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Generalized linear mixed models (GLMMs) are a cornerstone data analysis strategy in behavioral research because of their robustness in handling non-normally distributed variables. Recently, their integration with ordered beta regression (OBR), a novel statistical tool for managing percentage data, has opened new avenues for analyzing continuous response data. Here, we applied this combined approach to investigate nuanced differences between the 3xTg-AD model of Alzheimer's disease (AD) and their C57BL/6 non-transgenic (NTg) counterparts with normal aging in a 5-day Morris Water Maze (MWM) test protocol. Our longitudinal study included 22 3xTg-AD mice and 15 NTg mice (both male and female) assessed at 12 and 16 months of age. By identifying and analyzing multiple swimming strategies during three different paradigms (cue, place task, and removal), we uncovered genotypic differences in all paradigms. Thus, the NTg group exhibited a higher percentage of direct search behaviors, while an association between circling episodes and 3xTg-AD animals was found. Furthermore, we also propose a novel metric—the "Cognitive Flexibility Index"—which proved sensitive in detecting sex-related differences. Overall, our integrated GLMMs-OBR approach provides a comprehensive insight into mouse behavior in the MWM test, shedding light on the effects of aging and AD pathology. [ABSTRACT FROM AUTHOR]

The Food Finding Test (FFT) olfactory paradigm without overnight food deprivation examined olfaction in aged (16-months-old) animals. Ethograms of three goal-directed behaviors towards hidden food (sniffing, finding and eating) elicited in male and female 3xTg-AD mice for Alzheimer's disease (AD) and their age-matched C57BL/6 wild-type counterparts with normal aging were meticulously analyzed with the support of video recordings. The new FFT protocol elicited longer ethograms than previously reported with the standard deprivation protocol. However, it was sensitive when identifying genotype- and sex-dependent olfactory signatures for the temporal patterns of slow sniffing, finding, and eating in AD and males, but it had a striking consistency in females. The impact of forced social isolation was studied and it was found to exert sex-dependent modifications of the ethogram, mostly in males. Still, in both sexes, a functional derangement was detected since the internal correlations among the behaviors decreased or were lost under isolated conditions. In conclusion, the new paradigm without overnight deprivation was sensitive to sex (males), genotype (AD), and social context (isolation-dependent changes) in its ethogram and functional correlation. At the translational level, it is a warning about the impact of isolation in the advanced stages of the disease, paying notable attention to the male sex. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic was one of this century's deadliest and most widespread viral outbreaks, with higher mortality rates in men than women. Disruptions in funeral rituals and customs, no social recognition of the losses, and limited social support have complicated the grieving process and are linked to disenfranchised (not openly acknowledged, socially recognized, or publicly mourned) grief. Depression is also highly comorbid with complicated grief. Losing a spouse can be devastating, and this is more severe for women with limited or no resources, who are vulnerable because of the patriarchal society. In the current COVID-19 era, increased uncertainty and disenfranchised grief can worsen the clinical scenario and hamper interventions, as highlighted by the present case report on disenfranchised grief with depressive symptoms in a 30-year-old woman from rural India who, after a year of marriage, lost her husband due to COVID-19. This case study emphasizes the impact of multiple types of disadvantages due to sociodemographic and cultural determinants that can complicate the grieving process in the current context. The bioecological model of grief recovery considers individual features and societal/environmental factors to postulate the appropriate intervention. Finding meaning and purpose in life and restoration-oriented coping were successful for the clinical management of the patient. [ABSTRACT FROM AUTHOR]

Depression, stress, anxiety disorders, and PTSD are some of the mental health problems that are prevalent among immigrant populations despite being underdiagnosed. Stigma, difficulties in adapting, cultural barriers, and reduced access to mental health support can seriously hamper their ability to build resilience and recover. Other limitations include assuming that therapies can be universally applied, the lack of sufficient evidence on mental health issues of this population, and the use of therapeutic models developed on Caucasian populations. Here, professional guidance to find the meaning of life through interventions such as logotherapy could help them in this process. The present work systematically reviewed studies investigating the effectiveness of logotherapy in diverse populations and its relevance to a Muslim immigrant population in Europe. Following PRISMA guidelines and the keywords 'logotherapy, mental health problems, immigrant, and treatment', the search identified 16 relevant studies conducted since 2005. The studies revealed that logotherapy could be implemented through paradoxical intention, de-reflection, Socratic dialogue, and attitude modification. All these techniques have the potential to help the client to realize long-term relief for underlying stressors associated with migration and settling in a new location. Though data on logotherapy are still scarce, it is evident that it deserves more research so that a structured, evidence-based, and effective therapy for Muslim immigrants in Europe can be developed and tested. In this regard, we propose that the four logotherapy techniques have huge potential in helping psychiatrists develop an effective therapy for mental health problems among these immigrant populations confronting adversity. [ABSTRACT FROM AUTHOR]

Low plasma sex hormone‐binding globulin (SHBG) levels are present in fatty liver disease, which represents a spectrum of diseases ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. We have previously determined that fat accumulation reduces SHBG production in different nonalcoholic fatty liver disease mouse models. In the present work, we are interested in elucidating the molecular mechanisms reducing SHBG plasma levels in liver fibrosis. For this purpose, in vivo studies were performed using the human SHBG transgenic mice developing liver fibrosis induced by carbon tetrachloride (CCl4). Our results clearly showed that CCl4 induced liver fibrosis and reduced SHBG production by reducing hepatocyte nuclear factor 4 alpha (HNF‐4α). The SHBG reduction could be influenced by the increase in transforming growth factor‐beta 1 (TGF‐β1), which was increased in mice developing liver fibrosis. Therefore, we decided to evaluate the role of TGF‐β1 in regulating hepatic SHBG production. Results obtained in both HepG2 cells and human SHBG transgenic mice showed that TGF‐β1 reduced significantly SHBG messenger RNA and protein levels. Mechanistically TGF‐β1 downregulated P1‐HNF‐4α isoforms and increased P2‐HNF‐4α isoforms via Smad3 and Stat3 pathways through TGF‐β1 receptor I, resulting in transcriptional repression of the SHBG gene. Taken together, we found for the first time that TGF‐β1 is a new factor regulating hepatic SHBG production in liver fibrosis. Further research is needed to determine the role of this reduction in hepatic SHBG production in the progression of nonalcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

