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With the rapid advances in technology and life science, biological security is now at a defining moment. The mandate of the 2022 Biological and Toxin Weapons Convention 9th Review Conference emphasised the urgent need for new tools to strengthen the Convention. In this paper, we review the development and efforts of the International Nuclear Security Education Network (INSEN) to provide examples of best practice for implementation of the newly founded International Biological Security Education Network (IBSEN). Learning from the lessons of the INSEN, the sustainability of the network through continuous engagement of its members is essential for the further development of global biosecurity education.

Abstract Background Auditory reaction time (ART) and visual reaction time (VRT) are critical for patients with stroke, especially during balance training. According to the research, most patients with stroke are fatigued at sub-maximal levels during their stroke rehabilitation. Sub-maximal physical fatigue may affect ART and VRT and impede stroke rehabilitation. Hence, it is important to study the effect of submaximal physical fatigue on ART and VRT. A pilot study on healthy adults paves the way for further research on stroke rehabilitation. The purpose of this research is to find out if submaximal physical fatigue affects ART and VRT in healthy adults. In addition, this study also determines if ART and VRT recover to baseline after 15 min of rest post-fatigue session. Furthermore, the goal is to determine whether sub-maximal physical fatigue has a greater effect on ART or VRT. Methods A repeated measures within-subject design was used in the study. Eighteen healthy participants (median age 24 years) completed two sessions of a sub-maximal fatigue protocol on a cycle ergometer until they reached a rating of perceived exertion (RPE) of 15 on a scale of 6–20. Two different fatigue sessions were conducted (one to study the effects of fatigue on ART and the other for VRT). ART or VRT was measured on computer software before (PRE), immediately after (POST-0), and 15 min after (POST-15) the sub-maximal physical fatigue protocol. Results The value of median ART increased significantly from PRE to POST-0 (P = 0.002) and it decreased significantly at POST-15 (P = 0.010). Similarly, the value of mean VRT increased from PRE to POST-0 (P = 0.001) before decreasing significantly at POST-15 (P = 0.001). There was no significant difference between the effects of submaximal fatigue on ART and VRT (P = 0.156). Conclusion Due to submaximal physical fatigue, ART and VRT were slower, but they returned to baseline after 15 min of rest. Submaximal physical fatigue had an equal impact on ART and VRT. As balance training requires quicker ART and VRT for optimal outcomes, it may be better if the physiotherapists consider a 15-min rest period between the exercise and balance training in patients with stroke.

Abstract Background Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5 −/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5 −/y rats. Methods To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology. Results Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5 −/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca2+ permeable AMPA receptor mediated currents are unchanged in Cdkl5 −/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses. Conclusions Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity. Limitations This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD.

In this paper we highlight how the apparent double coverage of toxins and bioregulators by both the Biological and Toxin Weapons Convention (BTWC) and the Chemical Weapons Convention (CWC) in fact masks a regulatory gap that has left such potentially dangerous agents neglected by both the control regimes during a period of rapid advances in relevant chemical, life and associated sciences and technologies. We first review what toxins, bioregulators and other mid-spectrum agents are and why they are of such concern and then examine how they are regulated under the BTWC and CWC. This paper then examines an illustrative range of contemporary chemical and life science research and associated activities of concern drawn from case study research on China, India, Iran, Russia, Syria and the United States, and assesses how the CWC and BTWC States Parties have inadequately addressed these threats. We then examine how both the CWC and BTWC Review Conferences failed to address these long-term challenges, and we end by providing a series of recommendations for how both regimes can be strengthened in this area.

Abstract Cancer’s complexity is in part due to the presence of intratumor heterogeneity and the dynamic nature of cancer cell plasticity, which create substantial obstacles in effective cancer management. Variability within a tumor arises from the existence of diverse populations of cancer cells, impacting the progression, spread, and resistance to treatments. At the core of this variability is the concept of cellular plasticity - the intrinsic ability of cancer cells to alter their molecular and cellular identity in reaction to environmental and genetic changes. This adaptability is a cornerstone of cancer’s persistence and progression, making it a formidable target for treatments. Emerging studies have emphasized the critical role of such plasticity in fostering tumor diversity, which in turn influences the course of the disease and the effectiveness of therapeutic strategies. The transformative nature of cancer involves a network of signal transduction pathways, notably those that drive the epithelial-to-mesenchymal transition and metabolic remodeling, shaping the evolutionary path of cancer cells. Despite advancements, our understanding of the precise molecular machinations and signaling networks driving these changes is still evolving, underscoring the necessity for further research. This editorial presents a series entitled “Signaling Cancer Cell Plasticity and Intratumor Heterogeneity” in Cell Communication and Signaling, dedicated to unraveling these complex processes and proposing new avenues for therapeutic intervention.

