Loss of NLRP6 increases the severity of kidney fibrosis.

While NLRP3 contributes to kidney fibrosis, the function of most NOD-like receptors (NLRs) in chronic kidney disease (CKD) remains unexplored. To identify further NLR members involved in the pathogenesis of CKD, we searched for NLR genes expressed by normal kidneys and differentially expressed in human CKD transcriptomics databases. For NLRP6, lower kidney expression correlated with decreasing glomerular filtration rate. The role and molecular mechanisms of Nlrp6 in kidney fibrosis were explored in wild-type and Nlrp6-deficient mice and cell cultures. Data mining of single-cell transcriptomics databases identified proximal tubular cells as the main site of Nlrp6 expression in normal human kidneys and tubular cell Nlrp6 was lost in CKD. We confirmed kidney Nlrp6 downregulation following murine unilateral ureteral obstruction. Nlrp6-deficient mice had higher kidney p38 MAPK activation and more severe kidney inflammation and fibrosis. Similar results were obtained in adenine-induced kidney fibrosis. Mechanistically, profibrotic cytokines transforming growth factor beta 1 (TGF-ß1) and TWEAK decreased Nlrp6 expression in cultured tubular cells, and Nlrp6 downregulation resulted in increased TGF-ß1 and CTGF expression through p38 MAPK activation, as well as in downregulation of the antifibrotic factor Klotho, suggesting that loss of Nlrp6 promotes maladaptive tubular cell responses. The pattern of gene expression following Nlrp6 targeting in cultured proximal tubular cells was consistent with maladaptive transitions for proximal tubular cells described in single-cell transcriptomics datasets. In conclusion, endogenous constitutive Nlrp6 dampens sterile kidney inflammation and fibrosis. Loss of Nlrp6 expression by tubular cells may contribute to CKD progression.

Assessing the Feasibility of a Faith-Based Colorectal Cancer Education and Screening Intervention for Latino Men in Pennsylvania.

Introduction: Limited health knowledge, literacy, engagement in preventive health services, participation in health promotion behaviors, and cultural factors place Latino men at high risk for colorectal cancer (CRC). This pilot study aimed to determine the feasibility and acceptability of a faith-based cancer education intervention focusing on Latino men between 45 and 74 years old. Methods: This pilot study used a single group pre- and post-intervention research design to compare changes in knowledge, perceived benefit of screening, perceived susceptibility and severity of CRC, and the completion of CRC screening after the intervention. Results: In this study, Latino men were willing to participate in a CRC educational intervention supported by a faith-based institution. The participants had limited knowledge about CRC, yet most recognized that screening is beneficial and that getting CRC is serious. Sixty percent of the participants completed the fecal immunochemical screening test, which showed that the intervention impacted the screening uptake among this group. Conclusion: The findings of this study support the further development of faith-based interventions focusing on Latino men.

Lupeol Acetate and α-Amyrin Terpenes Activity against Trypanosoma cruzi: Insights into Toxicity and Potential Mechanisms of Action.

BACKGROUND: Chagas disease is a potentially fatal disease caused by the parasite Trypanosoma cruzi. There is growing scientific interest in finding new and better therapeutic alternatives for this disease's treatment. METHODS: A total of 81 terpene compounds with potential trypanocidal activity were screened and found to have potential T. cruzi cysteine synthase (TcCS) inhibition using molecular docking, molecular dynamics, ADME and PAIN property analyses and in vitro susceptibility assays. RESULTS: Molecular docking analyses revealed energy ranges from -10.5 to -4.9 kcal/mol in the 81 tested compounds, where pentacyclic triterpenes were the best. Six compounds were selected to assess the stability of the TcCS-ligand complexes, of which lupeol acetate (ACLUPE) and α-amyrin (AMIR) exhibited the highest stability during 200 ns of molecular dynamics analysis. Such stability was primarily due to their hydrophobic interactions with the amino acids located in the enzyme's active site. In addition, ACLUPE and AMIR exhibited lipophilic characteristics, low intestinal absorption and no structural interferences or toxicity. Finally, selective index for ACLUPE was >5.94, with moderate potency in the trypomastigote stage (EC50 = 15.82 ± 3.7 µg/mL). AMIR's selective index was >9.36 and it was moderately potent in the amastigote stage (IC50 = 9.08 ± 23.85 µg/mL). CONCLUSIONS: The present study proposes a rational approach for exploring lupeol acetate and α-amyrin terpene compounds to design new drugs candidates for Chagas disease.

