Gene expression is influenced due to 'nano' and 'ionic' copper in pre-formed Pseudomonas aeruginosa biofilms.

Today, researchers across the globe suggest the use of antimicrobial coatings containing copper nanoparticles (CuNPs) complementing the traditional protocols to prevent hospital-acquired infections (HAIs). Since Pseudomonas aeruginosa is one of the commonest opportunistic pathogens, we assessed the anti-biofilm activity of CuNPs in P. aeruginosa MTCC 3541 and compared it with Cu2+ (copper sulphate) since the latter continues to be used as an antimicrobial-of-choice in food industries, agriculture and water treatment. In this study, we synthesized and characterized stable poly-acrylic acid (PAA) coated CuNPs with a size of 66-150 nm and zeta potential -13 mV. Pseudomonas aeruginosa MTCC 3541 biofilms were highly resistant to both CuNPs and Cu2+ (minimum biofilm inhibitory concentration, MBIC 300 and >600 µg/mL respectively). Scanning electron microscopy revealed alterations in cell morphology upon treatment with CuNPs. A closer analysis of the biofilm-specific gene expression (qRT-PCR) revealed that CuNPs downregulated the genes involved in biofilm matrix formation, motility, efflux, membrane lipoprotein synthesis and DNA replication. Both, CuNPs and Cu2+ up regulated copper resistance and biofilm dispersion genes. Copper did not affect the bacterial communication system as evidenced by downregulation of the negative regulator of quorum sensing. The gene expression analysis reveals multiple cellular targets for CuNPs and ionic Cu. The present study highlights the fact that CuNPs affect the membrane functions adversely damaging the cell surface. In pre-formed biofilms, CuNPs were more toxic and displayed distinct responses attributable due to 'nano' and 'ionic' copper. Our findings thus support the use of CuNPs for curbing HAIs.

Electrochemical impedance spectroscopy reveals a new mechanism based on competitive binding between Tris and protein on a conductive biomimetic polydopamine surface.

A novel mechanism was developed to study the interaction of mussel inspired polydopamine surfaces with bovine serum albumin using cyclic voltammetry and electrochemical impedance spectroscopy supplemented with XPS, IR spectroscopy, UV spectroscopy and atomic force microscopy. The polydopamine surfaces reveal different mechanisms that give a new insight into understanding the interaction with BSA under the variable conditions used for PDA preparation and BSA adsorption. The study provides an in-depth analysis of the orientations and interactions of BSA with polydopamine surfaces. The protein interaction behavior changed significantly in different environments including different pH values and concentrations of buffer and it revealed a competitive binding mechanism of protein binding. The study provides an outlook for studying the interaction of protein foulants with PDA, which should be carried out in nucleophilic buffers, while the covalent binding or immobilization of biomolecules to PDA surfaces should be carried out in non-nucleophilic buffer for higher efficiency.

Polydopamine films change their physicochemical and antimicrobial properties with a change in reaction conditions.

The morphology and physicochemical properties of polydopamine are not totally inherent and undergo changes with differing reaction conditions like the choice of solvent used for polymerization. The polymerisation of dopamine to polydopamine carried out in different solvents like sodium hydroxide, sodium bicarbonate, PBS and Tris leads to polydopamine with exceptionally different morphological and physicochemical features with each solvent. Additionally, the different physicochemical characteristics and morphologies bestow the polymer films with different extents of antimicrobial activity. Moreover, the findings supported by chemical evidence from X-ray photoelectron spectroscopy reveal that higher antibacterial activities were obtained against E. coli and S. aureus with polydopamine films prepared by Tris and NaOH solvent induced polymerization. The antibacterial activity observed in saline was found to be higher than that in PBS medium for both E. coli and S. aureus. The higher antibacterial activity of polydopamine films prepared in Tris and NaOH solvents was attributed to the covalent incorporation of -OH groups on the surface provided by nucleophilic Tris and NaOH solvents during the polymerisation process. The distinct physicochemical and morphological changes were supported by the results from contact angle measurements, FE-SEM, EDAX, AFM, and XPS analysis. The present finding provides insight into the different chemistry, morphologies and properties of the designed polydopamine films with controlled antibacterial/antifouling properties. Additionally, new insights into the mechanism of formation, physicochemical changes in morphology and properties of polydopamine coatings were revealed.

Hooking She3p onto She2p for myosin-mediated cytoplasmic mRNA transport.

