HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III.

Molecular chaperones are critical for protein homeostasis and are implicated in several human pathologies such as neurodegeneration and cancer. While the binding of chaperones to nascent and misfolded proteins has been studied in great detail, the direct interaction between chaperones and RNA has not been systematically investigated. Here, we provide the evidence for widespread interaction between chaperones and RNA in human cells. We show that the major chaperone heat shock protein 70 (HSP70) binds to non-coding RNA transcribed by RNA polymerase III (RNA Pol III) such as tRNA and 5S rRNA. Global chromatin profiling revealed that HSP70 binds genomic sites of transcription by RNA Pol III. Detailed biochemical analyses showed that HSP70 alleviates the inhibitory effect of cognate tRNA transcript on tRNA gene transcription. Thus, our study uncovers an unexpected role of HSP70-RNA interaction in the biogenesis of a specific class of non-coding RNA with wider implications in cancer therapeutics.

Optical source apportionment of aqueous brown carbon (BrC) on a daytime and nighttime basis in the eastern Indo-Gangetic Plain (IGP) and insights from 13C and 15N isotopic signatures.

This study reports day-night and seasonal variations of aqueous brown carbon (BrCaq) and constituent humic-like substances (HULIS) (neutral and acidic HULIS: HULIS-n and HULIS-a) from the eastern Indo-Gangetic Plain (IGP) of India during 2019-2020. This is followed by the application of the receptor model positive matrix factorization (PMF) for optical source apportionment of BrCaq and the use of stable isotopic ratios (δ13C and δ15N) to understand atmospheric processing. Nighttime BrCaq absorption and mass absorption efficiencies (MAE) were enhanced by 40-150 % and 50-190 %, respectively, compared to the daytime across seasons, possibly as a combined effect from daytime photobleaching, dark-phase secondary formation, and increased nighttime emissions. MAE250 nm/MAE365 nm (i.e., E2/E3) ratios and Angstrom Exponents revealed that BrCaq and HULIS-n were relatively more aromatic and conjugated during the biomass burning-dominated periods while BrCaq and HULIS-a were comprised mostly of non-conjugated aliphatic structures from secondary processes during the photochemistry-dominated summer. The relative radiative forcing of BrCaq with respect to elemental carbon (EC) was 10-12 % in the post-monsoon and winter in the 300-400 nm range. Optical source apportionment using PMF revealed that BrCaq absorption at 300, 365 and 420 nm wavelengths in the eastern IGP is mostly from biomass burning (60-75 %), followed by combined marine and fossil fuel-derived sources (24-31 %), and secondary processes (up to 10 %). Source-specific MAEs at 365 nm were estimated to be the highest for the combined marine and fossil fuel source (1.34 m2 g-1) followed by biomass burning (0.78 m2 g-1) and secondary processing (0.13 m2 g-1). Finally, δ13C and δ15N isotopic analysis confirmed the importance of summertime photochemistry and wintertime NO3--dominated chemistry in constraining BrC characteristics. Overall, the quantitative apportionment of BrCaq sources and processing reported here can be expected to lead to targeted source-specific measurements and a better understanding of BrC climate forcing in the future.

SPTing across condensates: SEC-mediated translocation of SPT complex from pausing condensates to elongation condensates.

Several independent studies in the last few years have suggested that phase separation and biomolecular condensation play a critical role in regulating different transcription steps from initiation to pausing and elongation. However, how components of the transcription machinery translocate among different types of condensates during transcription remains poorly understood. Guo et al have now identified a potential mechanism underlying translocation of the DSIF complex from pausing to elongation condensates during promoter pause release, as reported in this issue of EMBO reports.

Are fireworks a significant episodic source of brown carbon?

