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As transsexual and transgender identity and experience have emerged from the outer boundaries of sexual identity and have become part of mainstream awareness of the full potential for sexual self-definition, cultural response has ranged widely. Responses include acceptance and approval; moderate levels of anxiety concerning perceptions of gender, sexual identity, and sex; obsessive fascination with the "otherness," the "not-me-ness" of those identifying as transsexual or transgender; the desire of non-trans-people to co-opt the experience of trans-people without personal risk; alarm at the reification of gender roles in what some people hoped would be a non-gender-defined, gender-neutral future. And more.

Elia Kazan's 1963 film, America America is a tribute to the immigrant experience of his own forebears, and has relevance to the refugee crisis of today. In stark black and white cinematography, the film provides insight into the refugee-immigrant experience, personified in Stavros, a young man longing for freedom, obsessed with an idealized America. His hope and innocence cannot safeguard him. His memories of his happy childhood and loving family create idealizing transferences to a world of others who manipulate and betray him as he undertakes his quest. Eventually he too learns to manipulate and betray, unconsciously identifying with the aggressor. History will offer ethical challenges, the black and white cinematography mirroring the black and white perception of good and bad, the shades of grey evoking a maturation of understanding.

Teaching professional ethics in psychoanalytic institutes begins with two assumptions: (1) Students learn not only a code of ethics, they learn to develop their inner ethicist. (2) Institutes do not "train" students to become versed in a professional discipline, institutes educate, so students acquire a complex range of knowledge, developing intellectually and emotionally. Studying professional ethics begins with questions concerning freedom, free will, and responsibility, allowing students to contemplate emotionally charged topics: power politics, collegial relationships, organizational malfeasance, and boundary violations. Another area of concern involves the ability to observe and manage countertransference. Another related theme is trust: trust in supervisors, training analysts, instructors, and one's own ability to process countertransference. Processing countertransference is a necessary ethical obligation. Instructors need to be aware of the emotional stresses involved in studying professional ethics, particularly in discussions of sexual boundary violations. Students developing an ethical stance can enhance creativity in psychoanalytic work.

Developmental issues arising from the dilemma of the protogay male child (as defined by Blum and Pfetzing in 1997) and the assaults to his sense of self are discussed in the context of the impact of the analytic attitude. Clinical material is offered as a 50-year-old gay man, troubled by his inability to form a lasting loving relationship with a man, experiences integration in the analytic relationship, stemming from what he describes as the "Yes" offered by his female analyst.

Ischemic stroke (IS) is a leading cause of morbidity and mortality globally and triggers a series of reactions leading to primary and secondary brain injuries and permanent neurological deficits. Microglia in the central nervous system play dual roles in neuroprotection and responding to ischemic brain damage. Here, an IS model is employed to determine the involvement of microglia in phagocytosis at excitatory synapses. Additionally, the effects of pharmacological depletion of microglia are investigated on improving neurobehavioral outcomes and mitigating brain injury. RNA sequencing of microglia reveals an increase in phagocytosis‐associated pathway activity and gene expression, and C‐type lectin domain family 7 member A (Clec7a) is identified as a key regulator of this process. Manipulating microglial Clec7a expression can potentially regulate microglial phagocytosis of synapses, thereby preventing synaptic loss and improving neurobehavioral outcomes after IS. It is further demonstrat that microglial Clec7a interacts with neuronal myeloid differentiation protein 2 (MD2), a key molecule mediating poststroke neurological injury, and propose the novel hypothesis that MD2 is a ligand for microglial Clec7a. These findings suggest that microglial Clec7a plays a critical role in mediating synaptic phagocytosis in a mouse model of IS, suggesting that Clec7a may be a therapeutic target for IS. [ABSTRACT FROM AUTHOR]

