Indole-derived water-soluble N,O bi-dentate ligand-based mononuclear transition metal complexes: in silico and in vitro biological screening,molecular docking and macromolecule interaction studies

Abstract

A novel tryptophan-derived Schiff base ligand (potassium (E)-2-((4-chloro-3-nitrobenzylidene)amino)-3-(1H-indol-3-yl)propanoate) and a series of its transition metal complexes of the types [ML₂] and [ML(1,10-phen)₂]Cl where M?=?Cu(II), Co(II), Ni(II) and Zn(II) were prepared. They were analyzed by various spectral and physicochemical studies. The XRD data were also used to determine the average lattice parameters and crystalline size of the compounds. All the synthesized compounds were tested against a series of five bacterial and fungal strains. The obtained results showed that the biological activity of free ligand was increased on complexation. PASS online software predicts the various biological activities of ligand such as enzyme inhibitor, antiviral, analgesic and antituberculosis. The in silico theoretical prediction of synthesized compounds is also deliberated by Swiss ADME predictor which gives the properties of molecular hydrophobicity (log P), topological polar surface area (TPSA) and oral bioavailability score. The binding energy of the docked molecule with macromolecules 1BNA and 3EQM is also determined by using Hex 8.0 software. The ligand has the least binding energy score which signifies that the potential of binding is greater in the receptor. Moreover, the interactions of complexes with DNA have been explored by electronic absorption titration, fluorescence emission titration, viscosity measurements and gel electrophoresis.

• Highlights

• Synthesis and characterization of novel indole-derived compounds.

• X-ray diffraction studies demonstrate average crystalline size of the compounds.

• Metal complexes act as good metallointercalators.

• Metal complexes show higher antimicrobial activity compared to ligand.

• Prediction of biological activities of the ligand by PASS online software.

• Drug-like nature and bioavailability of synthesized compounds predicted by Swiss ADME predictor

• Docking of the synthesized compounds with 1BNA and 3EQM using HEX 8.0 software.

Communicated by Ramaswamy H. Sarma     

Enhancement of solubilization and biodegradation of petroleum by biosurfactant from Rhodococcus erythropolis HX-2

Abstract

The demand to repair areas contaminated with hydrocarbon products has led to the development of new technologies for the treatment of contaminants in an unconventional method, that is, no physical or chemical methods are used. Biosurfactants are amphiphilic biomolecules produced by microorganisms that can be used in environments contaminated by petroleum products due to their unexceptionable tensile properties. Petroleum degrading strain Rhodococcus erythropolis HX-2 was found to be an effective producer of biosurfactants. The resulting biosurfactant (named NK) exhibits high physicochemical properties in terms of surface activity. It is capable of reducing surface tension from 54.99 to 28.89?mN/m and critical micelle concentration (CMC) is 100?mg/L. NK was found to be a substitute for chemically synthesized surfactants because of its higher solubilization efficiency for petroleum and polycyclic aromatic hydrocarbons, superior to SDS, Tween 80, Triton X-100 and Rhamnolipid (a wide used biosurfactant). In addition, it exhibits favorable emulsion stability over a wide range of pH (3–10), temperature (20–100?°C) and salinity ranges (5–20?g/L). It was found that the addition of biosurfactant can improve the efficiency of petroleum degradation, therefore it has potential applications in bioremediation.

• Highlights

• Rhodococcus erythropolis HX-2 is an effective petroleum degrading strain.

• HX-2 is a potential source of biosurfactant production.

• The biosurfactant NK reduces surface tension and exhibits high emulsification activity.

• The biosurfactant NK is effective over a wide range of temperatures, pH and salinity.

• The biosurfactant NK shows high solubilization efficiency for petroleum as well as polycyclic aromatic hydrocarbons.

