Effect of the Graphene- Ni/NiFe2O4 Composite on Bacterial Inhibition Mediated by Protein Degradation.

Recent investigations have demonstrated that nickel ferrite nanoparticles and their derivatives have toxicity effects on bacterial cells. In this study, we have prepared nickel ferrite nanoparticles (Ni/NiFe2O4) and nickel/nickel ferrite graphene oxide (Ni/NiFe2O4-GO) nanocomposite and evaluated their toxic effects on E. coli cells ATCC 25922. The prepared nanomaterials were characterized using X-ray diffraction, Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometry techniques. The toxicity was evaluated using variations in cell viability, cell morphology, protein degradation, and oxidative stress. Ni/NiFe2O4-GO nanocomposites likewise prompt oxidative stress proved by the age of reactive oxygen species (ROS) and exhaustion of antioxidant glutathione. This is the first report indicating that Ni/NiFe2O4-GO nanocomposite-initiated cell death in E. coli through ROS age and oxidative stress.

Malaria amongst febrile children: call for a pediatric malaria assessment tool.

In 2017, malaria accounted for 435 000 deaths worldwide. Eleven percent (11%) of these deaths occurred in the Democratic Republic of Congo (DRC), where malaria continues to be a leading cause of morbidity and mortality. Children are amongst the most vulnerable to malaria, which causes 40% of childhood deaths in the country. Although many risk factors for developing malaria have been identified, there is a paucity of data available on the sociodemographic risk factors for pediatric malaria. A cross-sectional study including 131 febrile children aged 2 months to 14 years presenting to Heal Africa Hospital due to febrile illness. Guardians of participants answered a questionnaire about household and maternal characteristics, as well as child symptomatology. Malaria status was confirmed via blood smear. Results were analyzed using the chi-square test, likelihood ratios and a logistic regression. The absence of father as head of household (p=0.011) and gestational malaria (p=0.044) were significantly associated with pediatric malaria. This study provides insight into sociodemographic risk factors associated with pediatric malaria in the DRC. While further investigation is required, this study highlights the benefit of considering these factors when approaching the febrile child. A pediatric malaria assessment tool incorporating socio-demographics, symptoms and physical exam findings may guide investigations to reduce unnecessary testing and provide better patient-centred care.

Antimicrobial Prescribing during Infant Hospital Admissions in a Birth Cohort in Dhaka, Bangladesh.

Empirical antimicrobial use is common in hospitalized infants and may contribute to antimicrobial resistance in low- and middle-income countries. In this observational birth cohort study nested in a randomized controlled trial in Dhaka, Bangladesh, inpatient antimicrobial prescription data were extracted from serious adverse event forms completed for hospitalizations of infants (0-12 months of age). The primary outcome was the proportion of inpatient admissions where systemic antimicrobials were prescribed. Infant and hospitalization-related factors associated with antimicrobial prescriptions were determined. Among 1254 infants, there were 448 admissions to 32 facilities from 2014 to 2016. Antimicrobials were prescribed in 73% of admissions with a mean antimicrobial exposure rate of 0.25 antimicrobials per day of admission [95% confidence intervals (95% CIs): 0.24-0.27]. The most common antibiotics were aminoglycosides (29%), penicillins (26%) and third-generation cephalosporins (25%). In all, 58% of antibiotics were classified as 'access', 38% 'watch' and 1% 'reserve' using the World Health Organization (WHO) Essential Medicines List classification. WHO-recommended antimicrobial regimens were used in 68% of neonatal sepsis and 9% of lower respiratory tract infection (LRTI) admissions. 'Watch' antimicrobials were used in 26% of neonatal sepsis and 76% of LRTI admissions. Compared with private facilities, antimicrobial prescription rates were lower at government [rate ratio (RR) 0.71; 95% CI: 0.61-0.83] and charitable facilities (RR 0.39; 95% CI: 0.28-0.53), after adjustment for household wealth index and parental education. Younger infant age, older maternal age and longer admission were associated with higher prescription rates. These findings highlight the need for paediatric antimicrobial stewardship programs in Bangladesh.

Illuminating dark fishing fleets in North Korea.

Illegal, unreported, and unregulated fishing threatens resource sustainability and equity. A major challenge with such activity is that most fishing vessels do not broadcast their positions and are "dark" in public monitoring systems. Combining four satellite technologies, we identify widespread illegal fishing by dark fleets in the waters between the Koreas, Japan, and Russia. We find >900 vessels of Chinese origin in 2017 and >700 in 2018 fished illegally in North Korean waters, catching an estimated amount of Todarodes pacificus approximating that of Japan and South Korea combined (>164,000 metric tons worth >$440 million). We further find ~3000 small-scale North Korean vessels fished, mostly illegally, in Russian waters. These results can inform independent oversight of transboundary fisheries and foreshadow a new era in satellite monitoring of fisheries.

Cytotoxicity of apo bovine α-lactalbumin complexed with La3+ on cancer cells supported by its high resolution crystal structure.