When dysregulated, skin fibrosis can lead to a multitude of pathologies. We provide a framework for understanding the wide clinical spectrum, mechanisms, and management of cutaneous fibrosis encompassing a variety of matrix disorders, fibrohistiocytic neoplasms, injury-induced scarring, and autoimmune scleroses. Underlying such entities are common mechanistic pathways that leverage morphogenic signaling, immune activation, and mechanotransduction to modulate fibroblast function. In light of the limited array of available treatments for cutaneous fibrosis, scientific insights have opened new therapeutic and investigative avenues for conditions that still lack effective interventions. [ABSTRACT FROM AUTHOR]

Aging is a complex multifactorial process associated with epigenome dysregulation, increased cellular senescence, and decreased rejuvenation capacity. Short-term cyclic expression of octamer-binding transcription factor 4 (Oct4), sex-determining region Y-box 2 (Sox2), Kruppel-like factor 4 (Klf4), and cellular myelocytomatosis oncogene (cMyc) (OSKM) in wild-type mice improves health but fails to distinguish cell states, posing risks to healthy cells. Here, we delivered a single dose of adeno-associated viruses (AAVs) harboring OSK under the control of the cyclin-dependent kinase inhibitor 2a (Cdkn2a) promoter to specifically partially reprogram aged and stressed cells in a mouse model of Hutchinson-Gilford progeria syndrome (HGPS). Mice showed reduced expression of proinflammatory cytokines and extended life spans upon aged cell–specific OSK expression. The bone marrow and spleen, in particular, showed pronounced gene expression changes, and partial reprogramming in aged HGPS mice led to a shift in the cellular composition of the hematopoietic stem cell compartment toward that of young mice. Administration of AAVs carrying Cdkn2a-OSK to naturally aged wild-type mice also delayed aging phenotypes and extended life spans without altering the incidence of tumor development. Furthermore, intradermal injection of AAVs carrying Cdkn2a-OSK led to improved wound healing in aged wild-type mice. Expression of CDKN2A-OSK in aging or stressed human primary fibroblasts led to reduced expression of inflammation-related genes but did not alter the expression of cell cycle–related genes. This targeted partial reprogramming approach may therefore facilitate the development of strategies to improve health and life span and enhance resilience in the elderly. Editor's summary: Partial cellular reprogramming via cyclic expression of octamer-binding transcription factor 4, sex-determining region Y-box 2, Kruppel-like factor 4, and cellular myelocytomatosis oncogene (OSKM) improves health and life span in mouse models but may lead to tumor induction or organ damage. Here, Sahu and colleagues used adeno-associated viruses to deliver OSK under the control of the cyclin-dependent kinase inhibitor 2a (Cdkn2a) promoter to specifically target stressed and senescent cells in a mouse model of Hutchinson-Guilford progeria syndrome. Treatment extended life spans and improved overall fitness, associated with a shift in the transcriptome toward that seen in younger mice. Similar effects occurred in aged wild-type mice and treatment did not increase tumor occurrence, suggesting that targeting partial cellular reprogramming to specific cell populations may be a more viable rejuvenation strategy moving forward. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Robust structural remodeling and synaptic plasticity occurs within spinal autonomic circuitry after severe high-level spinal cord injury (SCI). As a result, normally innocuous visceral or somatic stimuli elicit uncontrolled activation of spinal sympathetic reflexes that contribute to systemic disease and organ-specific pathology. How hyperexcitable sympathetic circuitry forms is unknown, but local cues from neighboring glia likely help mold these maladaptive neuronal networks. Here, we used a mouse model of SCI to show that microglia surrounded active glutamatergic interneurons and subsequently coordinated multi-segmental excitatory synaptogenesis and expansion of sympathetic networks that control immune, neuroendocrine, and cardiovascular functions. Depleting microglia during critical periods of circuit remodeling after SCI prevented maladaptive synaptic and structural plasticity in autonomic networks, decreased the frequency and severity of autonomic dysreflexia, and prevented SCI-induced immunosuppression. Forced turnover of microglia in microglia-depleted mice restored structural and functional indices of pathological dysautonomia, providing further evidence that microglia are key effectors of autonomic plasticity. Additional data show that microglia-dependent autonomic plasticity required expression of triggering receptor expressed on myeloid cells 2 (Trem2) and α2δ-1–dependent synaptogenesis. These data suggest that microglia are primary effectors of autonomic neuroplasticity and dysautonomia after SCI in mice. Manipulating microglia may be a strategy to limit autonomic complications after SCI or other forms of neurologic disease. Editor's summary: Spinal cord injuries (SCIs) above the mid-thoracic vertebrae disrupt central control over spinal autonomic circuits. The cellular drivers of the subsequent circuit remodeling that can lead to autonomic dysfunctions remain to be identified. Here, Brennan et al. used a mouse model of thoracic SCI and demonstrated that microglia depletion prevented SCI-associated autonomic circuit expansion as well as neuroendocrine dysregulation, immune dysfunction, and autonomic dysreflexia (AD). These results identify microglia as potential target to prevent maladaptive autonomic circuit remodeling. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]