     

Tracing the Early Emergence of Microbial Sulfur Metabolisms

Abstract

Hydrogen sulfide (nH₂S) and sulfur oxide (SO _n ; n?=?1, 2, 3) gases in early Earth’s globally anoxic atmosphere were subjected to gas-phase chemical transformations by UV light. A principal photolysis pathway at that time produced elemental sulfur aerosols with mass-independently fractionated (MIF) isotopic values carrying variable minor isotope (³³S, ³⁶S) compositions. These rained into the sulfate-deficient Archean (ca. 3.85–2.5 Ga) oceans to react with [Fe²⁺]_aq and form sedimentary sulfides. The MIF-bearing sulfides were incorporated into Archean sediments, including banded iron formations (BIF). Such aerosols may also have fueled microbial sulfur metabolisms, and thus are traceable by the MIF sulfur isotopes. Yet, data show that before ～3.5 Ga mass-dependent³⁴S/³²S values in Early Archean sediments tend to fall within a narrow (±0.1%) range even as they carry mass-independent values. By about 3.5 Ga, ³⁴S/³²S values show much greater changes (>1%) in range congruent with microbial metabolic processing. Here, we trace probable pathways of elemental sulfur aerosols into Archean sediments, and couple our study with analysis of the evolutionary relationships of enzymes involved in sulfur metabolism to explain the observed trends. Our model explains why elemental sulfur aerosols were apparently not utilized by the Eoarchean (pre-3.65 Ga) biosphere even though an immediate precursor to the required enzyme may have already been present.

• Highlights

• Evolution of microbial sulfur metabolisms is tracked by multiple sulfur isotopes

• Alkaline hydrothermal vents were an abode for early microbial life

• Sulfite detoxification prompted anaerobic respiration

• Reversal of respiratory electron transport chain (ETC) stimulated photothiotrophy

• Surplus e- acceptors permitted the emergence of elemental sulfur reduction

     

Extraction of watermelon seed proteins with enhanced functional properties using ultrasound

Abstract

Watermelon seed is the potential source of value-added proteins, oils, and carbohydrates. The present study evaluates the extraction, and functional properties of watermelon seed protein (WMSP) obtained by ultrasound-assisted extraction (UAE) method from watermelon seed (WMS). The optimization of various operating parameters, such as pH (9), WMS powder to solvent ratio (1:50 w/v), temperature (30?±?2?°C), ultrasound power (90?W), frequency (25?kHz), and duty cycle (75%) has been carried out. The extraction yield obtained was 87% and the extraction time was lowered down to 9?min from 120?min of conventional batch extraction. It contains all essential amino acids in an adequate amount required for adults as per FAO/WHO guidelines while for 2–5?years old children, the content of valine and isoleucine are above the required range. Methionine and lysine contents are adequate for both children and adults. Functional properties of ultrasonic extracted proteins were found superior to conventionally extracted proteins.

• highlights

• The UAE method is more efficient for watermelon seed protein extraction.

• Impact of extraction parameters on the extraction yield was studied.

• Protein isolate with enhanced functional properties was obtained.

• Essential amino acid content was determined.

     

Differential Complex Formation via Paralogs in the Human Sin3 Protein Interaction Network

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Highlights

• •Sin3 paralog identity influences Sin3 complex composition.
• •Chemical cross-linking mass spectrometry identifies domains in SIN3A and SIN3B that mediate complex formation.
• •Complex subunit homology to yeast Sin3 complex components may assist in defining distinct forms of the Sin3 complex in humans.
• •A nuclear import signal within SIN3B is identified via chemical cross-linking mass spectrometry.

     

Metabolomic Fingerprint of Heart Failure with Preserved Ejection Fraction

BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). Therefore, we hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis.ConclusionsThe metabolomics approach employed in this study identified a unique metabolomic fingerprint of HFpEF that is distinct from that of HFrEF. This metabolomic fingerprint has been utilized to identify two novel panels of metabolites that can separate HFpEF patients from both non-HF controls and HFrEF patients.

