Blood-Based Protein Changes in Childhood Are Associated With increased risk for later psychotic disorder: evidence from a nested case–control study of the ALSPAC Longitudinal Birth Cohort

The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who also participated in psychiatric assessment interviews at age 18. Protein expression levels at age 11 were compared between individuals who developed PD at age 18 (n = 37) with population-based age-matched controls (n = 38). Sixty out of 181 plasma proteins profiled were found to be differentially expressed (P < .05) in children with an outcome of the PD. Thirty-four of these proteins were found to be differentially expressed following correction for multiple comparisons. Pathway analysis implicated the complement and coagulation cascade. A second, targeted proteomic approach was used to verify these findings in age 11 plasma from subjects who reported psychotic experiences at age 18 (n = 40) in comparison to age-matched controls (n = 66). Our findings indicate that the complement and coagulation system is dysregulated in the blood during childhood before the development of the PD

“Put your personality into the call”: A qualitative interview study illuminating strategies for improving men’s engagement on crisis helplines

Abstract Background Crisis telephone helplines are an integral part of community suicide prevention. Despite high male suicide rates, men’s experiences of these services are poorly understood. The current study explored men’s perspectives of their interactions with helpline counsellors to understand how their engagement on helplines can be enhanced. Method Sixteen men (19–71 years) who had previously used a mental health or crisis helpline in Australia completed individual semi-structured interviews about their experiences. Data were analysed using interpretive descriptive methodologies. Results Two themes derived from the data related to how men engaged with counsellors on helpline services. First, men emphasized the importance of helpline counsellors creating and maintaining an authentic connection across the call, providing suggestions for strategies to secure connection. Second, men discussed how counsellors can facilitate outcomes through offering space for their narratives and aiding in referrals to other support services when required. Conclusions Findings highlight the value of crisis helplines for men’s suicide prevention services while identifying target areas to improve engagement. We discuss implications for the findings including suggestions for gender-sensitive care within crisis helplines

Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation

Multiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is attributed to crosstalk between plasma cells and the bone marrow microenvironment, where extracellular vesicles (EVs) play a role. In this study, EVs secreted from a panel of MM cell lines were isolated from conditioned media by ultracentrifugation and fluorescently stained EVs were co-cultured with THP-1 monocyte cells. MM EVs from three cell lines displayed a differential yet dose-dependent uptake by THP-1 cells, with H929 EVs displaying the greatest EV uptake compared to MM.1s and U266 EVs suggesting that uptake efficiency is dependent on the cell line of origin. Furthermore, MM EVs increased the secretion of MMP-9 and IL-6 from monocytes, with H929 EVs inducing the greatest effect, consistent with the greatest uptake efficiency. Moreover, monocyte-conditioned media collected following H929 EV uptake significantly increased the migration and proliferation of MM cells. Finally, EV proteome analysis revealed differential cargo enrichment that correlates with disease progression including a significant enrichment of spliceosome-related proteins in H929 EVs compared to the U266 and MM.1s EVs. Overall, this study demonstrates that MM-derived EVs modulate monocyte function to promote tumour growth and metastasis and reveals possible molecular mechanisms involved

Male-Type Depression Mediates the Relationship between Avoidant Coping and Suicidal Ideation in Men

Despite known links between men&rsquo;s avoidant coping behaviours (e.g., distraction, denial, substance use) and suicide risk, little research has explored the mechanisms underpinning this relationship. This study sought to examine whether male-type depression symptoms (e.g., anger, aggression, emotion suppression), assessed by the Male Depression Risk Scale, mediate the association between avoidant coping and suicide/self-harm ideation in men. Data were drawn from an online survey of a community sample of 606 Australian men (M age = 50.11 years; SD = 15.00), conducted during the COVID-19 pandemic. Mediation analyses were applied to examine the effect of male-type depression on the association between avoidant coping and suicidal/self-harm ideation, controlling for age, resilience and the experience of two psychosocial stressors during the COVID-19 pandemic (financial stress and government restrictions). Avoidant coping was associated with suicidal/self-harm ideation, r = 0.45, p &lt; 0.001. Results supported a mediating role of male-type depression symptoms in this relationship, R2= 0.29, PM = 0.36, p &lt; 0.001, underscoring the importance of screening for male-type depression symptoms to better identify men at risk of suicidal/self-harm ideation. Results also suggest a need to support men to develop effective coping strategies, particularly in the context of common psychosocial stressors experienced during the COVID-19 pandemic and beyond

