Bis(tetraphenylphosphonium) di-μ-iodido-bis[diiodidopalladate(II)].

The title compound, (PPh4)2[Pd2I6], was obtained unintentionally as the product of an attempted synthesis of a tripalladium sandwich complex. The molecular dimensions are unexceptional and the Pd---Pd distance, at 3.8183 (12) A,is much too long for any Pd—Pd interaction. Pd has a typical square-planar coordination geometry and the centrosymmetric anion is essentially planar

Modulation of DNA loop lifetimes by the free energy of loop formation

Storage and retrieval of the genetic information in cells is a dynamic process that requires the DNA to undergo dramatic structural rearrangements. DNA looping is a prominent example of such a structural rearrangement that is essential for transcriptional regulation in both prokaryotes and eukaryotes, and the speed of such regulations affects the fitness of individuals. Here, we examine the in vitro looping dynamics of the classic Lac repressor gene-regulatory motif. We show that both loop association and loop dissociation at the DNA-repressor junctions depend on the elastic deformation of the DNA and protein, and that both looping and unlooping rates approximately scale with the looping J factor, which reflects the system's deformation free energy. We explain this observation by transition state theory and model the DNA-protein complex as an effective worm-like chain with twist. We introduce a finite protein-DNA binding interaction length, in competition with the characteristic DNA deformation length scale, as the physical origin of the previously unidentified loop dissociation dynamics observed here, and discuss the robustness of this behavior to perturbations in several polymer parameters

Using the behaviour change wheel and person-based approach to develop a digital self-management intervention for patients with adrenal insufficiency: the Support AI study protocol

Introduction: Most patients with Adrenal insufficiency (AI) require lifelong glucocorticoid replacement. They need to increase glucocorticoids during physical illness or major stressful situations and require parenteral hydrocortisone in the event of an adrenal crisis. Patients with AI have impaired quality of life and high mortality; approximately 1 in 6-12 patients are hospitalised at least once/year from a potentially preventable adrenal crisis. Adoption of self-management behaviours are crucial; these include adherence to medication, following “sick day rules” and associated behaviours that aid prevention and treatment of adrenal crisis such as symptom monitoring, having extra tablets, carrying a medical-alert ID and injection kit, and self-injecting when necessary. Current patient education is ineffective at supporting self-management behaviour change or reducing adrenal crisis-related hospitalisations. This research study aims to gain an in-depth understanding of the barriers and enablers to self-management for patients with AI and to develop an evidence-based digital self-management behaviour change intervention. / Methods: The study is conducted in accordance with the MRC Framework for developing complex interventions. Underpinned by the Behaviour Change Wheel (BCW), the Theoretical Domains Framework (TDF), and the Person-Based Approach, this research will be conducted in two phases: Phase 1 will involve a sequential qualitative/quantitative mixed-methods study involving focus group interviews followed by a cross-sectional survey with patients with AI recruited from patient advocacy groups and endocrine clinics in the UK. Phase 2 will develop the Support AI, a website-based digital behaviour change intervention (DBCI) informed by Phase 1 findings to support self-management for patients with AI. The most appropriate behaviour change techniques (BCTs) will be selected utilising a nominal group technique with an Expert Panel of 10-15 key stakeholders. The design of the Support AI website will be guided by the Person-Based Approach using an Agile iterative “think-aloud” technique with 12-15 participants over 3 usability testing iterations. / Conclusion: A theory- and evidence-based digital behaviour change intervention will be developed which will be tested in a feasibility randomised trial following completion of this study. The projected benefit includes cost-effective health care service (reduced hospitalisations and demand for specialist services) and improved health outcomes and quality of life for patients with AI

De novo design of bioactive protein switches.

Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering

Investigating Remote-sensing Techniques to Reveal Stealth Coronal Mass Ejections

Eruptions of coronal mass ejections (CMEs) from the Sun are usually associated with a number of signatures that can be identified in solar disc imagery. However, there are cases in which a CME that is well observed in coronagraph data is missing a clear low-coronal counterpart. These events have received attention during recent years, mainly as a result of the increased availability of multi-point observations, and are now known as 'stealth CMEs'. In this work, we analyse examples of stealth CMEs featuring various levels of ambiguity. All the selected case studies produced a large-scale CME detected by coronagraphs and were observed from at least one secondary viewpoint, enabling a priori knowledge of their approximate source region. To each event, we apply several image processing and geometric techniques with the aim to evaluate whether such methods can provide additional information compared to the study of "normal" intensity images. We are able to identify at least weak eruptive signatures for all events upon careful investigation of remote-sensing data, noting that differently processed images may be needed to properly interpret and analyse elusive observations. We also find that the effectiveness of geometric techniques strongly depends on the CME propagation direction with respect to the observers and the relative spacecraft separation. Being able to observe and therefore forecast stealth CMEs is of great importance in the context of space weather, since such events are occasionally the solar counterparts of so-called 'problem geomagnetic storms'.Comment: 26 pages, 8 figures, 1 table, accepted for publication in Frontiers in Astronomy and Space Science

Adjustment of global precipitation data for enhanced hydrologic modeling of tropical Andean watersheds