Collective mourning is an expression of societal maturity, cohesion, and respect. The world is in grief, but in early January 2020, before nobody could even imagine that SARS-CoV-2 would turn into the COVID-19 pandemic, a music video version of a pop ballad about love and isolation was spread across a Chinese social network. The song 'You Are Not Alone' was adapted as a cover by young foreigners living in China to express their support to bereaved families and frontline workers and encourage the people of China, their second home. At that time, the rest of the world looked to distant China but could hardly expect to face the same adversity months later. The authors reported that the music video was a spontaneous artistic expression copying such traumatic events and the mourning process. The present work analyses how the music was blended with lyrics and images describing the outbreak in Wuhan to reach their goal. The original song and this shortened version for China were compared regarding musical and lyric structures and main characteristics. Additionally, an analysis of the two videos was done regarding cinemetric variables and non-verbal communication that emphasized the power of songs to express deep sorrow and sympathy but also to give hope. Psychological first aid, the five stages of the mourning process by Kübler-Ross, the dual-process model by Stroebe and Schut, and Taylor's tend-to-befriend provided a better understanding of the translation from interpersonal to societal mourning. Finally, other memorable songs that society spontaneously chose to be performed alone or together to cope with sudden and dramatic situations, mitigate physical distancing, and alleviate human suffering are discussed. Music, lyrics, and artistic performance are playing a key role in building social and emotional ties during this pandemic, hampering individual and social pain and sorrow despite cultural barriers. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) patients suffer from circadian rhythm alterations involving sleep, thermoregulation, and movement activity disorders. The latter affects their daily patterns of physical activity (PA) and willingness to perform voluntary exercise, impeding benefit from routine PA practice. Neuropsychiatric symptoms (NPS) have been postulated to influence human physical activity engagement. However, there is no clarity on whether animal models can replicate these effects. Herein, we evaluated the behavioral circadian rhythmicity of voluntary physical exercise (VPE) in a group of 14-month-old 3xTg-AD animals of both sexes at advanced stages of the disease and compared their performance according to the presence of NPS-like symptoms. Mice (n = 9 females and n = 7 males) were provided with an in-cage running wheel for 30 days with daily control of the diurnal and nocturnal amount of VPE performed. Using a Linear Mixed Model Analysis, we found that all animals kept similar nocturnal patterns of VPE. However, sex-dependent differences associated with previous novelty inhibition (NI) response, an NPS-like symptom frequently observed in this model, were found during diurnal periods. Thus, males with high NI showed significantly higher levels of VPE compared with high NI females. No sex differences were found in low NI animals. Our results suggest that the influence of NPS-like symptoms in VPA engagement may vary depending on the sex of 3xTg-AD mice. Further studies are needed to help us to elucidate molecular and genetic factors associated with these differences. [ABSTRACT FROM AUTHOR]

This paper aims to provide theoretically informed practical proposals for the improvement of current drug policies, which are based on a biological model of disease and the criminalization of people who use drugs. First, we present alternatives to a biologically-oriented scientific conception centered around neuroscientific postulates, which support the idea that the etiology of addiction materializes in the brain, in favor of models based on the social sciences where context plays a relevant role in the description and management approaches regarding different uses of psychoactive substances. Second, epistemological models and proposals are offered from a practical perspective to sustain or implement policies and programs in accordance with a more sustainable approach based on the elimination of stigma and the promotion of political participation of people who use drugs. In short, drug policies based on human rights. [ABSTRACT FROM AUTHOR]

The continuously expanding field of Alzheimer's disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as alterations in the peripheral organs could be related to disease progression. One emerging hypothesis is organ involvement in the process of Aβ clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Abstract The increase of prevalence of mental health problems in the elderly due to the aging of the population becomes an outstanding issue since in most individuals it happens in an already complex multimorbid scenario that may include frailty and age-related medical conditions. Depression, soon the major cause of global disease burden, can be found as an age-related comorbidity and frailty, or as part of neurodegenerative diseases and where females are more vulnerable to it. Thought the multifactorial aetiology and heterogeneous nature of depression render it difficult to be modelled in animals, active behaviours elicited in the Forced Swimming Test (FST) are used to screen antidepressant treatments. However, interpretation of immobility remains controversial. The present work addressed this issue in very-old (21 months) female C57bl/6 × 129 mice, also with the concern that a '6 minutes × 2 days' protocol can result demanding for a very-old animal and confounding factors may also arise. Animals were behaviourally assessed for sensorimotor functions, emotionality and anxiety-like behaviours, novelty seeking, and immobility in a 2-days FST. The predictive value of the first day evidenced that one single assay as sufficient for the assessment of immobility, and that the repeated test did not increase the immobility response. Moreover, sensorimotor tasks, neophobia in the corner test and emotional behaviour in the dark-light box correlated with FST immobility, contributing to the response. The results support the concern of geroscience on the relevance of using aged animals but also aware about taking into account the complexity of their comorbid scenario. Highlights • In 21-month-old females, first FST assay strongly predicted immobility in the 24 h repeated test. • Comorbid sensorimotor and emotional profiles are correlated with the FST-immobility performance. • Equilibrium strongly correlated (negative) with FST-immobility over the time and days. • Neophobia and emotionality correlated (negative) with FST-immobility. • Activity in the open-field and the hole-board test correlated (positively) with immobility. [ABSTRACT FROM AUTHOR]

Modeling of Alzheimer's disease (AD), classically focused on the subject-environment interaction, foresees current social neuroscience efforts as improving the predictive validity of new strategies. Here we studied social functioning among congeners in 13-14-month-old mice with normal aging in naturalistic and experimental conditions and depicted behavioral signatures of dysfunction in age-matched 3xTg-AD mice. The most sensitive variables were vibrating tail, digging, body/face and self-grooming, that can be easily used in housing routines and the assessment of strategies. Sex-specific signatures (vibrating tail, digging, and grooming) defined female 3xTg-AD mice ethogram. All animals sleep huddled while barbering was only found in females with normal aging. [ABSTRACT FROM AUTHOR]

Ongoing and future changes in wind and temperature are predicted to alter upper ocean vertical mixing across the Southern Ocean. How these changes will affect primary production (PP) remains unclear as mixing influences the two controlling factors: light and iron. We used a large ensemble of 1‐D‐biogeochemical model simulations to explore the impacts of changes in mixed‐layer depths on PP in the Southern Ocean. In summer, shoaling mixed‐layer depth always reduced depth‐integrated PP, despite increasing production rates. In winter, shoaling mixed layers had a two‐staged impact: for moderate shoaling PP increased as light conditions improved, but more pronounced shoaling decreased iron supply, which reduced PP. The fraction of PP exported below 100 m also presented a nonmonotonic behavior. This suggests a potential future shift from a situation where reduced winter mixing increases PP and export, to a situation where PP and export may collapse if the ML shoals above a threshold depth. Plain Language Summary: In the Southern Ocean, atmospheric warming associated to climate change is altering the depth at which surface waters are stirred, the so‐called mixed‐layer depth. A change in the mixed‐layer depth impacts the phytoplankton cells that inhabit it by altering their two main limiting factors: iron and light. However, the sign and magnitude of this impact are still not clear. In this work we used mathematical simulations to explain how changes in the seasonal mixed‐layer depth modify the supply of iron and the amount of light, and how these changes impact phytoplankton activity. Our results show that mixed‐layer depth changes in summer and in winter have different impacts. Reducing summer mixed‐layer depth did not change the iron supply, but it reduced the volume of water where phytoplankton thrived. In winter, shallower mixed‐layer depth altered iron and light but in opposed ways. At first, phytoplankton increased its activity as more light became available. However, a continued shallowing of the mixed‐layer depth eventually reduced the iron supply and the phytoplankton activity. Our study proposes a new interpretation on how ongoing changes in the Southern Ocean impact phytoplankton activity and alerts of the presence of threshold depths for the winter mixed layer above which phytoplankton may struggle to survive. Key Points: Moderate shoaling of winter mixed layer causes increase in primary production, but shoaling below a threshold depth can lead to a collapseReversal in this response is due to balancing effects of iron and light limitation and associated with a change in community structure and export efficiencyInterestingly, shoaling summer mixed layer always reduces PP and export because of a reduction of the productive volume [ABSTRACT FROM AUTHOR]

This document introduces a collection of research papers on emerging translational research in neurology and psychiatry. The papers cover advancements in neuroimaging, neurostimulation, neurodegenerative disorders, neuroinflammatory disorders, and neuropsychiatric disorders. The research presented in the papers explores groundbreaking techniques for modulating brain activity, strategies for neural regeneration and repair, and the complexity of mental health and effective treatment strategies. The document discusses various topics related to neuroscience and mental health, including neural regeneration and repair, biomarkers in neurological disorders, diagnosis and treatment of depression, neural oscillations in cognitive functions, genetic variants in psychiatric disorders, and neurotransmission and neuroprotection in neural function and integrity. It also reviews two papers on neuromodulation and neuroregeneration, one focusing on facial nerve and muscle recovery after injury and the other establishing a mouse model for a gynecological disorder. The document emphasizes the importance of multidisciplinary approaches and collaboration in understanding and treating neurological and psychiatric diseases. [Extracted from the article]