Timing of archaic hominin occupation of Denisova Cave in southern Siberia

Unique bell-shaped underwater speleothems were recently reported from the deep (∼ 55 m) meromictic El Zapote sinkhole (cenote) on the Yucatán Peninsula, Mexico. The local diving community has termed these speleothems as Hells Bells because of their shape and appearance in a dark environment in ∼ 28–38 m water depth above a sulfidic halocline. It was also suggested that Hells Bells form under water, yet the mystery of their formation remained unresolved. Therefore, we conducted detailed hydrogeochemical and geochemical analyses of the water column and Hells Bells speleothems including stable carbon isotopes. Based on the comprehensive results presented in this study we deduce that both biogeochemical processes in the pelagic redoxcline and a dynamic halocline elevation of El Zapote cenote are essential for Hells Bells formation. Hells Bells most likely form in the redoxcline, a narrow 1–2 m thick water layer immediately above the halocline where a pelagic chemolithoautotrophic microbial community thrives from the upward diffusion of reduced carbon, nitrogen and sulfur species released from organic matter degradation in organic-rich debris. We hypothesize that chemolithoautotrophy, in particular proton-consuming nitrate-driven anaerobic sulfide oxidation, favors calcite precipitation in the redoxcline and hence Hells Bells formation. A dynamic elevation of the halocline as a hydraulic response to droughts, annual tidal variability and recharge events is further discussed, which might explain the shape of Hells Bells as well as their occurrence over a range of 10 m water depth. Finally, we infer that highly stagnant conditions, i.e., a thick halocline, a low-light environment and sufficient input of organic material into a deep meromictic cenote are apparent prerequisites for Hells Bells formation. This might explain their exclusivity to only a few cenotes in a restricted area of the northeastern Yucatán Peninsula

Timing of archaic hominin occupation of Denisova Cave in southern Siberia

Unique bell-shaped underwater speleothems were recently reported from the deep (∼ 55 m) meromictic El Zapote sinkhole (cenote) on the Yucatán Peninsula, Mexico. The local diving community has termed these speleothems as Hells Bells because of their shape and appearance in a dark environment in ∼ 28–38 m water depth above a sulfidic halocline. It was also suggested that Hells Bells form under water, yet the mystery of their formation remained unresolved. Therefore, we conducted detailed hydrogeochemical and geochemical analyses of the water column and Hells Bells speleothems including stable carbon isotopes. Based on the comprehensive results presented in this study we deduce that both biogeochemical processes in the pelagic redoxcline and a dynamic halocline elevation of El Zapote cenote are essential for Hells Bells formation. Hells Bells most likely form in the redoxcline, a narrow 1–2 m thick water layer immediately above the halocline where a pelagic chemolithoautotrophic microbial community thrives from the upward diffusion of reduced carbon, nitrogen and sulfur species released from organic matter degradation in organic-rich debris. We hypothesize that chemolithoautotrophy, in particular proton-consuming nitrate-driven anaerobic sulfide oxidation, favors calcite precipitation in the redoxcline and hence Hells Bells formation. A dynamic elevation of the halocline as a hydraulic response to droughts, annual tidal variability and recharge events is further discussed, which might explain the shape of Hells Bells as well as their occurrence over a range of 10 m water depth. Finally, we infer that highly stagnant conditions, i.e., a thick halocline, a low-light environment and sufficient input of organic material into a deep meromictic cenote are apparent prerequisites for Hells Bells formation. This might explain their exclusivity to only a few cenotes in a restricted area of the northeastern Yucatán Peninsula

Archaeological evidence for two separate dispersals of Neanderthals into southern Siberia

Neanderthals were once widespread across Europe and western Asia. They also penetrated into the Altai Mountains of southern Siberia, but the geographical origin of these populations and the timing of their dispersal have remained elusive. Here we describe an archaeological assemblage from Chagyrskaya Cave, situated in the Altai foothills, where around 90,000 Middle Paleolithic artifacts and 74 Neanderthal remains have been recovered from deposits dating to between 59 and 49 thousand years ago (age range at 95.4% probability). Environmental reconstructions suggest that the Chagyrskaya hominins were adapted to the dry steppe and hunted bison. Their distinctive toolkit closely resembles Micoquian assemblages from central and eastern Europe, including the northern Caucasus, more than 3,000 kilometers to the west of Chagyrskaya Cave. At other Altai sites, evidence of earlier Neanderthal populations lacking associated Micoquian-like artifacts implies two or more Neanderthal incursions into this region. We identify eastern Europe as the most probable ancestral source region for the Chagyrskaya toolmakers, supported by DNA results linking the Neanderthal remains with populations in northern Croatia and the northern Caucasus, and providing a rare example of a long-distance, intercontinental population movement associated with a distinctive Paleolithic toolkit

Pleistocene sediment DNA reveals hominin and faunal turnovers at Denisova Cave

Denisova Cave in southern Siberia is the type locality of the Denisovans, an archaic hominin group who were related to Neanderthals1–4. The dozen hominin remains recovered from the deposits also include Neanderthals5,6 and the child of a Neanderthal and a Denisovan7, which suggests that Denisova Cave was a contact zone between these archaic hominins. However, uncertainties persist about the order in which these groups appeared at the site, the timing and environmental context of hominin occupation, and the association of particular hominin groups with archaeological assemblages5,8–11. Here we report the analysis of DNA from 728 sediment samples that were collected in a grid-like manner from layers dating to the Pleistocene epoch. We retrieved ancient faunal and hominin mitochondrial (mt)DNA from 685 and 175 samples, respectively. The earliest evidence for hominin mtDNA is of Denisovans, and is associated with early Middle Palaeolithic stone tools that were deposited approximately 250,000 to 170,000 years ago; Neanderthal mtDNA first appears towards the end of this period. We detect a turnover in the mtDNA of Denisovans that coincides with changes in the composition of faunal mtDNA, and evidence that Denisovans and Neanderthals occupied the site repeatedly—possibly until, or after, the onset of the Initial Upper Palaeolithic at least 45,000 years ago, when modern human mtDNA is first recorded in the sediments