Artificial Metalloproteins with Dinuclear Iron-Hydroxido Centers.

Dinuclear iron centers with a bridging hydroxido or oxido ligand form active sites within a variety of metalloproteins. A key feature of these sites is the ability of the protein to control the structures around the Fe centers, which leads to entatic states that are essential for function. To simulate this controlled environment, artificial proteins have been engineered using biotin-streptavidin (Sav) technology in which Fe complexes from adjacent subunits can assemble to form [FeIII-(µ-OH)-FeIII] cores. The assembly process is promoted by the site-specific localization of the Fe complexes within a subunit through the designed mutation of a tyrosinate side chain to coordinate the Fe centers. An important outcome is that the Sav host can regulate the Fe···Fe separation, which is known to be important for function in natural metalloproteins. Spectroscopic and structural studies from X-ray diffraction methods revealed uncommonly long Fe···Fe separations that change by less than 0.3 Å upon the binding of additional bridging ligands. The structural constraints imposed by the protein host on the di-Fe cores are unique and create examples of active sites having entatic states within engineered artificial metalloproteins.

Association of alpha hemoglobin-stabilizing protein (AHSP) gene mutation and disease severity among HbE-beta thalassemia patients.

In this study, we aimed to investigate the pattern and association of genetic mutations occurring within the alpha hemoglobin-stabilizing protein (AHSP) gene among HbE beta thalassemia patients with varying phenotypic expressions. Fifty-four diagnosed cases of HbE beta thalassemia (transfusion dependent and independent) were included in the study. Among them, 38 patients with similar genotypes (IVS 1-5, alpha gene deletion and triplication, Xmn polymorphism) were selected for further analysis. AHSP gene sequencing was done for these 38 samples to study associated mutations in AHSP gene. HbE beta thalassemia patients with similar genotypes but different phenotypic expressions were found to have mutations in the AHSP gene. There were five mutations found most prevalent among the samples analyzed for AHSP gene sequencing. Among these, two mutations were from intron 1 region of AHSP and three mutations were found in exon 3. The most prevalent mutation was found at the Oct binding site at intron 1 of AHSP. The mutations in exon 3 were more prevalent among the TDT groups. A mutation in exon 3 changing the amino acid (33rd) from serine to phenylalanine was found to be associated with only TDT group. This study documents that among the HbE beta thalassemia patients with varying severity, an exon mutation in AHSP is significantly prevalent only among the TDT group. Further understanding of the mechanism will shed light upon the impact of AHSP in modifying the disease severity in thalassemia.

A phototunable anion receptor for C-HX interactions with benzoate anions.

A supramolecular receptor consisting of two anthracene moieties with binding motifs for binding of benzoate anions is reported here. NMR studies indicate that the binding involves π-π interactions and CHX interactions. Upon exposure to >350 nm light, the receptor undergoes a [4 + 4] photoelectrocyclization restricting the access to the binding site for benzoate. The reverse reaction works in the presence of the dual stimuli of 254 nm light and the benzoate anions. The work thus demonstrates a light mediated dynamic control of the binding pocket of a supramolecular anion receptor.

Efficacy of decitabine as hemoglobin F inducer in HbE/ß-thalassemia.

To study safety, efficacy (hemoglobin and hemoglobin F percentage increment in non-transfusion-dependent patients and decrease in transfusion frequency in transfusion-dependent patients), and determinants of response of decitabine in patients with HbE/ß-thalassemia. Thirty patients of HbE/ß-thalassemia (age > 18 years) were enrolled. Both transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) patients were included after obtaining informed consent. Participants received 0.2 mg/kg of 5-aza-2'-deoxycytidine (decitabine) subcutaneously on 2 consecutive days a week for at least 12 weeks. Complete hemogram was done every 2 weeks and HPLC at every 4-week interval, until 2 months after last dose of drug for response assessment. Various factors like XMN1 polymorphism, IVS 1-5, alpha deletion, alpha triplication, baseline hemoglobin F, and baseline total hemoglobin were evaluated as determinants of response. Mean therapy period was 20.32 weeks. For NTDT group, peak mean increment in hemoglobin was 0.938 g/dl (p value < .001) and hemoglobin F percentage was 9.62% (p value < .001). Transfusion requirement decreased to 0.25 units compared to 0.96 units per patient per month for TDT patients over a period of last 1 year. Common side effects were respiratory tract infection (grade I/II) in three patients, chest tightness in one patient (grade I), and gastric erosion (grade III) in one patient. Decitabine is safe and efficacious in HbE/ß-thalassemia.

Plant-nano interactions: A new insight of nano-phytotoxicity.