Cancer remains one of the biggest threats to human society. There are massive demands for compounds to selectively kill cancerous cells. Earlier studies have shown that bovine α -lactalbumin made lethal to tumor cells (BAMLET) becomes cytotoxic against cancer cells in complex with oleic acid {Hoque, M. et. al., PLoSOne 8, e68390 (2013)}. In our study, we obtained bovine α-lactalbumin complexed with lanthanum ion (La3+-B-α-LA) and determined its high resolution crystal structure. The natural calcium binding site of bovine α-lactalbumin is replaced by lanthanum. The La3+ complex formation by B-α-apo-LA was also supported by various biophysical methods. Interestingly, our complex, La3+-B-α-LA exhibits much greater anticancer activity against breast cancer cells as compared to the reported BAMLET-oleic acid complex. This study shows that La3+-B-α-LA complex is preferentially more toxic to MCF-7 cells as compared to KB (oral cancer) and HeLa (cervical) cells, while almost non-toxic to the healthy cells that we studied. Our data indicates that the cytotoxicity of La3+-B-α-LA against cancer cells is through apoptotic path way. The higher anticancer activity of La3+-B-α-LA is attributable to the requisite structural changes induced in the protein by La3+ binding as supported by the crystal structure of the complex.

Colorimetric and fluorimetric detection of Hg2+ and Cr3+ by boronic acid conjugated rhodamine derivatives: Mechanistic aspects and their bio-imaging application in bacterial cells.

Colorimetric and fluorimetric detection of toxic metal ions such as Hg2+ and Cr3+ has gained tremendous popularity over the conventional methods due to their operational simplicity, high selectivity, and speediness. Although numerous colorimetric and fluorescent receptors for Hg2+ or Cr3+ were reported in the literature, boronic acid-based receptors for these metal ions are rather scarce in the literature. Hence, in the present study dual function boronic acid conjugated rhodamine derivatives were developed, and their toxic metal ion detection abilities were studied by absorption, emission and visual detection methods. Absorption and emission spectral studies revealed that these derivatives displayed selectivity towards Hg2+, Cr3+ and Fe3+ among the other metal ions studied by forming new absorption band. Both the derivatives exhibited colorimetric response towards Hg2+ and Cr3+ by the change in color of the solution to pink and reddish pink with Fe3+. The detailed mechanism involved in the detection of Hg2+ was deduced by 1H NMR and ESI-MS studies. Further, these derivatives were used for fluorescence imaging of Hg2+ and Cr3+ in S. aureus bacterial cells. Thus the present manuscript demonstrated the use of boronic acid conjugated rhodamine derivatives as a dual function (colorimetric and fluorescent) probes and as imaging agents for Hg2+ and Cr3+, which are known for their toxic influence on bacterial cells.

Biosynthesis of silver nanoparticles by Pseudomonas spp. isolated from effluent of an electroplating industry.

The aim of this study was to isolate and screen bacteria from soil and effluent of electroplating industries for the synthesis of silver nanoparticles and characterize the potential isolate. Soil and effluent of electroplating industries from Mumbai were screened for bacteria capable of synthesizing silver nanoparticles. From two soils and eight effluent samples 20 bacterial isolates were obtained, of these, one was found to synthesize silver nanoparticles. Synthesis of silver nanoparticle by bacteria was confirmed by undertaking characterization studies of nanoparticles that involved spectroscopy and electron microscopic techniques. The potential bacteria was found to be Gram-negative short rods with its biochemical test indicating Pseudomonas spp. Molecular characterization of the isolate by 16S r DNA sequencing was carried out which confirmed its relation to Pseudomonas hibiscicola ATCC 19867. Stable nanoparticles synthesized were 50 nm in size and variable shapes as seen in SEM micrographs. The XRD and FTIR confirmed the crystalline structure of nanoparticles and presence of biomolecules mainly proteins as agents for reduction and capping of nanoparticles. The study demonstrates synthesis of nanoparticles by bacteria from effluent of electroplating industry. This can be used for large scale synthesis of nanoparticles by cost effective and environmentally benign mode of synthesis.

Expression, Purification, and Properties of a Human Arachidonoyl-Specific Isoform of Diacylglycerol Kinase.

Diacylglycerol kinase ε (DGKε) catalyzes the phosphorylation of diacylglycerol, producing phosphatidic acid. DGKε demonstrates exquisite specificity for the acyl chains of diacylglycerol. This contributes to the enrichment of particular acyl chains within the lipids of the phosphatidylinositol cycle. Phosphatidylinositol is highly enriched with 1-stearoyl-2-arachidonoyl, which is important for maintaining cellular health. Dysregulation of DGKε perturbs lipid signaling and biosynthesis, which has been linked to epilepsy, Huntington's disease, and heart disease. Recessive loss-of-function mutations in the DGKε gene cause atypical hemolytic uremic syndrome. Because DGKε has never been purified, little is known about its molecular properties. We expressed human DGKε and a truncated version lacking the first 40 residues (DGKεΔ40) and purified both proteins to near homogeneity using nickel affinity chromatography. Kinase activity measurements showed that both purified constructs retained their acyl chain specificity for diacylglycerol with an activity level comparable to that of N-terminally FLAG epitope-tagged forms of these proteins expressed in COS7 cells. Both constructs lost activity upon being stored, particularly upon freezing and thawing, which was minimized by the addition of glycerol. Circular dichroism revealed that DGKε and DGKεΔ40 both contain significant amounts of α-helical and ß structure and exhibit biphasic thermal denaturations. The loss of secondary structure upon heating was irreversible for both constructs, with relatively little effect of added dioleoylphosphatidylcholine. The addition of 50% glycerol stabilized both constructs and facilitated refolding of their secondary structures after heating. This is the first successful purification and characterization of DGKε's enzymatic and conformational properties. The purification of DGKε permits detailed analyses of this unique enzyme and will improve our understanding of DGKε-related diseases.

