When two sheets of graphene stack in a twisted bilayer graphene (tBLG) configuration, the resulting constrained overlap between interplanar 2p orbitals produce angle-tunable electronic absorption ...resonances. By applying a novel combination of multiphoton transient absorption (TA) microscopy and TEM, we resolve the electronic structure and ensuing relaxation by probing resonant excitations of single tBLG domains. Strikingly, we find that the transient electronic population in resonantly excited tBLG domains is enhanced many fold, forming a major electronic relaxation bottleneck. Two-photon TA microscopy shows this bottleneck effect originates from a strongly bound, dark exciton state lying ∼0.37 eV below the 1-photon absorption resonance. This stable coexistence of strongly bound excitons alongside free-electron continuum states has not been previously observed in a metallic, 2D material.
ADP‐glucose pyrophosphorylase is a key regulatory enzyme involved in starch and glycogen synthesis in plants and bacteria, respectively. It has been hypothesized that inter‐subunit communications are ...important for the allosteric effect in this enzyme. However, no specific interactions have been identified as part of the regulatory signal. The enzyme from Agrobacterium tumefaciens is a homotetramer allosterically regulated by fructose 6‐phosphate and pyruvate. Three pairs of distinct subunit‐subunit interfaces are present. Here we focus on an interface that features two symmetrical interactions between Arg11 and Asp141 from one subunit with residues Asp141 and Arg11 of the neighbor subunit, respectively. Previously, scanning mutagenesis showed that a mutation at the Arg11 position disrupted the activation of the enzyme. Considering the distance of these residues from the allosteric and catalytic sites, we hypothesized that the interaction between Arg11 and Asp141 is critical for allosteric signaling rather than effector binding. To prove our hypothesis, we mutated those two sites (D141A, D141E, D141N, D141R, R11D, and R11K) and performed kinetic and binding analysis. Mutations that altered the charge affected the regulation the most. To prove that the interaction per se (rather than the presence of specific residues) is critical, we partially rescued the R11D protein by introducing a second mutation (R11D/D141R). This could not restore the activator effect on kcat, but it did rescue the effect on substrate affinity. Our results indicate the critical functional role of Arg11 and Asp141 to relay the allosteric signal in this subunit interface.
Introduction:
Systemic sclerosis (aka scleroderma) is an autoimmune disease with no known definitive etiology, but genetic, infectious, and non-infectious exposures have been associated with its ...occurrence. Previous studies have shown that systemic sclerosis can be a paraneoplastic phenomenon and may be associated with increased risk of malignancy, most commonly lung, skin, and breast cancers. The association of renal cell carcinoma with systemic sclerosis is rare.
Case Description:
Here, we present a case of a 75-year-old male patient with a rapidly progressive scleroderma despite the initial treatment with methotrexate and prednisone 5 mg daily. Shortly after the diagnosis of scleroderma, the patient was found to have a renal mass. The patient underwent a right partial nephrectomy revealing papillary renal cell carcinoma. The surgical margin was negative indicating complete removal of the cancer. The patient, later, developed scleroderma renal crisis and progressed to end-stage renal disease despite treatment with captopril, mycophenolate mofetil, plasmapheresis, and intravenous immunoglobulin.
Conclusions:
The purpose of this case report and literature review is to highlight that diffuse scleroderma can potentially be paraneoplastic from a renal cell carcinoma and to add more data to the literature given there are only a handful of reported cases. Our patient is unique in the sense that he was discovered to have renal cell carcinoma shortly after being diagnosed with scleroderma suggesting a paraneoplastic etiology yet continued to worsen despite full resection of the renal cell carcinoma. This is in contrast to the other reported cases of renal cell carcinoma associated scleroderma where scleroderma worsened around the time of the diagnosis of renal cell carcinoma and improved after nephrectomy. There also are case reports of the patients with renal cell carcinoma associated scleroderma where the patient had scleroderma for several years before the diagnosis of renal cell carcinoma, which raises the question, if scleroderma could also represent a risk factor for developing renal cell carcinoma.