Mapping the endocytic vesicular acidification process is of prior importance to better understand the health and pathological processes of cells. Herein, by integrating a pH-sensitive i-motif and a pair of fluorescence resonance energy transfer (FRET) into a tetrahedral DNA framework (TDF), we develop a pH-responsive DNA nanomachine, allowing for efficient sensing of pH from 7.0 to 5.5 via the pH-triggered spatial proximity modulation of FRET. The inheriting endo-lysosome-targeting ability of TDF enables spatiotemporal tracking of endocytic vesicle acidification during the endosomal maturation process. Analysis of pH-dependent FRET response at single fluorescent spot level reveals the significant difference of endocytic vesicular acidification between normal and cancer cells. The performance of pH-responsive DNA nanomachine underlines its potential for studies on vesicle acidification-related pathologies as a universal platform., (© 2024 Wiley-VCH GmbH.)

Diabetic retinopathy (DR) is recognized as the most prevalent retinal degenerative disorder. Inflammatory response usually precedes microvascular alteration and is the primary factor of diabetic retinopathy. Activated microglia express many pro-inflammatory cytokines that exacerbate retina inflammation and disruption. In the present study, we found that MSCs alleviated blood-retina barrier (BRB) breakdown in diabetic rats, as evidenced by reduced retinal edema, decreased vascular leakage, and increased occludin expression. The MSC-treated retinal microglia exhibited reduced expression of M1-phenotype markers in the diabetic rats, including inducible nitric oxide synthase (iNOS), CD16, and pro-inflammatory cytokines. On the other hand, MSCs increased the expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206, and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is activated in DR and inhibited after MSC treatment. Consistent with in vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro. Overexpression of HMGB1 in microglia reversed the effects of MSC treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs' regulatory effects on microglia polarization. Collectively, MSCs exert beneficial effects on DR by polarizing microglia from M1 toward M2 phenotype via inhibiting the HMGB1/TLR4 signaling pathway., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite the success of programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) inhibitors in treating solid tumors, only a proportion of patients respond. Here, we describe a first-in-class bifunctional therapeutic molecule, STAR0602, that comprises an antibody targeting germline Vβ6 and Vβ10 T cell receptors (TCRs) fused to human interleukin-2 (IL-2) and simultaneously engages a nonclonal mode of TCR activation with costimulation to promote activation and expansion of αβ T cell subsets expressing distinct variable β (Vβ) TCR chains. In solution, STAR0602 binds IL-2 receptors in cis with Vβ6/Vβ10 TCRs on the same T cell, promoting expansion of human Vβ6 and Vβ10 CD4+ and CD8+ T cells that acquire an atypical central memory phenotype. Monotherapy with a mouse surrogate molecule induced durable tumor regression across six murine solid tumor models, including several refractory to anti–PD-1. Analysis of murine tumor-infiltrating lymphocyte (TIL) transcriptomes revealed that expanded Vβ T cells acquired a distinct effector memory phenotype with suppression of genes associated with T cell exhaustion and TCR signaling repression. Sequencing of TIL TCRs also revealed an increased T cell repertoire diversity within targeted Vβ T cell subsets, suggesting clonal revival of tumor T cell responses. These immunological and antitumor effects in mice were recapitulated in studies of STAR0602 in nonhuman primates and human ex vivo models, wherein STAR0602 boosted human antigen-specific T cell responses and killing of tumor organoids. Thus, STAR0602 represents a distinct class of T cell–activating molecules with the potential to deliver enhanced antitumor activity in checkpoint inhibitor–refractory settings. Editor's summary: Activating T cells by targeting T cell receptors (TCRs), costimulatory receptors, or cytokine receptors represents an attractive approach to improving antitumor T cell responses; however, these approaches often do not sufficiently stimulate T cell responses and can cause severe toxicities that have impeded their translation into the clinic. To address this, Hsu et al. developed a bifunctional therapeutic molecule called STAR0602, comprising an antibody specific to human TCR Vβ6 and Vβ10 chains fused to a human interleukin-2 (IL-2) molecule, which selectively activates a subset of T cells through both the TCR and IL-2 receptor signaling pathways. STAR0602 promoted specific expansion of human Vβ6- and Vβ10-expressing T cells and promoted killing of human tumor organoids in vitro. In vivo studies showed that a murine surrogate molecule promoted durable control of tumor burden in six solid tumor models. These data, along with favorable safety data, support further development of STAR0602 and similar TCR-targeting antibody fusion molecules. —Courtney Malo [ABSTRACT FROM AUTHOR]

