Lithium response in bipolar disorder: Epigenome-wide DNA methylation signatures and epigenetic aging.

Lithium (Li) is the first-line treatment for bipolar disorder (BD) even though only 30 % of BD patients are considered excellent responders. The mechanisms by which Li exerts its action are not clearly understood, but it has been suggested that specific epigenetic mechanisms, such as methylation processes, may play a role. In this regard, DNA methylation patterns can be used to estimate epigenetic age (EpiAge), which is accelerated in BD patients and reversed by Li treatment. Our first aim was to compare the DNA methylation profile in peripheral blood between BD patients categorized as excellent responders to Li (Ex-Rp) and non-responders (N-Rp). Secondly, EpiAge was estimated to detect differential age acceleration between the two groups. A total of 130 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) between Ex-Rp (n = 26) and N-Rp (n = 37) were identified (FDR adjusted p-value < 0.05). We found 122 genes mapping the DMPs and DMRs, nine of which (HOXB6, HOXB3, HOXB-AS3, TENM2, CACNA1B, ANK3, EEF2K, CYP1A1, and SORCS2) had previously been linked to Li response. We found genes related to the GSK3ß pathway to be highly represented. Using FUMA, we found enrichment in Gene Ontology Cell Component for the synapse. Gene network analysis highlighted functions related to the cell cycle, nervous system development and function, and gene expression. No significant differences in age acceleration were found between Ex-Rp and N-Rp for any of the epigenetic clocks analysed. Our findings indicate that a specific methylation pattern could determine the response to Li in BD patients. We also found that a significant portion of the differentially methylated genes are closely associated with the GSK3ß pathway, reinforcing the role of this system in Li response. Future longitudinal studies with larger samples will help to elucidate the epigenetic mechanisms underlying Li response.

Fingermark ridge drift: Influencing factors of a not-so-rare aging phenomenon.

Fingermark ridge drift is a random modification of (aged) fingermark patterns at a ridge scale. This phenomenon was previously proven to alter key elements used for identifications, such as the appearance of minutiae. Little is currently reported on the underlying factors contributing to its occurrence. The present study was designed to investigate further the variables of a previous study by including a total of 768 fingermarks from a male and female, two substrates (glazed ceramic tile and plastic), two distinct color powder developers (carbon black and titanium dioxide), three indoor lighting conditions (direct natural light, shade, and darkness), and two secretion types (sebaceous- and eccrine-rich). Fingermarks were aged for 2-72 days, powdered, photographed, and drift detected by three independent observers. All aged fingermarks (672) were compared relative to fresh fingermarks (96), and ridge drift was observed in 42 of 672 (6%) fingermarks, while 168 (25%) were reported as indeterminate results. While ridge drift was detected in multiple fingermarks across all independent variables, statistical analysis using a multinomial logistics model showed that only powder type, secretion type, and the substrate indicated a significant correlation with increased incidences of this phenomenon. There was no significant correlation with the donor, time since deposition, or the environmental lighting conditions used. The highest incidence occurred when carbon black powder was used on a plastic substrate (>10%). The average observation of ridge drift is 6% of samples supporting that this phenomenon is not a rare event, particularly considering the conservative analysis approach implemented.

A Small Population Study on Friction Skin Ridges: Differences in Ridge Widths Between Latent and Inked Fingerprints.

Morphological changes in the width of latent fingermark ridges occur naturally over time. This could be used to examine the aging process of latents and eventually estimate time of deposition. In a crime context, it is common practice to compare a questioned (aged) fingermark with a database of known (inked) prints. Therefore, in the absence of fresh fingermarks for aging purposes, it is of interest to reveal correlations between these two categories of fingerprints with regard to the widths of their ridges. The present study explores correlations of ridge widths between flat and rolled inked prints with latent fingermarks visualized with carbon black (CB) and titanium dioxide (TiO2 )-based powders among a small population of ten donors. Results revealed consistent differences between the ridge widths of latent and inked prints as well as flat and rolled impressions. Latent fingermarks visualized with CB and TiO2 powders showed ridges with comparable widths.

Two novel ligand-independent variants of the VEGFR-1 receptor are expressed in human testis and spermatozoa, one of them with the ability to activate SRC proto-oncogene tyrosine kinases.

The vascular endothelial growth factor receptor 1 (VEGFR-1) family of receptors is preferentially expressed in endothelial cells, with the full-length and mostly the soluble (sVEGFR-1) isoforms being the most expressed ones. Surprisingly, cancer cells (MDA-MB-231) express, instead, alternative intracellular VEGFR-1 variants. We wondered if these variants, that are no longer dependent on ligands for activation, were expressed in a physiological context, specifically in spermatogenic cells, and whether their expression was maintained in spermatozoa and required for human fertility. By interrogating a human library of mature testis cDNA, we characterized two new truncated intracellular variants different from the ones previously described in cancer cells. The new isoforms were transcribed from alternative transcription start sites (aTSS) located respectively in intron-19 (i19VEGFR-1) and intron-28 (i28VEGFR-1) of the VEGFR-1 gene (GenBank accession numbers JF509744 and JF509745) and expressed in mature testis and spermatozoa. In this paper, we describe the characterization of these isoforms by RT-PCR, northern blot, and western blot, their preferential expression in human mature testis and spermatozoa, and the elements that punctuate their proximal promoters and suggest cues for their expression in spermatogenic cells. Mechanistically, we show that i19VEGFR-1 has a strong ability to phosphorylate and activate SRC proto-oncogene non-receptor tyrosine kinases and a significant bias toward a decrease in expression in patients considered infertile by WHO criteria.

Latent Fingermark Aging Patterns (Part IV): Ridge Width as One Indicator of Degradation.

