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Fear-related psychopathologies, such as post-traumatic stress disorder, are linked to dysfunction in neural circuits that govern fear memory and arousal. The lateral hypothalamus (LH) and zona incerta (ZI) regulate fear, but our understanding of the precise neural circuits and cell types involved remains limited. Here, we examined the role of relaxin family peptide receptor 3 (RXFP3) expressing cells in the LH/ZI in conditioned fear expression and general arousal in male RXFP3-Cre mice. We found that LH/ZI RXFP3+ (LH/ZI RXFP3 ) cells projected strongly to fear learning, stress, and arousal centres, notably, the periaqueductal grey, lateral habenula, and nucleus reuniens. These cells do not express hypocretin/orexin or melanin-concentrating hormone but display putative efferent connectivity with LH hypocretin/orexin+ neurons and dopaminergic A13 cells. Following Pavlovian fear conditioning, chemogenetically activating LH/ZI RXFP3 cells reduced fear expression (freezing) overall but also induced jumping behaviour and increased locomotor activity. Therefore, the decreased freezing was more likely to reflect enhanced arousal rather than reduced fear. Indeed, stimulating these cells produced distinct patterns of coactivation between several motor, stress, and arousal regions, as measured by Fos expression. These results suggest that activating LH/ZI RXFP3 cells generates brain-wide activation patterns that augment behavioural arousal., (© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Movement sonification has emerged as a promising approach for rehabilitation and motion control. Despite significant advancements in sensor technologies, challenges remain in developing cost-effective, user-friendly, and reliable systems for gait detection and sonification. This study introduces a novel wearable personalised sonification and biofeedback device to enhance movement awareness for individuals with irregular gait and posture. Through the integration of inertial measurement units (IMUs), MATLAB, and sophisticated audio feedback mechanisms, the device offers real-time, intuitive cues to facilitate gait correction and improve functional mobility. Utilising a single wearable sensor attached to the L4 vertebrae, the system captures kinematic parameters to generate auditory feedback through discrete and continuous tones corresponding to heel strike events and sagittal plane rotations. A preliminary test that involved 20 participants under various audio feedback conditions was conducted to assess the system's accuracy, reliability, and user synchronisation. The results indicate a promising improvement in movement awareness facilitated by auditory cues. This suggests a potential for enhancing gait and balance, particularly beneficial for individuals with compromised gait or those undergoing a rehabilitation process. This paper details the development process, experimental setup, and initial findings, discussing the integration challenges and future research directions. It also presents a novel approach to providing real-time feedback to participants about their balance, potentially enabling them to make immediate adjustments to their posture and movement. Future research should evaluate this method in varied real-world settings and populations, including the elderly and individuals with Parkinson's disease.

Background: The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved., Objective: The overall objective of this study was to investigate the direct impact of corticosterone challenge on a tractable epididymal epithelial cell line (i.e., mECap18 cells), in terms of driving adaptation of the cellular proteome and phosphoproteome signaling networks., Materials and Methods: The newly developed phosphoproteomic platform EasyPhos coupled with sequencing via an Orbitrap Exploris 480 mass spectrometer, was applied to survey global changes in the mECap18 cell (phospho)proteome resulting from sub-chronic (10-day) corticosterone challenge., Results: The imposed corticosterone exposure regimen elicited relatively subtle modifications of the global mECap18 proteome (i.e., only 73 out of 4171 [∼1.8%] proteins displayed altered abundance). By contrast, ∼15% of the mECap18 phosphoproteome was substantially altered following corticosterone challenge. In silico analysis of the corresponding parent proteins revealed an activation of pathways linked to DNA damage repair and oxidative stress responses as well as a reciprocal inhibition of pathways associated with organismal death. Corticosterone challenge also induced the phosphorylation of several proteins linked to the biogenesis of microRNAs. Accordingly, orthogonal validation strategies confirmed an increase in DNA damage, which was ameliorated upon selective kinase inhibition, and an altered abundance profile of a subset of microRNAs in corticosterone-treated cells., Conclusions: Together, these data confirm that epididymal epithelial cells are reactive to corticosterone challenge, and that their response is tightly coupled to the opposing action of cellular kinases and phosphatases., (© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Plant roots are functionally heterogeneous in cellular architecture, transcriptome profile, metabolic state, and microbial immunity. We hypothesized that axial differentiation may also impact spatial colonization by root microbiota along the root axis. We developed two growth systems, ArtSoil and CD-Rhizotron, to grow and then dissect Arabidopsis thaliana roots into three segments. We demonstrate that distinct endospheric and rhizosphere bacterial communities colonize the segments, supporting the hypothesis of microbiota differentiation along the axis. Root metabolite profiling of each segment reveals differential metabolite enrichment and specificity. Bioinformatic analyses and GUS histochemistry indicate microbe-induced