Hasil untuk "Biochemistry"

A. C. Hulme

D. Plummer

R. Pennington

Raymond L. Blakley

A. Branen

M. J. Sullivan, H. Green, F. Cobb

S. Glantz, W. Parmley

M. Linder

D. Voet, J. Voet

A. Merrill, E. Schmelz, D. Dillehay et al.

The "sphingosin" backbone of sphingolipids was so named by J. L. W. Thudichum in 1884 for its enigmatic ("Sphinx-like") properties. Although still an elusive class of lipids, research on the involvement of sphingolipids in the signal transduction pathways that mediate cell growth, differentiation, multiple cell functions, and cell death has been rapidly expanding our understanding of these compounds. In addition to the newly discovered role of ceramide as an intracellular second messenger for tumor necrosis factor-alpha, IL-1beta, and other cytokines, sphingosine, sphingosine-1-phosphate, and other sphingolipid metabolites have recently been demonstrated to modulate cellular calcium homeostasis and cell proliferation. Perturbation of sphingolipid metabolism using synthetic and naturally occurring inhibitors of key enzymes of the biosynthetic pathways is aiding the characterization of these processes; for examples, inhibition of cerebroside synthase has indicated a role for ceramide in cellular stress responses including heat shock, and inhibition of ceramide synthase (by fumonisins) has revealed the role of disruption of sphingolipid metabolism in several animal diseases. Fumonisins are currently the focus of a FDA long-term tumor study. This review summarizes recent research on (i) the role of sphingolipids as important components of the diet, (ii) the role of sphingoid base metabolites and the ceramide cycle in expression of genes regulating cell growth, differentiation, and apoptosis, (iii) the use of cerebroside synthase inhibitors as tools for understanding the role of sphingolipids as mediators of cell cycle progression, renal disease, and stress responses, and (iv) the involvement of disrupted sphingolipid metabolism in animal disease and cellular deregulation associated with exposure to inhibitors of ceramide synthase and serine palmitoyltransferase, key enzymes in de novo sphingolipid biosynthesis. These findings illustrate how an understanding of the function of sphingolipids can help solve questions in toxicology and this is undoubtedly only the beginning of this story.

R. Kolodner

The process of mismatch repair was first postulated to explain the results of experiments on genetic recombination and bacterial mutagenesis. Mismatch repair has long been known to play a major role in two cellular processes: (1) the repair of errors made during DNA replication or as the result of some types of chemical damage to DNA and DNA precursors; and (2) the processing of recombination intermediates to yield new configurations of genetic markers. More recent studies have suggested that mismatch repair may also be crucial for (1) the regulation of recombination events between divergent DNA sequences that could result in different types of genetic instability (Rayssiguier et al. 1989; Selva et al. 1995; Datta et al. 1996), (2) some types of nucleotide excision repair responsible for repair of physicallchemical damage to DNA (Karran and Marinus 1982; Fram et al. 1985; Feng et al. 1991; Mellon and Champe 1996), and (3) participating in a cell-cycle checkpoint control system by recognizing certain types of DNA damage and triggering cell-cycle arrest or other responses to DNA damage (Hawn et al. 1995; Anthoney et al. 1996). The most extensively characterized general mismatch repair system is the Escherichia coli MutHLS system, which repairs a broad spectrum of mispaired bases and has been reconstituted with purified enzymes. Eukaryotes are known to contain a mismatch repair system that has at least some components that are highly related to key components of the bacterial MutHLS mismatch repair system. The observation that defects in mismatch repair genes are linked to both inherited cancer susceptibility and some sporadic cancers has generated considerable interest in the gene products that function in eukaryotic mismatch repair. The goal of this review is to discuss recent studies on the mechanisms of MutHLSlike mismatch repair in the yeast Saccharomyces cerevisiae and in humans and to relate insights derived from these studies to human cancer genetics. Given space constraints, i t is difficult to cover everything known about mismatch repair or to reference all of the relevant work that has been done in this area. However, a brief overview of the E. coli MutHLS pathway is presented below to allow comparison of the E. coli and eukaryotic mismatch repair pathways and proteins. For more detailed information, particularly related to bacterial mismatch repair, base-specific mismatch repair systems, and cancer genetics, see other recent reviews (Modrich 1991; Eshleman and Markowitz 1995; Fishel and Kolodner 1995; Friedberg et al. 1995; Kolodner 1995; Marra and Boland 1995; Modrich and Lahue 1996).