We hypothesize that firework events involving the combustion of charcoal fuel, organic binders, metal salts, and cellulose-based wrapping material could be significant transient sources of aerosol brown carbon (BrC). To test this, we couple high time-resolution (1 min) measurements of black carbon (BC) and BrC absorption from a 7-wavelength aethalometer with time-integrated (12-24 h) measurements of filter extracts, i.e., UV-visible, fluorescence, and Fourier-transformed infrared (FT-IR) signatures of BrC, total and water-soluble organic carbon (OC and WSOC), ionic species, and firework tracer metals during a sampling campaign covering the Diwali fireworks episode in India. In sharp contrast to BC, BrC absorption shows a distinct and considerable rise of 2-4 times during the Diwali period, especially during the hours of peak firework activity, as compared to the background. Fluorescence profiles suggest enrichment of humic-like substances (HULIS) in the firework plume, while the enhancement of BrC absorption in the 400-500 nm range suggests the presence of nitroaromatic compounds (NACs). Considerable contributions of WSOC and secondary organics to OC (44.1% and 31.2%, respectively) and of the water-soluble fraction of BrC to total BrC absorption (71.0%) during the Diwali period point toward an atmospherically processed, polar signature of firework-related BrC, which is further confirmed by FT-IR profiles. This aqueous BrC exerts a short-lived but strong effect on atmospheric forcing (12.0% vis-à-vis BC in the UV spectrum), which could affect tropospheric chemistry via UV attenuation and lead to a stabilization of the post-Diwali atmosphere, resulting in enhanced pollutant build-up and exposure.

Immunogenic and neutralization efficacy of recombinant perfringolysin O of Clostridium perfringens and its C-terminal receptor-binding domain in a murine model.

Clostridium perfringens is a Gram-positive anaerobe ubiquitously present in different environments, including the gut of humans and animals. C. perfringens have been classified in the seven toxinotypes based on the secreted toxins that cause different diseases in humans and animals. Perfringolysin O (PFO), a cholesterol-dependent pore-forming cytolysin, is one of the potent toxins secreted by almost all C. perfringens isolates. The PFO acts in synergy with α-toxin in the progression of gas gangrene in humans and necrohemorrhagic enteritis in the calves.C. perfringens infections spread very fast, and the animals die within a few hours of the onset of infection. This necessitates the use of vaccines to control clostridial infections. Though the vaccine potential of other toxins has been reported, PFO has remained unexplored. The present study describes the immunogenic and protective potential of native recombinant PFO (WTrPFO). Since the PFO is toxic to the host cells, the non-toxic C-terminal domain of PFO (rPFOC-ter) was also assessed for its immunogenicity and protective efficacy. Immunization of mice with the purified soluble recombinant histidine-tagged WTrPFO and rPFOC-ter, expressed in E. coli, generated robust mixed immune response and T cell memory. Pre-incubation of the WTrPFO with anti-WTrPFO and rPFOC-ter antisera negated its hemolytic activity in mice RBCs, as well as its cytotoxic effect in mice peritoneal macrophages in vitro. Thus, immunization with the WTrPFO and its non-toxic C-terminal domain generated neutralizing antibodies, suggesting their vaccine potential against the PFO. Thus, the non-toxic C-terminal domain of PFO could serve as an alternative to PFO as a vaccine candidate.

Hierarchical structure and mechanical properties of fish scales from Lutjanidae with different habitat depths.

In recent days, many researchers are focusing on emerging a new class of bio-inspired architectured materials. The primary strategy of these architecture designs is directly dependent on the types of available literature based on higher-ordered species such as nacre and fish scales. In this study, the authors have investigated the microstructural features and mechanical properties of five different ray-finned fish scales from Lutjanidae family collected in Iran. It was found that habitat depth and habits may result in significant changes in scale's surface morphology and mechanical properties. Interestingly, the variations in cross-sectional microstructural features such as fibre orientation and layer thickness ratios in scales did not show noticeable differences. It has also been proved that the mechanical performance of fish scales is influenced by the shape, array pattern and compactness of strips on posterior edges in a scale. Moreover, the radii count at anterior positions is higher in fishes living in wide-ranging depth; it supports in achieving higher scale stiffness and flexibility during movement. Consideration of these factors may help in optimising the performance of newly designed architectured materials subjected to mechanical loadings.

Stress-induced nuclear condensation of NELF drives transcriptional downregulation.