Clinical Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02052804","term_id":"NCT02052804"}}NCT02052804     

Brain organoids: an ensemble of bioassays to investigate human neurodevelopment and disease

AbstractUnderstanding etiology of human neurological and psychiatric diseases is challenging. Genomic changes, protracted development, and histological features unique to human brain development limit the disease aspects that can be investigated using model organisms. Hence, in order to study phenotypes associated with human brain development, function, and disease, it is necessary to use alternative experimental systems that are accessible, ethically justified, and replicate human context. Human pluripotent stem cell (hPSC)-derived brain organoids offer such a system, which recapitulates features of early human neurodevelopment in vitro, including the generation, proliferation, and differentiation of neural progenitors into neurons and glial cells and the complex interactions among the diverse, emergent cell types of the developing brain in three-dimensions (3-D). In recent years, numerous brain organoid protocols and related techniques have been developed to recapitulate aspects of embryonic and fetal brain development in a reproducible and predictable manner. Altogether, these different organoid technologies provide distinct bioassays to unravel novel, disease-associated phenotypes and mechanisms. In this review, we summarize how the diverse brain organoid methods can be utilized to enhance our understanding of brain disorders.Facts

• Brain organoids offer an in vitro approach to study aspects of human brain development and disease.
• Diverse brain organoid techniques offer bioassays to investigate new phenotypes associated with human brain disorders that are difficult to study in monolayer cultures.
• Brain organoids have been particularly useful to study phenomena and diseases associated with neural progenitor morphology, survival, proliferation, and differentiation.

Open question

• Future brain organoid research needs to aim at later stages of neurodevelopment, linked with neuronal activity and connections, to unravel further disease-associated phenotypes.
• Continued improvement of existing organoid protocols is required to generate standardized methods that recapitulate in vivo-like spatial diversity and complexity.

Subject terms: Neuroscience, Neurological disorders

     

Glycocalyx damage biomarkers in healthy controls,abdominal surgery,and sepsis: a scoping review

Abstract

Objective

Despite wide interest in glycocalyx biomarkers, their values in healthy individuals, patients after abdominal surgery, and septic patients have been poorly understood.     

Identification of a Multiplex Biomarker Panel for Hypertrophic Cardiomyopathy Using Quantitative Proteomics and Machine Learning

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Highlights

• •Quantitative proteomics and machine learning to study plasma biomarkers in HCM.
• •Six peptides are increased in plasma of LVH+ HCM compared to controls.
• •Peptide biomarkers correlate with imaging markers of phenotype severity.
• •Peptide biomarkers correlate with the estimated sudden cardiac death risk.

     

Tape stripping the stratum corneum for biomarkers of ultraviolet radiation exposure at sub-erythemal dosages: a study in human volunteers

Abstract

Purpose

Prevalence of skin cancer is rapidly increasing. There is a need for non-invasive biomarkers to assess efficacy of prevention strategies aiming at reduction of exposure to ultraviolet radiation (UVR). Recently, stratum corneum (SC) biomarkers were applied in various inflammatory skin diseases. Here, we explore their suitability as candidate biomarkers for UVR.     

An in-depth Comparison of the Pediatric and Adult Urinary N-glycomes

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Highlights

• •N-glycan patterns are distinct in pediatric and adult urine.
• •Sex differences of N-glycans are much larger in adults.
• •Pediatric urine has almost no sex differences in N-glycan levels.
• •In adults, the majority of N-glycans were more abundant in males.

     

Environmental payback periods of reusable alternatives to single-use plastic kitchenware products

Purpose

Many consumers are transitioning away from single-use plastic products and turning to reusable alternatives. Oftentimes, this change is being made with the assumption that these alternatives have fewer environmental impacts; however, reusable products are frequently made from more environmentally intensive materials and have use phase impacts. This study used LCA to examine the GWP, water consumption, and primary nonrenewable energy use associated with reusable alternatives for single-use plastic kitchenware products and determined environmental payback periods.

Methods

The environmental impacts for each reusable alternative are calculated on the functional units of 1 use, 1 year (5 uses/week), and 5 years (5 uses/week). Payback periods are calculated for each reusable alternative and defined as the number of times a consumer must reuse an alternative in order for the environmental impact per use to be equivalent to the environmental impact for the single-use product. The research explored the sensitivity of the results to different consumer washing and reuse behaviors, as well as local conditions such as overall transportation distances and the carbon intensity of different electricity grids. Product types studied included straws (4 reusable, 2 single-use), sandwich storage (2 reusable, 3 single-use), coffee cups (3 reusable, 2 single-use), and forks (1 single-use, 3 reusable).