Prabhakar Yellanur Konda, Vijayakumar Poondla, Krishna Kumar Jaiswal et al.

Niko Vlahakis, Arden Clauss, Jose A. Rodriguez

High-energy electrons induce sample damage and motion at the nanoscale to fundamentally limit the determination of molecular structures by electron diffraction. Using a fast event-based electron counting (EBEC) detector, we characterize beam-induced, dynamic, molecular crystal lattice reorientations (BIRs). These changes are sufficiently large to bring reciprocal lattice points entirely in or out of intersection with the sphere of reflection, occur as early events in the decay of diffracted signal due to radiolytic damage, and coincide with beam-induced migrations of crystal bend contours within the same fluence regime and at the same illuminated location on a crystal. These effects are observed in crystals of biotin, a series of amino acid metal chelates, and a six-residue peptide, suggesting that incident electrons inevitably warp molecular lattices. The precise orientation changes experienced by a given microcrystal are unpredictable but are measurable by indexing individual diffraction patterns during beam-induced decay. Reorientations can often tilt a crystal lattice several degrees away from its initial position before irradiation, and for an especially beam-sensitive Zn(II)-methionine chelate, are associated with dramatic crystal quakes prior to 1 e− Å−2 electron beam fluence accumulates. Since BIR coincides with the early stages of beam-induced damage, it echoes the beam-induced motion observed in single-particle cryoEM. As with motion correction for cryoEM imaging experiments, accounting for BIR-induced errors during data processing could improve the accuracy of MicroED data.

Feng Zhao, Jinjie Zhu, Yang Li et al.

This paper investigates optimal fluctuations for chemical reaction systems with N species, M reactions, and general rate law. In the limit of large volume, large fluctuations for such models occur with overwhelming probability in the vicinity of the so-called optimal path, which is a basic consequence of the Freidlin-Wentzell theory, and is vital in biochemistry as it unveils the almost deterministic mechanism concealed behind rare noisy phenomena such as escapes from the attractive domain of a stable state and transitions between different metastable states. In this study, an alternative description for optimal fluctuations is proposed in both non-stationary and stationary settings by means of a quantity called prehistory probability in the same setting, respectively. The evolution law of each of them is derived, showing their relationship with the time reversal of a specified family of probability distributions respectively. The law of large numbers and the central limit theorem for the reversed processes are then proved. In doing so, the prehistorical approach to optimal fluctuations for Langevin dynamics is naturally generalized to the present case, thereby suggesting a strong connection between optimal fluctuations and the time reversal of the chemical reaction model.

Yujing Lu, Ling Zhong, Jing Yang et al.

Chart Question Answering (CQA) evaluates Multimodal Large Language Models (MLLMs) on visual understanding and reasoning over chart data. However, existing benchmarks mostly test surface-level parsing, such as reading labels and legends, while overlooking deeper scientific reasoning. We propose DomainCQA, a framework for constructing domain-specific CQA benchmarks that emphasize both visual comprehension and knowledge-intensive reasoning. It integrates complexity-aware chart selection, multitier QA generation, and expert validation. Applied to astronomy, DomainCQA yields AstroChart, a benchmark of 1,690 QA pairs over 482 charts, exposing persistent weaknesses in fine-grained perception, numerical reasoning, and domain knowledge integration across 21 MLLMs. Fine-tuning on AstroChart improves performance across fundamental and advanced tasks. Pilot QA sets in biochemistry, economics, medicine, and social science further demonstrate DomainCQA's generality. Together, our results establish DomainCQA as a unified pipeline for constructing and augmenting domain-specific chart reasoning benchmarks.

