The dynamic genetic determinants of increased transcriptional divergence in spermatids.

Cis-genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- and trans-effects act across continuous trajectories of cellular differentiation in vivo is poorly understood. Here, we quantify allele-specific expression during spermatogenic differentiation at single-cell resolution in an F1 hybrid mouse system, allowing for the comprehensive characterisation of cis- and trans-genetic effects, including their dynamics across cellular differentiation. Collectively, almost half of the genes subject to genetic regulation show evidence for dynamic cis-effects that vary during differentiation. Our system also allows us to robustly identify dynamic trans-effects, which are less pervasive than cis-effects. In aggregate, genetic effects were strongest in round spermatids, which parallels their increased transcriptional divergence we identified between species. Our approach provides a comprehensive quantification of the variability of genetic effects in vivo, and demonstrates a widely applicable strategy to dissect the impact of regulatory variants on gene regulation in dynamic systems.

Children's rehearsal development parallels that of self-talk in other executive functions.

Rehearsal is a form of self-talk used to support short-term memory. Historically, the study of rehearsal development has diverged from the study of self-talk more generally. The current experiment examines whether two characteristics of self-talk (impact of task difficulty and self-talk's narrative vs. planning purpose) are also observed in rehearsal. Eighty children, ages 4-7, were tasked with remembering the three-item and six-item lists over a 15-s delay. Children's spontaneous use of fixed rehearsal (i.e., immediate repetition of a just-presented item) and cumulative rehearsal (i.e., cycling through multiple items at a time) was documented from video recordings. Four-year-olds narrated item presentations using fixed rehearsal. Six- and seven-year-olds proactively planned for recall by engaging cumulative rehearsal. Five-year-olds used both forms of rehearsal, but their frequency of cumulative rehearsal was dependent on list length. Therefore, rehearsal is susceptible to task manipulations that affect other forms of self-talk. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Self-generated strategies in the phonological similarity effect.

Strategy use is an important source of individual differences during immediate serial reconstruction. However, not all strategies are equally suited for all tasks. Therefore, assessing participants' dynamic strategy selection across contexts is an important next step for reliable interpretation of individual differences in short-term memory span - in both experimental and clinical settings. Strategy use during reconstruction of phonologically similar and phonologically distinct word sets was directly assessed using a self-report questionnaire. In two experiments, participants reported consistent use of phonological strategies across word sets; however, participants reported additionally using non-phonological strategies (i.e., mental imagery and sentence generation) when tasked with remembering phonologically similar words. In particular, strategy selection was most impacted when the phonologically similar word set was either the only word set or the first word set participants received. When the phonologically similar lists were presented after a classic list of phonologically distinct words, participants continued using the phonological strategies that had been effective for the distinct lists. Moreover, in both experiments, accuracy of phonologically similar lists was better predicted by use of non-phonological strategies than use of phonological strategies. Specifically, reported use of verbalization or rehearsal did not predict accuracy, but participants who reported regularly using mental imagery and/or sentence generation (typically in conjunction with rehearsal) displayed greater serial memory for similar words. These results do not undermine the general assumptions of the phonological similarity effect, but they do indicate that its interpretation is less straightforward than previously thought.

Emission ratio determination from road vehicles using a range of remote emission sensing techniques.