Rodent studies have shown that alternative splicing in neurons plays important roles in development and maturity, and is regulatable by signals such as electrical activity. However, rodent-human similarities are less well explored. We compared basal and activity-dependent exon splicing in cortical-patterned human ESC-derived neurons with that in cortical mouse ESC-derived neurons, primary mouse cortical neurons at two developmental stages, and mouse hippocampal neurons, focussing on conserved orthologous exons. Both basal exon inclusion levels and activity-dependent changes in splicing showed human-mouse correlation. Conserved activity regulated exons are enriched in RBFOX, SAM68, NOVA and PTBP targets, and centered on cytoskeletal organization, mRNA processing, and synaptic signaling genes. However, human-mouse correlations were weaker than inter-mouse comparisons of neurons from different brain regions, developmental stages and origin (ESC vs. primary), suggestive of some inter-species divergence. The set of genes where activity-dependent splicing was observed only in human neurons were dominated by those involved in lipid biosynthesis, signaling and trafficking. Study of human exon splicing in mouse Tc1 neurons carrying human chromosome-21 showed that neuronal basal exon inclusion was influenced by cis-acting sequences, although may not be sufficient to confer activity-responsiveness in an allospecific environment. Overall, these comparisons suggest that neuronal alternative splicing should be confirmed in a human-relevant system even when exon structure is evolutionarily conserved.

Abstract Mantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention. We interrogated BCR signaling proteins (SYK, LCK, BTK, PLCγ2, p38, AKT, NF-κB p65, and STAT5) in 30 primary MCL samples using phospho-specific flow cytometry. Anti-IgM modulation induced heterogeneous BCR signaling responses among samples allowing the identification of two clusters with differential responses. The cluster with higher response was associated with shorter progression free survival (PFS) and overall survival (OS). Moreover, higher constitutive AKT activity was predictive of inferior response to the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL.

Objective The metatarsophalangeal joints (MTPJs) are the most common location for synovitis in people with rheumatoid arthritis (RA), yet their association with plantar foot pressures has received very little attention. This study aimed to determine whether plantar pressures differed based on sonographic evidence of MTPJ synovitis in people with RA. Method Ultrasound was used to assess synovitis (grey scale synovial hypertrophy and power Doppler signal) in MTPJs 1 to 5 using the combined EULAR/Outcome Measures in Rheumatology scoring system. Peak pressure (PP) and pressure time integrals (PTIs) were assessed during barefoot walking for seven plantar foot regions (heel, midfoot, first metatarsal, second metatarsal, third to fifth metatarsals, hallux, lesser toes). Mixed‐effects linear regression was used to determine the difference in PP and PTI between MTPJs with none/minimal synovitis and MTPJs with moderate/severe synovitis. Results Thirty‐five participants with RA were included. Mean age was 66.3 years and mean disease duration was 22.2 years. Participants with sonographic evidence of moderate/severe synovitis at the first MTPJ had reduced PTI at the hallux compared with those with none/minimal synovitis at this joint (P = 0.039). Participants with moderate/severe synovitis at the second MTPJ and fourth MTPJ had reduced PP and reduced PTI at lesser toes compared with those with none/minimal synovitis in these joints (all P ≤ 0.048). No significant differences were observed for synovitis in other joints. Conclusion These findings may be suggestive of an inverse relationship between plantar pressure and soft tissue pathology, which is consistent with an offloading strategy and reduced use of the toes during propulsion.