accumulation of SWEET2, 4, and 12 sugar uniporters. Profiling of root segments from sweet mutants shows altered spatial metabolic profiles and reorganization of endospheric root microbiota. This work reveals the interdependency between root metabolites and microbial colonization and the contribution of SWEETs to spatial diversity and stability of microbial ecosystem., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Previous studies on paternal epigenetic inheritance have shown that sperm RNAs play a role in this type of inheritance. The microinjection of sperm small noncoding RNAs into fertilised mouse oocytes induces reprogramming of the early embryo, which is thought to be responsible for the differences observed in adult phenotype. While sperm long noncoding RNAs (lncRNAs) have also been investigated in a previous study, their microinjection into fertilised oocytes did not yield conclusive results regarding their role in modulating brain development and adult behavioural phenotypes. Therefore, in the current study we sought to investigate this further. We used our previously established paternal corticosterone (stress hormone) model to assess sperm lncRNA expression using CaptureSeq, a sequencing technique that is more sensitive than the ones used in other studies in the field. Paternal corticosterone exposure led to dysregulation of sperm long noncoding RNA expression, which encompassed lncRNAs, circular RNAs and transposable element transcripts. Although they have limited functional annotation, bioinformatic approaches indicated the potential of these lncRNAs in regulating brain development and function. We then separated and isolated the sperm lncRNAs and performed microinjections into fertilised oocytes, to generate embryos with modulated lncRNA populations. We observed that the resulting adult offspring had lower body weight and altered anxiety and affective behavioural responses, demonstrating roles for lncRNAs in modulating development and brain function. This study provides novel insights into the roles of lncRNAs in epigenetic inheritance, including impacts on brain development and behaviours of relevance to affective disorders., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Rationale: Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models., Objective: The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task., Methods: NL3 R451C and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed., Results: In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3 R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3 R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3 R451C mice., Conclusions: NL3 R451C mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3 R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Studies have shown that paternal stress prior to conception can influence the innate behaviours of their offspring. The evolutionary impacts of such intergenerational effects are therefore of considerable interest. Our group previously showed in a model of daily stress that glucocorticoid treatment of adult male mouse breeders prior to conception leads to increased anxiety-related behaviours in male offspring. Here, we aimed to understand the transgenerational effects of paternal stress exposure on the social behaviour of progeny and its potential influence on reproductive success., Results: We assessed social parameters including social reward, male attractiveness and social dominance, in the offspring (F1) and grand-offspring (F2). We report that paternal corticosterone treatment was associated with increased display of subordination towards other male mice. Those mice were unexpectedly more attractive to female mice while expressing reduced levels of the key rodent pheromone Darcin, contrary to its conventional role in driving female attraction. We investigated the epigenetic regulation of major urinary protein (Mup) expression by performing the first Oxford Nanopore direct methylation of sperm DNA in a mouse model of stress, but found no differences in Mup genes that could be attributed to corticosterone-treatment. Furthermore, no overt differences of the prefrontal cortex transcriptome were found in F1 offspring, implying that peripheral mechanisms are likely contributing to the phenotypic differences. Interestingly, no phenotypic differences were observed in the F2 grand-offspring., Conclusions: Overall, our findings highlight the potential of moderate paternal stress to affect intergenerational (mal)adaptive responses, informing future studies of adaptiveness in rodents, humans and other species., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Mortality from stroke remains high in Australia, especially for patients located outside the metropolitan cities. This is because they have limited access to specialized stroke facilities for optimal stroke treatment. Mobile stroke units have the capability to take CT scanners out to the patient however current CT commercial scanner designs are large and heavy. As such, this paper aims to design and develop a lightweight CT scanner for use in a mobile stroke unit (either road-based or air-based ambulance) to bring healthcare solution to patients in the rural and remote areas. We used the engineering design optimization approach to redesign and reduce the weight of the existing CT scanner with without compromised it structural performance. We managed to reduce the weight the CT scanner by three-fold while reducing design costs by allowing numerous simulations to be performed using computer software to achieve our design goals. The results are not only useful to optimize CT scanner structure to retrofit on a mobile stroke unit, but also bring the medical device solution to the market and support scalable solution to the larger community. Such an advance will allow for improved equity in healthcare whereby patients can be treated irrespective of location.

