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Combining high‐throughput generation and high‐content imaging of embryo models will enable large‐scale screening assays in the fields of (embryo) toxicity, drug development, embryogenesis, and reproductive medicine. This study shows the continuous culture and in situ (i.e., in microwell) imaging‐based readout of a 3D stem cell‐based model of peri‐implantation epiblast (Epi)/extraembryonic endoderm (XEn) development with an expanded pro‐amniotic cavity (PAC) (E3.5 E5.5), namely XEn/EPiCs. Automated image analysis and supervised machine learning permit the identification of embryonic morphogenesis, tissue compartmentalization, cell differentiation, and consecutive classification. Screens with signaling pathway modulators at different time windows provide spatiotemporal information on their phenotypic effect on developmental processes leading to the formation of XEn/EPiCs. Exposure of the biological model in the microwell platform to pathway modulators at two time windows, namely 0–72 h and 48–120 h, show that Wnt and Fgf/MAPK pathway modulators affect Epi differentiation and its polarization, while modulation of BMP and Tgfβ/Nodal pathway affects XEn specification and epithelialization. Further, their collective role is identified in the timing of the formation and expansion of PAC. The newly developed, scalable culture and analysis platform, thereby, provides a unique opportunity to quantitatively and systematically study effects of pathway modulators on early embryonic development. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNA-seq) has become a popular technique for interrogating the diversity and dynamic nature of cellular gene expression and has numerous advantages in immunology. For example, scRNA-seq, in contrast to bulk RNA sequencing, can discern cellular subtypes within a population, which is important for heterogenous populations such as T cells. Moreover, recent advancements in the technology allow the parallel capturing of the highly diverse T-cell receptor (TCR) sequence with the gene expression. However, the field of single-cell RNA sequencing data analysis is still hampered by a lack of gold-standard cell phenotype annotation. This problem is particularly evident in the case of T cells due to the heterogeneity in both their gene expression and their TCR. While current cell phenotype annotation tools can differentiate major cell populations from each other, labelling T-cell subtypes remains problematic. In this review, we identify the common automated strategy for annotating T cells and their subpopulations, and also describe what crucial information is still missing from these tools. [ABSTRACT FROM AUTHOR]

Background/Aim: has shown that sketching while narrating facilitates the elicitation of information and verbal veracity cues in single interviews. We examined if these effects are retained when suspects are shown their sketch after one week in a repeated interview. Method: Participants (N = 173) completed a mock mission and then told the truth or lied about it in an immediate interview (interview 1). Participants either verbally reported the mission (Free recall condition) or sketched it while describing what they were sketching (sketch condition). After one week, all participants were asked for a free recall without sketching (interview 2). Half of the participants in the Sketch condition had access to their sketch while they verbally reported the event whereas the remaining half did not access the sketch. Results: Truth tellers provided more information than lie tellers in both interviews, and sketching elicited more information than a free recall but only in Interview 1. Participants who had access to their sketch in interview 2 repeated more information than those who did not have access, but accessing the sketch did not have an effect on veracity cues. Conclusions: Thus, sketching enhanced the elicitation of information in Interview 1 and access to the sketch in interview 2 seemed helpful for recalling previously reported information. [ABSTRACT FROM AUTHOR]

Abstract The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it has not been possible to efficiently generate Purkinje neuron (PN) progenitors from human or mouse pluripotent stem cells, let alone to develop a methodology for in vivo transplantation in the adult cerebellum. Here, we present a protocol to obtain an expandable population of cerebellar neuron progenitors from mouse embryonic stem cells. Our protocol is characterized by applying factors that promote proliferation of cerebellar progenitors. Cerebellar progenitors isolated in culture from cell aggregates contained a stable subpopulation of PN progenitors that could be expanded for up to 6 passages. When transplanted into the adult cerebellum of either wild-type mice or a strain lacking Purkinje cells (L7cre-ERCC1 knockout), GFP-labeled progenitors differentiated in vivo to establish a population of calbindin-positive cells in the molecular layer with dendritic trees typical of mature PNs. We conclude that this protocol may be useful for the generation and maturation of PNs, highlighting the potential for development of a regenerative medicine approach to the treatment of cerebellar neurodegenerative diseases.

