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Satish, B.

Publications and source records attributed to Satish, B..

3 recordsLinked to original sources

Magnetic compass orientation behaviour of Eurasian blackcaps at the predicted 110-120 MHz upper cut-off frequency for radiofrequency-field effects

Night-migratory songbirds use the Earths magnetic field to guide their migratory journeys. Most evidence suggests that the magnetic compass sensor is a flavin-tryptophan radical pair whose operation is disrupted by broadband radiofrequency (RF) fields at frequencies up to [~]116 MHz. Here, we test whether broadband 110-120 MHz RF fields affect the magnetic orientation behaviour of night-migratory Eurasian blackcaps (Sylvia atricapilla). We found that the birds oriented in their expected migratory direction in the natural geomagnetic field (NMF) control condition and that they turned their orientation [~]120{degrees} when the field was rotated 120{degrees} horizontally (changed magnetic field, CMF). When they were exposed to broadband 110-120 MHz RF fields, the birds continued to orient in the appropriate direction in the NMF. In the CMF, we found orientation behaviour that was not consistent with the expected direction. We conclude that the birds could still orient when exposed to 110-120 MHz fields, but speculate that their magnetic orientation capabilities might have been somewhat reduced compared to the control condition. We suggest that 110-120 MHz could represent a grey zone of reduced magnetic orientation capability centred at the cut-off frequency predicted for a flavin-based radical pair (probably in the flavoprotein cryptochrome).

animal behavior and cognition↗

NR4A1 limits CD8⁺ T Cell effector responses and protection in tuberculosis

During Mycobacterium tuberculosis (Mtb) infection, CD8+ T cells exhibit dysfunction with impaired cytotoxicity and limited localization to granuloma cores. Using knockout mice, adoptive-transfer models and validation in macaque and human datasets, we identified the nuclear receptor NR4A1 as a key restrainer of CD8+ T cell immunity in tuberculosis (TB). Mtb-infected Nr4a1-/- mice displayed reduced bacterial burden, attenuated pathology, higher lung CD8+/CD4+ T cell ratios, and enhanced CD8+ T cell effector functions. Bulk and single-cell RNA sequencing revealed suppression of gene expression program linked with exhaustion, and expansion of Nkg7+ and Granzyme+ cytotoxic CD8+ T cell subsets in Nr4a1-/- mice. Spatial analyses demonstrated increased infiltration of Nkg7+ activated CD8+ T cells in Nr4a1-/- lesions. ChIP-qPCR showed NR4A1 binding to Nkg7 promoter, and Nkg7 knockdown abrogated the enhanced cytotoxicity of Nr4a1-/- CD8+ T cells. Pharmacologic inhibition of NR4A1 reduced Mtb burden and pathology, and restored Nkg7 expression and CD8+ T cell infiltration in the lung. Together, these findings identify NR4A1 as a negative regulator of CD8+ T cell-mediated immunity in TB and suggest the NR4A1-NKG7 axis as a novel host-directed therapeutic target. A one-sentence summary of your paperNR4A1 suppresses CD8+ T cell infiltration and cytotoxicity in TB lesions, and its inhibition enhances host resistance to Mtb infection.

immunology↗

Cryptochrome 4b protein is likely irrelevant for the radical pair based magnetoreception in the European robin

Avian cryptochrome 4 (Cry4) protein is a putative magnetosensitive molecule facilitating precise long-distance navigation in migratory birds. Two splice variants of Cry4 were reported in European robin (Erithacus rubecula), namely ErCry4a and ErCry4b. It is known that ErCry4a protein exhibits electron transfer between the flavin adenine dinucleotide (FAD) cofactor and tryptophan residues that generates magnetically sensitive radical pairs for magnetoreception. However, little is known about the ErCry4b isoform. We therefore characterized the properties of ErCry4b to see whether it fulfills prerequisites to be a radical pair magnetic sensor molecule. Our results show that ErCry4b protein does not bind FAD in vitro. Computational structure simulations revealed that the FAD non-binding in ErCry4b is likely due to protein structure dynamics. Furthermore, ErCry4b protein abundance in the robin retina, cerebellum and liver is below the detection limit of immunoprecipitation assays coupled with mass spectrometry. Meanwhile, transcript analyses show that ErCRY4b mRNA abundance is 10 times less than ErCRY4b in the retina. In conclusion, ErCry4b does not fulfill the prerequisites to be a radical pair based magnetic sensing molecule due to the lack of FAD binding, and it might not even be expressed as a functional protein in the European robin.

biochemistry↗