Based on our findings, we recommend the implementation of ecosystem-based and adaptive management strategies, such as (1) monitoring the status of key ecosystem attributes kelp distribution and abundance, and densities of sea urchins and their predators, (2) developing management responses to threshold levels of these attributes, and (3) creating quantitative restoration suitability indices for informing kelp restoration efforts.Tissue clearing is one of the most powerful strategies for a comprehensive analysis of disease progression. Here, we established an integrated pipeline that combines tissue clearing, 3D imaging, and machine learning and applied to a mouse tumour model of experimental lung metastasis using human lung adenocarcinoma A549 cells. This pipeline provided the spatial information of the tumour microenvironment. We further explored the role of transforming growth factor-β (TGF-β) in cancer metastasis. TGF-β-stimulated cancer cells enhanced metastatic colonization of unstimulated-cancer cells in vivo when both cells were mixed. RNA-sequencing analysis showed that expression of the genes related to coagulation and inflammation were up-regulated in TGF-β-stimulated cancer cells. Further, whole-organ analysis revealed accumulation of platelets or macrophages with TGF-β-stimulated cancer cells, suggesting that TGF-β might promote remodelling of the tumour microenvironment, enhancing the colonization of cancer cells. Hence, our integrated pipeline for 3D profiling will help the understanding of the tumour microenvironment.As an active interface between the host and their diet, the gut microbiota influences host metabolic adaptation; however, the contributions of fungi have been overlooked. Here, we investigate whether variations in gut mycobiome abundance and composition correlate with key features of host metabolism. We obtained animals from four commercial sources in parallel to test if differing starting mycobiomes can shape host adaptation in response to processed diets. We show that the gut mycobiome of healthy mice is shaped by the environment, including diet, and significantly correlates with metabolic outcomes. We demonstrate that exposure to processed diet leads to persistent differences in fungal communities that significantly associate with differential deposition of body mass in male mice compared to mice fed standardized diet. Fat deposition in the liver, transcriptional adaptation of metabolically active tissues and serum metabolic biomarker levels are linked with alterations in fungal community diversity and composition. Specifically, variation in fungi from the genera Thermomyces and Saccharomyces most strongly associate with metabolic disturbance and weight gain. These data suggest that host-microbe metabolic interactions may be influenced by variability in the mycobiome. This work highlights the potential significance of the gut mycobiome in health and has implications for human and experimental metabolic studies.Bion (1970) saw his concept of 'O' as the central psychoanalytic perspective. It is a waking dream state, seen also as an essentially "religious" or spiritual perspective. While religious ideas may seem far afield in a discussion of fundamental elements of psychoanalysis, the word "spiritual" here refers simply to metaphysical matters of the spirit, mind, or personality, three terms used interchangeably by Bion. This essential experience of 'O' is seen as a selfless state, which the author clearly distinguishes from pathological states of selflessness, mindlessness, or nothingness often seen in patients who suffered early emotional trauma. Philosophical ideas about being and non-being help to clarify the difference. The challenges in finding an effective language to communicate verbally with pre-verbal states are explored through detailed clinical examples of working with often intractable states of resistance to being.Bipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30-40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of "clock genes" and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms. However, circadian rhythms have not been evaluated in BD patient neurons from Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients characterized for lithium responsiveness and matched controls. We identified strong circadian rhythms in Per2-luc expression in NPCs and neurons from controls and Li-R, but NPC rhythms in Li-R had a shorter circadian period. Li-NR rhythms were low amplitude and profoundly weakened. In NPCs and neurons, expression of PER2 was higher in both BD groups compared to controls. In neurons, PER2 protein levels were higher in BD than controls, especially in Li-NR samples. In single cells, NPC and neuron rhythms in both BD groups were desynchronized compared to controls. Lithium lengthened period in Li-R and control neurons but failed to alter rhythms in Li-NR. In contrast, temperature entrainment increased amplitude across all groups, and partly restored rhythms in Li-NR neurons. We conclude that neuronal circadian rhythm abnormalities are present in BD and most pronounced in Li-NR. Rhythm deficits in BD may be partly reversible through stimulation of entrainment pathways.Prion diseases are fatal neurodegenerative conditions with highly accurate CSF and imaging diagnostic tests, but major unmet needs for blood biomarkers. Using ultrasensitive immuno-assays, we measured tau and neurofilament light chain (NfL) protein concentrations in 709 plasma samples taken from 377 individuals with prion disease during a 12 year prospective clinical study, alongside healthy and neurological control groups. https://www.selleckchem.com/products/bms303141.html This provides an unprecedented opportunity to evaluate their potential as biomarkers. Plasma tau and NfL were increased across all prion disease types. For distinguishing sCJD from control groups including clinically-relevant "CJD mimics", both show considerable diagnostic value. In sCJD, NfL was substantially elevated in every sample tested, including during early disease with minimal functional impairment and in all follow-up samples. Plasma tau was independently associated with rate of clinical progression in sCJD, while plasma NfL showed independent association with severity of functional impairment. |