Abstract Prostate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate of 95% in advanced stages. A myriad of molecular events and mutations, including the accumulation of oncometabolites, underpin the genesis and progression of this cancer type. Despite growing research demonstrating the pivotal role of oncometabolites in supporting various cancers, including prostate cancer, the root causes of their accumulation, especially in the absence of enzymatic mutations, remain elusive. Consequently, identifying a tangible therapeutic target poses a formidable challenge. In this review, we aim to delve deeper into the implications of oncometabolite accumulation in prostate cancer. We center our focus on the consequential epigenetic alterations and impacts on cancer stem cells, with the ultimate goal of outlining novel therapeutic strategies. Graphical Abstract

Objective: To elucidate the characteristics of infertile couples residing in the rural area of Nagekeo Regency and assess the outcomes of their participation in the local pregnancy program. Methods: We conducted a descriptive study at Aeramo Regional General Hospital (RGH) in Nagekeo Regency, Flores, East Nusa Tenggara (ENT), utilizing a total sampling technique from January 2020 to April 2022. A total of 56 couples participated in this study. Results: The analysis revealed that infertile couples at Aeramo RGH were typically aged between 23 and 35 years, with an average infertility duration exceeding 4 years. Primary infertility was the predominant condition (89.3%), with 55.4% of male partners exhibiting obesity. A significant number of male participants reported alcohol and cigarette consumption. Data were insufficient to determine the prevalence of infertility in men versus women. Notably, the outcomes of the pregnancy program in this region did not demonstrate significant improvements. Conclusions: This study identified potential risk factors such as smoking, alcohol consumption, and obesity that may contribute to infertility; however, it did not establish a strong correlation between these factors and infertility. Moreover, the pregnancy program's outcomes were inconclusive, likely due to limited diagnostic and treatment resources in the area. Keyword: infertility characteristics, pregnancy program, pregnancy outcomes. Abstrak Tujuan : Mendeskripsikan karakteristik pasangan infertil di Kabupaten Nagekeo serta mengetahui hasil luaran kehamilan bagi pasangan yang mengikuti program kehamilan di daerah tersebut. Metode : Penelitian ini merupakan penelitian deskriptif yang dilakukan di Rumah Sakit Umum Daerah (RSUD) Aeramo, Kabupaten Nagekeo, Flores, Nusa Tenggara Timur. Dengan menggunakan teknik total sampling pada periode Januari 2020 - April 2022, terdapat 56 pasangan yang bergabung dalam penelitian ini. Hasil : Hasil penelitian kemudian dianalisis secara univariat dan didapatkan usia pasangan infertil di Aeramo RGH adalah antara 23 - 35 tahun dengan durasi infertilitas lebih dari 4 tahun. Infertilitas primer dan obesitas pada pria mendominasi masing-masing kelompok yaitu 89,3% dan 55,4%. Mayoritas pria mengonsumsi alkohol dan rokok. Tidak ditemukan data yang cukup untuk menentukan apakah infertilitas terjadi pada pria atau wanita. Hasil dari program kehamilan yang dilakukan di daerah ini belum menunjukkan hasil yang signifikan. Kesimpulan : Karakteristik yang memicu faktor risiko seperti merokok, mengkonsumsi alkohol dan obesitas. Meskipun pada penelitian ini belum didapatkan korelasi yang kuat dari faktor risiko tersebut pada infertilitas. Hasil dari program kehamilan belum menunjukkan hasil yang signifikan karena modalitas diagnostik dan pengobatan yang sangat terbatas. Kata kunci : karakteristik infertilitas, luaran kehamilan, program hamil.

Citrus virus A (CiVA) was detected for the first time in Australia in a living pathogen collection. Buds were originally collected from a Washington navel field tree prior to 1970 and graft-inoculated onto a Symons sweet orange indicator plant. The virus was detected using conventional and quantitative reverse transcription polymerase chain reactions and high-throughput sequencing. This variant shares 96.3% (RNA1) and 96.7% (RNA2) nucleotide identity with isolates of CiVA from South Africa and China, respectively. Foliar symptoms of leaf flecking and oak leaf patterns, consistent with detections of CiVA in other regions, were observed on the foliage of the original accession and inoculated indicator plants. Subsequent surveys of an Australian citrus variety collection detected a different CiVA sequence variant in two accessions of Pera sweet orange; this variant had 97% similarity to the other Australian variant.

