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In response to physiological and psychogenic stressors, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates the systemic release of glucocorticoids (GCs). By virtue of nearly ubiquitous expression of the GC receptor and the multifaceted metabolic, cardiovascular, cognitive, and immunologic functions of GCs, this system plays an essential role in the response to stress and restoration of an homeostatic state. GCs act on almost all types of immune cells and were long recognized to perform salient immunosuppressive and anti-inflammatory functions through various genomic and non-genomic mechanisms. These renowned effects of the steroid hormone have been exploited in the clinic for the past 70 years and synthetic GC derivatives are commonly used for the therapy of various allergic, autoimmune, inflammatory, and hematological disorders. The role of the HPA axis and GCs in restraining immune responses across the organism is however still debated in light of accumulating evidence suggesting that GCs can also have both permissive and stimulatory effects on the immune system under specific conditions. Such paradoxical actions of GCs are particularly evident in the brain, where substantial data support either a beneficial or detrimental role of the steroid hormone. In this review, we examine the roles of GCs on the innate immune system with a particular focus on the CNS compartment. We also dissect the numerous molecular mechanisms through which GCs exert their effects and discuss the various parameters influencing the paradoxical immunomodulatory functions of GCs in the brain.

Hormones control the major biological functions of stress response, growth, metabolism, and reproduction. In animals, these hormones show pronounced seasonality, with different set-points for different seasons. In humans, the seasonality of these hormones remains unclear, due to a lack of datasets large enough to discern common patterns and cover all hormones. Here, we analyze an Israeli health record on 46 million person-years, including millions of hormone blood tests. We find clear seasonal patterns: The effector hormones peak in winter−spring, whereas most of their upstream regulating pituitary hormones peak only months later, in summer. This delay of months is unexpected because known delays in the hormone circuits last hours. We explain the precise delays and amplitudes by proposing and testing a mechanism for the circannual clock: The gland masses grow with a timescale of months due to trophic effects of the hormones, generating a feedback circuit with a natural frequency of about a year that can entrain to the seasons. Thus, humans may show coordinated seasonal set-points with a winter−spring peak in the growth, stress, metabolism, and reproduction axes.

Abstract The past decade has seen several critical advances in our understanding of hypothalamic–pituitary–adrenal (HPA) axis regulation. Homeostatic physiological circuits need to integrate multiple internal and external stimuli and provide a dynamic output appropriate for the response parameters of their target tissues. The HPA axis is an example of such a homeostatic system. Recent studies have shown that circadian rhythmicity of the major output of this system—the adrenal glucocorticoid hormones corticosterone in rodent and predominately cortisol in man—comprises varying amplitude pulses that exist due to a subhypothalamic pulse generator. Oscillating endogenous glucocorticoid signals interact with regulatory systems within individual parts of the axis including the adrenal gland itself, where a regulatory network can further modify the pulsatile release of hormone. The HPA axis output is in the form of a dynamic oscillating glucocorticoid signal that needs to be decoded at the cellular level. If the pulsatile signal is abolished by the administration of a long-acting synthetic glucocorticoid, the resulting disruption in physiological regulation has the potential to negatively impact many glucocorticoid-dependent bodily systems. Even subtle alterations to the dynamics of the system, during chronic stress or certain disease states, can potentially result in changes in functional output of multiple cells and tissues throughout the body, altering metabolic processes, behavior, affective state, and cognitive function in susceptible individuals. The recent development of a novel chronotherapy, which can deliver both circadian and ultradian patterns, provides great promise for patients on glucocorticoid treatment. Graphical Abstract Graphical Abstract

Orthogonal Frequency Division Multiplexing (OFDM) is considered as a strong candidate for future wireless communication because it is marked by its higher frequency multiplicity and greater immunity to multipath fading. However, the main drawback of OFDM is its high amplitude fluctuations measured by peak-to-average power ratio (PAPR), which leads to power inefficiency and requires expensive high power amplifier (HPA) with very good linearity. In this paper, we propose selected mapping (SLM) with predistortion technique to decrease the nonlinear distortion and to improve the power efficiency of the nonlinear HPA. In the proposed method SLM reduces the PAPR and improves the power efficiency, the predistorter improves the bit error rate (BER) performance of the system. The PAPR reduction is possible with SLM when compared with original OFDM. After reducing the PAPR with SLM the data goes into the HPA with and without predistorter. The BER performance curves of SLM method with or without predistorter shows that, predistorter operates more effectively in SLM method than original OFDM system. At 4 dB IBO (input backoff) the conventional method with predistorter achieves 1.8 dB SNR gain than conventional method without a predistorter and at 6 dB IBO the BER performance is towards the ideal linear amplifier. The proposed system will be evaluated for OFDM system in the presence of a nonlinear power amplifier.