Summary
Interactions between the Bruton tyrosine kinase (BTK) inhibitor PCI‐32765 and the proteasome inhibitor (bortezomib) were examined in diffuse large‐B cell lymphoma (DLBCL) and mantle cell ...lymphoma (MCL) cells, including those highly resistant to bortezomib. Co‐administration of PCI‐32765/bortezomib synergistically increased mitochondrial injury and apoptosis in germinal centre‐ or activated B‐cell‐like‐DLBCL cells and in MCL cells. These events were accompanied by marked AKT and nuclear factor (NF)‐κB (NFKB1) inactivation, down‐regulation of Mcl‐1 (MCL1), Bcl‐xL (BCL2L1), and XIAP, and enhanced DNA damage (e.g., γH2A.X formation) and endoplasmic reticulum (ER) stress. Similar interactions were observed in highly bortezomib‐resistant DLBCL and MCL cells, and in primary DLBCL cells. In contrast, PCI‐32765/bortezomib regimens displayed minimal toxicity toward normal CD34+ bone marrow cells. Transfection of DLBCL cells with a constitutively active AKT construct attenuated AKT inactivation and significantly diminished cell death, whereas expression of an NF‐κB “super‐repressor” (IκBαser34/36) increased both PCI‐32765 and bortezomib lethality. Moreover, cells in which the ER stress response was disabled by a dominant‐negative eIF2α construct were resistant to this regimen. Finally, combined exposure to PCI‐32765 and bortezomib resulted in more pronounced and sustained reactive oxygen species (ROS) generation, and ROS scavengers significantly diminished lethality. Given promising early clinical results for PCI‐32765 in DLBCL and MCL, a strategy combining BTK/proteasome inhibitor warrants attention in these malignancies.
Phycocyanin (PC) is the principal pigment protein in the light-harvesting antenna of cyanobacteria. Here the biochemical characterization and the 1.51 Å crystal structure of PC from cyanobacterium ...Nostoc sp. WR13 (Nst-PC) is reported. The P63 crystal lattice is composed of the minimal biological entities of Nst-PC, the (αβ)3 trimeric rings. The structure has been refined to R factor 11.5% (Rfree 15.4%) using anisotropic atomic B factors. A phylogenetic study shows that the α and β chains of Nst-PC are significantly clustered in a distinct clade with Acaryochloris marina. The structure was examined to look for any significant differences between Nst-PC and PC from non-desert species. Only minor differences were found in the chromophore microenvironments. The tentative energy transfer pathways in Nst-PC were modeled based on simple structural considerations.
•The cyanobacterium Nostoc sp. WR13 is isolated from the desert Rann of Kachchh.•Crystal structure of phycocyanin purified from desert cyanobacterium is reported.•Evolution of pcA and pcB gene is shown by phylogenetic study.•Energy transfer pathway between chromophores of αβ heterodimer has been predicted.
Anthocyanins are a major group of plant pigments that have antioxidant activities. Pigments play a major role in human health and have attracted a lot of attention globally. Many factors affect ...anthocyanin yields, such as solvent type, incubation time, solvent-to-sample ratio, sample type, and temperature. The first parameter was tested, and the rest were considered constant in this experiment. A total of nine organic and water-based solvents (methanol and chloroform: methanol, acetone, ethanol, water) and their combinations were compared to extract anthocyanins from freshly-pureed strawberries. Solvents changed anthocyanin yield, color parameters, and profile. The color parameters of a* values lower than 30, L* values higher than 85, hue angle more than 40, and chroma less than 30 indicated some color degradation in strawberry anthocyanins. Therefore, the best solvents for anthocyanin assessment were methanol and methanol: water. The second-best solvent was the pH differential buffers. Other solvents such as ethanol, chloroform: methanol, water, and water-based solvents extracted considerable amounts of anthocyanins; however, they showed some degree of color degradation, evidenced by the color parameters. Acetone did not yield a stable extract which degraded over 48 h of storage at 4 °C. The extraction solvent determined the main anthocyanin of the anthocyanins profile. Pelargonidin was the major anthocyanin in chloroform: methanol solvent, while delphinidin was dominant in all other solvents.
Context and Aim: There is increasing prevalence of post-COVID fungal infection of rhinoorbitocerebral region especially mucormycosis and aspergillosis in India.1 Early diagnosis of these fungal ...infections are of utmost importance, since it may improve outcome and survival.2,3,4,5,6,7,8 The objective of this study was to evaluate and compare routine laboratory diagnostic methods, that is, histopathological examination, KOH wet mount and fungal culture in the diagnosis of post-COVID fungal infections. Materials and Methods: A total of 106 specimens of clinically suspected patients of post-COVID fungal infection of rhinoorbitocerebral region received in histopathology department were included in this study. The data of KOH wet mount and culture were acquired from the microbiology department after histopathological examination. Result: Approximately 88.68% of patients were diagnosed having fungal infections by one of the laboratory methods. The sensitivity of histopathological examination was highest (79.78%), followed by KOH wet mount (58.51%) and fungal culture (35.10%). Rhizopus species of zygomycetes group were the most common isolate (24.24%) on SDA culture. Overall 76% concordance was found between histopathological examination and fungal culture report for morphological identification of fungi. Conclusion: For the diagnosis of post-COVID fungal infection of Rhino-orbito-cerebral region, histopathological examination is was found to be more sensitive and rapid method to detect fungal hyphae. It leads to early treatment, prevents morbidity and mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•The isolation of P. stutzeri MP4687 from cattle rumen.•The complete genome sequencing and comparative analysis of P. stuteri.•Adaptation to the rumen environment.•The strain has complete LCB ...hydrolyzing potential.