Results and discussion

Environmental impacts associated with the reusable alternatives were highly dependent on the use phase due to dishwashing, making payback period sensitive to washing frequency and method, and for GWP, carbon intensity of the energy grid (used for water heating). For single-use products, the material/manufacturing phase was the largest contributor to overall impacts. It was found that nine of the twelve reusable alternatives were able to breakeven in all three environmental indicators. The coffee cup product type was the only product type to have one reusable alternative, the ceramic mug, and have the shortest payback period for all three impact categories. Both the bamboo straw and beeswax wrap were unable to breakeven in any scenario due to high use phase impacts from manual washing.

Conclusions

The research found that reusable alternatives can payback the environmental impacts of GWP, water consumption, and energy use associated with their more resource intensive materials, but it is dependent on number of uses, consumer behavior, and for GWP, carbon intensity of the energy grid. A key takeaway is that consumer behavior and use patterns influence the ultimate environmental impact of reusable kitchenware products.

Recommendations

Some recommendations for consumers looking to reduce the overall impact of kitchenware products include the following:

1. 1)

   Not always assuming reusable is the best option.

2. 2)

   Extending product lifetime.

3. 3)

   Researching which reusable option has the lowest impact.

4. 4)

   Following best practice washing behaviors.

5. 5)

   Not washing products after every use.

6. 6)

   Advocating for integration of renewables into the local energy grid.

7. 7)

   Reducing consumption of these product types (reusable or single-use).

     

Characterizing Patients with Recurrent Urinary Tract Infections in Vesicoureteral Reflux: A Pilot Study of the Urinary Proteome

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Highlights

• •Urinary proteomes of patients with recurrent UTI, renal scarring, and VUR.
• •80 proteins differentially expressed, compared to healthy controls.
• •62 proteins may be indicative of susceptibility for UTI.
• •Altered acute phase response, extracellular matrix and carbohydrate metabolism.

     

The Capture of a Disabled Proteasome Identifies Erg25 as a Substrate for Endoplasmic Reticulum Associated Degradation

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Highlights

• •Epitope-tagging of a proteasome subunit allows for facile immuno-isolation.
• •An engineered yeast strain permits capture of proteasome-associated substrates.
• •MS/MS identified all 33 resident proteasome subunits in the 20S and 19S particles.
• •Analysis of associated proteins and characterization of newly identified ERAD substrate.

     

Immune Signature Against Plasmodium falciparum Antigens Predicts Clinical Immunity in Distinct Malaria Endemic Communities

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Highlights

• •A predictive modelling framework has been established to analyze IgG antibody responses against a large panel of P. falciparum-specific antigens to identify a specific antigen signature of NAI.
• •An individual's immune status can be accurately predicted by measuring IgG responses against a small set of 15 defined parasite antigens.
• •Proteins identified in the 15-antigen signature represent potential candidates for next-generation malaria vaccines or biomarkers for monitoring the impact of malaria interventions.
• •The developed predictive framework can be adapted for developing novel surveillance and intervention tools for other infectious diseases.

     

AMPK Interactome Reveals New Function in Non-homologous End Joining DNA Repair

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Highlights

• •Each component of the AMPK trimeric complex was profiled by interaction proteomics.
• •The subunit composition of the AMPK complex directs interactions to distinct proteins.
• •AMPK interacts with Artemis and plays a role in Non-Homologous End Joining.

     

Serum Protein Profiling Reveals a Landscape of Inflammation and Immune Signaling in Early-stage COVID-19 Infection

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Highlights

• •In-depth profiling of the serum proteome in early-stage COVID-19 patients.
• •A landscape of inflammation and immune signaling related to the SARS-CoV-2 infection.
• •CCL2 and CXCL10 medicated cytokine signaling pathways may correlate with neutrophil and lymphocyte respectively.

     

Mortality in cardiogenic shock is stronger associated to clinical factors than contemporary biomarkers reflecting neurohormonal stress and inflammatory activation

Abstract

Purpose

To validate the IABP-SHOCK II risk score in a Danish cohort and assess the association between the IABP-SHOCK II risk score and admission concentration of biomarkers reflecting neurohormonal – (Copeptin, Pro-atrial natriuretic peptide (proANP), Mid-regional pro-adrenomedullin (MRproADM)) and inflammatory (ST2) activation in patients with CS complicating ST segment elevation myocardial infarction (STEMI).