A substantial fraction of the bacterial cytosol is occupied by catalysts and their substrates. While a higher volume density of catalysts and substrates might boost biochemical fluxes, the resulting molecular crowding can slow down diffusion, perturb the reactions' Gibbs free energies, and reduce the catalytic efficiency of proteins. Due to these tradeoffs, dry mass density likely possesses an optimum that facilitates maximal cellular growth and that is interdependent on the cytosolic molecule size distribution. Here, we analyze the balanced growth of a model cell, accounting systematically for crowding effects on reaction kinetics. Its optimal cytosolic volume occupancy depends on the nutrient-dependent resource allocation into large ribosomal vs. small metabolic macromolecules, reflecting a tradeoff between the saturation of metabolic enzymes, favoring larger occupancies with higher encounter rates, and the inhibition of the ribosomes, favoring lower occupancies with unhindered diffusion of tRNAs. Our predictions across growth rates are quantitatively consistent with the experimentally observed reduction in volume occupancy on rich media compared to minimal media in E. coli. Strong deviations from optimal cytosolic occupancy only lead to minute reductions in growth rate, which are nevertheless evolutionarily relevant due to large bacterial population sizes. In sum, cytosolic density variation in bacterial cells appears to be consistent with an optimality principle of cellular efficiency., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pang, Lercher. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

White-matter brain abnormalities have been found across a variety of psychiatric disorders. The extent of white matter pathology is proposed to be predictive of the severity of anxiety disorders. However, it is still unknown whether disruptions of white matter integrity precede, and are sufficient to give rise to, the behavioural symptoms. Interestingly, mood disturbances feature prominently in central demyelinating diseases such as multiple sclerosis. It is unclear whether the greater frequency of neuropsychiatric symptoms is linked to underlying neuropathology. In this study, we characterised male and female Tyro3 knockout (KO) mice using a variety of behavioural paradigms. Anxiety-related behaviours were assessed with the elevated-plus maze and light-dark box. Fear memory processing was assessed using fear conditioning and extinction paradigms. Finally, we assessed immobility time in the Porsolt swim test as a measure of depression-related behavioural despair. Surprisingly, loss of Tyro3 did not lead to manifestation of major shifts in baseline behaviour. We noted significant differences in habituation to novel environments and post-conditioning freezing levels of female Tyro3 KO mice, which are consistent with the female bias in anxiety disorders and could be indicative of maladaptive stress-responses. This study has demonstrated that white matter pathology related to a loss of Tyro3 is associated with pro-anxiety behavioural responses of female mice. Future studies could probe their contribution to increased risk for neuropsychiatric disorders when combined with stressful triggering events., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Paternal preconceptional health factors, such as exposures to stress, diet and exercise, have been found to significantly influence offspring phenotypes in a range of animal models. Preclinical studies have provided evidence that paternal stress is associated with increased stress responsivity and anxiety-related traits, particularly in male offspring. It was previously reported that a paternal history of maternal separation (MS) led to male offspring (PatMS) displaying reduced cautious behavior during exploration of a novel environment. The neural basis for that absence of behavioral moderation is unclear. Here, we investigated the adaptive behavioral responses of control and PatMS male offspring in the predator odor risk-assessment task (PORT). PatMS mice failed to moderate their behaviors in the presence of a predator odor 2,4,5-trimethylthiazoline (TMT). c-Fos mapping revealed reduced cellular activation in fear-regulating brain regions of PatMS mice, such as in the cingulate cortex, dentate gyrus of the hippocampus and the basolateral amygdala. Expression of the paternally imprinted gene Grb10 (previously identified as a key molecular regulator of risk-taking behavior) was unaltered in PatMS mice. However, other paternal imprinted genes such as Igf2 and PEG3 were differentially expressed in PatMS mice. Overall, our study provides the first evidence of an intergenerational influence of preconceptional paternal stress exposure on offspring brain zunction relevant to risk-taking behavior, which is also independent of Grb10 gene expression., (© 2023 The Author(s).)