A Theoretical Analysis of Interaction Energies and Intermolecular Interactions between Amphotericin B and Potential Bioconjugates Used in the Modification of Nanocarriers for Drug Delivery.

Amphotericin B (AmB) is an antibiotic with a wide spectrum of action and low multidrug resistance, although it exhibits self-aggregation, low specificity, and solubility in aqueous media. An alternative for its oral administration is its encapsulation in polymers modified with bioconjugates. The aim of the present computational research is to determine the affinity between AmB and six bioconjugates to define which one could be more suitable. The CAM-B3LYP-D3/6-31+G(d,p) method was used for all computational calculations. The dimerization enthalpy of the most stable and abundant systems at pH = 7 allows obtaining this affinity order: AmB_1,2-distearoyl-sn-glycerol-3-phosphorylethanolamine (DSPE) > AmB_γ-cyclodextrin > AmB_DSPEc > AmB_retinol > AmB_cholesterol > AmB_dodecanol, where DSPEc is a DSPE analog. Quantum theory of atoms in molecules, the non-covalent interactions index, and natural bond orbital analysis revealed the highest abundance of noncovalent interactions for AmB-DSPE (51), about twice the number of interactions of the other dimers. Depending on the interactions' strength and abundance of the AmB-DSPE dimer, these are classified as strong: O-H---O (2), N-H---O (3) and weak: C-H---O (25), H---H (18), C-H---C (3). Although the C-H---O hydrogen bond is weak, the number of interactions involved in all dimers cannot be underestimated. Thus, non-covalent interactions drive the stabilization of copolymers, and from our analysis, the most promising candidates for encapsulating are DSPE and γ-cyclodextrin.

Roles of GR Isoforms and Hsp90-binding Immunophilins in the Modulation of Glucocorticoid Biological Responses.

Glucocorticoid steroids play cardinal roles during the life span of an individual, modulating almost all aspects of the physiology, including the metabolism of carbohydrates, lipids and amino acids, as well as the immune response, neurological biology, stress adaptation, apoptosis, cell division, cell fate, inflammatory responses, etc. Glucocorticoids exert their biological effects by activation of the glucocorticoid receptor (GR), a bona fide ligand-activated transcription factor belonging to the nuclear receptor superfamily. The GR is expressed in virtually all cells of the human body showing isoformic versions and also transcription variants. GR forms oligomeric heterocomplexes that include the 90-kDa heat-shock protein (Hsp90) as an essential hub of the chaperone oligomer. The nature of chaperones associated with this heterocomplex is responsible for the modulation of the subcellular localization of the GR and its biological actions in a given tissue or cell type. In this sense, the discovery that immunophilins containing tetratricopeptide repeats (TPR) domains are responsible for the GR cytoplasmic transport mechanism and the nuclear retention half-time of the receptor opened new trends in our understanding of its complex mechanism of action. Because the properties of GR ligands influence these protein-protein interactions, specific steroid•receptor complexes may confer the GR different features providing new therapeutic opportunities to manage the disease. In this article, we analyze multiple aspects of the GR mechanism of action, some properties of the GR isoforms, and the latest findings revealing the roles of Hsp90-binding immunophilins to manage the glucocorticoid biological response.

Plasma metabolome of healthy and Rhodococcus equi-infected foals over time.