The psychogenetically selected Roman high- (RHA) and low-avoidance (RLA) rats are being proposed as a valuable animal model of individual vulnerability to the two distinct neurobiological mechanisms of behavioral sensitization to psychostimulants, namely induction and expression. Most hallmarks of their divergent phenotypes are also found in the inbred RHA (RHA-I) and RLA (RLA-I) strains. For instance, they differ in the expression of sensitization to amphetamine. However, the pattern of spontaneous activity of the inbred rats seems to differ from that of outbred Roman strains. The present work shows the relevance of analyzing spontaneous activity as a covariant in order to determine the significance of day effect in the induction of behavioral sensitization to amphetamine (regime: 11 days, 1 mg/kg, i.p.) in the inbred strains and, for comparison, the standard low activity Sprague-Dawley (SD) strain. Our results also confirm that, in parallel to the outbred strains, only inbred RHA rats showed sensitization during the induction phase, here detectable from day 9 of treatment, while RLA-I and SD strains did not. Inbred RLA rats provide an interesting model to study individual resistance to sensitization, with nuances due to their underlying high spontaneous activity phenotype. [ABSTRACT FROM AUTHOR]

Bizarre behaviors (BB) are elicited in animals during stressful conditions and represent behavioral markers of disease/sickness relevant to animal welfare. These behaviors are disregarded in most experimental screenings due to their low incidence and short duration, despite their translational value mimicking disruptive behaviors associated with neurological/psychiatric diseases. However, we previously reported experimental conditions with conspicuous BB incidence: (1) 3xTg-AD mice for Alzheimer's disease vs. wild-types; (2) the open-field test (OF) vs. other tests; (3) +6 months of age; (4) female sex; (5) older age (+13 months) male 3xTg-AD mice also exhibit more circling behavior (BB-CB) than control mice; (6) early neonatal handling reduces BB; whereas (7) BB are enhanced by d-galactose-induced accelerated aging. In the present work, we studied the BB patterns elicited in the OF using a longitudinal design with sixty-six 13-month-old male/female mice with normal/AD-pathological aging under social/isolated housing conditions, and aimed to explore the effects of intrinsic (genotype, sex) and extrinsic (environment) factors (n = 7–8/group). BB were recorded in 39% of animals. Sex, re-testing at an older age, and genotype factors differentiated two BB patterns: higher circling behavior (BB-CB, n = 12) in wild-types and males, but higher backward movements (BB-BM, n = 14) in 3xTg-AD, female, and older age mice. Isolation increased the incidence of freezing, mostly in 3xTg-AD mice, and exerted a modulatory role in BB, but interaction effects with other factors led to a residual significance. The results point to BB-BM as the most pervasive BB pattern in this animal model, which is also sensitive to the progress of aging/disease. [ABSTRACT FROM AUTHOR]

The severity of sensory involution during aging is critical for perceiving and recognizing the world. In addition, sensory deficits significantly increase the risk of older adults' biological, mental, and social decline. Conversely, the loss of smell is an early biomarker of neurodegeneration in Alzheimer's (AD) and Parkinson's diseases. The worsening of these neurodegenerative diseases also involves physical deterioration, social deficits, and isolation. In the present translational work, a new food finding test (FFT) olfactory paradigm without food deprivation was used to investigate olfaction in old animals. The effects of social isolation in 12-months-old female 3xTg-AD mice, a genetic model of AD, and their age-matched wild-type counterparts, the gold-standard C57BL/6 mice, were also studied. The animals were placed in a test cage and were observed until reaching the criteria for three goal-directed behaviors, 'Sniffing', 'Finding' and 'Eating', towards the hidden food. Video recordings were analyzed blind to the genotype and social condition in order to determine the behaviors' ethogram and functional correlations. The results showed that the FFT paradigm without food deprivation elicited longer ethograms than previously reported with the standard overnight food deprivation protocol. However, it identified the genotype-dependent olfactory signatures in normal and AD-pathological aging. Social isolation slightly increased the latencies, but the olfactory signatures were preserved. However, a functional derangement was detected since the internal correlation among the three goal-directed behaviors was lost under isolation. In conclusion, the new paradigm without overnight deprivation was sensitive to genotype and isolation changes in the ethogram and function and can be used to study old animals. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB), also known as Butterfly skin, is a term for a heterogeneous group of rare genodermatosis disorders resulting in painful mucocutaneous blisters and extreme fragility with minor trauma or friction. The low prevalence and heterogeneity of EB, clinically classified into 4 major groups and over 30 subtypes, lead to significant psychological and social research constraints. An inverse correlation between disease severity and quality of life in patients and their families has been described. Psycho-social aspects in people with more severe subtypes of EB and body dysmorphia refer to loss of self-esteem and coping skills, low self-control, intense fear, anxiety, depression, and social isolation. On the other hand, acute, chronic, and procedural pain, common comorbidities in EB, can negatively affect cognition and interfere with academic and professional achievements. Here, we present the first case report of a current international project that searches for reference models for children and young people with EB and the creation of a guidebook with different life stories of strategies and skills proven to help achieve academic/professional success despite EB's condition. We analyze the semistructured interview with Sonia Ortiz Romero, alias 'Mariposa de cristal', an expert patient with dystrophic EB and co-founder of 'Son mis alas, I.A.P' ('They are my wings, NGO'), together with his brother Marcos Humberto. Her storytelling illustrates challenges, rewards, and limiting factors that make their Mexican association a successful case in helping other EB patients in Santiago Tianguistenco with their physical, psychological, and social well-being, as well as raising social awareness. [ABSTRACT FROM AUTHOR]

Epidermolysis Bullosa (EB) is a chronic disease with multiple clinical presentations, depending on the subtype. It is characterized by the structural fragility of skin and tissues which results in lesions. Its low prevalence contributes to the lack of knowledge of the disease by the general population and the health sector. The disorder's heterogeneity adds challenges in describing psycho-social affectations. Therefore, our current international project searches for reference models for children and young people with EB, as well as the elaboration of a guidebook with different life stories for them to learn about skills and strategies proven to help to achieve personal/professional success despite the EB condition. In the present work, a qualitative and phenomenological interview with Karen Puga, an expert adult patient with dystrophic EB from Mexico, explored several social dimensions/ages affected in EB and their impact on self-esteem. The semi-structured interview depicted several life events and experiences related to her psycho-social maturation that the patient identified as the most negative or positive. The most severe obstacles were experienced during childhood in the scholarly scenario. However, some of those classmates later became friendly adults, providing evidence of the temporality of some adverse life events and the relevance of maturation and resilience processes, both of herself and her counterparts. Her parents' professional profiles (nurses) and the essential role of her sister were described as foundational for her well-being and self-esteem. Multidimensional understanding of affective relationships, sexuality, and positive engagement in professional activities illustrated the development of positive dimensions of her adulthood despite the complexity of psycho-social factors in EB. [ABSTRACT FROM AUTHOR]

The crosstalk between obesity, diabetes, steatohepatitis, and dementia creates a controversial scenario when also studied using animal models. In the present work, this crosstalk was investigated in male and female 3xTg-AD mice for Alzheimer's disease (AD) at different ages/stages and compared to sex- and age-matched counterparts with normal aging. The relevance of the genetic background and classical intrinsic factors (AD genotype and sex) were determined using a retrospective analysis of population data and an experimental design. Age/stage of disease was considered a source of stochastic and non-stochastic factors. Data from two different colonies of 3xTg-AD mice with distinct genetic backgrounds were analyzed to verify the functional interplay between the studied factors. Data from asymptomatic/prodromal to early/advanced stages of the disease were screened. Then, all factors' relationships were studied in an experimental design using the same set of animals. The population data unveiled that the genetic background and sex effects were confirmed with regards to the variable body weight, with changes during disease development and progress. Sexual dimorphism was found as an important factor in glucose metabolism. Statistically significant differences in glucose tolerance and behavioral assessment (exploration, anxiety, and cognition in a two-days open-field paradigm) were found when all the factors were analyzed. In summary, the present study shows that all the studied factors should always be considered when assessing the outcome of the research interventions in the field because they have a distinct functional interplay through the process of normal and AD-pathological aging and from a gendered perspective. [ABSTRACT FROM AUTHOR]

The centromere is a specialized chromosomal structure that dictates kinetochore assembly and, thus, is essential for accurate chromosome segregation. Centromere identity is determined epigenetically by the presence of a centromere-specific histone H3 variant, CENP-A, that replaces canonical H3 in centromeric chromatin. Here, we discuss recent work by Roulland et al. that identifies structural elements of the nucleosome as essential determinants of centromere function. In particular, CENP-A nucleosomes have flexible DNA ends due to the short αN helix of CENP-A. The higher flexibility of the DNA ends of centromeric nucleosomes impairs binding of linker histones H1, while it facilitates binding of other essential centromeric proteins, such as CENP-C, and is required for mitotic fidelity. This work extends previous observations indicating that the differential structural properties of CENP-A nucleosomes are on the basis of its contribution to centromere identity and function. Here, we discuss the implications of this work and the questions arising from it. [ABSTRACT FROM AUTHOR]

Pre-clinical research in aging is hampered by the scarcity of studies modeling its heterogeneity and complexity forged by pathophysiological conditions throughout the life cycle and under the sex perspective. In the case of Alzheimer's disease, the leading cause of dementia in older adults, we recently described in female wildtype and APP23 mice a survival bias and non-linear chronology of behavioral signatures from middle age to long life. Here, we present a comprehensive and multidimensional (physical, cognitive, and neuropsychiatric-like symptoms) screening and underlying neuropathological signatures in male and female 3xTg-AD mice at 2, 4, 6, 12, and 16 months of age and compared to their non-transgenic counterparts with gold-standard C57BL/6J background. Most variables studied detected age-related differences, whereas the genotype factor was specific to horizontal and vertical activities, thigmotaxis, coping with stress strategies, working memory, and frailty index. A sex effect was predominantly observed in classical emotional variables and physical status. Sixteen-month-old mice exhibited non-linear age- and genotype-dependent behavioral signatures, with higher heterogeneity in females, and worsened in naturalistically isolated males, suggesting distinct compensatory mechanisms and survival bias. The underlying temporal and spatial progression of Aβ and tau pathologies pointed to a relevant cortico-limbic substrate roadmap: premorbid intracellular Aβ immunoreactivity and pSer202/pThr205 tau phosphorylation in the amygdala and ventral hippocampus, and the entorhinal cortex and ventral hippocampus as the areas most affected by Aβ plaques. Therefore, depicting phenotypic signatures and neuropathological correlates can be critical to unveiling preventive/therapeutic research and intervention windows and studying adaptative behaviors and maladaptive responses relevant to psychopathology. [ABSTRACT FROM AUTHOR]

Chronic administration of d‐galactose (d‐gal) in rodents reproduces the overproduction of reactive oxygen species of physiological aging. The present research shows for the first time distinct signatures on d‐gal‐induced aging (500 mg/kg, 6 weeks) and the preventive and protective potential of two vitamin D (50 IU) supplementation regimens (pre‐induction and simultaneous, respectively) in two vital organs (heart and brain). d‐gal‐induced notorious alterations in working memory, a strong increase in brain malondialdehyde (MDA) oxidative levels, and strong downregulation of sirtuin 1 (SIRT1) in the heart and hippocampus and of calstabin2 in the heart. Cardiac and brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic antioxidant capacities were damaged, brain calstabin2 was downregulated, and neuropathology was observed. Heart damage also included a moderate increase in MDA levels, serologic lactate dehydrogenase (LDH), total creatine kinase (CK) activities, and histopathological alterations. The used dose of vitamin D was enough to prevent cognitive impairment, avoid muscular damage, hamper cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation. Most importantly, the potencies of the two preventive schedules depended on the tissue and level of study. The pre‐induction schedule prevented d‐gal‐induced aging by 1 order of magnitude higher than simultaneous administration in all the variables studied except for SIRT1, whose strong downregulation induced by d‐gal was equally prevented by both schedules. The benefits of vitamin D for oxidative stress were stronger in the brain than in the heart. Brain MDA levels were more sensitive to damage, while SOD and GPx antioxidant enzymatic activities were in the heart. In this order, the magnitude of SOD, MDA, and GPx oxidative stress markers was sensitive to prevention. In summary, the results unveiled distinct aging induction, preventive signatures, and sensitivity of markers depending on different levels of study and tissues, which are relevant from a mechanistic view and in the design of targeted interventions. [ABSTRACT FROM AUTHOR]

Motor performance facilitates the understanding of the functional state related to the progression of Alzheimer's disease (AD). At the translational level, this brief report refines the characterization of the motor dysfunction of the 3xTg-AD mouse model in different motor tasks, focusing on the abnormal clasping reflex and coordination impairments measured through the Phenotype Scoring System four items screening originally developed for models of ataxia. We studied male 3xTg-AD mice at 6, 12, and 16 months of age (mimicking the early, advanced, and late stages of the disease, respectively) and their age-matched non-transgenic counterparts with normal aging. According to the score, incidence, or severity of the four items and the total score, the 3xTg-AD mice showed deficiencies in all score elements. Clasping was increased independently of age, and its severity worsened with repeated testing. In contrast, the impairment of coordination worsened with the progress of the disease. The gait score was sensitive to genotype since early stages, and the worse ledge score was evident at 16 months. Kyphosis and ledge scores were sensitive to age. The impairments and functional limitations of male 3xTg-AD mice related to the stages of AD provide a scenario that allows understanding the heterogeneity of non-cognitive symptoms. • Male 3xTg-AD mice exhibited impairment in all items of the physical phenotype score. • Clasping increased independently of age and severity worsened with repeated testing. • The impairment of coordination worsened with the progress of the disease. • Gait score was sensitive to genotype and worse ledge score was evident at 16 months. • Kyphosis and ledge scores were sensitive to the age effect. [ABSTRACT FROM AUTHOR]

Forced Swimming Test (FST) models behavioural despair in animals by loss of motivation to respond or the refusal to escape. The present study was aimed at characterizing genetic (genotype and gender) and environmental factors (age/stage of disease and rearing conditions: C, standard; H, early postnatal handling; EE, environmental enrichment consisting in physical exercise as well as social and object enrichment) that may modulate the poor behavioural and cognitive flexibility response we have recently described in 12-month-old male 3xTg-AD mice in the FST. The comprehensive analysis of the ethogram shown in the FST considered the intervals of the test (0–2 and 2–6 min), all the elicited behavioural responses (immobility, swimming and climbing) and their features (total duration and frequency of episodes). The long persistence of behaviours found in 17-month-old (late-stages of disease) 3xTg-AD mice was comparable to that recently described in males at 12 months of age (beginning of advanced stages) but also suggested increased age-dependent frailty in both genotypes. The poor behavioral flexibility of 3xTg-AD mice to elicit the behavioural despair shown by the NTg mice, was also found in the female gender. Finally, the present work demonstrates that early-life interventions were able to improve the time and frequency of episodes of immobility, being more evident in the female gender of both old NTg and 3xTg-AD mice. Ontogenic modulation by early-postnatal handling resulted in a more effective long-term improvement of the elicited behaviours in the FST than that achieved by environmental enrichment. The results talk in favor of the beneficence of early-life interventions on ageing in both healthy and disease conditions. [ABSTRACT FROM AUTHOR]

In this study, we document the regional variations of bloom phenology in the Southern Ocean, based on a 13-year product of ocean colour measurements co-located with observation-based estimates of the mixed-layer depth. One key aspect of our work is to discriminate between mixed-layer integrated blooms and surface blooms. By segregating blooms that occur before or after the winter solstice and blooms where integrated and surface biomass increase together or display a lag, we define three dominating Southern Ocean bloom regimes. While the regime definitions are solely based on bloom timing characteristics, the three regimes organize coherently in geographical space, and are associated with distinct dynamical regions of the Southern Ocean: the subtropics, the subantarctic, and the Antarctic Circumpolar Current region. All regimes have their mixed-layer integrated onset between autumn and winter, when the daylength is short and the mixed layer actively mixes and deepens. We discuss how these autumn-winter bloom onsets are controlled by either nutrient entrainment and/or reduction in prey-grazer encounter rate. In addition to the autumn-winter biomass increase, the subantarctic regime has a significant spring biomass growth associated with the shutdown of turbulence when air-sea heat flux switches from surface cooling to surface warming. [ABSTRACT FROM AUTHOR]

The seasonal cycle of phytoplankton biomass in the Southern Ocean (SO) is characterized by a period of rapid accumulation, known as bloom, that is typical of high-latitude regions. Recent studies have illustrated how spatial and temporal dynamics of blooms in the SO are more complex than in other oceans. This complexity is likely related to differences in vertical mixing and the iron availability. In this work, we examine the sensitivity of bloom dynamics to changes in vertical mixing and iron availability using a biogeochemical model. Under idealized physical forcing, we produce seasonal cycles of phytoplankton for an ensemble of SO scenarios and we describe the bloom dynamics in terms of the net biomass accumulation rate. Based on this metric, we define three crucial bloom phases: the onset, the climax, and the apex. For the ensemble of modelled blooms, onsets always occur in winter and can be either bottom-up (increase in productivity) or top-down (decrease in grazing) controlled. Climaxes are mostly found in spring and their magnitudes are bottom-up controlled. Apexes are always found in late spring and strongly top-down controlled. Our results show that while a "strict" onset definition is consistent with a winter onset, the surface spring bloom is associated with the climax of the integrated bloom. Furthermore, we demonstrate that onset phase can be distinguished from climax phase using appropriate bloom detection methods based on surface satellite-based products. The ensemble of these results suggests that Sverdrup's blooming conditions are not indicative of the bloom onset but of the climax We conclude that the recent bloom onset debate may partly be due to a confusion between what is defined here as the bloom onset and the climax, and that the SO observed complexity is due to the factors that control the climax. [ABSTRACT FROM AUTHOR]

Search strategies in the Morris water maze provide useful insights on cognitive function that may reveal genotype differences not reflected by escape latency or distance. Its analysis is pointed out as a complementary tool to better define the phenotype and the effect of treatments in animal models in which both cognitive impairment and behavioral symptoms reproduce the clinical complexity of the Alzheimer's disease patient. Here, we studied the performance of 13-month-old male 3xTg-AD mice in 3 different paradigms (cue learning, place task, and probe trial) and as compared with age-matched nontransgenic mice. The quantitative analysis (escape latency, distance, and speed) showed that in all tasks, the cognitive performance of 3xTg-AD mice was interfered with by a persistent hyperactive pattern. Their worse cognitive function was revealed by the qualitative features of nonsearch behaviors (floating and circling) and search strategies (single and /mixed, goal directed and nongoal directed). The search pattern was based on mixed and nongoal-directed strategies, in contrast to the single and goal-directed strategies used by controls. In the place task, poor cognitive flexibility of 3xTg-AD mice was also shown in persistence of search in the cue-trained position and the need to correct the strategy to find the new location. Trials involving a naive situation (first trial of the cue task) or the difficulty of a new task (first trial of the place task and the probe trial) were the most suitable to show the deficits. This qualitative analysis may also be useful in the assessment of preventive or therapeutical treatments. [ABSTRACT FROM AUTHOR]

Forced Swimming Test (FST) models behavioural despair in animals by loss of motivation to respond or the refusal to escape. The present study characterizes the behavioural responses of 12-month-old male 3xTg-AD mice in FST as compared to age-matched no-transgenic (NTg) mice. Paradoxical results were consistently found from what would be expected from their BPSD (Behavioural and Psychological Symptoms of Dementia)-like profile. The comprehensive analysis of the ethogram shown in the FST considered the intervals of the test (0-2 and 2-6 min), all the elicited behavioural responses (immobility, swimming and climbing) and their features (total duration, frequency of episodes and mean duration). Both genotypes showed equal number of swimming episodes and climbing attempts during the first interval, that resulted in high swimming times, short climbing and scarce immobility. Thereafter, the NTg mice showed a behavioural shift over time and the immobility response showed up. In contrast, all the measures consistently evidenced that 3xTg-AD persisted with the previous behavioural pattern. Genotype differences consisted in less number of episodes of immobility and swimming, and a low immobility time in favour of swimming. No differences were found in 'climbing' attempts. The behavioural response observed is discussed as a lack of ability of 3xTg-AD mice to shift behaviour over time that may result of poorest cognitive flexibility and copying with stress strategies more than behavioural despair per se. [ABSTRACT FROM AUTHOR]

Canine adenovirus type 2 vectors (CAV-2) are promising tools to treat global central nervous system (CNS) disorders because of their preferential transduction of neurons and efficient retrograde axonal transport. Here we tested the potential of a helper-dependent CAV-2 vector expressing β-glucuronidase (HD-RIGIE) in a mouse model of mucopolysaccharidosis type VII (MPS VII), a lysosomal storage disease caused by deficiency in β-glucuronidase activity. MPS VII leads to glycosaminoglycan accumulation into enlarged vesicles in peripheral tissues and the CNS, resulting in peripheral and neuronal dysfunction. After intracranial administration of HD-RIGIE, we show long-term expression of β-glucuronidase that led to correction of neuropathology around the injection site and in distal areas. This phenotypic correction correlated with a decrease in secondary-elevated lysosomal enzyme activity and glycosaminoglycan levels, consistent with global biochemical correction. Moreover, HD-RIGIE-treated mice show significant cognitive improvement. Thus, injections of HD-CAV-2 vectors in the brain allow a global and sustained expression and may have implications for brain therapy in patients with lysosomal storage disease. [ABSTRACT FROM AUTHOR]

High throughput methods such as next generation sequencing are increasingly used in molecular diagnosis. The aim of this study was to develop a workflow for the detection of BRCA1 and BRCA2 mutations using massive parallel sequencing in a 454 GS Junior bench top sequencer. Our approach was first validated in a panel of 23 patients containing 62 unique variants that had been previously Sanger sequenced. Subsequently, 101 patients with familial breast and ovarian cancer were studied. BRCA1 and BRCA2 exon enrichment has been performed by PCR amplification using the BRCA MASTR kit (Multi-plicom). Bio-informatic analysis of reads is performed with the AVA software v2.7 (Roche). In total, all 62 variants were detected resulting in a sensitivity of 100%. 71 false positives were called resulting in a specificity of 97.35%. All of them correspond to deletions located in homopolymeric stretches. The analysis of the homopolymers stretches of 6 bp or longer using the BRCA HP kit (Multiplicom) increased the specificity of the detection of BRCA1 and BRCA2 mutations to 99.99%. We show here that massive parallel pyro-sequencing can be used as a diagnostic strategy to test for BRCA1 and BRCA2 mutations meeting very stringent sensitivity and specificity parameters replacing traditional Sanger sequencing with a lower cost. [ABSTRACT FROM AUTHOR]

Highlights: [•] Bizarre behaviors in 3xTg-AD mice were conspicuous and measurable early-BPSD. [•] They consisted in stereotyped-rearing and stretching, backward movements and jumps. [•] Female gender was the most suitable to study bizarre movements and risk assessment. [•] Handling reduced bizarre behaviors and freezing whereas potentiated risk assessment. [•] Besides, handling induced selective effects on locomotor activity and emotionality. [ABSTRACT FROM AUTHOR]

Highlights: [•] We present a framework for a rapid performance analysis on parallel applications. [•] Framework results cover: source code locations and quantification of the problem. [•] It uses hardware counters to determine which processor component is the bottleneck. [•] The framework is applied to three applications with improvements from 10% to 30%. [Copyright &y& Elsevier]

Highlights: [•] Nesting behaviour is impaired in parental structures and in isolated 3xTg-AD mice. [•] The impairment is worse in females and with the progress of the disease. [•] The temporal course and the nesting material are relevant to show the impairment. [•] Paper towel consistently showed the deficits that were hidden using nestle cotton. [•] The onset of the behaviour using cotton provided evidence of deficits. [ABSTRACT FROM AUTHOR]

Background: Different studies have established that cholinergic neurodegeneration could be a major pathological feature of Alzheimer's disease (AD). Thus, enhancement of the central cholinergic neurotransmission has been regarded as one of the most promising strategies for the symptomatic treatment of AD, mainly by means of reversible acetylcholinesterase inhibitors (AChEls). The cognitive-enhancing properties of both huprine X, a new AChEl, and the structurally related huperzine A, as well as their effects on the regulation of several neurochemical processes related to AD have been studied in triple transgenic mice (3xTg-AD). Methods: Seven-month-old homozygous 3xTg-AD male mice, which received chronic intraperitoneal treatment with either saline, huprine X (0.12 µmol-kg-1) or huperzine A (0.8 µmol-kg-1) were subjected to a battery of behavioural tests after 3 weeks of treatment and thereafter the brains were dissected to study the neurochemical effects induced by the two AChEls. Results: Treatments with huprine X and huperzine A improved learning and memory in the Morris water maze and some indicators of emotionality without inducing important adverse effects. Moreover, huprine X and huperzine A activate protein kinase C/mitogen-activated protein kinase pathway signalling, ct-secretases (ADAM 10 and TACE) and increase the fraction of phospho-glycogen synthase kinase 3-β. Conclusion: Results obtained herein using a sample of 3xTg-AD animals strongly suggest that the treatment with the two AChEls not only improves the cognitive performance of the animals but also induces some neurochemical changes that could contribute to the beneficial effects observed. [ABSTRACT FROM AUTHOR]

Background: Different studies have established that cholinergic neurodegeneration could be a major pathological feature of Alzheimer's disease (AD). Thus, enhancement of the central cholinergic neurotransmission has been regarded as one of the most promising strategies for the symptomatic treatment of AD, mainly by means of reversible acetylcholinesterase inhibitors (AChEIs). The cognitive-enhancing properties of both huprine X, a new AChEI, and the structurally related huperzine A, as well as their effects on the regulation of several neurochemical processes related to AD have been studied in triple transgenic mice (3xTg-AD). Methods: Seven-month-old homozygous 3xTg-AD male mice, which received chronic intraperitoneal treatment with either saline, huprine X (0.12 μmol·kg-1) or huperzine A (0.8 μmol·kg-1) were subjected to a battery of behavioural tests after 3 weeks of treatment and thereafter the brains were dissected to study the neurochemical effects induced by the two AChEIs. Results: Treatments with huprine X and huperzine A improved learning and memory in the Morris water maze and some indicators of emotionality without inducing important adverse effects. Moreover, huprine X and huperzine A activate protein kinase C/mitogen-activated protein kinase pathway signalling, α-secretases (ADAM 10 and TACE) and increase the fraction of phospho-glycogen synthase kinase 3-β. Conclusion: Results obtained herein using a sample of 3xTg-AD animals strongly suggest that the treatment with the two AChEIs not only improves the cognitive performance of the animals but also induces some neurochemical changes that could contribute to the beneficial effects observed. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A sample of 351 adults (women/men 4:1) aged 18 to 60 participated in an online survey administered during the first two waves (15 March–25 April and 10 October–25 November 2020) of the COVID-19 pandemic in Ukraine. The user ethnography profile was Generation Z (born in the 1990s), female (81.2%), Instagrammer (60.3%), unmarried (56.9%) and student (42.9%). An increased time spent on social media (3.18 h/day), searching for COVID-19-related information (1.01 h/day) after the first COVID-19 case and the observation of fake news that went viral (58.8%) decreased in the second wave. Alterations (increase or reduction) in sleep patterns (46.7%) and changes (increase or loss) in appetite (32.7%) affected participants' well-being, but only sleep ameliorated in the second wave. Mental health reports unveiled moderate perceived stress (PSS-10: 20.61 ± 1.13) and mild anxiety (GAD-7: 14.17 ± 0.22), which improved in the second wave. A higher prevalence of severe anxiety (8.5%) was found among individuals in the first survey (8.5%) than those in the second (3.3%). Social media counteracted physical distance policies and played as an immediate source of (mis)information for users, but also anticipated the impact of the most uncertain times of this COVID-19 physical health crisis on well-being and mental health. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases such as Alzheimer's disease (AD) can be understood in the context of the aging of neuroimmune communication. Although the contribution to AD of the immune cells present in the brain is accepted, the role of the peripheral immune system is less well known. The present review examines the behavior and the function and redox state of peripheral immune cells in a triple-transgenic mouse model (3×Tg-AD). These animals develop both beta-amyloid plaques and neurofibrillary tangles with a temporal- and regional-specific profile that closely mimics their development in the human AD brain. We have observed age and sex-related changes in several aspects of behavior and immune cell functions, which demonstrate premature aging. Lifestyle strategies such as physical exercise and environmental enrichment can improve these aspects. We propose that the analysis of the function and redox state of peripheral immune cells can be a useful tool for measuring the progression of AD. [ABSTRACT FROM AUTHOR]

Current sonar and radar applications use interferometry to estimate the arrival angles of backscattered signals. This direction-finding method is based on a phase-difference measurement between two close receiving arrays. To model the associated bathymetric error, it is necessary to know the second-order moment of the interferometric phase estimator. This paper explains the connection between bathymetric variance and interferometric phase variance and the difficulty in the evaluation of the phase second-order estimation. Thus, a brief statistical overview of the interferometric phase estimator for fully developed speckle signals (called here RMPC for random modulus partially correlated signals) is introduced in this paper. The focus of this paper is the derivation of simple empirical variance that matches the exact values in both single-look and multilook cases. For the sake of constituency, the construction of these empirical approximations is based on a modified asymptotic expression of the second order for the phase estimator assuming high signal-to-noise ratio. In order to perform these derivations, it appears necessary to introduce a new kind of signal (namely, CMPC for constant modulus partially correlated signal) whose modulus is assumed constant. This family of signals, whose physical existence is also investigated, appears as an alternative way to derive RMPC empirical formulas. The link between RMPC and CMPC signals is established through the conditional expectation of the signal modulus. Finally, the existence of these two statistical behaviors is tested over real underwater data. [ABSTRACT FROM AUTHOR]

Abstract: For the purpose of generating meaningful stochastic ensembles of radar estimates of rainfall, a relatively simple and objective method of separating a radar rainfall image into signal and noise is described. An alternative noise field, with the same spectrum as the original noise, can then be simulated and combined with the signal field of each successive image, to generate an ensemble member for performing sensitivity studies. The method is based on identifying the appropriate wavelength in the power spectrum which defines the variance threshold used to separate noise from signal. The algorithm is explained and figures illustrate the efficacy of the procedure. [Copyright &y& Elsevier]

Abstract: Real time availability and high space–time resolution of radar based quantitative precipitation estimates (QPE) are appealing features for spatially detailed hydrological prediction and forecasting applications using distributed hydrological models. However, the data obtained remain an important source of uncertainty for hydrological predictions. Insight into the characteristics of this uncertainty is still limited and its quantification is a challenging task. This work studies the characteristics of radar QPE uncertainties and its implications on both hydrological modelling results and hydrological model parameter estimates. The uncertainty of a real time radar QPE product available in 10minute intervals on a 1km2 grid is quantified by comparison to a reference precipitation field, which includes additional observations from rain gauge records. Based on this analysis a probabilistic model is proposed that describes the uncertainty structure of the radar QPE field. An ensemble of precipitation fields is generated that represents a quantitative estimate of radar QPE uncertainty from the sampling of the probabilistic model. On this basis the implications of radar QPE uncertainty on distributed hydrological model predictions are studied. The methodology proposed is applied to a real-world case study using the river basin of the Besòs in Spain as a test bed. The feasibility of the approach to condense the knowledge about radar QPE uncertainty in a probabilistic model and to map this uncertainty to the response of a hydrological model using an ensemble of precipitation fields is demonstrated. The results show that the probabilistic use of radar QPE may add valuable information to hydrological predictions and may reduce the bias of hydrological model parameter estimates. [Copyright &y& Elsevier]

Background: Centromere identity is determined epigenetically by deposition of CenH3, a centromere-specific histone H3 variant that dictates kinetochore assembly. The molecular basis of the contribution of CenH3 to centromere/kinetochore functions is, however, incompletely understood, as its interactions with the rest of centromere/kinetochore components remain largely uncharacterised at the molecular/structural level. Principal Findings: Here, we report on the contribution of Drosophila CenH3CID to recruitment of BubR1, a conserved kinetochore protein that is a core component of the spindle attachment checkpoint (SAC). This interaction is mediated by the N-terminal domain of CenH3CID (NCenH3CID), as tethering NCenH3CID to an ectopic reporter construct results in BubR1 recruitment and BubR1-dependent silencing of the reporter gene. Here, we also show that this interaction depends on a short arginine (R)-rich motif and that, most remarkably, it appears to be evolutionarily conserved, as tethering constructs carrying the highly divergent NCenH3 of budding yeast and human also induce silencing of the reporter. Interestingly, though NCenH3 shows an exceedingly low degree of conservation, the presence of R-rich motives is a common feature of NCenH3 from distant species. Finally, our results also indicate that two other conserved sequence motives within NCenH3CID might also be involved in interactions with kinetochore components. Conclusions: These results unveil an unexpected contribution of the hypervariable N-domain of CenH3 to recruitment of kinetochore components, identifying simple R-rich motives within it as evolutionary conserved structural determinants involved in BubR1 recruitment. [ABSTRACT FROM AUTHOR]

There are very few reports on the production of microgreens, a new category of salad crops, the shoots of which are harvested at the seedling stage. A series of cultural studies was conducted with the objective of lessening greenhouse production time and lowering production costs of microgreen table beet (Beta vulgaris L.). Sowing seed balls at a commercially recommended rate (201 g·m-2; 11,256·seed balls·m-2) resulted in greater shoot fresh weight·m-2 at 15 days after planting than sowing seed balls at lower rates, although individual shoots were lighter. Sowing seed balls that were germinated before sowing (pregerminated) in fine-grade exfoliated vermiculite moistened with 150% water (wt. per vermiculite dry wt.) for 5 days at 20°C resulted in 26% greater shoot fresh weight·m-2 at 15 days after planting than sowing nontreated seed balls. Combining preplanting fertilization of the peat-lite with calcium nitrate at 2000 mg·L-1 of N (150 mL·L-1of medium) with daily postplanting solution fertilization with 150 mg·L-1 of N led to a further increase in shoot fresh weight·m-2 of 21% (nontreated seed balls) and 22% (pregerminated seed balls) compared to other fertilization regimes (excluding the check). Germinating, and extruding, seed balls in hydrophilic polymer (hydroxyethyl cellulose gel) advanced microgreen growth but not to the extent achieved with vermiculite as the pregermination medium. Irrespective of seed ball treatment, producing microgreens in troughs using the hydroponic nutrient film technique, compared to production in trays containing peat-lite, increased shoot fresh weight·m-2. Depending on seed ball treatment, economic yield was increased 33% to 98% by 7 days after planting and 75% to 144% by 15 days after planting. The greatest shoot fresh weight·m-2 at 15 days after planting (10.14 kg·m-2) was achieved using seed balls pregerminated in moist vermiculite and subsequent growth using the nutrient film technique. [ABSTRACT FROM AUTHOR]

Abstract: The behavioural effects of huprine X, a new anticholinesterasic inhibitor, as well as its effects on the regulation of protein kinase C (PKC), mitogen activated protein kinase (MAPK) and α-secretase (ADAM10 and TACE/ADAM17) related to amyloid precursor protein (APP) processing remain to be established. In the present work, 12month old 126/Sv×C57b/6 male mice which received chronic i.p. treatment with either saline, huprine X (0.04µmolkg− 1) or huprine X (0.12µmolkg− 1), were submitted to a battery of behavioural tests and thereafter the brains were dissected to study the neurochemical effects induced by huprine X. The results show that, in a dose dependent manner, huprine X facilitates learning and memory in the Morris water maze and improves some indicators of emotionality without inducing adverse effects, affecting motor activity nor anxiety-like behaviours, as measured in the open-field and corner tests. Moreover activation of downstream PKC/MAPK signaling pathways may underly these behavioural effects as well as the stimulation of the non-amyloidogenic processing of APP. Results obtained herein using a sample of aged animals strongly suggest that huprine X constitutes a promising therapeutic agent for the treatment of cholinergic dysfunction underlying aging and/or dementias. [Copyright &y& Elsevier]

Background: Alzheimer''s disease (AD) is characterized by progressive memory decline and neuropsychiatric symptoms. Despite common emotional symptoms in AD such as anxiety and fear are associated with a more rapid cognitive decline, the pathological mechanisms involved in these behavioral changes remain largely elusive. In this study, we examined the pathological mechanisms of emotional behavior in well-established AD transgenic mice expressing human mutant β-amyloid (Aβ) precursor protein (APPInd and APPSw,Ind) and tau (3xTg-AD). Methods: We evaluated unconditioned and conditioned fear-induced freezing behavior and spatial memory in APPInd, APPSw,Ind, and 3xTg-AD transgenic mice. The Aβ and tau pathologies and signaling pathways involved in emotional processing were studied by immunohistochemistry and immunoblotting analyses. Results: The APPInd/APPSw,Ind and 3xTg-AD transgenic mice displayed at early ages enhanced innate and conditioned fear symptoms and spatial memory deficits coinciding with enhanced accumulation of Aβ in γ-aminobutyric acid (GABA)ergic and glutamatergic neurons, respectively, of the basolateral amygdala (BLA). Similarly, the number of neurons with intraneuronal Aβ40 and Aβ42 was significantly increased in the BLA of human AD brains. Fear responses might reflect an influence of anxiety, because the anxiolytic compounds valproate, diazepam, and buspirone reduced efficiently unconditioned and conditioned fear responses in APP transgenic mice. In addition, phosphorylation of extracellular signal-regulated kinase (ERK)1/2, which is critical for acquisition and consolidation of fear conditioning, was increased in the amygdala of APP transgenic mice after cued conditioning. Conclusions: We propose a deleterious role of intraneuronal Aβ on amygdala-dependent emotional responses by affecting the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway. [Copyright &y& Elsevier]

