Common-path interferometric label-free protein sensing with resonant dielectric nanostructures

Research toward photonic biosensors for point-of-care applications and personalized medicine is driven by the need for high-sensitivity, low-cost, and reliable technology. Among the most sensitive modalities, interferometry offers particularly high performance, but typically lacks the required operational simplicity and robustness. Here, we introduce a common-path interferometric sensor based on guided-mode resonances to combine high performance with inherent stability. The sensor exploits the simultaneous excitation of two orthogonally polarized modes, and detects the relative phase change caused by biomolecular binding on the sensor surface. The wide dynamic range of the sensor, which is essential for fabrication and angle tolerance, as well as versatility, is controlled by integrating multiple, tuned structures in the field of view. This approach circumvents the trade-off between sensitivity and dynamic range, typical of other phase-sensitive modalities, without increasing complexity. Our sensor enables the challenging label-free detection of procalcitonin, a small protein (13 kDa) and biomarker for infection, at the clinically relevant concentration of 1 pg mL−1, with a signal-to-noise ratio of 35. This result indicates the utility for an exemplary application in antibiotic guidance, and opens possibilities for detecting further clinically or environmentally relevant small molecules with an intrinsically simple and robust sensing modality

“It is all about the fear of being discriminated [against]…the person suffering from HIV will not be accepted”: a qualitative study exploring the reasons for loss to follow-up among HIV-positive youth in Kisumu, Kenya

BACKGROUND: Youth represent 40% of all new HIV infections in the world, 80% of which live in sub-Saharan Africa. Youth living with HIV (YLWH) are more likely to become lost to follow-up (LTFU) from care compared to all other age groups. This study explored the reasons for LTFU among YLWH in Kenya. METHODS: Data was collected from: (1) Focus group Discussions (n = 18) with community health workers who work with LTFU youth. (2) Semi-structured interviews (n = 27) with HIV + youth (15–21 years old) that had not received HIV care for at least four months. (3) Semi-structured interviews (n = 10) with educators selected from schools attended by LTFU interview participants. Transcripts were coded and analyzed employing grounded theory. RESULTS: HIV-related stigma was the overarching factor that led to LTFU among HIV + youth. Stigma operated on multiple levels to influence LTFU, including in the home/family, at school, and at the clinic. In all three settings, participants’ fear of stigma due to disclosure of their HIV status contributed to LTFU. Likewise, in the three settings, the dependent relationships between youth and the key adult figures in their lives were also adversely impacted by stigma and resultant lack of disclosure. Thus, at all three settings stigma influenced fear of disclosure, which in turn impacted negatively on dependent relationships with adults on whom they rely (i.e. parents, teachers and clinicians) leading to LTFU. CONCLUSIONS: Interventions focusing on reduction of stigma, increasing safe disclosure of HIV status, and improved dependent relationships may improve retention in care of YLWH

Population Genetic Structure of the Grasshopper Eyprepocnemis plorans in the South and East of the Iberian Peninsula

The grasshopper Eyprepocnemis plorans subsp. plorans harbors a very widespread polymorphism for supernumerary (B) chromosomes which appear to have arisen recently. These chromosomes behave as genomic parasites because they are harmful for the individuals carrying them and show meiotic drive in the initial stages of population invasion. The rapid increase in B chromosome frequency at intrapopulation level is thus granted by meiotic drive, but its spread among populations most likely depends on interpopulation gene flow. We analyze here the population genetic structure in 10 natural populations from two regions (in the south and east) of the Iberian Peninsula. The southern populations were coastal whereas the eastern ones were inland populations located at 260–655 m altitude. The analysis of 97 ISSR markers revealed significant genetic differentiation among populations (average GST = 0.129), and the Structure software and AMOVA indicated a significant genetic differentiation between southern and eastern populations. There was also significant isolation by distance (IBD) between populations. Remarkably, these results were roughly similar to those found when only the markers showing low or no dropout were included, suggesting that allelic dropout had negligible effects on population genetic analysis. We conclude that high gene flow helped this parasitic B chromosome to spread through most of the geographical range of the subspecies E. plorans plorans.This study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER funds. MIMP was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación

Modulation of the expression of components of the stress response by dietary arachidonic acid in European sea bass (Dicentrarchus labrax) larvae

This study reports for the first time in European sea bass, Dicentrarchus labrax (L.), larvae, the effect of different levels of dietary arachidonic acid (ARA; 20:4n-6) on the expression of genes related to the fish stress response. Copies of mRNA from genes related to steroidogenesis (StAR (steroidogenic acute regulatory protein), c-Fos, and CYP11β (11β- hydroxylase gene)), glucocorticoid receptor complex (GR (glucorticoid receptor) and HSP (heat shock proteins) 70 and 90) and antioxidative stress (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX)) were quantified. Eighteen day-old larvae were fed for 14 days with three experimental diets with increasing levels of ARA (0.3, 0.6 and 1.2% d.w.) and similar levels of docosahexaenoic (DHA; 22:6n-3) and eicosapentaenoic (EPA; 20:5n-3) acids (5 and 3%, respectively). The quantification of stress-related genes transcripts was conducted by One-Step TaqMan real time RT-PCR with the standard curve method (absolute quantification). Increase dietary levels of ARA induced a significantly (p<0.05) down-regulation of genes related to cortisol synthesis, such as StAR and CYP11β and up-regulated genes related to glucocorticoid receptor complex, such as HSP70 and GR. No effects were observed on antioxidant enzymes gene expression. These results revealed the regulatory role of dietary ARA on the expression of stress-related genes in European sea bass larvae

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

An integrated expression atlas of miRNAs and their promoters in human and mouse

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions

Structure property studies of fibres from various parts of the coconut tree

Fibres from different structural parts of the coconut palm tree (Cocos nucifera, linn.)13; have been examined for properties such as size, density, electrical resistivity, ultimate fracture mode, microfibrillar angle as well as cellulose and lignin contents of these fibres have been determined. The observed properties have been related to the internal structure and chemical composition of the fibres. Some potential uses of these fibres have been listed

Mechanical properties of banana fibres (Musa sepientum)

The stress-strain curve for banana fibre i s determined. Properties such as the initial13; modulus (YM), ultimate tensile strength (UTS) and percentage elongation are evaluated as13; a function of fibre diameter, test length and speed of testing. It is found that YM, UTS13; and % elongation show l i t t l e variation in their values for fibres of diameter ranging from13; 50 to 250pm. The UTS and breaking strain are found to decrease with an increase in the13; test length while both breaking strength and breaking strain remain constant with the13; increase of speed of testing from 0.5 to 100 x m and after they both decrease. These observed properties are explained on the basis of the internal structure of the fibre, namely, the number of cells, spiral angle and the number of defects. Scanning electron microscopic (SEM) studies of the fractured surfaces of these fibres indiacte that the failure is due to pull-out of microfibrils panied by tearing of cell walls; the tendency for fibre pull-out seems to decrease with increasing speed of testing

THE LIMITS OF CONDITIONAL STABILITY FOR SINGLE-PHASE NATURAL CIRCULATION WITH THROUGHFLOW IN A FIGURE-OF-8 LOOP

This paper is based on the investigations on the stability of natural circulation with throughflow in a figure-of-eight loop, a configuration that is employed in the pressure tube type heavy water reactors. The investigations have been both experimental as well as theoretical. The latter include both the linear stability analysis as well as the nonlinear finite difference analysis. The finite difference analysis has been used not only to identify the limits of the stable and unstable regimes but also used to identify the limits of the conditionally stable regime. Good agreement is found between theory and experiment