Graphene oxide exhibits differential mechanistic action towards Gram-positive and Gram-negative bacteria

The antibacterial nature of graphene oxide (GO) has stimulated wide interest in the medical field. Although the antibacterial activity of GO towards bacteria has been well studied, a deeper understanding of the mechanism of action of GO is still lacking. The objective of the study was to elucidate the difference in the interactions of GO towards Gram-positive and Gram-negative bacteria. The synthesized GO was characterized by Ultraviolet–visible spectroscopy (UV–vis), Raman and Attenuated Total Reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR). Viability, time-kill and Lactose Dehydrogenase (LDH) release assays were carried out along with FESEM, TEM and ATR-FTIR analysis of GO treated bacterial cells. Characterizations of synthesized GO confirmed the transition of graphene to GO and the antibacterial activity of GO was concentration and time-dependent. Loss of membrane integrity in bacteria was enhanced with increasing GO concentrations and this corresponded to the elevated release of LDH in the reaction medium. Surface morphology of GO treated bacterial culture showed apparent differences in the mechanism of action of GO towards Gram-positive and Gram-negative bacteria where cell entrapment was mainly observed for Gram-positive Staphylococcus aureus and Enterococcus faecalis whereas membrane disruption due to physical contact was noted for Gram-negative Escherichia coli and Pseudomonas aeruginosa. ATR-FTIR characterizations of the GO treated bacterial cells showed changes in the fatty acids, amide I and amide II of proteins, peptides and amino acid regions compared to untreated bacterial cells. Therefore, the data generated further enhance our understanding of the antibacterial activity of GO towards bacteria

Non-randomness of the anatomical distribution of tumors

Background: Why does a tumor start where it does within an organ? Location is traditionally viewed as a random event, yet the statistics of the location of tumors argues against this being a random occurrence. There are numerous examples including that of breast cancer. More than half of invasive breast cancer tumors start in the upper outer quadrant of the breast near the armpit, even though it is estimated that only 35 to 40% of breast tissue is in this quadrant. This suggests that there is an unknown microenvironmental factor that significantly increases the risk of cancer in a spatial manner and that is not solely due to genes or toxins. We hypothesize that tumors are more prone to form in healthy tissue at microvascular ‘hot spots’ where there is a high local concentration of microvessels providing an increased blood flow that ensures an ample supply of oxygen, nutrients, and receptors for growth factors that promote the generation of new blood vessels. Results: To show the plausibility of our hypothesis, we calculated the fractional probability that there is at least one microvascular hot spot in each region of the breast assuming a Poisson distribution of microvessels in two-dimensional cross sections of breast tissue. We modulated the microvessel density in various regions of the breast according to the total hemoglobin concentration measured by near infrared diffuse optical spectroscopy in different regions of the breast. Defining a hot spot to be a circle of radius 200 μm with at least 5 microvessels, and using a previously measured mean microvessel density of 1 microvessel/mm2, we find good agreement of the fractional probability of at least one hot spot in different regions of the breast with the observed invasive tumor occurrence. However, there is no reason to believe that the microvascular distribution obeys a Poisson distribution. Conclusions: The spatial location of a tumor in an organ is not entirely random, indicating an unknown risk factor. Much work needs to be done to understand why a tumor occurs where it does. Electronic supplementary material The online version of this article (10.1186/s41236-017-0006-7) contains supplementary material, which is available to authorized users

Dicer recognizes the 5′ end of RNA for efficient and accurate processing

A hallmark of RNA silencing is a class of approximately 22-nucleotide RNAs that are processed from double-stranded RNA precursors by Dicer. Accurate processing by Dicer is crucial for the functionality of microRNAs (miRNAs). The current model posits that Dicer selects cleavage sites by measuring a set distance from the 3′ overhang of the double-stranded RNA terminus. Here we report that human Dicer anchors not only the 3′ end but also the 5′ end, with the cleavage site determined mainly by the distance (~22 nucleotides) from the 5′ end (5′ counting rule). This cleavage requires a 5′-terminal phosphate group. Further, we identify a novel basic motif (5′ pocket) in human Dicer that recognizes the 5′-phosphorylated end. The 5′ counting rule and the 5′ anchoring residues are conserved in Drosophila Dicer-1, but not in Giardia Dicer. Mutations in the 5′ pocket reduce processing efficiency and alter cleavage sites in vitro. Consistently, miRNA biogenesis is perturbed in vivo when Dicer-null embryonic stem cells are replenished with the 5′-pocket mutant. Thus, 5′-end recognition by Dicer is important for precise and effective biogenesis of miRNAs. Insights from this study should also afford practical benefits to the design of small hairpin RNAs