Aesthetic sensibility is a feature of an ontological approach to psychoanalysis. The author writes about an analysis that switched to video work during the COVID-19 pandemic. Without co-presence, the analyst found sensorial substitutes for in-person contact with the patient through her aesthetic experiences of a film, a song, and a poem, which served as transitional spaces for analytic functioning. This was central in facilitating an affective, embodied contact – a felt-sense – with the experience of separation during the pandemic. The analyst's aesthetic engagement can enable connectivity within the analytic field and mediate an expansion of consciousness in analytic work. [ABSTRACT FROM AUTHOR]

Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung-migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This protection is associated with a lymphocytic infiltrate, including increased accumulation of pulmonary SCV2-specific CD8+ T cells, and anti-CD8 antibody depletion abrogated the N. brasiliensis–mediated reduction in viral loads. Pulmonary macrophages with a type 2 transcriptional and epigenetic signature persist in the lungs of N. brasiliensis–exposed mice after clearance of the parasite and establish a primed environment for increased CD8+ T cell recruitment and activation. Accordingly, depletion of macrophages ablated the augmented viral clearance and accumulation of CD8+ T cells driven by prior N. brasiliensis infection. Together, these findings support the concept that lung-migrating helminths can limit disease severity during SCV2 infection through macrophage-dependent enhancement of antiviral CD8+ T cell responses. Editor's summary: Parasitic helminths generate a type 2 immune response that can persist even after clearance of the infection, but how this affects subsequent immunity against viral infections remains unclear. Using a mouse model of roundworm infection with Nippostrongylus brasiliensis, Oyesola et al. found that prior exposure to lung-migrating helminths protects transgenic K18-hACE2 mice against SARS-CoV-2 infection. Pulmonary macrophages from N. brasiliensis–infected mice adopted a type 2 transcriptional and epigenetic signature that persisted after parasite clearance and at least 45 days after infection. SARS-CoV-2–specific CD8+ T cell responses were driven by alveolar macrophages and required for helminth-mediated protection. These results demonstrate that lung-migrating helminths reprogram lung immune homeostasis, leading to enhanced protection against subsequent SARS-CoV-2 infection. —Claire Olingy [ABSTRACT FROM AUTHOR]