The development of remote emission sensing techniques such as plume chasing and point sampling has progressed significantly and is providing new insight into vehicle emissions behaviour. However, the analysis of remote emission sensing data can be highly challenging and there is currently no standardised method available. In this study we present a single data processing approach to quantify vehicle exhaust emissions measured using a range of remote emission sensing techniques. The method uses rolling regression calculated over short time intervals to derive the characteristics of diluting plumes. We apply the method to high time-resolution plume chasing and point sampling data to quantify gaseous exhaust emission ratios from individual vehicles. Data from a series of vehicle emission characterisation experiments conducted under controlled conditions is used to demonstrate the potential of this approach. First, the method is validated through comparison with on-board emission measurements. Second, the ability of this approach to detect changes in NOx / CO2 ratios associated with aftertreatment system tampering and different engine operating conditions is shown. Third, the flexibility of the approach is demonstrated by varying the pollutants used as regression variables and quantifying the NO2 / NOx ratios for different vehicle types. A higher proportion of total NOx is emitted as NO2 when the selective catalytic reduction system of the measured heavy duty truck is tampered. In addition, the applicability of this approach to urban environments is illustrated using mobile measurements conducted in Milan, Italy in 2021. Emissions from local combustion sources are distinguished from a complex urban background and the spatiotemporal variability in emissions is shown. The mean NOx / CO2 ratio of 1.61 ppb/ppm is considered representative of the local vehicle fleet. It is envisaged that this approach can be used to quantify emissions from a range of mobile and stationary fuel combustion sources, including non-road vehicles, ships, trains, boilers and incinerators.

The Detection of Foreign Items in Laundry Industry by Dual-Energy X-ray Transmission-Advantages and Limits.

Firefighters, paramedics, nursing staff, and other occupational groups are in constant need of fast and proper cleaning of their professional workwear, not only during a pandemic. Thus, laundry technology needs to become more efficient and automated. Unfortunately, some steps of the cleaning process, such as finding and removing foreign items from pockets or belts, are still completed manually. This is not just time-consuming but potentially dangerous for the workers due to the hazardous nature of items such as scissors, scalpels, or syringes. Additionally, some items may damage the garments by staining or harm the laundry machines, causing malfunctions and process failure. On the one hand, these foreign items are often hidden inside the clothes, making detection very challenging with conventional superficial sensors. On the other hand, these items can be diverse and cannot be detected by metal detectors alone. X-ray transmission has proven to be a powerful tool for detecting items inside of objects. The dual-energy approach (DE-XRT) even allows obtaining quantitative information about the chemical composition of the measured materials. In this study, working garments were accompanied and filled with realistic foreign items. The potential of DE-XRT to detect those items was successfully shown.

RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin.

Pausing of RNA polymerase II (Pol II) close to promoters is a common regulatory step in RNA synthesis, and is coordinated by a ribonucleoprotein complex scaffolded by the noncoding RNA RN7SK. The function of RN7SK-regulated gene transcription in adult tissue homoeostasis is currently unknown. Here, we deplete RN7SK during mouse and human epidermal stem cell differentiation. Unexpectedly, loss of this small nuclear RNA specifically reduces transcription of numerous cell cycle regulators leading to cell cycle exit and differentiation. Mechanistically, we show that RN7SK is required for efficient transcription of highly expressed gene pairs with bidirectional promoters, which in the epidermis co-regulated cell cycle and chromosome organization. The reduction in transcription involves impaired splicing and RNA decay, but occurs in the absence of chromatin remodelling at promoters and putative enhancers. Thus, RN7SK is directly required for efficient Pol II transcription of highly transcribed bidirectional gene pairs, and thereby exerts tissue-specific functions, such as maintaining a cycling cell population in the epidermis.

Potential of Dual and Multi Energy XRT and CT Analyses on Iron Formations.

Dual and multi energy X-ray transmission imaging (DE-/ME-XRT) are powerful tools to acquire quantitative material characteristics of diverse samples without destruction. As those X-ray imaging techniques are based on the projection onto the imaging plane, only two-dimensional data can be obtained. To acquire three-dimensional information and a complete examination on topology and spatial trends of materials, computed tomography (CT) can be used. In combination, these methods may offer a robust non-destructive testing technique for research and industrial applications. For example, the iron ore mining and processing industry requires the ratio of economic iron minerals to siliceous waste material for resource and reserve estimations, and for efficient sorting prior to beneficiation, to avoid equipment destruction due to highly abrasive quartz. While XRT provides information concerning the thickness, areal density and mass fraction of iron and the respective background material, CT may deliver size, distribution and orientation of internal structures. Our study shows that the data provided by XRT and CT is reliable and, together with data processing, can be successfully applied for distinguishing iron oxide rich parts from waste. Furthermore, heavy element bearing minerals such as baryte, uraninite, galena and monazite can be detected.

