Relationships among classifications of ayurvedic medicine diagnostics for imbalances and western measures of psychological states: An exploratory study.

BackgroundAccording to Ayurveda, the traditional medical system of India, doshas are a combination of characteristics based on a five-element philosophy that drive our mental and physical tendencies. When the doshas, or functional principles, are out of balance in quality or quantity, wellbeing is adversely affected and symptoms manifest.ObjectiveThis study examined relationships among imbalances in the doshas (termed Vikruti) reported via questionnaire and Western measures of psychological states.Materials and methodsStudy participants were 101 women (n = 81) and men (n = 20), mean age 53.9 years (SD = 11.7; range 32-80). Participants completed questionnaires to categorize their Vikruti type and psychological states, which included depressed mood (CESD), anxiety (PROMIS), rumination & reflection (RRQ), mindfulness (MAAS), stress (PSS), and quality of life (Ryff).ResultsMultivariate general linear modeling, controlling for age, gender and body mass index (BMI), showed that Vata imbalance was associated with more anxiety (p ≤ 0.05), more rumination (p ≤ 0.01), less mindfulness (p ≤ 0.05), and lower overall quality of life (p ≤ 0.01). Pitta imbalance was associated with poorer mood (p ≤ 0.01) and less mindfulness (p ≤ 0.05), more anxiety (p ≤ 0.05) and stress (p ≤ 0.05). Kapha imbalance was associated with more stress (p ≤ 0.05), more rumination (p ≤ 0.05) and less reflection (p ≤ 0.05).ConclusionThese findings suggest that symptoms of mind-body imbalances in Ayurveda are differentially associated with western assessments of psychological states. Ayurvedic dosha assessment may be an effective way to assess physical as well as emotional wellbeing in research and clinical settings

Salivary Cortisol Mediates Effects of Poverty and Parenting on Executive Functions in Early Childhood

In a predominantly low-income population-based longitudinal sample of 1,292 children followed from birth, higher level of salivary cortisol assessed at ages 7, 15, and 24 months was uniquely associated with lower executive function ability and to a lesser extent IQ at age 3 years. Measures of positive and negative aspects of parenting and household risk were also uniquely related to both executive functions and IQ. The effect of positive parenting on executive functions was partially mediated through cortisol. Typical or resting level of cortisol was increased in African American relative to White participants. In combination with positive and negative parenting and household risk, cortisol mediated effects of African American ethnicity, income-to-need, and maternal education on child cognitive ability.

16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.

The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa

Nanocuration workflows: Establishing best practices for identifying, inputting, and sharing data to inform decisions on nanomaterials

There is a critical opportunity in the field of nanoscience to compare and integrate information across diverse fields of study through informatics (i.e., nanoinformatics). This paper is one in a series of articles on the data curation process in nanoinformatics (nanocuration). Other articles in this series discuss key aspects of nanocuration (temporal metadata, data completeness, database integration), while the focus of this article is on the nanocuration workflow, or the process of identifying, inputting, and reviewing nanomaterial data in a data repository. In particular, the article discusses: 1) the rationale and importance of a defined workflow in nanocuration, 2) the influence of organizational goals or purpose on the workflow, 3) established workflow practices in other fields, 4) current workflow practices in nanocuration, 5) key challenges for workflows in emerging fields like nanomaterials, 6) examples to make these challenges more tangible, and 7) recommendations to address the identified challenges. Throughout the article, there is an emphasis on illustrating key concepts and current practices in the field. Data on current practices in the field are from a group of stakeholders active in nanocuration. In general, the development of workflows for nanocuration is nascent, with few individuals formally trained in data curation or utilizing available nanocuration resources (e.g., ISA-TAB-Nano). Additional emphasis on the potential benefits of cultivating nanomaterial data via nanocuration processes (e.g., capability to analyze data from across research groups) and providing nanocuration resources (e.g., training) will likely prove crucial for the wider application of nanocuration workflows in the scientific community

Nucleolar and spindle-associated protein 1 (NUSAP1) interacts with a SUMO E3 ligase complex during chromosome segregation

The mitotic spindle is composed of dynamic microtubules and associated proteins that together direct chromosome movement during mitosis. The spindle plays a vital role in accurate chromosome segregation fidelity and is a therapeutic target in cancer. Nevertheless, the molecular mechanisms by which many spindle-associated proteins function remains unknown. The nucleolar and spindle-associated protein NUSAP1 is a microtubule-binding protein implicated in spindle stability and chromosome segregation. We show here that NUSAP1 localizes to dynamic spindle microtubules in a unique chromosome-centric pattern, in the vicinity of overlapping microtubules, during metaphase and anaphase of mitosis. Mass spectrometry-based analysis of endogenous NUSAP1 interacting proteins uncovered a cell cycle-regulated interaction between the RanBP2-RanGAP1-UBC9 SUMO E3 ligase complex and NUSAP1. Like NUSAP1 depletion, RanBP2 depletion impaired the response of cells to the microtubule poison Taxol. NUSAP1 contains a conserved SAP domain (SAF-A/B, Acinus, and PIAS). SAP domains are common among many other SUMO E3s, and are implicated in substrate recognition and ligase activity. We speculate that NUSAP1 contributes to accurate chromosome segregation by acting as a co-factor for RanBP2-RanGAP1-UBC9 during cell division