The segregation of approximately two dozen distinct mRNAs from yeast mother to daughter cell cytoplasm is a classical paradigm for eukaryotic mRNA transport. The information for transport resides in an mRNA element 40-100 nt in length, known as "zipcode." Targeted transport requires properly positioned actin filaments and cooperative loading of mRNA cargo to myosin. Cargo loading to myosin uses myosin 4 protein (Myo4p), swi5p-dependent HO expression 2 protein (She2p) and 3 protein (She3p), and zipcode. We previously determined a crystal structure of Myo4p and She3p, their 1:2 stoichiometry and interactome; we furthermore showed that the motor complex assembly requires two Myo4p⋅She3p heterotrimers, one She2p tetramer, and at least a single zipcode to yield a stable complex of [Myo4p⋅She3p⋅She2p⋅zipcode] in 2:4:4:1 stoichiometry in vitro. Here, we report a structure at 2.8-Šresolution of a cocrystal of a She2p tetramer bound to a segment of She3p. In this crystal structure, the She3p segment forms a striking hook that binds to a shallow hydrophobic pocket on the surface of each She2p subunit of the tetramer. Both She3p hook and cognate She2p binding pocket are composed of highly conserved residues. We also discovered a highly conserved region of She3p upstream of its hook region. Because this region consists of basic and aromatic residues, it likely represents part of She3p's binding activity for zipcode. Because She2p also exhibits zipcode-binding activity, we suggest that "hooking" She3p onto She2p aligns each of their zipcode-binding activities into a high-affinity site, thereby linking motor assembly to zipcode.

Structure of a myosin•adaptor complex and pairing by cargo.

Myosin 4 protein (Myo4p), one of five distinct myosins of yeast, is dedicated to cytoplasmic transport of two types of cargos, zipcoded messenger ribonucleoprotein particles (mRNPs) and tubular endoplasmic reticulum (tER). Neither cargo binds directly to Myo4p. Instead, swi5p-dependent HO expression 3 protein (She3p) serves as an "adaptor" that contains three binding modules, one for Myo4p and one each for zipcoded mRNP and tER. The assembly of a transport-competent motor complex is poorly understood. Here, we report that Myo4p•She3p forms a stable 1:2 heterotrimer in solution. In the Myo4p•She3p crystal structure, Myo4p's C-terminal domain (CTD) assumes a lobster claw-shaped form, the minor prong of which adheres to a pseudocoiled-coil region of She3p. The extensive Myo4p•She3p interactome buries 3,812 Å(2) surface area and is primarily hydrophobic. Because the Myo4p•She3p heterotrimer contains only one myosin molecule, it is not transport-competent. By stepwise reconstitution, we found a single molecule of synthetic oligonucleotide (representing the mRNA zipcode element) bound to a single tetramer of zipcode binding protein She2p to be sufficient for Myo4p•She3p dimerization. Therefore, cargo initiates cross-linking of two Myo4p•She3p heterotrimers to an ensemble that contains two myosin molecules obligatory for movement. An additional crystal structure comprising an overlapping upstream portion of She3p showed continuation of the pseudocoiled-coil structure and revealed another highly conserved surface region. We suggest this region as a candidate binding site for a yet unidentified tER ligand. We propose a model whereby zipcoded mRNP and/or tER ligands couple two Myo4p•She3p heterotrimers and thereby generate a transport-competent motor complex either for separate transport or cotransport of these two cargos.

Nasopalatine duct cyst mimicking an endodontic periapical lesion: a case report.

Lesions of nonendodontic origin, such as nasopalatine or globulomaxillary cysts, may mimic periapical radiolucencies associated with pulpal pathosis, and incorrect diagnosis may lead to unnecessary endodontic treatment. Horizontal root fractures most commonly affect the maxillary central and lateral incisors. Prognosis depends largely on the level of fracture; fractures in the apical third have the best prognosis, and those in the cervical third have the worst. This case report discusses surgical and restorative management of a patient who had a nasopalatine cyst that had been misdiagnosed and treated as an endodontic lesion of the maxillary right central incisor as well as a midroot horizontal fracture of the adjacent lateral incisor.

The N-terminal transactivation domain of the glucocorticoid receptor mediates apoptosis of human small cell lung cancer cells.

Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis. These cancers are deficient in glucocorticoid receptor (GR) expression, and therefore, resistant to glucocorticoids. Overexpression of the GR both in vivo and in vitro leads to apoptotic cell death suggesting that loss of GR is favorable for cancer growth. Indeed, the GR promoter is silenced in SCLC cells by methylation. We now show that treatment of the SCLC cell line (DMS79) cells with the demethylating agent, 5-aza-2'-deoxycytidine (5-aza), results in significant endogenous re-expression of both GRα and the ligand-independent GR-P. The GR gene has a complex promoter region comprising nine alternative promoters, the proximal seven of which lie within a CpG island. The endogenous re-expression seen is attributed to the constitutive promoters 1B and 1C and 1J but predominantly 1F, which we show to be heavily methylated in SCLC cells. Flow cytometric analysis using the apoptotic marker, Annexin V, shows that this endogenous re-expression is sufficient to drive the SCLC cells to apoptosis. Apoptotic induction is specific to GR re-expression as cotreatment with 5-aza and the GR antagonist, RU486 prevented apoptosis. Of the three functional GR domains (the DNA binding domain, ligand binding domain, and transactivation domain), we identified that the transactivation domain is essential for apoptosis in SCLC. The discovery that endogenous re-expression of the GR in SCLC cells is sufficient to induce apoptotic cell death by reversing a cancer-driven DNA methylation effect may lead to the development of novel adjunct therapies.

Transformation and stabilization of pyrogenic organic matter in a temperate forest field experiment.

Pyrogenic organic matter (PyOM) decomposes on centennial timescale in soils, but the processes regulating its decay are poorly understood. We conducted one of the first studies of PyOM and wood decomposition in a temperate forest using isotopically labeled organic substrate, and quantified microbial incorporation and physico-chemical transformations of PyOM in situ. Stable-isotope (¹³C and ¹5N) enriched PyOM and its precursor wood were added to the soil at 2 cm depth at ambient (N0) and increased (N+) levels of nitrogen fertilization. The carbon (C) and nitrogen (N) of added PyOM or wood were tracked through soil to 15 cm depth, in physically separated soil density fractions and in benzene polycarboxylic acids (BPCA) molecular markers. After 10 months in situ, more PyOM-derived C (>99% of initial 13C-PyOM) and N (90% of initial ¹5N-PyOM) was recovered than wood derived C (48% of 13C-wood) and N(89% under N0 and 48% under N+). PyOM-C and wood-C migrated at the rate of 126 mm yr ⁻¹ with 3-4% of PyOMC and 4-8% of wood-C recovered below the application depth. Most PyOM C was recovered in the free light fraction(fLF) (74%), with 20% in aggregate-occluded and 6% in mineral associated fractions ­ fractions that typically have much slower turnover times. In contrast, wood C was recovered mainly in occluded (33%) or dense fraction (27%).PyOM addition induced loss of native C from soil (priming effect), particularly in fLF (13%). The total BPCA-C content did not change but after 10 months the degree of aromatic condensation of PyOM decreased, as determined by relative contribution of benzene hexa-carboxylic acid (B6CA) to the total BPCA C. Soil microbial biomass assimilated 6-10% of C from the wood, while PyOM contributions was negligible (0.14­0.18%). The addition of N had no effect on the dynamics of PyOM while limited effect on wood.

Fetal Appendiceal Perforation Masquerading as Meconium Peritonitis: A Report of a Rare Case.

Intrauterine appendicular perforation leading to meconium peritonitis is exceptionally rare, with few reported cases in the literature. This case underscores the diagnostic challenges and high mortality associated with neonatal appendicular perforation. Neonatal appendicitis and subsequent perforation are uncommon due to the funnel shape of the fetal appendix, which reduces susceptibility to luminal obstruction. While advances in neonatal care and diagnostic modalities have improved outcomes, challenges persist in timely diagnosis and management. We present the case of a preterm infant, one of dichorionic-diamniotic (DCDA) twins delivered via cesarean section, who developed gross abdominal distension and respiratory distress shortly after birth. Diagnostic abdominocentesis revealed meconium-stained fluid, prompting further investigation with imaging and subsequent exploratory laparotomy. Extensive adhesions and cecal perforation were observed, necessitating a cecostomy. Despite interventions, the infant's condition deteriorated, leading to a fatal outcome. Intrauterine appendicular perforation leading to meconium peritonitis is a rare and difficult-to-diagnose condition. Antenatal suspicion and early surgical intervention are crucial for improving outcomes. Factors contributing to neonatal appendicular perforation include ischemia, obstruction, and infective etiologies. Neonatal appendicular perforation is a rare but life-threatening condition requiring a high index of suspicion for prompt diagnosis and management. Advances in diagnostic tools and antenatal monitoring have contributed to improved outcomes, highlighting the importance of considering this diagnosis in cases of unexplained neonatal abdominal distension.

