-
rabindra.tharu.np@gmail.com
·
Micronuclear collapse from oxidative damage
Chromosome-containing micronuclei are a hallmark of aggressive cancers. Micronuclei frequently undergo irreversible collapse, exposing their enclosed chromatin to the cytosol. Micronuclear rupture catalyzes chromosomal rearrangements, epigenetic abnormalities, and inflammation, yet mechanisms safeguarding micronuclear integrity are poorly understood. In this study, we found that mitochondria-derived reactive oxygen species (ROS) disrupt micronuclei by promoting a noncanonical function…
-
rabindra.tharu.np@gmail.com
·
The marine biodiversity impact of the Late Miocene Mediterranean salinity crisis
Massive salt accumulations, or salt giants, have formed in highly restricted marine basins throughout geological history, but their impact on biodiversity has been only patchily studied. The salt giant in the Mediterranean Sea formed as a result of the restriction of its gateway to the Atlantic during the Messinian Salinity Crisis (MSC) 5.97 to 5.33…
-
rabindra.tharu.np@gmail.com
·
A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements
Chromosomal instability (CIN) generates micronuclei-aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, which exposes DNA to the cytoplasm. We found that the autophagic receptor p62/SQSTM1 modulates micronuclear stability, influencing chromosome fragmentation and rearrangements. Mechanistically, proximity of micronuclei…
-
rabindra.tharu.np@gmail.com
·
Phage-triggered reverse transcription assembles a toxic repetitive gene from a noncoding RNA
Reverse transcription has frequently been co-opted for cellular functions and in prokaryotes is associated with protection against viral infection, but the underlying mechanisms of defense are generally unknown. Here, we show that in the DRT2 defense system, the reverse transcriptase binds a neighboring pseudoknotted noncoding RNA. Upon bacteriophage infection, a template region of this RNA…
-
rabindra.tharu.np@gmail.com
·
Reductive samarium (electro)catalysis enabled by Sm(III)-alkoxide protonolysis
Samarium diiodide (SmI) is a privileged, single-electron reductant deployed in diverse synthetic settings. However, generalizable methods for catalytic turnover remain elusive because of the well-known challenge associated with cleaving strong Sm-O bonds. Prior efforts have focused on the use of highly reactive oxophiles to enable catalyst turnover. However, such approaches give rise to complex catalyst…
-
rabindra.tharu.np@gmail.com
·
The actin-spectrin submembrane scaffold restricts endocytosis along proximal axons
Clathrin-mediated endocytosis has characteristic features in neuronal dendrites and presynapses, but how membrane proteins are internalized along the axon shaft remains unclear. We focused on clathrin-coated structures and endocytosis along the axon initial segment (AIS) and their relationship to the periodic actin-spectrin scaffold that lines the axonal plasma membrane. A combination of super-resolution microscopy and…
-
rabindra.tharu.np@gmail.com
·
Mechanisms of minor pole-mediated spindle bipolarization in human oocytes
Spindle bipolarization, the process of a microtubule mass transforming into a bipolar spindle, is a prerequisite for accurate chromosome segregation. In contrast to mitotic cells, the process and mechanism of spindle bipolarization in human oocytes remains unclear. Using high-resolution imaging in more than 1800 human oocytes, we revealed a typical state of multipolar intermediates that…
-
rabindra.tharu.np@gmail.com
·
Climate policies that achieved major emission reductions: Global evidence from two decades
Meeting the Paris Agreement’s climate targets necessitates better knowledge about which climate policies work in reducing emissions at the necessary scale. We provide a global, systematic ex post evaluation to identify policy combinations that have led to large emission reductions out of 1500 climate policies implemented between 1998 and 2022 across 41 countries from six…
-
rabindra.tharu.np@gmail.com
·
Accurate computation of quantum excited states with neural networks
We present an algorithm to estimate the excited states of a quantum system by variational Monte Carlo, which has no free parameters and requires no orthogonalization of the states, instead transforming the problem into that of finding the ground state of an expanded system. Arbitrary observables can be calculated, including off-diagonal expectations, such as the…
-
rabindra.tharu.np@gmail.com
·
PERK-ATAD3A interaction provides a subcellular safe haven for protein synthesis during ER stress
Endoplasmic reticulum (ER) stress induces the repression of protein synthesis throughout the cell. Attempts to understand how localized stress leads to widespread repression have been limited by difficulties in resolving translation rates at the subcellular level. Here, using live-cell imaging of reporter mRNA translation, we unexpectedly found that during ER stress, active translation at mitochondria…