BACKGROUND: Foals that develop pulmonary ultrasonographic lesions on Rhodococcus equi (R. equi) endemic farms are treated with antibiotics because those at risk of developing clinical pneumonia (~20%) cannot be recognised early. Candidate biomarkers identified using metabolomics may aid targeted treatment strategies against R. equi. OBJECTIVES: (1) To describe how foal ageing affects their plasma metabolome (birth to 8 weeks) and (2) to establish the effects that experimental infection with Rhodococcus equi (R. equi) has on foal metabolome. STUDY DESIGN: Experimental study. METHODS: Nine healthy newborn foals were experimentally infected with R. equi as described in a previous study. Foals were treated with oral antibiotics if they developed clinical pneumonia (n = 4, clinical group) or remained untreated if they showed no signs of disease (n = 5, subclinical group). A group of unchallenged foals (n = 4) was also included in the study. By the end of the study period (8 weeks), all foals were free of disease. This status was confirmed with transtracheal wash fluid evaluation and culture as well as thoracic ultrasonography. Plasma metabolomics was determined by GC-MS weekly for the study duration (8 weeks). RESULTS: Foals' plasma metabolome was altered by ageing (birth to 8 weeks) and experimental infection with R. equi as demonstrated using multivariate statistical analysis. The intensities of 25 and 28 metabolites were altered by ageing and infection (p < 0.05) respectively. Furthermore, 20 metabolites changed by more than 2-fold between clinical and subclinical groups. MAIN LIMITATIONS: The number of foals is limited. Foals were experimentally infected with R. equi. CONCLUSIONS: Ageing and R. equi infection induced changes in the plasma metabolome of foals. These results provide an initial description of foal's plasma metabolome and serve as background for future identification of R. equi pneumonia biomarkers.

INTRODUCTION/CONTEXTE: Les poulains qui développent des lésions pulmonaires échographiques dans les fermes d'élevage où Rhodococcus equi (R. equi) est endémique sont traités avec antibiotiques car ceux à risque de développer des lésions cliniques (~20%) ne peuvent être identifiés précocement. Certains biomarqueurs identifiés par le biais de la métabolomique pourraient aider à orienter les stratégies de traitement pour R. equi. OBJECTIFS: (1) Décrire les changements de métabolome plasmatique qui surviennent chez les poulains en lien avec l'âge (naissance jusqu'à 8 semaines d'âge) et (2) Établir les effets d'une infection expérimentale à Rhodococcus Equi sur le métabolome des poulains. TYPE D'ÉTUDE: Étude expérimentale. MÉTHODES: Neufs poulains nouveaux-nés en santé ont été infectés de façon expérimentale par R. equi tel que décrit précédemment. Ils ont été traités avec des antibiotiques s'ils ont développé une pneumonie clinique (n = 4, groupe clinique) ou ont simplement été suivi dans le temps s'ils n'ont pas montré de signes de la maladie (n = 5, groupe sous-clinique). Un groupe de poulains sains (n = 4) était aussi inclus dans l'étude. À la fin de l'étude (8 semaines), tous les poulains étaient sains tel que confirmé par l'évaluation et la culture de leur fluide de lavage transtrachéal de même qu'à l'échographie thoracique. Les métabolomiques plasmastiques ont été déterminées par GC-MS de façon hebdomadaire pour la durée de l'étude (8 semaines). RÉSULTATS: À la fois l'âge et l'infection expérimentale ont altéré le métabolome plasmatique des poulains tel que démontré par l'analyse statistique multivariée. L'âge a altéré l'intensité de 25 métabolites et l'infection a modifié l'intensité de 28 métabolites (p < 0.05). De plus, 20 métabolites ont changé de plus de 2 fois leur valeur initiale, entre les groupes cliniques et sous-cliniques. LIMITES PRINCIPALES: Le nombre de poulains reste limité. Les poulains ont été infecté par R. equi de façon expérimentale. CONCLUSIONS: Le vieillissement et l'infection par R. equi induisent des changements dans le métabolome plasmatique des poulains. Ces résultats représentent une description initiale du métabolome plasmatique chez le poulain et peuvent servir de base pour l'identification future de biomarqueurs pour la détection de pneumonie à Rhodococcus equi.

The transcription factor Fosl1 preserves Klotho expression and protects from acute kidney injury.