Conventional heating ventilation and air-conditioning (HVAC) controllers have been designed to mainly control the temperature of a confined compartment, such as a room or a cabin of a vehicle. Other important parameters related to the thermal comfort and indoor air quality (IAQ) of the confined compartment have often been ignored. In this project, IAQ in the vehicle cabin was represented by its carbon dioxide (CO 2 ) concentration, and the occupants' thermal comfort levels were estimated with the predicted mean vote (PMV) index. A new fuzzy logic controller (FLC) was designed and developed using the MATLAB fuzzy logic toolbox and Simulink to provide a nonlinear mapping between the measured values, i.e., PMV, temperature, CO 2 , and control parameters (recirculation flaps, blower's speed, and refrigerant mass flow rate) of a vehicle HVAC system. The new FLC aimed to regulate both in-cabin PMV and CO 2 values without significantly increasing overall energy consumption. To evaluate the effectiveness of the proposed FLC, a cabin simulator was used to mimic the effects of different HVAC variables and indoor/outdoor environmental settings, which represented the in-cabin PMV and IAQ readings. Results demonstrated that the new FLC was effective in regulating the in-cabin PMV level and CO 2 concentration, at desirable levels, by adaptively controlling the opening and closing of the recirculation flap based on in-cabin temperature and CO 2 readings, while maintaining an average-to-good energy consumption level. The proposed FLC could be applied to a large variety of HVAC systems by utilizing low-cost sensors, without the need to significantly modify the internal design of the HVAC system.

Continuous Auditory Feedback (CAF) can have profound effects when used to guide bodily movements. CAF is defined as auditory feedback that responds dynamically to continuous streams of data. A large number of studies have used CAF to communicate dynamic human efforts in the body. In contrast, this study uses motion sensor data at the knee and hip joints, which were converted to auditory sounds, to communicate the dynamic phases of walking gait through shifts in tonal brightness and loudness of two tones with harmonic relationships. As a proof-of-concept study, our aim was to determine if CAF mapped to hip and knee movements affects a person's gait. A total of 10 participants, five males and five females, participated in a gait analysis in a Biomechanics lab in relation to the various sound conditions. Quantitative results revealed that CAF has a significant effect on cadence. Notably, females had a higher cadence compared with males. Qualitative responses suggested that participants were aware of a relationship between the rotation of the knee and hip as the rise and fall of audio tonal brightness to concentrate or synchronize their gait. We defined this as a brightness-rotation relationship. Based on these findings, we propose future investigations to further understand and extend this brightness-rotation relationship and develop reliable models of CAF to support movement awareness for gait training and rehabilitation program. These investigations will inform future development of wearable systems of on-body sensing and auditory feedback for this awareness and rehabilitation., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 IPEM. Published by Elsevier Ltd. All rights reserved.)