Global gridded precipitation is an essential driving input for hydrologic models to simulate runoff dynamics in large river basins. However, the data often fail to adequately represent precipitation variability in mountainous regions due to orographic effects and sparse and highly uncertain gauge data. Water balance simulations in tropical montane regions covered by cloud forests are especially challenging because of the additional water input from cloud water interception. The ISI-MIP2 hydrologic model ensemble encountered these problems for Andean sub-basins of the Upper Amazon Basin, where all models significantly underestimated observed runoff. In this paper, we propose simple yet plausible ways to adjust global precipitation data provided by WFDEI, the WATCH Forcing Data methodology applied to ERA-Interim reanalysis, for tropical montane watersheds. The modifications were based on plausible reasoning and freely available tropics-wide data: (i) a high-resolution climatology of the Tropical Rainfall Measuring Mission (TRMM) and (ii) the percentage of tropical montane cloud forest cover. Using the modified precipitation data, runoff predictions significantly improved for all hydrologic models considered. The precipitation adjustment methods presented here have the potential to enhance other global precipitation products for hydrologic model applications in the Upper Amazon Basin as well as in other tropical montane watersheds

Expanded Food and Nutrition Education Program (EFNEP) Paraprofessional Supervision: Crucial Components for Program Success

The Expanded Food and Nutrition Education Program (EFNEP) national leadership and university program partners initiated a discussion about EFNEP paraprofessional supervision due to concerns raised by state coordinators and a belief that the quality and adequacy of paraprofessional supervision have a considerable impact on program outcomes and effectiveness. An EFNEP Paraprofessional Supervision Committee was formed and tasked with developing a framework of paraprofessional supervisory components necessary for effective local supervision of EFNEP within various university and state contexts. The committee conceptualized EFNEP supervision as consisting of three crucial components: responsibilities; traits and skills; and critical support. Responsibilities outline the day-to-day tasks that EFNEP supervisors are expected to complete. Traits and skills underscore the qualities and behaviors that assist a supervisor with the effective implementation of duties, and are categorized as essential, important, or helpful. Critical support articulates the core functions that are shared by the EFNEP supervisor and those who support the supervisor and the program, both specifically and more generally, including administrators and directors. The committee outlined a call to action to address the needs expressed by those who implement EFNEP on a daily basis. The committee proposes that applying and further developing these crucial components will strengthen EFNEP supervision and enhance the program’s effectiveness.https://lib.dr.iastate.edu/extension_pubs/1252/thumbnail.jp

Activated gliosis, accumulation of amyloid β, and hyperphosphorylation of tau in aging canines with and without cognitive decline

Canine cognitive dysfunction (CCD) syndrome is a well-recognized naturally occurring disease in aged dogs, with a remarkably similar disease course, both in its clinical presentation and neuropathological changes, as humans with Alzheimer’s disease (AD). Similar to human AD patients this naturally occurring disease is found in the aging canine population however, there is little understanding of how the canine brain ages pathologically. It is well known that in neurodegenerative diseases, there is an increase in inflamed glial cells as well as an accumulation of hyperphosphorylation of tau (P-tau) and amyloid beta (Aβ1-42). These pathologies increase neurotoxic signaling and eventual neuronal loss. We assessed these brain pathologies in aged canines and found an increase in the number of glial cells, both astrocytes and microglia, and the activation of astrocytes indicative of neuroinflammation. A rise in the aggregated protein Aβ1-42 and hyperphosphorylated tau, at Threonine 181 and 217, in the cortical brain regions of aging canines. We then asked if any of these aged canines had CCD utilizing the only current diagnostic, owner questionnaires, verifying positive or severe CCD had pathologies of gliosis and accumulation of Aβ1-42 like their aged, matched controls. However uniquely the CCD dogs had P-tau at T217. Therefore, this phosphorylation site of tau at threonine 217 may be a predictor for CCD

Association of β-amyloid level, clinical progression and longitudinal cognitive change in normal older individuals

Objective To determine the effect of β-amyloid (Aβ) level on progression risk to mild cognitive impairment (MCI) or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals. Methods All CN from the Australian Imaging Biomarkers and Lifestyle study with Aβ PET and ≥ 3 years follow-up were included (n = 534; age 72 ± 6 years; 27% Aβ positive; follow-up 5.3 ± 1.7 years). Aβ level was divided using the standardized 0–100 Centiloid scale: \u3c 15 CL negative, 15–25 CL uncertain, 26–50 CL moderate, 51–100 CL high, \u3e 100 CL very high, noting \u3e 25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess risk of progression and cognitive decline. Results Aβ levels in 63% were negative, 10% uncertain, 10% moderate, 14% high, and 3% very high. Fifty-seven (11%) progressed to MCI or dementia. Compared to negative Aβ, the hazard ratio for progression for moderate Aβ was 3.2 (95% confidence interval [CI] 1.3–7.6; p \u3c 0.05), for high was 7.0 (95% CI 3.7–13.3; p \u3c 0.001), and for very high was 11.4 (95% CI 5.1–25.8; p \u3c 0.001). Decline in cognitive composite score was minimal in the moderate group (−0.02 SD/year, p = 0.05), while the high and very high declined substantially (high −0.08 SD/year, p \u3c 0.001; very high −0.35 SD/year, p \u3c 0.001). Conclusion The risk of MCI or dementia over 5 years in older CN is related to Aβ level on PET, 5% if negative vs 25% if positive but ranging from 12% if 26–50 CL to 28% if 51–100 CL and 50% if \u3e 100 CL. This information may be useful for dementia risk counseling and aid design of preclinical AD trials