Increased expression of AP-1 transcription factor components has been reported in acute kidney injury (AKI). However, the role of specific components, such as Fosl1, in tubular cells or AKI is unknown. Upstream regulator analysis of murine nephrotoxic AKI transcriptomics identified AP-1 as highly upregulated. Among AP-1 canonical components, Fosl1 was found to be upregulated in two transcriptomics datasets from nephrotoxic murine AKI induced by folic acid or cisplatin and from proximal tubular cells exposed to TWEAK, a cytokine mediator of AKI. Fosl1 was minimally expressed in the kidneys of control uninjured mice. Increased Fosl1 protein was localized to proximal tubular cell nuclei in AKI. In human AKI, FOSL1 was found present in proximal tubular cells in kidney sections and in urine along with increased urinary FOSL1 mRNA. Selective Fosl1 deficiency in proximal tubular cells (Fosl1Δtub) increased the severity of murine cisplatin- or folate-induced AKI as characterized by lower kidney function, more severe kidney inflammation and Klotho downregulation. Indeed, elevated AP-1 activity was observed after cisplatin-induced AKI in Fosl1Δtub mice compared to wild-type mice. More severe Klotho downregulation preceded more severe kidney dysfunction. The Klotho promoter was enriched in Fosl1 binding sites and Fosl1 bound to the Klotho promoter in cisplatin-AKI. In cultured proximal tubular cells, Fosl1 targeting increased the proinflammatory response and downregulated Klotho. In vivo, recombinant Klotho administration protected Fosl1Δtub mice from cisplatin-AKI. Thus, increased proximal tubular Fosl1 expression during AKI is an adaptive response, preserves Klotho, and limits the severity of tubular cell injury and AKI.

Experimental and theoretical study of the mechanism and rate constants of the sequential 5-exo-trig spirocyclization involving vinyl, aryl and N-alkoxyaminyl radicals.

In this research the sequential generation and cyclization of N-alkoxyaminyl radicals to produce 1-azaspiro[4.4]nonane, a prominent scaffold in organic and medicinal chemistry, was studied. Competition experiments in benzene at 80 °C with brominated oxime ethers using Bu3SnH as chain transfer and AIBN as the initiator generated vinyl or aryl radicals which were captured by oxime ethers, allowing approximate 5-exo-trig cyclization constants at 4.6 × 108 s-1 and 9.9 × 108 s-1 respectively to be established. Similar results were obtained by kinetic studies using the transition state theory (TST) from ab initio calculations with density functional theory (DFT) using the M06-2X, B3LYP, mPW1PW91 and TPSSh functionals in combination with the 6-311+G(d, p) basis set. Additionally, it was found that the 5-exo-trig cyclization of the N-alkoxyaminyl radical onto CC double bonds is a reversible process whose constants were determined to be in the range of 6.2 × 100 s-1 and 3.5 × 106 s-1 at 80 °C, depending on the nature of the substituents. The calculation of the radical stabilization energy (RSE) shows that the N-alkoxyaminyl radical is a very stable species and its reactivity in the addition on alkenes is governed by its nucleophilic character and the stability of the carbon-centered radical formed after cyclization. The reduction constant of the N-alkoxyaminyl radical with Bu3SnH in the gas phase at 80 °C was also estimated to be 3.4 × 100 M-1 s-1 through computational calculations. This information facilitates the rational planning of cascades and other methodologies applied to the construction of carbocyclic and aza-heterocyclic compounds.