Dose-response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose-response curves. The shape of the dose-response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose-response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose-response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose-response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Stroke continues to be a major cause of mortality globally. Post-stroke treatment is complicated by the heterogenous nature of pathology and the emergence of secondary psychological symptoms are an additional challenge to the recovery process. Poststroke depression (PSD) is a common co-morbidity and is a major impediment to recovery. While selective serotonin reuptake inhibitors (SSRIs) have proven to be clinically efficacious in treating PSD, the pathogenic processes that underlie the manifestation of depressive mood post-stroke remains unclear. Furthermore, the use of SSRIs is associated with risks of intracerebral haemorrhage, so alternative treatment options need to be continuously explored. Exercise has been demonstrated to be beneficial for improving mood in humans and preclinical models of neurological conditions. Little is known of the mood-related benefits of physical exercise post-stroke. Using the middle cerebral artery occlusion (MCAO) mouse model of cerebral ischaemia, we investigated whether behavioural deficits emerge post-MCAO and could be rescued by voluntary wheel-running. We report that MCAO induced hypo-locomotion and anhedonia-related behaviours, with some improvements conferred by wheel-running. Serotonin transporter gene expression was increased in the MCAO hippocampus and frontal cortex, but this increase remained despite wheel-running. Wheel-running associated up-regulation of BDNF gene expression was unaffected in MCAO mice, reflecting conservation of key neuroplasticity molecular pathways. Taken together, our results highlight the need for further research into serotonergic modulation of the affective symptoms of stroke., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cognitive impairments associated with advanced age involve alterations in the hippocampus that changes with experience throughout life. The hippocampus is critical for cognitive flexibility involved with extinction and reinstatement of conditioned fear. It is widely accepted that regular exercise can be beneficial for hippocampal function. Therefore, we asked whether chronic voluntary exercise in middle-aged mice can improve extinction and/or reinstatement of conditioned fear compared with standard-housing. Eight-month-old male and female C57Bl/6J mice had access to a running wheel or remained in standard-housing until 11 months of age. Alongside control standard-housed young adult (3-month-old) mice, they received tone-footshock pairings, which were subsequently extinguished with tone-alone presentations the next day. Half of the mice then received a reminder in the form of a single footshock. Male and female 11-month-old mice housed in standard conditions exhibited impaired reinstatement compared with young adult mice. However, for males that had access to a running wheel from 8 months of age, the reminder treatment rescued reinstatement ability. This was not observed in females. Additionally, exercise during middle age in both sexes increased expression of brain-derived neurotrophic factor ( Bdnf ) mRNA in the hippocampus, specifically exon 4 mRNA. These results show that, at least for males, physical exercise is beneficial for reducing age-related decline in cognitive abilities. Despite not affecting reinstatement, exercise also increased Bdnf gene expression in the female hippocampus, which could potentially benefit other forms of hippocampus-dependent cognition., Competing Interests: The authors declare that there are no competing interests associated with the manuscript., (© 2022 The Author(s).)

The global consumption of highly processed, calorie-dense foods has contributed to an epidemic of overweight and obesity, along with negative consequences for metabolic dysfunction and disease susceptibility. As it becomes apparent that overweight and obesity have ripple effects through generations, understanding of the processes involved is required, in both maternal and paternal epigenetic inheritance. We focused on the patrilineal effects of a Western-style high-fat (21%) and high-sugar (34%) diet (WD) compared to control diet (CD) during adolescence and investigated F0 and F1 mice for physiological and behavioral changes. F0 males (fathers) showed increased body weight, impaired glycemic control, and decreased attractiveness to females. Paternal WD caused significant phenotypic changes in F1 offspring, including higher body weights of pups, increased Actinobacteria abundance in the gut microbiota (ascertained using 16S microbiome profiling), a food preference for WD pellets, increased male dominance and attractiveness to females, as well as decreased behavioral despair. These results collectively demonstrate the long-term intergenerational effects of a Western-style diet during paternal adolescence. The behavioral and physiological alterations in F1 offspring provide evidence of adaptive paternal programming via epigenetic inheritance. These findings have important implications for understanding paternally mediated intergenerational inheritance, and its relevance to offspring health and disease susceptibility., (© 2021 Federation of American Societies for Experimental Biology.)