Persons with schizophrenia exhibit sensitivity to stress and negative affect (NA), both strongly correlated with poor functional outcome. This theoretical review suggests that NA reflects a “fragile brain,” ie, vulnerable to stress, including events not experienced as stressful by healthy individuals. Based on postmortem evidence of altered gamma-aminobutyric acid (GABA) function in parvalbumin positive interneurons (PVI), animal models of PVI abnormalities and neuroimaging data with GABAergic challenge, it is suggested that GABAergic disruptions weaken cortical regions, which leads to stress vulnerability and excessive NA. Neurocircuits that respond to stressful and salient environmental stimuli, such as the hypothalamic-pituitary-adrenal axis and the amygdala, are highly dysregulated in schizophrenia, exhibiting hypo- and hyper-activity. PVI abnormalities in lateral prefrontal cortex and hippocampus have been hypothesized to affect cognitive function and positive symptoms, respectively; in the medial frontal cortex (dorsal anterior cingulate cortex and dorsal medial prefrontal cortex), these abnormalities may lead to vulnerability to stress, NA and dysregulation of stress responsive systems. Given that postmortem PVI disruptions have been identified in other conditions, such as bipolar disorder and autism, stress vulnerability may reflect a transdiagnostic dimension of psychopathology.

The hypothalamic-pituitary-adrenal axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis. Abnormal development of the hypothalamic-pituitary-adrenal (HPA) axis can further result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery. Together, these changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood. In this review, we will discuss the regulation of the HPA axis and its development. We will also examine the maternal-fetal hypothalamic-pituitary-adrenal axis and disruption of the normal fetal environment which becomes a major risk factor for many neurodevelopmental pathologies in adulthood, such as major depressive disorder, anxiety, schizophrenia, and others.

This review describes stress-related biological mechanisms linking interpersonal racism to life course health trajectories among African Americans. Interpersonal racism, a form of social exclusion enacted via discrimination, remains a salient issue in the lives of African Americans, and it triggers a cascade of biological processes originating as perceived social exclusion and registering as social pain. Exposure to discrimination increases sympathetic nervous system activation and upregulates the HPA axis, increasing physiological wear and tear and elevating the risks of cardiometabolic conditions. Consequently, discrimination is associated with morbidities including low birth weight, hypertension, abdominal obesity, and cardiovascular disease. Biological measures can provide important analytic tools to study the interactions between social experiences such as racial discrimination and health outcomes over the life course. We make future recommendations for the study of discrimination and health outcomes, including the integration of neuroscience, genomics, and new health technologies; interdisciplinary engagement; and the diversification of scholars engaged in biosocial inequities research.

Investigating the developmental sequelae of early life stress has provided researchers the opportunity to examine adaptive responses to extreme environments. A large body of work has established mechanisms by which the stressful experiences of childhood poverty, maltreatment, and institutional care can impact the brain and the distributed stress systems of the body. These mechanisms are reviewed briefly to lay the foundation upon which the current neuroimaging literature has been built. More recently, developmental cognitive neuroscientists have identified a number of the effects of early adversity, including differential behavior and brain function. Among the most consistent of these findings are differences in the processing of emotion and reward-related information. The neural correlates of emotion processing, particularly frontolimbic functional connectivity, have been well studied in early life stress samples with results indicating accelerated maturation following early adversity. Reward processing has received less attention, but here the evidence suggests a deficit in reward sensitivity. It is as yet unknown whether the accelerated maturation of emotion-regulation circuits comes at the cost of delayed development in other systems, most notably the reward system. This review addresses the early life stress neuroimaging literature that has investigated emotion and reward processing, identifying important next steps in the study of brain function following adversity. •Early life stress alters functional connectivity in emotion and reward circuits.•Early adversity may result in accelerated maturation of emotion processing systems.•Accelerated maturation of emotion processing may slow development of other systems.•Functional connectivity is a tool for studying psychopathology after early adversity.

Kubernetes, an open-source container orchestration platform, enables high availability and scalability through diverse autoscaling mechanisms such as Horizontal Pod Autoscaler (HPA), Vertical Pod Autoscaler and Cluster Autoscaler. Amongst them, HPA helps provide seamless service by dynamically scaling up and down the number of resource units, called pods, without having to restart the whole system. Kubernetes monitors default Resource Metrics including CPU and memory usage of host machines and their pods. On the other hand, Custom Metrics, provided by external software such as Prometheus, are customizable to monitor a wide collection of metrics. In this paper, we investigate HPA through diverse experiments to provide critical knowledge on its operational behaviors. We also discuss the essential difference between Kubernetes Resource Metrics (KRM) and Prometheus Custom Metrics (PCM) and how they affect HPA’s performance. Lastly, we provide deeper insights and lessons on how to optimize the performance of HPA for researchers, developers, and system administrators working with Kubernetes in the future.

The system physiology approaches that emerge in western countries in recent years echo the holistic view of ancient Traditional Chinese Medicine (TCM) practices that deal with the root, rather than only the symptoms of diseases. Particularly, TCM practices, including acupuncture, emphasize the mobilization of self-healing mechanisms to bring back body homeostasis. Acupuncture has been practiced for over two thousand years to modulate body physiology via stimulation at specific body regions (acupoints). With the development of various research on acupuncture therapy, its regulatory effect on the immune system has been gradually recognized, especially on immunological diseases, including infectious and allergic diseases. In this study, we reviewed the immunomodulatory mechanism of acupuncture and systematically integrates existing research to respectively elucidate the modulatory mechanisms of acupuncture on the innate immune system, adaptive immune system, and well-known neuroanatomical mechanisms, including intact somatosensory-autonomic reflex pathway. With the advances made in recent systems physiology studies, we now have a great opportunity to gain insight into how acupuncture modulates immunity, and subsequently improves its efficacy.