Iron-histidine resonance raman band of deoxyheme proteins: effects of anharmonic coupling and glass-liquid phase transition

Weak anharmonic coupling of two soft molecular vibrations is shown to cause pronounced temperature dependence of the corresponding resonance Raman bands. The developed theory is used to interpret the temperature dependence of the iron-histidine band of deoxyheme proteins and model compounds. It is shown that anharmonic coupling of the iron-histidine and heme doming vibrations must cause pronounced broadening of the band, its asymmetry, and shift of its maximum to the red upon heating. It also can lead to a structured shape of this band at room temperature. Proper consideration of the anharmonic coupling allows simulation of the temperature dependence of the iron-histidine band shape of horse heart myoglobin in the temperature interval of 10-300 K, using the minimum number of necessary parameters. Analysis of this temperature dependence clearly shows that the iron-histidine band of deoxyheme proteins is sensitive to the glass-liquid phase transition in the protein hydration shell, which takes place at 160-190 K.     

Prostate apoptosis response-4 and tumor suppression: it’s not just about apoptosis anymore

The tumor suppressor prostate apoptosis response-4 (Par-4) has recently turned ‘twenty-five’. Beyond its indisputable role as an apoptosis inducer, an increasing and sometimes bewildering, new roles for Par-4 are being reported. These roles include its ability to regulate autophagy, senescence, and metastasis. This growing range of responses to Par-4 is reflected by our increasing understanding of the various mechanisms through which Par-4 can function. In this review, we summarize the existing knowledge on Par-4 tumor suppressive mechanisms, and discuss how the interaction of Par-4 with different regulators influence cell fate. This review also highlights the new secretory pathway that has emerged and the likely discussion on its clinical implications.Subject terms: Tumour-suppressor proteins, Apoptosis, Stress signalling, Target identification     

Transcriptomic profiling of nonneoplastic cortical tissues reveals epileptogenic mechanisms in dysembryoplastic neuroepithelial tumors

Functional & Integrative Genomics - Low-grade dysembryoplastic neuroepithelial tumors (DNTs) are a frequent cause of drug-refractory epilepsy. Molecular mechanisms underlying seizure generation...     

Envelope diversity, characteristics of V3 region and predicted co-receptor usage of human immunodeficiency viruses infecting north indians

Subtypes of human immunodeficiency virus type 1 circulating in 21 north Indian patients were characterized based on the partial sequence of the gp120 envelope protein. A majority of viruses (85.7%, 18/21) were subtype C, while 14.3% (3/21) were subtype A. Sequence analysis revealed that the V3 region was highly conserved compared with V4 and V5. The predicted use of co-receptors indicated exclusive usage of R5, except for two subtype A viruses (AIIMS279 and AIIMS281). Our results demonstrate conservation within the V3 loop of subtype C viruses, and suggest the emergence of non-clade C viruses in the north Indian population.     

Study on Folate Binding Domain of Dihydrofolate Reductase in Different Plant species and Human beings

Data base (NCBI and TIGR) searches are made to retrieve protein sequences of different plant species namely Medicago truncatula, Pisum sativum, Ricinus communis, Arabidopsis thaliana, Vitis vinifera, Glycine max, Daucus carota, Oryza sativa Japonica Group, Arabidopsis lyrata subsp. lyrata, Brachypodium distachyon, Oryza sativa Indica Group, Zea mays and careful alignment of derived sequences shows 95% or higher identity. Similarly, DHFR sequence of human being is also retrieved from NCBI. A phylogenetic tree is constructed from different plant and human DHFR domain using the Neighbour – Joining method in MEGA 5.05. Conservation score is performed by using PARALINE. Result suggests that folate binding domain of dihydrofolare reductase is conserved (score 8.06) and excepting some minor variations the basic structure of the domain in both plant species and human being is rather similar. Human DHFR domain contains PEKN sequence near active site, though proline is common for all the selected organisms but the other sequences are different in plants. The plant domain is always associated with TS (Thymidylate synthase). Plant based system is predicted to be an effective model for assessment of MTX (Methotrexate) and other antifolate drugs.     

Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis

Ferroptosis is a type of regulated cell death characterized by ROS accumulation and devastating lipid peroxidation (LPO). The role of acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, in the induction of apoptosis has been studied; however, to date its role in ferroptosis is unclear. In this study, we report that ASM plays a hitherto unanticipated role in promoting ferroptosis. Mechanistically, Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO. Inhibition of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) or removal of intracellular ROS, significantly reduced Era-induced ASM activation, suggesting that NADPH oxidase-derived ROS regulated ASM-initiated redox signaling in a positive feedback manner. Moreover, ASM-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutathione peroxidase 4 (GPX4) degradation and ferroptosis activation. Genetic or pharmacological inhibition of ASM diminishes Era-induced features of autophagy, GPX4 degradation, LPO, and subsequent ferroptosis. Importantly, genetic activation of ASM increases ferroptosis in cancer cells induced by various FINs. Collectively, these findings reveal that ASM plays a novel role in ferroptosis that could be exploited to improve pathological conditions that link to ferroptosis.Subject terms: Lipid peroxides, Cancer models, Macroautophagy, Lipid signalling     

Recent Advancement of p‐ and d‐Block Elements,Single Atoms,and Graphene‐Based Photoelectrochemical Electrodes for Water Splitting

Solar‐assisted photoelectrochemical (PEC) water splitting to produce hydrogen energy is considered the most promising solution for clean, green, and renewable sources of energy. For scaled production of hydrogen and oxygen, highly active, robust, and cost‐effective PEC electrodes are required. However, most of the available semiconductors as a PEC electrodes have poor light absorption, material degradation, charge separation, and transportability, which result in very low efficiency for photo‐water splitting. Generally, a promising photoelectrode is obtained when the surface of the semiconductor is modified/decorated with a suitable co‐catalyst because it increases the light absorbance spectrum and prevents electron–hole recombination during photoelectrode reactions. In this regard, numerous p‐ and d‐block elements, single atoms, and graphene‐based PEC electrodes have been widely used as semiconductor/co‐catalyst junctions to boost the performances of PEC overall water splitting. This review enumerates the recent progress and applications of p‐ and d‐block elements, single atoms, and graphene‐based PEC electrodes for water splitting. The focus is placed on fundamental mechanism, efficiency, cells design, and various aspects that contribute to the large‐scale prototype device. Finally, future perspectives, summary, challenges, and outlook for improving the activity of PEC photoelectrodes toward whole‐cell water splitting are addressed.