Sucrose, hexoses, and raffinose play key roles in the plant metabolism. Sucrose and raffinose, produced by photosynthesis, are translocated from leaves to flowers, developing seeds and roots. Translocation occurs in the sieve elements or sieve tubes of angiosperms. But how is sucrose loaded into and unloaded from the sieve elements? There seem to be two principal routes: one through plasmodesmata and one via the apoplasm. The best-studied transporters are the H+/SUCROSE TRANSPORTERs (SUTs) in the sieve element-companion cell complex. Sucrose is delivered to SUTs by SWEET sugar uniporters that release these key metabolites into the apoplasmic space. The H+/amino acid permeases and the UmamiT amino acid transporters are hypothesized to play analogous roles as the SUT-SWEET pair to transport amino acids. SWEETs and UmamiTs also act in many other important processes-for example, seed filling, nectar secretion, and pollen nutrition. We present information on cell type-specific enrichment of SWEET and UmamiT family members and propose several members to play redundant roles in the efflux of sucrose and amino acids across different cell types in the leaf. Pathogens hijack SWEETs and thus represent a major susceptibility of the plant. Here, we provide an update on the status of research on intercellular and long-distance translocation of key metabolites such as sucrose and amino acids, communication of the plants with the root microbiota via root exudates, discuss the existence of transporters for other important metabolites and provide potential perspectives that may direct future research activities., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Mental illness remains the greatest chronic health burden globally with few in-roads having been made despite significant advances in genomic knowledge in recent decades. The field of psychiatry is constantly challenged to bring new approaches and tools to address and treat the needs of vulnerable individuals and subpopulations, and that has to be supported by a continuous growth in knowledge. The majority of neuropsychiatric symptoms reflect complex gene-environment interactions, with epigenetics bridging the gap between genetic susceptibility and environmental stressors that trigger disease onset and drive the advancement of symptoms. It has more recently been demonstrated in preclinical models that epigenetics underpins the transgenerational inheritance of stress-related behavioural phenotypes in both paternal and maternal lineages, providing further supporting evidence for heritability in humans. However, unbiased prospective studies of this nature are practically impossible to conduct in humans so preclinical models remain our best option for researching the molecular pathophysiologies underlying many neuropsychiatric conditions. While rodents will remain the dominant model system for preclinical studies (especially for addressing complex behavioural phenotypes), there is scope to expand current research of the molecular and epigenetic pathologies by using invertebrate models. Here, we will discuss the utility and advantages of two alternative model organisms- Caenorhabditis elegans and Drosophila melanogaster -and summarise the compelling insights of the epigenetic regulation of transgenerational inheritance that are potentially relevant to human psychiatry., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

A non-invasive, no radiation, out-of-hospital automated system is proposed to identify low arch integrated in the design and manufacturing of personalized orthoses using parametric modelling. The aim of the design process is to integrate assistive technology with assessment and prevent low arch progressing to a more serious case - flatfoot. In the automated procedure, we developed an assessment method including reliable thresholds of foot type classification and test protocol to reduce interferences due to preceding activities, an automation to translate scanned data into parametric design for orthotic customization, finite element model evaluating effectiveness of the personalized design, and a personalized comparative test to evaluate the long-term improvement of foot arch shape. Our low arch threshold established by subject-specific 3D models reduced the misclassification rate from 55%, as previously reported to 6.9%. Individuals who engaged in sedentary activity (i.e. sitting) had the greater change in arch height compared to active activity (i.e. standing and walking), which is more likely to affect the obtained measure. Therefore, a test protocol now states that participants are not allowed to sit over 100 min prior the measurement to reduce such interference. We have proposed and tested an automated algorithm to translate scanned data including seven foot's parameters into customised parametric design of the insert. The method decreases the required time of orthotic computer-aided design from over 3 h to less than 2 min. A finite element analysis procedure was additionally developed to assess the performance of geometries and material of designed orthotic based on the distribution of plantar pressure and internal stress. The personalized comparative assessment based on midfoot contact area was carried out periodically for follow-up and the orthotic could be re-designed if necessary. The proposed automated procedure develops a pre-screening system to distinguish low arch and provide preventatives before it becomes symptomatic. Furthermore, non-symptom flatfoot can be detected at early stages and referred to medics for further diagnosis or treatment., (Copyright © 2021 IPEM. Published by Elsevier Ltd. All rights reserved.)