The conditionally replicating oncolytic adenovirus Delta24-RGD (Ad) is currently under investigation in clinical trials for glioblastoma, including in combination with temozolomide (TMZ), the standard chemotherapy for this tumor. Previously, we showed that the efficacy of Delta24-RGD in a murine model is primarily dependent on the virus-induced anti-tumor immune response. As observed with most chemotherapies, TMZ has pronounced immune-modulating effects. Here, we studied the combined effects of these treatments in a murine glioma model. In vitro, we observed a synergistic activity between Delta24-RGD and TMZ. In vivo, C57BL/6 mice bearing intracranial GL261 tumors were treated with TMZ for 5 days either prior to intratumoral Delta24-RGD injection (TMZ/Ad) or post virus injection (Ad/TMZ). Notably, the Ad/TMZ regimen led to similar tumoral CD8+ T cell influx as the virus-only treatment, but increased the ability of CD8+ T cells to specifically recognize the tumor cells. This was accompanied by improved survival. The TMZ/Ad regimen also improved survival significantly compared to controls, but not compared to virus alone. In this group, the influx of dendritic cells is impaired, followed by a significantly lower number of tumor-infiltrating CD8+ T cells and no recognition of tumor cells. Depletion of either CD4+ T cells or CD8+ T cells impaired the efficacy of Delta24-RGD, underscoring the role of these cells in therapeutic activity of the virus. Overall, we show that the addition of TMZ to Delta24-RGD treatment leads to a significant increase in survival and that the order of sequence of these treatments affects the CD8+T cell anti-tumor activity.

Meta-analytic findings indicate that the success of unmasking a deceptive interaction relies more on the performance of the liar than on that of the lie detector. Despite this finding, the lie characteristics and strategies of deception that enable good liars to evade detection are largely unknown. We conducted a survey (n = 194) to explore the association between laypeople's self-reported ability to deceive on the one hand, and their lie prevalence, characteristics, and deception strategies in daily life on the other. Higher self-reported ratings of deception ability were positively correlated with self-reports of telling more lies per day, telling inconsequential lies, lying to colleagues and friends, and communicating lies via face-to-face interactions. We also observed that self-reported good liars highly relied on verbal strategies of deception and they most commonly reported to i) embed their lies into truthful information, ii) keep the statement clear and simple, and iii) provide a plausible account. This study provides a starting point for future research exploring the meta-cognitions and patterns of skilled liars who may be most likely to evade detection.

Most of deception research has focused on past events that were either completely truthful or a complete fabrication. However, people often tell a mixture of truths and lies. This could enable investigators to make within-subjects comparisons between different themes discussed in one interview, which we examined in the current experiment. Seventy-three participants took part in the experiment and were asked to either tell the truth about two themes, or to tell the truth about one theme and lie about the second theme in a HUMINT setting. Results showed that examining the differences in the amount of detail provided by the interviewees for each theme- obtained through a Theme-Selection strategy (a within-subjects measure)- yielded stronger results than examining differences between truth tellers and liars based on the entire interview without accounting for themes (between-subjects measure). The present study therefore highlighted the effectiveness of within-subjects measurements to both discriminate truth tellers from liars and to discover which section of a statement is false.

Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better understand this underlying functionality, we first collected all known leishmaniasis-associated HLA variants in a thorough literature review. Next, we aligned and compared the protection- and risk-associated HLA-DRB1 allele sequences. This identified several amino acid polymorphisms that distinguish protection- from risk-associated HLA-DRB1 alleles. Subsequently, T cell epitope binding predictions were carried out across these alleles to map the impact of these polymorphisms on the epitope binding repertoires. For these predictions, we used epitopes derived from entire proteomes of multiple Leishmania species. Epitopes binding to protection-associated HLA-DRB1 alleles shared common binding core motifs, mapping to the identified HLA-DRB1 amino acid polymorphisms. These results strongly suggest that HLA polymorphism, resulting in differential antigen presentation, affects the association between HLA and leishmaniasis disease development. Finally, we established a valuable open-access resource of putative epitopes. A set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, was prioritized for further epitope discovery in the search for novel subunit-based vaccines.

Previous research indicated that drawing is a strategic tool in investigations. However, little research has been conducted to determine how to introduce a sketch instruction into an investigative interview. The current experiment compared sketching and speaking separately (sketch‐speak and speak‐sketch conditions) with sketching and speaking synchronously to determine which recall method gathered the most information and elicited the most cues to deceit. Participants (N = 180) watched a video, half were asked to tell the truth (to a friendly agent), whereas the other half were asked to lie (to a corrupt agent) about the video in an interview. Participants were asked either to (i) sketch then speak, (ii) speak then sketch, or (iii) speak and sketch synchronously. Verbal statements and sketches were coded for total details, number of people, number of self‐handicapping strategies and plausibility. The camera perspective of sketches was also examined. Truth tellers' sketches and verbal statements were rated as more plausible than those of lie tellers. This difference was found in all three recall methods with the largest effect emerging in the speaking and sketching synchronously condition. Truth tellers included more details than lie tellers in their verbal statements but not in their sketches. Conversely, truth tellers included more people than lie tellers in their sketches but not in their verbal responses. No veracity differences emerged in sketches nor verbal statements for self‐handicapping strategies. However, participants in the speaking and sketching synchronously recall method included more sketch self‐handicapping strategies than those in the other recall conditions. Additionally, participants in the speak and sketch synchronously method reported more verbal details than those who spoke and then sketched. Effects were not large enough between speaking in isolation of sketching and also sketching and speaking synchronously to determine which recall method is best to detect deceit. However, sketching and speaking synchronously emerged as the most beneficial method for information‐gathering. [ABSTRACT FROM AUTHOR]