The Psy-Security-Curriculum ensemble: British Values curriculum policy in English schools

Framed as being in response to terrorist attacks and concerns about religious bias in some English schools, ‘British Values’ (BV) curriculum policy forms part of the British Government’s Counter-Terrorism and Security Act, 2015. This includes a Duty on teachers in England to actively promote British Values to deter students from radicalisation. This paper, first, traces the history of Britishness in the curriculum to reveal a prevalence of nationalistic, colonial values. Next, an ensemble of recent policies and speeches focusing on British Values is analysed, using a psycho-political approach informed by anti-colonial scholarship. Finally, we interrogate two key critiques of the British Values curriculum discourse: the universality of British Values globally, and concerns over the securitisation of education. Findings indicate that the constitution of white British supremacist subjectivities operate through curriculum as a defence mechanism against perceived threats to white privilege, by normalising a racialised state-controlled social order. The focus is on ‘British’ values, but the analytic framework and findings have wider global significance

APC/C and SCF cyclin F Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry

The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/C(Cdh1) plays an important role in restricting S-phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box). We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. These data indicate that the coordinated, temporal ordering of cyclin F and Cdh1 degradation, organized in a double-negative feedback loop, represents a fundamental aspect of cell-cycle control. This mutual antagonism could be a feature of other oscillating systems

The E3 Ubiquitin Ligase SCF(Cyclin F) Transmits AKT Signaling to the Cell-Cycle Machinery

The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate. Cyclin F expression oscillates throughout the cell cycle, a rare feature among the 69 human F-box proteins, and all of its known substrates are involved in proliferation. AKT phosphorylation of cyclin F enhances its stability and promotes assembly into productive E3 ligase complexes. Importantly, expression of mutant versions of cyclin F that cannot be phosphorylated by AKT impair cell-cycle entry. Our data suggest that cyclin F transmits mitogen signaling through AKT to the core cell-cycle machinery. This discovery has potential implications for proliferative control in malignancies where AKT is activated

VprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell Cycle Transcription Factor FoxM1

The oncogenic transcription factor FoxM1 plays a vital role in cell cycle progression, is activated in numerous human malignancies, and is linked to chromosome instability. We characterize here a cullin 4-based E3 ubiquitin ligase and its substrate receptor, VprBP/DCAF1 (CRL4VprBP), which we show regulate FoxM1 ubiquitylation and degradation. Paradoxically, we also found that the substrate receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression strongly activates a FoxM1 transcriptional reporter. VprBP binding to CRL4 is reduced during mitosis, and our data suggest that VprBP activation of FoxM1 is ligase independent. This implies a nonproteolytic activation mechanism that is reminiscent of, yet distinct from, the ubiquitin-dependent transactivation of the oncoprotein Myc by other E3s. Significantly, VprBP protein levels were upregulated in high-grade serous ovarian patient tumors, where the FoxM1 signature is amplified. These data suggest that FoxM1 abundance and activity are controlled by VprBP and highlight the functional repurposing of E3 ligase substrate receptors independent of the ubiquitin system

Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control

The ubiquitin-proteasome system is essential for cell cycle progression. Cyclin F is a cell cycle-regulated substrate adapter F-box protein for the Skp1, CUL1, and F-box protein (SCF) family of E3 ubiquitin ligases. Despite its importance in cell cycle progression, identifying cyclin F-bound SCF complex (SCFCyclin F) substrates has remained challenging. Since cyclin F overexpression rescues a yeast mutant in the cdc4 gene, we considered the possibility that other genes that genetically modify cdc4 mutant lethality could also encode cyclin F substrates. We identified the mitochondrial and cytosolic deacylating enzyme sirtuin 5 (SIRT5) as a novel cyclin F substrate. SIRT5 has been implicated in metabolic processes, but its connection to the cell cycle is not known. We show that cyclin F interacts with and controls the ubiquitination, abundance, and stability of SIRT5. We show SIRT5 knockout results in a diminished G1 population and a subsequent increase in both S and G2/M. Global proteomic analyses reveal cyclin-dependent kinase (CDK) signaling changes congruent with the cell cycle changes in SIRT5 knockout cells. Together, these data demonstrate that SIRT5 is regulated by cyclin F and suggest a connection between SIRT5, cell cycle regulation, and metabolism