Exploratory data analysis of physicochemical parameters of natural antimicrobial and anticancer peptides: Unraveling the patterns and trends for the rational design of novel peptides.

Introduction: Peptide-based research has attained new avenues in the antibiotics and cancer drug resistance era. The basis of peptide design research lies in playing with or altering physicochemical parameters. Here in this work, we have done exploratory data analysis (EDA) of physicochemical parameters of antimicrobial peptides (AMPs) and anticancer peptides (ACPs), two promising therapeutics for microbial and cancer drug resistance to deduce patterns and trends. Methods: Briefly, we have captured the natural AMPs and ACPs data from the APD3 database. After cleaning the data manually and by CD-HIT web server, further data analysis has been done using Python-based packages, modlAMP and Pandas. We have extracted the descriptive statistics of 10 physicochemical parameters of AMPs and ACPs to build a comprehensive dataset containing all major parameters. The global analysis of datasets has been done using modlAMP to find the initial patterns in global data. The subsets of AMPs and ACPs were curated based on the length of the peptides and were analyzed by Pandas package to deduce the graphical profile of AMPs and ACPs. Results: EDA of AMPs and ACPs shows selectivity in the length and amino acid compositions. The distribution of physicochemical parameters in defined quartile ranges was observed in the descriptive statistical and graphical analysis. The preferred length range of AMPs and ACPs was found to be 21-30 amino acids, whereas few outliers in each parameter were evident after EDA analysis. Conclusion: The derived patterns from natural AMPs and ACPs can be used for the rational design of novel peptides. The statistical and graphical data distribution findings will help in combining the different parameters for potent design of novel AMPs and ACPs.

DP1, a multifaceted synthetic peptide: Mechanism of action, activity and clinical potential.

AIMS: Microbial infections remain a leading cause of mortality worldwide, with Staphylococcus aureus (S. aureus) being a prominent etiological agent, responsible for causing persistent bacterial infections in humans. It is a nosocomial, opportunistic pathogen, capable to propagate within the bloodstream and withstand therapeutic interventions. In the current study, a novel, indigenously designed synthetic antimicrobial peptide (sAMP) has been evaluated for its antimicrobial potential to inhibit the growth and proliferation of S. aureus. MAIN METHODS: The sAMP, designed peptide (DP1) was evaluated for its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against a panel of pathogenic bacterial strains. Membrane mechanistic studies were performed by measuring membrane conductivity via dielectric spectroscopy and visualizing changes in bacterial membrane structure through field emission scanning electron microscopy (FE-SEM). Further, DP1 was tested for its in vivo antimicrobial potential in an S. aureus-induced systemic infection model. KEY FINDINGS: The results indicated that DP1 has the potential to inhibit the growth and proliferation of a broad spectrum of Gram-positive, Gram-negative and multidrug-resistant (MDR) bacterial strains. Strong bactericidal effect attributed to change in electrical conductivity of the bacterial cells leading to membrane disruption was observed through dielectric spectroscopy and FE-SEM micrographs. Further, in the in vivo murine systemic infection study, 50 % reduction in S. aureus bioburden was observed within 1 day of the administration of DP1. SIGNIFICANCE: The results indicate that DP1 is a multifaceted peptide with potent bactericidal, antioxidant and therapeutic properties. It holds significance as a novel drug candidate to effectively combat S. aureus-mediated systemic infections.

In Vivo Acute Toxicity and Therapeutic Potential of a Synthetic Peptide, DP1 in a Staphylococcus aureus Infected Murine Wound Excision Model.

Bacterial infections at the surgical sites are one of the most prevalent skin infections that impair the healing mechanism. They account for about 20% of all types of infections and lead to approximately 75% of surgical-site infection-associated mortality. Several antibiotics, such as cephalosporins, fluoroquinolones, quinolones, penicillin, sulfonamides, etc., that are used to treat such wound infections not only counter infections but also disrupt the normal flora. Moreover, antibiotics, when used for a prolonged duration, may impair the formation of new blood vessels, delay collagen production, or inhibit the migration of certain cells involved in wound repair, leading to an impaired healing process. Therefore, there is a dire need for alternate therapeutic approaches against such infections. Antimicrobial peptides have gained considerable attention as a promising strategy to counter these pathogens and prevent the spread of infection. Recently, we have reported a designed peptide, DP1, and its broad-spectrum in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria. In the present study, in vivo acute toxicity of DP1 was evaluated and even at a high dose (20 mg/kg body weight) of DP1, a 100% survival of mice was observed. Subsequently, a Staphylococcus aureus-infected murine wound excision model was established to assess the wound healing efficacy of DP1. The study revealed significant wound healing vis-a-vis attenuated S. aureus bioburden at the wound site and also controlled the oxidative stress depicting anti-oxidant activity as well. Healing of the infected wounds was also verified by histopathological examination. Based on the results of this study, it can be concluded that DP1 improves wound resolution despite infections and promotes the healing mechanism. Hence, DP1 holds compelling potential as a novel antimicrobial drug that requires further explorations in clinical platforms.

SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function.

One of the mechanisms shaping the pathophysiology during the infection of enteric pathogen Salmonella Typhimurium is host PTM machinery utilization by the pathogen encoded effectors. Salmonella Typhimurium (S. Tm) during infection in host cells thrives in a vacuolated compartment, Salmonella containing vacuole (SCV), which sequentially acquires host endosomal and lysosomal markers. Long tubular structures, called as Salmonella induced filaments (SIFs), are further generated by S. Tm, which are known to be required for SCV's nutrient acquisition, membrane maintenance and stability. A tightly coordinated interaction involving prominent effector SifA and various host adapters PLEKHM1, PLEKHM2 and Rab GTPases govern SCV integrity and SIF formation. Here, we report for the first time that the functional regulation of SifA is modulated by PTM SUMOylation at its 11th lysine. S. Tm expressing SUMOylation deficient lysine 11 mutants of SifA (SifAK11R) is defective in intracellular proliferation due to compromised SIF formation and enhanced lysosomal acidification. Furthermore, murine competitive index experiments reveal defective in vivo proliferation and weakened virulence of SifAK11R mutant. Concisely, our data reveal that SifAK11R mutant nearly behaves like a SifA knockout strain which impacts Rab9-MPR mediated lysosomal acidification pathway, the outcome of which culminates in reduced bacterial load in in vitro and in vivo infection model systems. Our results bring forth a novel pathogen-host crosstalk mechanism where the SUMOylation of effector SifA regulated S. Tm intracellular survival.

Prevalence of antibiotic-resistant Gram-negative bacteria having extended-spectrum ß-lactamase phenotypes in polluted irrigation-purpose wastewaters from Indian agro-ecosystems.

Antibiotic resistance in bacteria has emerged as a serious public health threat worldwide. Aquatic environments including irrigation-purpose wastewaters facilitate the emergence and transmission of antibiotic-resistant bacteria and antibiotic resistance genes leading to detrimental effects on human health and environment sustainability. Considering the paramount threat of ever-increasing antibiotic resistance to human health, there is an urgent need for continuous environmental monitoring of antibiotic-resistant bacteria and antibiotic resistance genes in wastewater being used for irrigation in Indian agro-ecosystems. In this study, the prevalence of antibiotic resistance in Gram-negative bacteria isolated from irrigation-purpose wastewater samples from Sirmaur and Solan districts of Himachal Pradesh was determined. Bacterial isolates of genera Escherichia, Enterobacter, Hafnia, Shigella, Citrobacter, and Klebsiella obtained from 11 different geographical locations were found to exhibit resistance against ampicillin, amoxyclav, cefotaxime, co-trimoxazole, tobramycin, cefpodoxime and ceftazidime. However, all the isolates were sensitive to aminoglycoside antibiotic gentamicin. Enterobacter spp. and Escherichia coli showed predominance among all the isolates. Multidrug-resistance phenotype was observed with isolate AUK-06 (Enterobacter sp.) which exhibited resistant to five antibiotics. Isolate AUK-02 and AUK-09, both E. coli strains showed resistant phenotypes to four antibiotics each. Phenotypic detection revealed that six isolates were positive for extended-spectrum ß-lactamases which includes two isolates from Enterobacter spp. and E. coli each and one each from Shigella sp. and Citrobacter sp. Overall, the findings revealed the occurrence of antibiotic resistant and ESBL-positive bacterial isolates in wastewaters utilized for irrigation purpose in the study area and necessitate continuous monitoring and precautionary interventions. The outcomes of the study would be of significant clinical, epidemiological, and agro-environmental importance in designing effective wastewater management and environmental pollution control strategies.

A systematic review to summarize treatment patterns, guidelines, and characteristics of patients with renal cell carcinoma in the Asia-Pacific region.

INTRODUCTION: This systematic review evaluated treatment patterns and guidelines in advanced/metastatic and adjuvant renal cell carcinoma (RCC) in the Asia-Pacific region. AREAS COVERED: Embase, PubMed, and congresses were searched for observational studies and guidelines in accordance with PRISMA. Records published during 2016-2021 (2019-2021 for congresses) were included. EXPERT OPINION: Nine studies and three guidelines were identified overall. In advanced/metastatic RCC, the most common treatments were tyrosine kinase inhibitors (TKIs) (notably sunitinib: 33-100%) for first-line, and everolimus (13-85%) or axitinib (2-89%) for second-line therapy. In adjuvant RCC, sunitinib was most used (54%), followed by mammalian target of rapamycin inhibitors (mTORis, 27%) with immunotherapy being less common (16%). The guidelines provided varying recommendations for advanced/metastatic RCC. For first-line in advanced/metastatic clear cell RCC (the most common subtype), guidelines recommended mTORis (everolimus for poor-risk patients) (India, 2016); clinical study enrollment for high-risk patients or TKIs for low- to medium-risk patients (China, 2019); or immunotherapy based on survival benefits over sunitinib; dose adjustment was also recommended to manage TKI toxicities (Hong Kong, 2019). The landscape remained more static in the adjuvant setting, but best practice was uncertain. No clear trends were identified in patient characteristics.

Characterizing and demonstrating the role of Klebsiella SSN1 exopolysaccharide in osmotic stress tolerance using neutron radiography.

Exopolysaccharides (EPS) are organic macromolecules naturally secreted by many microorganisms. EPS is increasingly used for agriculture and industrial purposes. This study focuses on isolate Klebsiella pneumonia SSN1, Klebsiella quasipeumonniae SGM81 isolated from rhizosphere to explore its water retention efficiency under drought conditions. Neutron Radiography was used to visualise water distribution in the sand under normal and drought conditions in the presence and absence of EPS producing bacteria. The EPS production was studied by applying Box Behnken design (BBD) under drought stress which was artificially induced by using polyethene glycol 6000 under osmotic stress condition 3.65% w/v of EPS dry weight was obtained. The relative water content (RWC) is used to calculate the amount of water present in the sand and was further studied by Neutron Radiography imaging with appropriate controls. FTIR and HPLC were also carried out for the characterisation of the extracted EPS. The sand experiments revealed that after 24 h of evaporation, the highest RWC was maintained by SSN1 at 29.7% compared to SGM81 (19.06%). SSN1 was found to release L-arabinose as the main sugar of its EPS under drought stress conditions by HPLC method. The FTIR data indicated the presence of ß-glucans and polysaccharide α-pyranose between wavenumber 700 cm-1-1500 cm-1 and 1017 cm-1-1200 cm-1 respectively. The HPLC characterization of extracted EPS from osmotic stressed cells (run 3) displayed a peak designated to L-arabinose at 10.3 retention time (RT) for 132.4 mM concentration. While from run 5 with the controlled condition indicated the presence of L-rhamnose at 7.3 RT for 87 mM concentration. Neutron radiography enables the visualisation of water distribution in the sand as well as water transport in root-soil systems in situ. SSN1 has elicited EPS production in drought conditions with a low level of nitrogen and carbon.

Potential of novel dual Z-scheme carbon quantum dots decorated MnIn2S4/CdS/Bi2S3 heterojunction for environmental applications.

In this work, CQDs decorated MnIn2S4/CdS/Bi2S3 heterojunction was prepared successfully by hydrothermal technique for photocatalytic disinfection of Escherichia coli (E. coli) and mineralization of methyl orange (MO) dye. The charge transferal route and mineralization process in CQDs-MnIn2S4/CdS/Bi2S3 heterojunction were comprehensively investigated by advanced spectroscopic techniques. The improved visible-light activity and enhanced photo-generated charge transferal efficacy caused dual Z-scheme CQDs-MnIn2S4/CdS/Bi2S3 heterojunction to achieve boosted photodegradation ability. The catalytic degradation trend was followed as CQDs-MnIn2S4/CdS/Bi2S3 > MnIn2S4 > CdS > Bi2S3. The dye was mineralized within 180 min under visible light irradiation. The effect of reaction parameters, pH effect, catalyst dosage, and H2O2 addition on MO degradation was also investigated. The degradation rate was maximal at pH 4 with a pseudo-first-order rate constant, 0.0438 min-1. The assessment of antibacterial properties revealed that CQDs-MnIn2S4/CdS/Bi2S3 composite effectively inactivated E. coli under visible light. Scavenging experiments, transient photocurrent response, and electron spin resonance spectroscopy suggested that •[Formula: see text] and holes were the dominant reactive species. The Z-scheme heterojunction is recyclable up to ten photocatalytic cycles according to recycling experiments. This research indicates the importance of dual Z-scheme CQDs decorated MnIn2S4/CdS/Bi2S3 heterojunction in wastewater remediation.

Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics.

In recent years, the occurrence of a wide variety of drug-resistant diseases has led to an increase in interest in alternate therapies. Peptide-based drugs as an alternate therapy hold researchers' attention in various therapeutic fields such as neurology, dermatology, oncology, metabolic diseases, etc. Previously, they had been overlooked by pharmaceutical companies due to certain limitations such as proteolytic degradation, poor membrane permeability, low oral bioavailability, shorter half-life, and poor target specificity. Over the last two decades, these limitations have been countered by introducing various modification strategies such as backbone and side-chain modifications, amino acid substitution, etc. which improve their functionality. This has led to a substantial interest of researchers and pharmaceutical companies, moving the next generation of these therapeutics from fundamental research to the market. Various chemical and computational approaches are aiding the production of more stable and long-lasting peptides guiding the formulation of novel and advanced therapeutic agents. However, there is not a single article that talks about various peptide design approaches i.e., in-silico and in-vitro along with their applications and strategies to improve their efficacy. In this review, we try to bring different aspects of peptide-based therapeutics under one article with a clear focus to cover the missing links in the literature. This review draws emphasis on various in-silico approaches and modification-based peptide design strategies. It also highlights the recent progress made in peptide delivery methods important for their enhanced clinical efficacy. The article would provide a bird's-eye view to researchers aiming to develop peptides with therapeutic applications.

First report of Planomicrobium okeanokoites associated with Himantothallus grandifolius (Desmarestiales, Phaeophyta) from Southern Hemisphere.

Gram-positive, aerobic, motile, rod-shaped, mesophilic epiphytic bacterium Planomicrobium okeanokoites was isolated from the surface of endemic species Himantothallus grandifolius in Larsemann Hills, Eastern Antarctica. The diversity of epiphytic bacterial communities living on marine algae remains primarily unexplored; virtually no reports from Antarctic seaweeds. The present study used morpho-molecular approaches for the macroalgae and epiphytic bacterium characterization. Phylogenetic analysis was performed using mitochondrial genome encoded COX1 gene; chloroplast genome encodes rbcL; nuclear genome encoded large subunit ribosomal RNA gene (LSU rRNA) for Himantothallus grandifolius and ribosomal encoded 16S rRNA for Planomicrobium okeanokoites. Morphological and molecular data revealed that the isolate is identified as Himantothallus grandifolius, which belongs to Family Desmarestiaceae of Order Desmarestiales in Class Phaeophyceae showing 99.8% similarity to the sequences of Himantothallus grandifolius, from King George Island, Antarctica (HE866853). The isolated bacterial strain was identified on the basis of chemotaxonomic, morpho-phylogenetic, and biochemical assays. A phylogenetic study based on 16S rRNA gene sequences revealed that the epiphytic bacterial strain SLA-357 was closest related to the Planomicrobium okeanokoites showing 98.7% sequence similarity. The study revealed the first report of this species from the Southern Hemisphere to date. Also, there has been no report regarding the association between the Planomicrobium okeanokoites and Himantothallus grandifolius; however, there are some reports on this bacterium isolated from sediments, soils, and lakes from Northern Hemisphere. This study may open a gateway for further research to know about the mode of interactions and how they affect the physiology and metabolism of each other.

Scopoletin Improves Glucose Homeostasis in the High-Fructose High-Fat Diet-Induced Diabetes Model in Wistar Rats.

Antihyperglycemic action of scopoletin needs to be validated before considering it for clinical trials. The present study explored antihyperglycemic action of scopoletin in high-fructose high-fat diet (HFHFD)-induced diabetes in rats. The animal study was performed using 48 rats, 6 in each group. HFHFD was administered for model induction for 74 days. Rats in Group I (normal control [NC]) and group II (experimental control [EC]) received normal saline and HFHFD, respectively, throughout the study. Groups III, IV, V, and VI received oral scopoletin (1 mg/kg [low dose, LD], 5 mg/kg [medium dose, MD], 10 mg/kg [high dose, HD]), and metformin (250 mg/kg; positive control [PC] for efficacy), respectively, once daily from day 60 to 74, in addition to HFHFD. Group VII (10 mg/kg oral scopoletin safety group) and VIII (0.1 mg/kg oral warfarin; PC for safety) were separately used for bleeding time-clotting time (BTCT) assessment on days 60, 68, and 74. Groups I, VII, and VIII rats were studied for safety assessment. Later, animals were sacrificed for histological examination. Scopoletin-treated groups showed a significant decline in glucose levels, especially in the MD (5.18 ± 0.12) and HD group (5.271 ± 0.11) in comparison to the EC (6.37 ± 0.05) on day 74 (P < .05). Two weeks after scopoletin treatment, ß-cell function significantly improved (53.073 ± 4.67) in the MD group versus 29.323 ± 8.505 in the NC group (P < .05). A statistically significant difference was observed when the MD group (53.07 ± 4.67) was compared to the metformin-treated group (24.80 ± 3.24; P < .05). The safety assessment in the form of BTCT findings did not observe a difference among groups I, VII, and VIII (P > .05). The study showed that scopoletin dose-independently reversed insulin resistance. Consequently, scopoletin can be a potential candidate for antidiabetic drug development.

Mechanistic insights into immunopathogenesis of murine cerebral malaria: Cues from "young" C57BL/6J and BALB/c mice.