In this paper, we briefly discuss the historical issues concerning the Biological and Toxin Weapons Convention (BTWC) and analyse the current situation after the COVID-19 pandemic with emphasis on the new developments at 9th Review Conference of the BTWC. In particular, we discuss the mission of the new working group agreed at the review conference to identify, examine, and develop specific and effective measures, including possible legally binding measures and to make recommendations to strengthen and institutionalise the Convention in all its aspects, and compare it with productive activities associated with the Chemical Weapons Convention (CWC) and the World Health Organisation (WHO). The enhanced role for civil society in support of the BTWC is then proposed with some solid examples from our own recent projects. We hope this analysis will help to facilitate new thinking about strengthening BTWC in coming years.

Abstract Stakeholder acceptance and support is essential for long‐term success in species reintroductions, and assessing social feasibility of reintroductions within human‐occupied landscapes is an integral component of effective decision‐making. The Dalmatian pelican Pelecanus crispus is an extirpated British bird, and possible pelican reintroduction to British wetlands is under discussion. Any reintroduction planning must first assess local community awareness, attitudes, and acceptance of potential pelican arrival and associated habitat management, as part of wider socio‐ecological feasibility assessment. Pelicans are distinctive species with potential to increase support for wetland conservation, but might provoke conflict through real or perceived competition with landscape users such as fishers; such conflict is already seen within Britain between fishers and cormorants. We conducted an online survey of 590 respondents in the Somerset Levels and East Anglian Fens, Britain's largest wetland landscapes, to understand local views on pelican reintroduction, other reintroductions and wetland restoration, and to investigate correlates of varying attitudes toward coexistence with pelicans and five other waterbirds (grey heron, Eurasian bittern, little egret, common crane, great cormorant). Respondents had generally positive views about previous reintroductions of other species, and had overall positive attitudes toward all six waterbirds. Two‐thirds of respondents supported or strongly supported pelican reintroduction, but both benefits and concerns were identified in relation to its possible reintroduction. Anglers and hunters were more likely to hold negative attitudes toward pelicans, other waterbirds and wetland restoration. However, although anglers raised more concerns, they were not more likely to be unsupportive toward reintroduction. More socio‐demographic predictors were associated with negative attitudes toward restoration required to establish pelican habitat, suggesting that positive feelings toward biodiversity are outweighed by concerns around potential exclusion from local landscapes. Our findings suggest pelican reintroduction might be supported by local stakeholders. Attitudes toward cormorants do not represent a blueprint for attitudes toward pelicans, and anglers may support reintroduction if concerns around impacts to fish stocks are addressed. Community engagement for species‐specific and landscape‐scale actions require separate approaches, with landscape management planning needing to target a wider range of stakeholder groups with separate concerns to those about coexistence with pelicans. Read the free Plain Language Summary for this article on the Journal blog.

ABSTRACT: Photooxidation has long been affecting nutrient and sensory quality of fluid milk. Light oxidation starts from the activation of photosensitive compounds, followed by generation of singlet oxygen that reacts with vitamins, proteins, and lipids in milk. It is hypothesized that wavelength-tailored light schemes possessing spectral properties capable of avoiding excitation maxima of common photosensitizers in milk could slow the chemical degradation of light-exposed milk and thus preserve consumer acceptability. A series of 6 consumer tests with sample sizes from 95 to 119 participants tested hedonic responses to fluid milk samples exposed to light of varying wavelength spectra. For milk in clear plastic bottles (polyethylene terephthalate or high-density polyethylene), consumer panels generally liked milk exposed to light-emitting diodes eliminating wavelengths below 520 or 560 nm more than standard white light, or those eliminating other wavelength bands. This higher degree of liking coincided with panelists citing fewer off-flavors or aromas from these samples. Taken together, these observations suggest such light schemes can protect milk from light damage to some extent. Wavelength-tailored light schemes used in this study did not offer effective protection for milk in glass bottles. Dissolved oxygen, color, riboflavin loss, and hexanal content were instrumentally evaluated, but results failed to indicate significant signatures of light damage in milk compared with sensory measures. The appearance of milk bottles illuminated by the slightly greenish or yellowish light were less liked by consumers, suggesting further efforts on consumer education may be necessary if these light schemes were to be installed in retail dairy coolers.

