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Singh, J. P.

Publications and source records attributed to Singh, J. P..

3 recordsLinked to original sources

How does literacy affect speech processing? Not by enhancing cortical responses to speech, but by promoting connectivity of acoustic-phonetic and graphomotor cortices.

Previous research suggest that literacy, specifically learning alphabetic letter-to-phoneme mappings, modifies online speech processing, and enhances brain responses to speech in auditory areas associated with phonological processing (Dehaene et al., 2010). However, alphabets are not the only orthographic systems in use in the world, and hundreds of millions of individuals speak languages that are not written using alphabets. In order to make claims that literacy per se has broad and general consequences for brain responses to speech, one must seek confirmatory evidence from non-alphabetic literacy. To this end, we conducted a longitudinal fMRI study in India probing the effect of literacy in Devanagari, an abubgida, on functional connectivity and cerebral responses to speech in 91 variously literate Hindi-speaking individuals. Twenty-two completely illiterate participants underwent six months of reading and writing training. Devanagari literacy increases functional connectivity between acoustic-phonetic and graphomotor brain areas, but we find no evidence that literacy changes the way speech is processed, either in cross-sectional or longitudinal analyses. These findings shows that a radical reconfiguration of the neurofunctional substrates of online speech processing is not a universal result of learning to read, and raise the possibility that writing, not only reading, may be instrumental in moulding literate speech perception. Significance StatementIt has come to be accepted that a consequence of being able to read is enhanced auditory processing of speech, reflected by increased cortical responses in areas associated with phonological processing. Here we find no relationship between literacy and the magnitude of brain response to speech stimuli in individuals who speak Hindi, which is written using a non-alphabetic script, Devanagari - an abugida. We propose that the exact nature of the script under examination must be considered before making sweeping claims about the consequences of literacy for the brain. Further, we find evidence that literacy enhances functional connectivity between auditory processing areas and graphomotor areas, suggesting a mechanism whereby learning to write, not only to read, might influence speech perception.

neuroscience↗

Activation of GPR56, a novel adhesion GPCR, is necessary for nuclear androgen receptor signaling in prostate cells

The androgen receptor (AR) is activated in patients with castration resistant prostate cancer (CRPC) despite low circulating levels of androgen, suggesting that intracellular signaling pathways and non-androgenic factors may contribute to AR activation. Many G-protein coupled receptors (GPCR) and their ligands are also activated in these cells indicating a role for these in CRPC. Although a cross talk has been suggested between the two pathways, yet, the identity of GPCRs which may play a role in androgen signaling, is not established yet. We demonstrate that adhesion GPCR 205, also known as GPR56, can be activated by androgens to stimulate the Rho signaling pathway, a pathway that plays an important role in prostate tumor cell metastasis. Testosterone stimulation of GPR56 also activates the cAMP/ Protein kinase A (PKA) pathway, that is necessary for AR signaling. Knocking down the expression of GPR56 using siRNA, disrupts nuclear translocation of AR and transcription of prototypic AR target genes such as PSA. GPR56 expression is higher in all prostate tumor samples tested and cells expressing GPR56 exhibit increased proliferation. These findings provide new insights about androgen signaling and identify GPR56 as a possible therapeutic target in advanced prostate cancer patients.

cancer biology↗

Direct anabolic three carbon metabolism to a six carbon metabolite occurs in human heart and in vivo across mouse tissues

Anabolic metabolism of carbon in mammals is mediated via the one and two carbon carriers S-adenosyl methionine and acetyl-coenzyme A (acetyl-CoA). In contrast, anabolic metabolism using three carbon units via propionate is not thought to occur. Mammals are primarily thought to oxidize the 3-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. We found that this may not be absolute and that in mammals one non-oxidative fate of two units of propionyl-CoA is to condense to a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this pathway using purified protein extracts provided limited substrates and confirmed the product with a synthetic standard. In whole-body in vivo stable isotope tracing with infusion of 13C-labeled valine achieving steady state, 2M2PE-CoA formed via propionyl-CoA in multiple murine tissues including heart, kidney, and to a lesser degree in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three to six carbon reaction conserved in humans and mice that utilizes three carbons via propionate. Highlights- Synthesis and confirmation of structure 2-methyl-2-pentenoyl-CoA - In vivo fate of valine across organs includes formation of a 6-carbon metabolite from propionyl-CoA - Ex vivo metabolism of propionate in the human heart includes direct anabolism to a 6-carbon product - In both cases, this reaction occurred at physiologically relevant concentrations of propionate and valine - In vitro this pathway requires propionyl-CoA and NADH/NADPH as substrates

biochemistry↗