Verification of a National Emission Inventory and Influence of On-road Vehicle Manufacturer-Level Emissions.

Road vehicles make important contributions to a wide range of pollutant emissions from the street level to global scales. The quantification of emissions from road vehicles is, however, highly challenging given the number of individual sources involved and the myriad factors that influence emissions such as fuel type, emission standard, and driving behavior. In this work, we use highly detailed and comprehensive vehicle emission remote sensing measurements made under real driving conditions to develop new bottom-up inventories that can be compared to official national inventory totals. We find that the total UK passenger car and light-duty van emissions of nitrogen oxides (NOx) are underestimated by 24-32%, and up to 47% in urban areas, compared with the UK national inventory, despite agreement within 1.5% for total fuel used. Emissions of NOx at a country level are also shown to vary considerably depending on the mix of vehicle manufacturers in the fleet. Adopting the on-road mix of vehicle manufacturers for six European countries results in up to a 13.4% range in total emissions of NOx. Accounting for the manufacturer-specific fleets at a country level could have a significant impact on emission estimates of NOx and other pollutants across the European countries, which are not currently reflected in emission inventories.

Noncanonical functions of the serine-arginine-rich splicing factor (SR) family of proteins in development and disease.

Members of the serine/arginine (SR)-rich protein family of splicing factors play versatile roles in RNA processing steps and are often essential for normal development. Dynamic changes in RNA processing and turnover allow fast cellular adaptions to a changing microenvironment and thereby closely cooperate with transcription factor networks that establish cell identity within tissues. SR proteins play fundamental roles in the processing of pre-mRNAs by regulating constitutive and alternative splicing. More recently, SR proteins have also been implicated in other aspects of RNA metabolism such as mRNA stability, transport and translation. The- emerging noncanonical functions highlight the multifaceted functions of these SR proteins and identify them as important coordinators of gene expression programmes. Accordingly, most SR proteins are essential for normal cell function and their misregulation contributes to human diseases such as cancer.

Validation of the 4-aminophenol color test for the differentiation of marijuana-type and hemp-type cannabis.

The analysis of cannabis plant material submitted to seized-drug laboratories was significantly affected by the signing of the Agricultural Improvement Act of 2018, which defined hemp and removed it from the definition of marijuana in the Controlled Substances Act. As a result, field law enforcement personnel and forensic laboratories now are in need of implementing new protocols that can distinguish between marijuana-type and hemp-type cannabis. Colorimetric tests provide a cost-effective and efficient manner to presumptively identify materials prior to submission to a laboratory for analysis. This work presents the validation of the 4-aminophenol (4-AP) color test and demonstrates its utility for discriminating between marijuana-type and hemp-type cannabis (i.e., typification). Validation studies included the testing of numerous cannabinoid reference materials, household herbs, previously characterized cannabis plant samples, and real-case samples. The 4-AP test reliably produces a pink result when the level of Δ9 -tetrahydrocannabinol (THC) is approximately three times lower than the level of cannabidiol (CBD). A blue result is generated when the level of THC is approximately three times higher than that of CBD. Inconclusive results are observed when the levels of THC and CBD are within a factor of three from each other, demonstrating the limitations of the test under those scenarios.

Validation of two methods for the quantitative analysis of cocaine and opioids in biological matrices using LCMSMS.