Microglia play crucial roles in immune responses and contribute to fundamental biological processes within the central nervous system (CNS). In neurodegenerative diseases, microglia undergo functional changes and can have both protective and pathogenic roles. Microglia in the retina, as an extension of the CNS, have also been shown to be affected in many neurological diseases. While our understanding of how microglia contribute to pathological conditions is incomplete, non-invasive in vivo imaging of brain and retinal microglia in living subjects could provide valuable insights into their role in the neurodegenerative diseases and open new avenues for diagnostic biomarkers. This mini-review provides an overview of the current brain and retinal imaging tools for studying microglia in vivo. We focus on microglia targets, the advantages and limitations of in vivo microglia imaging approaches, and applications for evaluating the pathogenesis of neurological conditions, such as Alzheimer’s disease and multiple sclerosis.

Abstract Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes and mature myelin-forming oligodendrocytes – is a determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models, unbiased RNA sequencing, functional manipulation, and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned male mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.

Microglial endolysosomal (dys)function is strongly implicated in neurodegenerative disease. Transcriptomic studies show that a microglial state characterised by a set of genes involved in endolysosomal function is induced in both mouse Alzheimer’s disease (AD) models and human AD brain, and that the emergence of this state is emphasised in females. Cst7 (encoding cystatin F) is among the most highly upregulated genes in these microglia. However, despite such striking and robust upregulation, the function of Cst7 in neurodegenerative disease is not understood. Here, we crossed Cst7-/- mice with the AppNL-G-F mouse to test the role of Cst7 in a model of amyloid-driven AD. Surprisingly, we found that Cst7 plays a sexually dimorphic role regulating microglia in this model. In females, Cst7-/-AppNL-G-F microglia had greater endolysosomal gene expression, lysosomal burden, and amyloid beta (Aβ) burden in vivo and were more phagocytic in vitro. However, in males, Cst7-/-AppNL-G-F microglia were less inflammatory and had a reduction in lysosomal burden but had no change in Aβ burden. Overall, our study reveals functional roles for one of the most commonly upregulated genes in microglia across disease models, and the sex-specific profiles of Cst7-/--altered microglial disease phenotypes. More broadly, the findings raise important implications for AD including crucial questions on sexual dimorphism in neurodegenerative disease and the interplay between endolysosomal and inflammatory pathways in AD pathology.

Individuals with aphantasia report an inability to voluntarily visually image and reduced episodic memory, yet episodic accounts provided by witnesses and victims are fundamental for criminal justice. Using the mock-witness paradigm, we investigated eyewitness memory of individuals with aphantasia versus typical imagers. Participants viewed a mock crime and 48 hours later were interviewed about the event, randomly allocated to one of three conditions. Two interview conditions included techniques designed to support episodic retrieval mode, namely (i) Mental Reinstatement of Context (MRC) and (ii) Sketch Reinstatement of Context (Sketch-RC). A third Control condition did not include retrieval support. Aphantasic mock-eyewitnesses recalled 30% less correct information and accounts were less complete, but they made no more errors and were as accurate as typical imagers. Interaction effects revealed reduced correct recall and less complete accounts for aphantasic participants in MRC interviews versus Sketch-RC and Control. Aphantaisic participants in the Control outperformed those in both the Sketch-RC and MRC, although Sketch-RC improved completeness by 15% versus MRC. Our pattern of results indicates reduced mental imagery ability might be compensated for by alternative self-initiated cognitive strategies. Findings offer novel insights into episodic recall performance in information gathering interviews when ability to voluntarily visualize is impoverished.