Indranil Mal, Milan Kočí, Paolo Nicolini et al.

We present GridFF, an efficient method for simulating molecules on rigid substrates, derived from techniques used in protein-ligand docking in biochemistry. By projecting molecule-substrate interactions onto precomputed spatial grids with tricubic B-spline interpolation, GridFF reduces the computational cost by orders of magnitude compared to traditional pairwise atomistic models, without compromising the accuracy of forces or trajectories. The CPU implementation of GridFF in the open-source FireCore package provides a 100-1000x speedup over all-atom simulations using LAMMPS, while the GPU implementation - running thousands of system replicas in parallel - samples millions of configurations per second, enabling an exhaustive exploration of the configuration space of small flexible molecules on surfaces within minutes. Furthermore, as demonstrated in our previous application of a similar technique to high-resolution scanning probe microscopy, GridFF can be extended beyond empirical pairwise potentials to those derived from ab initio electron densities. Altogether, this unlocks accurate high-throughput modeling of molecular self-assembly, adsorption, and scanning probe manipulation in surface science.

Daniele Cappelletti, Aidan Howells, Chuang Xu

Stochastic reaction networks are mathematical models frequently used in, but not limited to, biochemistry. These models are continuous-time Markov chains whose transition rates depend on certain parameters called rate constants, which despite the name may not be constant in real-world applications. In this paper we study how random switching between different stochastic reaction networks with asymptotically linear rate functions affects the stability of the process. We give matrix conditions for both positive recurrence (indeed, exponentially ergodicity) and transience (indeed, evanescence) in both the regime with high switching rates and the regime with low switching rates. We then make use of these conditions to provide examples of processes whose stability behavior changes as the switching rate varies. We also explore what happens in the middle regime where the switching rates are neither high nor low and our theorems do not apply. Specifically, we show by examples that there can be arbitrarily many phase transitions between exponentially ergodicity and evanescence as the switching rate increases.

Tamir Shpiro, Ron Ruimy, Qinghui Yan et al.

New techniques for imaging electromagnetic near-fields in nanostructures drive advancements in nanotechnology, optoelectronics, materials science, and biochemistry. Most existing techniques probe near-fields along surfaces, lacking the ability to extract near-fields confined within the structure. Notable exceptions use free electrons to traverse through nanostructures, integrating the field along their trajectories, extracting 2D near-field projections rather than the complete field. Here, drawing inspiration from computed tomography (CT), we present a tomography concept providing full 3D reconstruction of vectorial time-harmonic near-fields. We develop a Radon-like algorithm incorporating the electron wave-nature and the time dependency of its interaction with vector fields. To show the prospects of electron near-field tomography, we propose and analyze its ability to resolve the sub-wavelength zigzag profile of highly confined hyperbolic polaritons and to reconstruct 3D phase singularities in a chiral near-field, raising exciting goals for next-generation experiments in ultrafast transmission electron microscopes.

Phanindra Dewan, Soumyadeep Mondal, Sumantra Sarkar

Many cellular proteins, such as ERK, undergo oscillation death when cells are compressed, initiating many developmental processes in organisms. Whether such a transition arises from these proteins' specific biochemistry or generic dynamical features remains unclear. In this paper, we show that coupling mechanics to the chemistry of Hopf oscillators, such as ERK, through mechanochemical feedback (MCF) can generically drive oscillation death upon compression. We demonstrate this result using an active solid, a 1D ring of Brusselators coupled through damped springs, which we term Harmonic Brusselator Ring (HBR). Because of MCF, HBR's dynamics is non-Hermitian and breaks $\mathcal{PT}$-symmetry in a scale-dependent manner, generating a rich array of patterns, including traveling pulses, chimera states, intermittent fluctuations, and collective oscillation death. Furthermore, MCF engenders three dynamic phase transitions that separate the observed patterns into four phases. The underlying symmetry of HBR implies that the observed patterns and phases may generically arise in many natural and synthetic systems.

D. Latchman