In response to stress, human cells coordinately downregulate transcription and translation of housekeeping genes. To downregulate transcription, the negative elongation factor (NELF) is recruited to gene promoters impairing RNA polymerase II elongation. Here we report that NELF rapidly forms nuclear condensates upon stress in human cells. Condensate formation requires NELF dephosphorylation and SUMOylation induced by stress. The intrinsically disordered region (IDR) in NELFA is necessary for nuclear NELF condensation and can be functionally replaced by the IDR of FUS or EWSR1 protein. We find that biomolecular condensation facilitates enhanced recruitment of NELF to promoters upon stress to drive transcriptional downregulation. Importantly, NELF condensation is required for cellular viability under stressful conditions. We propose that stress-induced NELF condensates reported here are nuclear counterparts of cytosolic stress granules. These two stress-inducible condensates may drive the coordinated downregulation of transcription and translation, likely forming a critical node of the stress survival strategy.

Structural and mechanical properties of fish scales for the bio-inspired design of flexible body armors: A review.

Natural protection offered to living beings is the result of millions of years of biological revolution. The protections provided in fishes, armadillos, and turtles by unique hierarchal designs help them to survive in surrounding environments. Natural armors offer protections with outstanding mechanical properties, such as high penetration resistance and toughness to weight ratio. The mechanical properties are not the only key features that make scales unique; they are also highly flexible and breathable. In this study, we aim to review the structural and mechanical characteristics of the scales from ray-finned or teleost fishes, which can be used for new bio-inspired armor designs. It is also essential to consider the hierarchical structure of extinct and existing natural armors. The basic characteristics, as mentioned above, are the foundation for developing high-performance, well-structured flexible natural armors. Furthermore, the present review justifies the importance of interaction between toughness, hardness, and deformability in well-engineered bio-inspired body armor. At last, some suggestions are proposed for the design and fabrication of new bio-inspired flexible body armors.

A new design and performance optimization of bio-inspired flexible protective equipment.

In this study, a new biomimetic design of protective equipment has been proposed. Basically, teleost fish scales combine a two-layered structure, a tough high mineralized bony layer with a relatively soft collagen and fiber-based sublayer arranged in a periodic overlapping design, which offers excellent flexibility and puncture resistance. For the biomimetic design of fish scales, a hard-ceramic layer with an ultra-high-molecular-weight polyethylene based-sublayer is used for the design of protective equipment. Finite element analysis of the bio-inspired protective design and its ballistic performance is done by a commercially available 3D simulation software LS-DYNA. Various design parameters, including the overlapping angle of adjacent scales, frictional coefficient between scales, number of Kevlar layers in the backing layer, ceramic types in the scale are discussed and analyzed to optimize the flexibility aspects of protective equipment. The ballistic performance of newly designed protective equipment with a failure pattern is examined as per the National Institute of Justice (NIJ) standards level III. Results based on experimental outcome and optimized parameters defined the critical performance limit of the protective equipment. Therefore, the results of this research provide valuable information related to ballistic safety equipment for improving the existing designs and/or fabricating innovative protective equipment.

Optical properties of aerosol brown carbon (BrC) in the eastern Indo-Gangetic Plain.

We report here measurements of aerosol black carbon (BC) and aqueous and methanol-extractable brown carbon (BrCaq and BrCme) from a receptor location in the eastern Indo-Gangetic Plain (IGP) under two aerosol regimes: the photochemistry-dominated summer and biomass burning (BB) dominated post-monsoon. We couple time-resolved measurements of BC and aerosol light absorption coefficients (babs) with time-integrated analysis of BrC UV-Vis and fluorescence characteristics, along with measurements of total and water-soluble organic carbon (OC and WSOC), and ionic species (NH4+, K+, NO3-). In the BB regime, BC and its BB-derived fraction (BCBB) increased by factors of 3-4 over summertime values. In comparison, babs_365_aq and babs_365_me (absorption coefficients of BrCaq and BrCme at 365 nm) increased by a factor of 5 (9.7 ± 7.8 vs 2.1 ± 1.4 Mm-1) and 2.5 (17.2 ± 9.0 vs 6.9 ± 2.9 Mm-1), respectively, in the BB period over summer, and were highly correlated (r = 0.82-0.87; p < 0.01) with the BB-tracer nssK+. The wavelength dependence of babs_BrC (Ångstrom exponent: 5.9-6.2) and the presence of characteristic fluorescence peaks at 420-430 nm suggested presence of humic-like substances (HULIS) in the aged BB aerosol, while significant association between BrCaq and NO3- (r = 0.73; p < 0.01) possibly indicated formation of water-soluble nitroaromatic compounds. BrCaq contributed 55% to total BrC absorption at 300-400 nm while that for the water-insoluble component (WI-BrC) increased from 41% at 340 nm to ~60% at 550 nm, suggesting formation of water-insoluble polycyclic aromatic hydrocarbons (PAHs) and/or N-PAHs. Mass absorption efficiencies at 365 nm (MAE365) of BrCaq and BrCme in the BB regime (0.95 ± 0.45 and 1.17 ± 0.78 m2 g-1, respectively) were in line with values expected from photobleaching of BB source emissions after transport to the eastern IGP. Overall, BrCaq and BrCme were significant components of light absorbing aerosol in the BB regime, with contributions of 9 ± 5% and 16 ± 7%, respectively, to radiative forcing vis-à-vis BC in the 300-400 nm range.