Whether nanoparticles (NPs) are boon or bane for society has been a centre of in-depth debate and key consideration in recent times. Exclusive physicochemical properties like small size, large surface area-to-volume ratio, robust catalytic activity, immense surface energy, magnetism and superior biocompatibility make NPs obligatory in many scientific, biomedical and industrial ventures. Nano-enabled products are newer entrants in the present era. To attenuate environmental stress and maximize crop yields, scientists are tempted to introduce NPs as augmented supplements in agriculture. The feasible approaches for NPs delivery are irrigation, foliar spraying or seed priming. Internalization of excessive NPs to plants endorses negative implications at higher trophic levels via biomagnification. The characteristics of NPs (dimensions, type, solubility, surface charge), applied concentration and duration of exposure are prime factors conferring nanotoxicity in plants. Several reports approved NPs persuaded toxicity can precisely mimic abiotic stress effects. The signature effects of nanotoxicity include poor root outgrowth, biomass reduction, oxidative stress evolution, lipid peroxidation, biomolecular damage, perturbed antioxidants, genotoxicity and nutrient imbalance in plants. NPs stress impels mitogen-activated protein kinase signaling cascade and urges stress responsive defence gene expression to counteract stress in plants. Exogenous supplementation of nitric oxide (NO), arbuscular mycorrhizal fungus (AMF), phytohormones, and melatonin (ME) is novel strategy to circumvent nanotoxicity. Briefly, this review appraises plants' physio-biochemical responses and adaptation scenarios to endure NPs stress. As NPs stress represents large-scale contaminants, advanced research is indispensable to avert indiscriminate NPs usage for synchronizing nano-security in multinational markets.

Application of green synthesized bimetallic nZVI-Cu nanoparticle as a sustainable alternative to chemical fertilizers to enhance growth and photosynthetic efficiency of rice seedlings.

Application of nanomaterials in agriculture has been extensively explored over the past decade leading to a wide ambit of nanoparticle-based agrochemicals. Metallic nanoparticles consisting of plant macro- and micro-nutrients have been used as nutritional supplements for plants through soil amendments, foliar sprays, or seed treatment. However, most of these studies emphasize monometallic nanoparticles which limit the range of usage and effectivity of such nanoparticles (NPs). Hence, we have employed a bimetallic nanoparticle (BNP) consisting of two different micro-nutrients (Cu & Fe) in rice plants to test its efficacy in terms of growth and photosynthesis. Several experiments were designed to assess growth (root-shoot length, relative water content) and photosynthetic parameters (pigment content, relative expression of rbcS, rbcL & ChlGetc.). To determine whether the treatment induced any oxidative stress or structural anomalies within the plant cells, histochemical staining, anti-oxidant enzyme activities, FTIR, and SEM micrographs were undertaken. Results indicated that foliar application of 5 mg L-1 BNP increased vigor and photosynthetic efficiency whereas 10 mg L-1 concentration induced oxidative stress to some extent. Furthermore, the BNP treatment did not perturb the structural integrity of the exposed plant parts and also did not induce any cytotoxicity. Application of BNPs in agriculture has not been explored extensively to date and this study is one of the first reports that not only documents the effectivity of Cu-Fe BNP but also critically explores the safety of its usage on rice plants making it a useful lead to design new BNPs and explore their efficacy.

Artificial Metalloproteins: At the Interface between Biology and Chemistry.

Artificial metalloproteins (ArMs) have recently gained significant interest due to their potential to address issues in a broad scope of applications, including biocatalysis, biotechnology, protein assembly, and model chemistry. ArMs are assembled by the incorporation of a non-native metallocofactor into a protein scaffold. This can be achieved by a number of methods that apply tools of chemical biology, computational de novo design, and synthetic chemistry. In this Perspective, we highlight select systems in the hope of demonstrating the breadth of ArM design strategies and applications and emphasize how these systems address problems that are otherwise difficult to do so with strictly biochemical or synthetic approaches.

COVID-19 pandemic and lockdown: cause of sleep disruption, depression, somatic pain, and increased screen exposure of office workers and students of India.

COVID-19 has brought the world into uncharted waters. Many countries are under lockdown, the economy has ground to a halt, and almost everyone is afraid of dire consequences. The unprecedented changes that came on so quickly due to the pandemic and stay-at-home confinement to accomplish social distancing and mitigate risk for infection pose many challenges. These include compromised health, well-being, and sleep as a consequence of disruption of the daily life routine, anxiety, worry, isolation, greater family and work stress, and excessive screen time. Our study of 203 corporate sector professionals performing '9-5' work from home during this phase of the pandemic and of 325 undergraduate and postgraduate university students substantiates, relative to the before lockdown condition, more extensive feelings of sleepiness, with significantly (p < .05) increased daytime nap duration, and depressive symptomatology (p < .001) that is a matter of concern. Moreover, the chronic stress of living through a pandemic led to a host of physical symptoms, like headaches, insomnia, digestive problems, hormonal imbalances, and fatigue.