AMLdb: a comprehensive multi-omics platform to identify biomarkers and drug targets for acute myeloid leukemia.

Acute myeloid leukemia (AML) is one of the leading leukemic malignancies in adults. The heterogeneity of the disease makes the diagnosis and treatment extremely difficult. With the advent of next-generation sequencing (NGS) technologies, exploration at the molecular level for the identification of biomarkers and drug targets has been the focus for the researchers to come up with novel therapies for better prognosis and survival outcomes of AML patients. However, the huge amount of data from NGS platforms requires a comprehensive AML platform to streamline literature mining efforts and save time. To facilitate this, we developed AMLdb, an interactive multi-omics platform that allows users to query, visualize, retrieve, and analyse AML related multi-omics data. AMLdb contains 86 datasets for gene expression profiles, 15 datasets for methylation profiles, CRISPR-Cas9 knockout screens of 26 AML cell lines, sensitivity of 26 AML cell lines to 288 drugs, mutations in 41 unique genes in 23 AML cell lines, and information on 41 experimentally validated biomarkers. In this study, we have reported five genes, i.e. CBFB, ENO1, IMPDH2, SEPHS2, and MYH9 identified via our analysis using AMLdb. ENO1 is uniquely identified gene which requires further investigation as a novel potential target while other reported genes have been previously confirmed as targets through experimental studies. Top of form we believe that these findings utilizing AMLdb can make it an invaluable resource to accelerate the development of effective therapies for AML and assisting the research community in advancing their understanding of AML pathogenesis. AMLdb is freely available at https://project.iith.ac.in/cgntlab/amldb.

Local interneurons in the murine visual thalamus have diverse receptive fields and can provide feature selective inhibition to relay cells.

By influencing the type and quality of information that relay cells transmit, local interneurons in thalamus have a powerful impact on cortex. To define the sensory features that these inhibitory neurons encode, we mapped receptive fields of optogenetically identified cells in the murine dorsolateral geniculate nucleus. Although few in number, local interneurons had diverse types of receptive fields, like their counterpart relay cells. This result differs markedly from visual cortex, where inhibitory cells are typically less selective than excitatory cells. To explore how thalamic interneurons might converge on relay cells, we took a computational approach. Using an evolutionary algorithm to search through a library of interneuron models generated from our results, we show that aggregated output from different groups of local interneurons can simulate the inhibitory component of the relay cell's receptive field. Thus, our work provides proof-of-concept that groups of diverse interneurons can supply feature-specific inhibition to relay cells.

Visual Information Processing in the Ventral Division of the Mouse Lateral Geniculate Nucleus of the Thalamus.

Even though the lateral geniculate nucleus of the thalamus (LGN) is associated with form vision, that is not its sole role. Only the dorsal portion of LGN (dLGN) projects to V1. The ventral division (vLGN) connects subcortically, sending inhibitory projections to sensorimotor structures, including the superior colliculus (SC) and regions associated with certain behavioral states, such as fear (Monavarfeshani et al., 2017; Salay et al., 2018). We combined computational, physiological, and anatomical approaches to explore visual processing in vLGN of mice of both sexes, making comparisons to dLGN and SC for perspective. Compatible with past, qualitative descriptions, the receptive fields we quantified in vLGN were larger than those in dLGN, and most cells preferred bright versus dark stimuli (Harrington, 1997). Dendritic arbors spanned the length and/or width of vLGN and were often asymmetric, positioned to collect input from large but discrete territories. By contrast, arbors in dLGN are compact (Krahe et al., 2011). Consistent with spatially coarse receptive fields in vLGN, visually evoked changes in spike timing were less precise than for dLGN and SC. Notably, however, the membrane currents and spikes of some cells in vLGN displayed gamma oscillations whose phase and strength varied with stimulus pattern, as for SC (Stitt et al., 2013). Thus, vLGN can engage its targets using oscillation-based and conventional rate codes. Finally, dark shadows activate SC and drive escape responses, whereas vLGN prefers bright stimuli. Thus, one function of long-range inhibitory projections from vLGN might be to enable movement by releasing motor targets, such as SC, from suppression.SIGNIFICANCE STATEMENT Only the dorsal lateral geniculate nucleus (dLGN) connects to cortex to serve form vision; the ventral division (vLGN) projects subcortically to sensorimotor nuclei, including the superior colliculus (SC), via long-range inhibitory connections. Here, we asked how vLGN processes visual information, making comparisons with dLGN and SC for perspective. Cells in vLGN versus dLGN had wider dendritic arbors, larger receptive fields, and fired with lower temporal precision, consistent with a modulatory role. Like SC, but not dLGN, visual stimuli entrained oscillations in vLGN, perhaps reflecting shared strategies for visuomotor processing. Finally, most neurons in vLGN preferred bright shapes, whereas dark stimuli activate SC and drive escape behaviors, suggesting that vLGN enables rapid movement by releasing target motor structures from inhibition.

