Post-mortem enamel surface texture alteration during taphonomic processes—do experimental approaches reflect natural phenomena?

Experimental approaches are often used to better understand the mechanisms behind and consequences of post-mortem alteration on proxies for diet reconstruction. Dental microwear texture analysis (DMTA) is such a dietary proxy, using dental wear features in extant and extinct taxa to reconstruct feeding behaviour and mechanical food properties. In fossil specimens especially, DMTA can be biased by post-mortem alteration caused by mechanical or chemical alteration of the enamel surface. Here we performed three different dental surface alteration experiments to assess the effect of common taphonomic processes by simplifying them: (1) tumbling in sediment suspension to simulate fluvial transport, (2) sandblasting to simulate mechanical erosion due to aeolian sediment transport, (3) acid etching to simulate chemical dissolution by stomach acid. For tumbling (1) we found alteration to be mainly dependent on sediment grain size fraction and that on specimens tumbled with sand fractions mainly post-mortem scratches formed on the dental surface, while specimens tumbled with a fine-gravel fraction showed post-mortem formed dales. Sandblasting (2) with loess caused only negligible alteration, however blasting with fine sand quartz particles resulted in significant destruction of enamel surfaces and formation of large post-mortem dales. Acid etching (3) using diluted hydrochloric acid solutions in concentrations similar to that of predator stomachs led to a complete etching of the whole dental surface, which did not resemble those of teeth recovered from owl pellets. The experiments resulted in post-mortem alteration comparable, but not identical to naturally occurring post-mortem alteration features. Nevertheless, this study serves as a first assessment and step towards further, more refined taphonomic experiments evaluating post-mortem alteration of dental microwear texture (DMT).

Panoramic visual statistics shape retina-wide organization of receptive fields

Visual systems have adapted to the structure of natural stimuli. In the retina, center-surround receptive fields (RFs) of retinal ganglion cells (RGCs) appear to efficiently encode natural sensory signals. Conventionally, it has been assumed that natural scenes are isotropic and homogeneous; thus, the RF properties are expected to be uniform across the visual field. However, natural scene statistics such as luminance and contrast are not uniform and vary significantly across elevation. Here, by combining theory and novel experimental approaches, we demonstrate that this inhomogeneity is exploited by RGC RFs across the entire retina to increase the coding efficiency. We formulated three predictions derived from the efficient coding theory: (i) optimal RFs should strengthen their surround from the dimmer ground to the brighter sky, (ii) RFs should simultaneously decrease their center size and (iii) RFs centered at the horizon should have a marked surround asymmetry due to a stark contrast drop-off. To test these predictions, we developed a new method to image high-resolution RFs of thousands of RGCs in individual retinas. We found that the RF properties match theoretical predictions, and consistently change their shape from dorsal to the ventral retina, with a distinct shift in the RF surround at the horizon. These effects are observed across RGC subtypes, which were thought to represent visual space homogeneously, indicating that functional retinal streams share common adaptations to visual scenes. Our work shows that RFs of mouse RGCs exploit the non-uniform, panoramic structure of natural scenes at a previously unappreciated scale, to increase coding efficiency.

Evaluation of biomarkers in the studies of keloid tissue after laser therapy

In this paper, we discuss what biomarkers to choose if there is a need to describe the results of laser therapy targeting keloid skin. We elevate the known cytomarkers (Krt14, Lgals7, Krt5, Dcn, Lum, Igfbp5, Cd31, Vwf, Stambpl1, Uqcrb, Cd3 and Acta2), biomarkers of the inflammatory response (Cd45/Ptprc, Adgre1, Ly6g, Il1b, Il4, Il13, Il22, Cxcl2 и Ccl17), as well as the proteins of extracellular matrix (type I and III collagens; precursors of COL5A1 and COLA1A; FTL, COL3A1, PGLS, CNN2, ANXA2, TPSAB1, COL12A1, precursors of APCS and ALB), and their encoding genes (FGF7, BAX, CCND1, MMP3, MMP9, CXCL1, -2, -5, -6 and -12; IL8, S100A7 and IL1A), those expression and co-location may potentially change the appearance and internal structure of damaged skin. We also describe how to choose biomarkers using the results genomic studies and their limitations. Moreover, we provide examples of how different groups of gene and protein biomarkers are used in experimental biology and clinical practice. According to the previously published data, well-known biomarkers verified on animal models, depend on their biological effects, let to characterize structural changes and changes in the composition of cells represented at the site of damage before and after the treatment. In addition, the published experimental and clinical data provide an opportunity to analyze the efficiency of new experimental approaches and compare them to each other.