Estudio teórico de la oxidación de CO con O2 usando catalizadores de Au-Pd y Au-Pt / Theoretical study of the CO Oxidation with O2 using Au-Pd and Au-Pt catalysts / Estudo teórico da oxidação de CO com O2 usando catalisadores de Au-Pd e Au-Pt

Resumen En el presente estudio se realizaron cálculos con base en la Teoría del Funcional de la Densidad Electrónica (DFT) con la aproximación B3PW91/LANL2DZ para optimizar los sistemas monometálicos y bimetálicos Au9, Au8Pd, Au8Pt, AuPd8, AuPt8, Pd9 y Pt9. Los materiales fueron teóricamente evaluados como catalizadores para la oxidación de monóxido de carbono (CO) y se determinó el sistema más favorable para la adsorción de esta molécula. La sustitución de átomos de Pt y Pd por átomos de Au en los nonámeros generó un cambio en la estructura tridimensional del sistema. El análisis de reactividad global mostró que el clúster más reactivo es PÍ9, seguido por AuPt s . Los índices de Fukui identificaron los sitios más susceptibles para un ataque nucleofílico de ambos clústeres. La adsorción de CO generó una cascada de oxidación que liberó ~4,5 eV, indicando que la reacción es altamente exotérmica y exergónica. Los clústeres AuPt s y Pt 9 mostraron los valores más bajos de energía de activación de la etapa determinante del mecanismo. En general, la sustitución de un átomo de platino (o paladio) por un átomo de oro no afecta la reactividad de los nonámeros y, por tanto, se infiere que el clúster AuPt s podría ser un catalizador promisorio en la oxidación de CO.

Abstract In the current study were development calculations based on Density Functional Theory (DFT) with the B3PW91/LANL2DZ approach for optimizing both monometallic and bimetallic systems: Au9, AusPd, Au8Pt, AuPds, AuPts, Pd9 y Pt9. Such materials were theoretically tested as catalyst for the oxidation of carbon monoxide (CO) and the most favorable system for its further adsorption was determined. The substitution of Pt and Pd by Au atoms in the nonamers generated a change in the tridimensional structure of the system. The global reactivity analysis showed that the most reactive cluster is Pt9 followed by AuPts. On the other hand, the Fukui indexes identified the most susceptible sites for a nucleophilic attack of both clusters. The CO adsorption generated an oxidation cascade which liberated ∼ 4.5 eV, indicating that the reaction is highly exothermic and exergonic. Both AuPt8 and Pt9 showed the lowest values of activation energy in the determining step of the mechanism. In general, the substitution of a Pt (Pd) atom by an Au atom does not affect the reactivity of the nonamers and then it is inferred that the AuPds cluster could be a promissory catalyst in the CO oxidation.

Resumo No presente estudo, cálculos baseados na Teoria do Funcional da Densidade Eletrônica (DFT) com a abordagem B3PW91/LANL2DZ foram realizados para otimizar sistemas monometálicos e bimetálicos Au9, Au8Pd, Au8Pt, AuPd8, AuPt8, Pd9 y Pt9. Tais materiais foram teoricamente avaliados como catalisadores para a oxidação do monóxido de carbono (CO) e foi determinado o sistema mais favorável para a adsorção desta molécula. A substituição dos átomos de Pt e Pd por átomos de Au nós não-nomes gerou uma mudança na estrutura tridimensional do sistema. A análise de reatividade global mostrou que o cluster mais reativo é Pt9, seguido por AuPt8. Os índices de Fukui identificaram os sítios mais suscetíveis ao ataque nucleofílico de ambos os clusters. A adsorção de CO gerou uma cascata de oxidação que liberou ~4,5 eV, indicando que a reação é altamente exotérmica e exergônica. Os aglomerados AuPt 8 y Pt 9 apresentaram os menores valores de energia de ativação do estágio determinante do mecanismo. Em geral, a substituição de um átomo de platina (ou paládio) por um átomo de ouro não afeta a reatividade dos não-nomes e, portanto, infere-se que o aglomerado AuPt 8 pode ser um catalisador promissor na oxidação do CO.

Very-High Dynamic Range, 10,000 Frames/Second Pixel Array Detector for Electron Microscopy.

Precision and accuracy of quantitative scanning transmission electron microscopy (STEM) methods such as ptychography, and the mapping of electric, magnetic, and strain fields depend on the dose. Reasonable acquisition time requires high beam current and the ability to quantitatively detect both large and minute changes in signal. A new hybrid pixel array detector (PAD), the second-generation Electron Microscope Pixel Array Detector (EMPAD-G2), addresses this challenge by advancing the technology of a previous generation PAD, the EMPAD. The EMPAD-G2 images continuously at a frame-rates up to 10 kHz with a dynamic range that spans from low-noise detection of single electrons to electron beam currents exceeding 180 pA per pixel, even at electron energies of 300 keV. The EMPAD-G2 enables rapid collection of high-quality STEM data that simultaneously contain full diffraction information from unsaturated bright-field disks to usable Kikuchi bands and higher-order Laue zones. Test results from 80 to 300 keV are presented, as are first experimental results demonstrating ptychographic reconstructions, strain and polarization maps. We introduce a new information metric, the maximum usable imaging speed (MUIS), to identify when a detector becomes electron-starved, saturated or its pixel count is mismatched with the beam current.

Axonal quantification of the white matter association fasciculi in cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus).

BACKGROUND: Cerebral white matter consists mainly of axons surrounded by myelin sheaths, which are grouped to form association, commissural, and projection fasciculi. The aim of our work was to quantify and compare under the microscope the axons of the white matter association fasciculi in the cerebral hemispheres of cow (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus) indirectly by identification of their myelin sheaths. MATERIALS AND METHODS: The samples were taken from 30 cerebral hemispheres: 10 cow, 10 pig and 10 rabbit (15 right and 15 left). They were obtained following a protocol based on the Talairach-Tournoux coordinate system for human and primate brains. The slides were stained with Luxol Fast Blue, observed by optical microscopy, and photographed at 600×. Samples were also prepared for observation in scanning transmission electron microscopy with osmium tetroxide. The myelin sheaths/axons were counted with the ImageJ software. RESULTS: Statistically significant differences in the number of myelin sheaths per 410 µm² were found in the inferior and superior longitudinal fasciculi between the left and right hemispheres of cows, with predominance of the right hemisphere; and in the inferior occipitofrontal fasciculus of the rabbit with predominance of the left hemisphere. CONCLUSIONS: The use of animal models for experiments in the cerebral fasciculi, especially pig, could give us a greater understanding of the behaviour of demyelinating and neurodegenerative diseases in humans.

Ateneo General de la Residencia de Psicopedagogía: Abordaje psicopedagógico en pacientes con perfil externalizante / General Athenaeum of the Psychopedagogical Residence: Psychopedagogical approach in patients with externalizing profile

Ateneo centrado en la intervención psicopedagógica en niños y niñas con conductas externalizantes, En una pirmera parte, se desarrollan algunos conceptos que forman parte del marco teórico del equipo, y más adelante, los referidos a la Terapia Cognitivo Conductual. Se define la conducta y sus funciones, diferenciando conductas internalizantes y externalizantes. Luego se ejemplifican las estrategias de la Terapia Cognitivo Conductual utilizadas en cada uno de los tres subsistemas (familia, escuela y niño/a) a partir de diferentes casos clínicos. Por último, se reflexiona invitando a seguir repensando las intervenciones y prácticas clínicas con pacientes con estas características.

Thermodynamics of the Isomerization of Monoterpene Epoxides.

In this contribution, the thermodynamic analysis of α- and ß-pinene epoxide isomerization over Fe and Cu supported on MCM-41 is presented using computational chemistry and group contribution methods (GCMs). Some physical-chemical data (T c, P c, v c, Z c, ω, T b, T fus) and thermodynamic (S°298.15, C p,298.15 °, C v,298.15 °, ΔH f,298.15 °, ΔG f,298.15 °, ΔH vb °, ΔH fus, C pL) properties obtained by different GCMs are reported for several monoterpenes and monoterpenoids, which significantly contribute to the knowledge of the properties of these compounds. Density functional theory (DFT), PBE-D3/6-311G(d,p), was employed for determining the Gibbs free energy and the heat of reaction associated with the transformation of monoterpene epoxides into aldehydes, ketones, and related oxygenated compounds in the presence of different solvents and at several temperatures. The calculations were compared with available data reported and the experimental results of the catalytic reactions. The transformation of α- and ß-pinene epoxides into aldehydes appears to be more spontaneous and favorable than their transformations into alcohols in a wide range of temperatures. These results are in agreement with the experiments over Fe/MCM-41 and Cu/MCM-41, where α-pinene epoxide isomerization yields campholenic aldehyde (50-80% selectivity) as the main product. The 1.7Fe/MCM-41 material was more active in all solvents than 1.3Cu/MCM-41 for both α- and ß-pinene epoxide isomerization. However, perillyl alcohol (20-70% selectivity) was the most favored for the isomerization reaction, except when ethyl acetate was the solvent. Enthalpy and Gibbs free energy of the studied reactions estimated by both GCMs and DFT calculations did not show large differences for most of the reactions at evaluated temperatures.

Role of Physical Activity and Cardiac Rehabilitation in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a standard treatment for several malignancies, and >50,000 HSCT are performed annually worldwide. As survival after HSCT improves, cardiovascular disease and associated risk factors have gained importance as a significant cause of morbidity and mortality in this cohort. In this article, we detail the risk factors for cardiovascular disease and their impact in patients undergoing HSCT. Additionally, we critically review the data on the impact of physical exercise in patients undergoing HSCT. Although limited by significant heterogeneity in methodologies, small sample sizes, attrition, and lack of long-term cardiovascular follow-up, most of these studies reinforce the beneficial effects of physical activity and exercise in this patient population. Cardiac rehabilitation (CR) is a structured exercise and lifestyle modification program that is typically instituted in patients who experience acute cardiovascular events. We review the data on CR in the oncologic and nononcologic populations with an aim of building a framework for use of CR in HSCT patients.

Patternable Mesoporous Thin Film Quantum Materials via Block Copolymer Self-Assembly: An Emergent Technology?

Recent developments in quantum materials hold promise for revolutionizing energy and information technologies. The use of soft matter self-assembly, for example, by employing block copolymers (BCPs) as structure directing or templating agents, offers facile pathways toward quantum metamaterials with highly tunable mesostructures via scalable solution processing. Here, we report the preparation of patternable mesoporous niobium carbonitride-type thin film superconductors through spin-coating of a hybrid solution containing an amphiphilic BCP swollen by niobia sol precursors and subsequent thermal processing in combination with photolithography. Spin-coated as-made BCP-niobia hybrid thin films on silicon substrates after optional photolithographic definition are heated in air to produce a porous oxide, and subsequently converted in a multistep process to carbonitrides via treatment with high temperatures in reactive gases including ammonia. Grazing incidence small-angle X-ray scattering suggests the presence of ordered mesostructures in as-made BCP-niobia films without further annealing, consistent with a distorted alternating gyroid morphology that is retained upon thermal treatments. Wide-angle X-ray scattering confirms the synthesis of phase-pure niobium carbonitride nanocrystals with rock-salt lattices within the mesoscale networks. Electrical transport measurements of unpatterned thin films show initial exponential rise in resistivity characteristic of thermal activation in granular systems down to 12.8 K, at which point resistivity drops to zero into a superconducting state. Magnetoresistance measurements determine the superconducting upper critical field to be over 16 T, demonstrating material quality on par with niobium carbonitrides obtained from traditional solid-state synthesis methods. We discuss how such cost-effective and scalable solution-based quantum materials fabrication approaches may be integrated into existing microelectronics processing, promising the emergence of a technology with tremendous academic and industrial potential by combining the capabilities of soft matter self-assembly with quantum materials.

Superconducting Quantum Metamaterials from Convergence of Soft and Hard Condensed Matter Science.

Superconducting quantum metamaterials are expected to exhibit a variety of novel properties, but have been a major challenge to prepare as a result of the lack of appropriate synthetic routes to high-quality materials. Here, the discovery of synthesis routes to block copolymer (BCP) self-assembly-directed niobium nitrides and carbonitrides is described. The resulting materials exhibit unusual structure retention even at temperatures as high as 1000 °C and resulting critical temperature, Tc , values comparable to their bulk analogues. Applying the concepts of soft matter self-assembly, it is demonstrated that a series of four different BCP-directed mesostructured superconductors are accessible from a single triblock terpolymer. Resulting materials display a mesostructure-dependent Tc without substantial variation of the XRD-measured lattice parameters. Finally, field-dependent magnetization measurements of a sample with double-gyroid morphology show abrupt jumps comparable in overall behavior to flux avalanches. Results suggest a fruitful convergence of soft and hard condensed matter science.

