Complete Duplication of Collecting System in a Horseshoe Kidney Presenting with Recurrent Urinary Tract Infections: Report of an Exceedingly Rare Congenital Anomaly and Review of Literature

We report the fifth case in the English literature of a horseshoe kidney with a complete ureteral duplication. Our case is unique in that the previous four cases occurred in the presence of a ureterocele, whereas our patient lacked this anomaly. Further, our patient was managed conservatively, whereas the previous four patients were managed with surgery

Inverse dynamic modelling of jumping in the red-legged running frog, Kassina maculata

Although the red-legged running frog, Kassina maculata, is secondarily a walker/runner, it retains the capacity for multiple locomotor modes, including jumping at a wide range of angles (nearly 70 deg). Using simultaneous hind limb kinematics and single-foot ground reaction forces, we performed inverse dynamics analyses to calculate moment arms and torques about the hind limb joints during jumping at different angles in K. maculata. We show that forward thrust is generated primarily at the hip and ankle, while body elevation is primarily driven by the ankle. Steeper jumps are achieved by increased thrust at the hip and ankle and greater downward rotation of the distal limb segments. Because of its proximity to the GRF vector, knee posture appears to be important in controlling torque directions about this joint and, potentially, torque magnitudes at more distal joints. Other factors correlated with higher jump angles include increased body angle in the preparatory phase, faster joint openings and increased joint excursion, higher ventrally directed force, and greater acceleration and velocity. Finally, we demonstrate that jumping performance in K. maculata does not appear to be compromised by presumed adaptation to walking/running. Our results provide new insights into how frogs engage in a wide range of locomotor behaviours and the multi-functionality of anuran limbs

The SDSS-III Baryon Oscillation Spectroscopic Survey: Quasar Target Selection for Data Release Nine

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg^2, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations in the distribution of Ly-alpha absorption from the spectra of a sample of ~150,000 z>2.2 quasars. Along with measuring the angular diameter distance at z\approx2.5, BOSS will provide the first direct measurement of the expansion rate of the Universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars over 2.2 < z < 3.5, where their colors overlap those of stars. During the first year of the BOSS survey, quasar target selection methods were developed and tested to meet the requirement of delivering at least 15 quasars deg^-2 in this redshift range, out of 40 targets deg^-2. To achieve these surface densities, the magnitude limit of the quasar targets was set at g <= 22.0 or r<=21.85. While detection of the BAO signature in the Ly-alpha absorption in quasar spectra does not require a uniform target selection, many other astrophysical studies do. We therefore defined a uniformly-selected subsample of 20 targets deg^-2, for which the selection efficiency is just over 50%. This "CORE" subsample will be fixed for Years Two through Five of the survey. In this paper we describe the evolution and implementation of the BOSS quasar target selection algorithms during the first two years of BOSS operations. We analyze the spectra obtained during the first year. 11,263 new z>2.2 quasars were spectroscopically confirmed by BOSS. Our current algorithms select an average of 15 z > 2.2 quasars deg^-2 from 40 targets deg^-2 using single-epoch SDSS imaging. Multi-epoch optical data and data at other wavelengths can further improve the efficiency and completeness of BOSS quasar target selection. [Abridged]Comment: 33 pages, 26 figures, 12 tables and a whole bunch of quasars. Submitted to Ap

Orientia tsutsugamushi ankyrin repeat-containing protein family members are Type 1 secretion system substrates that traffic to the host cell endoplasmic reticulum

Scrub typhus is an understudied, potentially fatal infection that threatens one billion persons in the Asia-Pacific region. How the causative obligate intracellular bacterium, Orientia tsutsugamushi, facilitates its intracellular survival and pathogenesis is poorly understood. Many intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) that traffic to distinct subcellular locations and modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank repertoires plus T1SS and T4SS components. Whether these potential virulence factors are expressed during infection, how the Anks are potentially secreted, and to where they localize in the host cell are not known. We determined that O. tsutsugamushi transcriptionally expresses 20 unique ank genes as well as genes for both T1SS and T4SS during infection of mammalian host cells. Examination of the Anks’ C-termini revealed that the majority of them resemble T1SS substrates. Escherichia coli expressing a functional T1SS was able to secrete chimeric hemolysin proteins bearing the C-termini of 19 of 20 O. tsutsugamushi Anks in an HlyBD-dependent manner. Thus, O. tsutsugamushi Anks C-termini are T1SS-compatible. Conversely, Coxiella burnetii could not secrete heterologously expressed Anks in a T4SS-dependent manner. Analysis of the subcellular distribution patterns of 20 ectopically expressed Anks revealed that, while 6 remained cytosolic or trafficked to the nucleus, 14 localized to, and in some cases, altered the morphology of the endoplasmic reticulum. This study identifies O. tsutsugamushi Anks as T1SS substrates and indicates that many display a tropism for the host cell secretory pathway