The proliferation of misuse of prescription and non-prescription opioids, in recent years, has caused an opioid epidemic in the United States. Forensic toxicology laboratories often encounter implications of abuse in both driving under the influence of drugs and death investigation cases. The Virginia Department of Forensic Science has seen over a 190% increase in the number of reported opioids in death investigation cases over the past several years. Traditionally, analyses are completed by individual drug class, which subsequently requires an individual case to be evaluated using multiple analytical techniques for comprehensive analysis. To ease the impact of increasing case submissions and case complexity, two liquid chromatography-tandem mass spectrometry (LCMSMS) methods for the quantitative analysis of opioids, cocaine, and cocaine metabolites in biological matrices have undergone a fit-for-purpose validation. The methods were compared to determine the advantages and disadvantages of each analytical technique. Two sample preparation techniques, protein precipitation and solid-phase extraction, were employed for quantitative validation. Validation aspects evaluated included accuracy and precision, sensitivity, linearity, matrix effects, recovery, carryover, interferences, dilution integrity, and post-extraction stability. The accuracy of the protein precipitation method ranged from 80 ± 3% to 101 ± 10%. The accuracy of the solid-phase extraction method ranged from 88 ± 9% to 119 ± 3%. Additionally, within-run and intermediate precision was within ±20% for both extraction techniques. Although ionization suppression was noted, it was determined to have minimal effect on the methods. The newly developed methods require less sample volume and combine four analytical techniques into one method, which significantly impacts laboratory productivity.

Underestimated Ammonia Emissions from Road Vehicles.

In this study, we use comprehensive vehicle emission remote sensing measurements of over 230,000 passenger cars to estimate total UK ammonia (NH3) emissions. Estimates are made using "top-down" and "bottom-up" methods that demonstrate good agreement to within 1.1% for total fuel consumed or CO2 emitted. A central component of this study is the comprehensive nature of the bottom-up emission estimates that combine highly detailed remote sensing emission data with over 4000 km of 1 Hz real driving data. Total annual UK NH3 emissions from gasoline passenger cars are estimated to be 7.8 ± 0.3 kt from the bottom-up estimate compared with 3.0 ± 1.7 kt reported by the UK national inventory. An important conclusion from the analysis is that both methodologies confirm that gasoline passenger car NH3 emissions are underestimated by a factor of about 2.6 compared with the 2018 UK National Atmospheric Emissions Inventory. Furthermore, we find that inventory estimates of urban emissions of NH3 for passenger cars are underestimated by a factor of 17.

Automatic human identification based on dental X-ray radiographs using computer vision.

A person may be identified by comparison between ante- and post-mortem dental panoramic radiographs (DPR). However, it is difficult to find reference material if the person is unknown. This is often the case when victims of crime or mass disaster are found. Computer vision can be a helpful solution to automate the finding of reference material in a large database of images. The purpose of the present study was to improve the automated identification of unknown individuals by comparison of ante- and post-mortem DPR using computer vision. The study includes 61,545 DPRs from 33,206 patients, acquired between October 2006 and June 2018. The matching process is based on the Speeded Up Robust Features (SURF) algorithm to find unique corresponding points between two DPRs (unknown person and database entry). The number of matching points found is an indicator for identification. All 43 individuals (100%) were successfully identified by comparison with the content of the feature database. The experimental setup was designed to identify unknown persons based on their DPR using an automatic algorithm system. The proposed tool is able to filter large databases with many entries of potentially matching partners. This identification method is suitable even if dental characteristics were removed or added in the past.

Loss of 5-methylcytosine alters the biogenesis of vault-derived small RNAs to coordinate epidermal differentiation.

The presence and absence of RNA modifications regulates RNA metabolism by modulating the binding of writer, reader, and eraser proteins. For 5-methylcytosine (m5C) however, it is largely unknown how it recruits or repels RNA-binding proteins. Here, we decipher the consequences of m5C deposition into the abundant non-coding vault RNA VTRNA1.1. Methylation of cytosine 69 in VTRNA1.1 occurs frequently in human cells, is exclusively mediated by NSUN2, and determines the processing of VTRNA1.1 into small-vault RNAs (svRNAs). We identify the serine/arginine rich splicing factor 2 (SRSF2) as a novel VTRNA1.1-binding protein that counteracts VTRNA1.1 processing by binding the non-methylated form with higher affinity. Both NSUN2 and SRSF2 orchestrate the production of distinct svRNAs. Finally, we discover a functional role of svRNAs in regulating the epidermal differentiation programme. Thus, our data reveal a direct role for m5C in the processing of VTRNA1.1 that involves SRSF2 and is crucial for efficient cellular differentiation.