Prospective Evaluation of Extracorporeal Shockwave Lithotripsy in Renal and Upper Ureteric Stone Treatment: Clinical Assessment and Results.

INTRODUCTION: Extracorporeal shockwave lithotripsy (ESWL) is a widely accepted non-invasive treatment for renal and upper ureteric stones smaller than 2 cm due to its safety and efficacy. Despite advancements in minimally invasive techniques, extracorporeal shockwave lithotripsy remains an important modality. AIMS AND OBJECTIVE: This prospective observational study aimed to evaluate the outcomes of ESWL in managing renal and upper ureteric stones measuring less than 2 cm in terms of stone clearance. MATERIAL AND METHODS: In a study conducted at a university-affiliated tertiary care hospital, 119 patients with renal and upper ureteric stones underwent extracorporeal shockwave lithotripsy over a 12-month period. Data on patient demographics, stone characteristics, treatment procedures, and complications were collected. Follow-up assessments were performed at two-week intervals for up to two months post-treatment. RESULTS: The mean age of patients was 39.78 years, with a mean stone size of 1.2 cm. Right kidney stones were more prevalent (61.3% [n=76]). Complications included fever (19.3% [n=23]), gross haematuria (24.3% [n=29]), and steinstrasse (21.8% [n=26]). The success rate of extracorporeal shockwave lithotripsy was 81.5% (n=97), with 18.5% (n=22) of patients requiring surgical intervention due to incomplete fragmentation or residual fragments >4 mm. Stone size and density played significant roles in treatment success. CONCLUSION: Despite advancements in minimally invasive techniques, ESWL retains its significance as a noninvasive and effective treatment option for renal and upper ureteric stones smaller than 2 cm. Its success depends on various factors, including the stone site, size, and composition. ESWL offers advantages such as minimal morbidity, shorter hospital stays, and better patient compliance. Complications such as steinstrasse are manageable with conservative measures or ancillary procedures. While ESWL may be losing ground in some cases, its noninvasive nature and favourable outcomes make it a valuable option in the armamentarium for stone management.

The role of continental evapotranspiration on water vapour isotopic variability in the troposphere.

Rainforests play an important role in hydrological and carbon cycles, both at regional and global scales. They pump large quantities of moisture from the soil to the atmosphere and are major rainfall hotspots of the world. Satellite-observed stable water isotope ratios have played an essential role in determining sources of moisture in the atmosphere. Satellites provide information about the processes involving vapour transport in different zones of the world, identifying sources of rainfall and distinguishing moisture transport in monsoonal systems. This paper focuses on major rainforests of the world (Southern Amazon, Congo and Northeast India) to understand the role of continental evapotranspiration in influencing tropospheric water vapour. We have used satellite measurements of 1H2H16O/1H216O from Atmospheric InfraRed Sounder (AIRS), evapotranspiration (ET), solar-induced fluorescence (SIF), precipitation (P), atmospheric reanalysis-derived moisture flux convergence (MFC) and wind to discern the role of ET in influencing water vapour isotopes. A global map of the correlation between δ2Hv and ET-P flux indicates that densely vegetated regions in the tropics show the highest positive correlation (r > 0.5). Using mixing models and observations of specific humidity and isotopic ratio over these forested regions, we discern the source of moisture in pre-wet and wet seasons.

Association of an Advance Care Planning Video and Communication Intervention With Documentation of Advance Care Planning Among Older Adults: A Nonrandomized Controlled Trial.