Frontotemporal lobar dementia mutant tau impairs axonal transport through a protein phosphatase 1γ-dependent mechanism

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Combs, B., Christensen, K. R., Richards, C., Kneynsberg, A., Mueller, R. L., Morris, S. L., Morfini, G., Brady, S. T., & Kanaan, N. M. Frontotemporal lobar dementia mutant tau impairs axonal transport through a protein phosphatase 1γ-dependent mechanism. Journal of Neuroscience, 41(45), (2021): 9431-9451, https://doi.org/10.1523/JNEUROSCI.1914-20.2021.Pathologic tau modifications are characteristic of Alzheimer's disease and related dementias, but mechanisms of tau toxicity continue to be debated. Inherited mutations in tau cause early onset frontotemporal lobar dementias (FTLD-tau) and are commonly used to model mechanisms of tau toxicity in tauopathies. Previous work in the isolated squid axoplasm model demonstrated that several pathogenic forms of tau inhibit axonal transport through a mechanism involving activation of protein phosphatase 1 (PP1). Here, we determined that P301L and R5L FTLD mutant tau proteins elicit a toxic effect on axonal transport as monomeric proteins. We evaluated interactions of wild-type or mutant tau with specific PP1 isoforms (α, β, and γ) to examine how the interaction contributes to this toxic effect using primary rat hippocampal neurons from both sexes. Pull-down and bioluminescence resonance energy transfer experiments revealed selective interactions of wild-type tau with PP1α and PP1γ isoforms, but not PP1β, which were significantly increased by the P301L tau mutation. The results from proximity ligation assays confirmed the interaction in primary hippocampal neurons. Moreover, expression of FTLD-linked mutant tau in these neurons enhanced levels of active PP1, also increasing the pausing frequency of fluorescently labeled vesicles in both anterograde and retrograde directions. Knockdown of PP1γ, but not PP1α, rescued the cargo-pausing effects of P301L and R5L tau, a result replicated by deleting a phosphatase-activating domain in the amino terminus of P301L tau. These findings support a model of tau toxicity involving aberrant activation of a specific PP1γ-dependent pathway that disrupts axonal transport in neurons.This work was supported by National Institutes of Health (NIH) Grants R01 NS082730 (N.M.K. and S.T.B.), R01 AG044372 (N.M.K.), and R01 AG067762 (N.M.K.); NIH/National Institute on Aging, Michigan Alzheimer's Disease Research Center Grant 5P30AG053760 (B.C.); Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Alzheimer's Research Program Award W81XWH-20-1-0174 (B.C.); Alzheimer's Association Research Grants 20-682085 (B.C.), R01 NS118177 (G.A.M.), and R21NS120126 (G.A.M.); Zenith Award from the Alzheimer's Association (S.T.B.); Tau Consortium/Rainwater Foundation (S.T.B.); Neurodegenerative Research (G.A.M.); and the Secchia Family Foundation (N.M.K.)

Tracking the evolution of hospice palliative care in Canada: A comparative case study analysis of seven provinces

<p>Abstract</p> <p>Background</p> <p>An aging population, rise in chronic illnesses, increase in life expectancy and shift towards care being provided at the community level are trends that are collectively creating an urgency to advance hospice palliative care (HPC) planning and provision in Canada. The purpose of this study was to analyze the evolution of HPC in seven provinces in Canada so as to inform such planning and provision elsewhere. We have endeavoured to undertake this research out of awareness that good future planning for health and social care, such as HPC, typically requires us to first look backwards before moving forward.</p> <p>Methods</p> <p>To identify key policy and practice events in HPC in Canada, as well as describe facilitators of and barriers to progress, a qualitative comparative case study design was used. Specifically, the evolution and development of HCP in 7 strategically selected provinces is compared. After choosing the case study provinces, the grey literature was searched to create a preliminary timeline for each that described the evolution of HPC beginning in 1970. Key informants (<it>n </it>= 42) were then interviewed to verify the content of each provincial timeline and to discuss barriers and facilitators to the development of HPC. Upon completion of the primary data collection, a face-to-face meeting of the research team was then held so as to conduct a comparative study analysis that focused on provincial commonalities and differences.</p> <p>Results</p> <p>Findings point to the fact that HPC continues to remain at the margins of the health care system. The development of HPC has encountered structural inheritances that have both sped up progress as well as slowed it down. These structural inheritances are: (1) foundational health policies (e.g., the Canada Health Act); (2) service structures and planning (e.g., the dominance of urban-focused initiatives); and (3) health system decisions (e.g., regionalization). As a response to these inheritances, circumventions of the established system of care were taken, often out of necessity. Three kinds of circumventions were identified from the data: (1) interventions to shift the system (e.g., the role of advocacy); (2) service innovations (e.g., educational initiatives); and (3) new alternative structures (e.g., the establishment of independent hospice organizations). Overall, the evolution of HPC across the case study provinces has been markedly slow, but steady and continuous.</p> <p>Conclusions</p> <p>HPC in Canada remains at the margins of the health care system. Its integration into the primary health care system may ensure dedicated and ongoing funding, enhanced access, quality and service responsiveness. Though demographics are expected to influence HPC demand in Canada, our study confirms that concerned citizens, advocacy organizations and local champions will continue to be the agents of change that make the necessary and lasting impacts on HPC in Canada.</p