The study of synthetic biology focusing on biosensor systems has resulted from a growing interest in developing customized biological devices with desired cellular functions. Recently, biosensors have been used for a variety of medical applications such as disease diagnosis, prevention, rehabilitation, patient health monitoring, and human health management. Meanwhile, the ability to track biomarkers based on biosensors allows researchers and medical practitioners to provide patients with individualized treatment regimens and health management. Biosensors that respond to electrochemical, optical, thermal, piezoelectric and magnetic signals have been developed and utilized for various disease therapies and biomedical applications. This study reviews recent developments in biosensor-based therapeutic tools by sensing diverse biomarkers in many diseases (e.g. cancer, infections, metabolic diseases), such as physical biomarkers (e.g. pressure, temperature) and chemical biomarkers (e.g. dissolved oxygen, glucose). Additionally, we highlight the challenges and problems of biosensor-based therapeutics and possible solutions for biosensor engineering thereof. Current biosensors enable for coarsely programable personal treatment and health management, however, new sensors with optimized dose-response functions, for example, fast response and tight-control performances, could significantly boost versatile uses in medical treatment in the coming future. [ABSTRACT FROM AUTHOR]

Type 2 immunity is associated with adipose tissue (AT) homeostasis and infection with parasitic helminths, but whether AT participates in immunity to these parasites is unknown. We found that the fat content of mesenteric AT (mAT) declined in mice during infection with a gut-restricted helminth. This was associated with the accumulation of metabolically activated, interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and extracellular matrix (ECM)–producing stromal cells. These cells shared transcriptional features, including the expression of Dpp4 and Pi16, with multipotent progenitor cells (MPC) that have been identified in numerous tissues and are reported to be capable of differentiating into fibroblasts and adipocytes. Concomitantly, mAT became infiltrated with resident T helper 2 (TH2) cells that responded to TSLP and IL-33 by producing stromal cell–stimulating cytokines, including transforming growth factor β1 (TGFβ1) and amphiregulin. These TH2 cells expressed genes previously associated with type 2 innate lymphoid cells (ILC2), including Nmur1, Calca, Klrg1, and Arg1, and persisted in mAT for at least 11 months after anthelmintic drug–mediated clearance of infection. We found that MPC and TH2 cells localized to ECM-rich interstitial spaces that appeared shared between mesenteric lymph node, mAT, and intestine. Stromal cell expression of epidermal growth factor receptor (EGFR), the receptor for amphiregulin, was required for immunity to infection. Our findings point to the importance of MPC and TH2 cell interactions within the interstitium in orchestrating AT remodeling and immunity to an intestinal infection. Adipose tissue affects parasitic infection: Adipose tissue has been linked to immune responses and protection against infection, but how it contributes to parasitic helminths remains unclear. Here, Kabat et al. used RNA-seq, metabolomics, flow cytometry, and histology to study the adipose tissue from mice infected with intestinal Heligmosomoides polygyrus. They found that helminth gut infection reduced mesenteric adipose tissue, which associated with increased infiltration of resident TH2 CD4+ T cells that produced TGFβ and amphiregulin. Via these factors, resident TH2s communicated with thymic stromal lymphopoietin and IL-33–producing stromal cells in the collagen-rich interstitial spaces of the mesenteric adipose tissue. Disrupting amphiregulin signaling in stromal cells led to worse H. polygyrus infection. Thus, TH2 and stromal cells communicate in the adipose tissue, contributing to anti-parasite immunity. [ABSTRACT FROM AUTHOR]

Repeated closed head injury (rCHI) is one of the most common brain injuries. Although extensive studies have focused on how to treat rCHI-induced brain injury and reduce the possibility of developing memory deficits, the prevention of rCHI-induced anxiety has received little research attention. The current study was designed to assess the effects of photobiomodulation (PBM) therapy in preventing anxiety following rCHI. The rCHI disease model was constructed by administering three repeated closed-head injuries within an interval 5 days. 2-min daily PBM therapy using an 808 nm continuous wave laser at 350 mW/cm 2 on the scalp was implemented for 20 days. We found that PBM significantly ameliorated rCHII-induced anxiety-like behaviors, neuronal apoptosis, neuronal injury, promotes astrocyte/microglial polarization to anti-inflammatory phenotype, preserves mitochondrial fusion-related protein MFN2, attenuates the elevated mitochondrial fission-related protein DRP1, and mitigates neuronal senescence. We concluded that PBM therapy possesses great potential in preventing anxiety following rCHI., (© 2023 Wiley-VCH GmbH.)

Processing and managing countertransference are part of the responsibilities of counsellors to fulfil their ethical obligation. The transcendental phenomenological design was applied in the present study to examine the subjective lived experiences of counsellors in managing their countertransference. The data of six Malaysian counsellors who reported experiencing countertransference were collected through audio recordings and in-depth phenomenological interviews. The collected data were analysed using Moustakas' data analysis method. Seven themes emerged from the study: self-reflection, professional consultation, recognising the occurrence of countertransference; personal self-care strategies; emotion regulation; preparation for cases; and physical and emotional separation. Each major theme was supported by subthemes. This study highlighted the effective ways for counsellors in managing their countertransference experiences throughout their professional helping journey. [ABSTRACT FROM AUTHOR]

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury. Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2. However, the extent to which thalamic inflammation is a driver or by-product of neurological deficits remains unknown. Here, we found that thalamic inflammation in mice was sufficient to phenocopy the cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms that develop after cortical injury. In our model, down-regulation of the GABA transporter GAT-3 in thalamic astrocytes mediated this neurological dysfunction. In addition, GAT-3 was decreased in regions of thalamic reactive astrocytes in mouse models of cortical injury. Enhancing GAT-3 in thalamic astrocytes prevented seizure risk, restored cortical states, and was protective against severe chemoconvulsant-induced seizures and mortality in a mouse model of traumatic brain injury, emphasizing the potential of therapeutically targeting this pathway. Together, our results identified a potential therapeutic target for reducing negative outcomes after brain injury. Halting astrocytes at the GAT3: Uncontrolled inflammation in the brain after an injury has been shown to contribute to increased seizure risk and cognitive impairments. The thalamus is a brain area particularly susceptible to damage after an injury. Here, Cho and colleagues showed that thalamic inflammation per se was sufficient to trigger the negative effects of brain injury by modulating the expression of the GABA-transported GAT3 in astrocytes. Restoring the expression of the GABA-transported GAT3 in this cell population reduced the negative outcomes associated with brain injury, suggesting that targeting astrocytes in the thalamus might be effective for preventing negative outcomes after brain injury. [ABSTRACT FROM AUTHOR]

The mammalian airways and lungs are exposed to a myriad of inhaled particulate matter, allergens, and pathogens. The immune system plays an essential role in protecting the host from respiratory pathogens, but a dysregulated immune response during respiratory infection can impair pathogen clearance and lead to immunopathology. Furthermore, inappropriate immunity to inhaled antigens can lead to pulmonary diseases. A complex network of epithelial, neural, stromal, and immune cells has evolved to sense and respond to inhaled antigens, including the decision to promote tolerance versus a rapid, robust, and targeted immune response. Although there has been great progress in understanding the mechanisms governing immunity to respiratory pathogens and aeroantigens, we are only beginning to develop an integrated understanding of the cellular networks governing tissue immunity within the lungs and how it changes after inflammation and over the human life course. An integrated model of airway and lung immunity will be necessary to improve mucosal vaccine design as well as prevent and treat acute and chronic inflammatory pulmonary diseases. Given the importance of immunology in pulmonary research, the American Thoracic Society convened a working group to highlight central areas of investigation to advance the science of lung immunology and improve human health. [ABSTRACT FROM AUTHOR]

Aim: The mental confusion and cognitive indecision of the staff in the university will cause mental confusion and negat ive consequences in individual and organizat ional dimensions. However, using the imagination and mental creativity of employees, which is known as a dream, can be used as a psychological tool for managers, so the purpose of this study was to design a model of employees' dream power in organizations. Method: The method of this research is applied in terms of purpose, with a qualitat iveexploratory approach and in terms of implementat ion using data-based technique. The tools used were semist ructured interviews with experts in this field, including professors of career counseling and organizational behavior and administrative managers of ShahidBeheshti University, wh ose number was selected using targeted snowball sampling based on the principle of saturation, 12 p eople. Findings: The results showed that a total of 40 catego ries and 364 stat istical codes were set in the form o f f ive causal categories, contexts, intervent ions, st r ategies and consequences. Conclusion: The results sh owed that the drawn model of employees' dr eam p ower can relat ively lead to leaps in organizational creativity and innovation and overcome the crisis o f burnout and inertia of the organization and managers can use this technique to train employees with high motivat ion. Pursue the competencies and goals of the organization beyond those mentioned. [ABSTRACT FROM AUTHOR]

Understanding circuit organization depends on identification of cell types. Recent advances in transcriptional profiling methods have enabled classification of cell types by their gene expression. While exceptionally powerful and high throughput, the ground-truth validation of these methods is difficult: If cell type is unknown, how does one assess whether a given analysis accurately captures neuronal identity? To shed light on the capabilities and limitations of solely using transcriptional profiling for cell-type classification, we performed 2 forms of transcriptional profiling--RNA-seq and quantitative RT-PCR, in single, unambiguously identified neurons from 2 small crustacean neuronal networks: The stomatogastric and cardiac ganglia. We then combined our knowledge of cell type with unbiased clustering analyses and supervised machine learning to determine how accurately functionally defined neuron types can be classified by expression profile alone. The results demonstrate that expression profile is able to capture neuronal identity most accurately when combined with multimodal information that allows for post hoc grouping, so analysis can proceed from a supervised perspective. Solely unsupervised clustering can lead to misidentification and an inability to distinguish between 2 or more cell types. Therefore, this study supports the general utility of cell identification by transcriptional profiling, but adds a caution: It is difficult or impossible to know under what conditions transcriptional profiling alone is capable of assigning cell identity. Only by combining multiple modalities of information such as physiology, morphology, or innervation target can neuronal identity be unambiguously determined. [ABSTRACT FROM AUTHOR]

Interleukin-2 (IL-2), the first cytokine that was molecularly cloned, was shown to be a T cell growth factor essential for the proliferation of T cells and the generation of effector and memory cells. On the basis of this activity, the earliest therapeutic application of IL-2 was to boost immune responses in cancer patients. Therefore, it was a surprise that genetic deletion of the cytokine or its receptor led not only to the expected immune deficiency but also to systemic autoimmunity and lymphoproliferation. Subsequent studies established that IL-2 is essential for the maintenance of Foxp3+ regulatory T cells (Treg cells), and in its absence, there is a profound deficiency of Treg cells and resulting autoimmunity. We now know that IL-2 promotes the generation, survival, and functional activity of Treg cells and thus has dual and opposing functions: maintaining Treg cells to control immune responses and stimulating conventional T cells to promote immune responses. It is well documented that certain IL-2 conformations result in selective targeting of Treg cells by increasing reliance on CD25 binding while compromising CD122 binding. Recent therapeutic strategies have emerged to use IL-2, monoclonal antibodies to IL-2, or IL-2 variants to boost Treg cell numbers and function to treat autoimmune diseases while dealing with the continuing challenges to minimize the generation of effector and memory cells, natural killer cells, and other innate lymphoid populations. [ABSTRACT FROM AUTHOR]

The article focuses on astroglial lineage was investigated in model systems of a developmental disorder with intellectual disability caused by mutant Harvey rat sarcoma viral oncogene homolog (HRAS) termed Costello syndrome. It mentions HRAS human induced pluripotent stem cells (iPSCs) and transgenic mice and farnesyl transferase inhibitor and knockdown of transcription factor SNAI2. It also mentions perineuronal net proteoglycans as well as increased parvalbumin expression in interneurons.

A growing body of evidence shows that aboveground and belowground communities and processes are intrinsically linked, and that feedbacks between these subsystems have important implications for community structure and ecosystem functioning. Almost all studies on this topic have been carried out from an empirical perspective and in specific ecological settings or contexts. Belowground interactions operate at different spatial and temporal scales. Due to the relatively low mobility and high survival of organisms in the soil, plants have longer lasting legacy effects belowground than aboveground. Our current challenge is to understand how aboveground–belowground biotic interactions operate across spatial and temporal scales, and how they depend on, as well as influence, the abiotic environment. Because empirical capacities are too limited to explore all possible combinations of interactions and environmental settings, we explore where and how they can be supported by theoretical approaches to develop testable predictions and to generalise empirical results. We review four key areas where a combined aboveground–belowground approach offers perspectives for enhancing ecological understanding, namely succession, agro-ecosystems, biological invasions and global change impacts on ecosystems. In plant succession, differences in scales between aboveground and belowground biota, as well as between species interactions and ecosystem processes, have important implications for the rate and direction of community change. Aboveground as well as belowground interactions either enhance or reduce rates of plant species replacement. Moreover, the outcomes of the interactions depend on abiotic conditions and plant life history characteristics, which may vary with successional position. We exemplify where translation of the current conceptual succession models into more predictive models can help targeting empirical studies and generalising their results. Then, we discuss how understanding succession may help to enhance managing arable crops, grasslands and invasive plants, as well as provide insights into the effects of global change on community re-organisation and ecosystem processes. [ABSTRACT FROM AUTHOR]

The article focuses on primitive disorders, in which patients lived in a state of profound psychological disorganization and disintegration and are trapped in a state of mind that attacks all links and all meaning. It says that primitive patients had experienced early attachment trauma which left them feeling a nobody, nowhere. It highlights the author's session with her patient who was a premature infant and had develop neurodevelopmental impairments in right hemisphere.

1. Wood frog (Rana sylvatica) tadpoles, hatched from egg masses collected in the field, were reared either with siblings only or in mixed groups of eight sibships. Sibships were marked with vital stains, released in a laboratory test pool, and their spatial distributions recorded over a 4-day period. 2. An analysis of nearest-neighbor distances suggests that tadpoles preferentially associated with familiar siblings over both familiar and unfamiliar non-siblings. Kinship preferences of R. sylvatica tadpoles, unlike those of other anurans that have been tested, thus appear largely unaffected by prior social experience. 3. Tadpoles reared in mixed sibship groups preferentially associated with the siblings with which they were reared over unfamiliar siblings exposed to a different set of sibships. In contrast, tadpoles did not discriminate either between siblings reared in different baskets within the same mixed group tank, or between siblings housed in different single-sibship containers. 4. Because R. sylvatica egg masses are usually deposited in communal clumps, an ability to recognize relatives not dependent on post-embryonic experience may have been selected. The possible adaptive significance of kin association among wood frog tadpoles is unknown; their schools probably do not represent kin groups, but larval distributions in natural ponds might reflect sibling association tendencies. 5. Kin recognition "labels" of non-sibling R. sylvatica tadpoles reared together, like those of R. cascadae tadpoles similarly reared, may converge as a result of social interactions. R. sylvatica tadpoles, unlike R. cascadae tadpoles, retain an ability to discriminate between familiar siblings and familiar non-siblings; hence label transference may be incomplete. [ABSTRACT FROM AUTHOR]