Forensic Odontology: Automatic Identification of Persons Comparing Antemortem and Postmortem Panoramic Radiographs Using Computer Vision.

PURPOSE: In forensic odontology the comparison between antemortem and postmortem panoramic radiographs (PRs) is a reliable method for person identification. The purpose of this study was to improve and automate identification of unknown people by comparison between antemortem and postmortem PR using computer vision. MATERIALS AND METHODS: The study includes 43 467 PRs from 24 545 patients (46 % females/54 % males). All PRs were filtered and evaluated with Matlab R2014b including the toolboxes image processing and computer vision system. The matching process used the SURF feature to find the corresponding points between two PRs (unknown person and database entry) out of the whole database. RESULTS: From 40 randomly selected persons, 34 persons (85 %) could be reliably identified by corresponding PR matching points between an already existing scan in the database and the most recent PR. The systematic matching yielded a maximum of 259 points for a successful identification between two different PRs of the same person and a maximum of 12 corresponding matching points for other non-identical persons in the database. Hence 12 matching points are the threshold for reliable assignment. CONCLUSION: Operating with an automatic PR system and computer vision could be a successful and reliable tool for identification purposes. The applied method distinguishes itself by virtue of its fast and reliable identification of persons by PR. This Identification method is suitable even if dental characteristics were removed or added in the past. The system seems to be robust for large amounts of data. KEY POINTS: · Computer vision allows an automated antemortem and postmortem comparison of panoramic radiographs (PRs) for person identification.. · The present method is able to find identical matching partners among huge datasets (big data) in a short computing time.. · The identification method is suitable even if dental characteristics were removed or added.. CITATION FORMAT: · Heinrich A, Güttler F, Wendt S et al. Forensic Odontology: Automatic Identification of Persons Comparing Antemortem and Postmortem Panoramic Radiographs Using Computer Vision. Fortschr Röntgenstr 2018; 190: 1152 - 1158.

Body dissatisfaction and suicidal ideation among psychiatric inpatients with eating disorders.

The current study the relationship between eating disorders (EDs) and suicidal ideation and suicide attempt in adult inpatients. In particular, the present study investigated one potential mechanism, body dissatisfaction (BD), which may contribute to increased risk for suicide in adult ED patients. A sample of 432 psychiatric inpatients ranging from 18 to 65 years of age participated in the current study. Findings indicated that patients who have higher levels of BD also had higher levels of passive and active suicidal ideation and previous suicide attempts. Higher levels of BD were also related to increased suicidal ideation after controlling for depression and emotion dysregulation. Although additional risk factors for suicide should be investigated in adults with EDs, this study provides evidence regarding the relationship between BD and risk for suicide ideation and attempt.

Considerations for skin carcinogenesis experiments using inducible transgenic mouse models.

OBJECTIVE: This study was designed to estimate the percentage of non-malignant skin tumours (papillomas) progressing to malignant squamous cell carcinomas (SCCs) in a carcinogenesis study using established transgenic mouse models. In our skin cancer model, we conditionally induced oncogenic point mutant alleles of p53 and k-ras in undifferentiated, basal cells of the epidermis. RESULTS: Upon activation of the transgenes through administration of tamoxifen, the vast majority of mice (> 80%) developed skin papillomas, yet primarily around the mouth. Since these tumours hindered the mice eating, they rapidly lost weight and needed to be culled before the papillomas progressed to SCCs. The mouth papillomas formed regardless of the route of application, including intraperitoneal injections, local application to the back skin, or subcutaneous insertion of a tamoxifen pellet. Implantation of a slow releasing tamoxifen pellet into 18 mice consistently led to papilloma formation, of which only one progressed to a malignant SCC. Thus, the challenges for skin carcinogenesis studies using this particular cancer mouse model are low conversion rates of papillomas to SCCs and high frequencies of mouth papilloma formation.