Acute effects of mobile phone radiations on subtle energy levels of teenagers using electrophotonic imaging technique: A randomized controlled study.

BACKGROUND: Mobile phones induce radio frequency electromagnetic field (RF-EMF) which has been found to affect subtle energy levels of adults through Electrophotonic Imaging (EPI) technique in a previous pilot study. MATERIALS AND METHODS: We enrolled 61 healthy right-handed healthy teenagers (22 males and 39 females) in the age range of 17.40 ± 0.24 years from educational institutes in Bengaluru. Subjects were randomly divided into two groups: (1) (mobile phone in ON mode [MPON] at right ear) and (2) mobile phone in OFF mode (MPOF). Subtle energy levels of various organs of the subjects were measured using gas discharge visualization Camera Pro device, in double-blind conditions, at two points of time: (1) baseline and (2) after 15 min of MPON/MPOF exposure. As the data were found normally distributed, paired and independent samples t-test were applied to perform within and between group comparisons, respectively. RESULTS: The subtle energy levels were significantly reduced after RF-EMF exposure in MPON group as compared to MPOF group for following areas: (a) Pancreas (P = 0.001), (b) thyroid gland (P = 0.002), (c) cerebral cortex (P < 0.01), (d) cerebral vessels (P < 0.05), (e) hypophysis (P = 0.013), (f) left ear and left eye (P < 0.01), (g) liver (P < 0.05), (h) right kidney (P < 0.05), (i) spleen (P < 0.04), and (j) immune system (P < 0.02). CONCLUSION: Fifteen minutes of RF-EMF exposure exerted quantifiable effects on subtle energy levels of endocrine glands, nervous system, liver, kidney, spleen, and immune system of healthy teenagers. Future studies should try to correlate these findings with respective biochemical markers and standard radio-imaging techniques.

Synaptic Contributions to Receptive Field Structure and Response Properties in the Rodent Lateral Geniculate Nucleus of the Thalamus.

Comparative physiological and anatomical studies have greatly advanced our understanding of sensory systems. Many lines of evidence show that the murine lateral geniculate nucleus (LGN) has unique attributes, compared with other species such as cat and monkey. For example, in rodent, thalamic receptive field structure is markedly diverse, and many cells are sensitive to stimulus orientation and direction. To explore shared and different strategies of synaptic integration across species, we made whole-cell recordings in vivo from the murine LGN during the presentation of visual stimuli, analyzed the results with different computational approaches, and compared our findings with those from cat. As for carnivores, murine cells with classical center-surround receptive fields had a "push-pull" structure of excitation and inhibition within a given On or Off subregion. These cells compose the largest single population in the murine LGN (∼40%), indicating that push-pull is key in the form vision pathway across species. For two cell types with overlapping On and Off responses, which recalled either W3 or suppressed-by-contrast ganglion cells in murine retina, inhibition took a different form and was most pronounced for spatially extensive stimuli. Other On-Off cells were selective for stimulus orientation and direction. In these cases, retinal inputs were tuned and, for oriented cells, the second-order subunit of the receptive field predicted the preferred angle. By contrast, suppression was not tuned and appeared to sharpen stimulus selectivity. Together, our results provide new perspectives on the role of excitation and inhibition in retinothalamic processing. SIGNIFICANCE STATEMENT: We explored the murine lateral geniculate nucleus from a comparative physiological perspective. In cat, most retinal cells have center-surround receptive fields and push-pull excitation and inhibition, including neurons with the smallest (highest acuity) receptive fields. The same is true for thalamic relay cells. In mouse retina, the most numerous cell type has the smallest receptive fields but lacks push-pull. The most common receptive field in rodent thalamus, however, is center-surround with push-pull. Thus, receptive field structure supersedes size per se for form vision. Further, for many orientation-selective cells, the second-order component of the receptive field aligned with stimulus preference, whereas suppression was untuned. Thus, inhibition may improve spatial resolution and sharpen other forms of selectivity in rodent lateral geniculate nucleus.