Abstract Background Autism spectrum condition or ‘autism’ is associated with numerous genetic risk factors including the polygenic 16p11.2 microdeletion. The balance between excitatory and inhibitory neurons in the cerebral cortex is hypothesised to be critical for the aetiology of autism making improved understanding of how risk factors impact on the development of these cells an important area of research. In the current study we aim to combine bioinformatics analysis of human foetal cerebral cortex gene expression data with anatomical and electrophysiological analysis of a 16p11.2 +/- rat model to investigate how genetic risk factors impact on inhibitory neuron development. Methods We performed bioinformatics analysis of single cell transcriptomes from gestational week (GW) 8–26 human foetal prefrontal cortex and anatomical and electrophysiological analysis of 16p11.2 +/- rat cerebral cortex and hippocampus at post-natal day (P) 21. Results We identified a subset of human interneurons (INs) first appearing at GW23 with enriched expression of a large fraction of risk factor transcripts including those expressed from the 16p11.2 locus. This suggests the hypothesis that these foetal INs are vulnerable to mutations causing autism. We investigated this in a rat model of the 16p11.2 microdeletion. We found no change in the numbers or position of either excitatory or inhibitory neurons in the somatosensory cortex or CA1 of 16p11.2 +/- rats but found that CA1 Sst INs were hyperexcitable with an enlarged axon initial segment, which was not the case for CA1 pyramidal cells. Limitations The human foetal gene expression data was acquired from cerebral cortex between gestational week (GW) 8 to 26. We cannot draw inferences about potential vulnerabilities to genetic autism risk factors for cells not present in the developing cerebral cortex at these stages. The analysis 16p11.2 +/- rat phenotypes reported in the current study was restricted to 3-week old (P21) animals around the time of weaning and to a single interneuron cell-type while in human 16p11.2 microdeletion carriers symptoms likely involve multiple cell types and manifest in the first few years of life and on into adulthood. Conclusions We have identified developing interneurons in human foetal cerebral cortex as potentially vulnerable to monogenic autism risk factors and the 16p11.2 microdeletion and report interneuron phenotypes in post-natal 16p11.2 +/- rats.

It is not easy to be optimistic about international security at the present time, but 9th Review Conference of the Biological Weapons Convention in December 2022 agreed a renewed effort to strengthen the Convention after decades of stagnation. In March 2023 an agreement was also reached on an agenda and timetable for this effort over the next 2 years. Scientists have a long history of providing valuable input to such meetings, in this paper, we discuss how such input might best be provided with complicated challenges now facing the BWC and concluded that there is much that could be done, but greater coordination amongst scientists is needed.

A variety of proteins can be encoded by a single gene via the differential splicing of exons. In neurons this form of alternative splicing can be controlled by activity-dependent calcium signaling, leading to the properties of proteins being altered, including ion channels, neurotransmitter receptors and synaptic cell adhesion molecules. The pre-synaptic cell adhesion molecule Neurexin 1 (Nrxn1) is alternatively spliced at splice-site 4 (SS4) which governs exon 22 inclusion (SS4+) and consequently postsynaptic NMDA receptor responses. Nrxn1 was reported to be subject to a delayed-onset shift in Nrxn1 SS4 splicing resulting in increased exon 22 inclusion, involving epigenetic mechanisms which, if disrupted, reduce memory stability. Exon inclusion at SS4 represented one of hundreds of exons reported to be subject to a genome-wide shift in fractional exon inclusion following membrane depolarization with high extracellular K+ that was delayed in onset. We report that high K+ does not increase the SS4+/SS4− ratio in cortical neurons, but does induce a delayed-onset NMDA receptor-dependent neuronal death. In mixed neuronal/astrocyte cultures this neuronal death results in an increase in the astrocyte: neuron ratio, and a misleading increase in SS4+/SS4− ratio attributable to astrocytes having a far higher SS4+/SS4− ratio than neurons, rather than any change in the neurons themselves. We reassessed the previously reported genome-wide delayed-onset shift in fractional exon inclusion after high K+ exposure. This revealed that the reported changes correlated strongly with differences in exon inclusion level between astrocytes and neurons, and was accompanied by a strong decrease in the ratio of neuron-specific: astrocyte-specific gene expression. As such, these changes can be explained by the neurotoxic nature of the stimulation paradigm, underlining the importance of NMDA receptor blockade when using high K+ depolarizing stimuli.