Importance: COVID-19 has disproportionately killed older adults and racial and ethnic minority individuals, raising questions about the relevance of advance care planning (ACP) in this population. Video decision aids and communication skills training offer scalable delivery models. Objective: To assess whether ACP video decision aids and a clinician communication intervention improved the rate of ACP documentation during an evolving pandemic, with a focus on African American and Hispanic patients. Design, Setting, and Participants: The Advance Care Planning: Communicating With Outpatients for Vital Informed Decisions trial was a pre-post, open-cohort nonrandomized controlled trial that compared ACP documentation across the baseline pre-COVID-19 period (September 15, 2019, to March 14, 2020), the COVID-19 wave 1 period (March 15, 2020, to September 14, 2020), and an intervention period (December 15, 2020, to June 14, 2021) at a New York metropolitan area ambulatory network of 22 clinics. All patients 65 years or older who had at least 1 clinic or telehealth visit during any of the 3 study periods were included. Main Outcomes and Measures: The primary outcome was ACP documentation. Results: A total of 14 107 patients (mean [SD] age, 81.0 [8.4] years; 8856 [62.8%] female; and 2248 [15.9%] African American or Hispanic) interacted with clinicians during the pre-COVID-19 period; 12 806 (mean [SD] age, 81.2 [8.5] years; 8047 [62.8%] female; and 1992 [15.6%] African American or Hispanic), during wave 1; and 15 106 (mean [SD] 80.9 [8.3] years; 9543 [63.2%] female; and 2535 [16.8%] African American or Hispanic), during the intervention period. Clinicians documented ACP in 3587 patients (23.8%) during the intervention period compared with 2525 (17.9%) during the pre-COVID-19 period (rate difference [RD], 5.8%; 95% CI, 0.9%-7.9%; P = .01) and 1598 (12.5%) during wave 1 (RD, 11.3%; 95% CI, 6.3%-12.1%; P < .001). Advance care planning was documented in 447 African American patients (30.0%) during the intervention period compared with 233 (18.1%) during the pre-COVID-19 period (RD, 11.9%; 95% CI, 4.1%-15.9%; P < .001) and 130 (11.0%) during wave 1 (RD, 19.1%; 95% CI, 11.7%-21.2%; P < .001). Advance care planning was documented for 222 Hispanic patients (21.2%) during the intervention period compared with 127 (13.2%) during the pre-COVID-19 period (RD, 8.0%; 95% CI, 2.1%-10.9%; P = .004) and 82 (10.2%) during wave 1 (RD, 11.1%; 95% CI, 5.5%-14.5%; P < .001). Conclusions and Relevance: This intervention, implemented during the evolving COVID-19 pandemic, was associated with higher rates of ACP documentation, especially for African American and Hispanic patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04660422.

Stable isotopic analysis of pyrogenic organic matter in soils by liquid chromatography-isotope-ratio mass spectrometry of benzene polycarboxylic acids.

Pyrogenic organic matter (PyOM), the incomplete combustion product of organic materials, is considered stable in soils and represents a potentially important terrestrial sink for atmospheric carbon dioxide. One well-established method of measuring PyOM in the environment is as benzene polycarboxylic acids (BPCAs), a compound-specific method, which allows both qualitative and quantitative estimation of PyOM. Until now, stable isotope measurement of PyOM carbon involved measurement of the trimethylsilyl (TMS) or methyl (Me) polycarboxylic acid derivatives by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). However, BPCA derivatives can contain as much as 150% derivative carbon, necessitating post-analysis correction for the accurate measurement of δ¹³C values, leading to increased measurement error. Here, we describe a method for δ¹³C isotope ratio measurement and quantification of BPCAs from soil-derived PyOM, based on ion-exchange chromatography (IEC-IRMS). The reproducibility of the δ¹³C measurement of individual BPCAs by IEC-IRMS was better than 0.35‰ (1σ). The δ¹³C-BPCA analysis of PyOM in soils, including at natural and artificially enriched ¹³C-abundance, produced accurate and precise δ¹³C measurements. Analysis of samples that differed in δ¹³C by as much as 900‰ revealed carryover of <1‰ between samples. The weighted sum of individual δ¹³C-BPCA measurements was correlated with previous isotopic measurements of whole PyOM, providing complementary information for bulk isotopic measurements. We discuss potential applications of δ¹³C-BPCA measurements, including the study of turnover rates of PyOM in soils and the partitioning of PyOM sources based on photosynthetic pathways.

Synthesis, molecular modeling and bio-evaluation of cycloalkyl fused 2-aminopyrimidines as antitubercular and antidiabetic agents.

An economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines and 9-(arylidene)-4-(aryl)-6,7,8,9-tetrahydro-5H-cycloheptapyrimidin-2-ylamines by the reaction of bis-benzylidene cycloalkanones and guanidine hydrochloride in presence of NaH has been developed. All the synthesized compounds were evaluated against Mycobacterium tuberculosis H(37)Rv strain and the α-glucosidase and glycogen phosphorylase enzymes. Few of the compounds have shown interesting in vitro activity with MIC up to 3.12 µg/mL against M. tuberculosis and very good inhibition of α-glucosidase and glycogen phosphorylase enzymes. The most potent non toxic compound 40 exhibited about 58% ex vivo activity at MIC of 3.12 µg/mL. The present study opens a new gate to synthesize antitubercular agents for diabetic TB patients. In silico docking studies indicate that mycobacterial dihydrofolate reductase is the possible target of these compounds.

In vivo protein corona on nanoparticles: does the control of all material parameters orient the biological behavior?

Nanomaterials have a huge potential in research fields from nanomedicine to medical devices. However, surface modifications of nanoparticles (NPs) and thus of their physicochemical properties failed to predict their biological behavior. This requires investigating the "missing link" at the nano-bio interface. The protein corona (PC), the set of proteins binding to the NPs surface, plays a critical role in particle recognition by the innate immune system. Still, in vitro incubation offers a limited understanding of biological interactions and fails to explain the in vivo fate. To date, several reports explained the impact of PC in vitro but its applications in the clinical field have been very limited. Furthermore, PC is often considered as a biological barrier reducing the targeting efficiency of nano vehicles. But the protein binding can actually be controlled by altering PC both in vitro and in vivo. Analyzing PC in vivo could accordingly provide a deep understanding of its biological effect and speed up the transfer to clinical applications. This review demonstrates the need for clarifications on the effect of PC in vivo and the control of its behavior by changing its physicochemical properties. It unfolds the recent in vivo developments to understand mechanisms and challenges at the nano-bio interface. Finally, it reports recent advances in the in vivo PC to overcome and control the limitations of the in vitro PC by employing PC as a boosting resource to prolong the NPs half-life, to improve their formulations and thereby to increase its use for biomedical applications.

Hemolysis tendency of anticancer nanoparticles changes with type of blood group antigen: An insight into blood nanoparticle interactions.

Different blood groups of ABO system have specific antigen which bestows them with different biochemical properties and hence they can show different hemolytic activity. In this report, hemolytic activity of thiol-functionalized Fe3O4-Au nanoparticles were studied in presence and absence of doxorubicin and the effect of various thiol coatings were correlated towards their hemolysis tendency. The nanoparticles were functionalized with four different amino thiols, cysteamine (CEA), cystamine (CA), cysteine (Cys) and cystine (Cyt) to form Fe3O4-Au CEA, Fe3O4-Au CA, Fe3O4-Au Cys and Fe3O4-Au Cyt nanoparticles which were loaded with anticancer drug, doxorubicin. The functionalization was characterized using ATR-FTIR, HR-TEM, XPS and other spectroscopic methods. Maximum drug encapsulation efficiency of 83% was observed with Fe3O4-Au CA nanoparticles. In-vitro experiments were performed on HeLa cells to check the cellular uptake and cytotoxicity using MTT assay. Hemolytic activity was then analyzed with all the blood groups (positive and negative). The amino acid functionalized, Fe3O4-Au Cys and Fe3O4-Au Cyt nanoparticles, shows lesser hemolysis compared to amino thiol functionalized Fe3O4-Au CEA, and Fe3O4-Au CA nanoparticles. In positive blood groups, the Fe3O4-Au CA nanoparticles shows the highest rate of hemolysis followed by Fe3O4-Au CEA, while the lowest hemolysis rate was observed for Fe3O4-Au Cyt nanoparticles. For negative blood groups, the thiol coated nanoparticles show more abrupt hemolysis rate depending upon the type of antigen.

Taurine-Conjugated Mussel-Inspired Iron Oxide Nanoparticles with an Elongated Shape for Effective Delivery of Doxorubicin into the Tumor Cells.

Multifunctional iron oxide magnetic nanoparticles, among them nanorods, were prepared with a mussel-inspired polydopamine (pDA) surface coating agent for cancer therapeutics. Taurine, a free sulfur-containing ß amino acid, was grafted on the pDA at the iron oxide nanoparticle surface to enhance its biocompatibility and targeted delivery action. Doxorubicin (DOX), an anticancer drug, was loaded on the prepared nanovehicles with an entrapment efficiency of 70.1%. Drug release kinetics were then analyzed using UV-vis and fluorescence spectroscopies, suggesting the pH-responsive behavior of the developed nanovehicle. The developed system was then tested on PC-3 cell lines to check its cellular response. Confocal microscopy observations and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) and Annexin V-FITC assays used to evaluate cell toxicity and apoptosis reveal a dose-dependent nature of nanorods and can overcome the side effects of using free DOX with a targeted action.

