorienting may be more difficult following gaze cues. Face-selective regions, identified with a face localizer, showed selective activations for gaze cues reflecting sensory processing but no attentional modulations. Therefore, no evidence was found linking face-selective regions to a hypothetical, specialized mechanism for orienting attention to gaze cues. However, a functional connectivity analysis showed greater connectivity between face-selective regions and right posterior IPS, posterior STS, and inferior frontal gyrus during gaze cueing, consistent with proposals that face-selective regions may send gaze signals to parts of the dorsal and ventral frontoparietal attention networks. Finally, although the default-mode network is thought to be involved in social cognition, this role does not extend to gaze orienting as these regions were more deactivated following gaze cues and showed less functional connectivity with face-selective regions during gaze cues.