IntroductionThe verbal deception literature is largely based upon North American and Western European monolingual English speaker interactions. This paper extends this literature by comparing the verbal behaviors of 88 south Asian bilinguals, conversing in either first (Hindi) or second (English) languages, and 48 British monolinguals conversing in English.MethodsAll participated in a live event following which they were interviewed having been incentivized to be either deceptive or truthful. Event details, complications, verifiable sources, and plausibility ratings were analyzed as a function of veracity, language and culture.ResultsMain effects revealed cross cultural similarities in both first and second language interviews whereby all liar’s verbal responses were impoverished and rated as less plausible than truthtellers. However, a series of cross-cultural interactions emerged whereby bi-lingual South Asian truthtellers and liars interviewed in first and second languages exhibited varying patterns of verbal behaviors, differences that have the potential to trigger erroneous assessments in practice.DiscussionDespite limitations, including concerns centered on the reductionary nature of deception research, our results highlight that while cultural context is important, impoverished, simple verbal accounts should trigger a ‘red flag’ for further attention irrespective of culture or interview language, since the cognitive load typically associated with formulating a deceptive account apparently emerges in a broadly similar manner.

In this article, we describe efforts to reduce barriers of entry to pre-college engineering in a rural community by training local teens to become maker-mentors and staff a mobile makerspace in their community. We bring a communities of practice frame to our inquiry, focusing on inbound and peripheral learning and identity trajectories as a mechanism for representing the maker-mentor experience. Through a longitudinal case study, we traced the individual trajectories of five maker-mentors over two years. We found a collection of interrelated factors present in those students who maintained inbound trajectories and those who remained on the periphery. Our research suggests that the maker-mentors who facilitated events in the community, taught younger community members about making, and co-facilitated with other maker-mentors were more likely to have inbound trajectories. We offer lessons learned from including a mentorship component in a pre-college maker program, an unusual design feature that afforded more opportunities to create inbound trajectories. A key affordance of the maker-mentor program was that it allowed teens to explore areas of making that were in line with their interests while still being a part of a larger community of practice. Understanding learning and identity trajectories will allow us to continually improve pre-college engineering programming and education opportunities that build on students' funds of knowledge.

How school librarians focus on activating critical thinking through traditional literacy development can proactively set the stage for the deep thinking that occurs in all literacy development. The critical-thinking skills students build while becoming accomplished readers and writers provide the foundation for learning in a variety of environments. This "Knowledge Quest" issue explores student engagement in understanding and using data and graphics, cultivating global and visual literacies, and applying inquiry processes--all of which require skills in observation, questioning, and making connections--skills that evolve through traditional literacy development. The school librarian's role in ensuring students master skills essential for success in their future academic and real-life experiences begins with supporting their development of critical thinking as learners work toward proficiency in traditional literacy tasks.

Autistic people experience social communication difficulties alongside specific memory difficulties than impact their ability to recall episodic events. Police interviewing techniques do not take account of these differences, and so are often ineffective. Here we introduce a novel Witness-Aimed First Account interview technique, designed to better support autistic witnesses by diminishing socio-cognitive and executive demands through encouraging participants to generate and direct their own discrete, parameter-bound event topics, before freely recalling information within each parameter-bound topic. Since witnessed events are rarely cohesive stories with a logical chain of events, we also explored witnesses' recall when the narrative structure of the to-be-remembered event was lost. Thirty-three autistic and 30 typically developing participants were interviewed about their memory for two videos depicting criminal events. Clip segments of one video were 'scrambled', disrupting the event's narrative structure; the other video was watched intact. Although both autistic and typically developing witnesses recalled fewer details with less accuracy from the scrambled video, Witness-Aimed First Account interviews resulted in more detailed and accurate recall from autistic and typically developing witnesses, for both scrambled and unscrambled videos. The Witness-Aimed First Account technique may be a useful tool to improve autistic and typically developing witnesses' accounts within a legally appropriate, non-leading framework.

Society's ability to collectively address global challenges will require efforts to include diverse voices, perspectives, and epistemologies. Building on critical design, which positions these challenges as requiring changes in our values and beliefs, we examine the nature and potential of a critical constructionist design framework within an Afrofuturist aesthetic. This framework invites Black youth to critically examine social, economic, and environmental systems by both connecting to personal and family histories as well as reflecting on local and lived experiences. We ground our discussion of this framework in an implementation where, in consultation with professional designers, artists, and scholars, five Black teen girls designed and produced a collection of critical artifacts. We invited participants to use their personal experiences in the present, as well as their family and cultural histories, to design futuristic artifacts that critique existing social inequities and environmental instability.