Gallego S, Llort A, Gros L, Sanchez de Toledo Jr J, Bueno J, Moreno A, Nieto J, Sanchez de Toledo J. Post-transplant lymphoproliferative disorders in children: The role of chemotherapy in the era of rituximab. Pediatr Transplantation 2010: 14: 61–66. © 2009 John Wiley & Sons A/S. PTLD are the most frequent neoplasms in children postorgan transplantation. We describe our experience in the treatment of 14 children (three with early and 11 with late-onset disease) treated with a step-wise protocol developed at our institution. Treatment consisted of reducing immunosuppressants, followed by rituximab and chemotherapy if required. Rituximab, incorporated into the protocol in 2001, has been determinant for the total chemotherapy burden patients need to achieve remission. In seven patients who did not receive rituximab, anthracycline total dose ranged from 160 to 240 mg/m2, while only one of the patients receiving rituximab required DOXO (range: 0–120 mg/m2) (p = 0.003). The use of alkylating agents was also notably lower in patients receiving rituximab (median dose = 1200 mg/m2) compared with those who did not receive rituximab (median dose = 5800 mg/m2) (p = 0.006). Twelve patients are in remission and two died, one from refractory disease and the other from septic shock. Two-year OS and EFS were 85.7% and 57%, respectively. In conclusion, our experience with the use of rituximab in children with PTLD after solid organ transplantation appeared to be associated with a lesser requirement for alkylating agents and anthracyclines compared with historical subjects, suggesting a reduction in the side effects of these agents. [ABSTRACT FROM AUTHOR]

The 3xTg-AD mouse develops a progressive Alzheimer's disease- (AD-) like brain pathology that causes cognitive- and neuropsychiatric-like symptoms of dementia. Since its neuroimmunoendocrine axis is likewise impaired, this mouse is also useful for modelling complex age-related neurodegeneration. This study analyzed behavioral, physiological, neurochemical, pathological and immunoendocrine alterations in male and female 3xTg-AD mice and assayed the effects of a short therapy of forced physical exercise at the moderate pathology stage of 6 months of age. Gender effects were observed in most AD-related pathology and dysfunctions. Five weeks of treadmill training produced beneficial effects, such as the reduction of brain oxidative stress and GABA-A receptor dysfunction in males and improvement of sensorimotor function in females. In both sexes, exercise decreased the brain amyloid β 42/40 ratio levels. The results highlight the importance of analyzing experimental therapies in both mouse model genders in order to improve our understanding of the disease and develop more appropriate therapies. [ABSTRACT FROM AUTHOR]

The centromere is a specialised chromosomal structure that regulates faithful chromosome segregation during cell division, as it dictates the site of assembly of the kinetochore, a critical structure that mediates binding of chromosomes to the spindle, monitors bipolar attachment and pulls chromosomes to the poles during anaphase. Identified more than a century ago as the primary constriction of condensed metaphase chromosomes, the centromere remained elusive to molecular characterisation for many years owed to its unusual enrichment in highly repetitive satellite DNA sequences, except in budding yeast. In the last decade, our understanding of centromere structure, organisation and function has increased tremendously. Nowadays, we know that centromere identity is determined epigenetically by the formation of a unique type of chromatin, which is characterised by the presence of the centromere-specific histone H3 variant CenH3, originally called CENP-A, which replaces canonical histone H3 at centromeres. CenH3-chromatin constitutes the physical and functional foundation for kinetochore assembly. This review explores recent studies addressing the structural and functional characterisation of CenH3-chromatin, its assembly and propagation during mitosis, and its contribution to kinetochore assembly. [ABSTRACT FROM AUTHOR]

• Kyphosis modified stride length and speed in gait in 3xTg-AD mice. • Bizarre gait patterns limit exploratory activity in transgenic mice. • Structural and postural kyphosis as a primary impaired that modifies gait in 3xTg-AD mice. • Bizarre gait patterns as secondary impaired to exploratory activity in 3xTg-AD mice. • Despite fraility, gait function is not impaired in non-trangenic mice. The shorter life spans of mice provide an exceptional experimental gerontology scenario. We previously described increased bizarre (disruptive) behaviors in the 6-month-old 3xTg-AD mice model for Alzheimer's disease (AD), compared to C57BL/6J wildtype (NTg), when confronting new environments. In the present work, we evaluated spontaneous gait and exploratory activity at old age, using 16-month-old mice. Male sex was chosen since sex-dependent psychomotor effects of aging are stronger in NTg males than females and, at this age, male 3 × Tg-AD mice are close to an end-of-life status due to increased mortality rates. Mice's behavior was evaluated in a transparent test box during the neophobia response. Stretching, jumping, backward movements and bizarre circling were identified during the gait and exploratory activity. The results corroborate that in the face of novelty and recognition of places, old 3xTg-AD mice exhibit increased bizarre behaviors than mice with normal aging. Furthermore, bizarre circling and backward movements delayed the elicitation of locomotion and exploration, in an already frail scenario, as shown by highly prevalent kyphosis in both groups. Thus, the translational study of co-occurrence of psychomotor impairments and anxiety-like behaviors can be helpful for understanding and managing the progressive functional deterioration shown in aging, especially in AD. [ABSTRACT FROM AUTHOR]

Abstract: Adenosine receptors in the central nervous system have been implicated in the modulation of different behavioural patterns and cognitive functions although the specific role of A2A receptor (A2AR) subtype in learning and memory is still unclear. In the present work we establish a novel transgenic rat strain, TGR(NSEhA2A), overexpressing adenosine A2ARs mainly in the cerebral cortex, the hippocampal formation, and the cerebellum. Thereafter, we explore the relevance of this A2ARs overexpression for learning and memory function. Animals were behaviourally assessed in several learning and memory tasks (6-arms radial tunnel maze, T-maze, object recognition, and several Morris water maze paradigms) and other tests for spontaneous motor activity (open field, hexagonal tunnel maze) and anxiety (plus maze) as modification of these behaviours may interfere with the assessment of cognitive function. Neither motor performance and emotional/anxious-like behaviours were altered by overexpression of A2ARs. TGR(NSEhA2A) showed normal hippocampal-dependent learning of spatial reference memory. However, they presented working memory deficits as detected by performance of constant errors in the blind arms of the 6 arm radial tunnel maze, reduced recognition of a novel object and a lack of learning improvement over four trials on the same day which was not observed over consecutive days in a repeated acquisition paradigm in the Morris water maze. Given the interdependence between adenosinic and dopaminergic function, the present results render the novel TGR(NSEhA2A) as a putative animal model for the working memory deficits and cognitive disruptions related to overstimulation of cortical A2ARs or to dopaminergic prefrontal dysfunction as seen in schizophrenic or Parkinson’s disease patients. [Copyright &y& Elsevier]