Spatially resolved distribution, sources and health risks of heavy metals in size-fractionated road dust from 57 sites across megacity Kolkata, India.

This work reports the first assessment of contamination levels, source contributions and health risks associated with heavy metals (HMs) in road dust from Kolkata, the second-most polluted metropolis in India. To this end, samples collected from 57 locations across 6 land-use categories: residential, roadside, traffic, railway, port and industrial areas in the city during 2018 were analyzed for 11 major and trace metals (Ca, Mg, Fe, Al, Mn, Ni, V, Cu, Zn, Cr, Pb) in three size fractions: <75 µm, 75-125 µm and 125-300 µm. Overall, Mn, Zn, Cr, Pb, V, Cu and Ni were enriched in the smallest fraction by factors of 1.2-2.7. Based on metal distribution across land-use categories, crustal dust (Fe, Al, V), construction activities (Ca, Mg), metallurgical processes (Pb), and non-exhaust abrasive emissions from brake, tire and paint wear (Cu, Zn, Cr) were found to be significant. HMs such as Cu, Zn, Cr and Pb were considerably enriched over background levels as suggested by three contamination indices: Enrichment Factor (EF; overall range: 2.4-12.0), Index of Geo-accumulation (Igeo; overall range: 1.1-3.4), and Pollution Index (PI; overall range: 3.1-15.6). Geospatial mapping identified HM contamination hotspots (integrated PI >4) in west-central and northern parts (the older sections) of the city represented by industrial, port, and traffic-congested residential areas. Using positive matrix factorization (PMF), the following sources were apportioned for the three size fractions: crustal dust (48-66%), construction activities (18-20%), vehicular abrasion (7-21%), industrial emissions (5-8%), a Cr-dominated mixed source (6%) and an unassigned source (7%). Finally, health risk assessment in the form of cumulative hazard index (HI) and incremental lifetime cancer risk (ILCR) found that children (mean HIchildren: 1.29 and ILCRchildren: 2E-04) are comparatively more vulnerable than adults (mean HIadults: 0.22 and ILCRadults: 8E-05) to HM exposure, with the ingestion exposure pathway dominating over dermal contact and inhalation.

Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1.

Molecular chaperones such as heat-shock proteins (HSPs) help in protein folding. Their function in the cytosol has been well studied. Notably, chaperones are also present in the nucleus, a compartment where proteins enter after completing de novo folding in the cytosol, and this raises an important question about chaperone function in the nucleus. We performed a systematic analysis of the nuclear pool of heat-shock protein 90. Three orthogonal and independent analyses led us to the core functional interactome of HSP90. Computational and biochemical analyses identify host cell factor C1 (HCFC1) as a transcriptional regulator that depends on HSP90 for its stability. HSP90 was required to maintain the expression of HCFC1-targeted cell-cycle genes. The regulatory nexus between HSP90 and the HCFC1 module identified in this study sheds light on the relevance of chaperones in the transcription of cell-cycle genes. Our study also suggests a therapeutic avenue of combining chaperone and transcription inhibitors for cancer treatment.