Finite-Element Modeling of Spontaneous Potential in an Axisymmetric Reservoir Model with Account of Its Shale Content

(1) This article is devoted to the development of a theoretical and algorithmic basis for numerical modeling of the spontaneous potential method (SP) as applied to the study of sandy-argillaceous reservoirs. (2) In terms of coupled flows, we consider a physical–mathematical model of SP signals from an electrochemical source, with regards to the case of fluid-saturated shaly sandstone. (3) An algorithm for 2D finite-element modeling of SP signals was developed and implemented in software, along with its internal and external testing with analytical solutions. The numerical SP modeling was carried out, determining the dependences on the reservoir thickness and porosity, the amount of argillaceous material and the type of minerals. We performed a comparative analysis of the simulated and field SP data, using the results of laboratory core examinations taken from wells in a number of fields in the Latitudinal Ob Region of Western Siberia. (4) The results of the study may be used either for the development of the existing SP techniques, by providing them with a consistent computational model, or for the design of new experimental approaches.

Reducing sources of variance in experimental procedures in in vitro research

Background: Lack of reproducibility in preclinical research poses ethical and economic challenges for biomedical science. Various institutional activities by society stakeholders of leading industrialised nations are currently underway with the aim of improving the situation. Such initiatives are usually concerned with high-level organisational issues and typically do not focus on improving experimental approaches per se. Addressing these is necessary in order to increase consistency and success rates of lab-to-lab repetitions. Methods: In this project, we statistically evaluated repetitive data of a very basic and widely applied lab procedure, namely quantifying the number of viable cells. The purpose of this was to assess the impact of different parameters and instrumentations which may constitute sources of variance in this procedure. Conclusion: By comparing the variability of data acquired under two different procedures, featuring improved stringency of protocol adherence, our project attempts to identify the sources and propose guidelines on how to reduce such fluctuations. We believe our work can contribute to tackling the repeatability crisis in biomedical research.

PTRF/Cavin-1 as a Novel RNA-Binding Protein Expedites the NF-κB/PD-L1 Axis by Stabilizing lncRNA NEAT1, Contributing to Tumorigenesis and Immune Evasion in Glioblastoma

BackgroundImmunotherapy, especially checkpoint inhibitors targeting PD-1 or PD-L1, has revolutionized cancer therapy. However, PD-1/PD-L1 inhibitors have not been investigated thoroughly in glioblastoma (GBM). Studies have shown that polymerase 1 and transcript release factor (PTRF/Cavin-1) has an immune-suppressive function in GBM. Thus, the relationship between PTRF and PD-L1 and their role in immune suppression requires further investigation in GBM.MethodsWe used public databases and bioinformatics analysis to investigate the relationship between PTRF and PD-L1. We next confirmed the predicted relationship between PTRF and PD-L1 in primary GBM cell lines by using different experimental approaches. RIP-Seq, RIP, ChIP, and qRT-PCR were conducted to explore the molecular mechanism of PTRF in immunosuppression.ResultsWe found that PTRF stabilizes lncRNA NEAT1 to induce NF-κB and PD-L1 and promotes immune evasion in GBM. PTRF was found to correlate with immunosuppression in the public GBM databases. PTRF increased the level of PD-L1 in primary cell lines from GBM patients. We carried out RIP-Seq of GBM cells and found that PTRF interacts with lncRNA NEAT1 and stabilizes its mRNA. PTRF also promoted the activity of NF-κB by suppressing UBXN1 expression via NEAT1 and enhanced the transcription of PD-L1 through NF-κB activation. Finally, PTRF promoted immune evasion in GBM cells by regulating PD-1 binding and PD-L1 mediated T cell cytotoxicity.ConclusionsIn summary, our study identified the PTRF-NEAT1-PD-L1 axis as a novel immune therapeutic target in GBM.

Cellular Physiology and Pathophysiology of EAAT Anion Channels

Excitatory amino acid transporters (EAATs) optimize the temporal resolution and energy demand of mammalian excitatory synapses by quickly removing glutamate from the synaptic cleft into surrounding neuronal and glial cells and ensuring low resting glutamate concentrations. In addition to secondary active glutamate transport, EAATs also function as anion channels. The channel function of these transporters is conserved in all homologs ranging from archaebacteria to mammals; however, its physiological roles are insufficiently understood. There are five human EAATs, which differ in their glutamate transport rates. Until recently the high-capacity transporters EAAT1, EAAT2, and EAAT3 were believed to conduct only negligible anion currents, with no obvious function in cell physiology. In contrast, the low-capacity glutamate transporters EAAT4 and EAAT5 are thought to regulate neuronal signaling as glutamate-gated channels. In recent years, new experimental approaches and novel animal models, together with the discovery of a human genetic disease caused by gain-of-function mutations in EAAT anion channels have enabled identification of the first physiological and pathophysiological roles of EAAT anion channels.