This fourth article of the series is taking an in-depth analysis at the visible aging of latent fingermarks regarding changes in ridge widths over time. The objective is to quantify and statistically describe significant ridge size variations under controlled indoor conditions. The effect of three environmental variables are examined: type of secretion (sebaceous- and eccrine-rich) and type of substrate (glass and polystyrene) when aged in three light conditions (direct natural light, shade, and dark). Prior to width measurements, fresh and aged fingermarks were powdered with titanium dioxide (TiO2 ) and sequentially photographed at predetermined times over 6 months. Three independent observers measured the ridges from thirty predetermined locations using strategically placed intersecting lines on the print. Results indicate that fingermarks deposited on glass are more resilient to degradation compared with those deposited on plastic. The presence of direct natural light plays a negligible role on degradation compared to secretion and substrate types.

Ridge Width Correlations between Inked Prints and Powdered Latent Fingerprints.

A methodology to estimate the time of latent fingerprint deposition would be of great value to law enforcement and courts. It has been observed that ridge topography changes as latent prints age, including the widths of ridges that could be measured as a function of time. Crime suspects are commonly identified using fingerprint databases that contain reference inked tenprints (flat and rolled impressions). These can be of interest in aging studies as they provide baseline information relating to the original (nonaged) ridges' widths. In practice, the age of latent fingerprints could be estimated following a comparison process between the evidentiary aged print and the corresponding reference inked print. The present article explores possible correlations between inked and fresh latent fingerprints deposited on different substrates and visualized with TiO2 . The results indicate that the ridge width of flat inked prints is most similar to fresh latent fingerprints, and these should be used as the comparison standard for future aging studies.

Latent Fingermark Aging Patterns (Part III): Discontinuity Index as One Indicator of Degradation.

This article is the third in a series of reports exploring quantifiable visual parameters of the aging process of latent fingermarks. On this occasion, research is focused on the occurrence of ridge discontinuities (i.e. breakages) as a function of time. Experiment variables included type of secretion (eccrine and sebaceous), substrate (glass and plastic), and exposure to natural light (dark, shade, and direct light) over a 6 months period. Fingermarks were sequentially visualized with titanium dioxide powder, photographed, and the number of naturally occurring ridge discontinuities subsequently evaluated. A semi-quantitative value, named Discontinuity Index, was used to better characterize this aging parameter. Results indicated that ridges of sebaceous depositions on glass were generally less affected by the environmental conditions compared with those on plastic surface. In addition, aging in darkness was not always the best condition for preservation, and the direct exposure to light seemed not to affect the degradation under certain conditions.

Latent Fingermark Aging Patterns (Part I): Minutiae Count as One Indicator of Degradation.

The authors are exploring degradation patterns of latent fingermarks over time which can be quantitatively determined in a predictable manner by visual means. Several physical degradation parameters for assessing this hypothesis are evaluated. This article analyzes the parameter "minutiae count" as a function of time. Experiment variables included were secretion type (sebaceous-rich and eccrine-rich), substrate (glass and plastic), and exposure to light (dark, shade, and direct light). Depositions were sequentially visualized with Titanium Dioxide powder over a period of 6 months, photographed, and number of minutiae recorded. Results revealed a significant decrease of minutiae for eccrine-rich marks on glass but insignificant for sebaceous-rich marks on the same surface. However, significant degradation was observed for both types of secretions on plastic. The authors conclude that the distinctive prevalence of minutiae changes over time indicates with a high degree of certainty the hypothesis is valid and deserves additional exploration.

Latent Fingermark Aging Patterns (Part II): Color Contrast Between Ridges and Furrows as One Indicator of Degradation.

Currently, no established methodology exists to determine degradation patterns of latent fingermarks by visual means. This article is the second in a series of reports exploring quantifiable degradation-related parameters, which focuses on color contrast changes between fingermark ridges and furrows over time. Experiment variables included type of secretion (eccrine and sebaceous), substrate (glass and plastic), and exposure to natural light (dark, shade, and direct light). Fingermarks were sequentially visualized with titanium dioxide powder and photographed. Image histogram profiles were evaluated and combined with statistical analysis of color data values. Results indicate that sebaceous depositions on glass were generally less degraded by the effect of environmental conditions compared with those on plastic. In addition, aging in darkness was not always the best condition for preservation, and direct exposure to light seemed to inhibit visual degradation under certain conditions. Overall, the technique provided sufficient sensitivity to discern degradation patterns of fingermarks.

Determination of latent fingerprint degradation patterns-a real fieldwork study.

For over a century, law enforcement agencies, forensic laboratories, and penal courts worldwide have used fingerprint impressions as reliable and conclusive evidence to identify perpetrators of criminal activity. Although fingerprint identification has been repeatedly proven as one of the most robust and definite forensic techniques, a measure of the rate at which latent fingerprints degrade over time has not been established effectively. Ideally, criminal investigators should be able not only to place any given individual at a crime scene but also be able to date the moment any latent fingerprints were deposited at the location. The present report aims to determine particular visual patterns of degradation of latent fingerprints exposed to certain monitored laboratory conditions simulating those in the field. Factors considered include temperature, relative humidity, air currents, composition of fingerprint depositions (sebaceous and eccrine), various exposures to daylight (direct, penumbra, and darkness), and type of physical substrate (glass and plastic) over a period of 6 months. The study employs a titanium dioxide-based powder as developer. Our results indicate that, contrary to common belief, certain latent fingerprints exposed to direct sunlight indoors degrade similarly to those in the dark where environmental conditions are more constant. While all sebaceous latent fingerprints on glass are still useful for identification after 6 months, diverse results are obtained with impressions on plastic; these demonstrate a much higher and faster degree of decay, making identification difficult or impossible, especially for eccrine depositions.