Cerebral malaria (CM), a major cause of mortality in children <5 years, presents disparity in pathophysiological features and poor prognosis compared to adults. Adult C57BL/6J mice infected with Plasmodium berghei ANKA (PbA) are widely used to understand CM pathogenesis compared to relatively less prone BALB/c mice; however, age and immune status of the host also influence disease sequelae and cerebral manifestations. Murine models of CM known so far do not project complete disease spectrum of pediatric CM. The present study was designed to dissect and differentiate CM immunopathogenesis in "young" BALB/c and C57BL/6J mice infected with PbA, in search of a competent mouse model mimicking pediatric CM. Multipronged approach including the analysis of blood-brain barrier (BBB) permeability and parasite infiltration, histopathology, nitric oxide levels, and pro/anti-inflammatory (TNF-α, IFN-γ, IL-4, and IL-10) cytokine expression were compared in the cortices of both young BALB/c and C57BL/6J mice. The results illustrate severe course of infection and typical CM like histopathological alterations including monocytic plugging in PbA-infected "young" BALB/c compared to C57BL/6J mice. The decreased expression of tight junction proteins (ZO-1 and Claudin-3) and Evan's blue extravasation was also more evident in BALB/c mice indicating a more permeable BBB. The increased cortical expression of TNF-α, IFN-γ, IL-4, IL-10, iNOS, eNOS, nNOS, and associated activation of brain resident cells in cortices of BALB/c with progressive parasitaemia depicts the cumulative involvement of host immune responses and parasite accumulation in progression of CM. Thus, the incongruity of cytokine balance resulted in worsening of disease manifestation in "young" BALB/c similar to pediatric CM.

Health Economic Studies of Surfactant Replacement Therapy in Neonates with Respiratory Distress Syndrome: A Systematic Literature Review.

BACKGROUND: Neonatal respiratory distress syndrome (RDS) is one of the most common problems for preterm infants, and symptoms include tachypnoea, grunting, retractions and cyanosis, which occur immediately after birth. Treatment with surfactants has reduced morbidity and mortality rates associated with neonatal RDS. OBJECTIVE: The objective of this review is to describe the treatment costs, healthcare resource utilization (HCRU) and economic evaluations of surfactant use in the treatment of neonates with RDS. METHODS: A systematic literature review (SLR) was performed to identify available economic evaluations and costs associated with neonatal RDS. Electronic searches were conducted in Embase, MEDLINE, MEDLINE In-Process, NHS EED, DARE and HTAD to identify studies published between 2011 and 2021. Supplementary searches of reference lists, conference proceedings, websites of global health technology assessment bodies and other relevant sources were conducted. Publications were screened by two independent reviewers for inclusion and followed the population, interventions, comparators and outcomes framework eligibility criteria. Quality assessment of the identified studies was performed. RESULTS: Eight publications included in this SLR met all eligibility criteria: three conference abstracts and five peer-reviewed original research articles. Four of these publications evaluated costs/HCRU, and five (three abstracts and two peer-reviewed articles) investigated economic evaluations (two from Russia, and one each from Italy, Spain and England). The main cost drivers and causes of increased HCRU were invasive ventilation, duration of hospitalization and RDS-associated complications. There were no significant differences in neonatal intensive care unit (NICU) length of stay or NICU total costs between infants treated with beractant (Survanta®), calfactant (Infasurf®) or poractant alfa (Curosurf®). However, treatment with poractant alfa was associated with reduced total costs compared with no treatment, continuous positive airway pressure (CPAP) alone or calsurf (Kelisu®), due to shorter duration of hospitalization and fewer complications. Early use of the surfactant after birth was more clinically effective and cost-effective than late intervention in infants with RDS. Poractant alfa was found to be cost-effective and cost-saving compared to beractant for the treatment of neonatal RDS in two Russian studies. CONCLUSION: There were no significant differences in NICU length of stay or NICU total costs between surfactants evaluated for treating neonates with RDS. However, early use of surfactant was found to be more clinically effective and cost-effective than late treatment. Treatment with poractant alfa was found to be cost-effective versus beractant and cost-saving compared with CPAP alone or beractant or CPAP in combination with calsurf. Limitations included the small number of studies, the geographic scope of the studies and the retrospective study design of the cost-effectiveness studies.

RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes.

Arl8b, an Arf-like GTP-binding protein, regulates cargo trafficking and positioning of lysosomes. However, it is unknown whether Arl8b regulates lysosomal cargo sorting. Here, we report that Arl8b binds to the Rab4 and Rab14 interaction partner, RUN and FYVE domain-containing protein (RUFY) 1, a known regulator of cargo sorting from recycling endosomes. Arl8b determines RUFY1 endosomal localization through regulating its interaction with Rab14. RUFY1 depletion led to a delay in CI-M6PR retrieval from endosomes to the TGN, resulting in impaired delivery of newly synthesized hydrolases to lysosomes. We identified the dynein-dynactin complex as an RUFY1 interaction partner, and similar to a subset of activating dynein adaptors, the coiled-coil region of RUFY1 was required for interaction with dynein and the ability to mediate dynein-dependent organelle clustering. Our findings suggest that Arl8b and RUFY1 play a novel role on recycling endosomes, from where this machinery regulates endosomes to TGN retrieval of CI-M6PR and, consequently, lysosomal cargo sorting.

Ameliorative Effect of Palm Oil in Aluminum Lactate Induced Biochemical and Histological Implications in Rat Brain.

α-Tocotrienol is one of the major constituents of palm oil. It is a well-known antioxidant and cholesterol-lowering neuroprotectant. To prevent the initiation of Alzheimer's like symptoms, much attention has been shifted to the major role played by antioxidants. Previous epidemiological reports correlate the increasing incidence of developing Alzheimer's disease (AD), to the aluminum (Al) content in drinking water. Al, being a ubiquitous element, has a long history of being particularly reactive towards multiple aspects of neurobiology. So, the current study examines the effect of Al-induced behavioral, biochemical, and histopathological changes in rat brain; and the ameliorative effect of palm oil in reducing the resulting neurotoxicity. The experimental design consisted of 4 groups: control group which received rodent chow diet and water ad libitum; Al group received aluminum lactate (50 mg/kg bw); Al + palm oil group was administered with Al (50 mg/kg bw) and palm oil (60 mg/kg bw); and palm oil group received palm oil (60 mg/kg bw). Al was given by oral gavage once daily for 6 weeks and palm oil was administered intraperitoneally. After 6 weeks of supplementation, Al + palm oil group showed significantly lower malondialdehyde (MDA) content, but higher superoxide dismutase (SOD), catalase (CAT), GST, and GPx activity as compared to Al group. Al group has significantly higher level of MDA content, but lower SOD, CAT, GST, and GPx activity as compared to control group. In conclusion, this study suggested that palm oil was effective in preventing the Al-induced brain damage in rats.

Agronomic and Environmental Determinants of Direct Seeded Rice in South Asia.

Rice (Oryza sativa L.) is the staple food of more than 50% of the world's population. Manual puddled transplanted rice (PTR) system is still the predominant method of rice establishment. However, due to declining water tables, increasing water scarcity, water, labor- and energy-intensive nature of PTR, high labor wages, adverse effects of puddling on soil health and succeeding crops, and high methane emissions, this production system is becoming less profitable. These factors trigger the need for an alternative crop establishment method. The direct-seeded rice (DSR) technique is gaining popularity because of its low input demand compared to PTR. It is done by sowing pre-germinated seeds in puddled soil (wet-DSR), standing water (water seeding), or dry seeding on a prepared seedbed (dry-DSR). DSR requires less water and labor (12-35%), reduces methane emissions (10-90%), improves soil physical properties, involves less drudgery and production cost (US$9-125 per hectare), and gives comparable yields. Upgraded short-duration and high-yielding varieties and efficient nutrient, weed, and resource management techniques encouraged the farmers to switch to DSR culture. However, several constraints are associated with this shift: more weeds, the emergence of weedy rice, herbicide resistance, nitrous oxide emissions, nutrient disorders, primarily N and micro-nutrients, and an increase in soil-borne pathogens lodging etc. These issues can be overcome if proper weed, water, and fertilizer management strategies are adopted. Techniques like stale bed technique, mulching, crop rotation, Sesbania co-culture, seed priming, pre-emergence and post-emergence spray, and a systematic weed monitoring program will help reduce weeds. Chemical to biotechnological methods like herbicide-resistant rice varieties and more competitive allelopathic varieties will be required for sustainable rice production. In addition, strategies like nitrification inhibitors and deep urea placement can be used to reduce N2O emissions. Developing site and soil-specific integrated packages will help in the broader adoption of DSR and reduce the environmental footprint of PTR. The present paper aims to identify the gaps and develop the best-bet agronomic practices and develop an integrated package of technologies for DSR, keeping in mind the advantages and constraints associated with DSR, and suggest some prospects. Eco-friendly, cost-effective DSR package offers sustainable rice production systems with fewer resources and low emissions.

Unleashing a novel function of Endonuclease G in mitochondrial genome instability.

Having its genome makes the mitochondrion a unique and semiautonomous organelle within cells. Mammalian mitochondrial DNA (mtDNA) is a double-stranded closed circular molecule of about 16 kb coding for 37 genes. Mutations, including deletions in the mitochondrial genome, can culminate in different human diseases. Mapping the deletion junctions suggests that the breakpoints are generally seen at hotspots. '9 bp deletion' (8271-8281), seen in the intergenic region of cytochrome c oxidase II/tRNALys, is the most common mitochondrial deletion. While it is associated with several diseases like myopathy, dystonia, and hepatocellular carcinoma, it has also been used as an evolutionary marker. However, the mechanism responsible for its fragility is unclear. In the current study, we show that Endonuclease G, a mitochondrial nuclease responsible for nonspecific cleavage of nuclear DNA during apoptosis, can induce breaks at sequences associated with '9 bp deletion' when it is present on a plasmid or in the mitochondrial genome. Through a series of in vitro and intracellular studies, we show that Endonuclease G binds to G-quadruplex structures formed at the hotspot and induces DNA breaks. Therefore, we uncover a new role for Endonuclease G in generating mtDNA deletions, which depends on the formation of G4 DNA within the mitochondrial genome. In summary, we identify a novel property of Endonuclease G, besides its role in apoptosis and the recently described 'elimination of paternal mitochondria during fertilisation.

Fractal Dimension and Radiomorphometric analysis of Orthopanoramic radiographs in patients with tobacco and areca nut associated oral mucosal lesions: A pilot in-vivo study in a North Indian cohort.

OBJECTIVE: The aim of this study was to determine the fractal dimension (FD) and radiomorphometric indices (RMIs) in the mandible from orthopantomographic radiographs in patients with oral lesions associated with smokeless/smoking tobacco (SLT/ST) and areca nut habits in a North Indian cohort. STUDY DESIGN: A prospective, cross-sectional, observational pilot study was conducted of 120 subjects, including controls and 3 study groups of 30 patients each with oral submucous fibrosis, tobacco pouch keratosis, and oral leukoplakia (OL). Two observers calculated FD and the RMIs of mandibular cortical thickness (MCT), panoramic mandibular index (PMI), and mandibular cortical index (MCI). RESULTS: Mean FD was significantly reduced compared to controls with all oral lesions (P < .05) and with all habits in 3 of 4 regions of interest (P < .05). MCT was significantly reduced with OL (P < .005) and in ST users (P < .05). PMI did not differ regarding lesion status or habits. Compared to the controls, MCI C2 type was significantly more common in all oral lesions (P ≤ .005) and all types of habit (P < .005). Inter- and intraobserver agreement was strong to excellent. CONCLUSIONS: FD and RMI values were significantly altered compared to controls in oral lesions associated with tobacco and areca nut habits and in the dominant type of habit.