We report the complete genome sequencing of novel Pseudomonas stutzeri strain MP4687 isolated from cattle rumen. Various strains of P. stutzeri have been reported from different environmental samples including oil-contaminated sites, crop roots, air, and human clinical samples, but not from rumen samples, which is being reported here for the first time. The genome of P. stutzeri MP4687 has a single replicon, 4.75 Mb chromosome and a G + C content of 63.45%. The genome encodes for 4,790 protein coding genes including 164 CAZymes and 345 carbohydrate processing genes. The isolate MP4687 harbors LCB hydrolyzing potential through endoglucanase (4.5 U/mL), xylanase (3.1 U/mL), β-glucosidase (3.3 U/mL) and β-xylosidase (1.9 U/mL) activities. The pangenome analysis further revealed that MP4687 has a very high number of unique genes (>2100) compared to other P. stutzeri genomes, which might have an important role in rumen functioning.
Display omitted
•Green Synthesized zinc oxide nanoparticles (GsZnO-Nps) via Moringa oleifera leaves extract.•Anti-Acne and Anti-Oxidant efficacy of multifunctional GsZnO-Nps.•Advance anti-microbial ...potency of GsZnO-Nps against standard drugs.
This article explores green synthesis as a strategic and sustainable route to fabricate potent zinc oxide nanoparticles. Natural green based antibacterial agents and alternatives are being introduced in the market however there is a dearth in green approach moringa based zinc oxide nanoparticles in personal care products and establishing efficacy. Moringa oleifera comprises various phytochemicals that act as non-toxic stabilizing and reducing agents. Green synthesized ZnO nanoparticles (GsZnO-Nps) were investigated for their morphological and physicochemical properties using various advanced characterizing techniques. The hexagonal wurtzite structure of GsZnO-Nps is determined by X-ray diffractometry (XRD), the average crystallite size is 13.82 nm, total crystallinity was 95.91 % and high specific-surface-area is 77.38 m2/g. Scanning Electron Microscope (SEM) revealed the formation of spherical nanoparticles having a diameter of 50 nm. UV–vis spectrum shows high bandgap energy of 3.36 eV. Results have shown that antioxidant efficacy of GsZnO-Nps is significantly higher than AR-Grade ZnO, evaluated by using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. Half-maximal inhibitory concentration (IC50) of GsZnO-Nps was 21.72 µg/mL and AR-Grade ZnO was 345.57 µg/mL. GsZnO-Nps (0.0183 g/mL) shows robust anti-acne efficacy against Cutibacterium acne (C. acne) organism which estimated by ZOI technique, have average ZOI of 33 mm, with standard error 0.577 mm. Antibacterial efficacy of GsZnO-Nps was established at different concentrations (10, 50, 100, and 200 µg/mL) against Gram-positive and Gram-negative pathogens by zone-of-inhibition (ZOI) method with respect to standard drugs. GsZnO-Nps at 200 µg/mL exhibits high ZOI of 26.75 mm against Escherichia coli (E. coli) and ZOI of 30 mm against Staphylococcus aureus (S. aureus) organisms respectively which is comparatively higher or equal to standard drugs. The minimum inhibitory concentration (MIC) of GsZnO-Nps is 500 µg/mL to inhibit the microbe's growth. GsZnO-Nps established the added benefits of moringa phytochemicals and is an excellent approach to developing eco-friendly and multi-functional versatile products having strong antioxidants, anti-acne and advanced antibacterial efficacy for numerous industrial applications like cosmetic, health hygiene products, drugs, therapeutic etc.
We previously described unique features of the IL-15 receptor (IL-15R)α. IL-15Rα by itself forms stable complexes with IL-15 on cell surfaces and presents IL-15 in trans to neighboring natural ...killer/T cells. Moreover, the membrane IL-15/IL-15Rα complexes (membIL-15) undergo endosomal internalization but survive lysosomal degradation, allowing the complexes to recycle back to the cell surface. Here, we show that membIL-15⁺ cells act as a persistent source of IL-15 for the surrounding microenvironment (intercellular reservoir effect). Additionally, membIL-15⁺ cells give rise to augmented retention of IL-15 in the circulation as well as in tissues. Curiously, IL-15 retention was particularly associated with lungs, rather than with lymph nodes, in normal unstimulated mice, which correlated with the preferential homing of antigen-specific CD8 T cells to lungs during their contraction phase in an IL-15Rα-dependent manner. Furthermore, membIL-15, unlike soluble IL-15, caused sustained IL-15 signal transduction in the target cells. Collectively, these characteristics define IL-15 as a unique cytokine with prolonged in vivo survival and sustained biological action on the target cells, which may account for the proposed persistent action of IL-15 that helps the long-term survival of functional CD8 memory T cells in vivo.
PDF