High-pressure small-angle X-ray scattering cell for biological solutions and soft materials.

Pressure is a fundamental thermodynamic parameter controlling the behavior of biological macromolecules. Pressure affects protein denaturation, kinetic parameters of enzymes, ligand binding, membrane permeability, ion trans-duction, expression of genetic information, viral infectivity, protein association and aggregation, and chemical processes. In many cases pressure alters the molecular shape. Small-angle X-ray scattering (SAXS) is a primary method to determine the shape and size of macromolecules. However, relatively few SAXS cells described in the literature are suitable for use at high pressures and with biological materials. Described here is a novel high-pressure SAXS sample cell that is suitable for general facility use by prioritization of ease of sample loading, temperature control, mechanical stability and X-ray background minimization. Cell operation at 14 keV is described, providing a q range of 0.01 < q < 0.7 Å-1, pressures of 0-400 MPa and an achievable temperature range of 0-80°C. The high-pressure SAXS cell has recently been commissioned on the ID7A beamline at the Cornell High Energy Synchrotron Source and is available to users on a peer-reviewed proposal basis.

Applying metabolomics to veterinary pharmacology and therapeutics.

Metabolomics is the large-scale study of low-molecular-weight substances in a biological system in a given physiological state at a given time point. Metabolomics can be applied to identify predictors of inter-individual variability in drug response, provide clinicians with data useful for decision-making processes in drug selection, and inform about the pharmacokinetics and pharmacodynamics of a drug. It is, therefore, an exceptional approach for gaining new understanding effects in the field of comparative veterinary pharmacology. However, the incorporation of metabolomics into veterinary pharmacology and toxicology is not yet widespread, and this is probably, at least in part, a result of its highly multidisciplinary nature. This article reviews the potential applications of metabolomics in veterinary pharmacology and therapeutics. It integrates key concepts for designing metabolomics studies and analyzing and interpreting metabolomics data, providing solid foundations for applying metabolomics to the study of drugs in all veterinary species.

Differential regulation of the glucocorticoid receptor nucleocytoplasmic shuttling by TPR-domain proteins.

A dimer of the heat-shock protein of 90-kDa (Hsp90) represents the critical core of the chaperone complex associated to the glucocorticoid receptor (GR) oligomer. The C-terminal end of the Hsp90 dimer shapes a functional acceptor site for co-chaperones carrying tetratricopeptide repeat (TPR) domains, where they bind in a mutually exclusive and competitive manner. They impact on the biological properties of the GR•Hsp90 complex and are major players of the GR transport machinery. Recently, we showed that the overexpression of a chimeric TPR peptide influences the subcellular distribution of GR. In this study, the functional role of endogenous proteins carrying TPR or TPR-like sequences on GR subcellular distribution was characterized. It is demonstrated that, contrarily to the positive influence of FKBP52 on GR nuclear accumulation, FKBP51 and 14-3-3 impaired this property. While SGT1α showed no significant effect, the overexpression of the Ser/Thr phosphatase PP5 resulted in a nearly equal nuclear-cytoplasmic redistribution of GR rather than its typical cytoplasmic localization in the absence of steroid. This observation led to analyse the influence of the phosphorylation status of GR, which resulted not linked to its nucleo-cytoplasmic shuttling mechanism. Nonetheless, it was evidenced that both PP5 and FKBP52 are related to the anchorage of the GR to nucleoskeleton structures. The influence of these TPR domain proteins on the steroid-dependent transcriptional activity of GR was also characterized. It is postulated that the pleiotropic actions of the GR in different cell types may be the consequence of the relative abundance of different TPR-domain interacting co-chaperones.