Population health and nurse education – time to step-up

Highlights•Contemporary trends in population health threaten the sustainability of current approaches to care delivery.•Health care professionals inevitably confront social injustices in their day-to-day work.•Nurses are ideally placed to make a critical impact on the health of populations.•Nurse educators need to create curricula which meaningfully integrate population health.•We outline three exemplars of innovative pedagogical approaches to spark the thinking of educators as to how they can enable nurses to make connections between practice and population health

Reproducible big data science: A case study in continuous FAIRness.

Big biomedical data create exciting opportunities for discovery, but make it difficult to capture analyses and outputs in forms that are findable, accessible, interoperable, and reusable (FAIR). In response, we describe tools that make it easy to capture, and assign identifiers to, data and code throughout the data lifecycle. We illustrate the use of these tools via a case study involving a multi-step analysis that creates an atlas of putative transcription factor binding sites from terabytes of ENCODE DNase I hypersensitive sites sequencing data. We show how the tools automate routine but complex tasks, capture analysis algorithms in understandable and reusable forms, and harness fast networks and powerful cloud computers to process data rapidly, all without sacrificing usability or reproducibility-thus ensuring that big data are not hard-to-(re)use data. We evaluate our approach via a user study, and show that 91% of participants were able to replicate a complex analysis involving considerable data volumes

The Sloan Digital Sky Survey Reverberation Mapping Project: Technical Overview

The Sloan Digital Sky Survey Reverberation Mapping project (SDSS-RM) is a dedicated multi-object RM experiment that has spectroscopically monitored a sample of 849 broad-line quasars in a single 7 deg$^2$ field with the SDSS-III BOSS spectrograph. The RM quasar sample is flux-limited to i_psf=21.7 mag, and covers a redshift range of 0.1<z<4.5. Optical spectroscopy was performed during 2014 Jan-Jul dark/grey time, with an average cadence of ~4 days, totaling more than 30 epochs. Supporting photometric monitoring in the g and i bands was conducted at multiple facilities including the CFHT and the Steward Observatory Bok telescopes in 2014, with a cadence of ~2 days and covering all lunar phases. The RM field (RA, DEC=14:14:49.00, +53:05:00.0) lies within the CFHT-LS W3 field, and coincides with the Pan-STARRS 1 (PS1) Medium Deep Field MD07, with three prior years of multi-band PS1 light curves. The SDSS-RM 6-month baseline program aims to detect time lags between the quasar continuum and broad line region (BLR) variability on timescales of up to several months (in the observed frame) for ~10% of the sample, and to anchor the time baseline for continued monitoring in the future to detect lags on longer timescales and at higher redshift. SDSS-RM is the first major program to systematically explore the potential of RM for broad-line quasars at z>0.3, and will investigate the prospects of RM with all major broad lines covered in optical spectroscopy. SDSS-RM will provide guidance on future multi-object RM campaigns on larger scales, and is aiming to deliver more than tens of BLR lag detections for a homogeneous sample of quasars. We describe the motivation, design and implementation of this program, and outline the science impact expected from the resulting data for RM and general quasar science.Comment: 25 pages, submitted to ApJS; project website at http://www.sdssrm.or

Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins

Bioinorganic canon states that active-site thiolate coordination promotes rapid electron transfer (ET) to and from type 1 copper proteins. In recent work, we have found that copper ET sites in proteins also can be constructed without thiolate ligation (called “type zero” sites). Here we report multifrequency electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopic data together with density functional theory (DFT) and spectroscopy-oriented configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1 centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding