Breaking the cycles of violence with narrative exposure: Development and feasibility of NETfacts, a community-based intervention for populations living under continuous threat.

Background: Interpersonal violence damages mental health and frequently leads to aggressive defence strategies. If survivors are subsequently blamed for the events, both consequences worsen. Stigma flourishes, especially when survivors are silenced so that details of the trauma remain unknown.

Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat.

Objective: Classical ATP-independent non-shivering thermogenesis enabled by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is activated, but not essential for survival, in the cold. It has long been suspected that futile ATP-consuming substrate cycles also contribute to thermogenesis and can partially compensate for the genetic ablation of UCP1 in mouse models. Futile ATP-dependent thermogenesis could thereby enable survival in the cold even when brown fat is less abundant or missing.

Isolation and Electron Microscopic Analysis of Liver Cancer Cell Mitochondria.

Isolation of mitochondria is a crucial method for examining molecular details of this organelle's manifold functions. Historically, mitochondrial isolations required large amounts of sample material which impeded their isolation from cultured cells. We have therefore developed a method allowing for controlled and reproducible isolation of intact and functional mitochondria from diverse cell types in culture.

When reintegration fails: Stigmatization drives the ongoing violence of ex-combatants in Eastern Democratic Republic of the Congo.

Reintegration of ex-combatants involves multiple challenges. In addition to the trauma-related psychological sequelae, social obstacles in the community can aggravate psychopathological aggressive tendencies and lead to the continuation of violence in civilian life. However, the association between others' negative attitudes and ex-combatants' ongoing perpetration of violence remains largely unexplored.

Treating trauma and aggression with narrative exposure therapy in former child and adult soldiers: A randomized controlled trial in Eastern DR Congo.

Objective: Individuals who return from armed groups present with a history of traumatic events including perpetration. Subsequent severe mental stress and heightened levels of reactive and appetitive aggression may persist and if left untreated, frequently impede peacebuilding and societal stability. In this study, we tested a revised adaptation of Narrative Exposure Therapy (NET; Schauer et al.

To add insult to injury: Stigmatization reinforces the trauma of rape survivors - Findings from the DR Congo.

Background: Survivors of sexual violence are frequently condemned and socially excluded. Myths about rape may translate into stigmatization, diminish disclosure, prevent help-seeking from support structures and worsen mental health. Areas of conflict or organized violence remain the evident hotspots of sexual victimization.

CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion.

Astrocyte-to-neuron conversion is a promising avenue for neuronal replacement therapy. Neurons are particularly dependent on mitochondrial function, but how well mitochondria adapt to the new fate is unknown. Here, we determined the comprehensive mitochondrial proteome of cortical astrocytes and neurons, identifying about 150 significantly enriched mitochondrial proteins for each cell type, including transporters, metabolic enzymes, and cell-type-specific antioxidants.

Trauma, Aggression, and Post Conflict Perpetration of Community Violence in Female Former Child Soldiers-A Study in Eastern DR Congo.

Objective: Former combatants are exposed to multiple traumatic stressors during conflict situations and usually participate in perpetration of violence. Ongoing perpetration of violence in post conflict areas, linked to mental health problems and appetitive aggression, destabilises peace keeping efforts. The aim of this study is to investigate lifetime exposure to violence and the relationship between this exposure and mental health and current violent behaviour in a sample of female former child soldiers with a history of perpetration of violence in Eastern DR Congo.

Mitochondrial Regulation of the 26S Proteasome.

The proteasome is the main proteolytic system for targeted protein degradation in the cell and is fine-tuned according to cellular needs. Here, we demonstrate that mitochondrial dysfunction and concomitant metabolic reprogramming of the tricarboxylic acid (TCA) cycle reduce the assembly and activity of the 26S proteasome. Both mitochondrial mutations in respiratory complex I and treatment with the anti-diabetic drug metformin impair 26S proteasome activity.

Metabolic implication of tigecycline as an efficacious second-line treatment for sorafenib-resistant hepatocellular carcinoma.

Sorafenib represents the current standard of care for patients with advanced-stage hepatocellular carcinoma (HCC). However, acquired drug resistance occurs frequently during therapy and is accompanied by rapid tumor regrowth after sorafenib therapy termination. To identify the mechanism of this therapy-limiting growth resumption, we established robust sorafenib resistance HCC cell models that exhibited mitochondrial dysfunction and chemotherapeutic crossresistance.

Regulatory myeloid cells paralyze T cells through cell-cell transfer of the metabolite methylglyoxal.

Regulatory myeloid immune cells, such as myeloid-derived suppressor cells (MDSCs), populate inflamed or cancerous tissue and block immune cell effector functions. The lack of mechanistic insight into MDSC suppressive activity and a marker for their identification has hampered attempts to overcome T cell inhibition and unleash anti-cancer immunity. Here, we report that human MDSCs were characterized by strongly reduced metabolism and conferred this compromised metabolic state to CD8 T cells, thereby paralyzing their effector functions.

A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol.

Mitochondrial fidelity is tightly linked to overall cellular homeostasis and is compromised in ageing and various pathologies. Mitochondrial malfunction needs to be relayed to the cytosol, where an integrated stress response is triggered by the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) in mammalian cells. eIF2α phosphorylation is mediated by the four eIF2α kinases GCN2, HRI, PERK and PKR, which are activated by diverse types of cellular stress.

The treatment of posttraumatic stress symptoms and aggression in female former child soldiers using adapted Narrative Exposure therapy - a RCT in Eastern Democratic Republic of Congo.

Objective: Women and girls make up a sizeable proportion of armed groups in conflict regions. However, compared to males, research into the mental health of female combatants is limited and there have been no investigations into treatments. Psychological sequalae amongst predominantly male former combatants most prominently include PTSD and appetitive aggression indicating a need for trauma-focused therapy that also addresses violent behaviour with additional components that strengthen social behaviour and inclusion.

Mitochondrial Alkbh1 localizes to mtRNA granules and its knockdown induces the mitochondrial UPR in humans and .

The Fe(II) and 2-oxoglutarate-dependent oxygenase Alkb homologue 1 (Alkbh1) has been shown to act on a wide range of substrates, like DNA, tRNA and histones. Thereby different enzymatic activities have been identified including, among others, demethylation of -methylcytosine (mC) in RNA- and single-stranded DNA oligonucleotides, demethylation of -methyladenosine (mA) in tRNA or formation of 5-formyl cytosine (fC) in tRNA. In accordance with the different substrates, Alkbh1 has also been proposed to reside in distinct cellular compartments in human and mouse cells, including the nucleus, cytoplasm and mitochondria.

Connecting lysosomes and mitochondria - a novel role for lipid metabolism in cancer cell death.

Background: The understanding of lysosomes has been expanded in recent research way beyond their view as cellular trash can. Lysosomes are pivotal in regulating metabolism, endocytosis and autophagy and are implicated in cancer. Recently it was discovered that the lysosomal V-ATPase, which is known to induce apoptosis, interferes with lipid metabolism in cancer, yet the interplay between these organelles is poorly understood.

The exceptional sensitivity of brain mitochondria to copper.

Wilson disease (WD) is characterized by a disrupted copper homeostasis resulting in dramatically increased copper levels, mainly in liver and brain. While copper damage to mitochondria is an established feature in WD livers, much less is known about such detrimental copper effects in other organs. We therefore assessed the mitochondrial sensitivity to copper in a tissue specific manner, namely of isolated rat liver, kidney, heart, and brain mitochondria.

Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis.

Selenoproteins are rare proteins among all kingdoms of life containing the 21 amino acid, selenocysteine. Selenocysteine resembles cysteine, differing only by the substitution of selenium for sulfur. Yet the actual advantage of selenolate- versus thiolate-based catalysis has remained enigmatic, as most of the known selenoproteins also exist as cysteine-containing homologs.

Data on chow, liver tissue and mitochondrial fatty acid compositions as well as mitochondrial proteome changes after feeding mice a western diet for 6-24 weeks.

The data presented in this article describe the fatty acid composition of chow, liver tissue and isolated liver mitochondria from mice fed for 6-24 weeks with a high caloric western diet (WD) in comparison to control diet (normal diet, ND). The fatty acid composition was measured via gas chromatography flame ionization detection (GC-FID). Moreover, WD-induced mitochondrial protein changes are presented in this work and were analyzed by mass spectrometry (LC-MS/MS).

Mitochondrial adaptation in steatotic mice.

Western lifestyle-associated malnutrition causes steatosis that may progress to liver inflammation and mitochondrial dysfunction has been suggested as a key factor in promoting this disease. Here we have molecularly, biochemically and biophysically analyzed mitochondria from steatotic wild type and immune-compromised mice fed a Western diet (WD) - enriched in saturated fatty acids (SFAs). WD-mitochondria demonstrated lipidomic changes, a decreased mitochondrial ATP production capacity and a significant sensitivity to calcium.

Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death.

Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear.

What if the Child Appears to Enjoy It? Moral Attitudes Toward Adult-Child Sex Among Men With and Without Pedohebephilia.

This study attempted to measure cognitions about adult-child sex by approaching the issue from a perspective of moral attitudes. We assessed ratings regarding direct and indirect harmfulness, nonconsent, exploitation, and differences in adults' and children's sexualities based on a description of adult-child sex without apparent child discomfort among an online sample of 120 pedohebephilic and 89 nonpedohebephilic German-speaking men. The results showed that only 7.

Methanobactin reverses acute liver failure in a rat model of Wilson disease.

In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration- and European Medicines Agency-approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper.

Nck adaptor proteins modulate differentiation and effector function of T cells.

Understanding the molecular mechanisms regulating T cell reactivity is required for successful reprogramming of immune responses in medical conditions, characterized by dysfunctions of the immune system. Nck proteins are cytoplasmic adaptors mediating diverse cellular functions, including TCR signaling. By enhancing TCR signal strength, Nck proteins influence thymic selection and regulate the size and sensitivity of the peripheral T cell repertoire.