Energy depletion and not ROS formation is a crucial step of glucolipotoxicity (GLTx) in pancreatic beta cells.

We have shown previously that genetic or pharmacological deletion of KATP channels protect against beta cell dysfunction induced by reactive oxygen species (ROS). Since it is assumed that glucolipotoxicity (GLTx) causes ROS production, we aimed to evaluate whether suppression of KATP channel activity can also prevent beta cell damage evoked by GLTx. We used an in vitro model of GLTx and measured distinct parameters of stimulus-secretion coupling. GLTx gradually induced disturbances of Ca2+ oscillations over 3 days. This impairment in Ca2+ dynamics was partially reversed in beta cells without functional KATP channels (SUR1-/-) and by the sulfonylurea gliclazide but not by tolbutamide. By contrast, the GLTx-induced suppression of glucose-induced insulin secretion could not be rescued by decreased KATP channel activity pointing to a direct interaction of GLTx with the secretory capacity. Accordingly, GLTx also suppressed KCl-induced insulin secretion. GLTx was not accompanied by decisively increased ROS production or enhanced apoptosis. Insulin content of beta cells was markedly reduced by GLTx, an effect not prevented by gliclazide. Since GLTx markedly diminished the mitochondrial membrane potential and cellular ATP content, lack of ATP is assumed to decrease insulin biosynthesis. The deleterious effect of GLTx is therefore caused by direct interference with the secretory capacity whereby reduction of insulin content is one important parameter. These findings deepen our understanding how GLTx damages beta cells and reveal that GLTx is disconnected from ROS formation, a notion important for targeting beta cells in the treatment of diabetes. Overall, GLTx-induced energy depletion may be a primary step in the cascade of events leading to loss of beta cell function in type-2 diabetes mellitus.

Clinical Barriers to Effective Treatment of Eating Disorders and Co-occurring Psychiatric Disorders in Transgendered Individuals.

Eating disorders (EDs) are complex and difficult to treat illnesses that are often chronic and disabling on their own accord or due to comorbidity with other psychiatric conditions. Historically, EDs have been viewed as illnesses of heterosexual, affluent white females. This stereotype increases the likelihood that these disorders will be underrecognized in the lesbian, gay, bisexual, and transgender community, as well as in different gender, socioeconomic, and ethnic populations. Our case report illustrates the clinical difficulties of managing a patient who presented to inpatient treatment with complaints of depression and suicidality, but who also had an active ED and was transgender.

Expression of Hsp27 and Hsp70 and vacuolization in the pituitary glands in cases of fatal hypothermia.

Hypothermia causes systemic cellular stress. The pituitary gland is an endocrine gland and plays an important role in thermoregulation. When the core body temperature drops, the pituitary gland is activated by stimulation of hypothalamic hormones. In this study, we investigated morphological alterations of the pituitary gland in cases of fatal hypothermia. Several morphological alterations of the anterior lobe of the pituitary gland, such as hemorrhage, vacuolization, and hyperemia, have been previously described in fatal hypothermia. However, the diagnostic value of these findings is controversial. We compared 11 cases of fatal hypothermia with 10 cases lacking antemortem hypothermic influences. In the presence of thermal cellular stress, the expression of heat shock proteins increases to protect cellular structures. Therefore, we immunohistochemically analyzed Hsp27 and Hsp70. Hsp27 expression was detected in 27.3% of the cases of fatal hypothermia and in 10.0% of the control cases, whereas Hsp70 expression was not detected in any case. Additionally, Sudan staining was performed to quantify fatty degeneration. A positive reaction was found in 45.5% of the study group and in 10.0% of the control group. This indicates that fatty degeneration might be a valuable marker when other macroscopic signs of hypothermia are absent.