Onset of summer monsoon in Northeast India is preceded by enhanced transpiration.

Variations in isotopic composition of water vapor in the atmosphere is an important indicator of the processes within the hydrological cycle. Isotopic signature of water vapor and precipitation can be helpful in partitioning evaporation and transpiration fluxes. It is well known that transpiration from forested regions supplies a significant amount of vapor to the atmosphere in monsoon and post-monsoon seasons. Here, we utilize observations from Tropospheric Emission Spectrometer (TES), Atmospheric Infra-Red Sounder (AIRS) and simulation models to ascertain that transpiration is dominant in the forests of Northeast India (NE) during pre-monsoon season. Our results show an increase in δD of 78.0 ± 7.1‰ and in specific humidity of 3.1 ± 0.2 g kg-1 during the pre-monsoon months of April-May compared to January-February. In the monsoon months of July-August, δD reduces by 53.0 ± 6.5‰ albeit the specific humidity increases by 3.4 ± 0.2 g kg-1. Using joint observations of specific humidity and isotope ratio in lower troposphere, we discern the moisture sources over NE India in pre-monsoon and monsoon seasons and posit the role of transpiration in continental recycling during pre-monsoon season.

Transcriptome analysis of silver nanoparticles treated Staphylococcus aureus reveals potential targets for biofilm inhibition.

The biofilms of Staphylococcus aureus on the implanted materials and chronic wounds are life-threatening and are a substantial financial burden on the healthcare system. Silver nanoparticles (SNP), known for their multi-level physiological effects in planktonic cells could be a promising agent in the treatment of biofilm-related infections also. To gain insight into the effects of SNP on various physiological processes in biofilms we studied the transcriptome of Staphylococcus aureus ATCC 29213. To distinguish between 'nanoparticles-specific' and 'ion-specific' effect of silver, we performed a comparative analysis of the functional genes in response to Ag+. As compared to untreated biofilms, 21% (i.e. 629 genes) and 28.5% (i. e. 830 genes) of the total functional coding genes were differentially regulated upon exposure to SNP and Ag+. Genes encoding capsular polysaccharides, intercellular adhesion, virulence were downregulated in SNP and Ag+ treated biofilms. Genes involved in carbohydrate, protein metabolism including DNA and RNA synthesis, oxidative stress etc. were differentially expressed. Further, activation of efflux pumps and multidrug export proteins was observed, which clearly indicates the presence of metal stress resistance determinants in S. aureus. Silver blocked the integration of mobile genetic elements in S. aureus genome. Our study points out quorum sensing and virulence determinants as possible targets for inhibition of biofilms possibly with/without existing antibiotics. However, further studies on these aspects are warranted. Scanning electron microscopy (SEM) and confocal microscopy revealed changes in biofilm morphology, architecture and thickness in presence of silver nanoparticles and ionic silver, substantiating the transcriptome data.

Glutathione conjugated superparamagnetic Fe3O4-Au core shell nanoparticles for pH controlled release of DOX.

Glutathione (GSH) coated gold­iron oxide core shell nanoparticles (GS-Au-Fe3O4) were prepared by coating glutathione shell on nanoparticles to reduce the dose dependent behaviour of anticancer drug, doxorubicin (DOX). The resultant nanoparticles were characterized using XPS, FTIR, HR-TEM with STEM profile to analyze the GSH shell over the surface. The GS-Au-Fe3O4 nanoparticles were loaded with DOX and maximum drug entrapment capacity of 54% was observed in 48 h. In-vitro drug release were evaluated using UV-vis and Fluorescence spectroscopy. The results show that drug release is facilitated under acidic conditions as well as by extracellular glutathione spiking. Cytotoxicity and cellular uptake was studied on HeLa cells where GS-Au-Fe3O4 nanoparticles lead to significantly higher uptake of DOX as compared to free drug. The use of glutathione conjugation thus act as an efficient drug delivery vehicle which requires significantly low concentration of GS-Au-Fe3O4 nanoparticles for DOX release besides triggering drug release by using redox active GSH.