Exoelectrogens Leading to Precise Reduction of Graphene Oxide by Flexibly Switching Their Environment during Respiration.

Reduced graphene oxide (RGO) has been prepared by a simple, cost-effective, and green route. In this work, graphene oxide (GO) has been reduced using Gram-negative facultative anaerobe S. dysenteriae, having exogenic properties of electron transfer via electron shuttling. Apparently, different concentrations of GO were successfully reduced with almost complete mass recovery. An effective role of lipopolysaccharide has been observed while comparing RGO reduced by S. dysenteriae and S. aureus. It was observed that the absence of lipopolysaccharide in Gram-positive S. aureus leads to a disrupted cell wall and that S.aureus could not survive in the presence of GO, leading to poor and inefficient reduction of GO, as shown in our results. However, S. dysenteriae having an outer lipopolysaccharide layer on its cell membrane reduced GO efficiently and the reduction process was extracellular for it. RGO prepared in our work has been characterized by X-ray diffraction, ζ potential, X-ray photoelectron spectroscopy, and Raman spectroscopy techniques, and the results were found to be in good agreement with those of chemically reduced GO. As agglomeration of RGO is the major issue to overcome while chemically reducing GO, we observed that RGO prepared by a bacterial route in our work has ζ potential value of -26.62 mV, good enough to avoid restacking of RGO. The role of exoelectrogens in electron transfer in the extracellular space has been depicted. Toxin released extracellularly during the process paves the way for reduction of GO due to its affinity towards oxygen.

Molecular properties of diacylglycerol kinase-epsilon in relation to function.

The epsilon isoform of mammalian diacylglycerol kinase (DGKϵ) is an enzyme that associates strongly with membranes and acts on a lipid substrate, diacylglycerol. The protein has one segment that is predicted to be a transmembrane helix, but appears to interconvert between a transmembrane helix and a re-entrant helix. Despite the hydrophobicity of this segment and the fact that the lipid substrate is also hydrophobic, removal of this hydrophobic segment by truncating the protein at the amino terminus has no effect on its enzymatic activity. The amino acid sequence of the catalytic segment of DGKϵ is highly homologous to that of a bacterial DGK, DgkB. This has allowed us to predict a conformation of DGKϵ based on the known crystal structure of DgkB. An important property of DGKϵ is that it is specific for diacylglycerol species containing an arachidonoyl group. The region of DGKϵ that interacts with this group is found within the accessory domain of the protein and not in the active site nor in the hydrophobic amino terminus. The nature of the acyl chain specificity of the enzyme indicates that DGKϵ is associated with the synthesis of phosphatidylinositol. Defects or deletion of the enzyme give rise to several disease states.

The role of oxidative stress in menopause.

This review will discuss the concept of reproductive aging, which includes the definition of menopause, its symptoms, and predisposing conditions. It will elaborate upon the contributory factors implicated in the pathogenesis of menopause, focusing most prominently on oxidative stress. Specifically, this paper will explain how oxidative stress, in the form of free radicals and antioxidant deficiencies, has been directly linked to the decline of estrogen during reproductive aging. Additionally, this paper will elaborate upon the treatment options aimed at mitigating the menopausal symptoms and hormonal deficiencies that can lead to various disease processes. Treatment options such as hormonal therapy, antioxidant supplementation, and lifestyle modification have been explored for their effectiveness in treating and preventing the symptoms and sequelae of menopause. The majority of information in this review was obtained through PubMed and the National Library of Medicine. While most references in this paper are original research articles, a limited number of references are comprehensive reviews on the topic.

Role of reactive nitrogen species in male infertility.

Reactive nitrogen species (RNS) is a subset of free oxygen radicals called reactive oxygen species (ROS). Physiological levels of ROS are necessary to maintain the reproductive functions such as cell signaling, tight junction regulation, production of hormones, capacitation, acrosomal reaction, sperm motility, and zona pellucida binding. However, an excess of RNS can adversely affect reproductive potential by causing testicular dysfunction, decreased gonadotropin secretion, and abnormal semen parameters. Because such levels of RNS have been demonstrated in males with fertility problems and routine semen analysis has not been able to accurately predict IVF outcomes, it is imperative that novel strategies be developed in order to both assess and treat oxidative stress. This article describes both physiological and pathological roles of this unique subset of ROS.