In Vivo Targeting of Organic Calcium Sensors via Genetically Selected Peptides

AbstractA library of constrained peptides that form stable folded structures was screened for aptamers that bind with high affinity to the fluorescent dye Texas red. Two selected clones had binding constants to Texas red of 25 and 80 pM as phage and binding had minimal effects on the fluorescence of Texas red. The peptides interact with distinct but overlapping regions of Texas red. One peptide bound to X-rhod calcium sensors, which share the same core fluorophore as Texas red. These dyes retained calcium sensitivity when bound to the peptide. This peptide was used to label a fusion protein with X-rhod-5F in vivo, and X-rhod sensed changes in calcium locally. Thus, minimal, constrained peptides can functionally bind to environmentally sensitive dyes or other organic agents in biological contexts, suggesting tools for in vivo imaging and analysis

The influence of gas expulsion and initial mass-segregation on the stellar mass-function of globular star clusters

Recently de Marchi, Paresce & Pulone (2007) studied a sample of twenty globular clusters and found that all clusters with high concentrations have steep stellar mass-functions while clusters with low concentration have comparatively shallow mass-functions. No globular clusters were found with a flat mass-function and high concentration. This seems curious since more concentrated star clusters are believed to be dynamically more evolved and should have lost more low-mass stars via evaporation, which would result in a shallower mass-function in the low-mass part. We show that this effect can be explained by residual-gas expulsion from initially mass-segregated star clusters, and is enhanced further through unresolved binaries. If gas expulsion is the correct mechanism to produce the observed trend, then observation of these parameters would allow to constrain cluster starting conditions such as star formation efficiency and the time-scale of gas expulsion.Comment: accepted for publication in MNRAS, 10 pages, 6 figure

Yaws.

Yaws is a non-venereal endemic treponemal infection caused by Treponema pallidum sub-species pertenue, a spirochaete bacterium closely related to Treponema pallidum ssp. pallidum, the agent of venereal syphilis. Yaws is a chronic, relapsing disease predominantly affecting children living in certain tropical regions. It spreads by skin-to-skin contact and, like syphilis, occurs in distinct clinical stages. It causes lesions of the skin, mucous membranes and bones which, without treatment, can become chronic and destructive. Treponema pallidum ssp. pertenue, like its sexually-transmitted counterpart, is exquisitely sensitive to penicillin. Infection with yaws or syphilis results in reactive treponemal serology and there is no widely available test to distinguish between these infections. Thus, migration of people from yaws-endemic areas to developed countries may present clinicians with diagnostic dilemmas. We review the epidemiology, clinical presentation and treatment of yaws

Influence of Thoracic Endovascular Aortic Repair on True Lumen Helical Morphology for Stanford Type B Dissections

Objective: Thoracic endovascular aortic repair (TEVAR) can change the morphology of the flow lumen in aortic dissections, which may affect aortic hemodynamics and function. This study characterizes how the helical morphology of the true lumen in type B aortic dissections is altered by TEVAR. Methods: Patients with type B aortic dissection who underwent computed tomography angiography before and after TEVAR were retrospectively reviewed. Images were used to construct three-dimensional stereolithographic surface models of the true lumen and whole aorta using custom software. Stereolithographic models were segmented and co-registered to determine helical morphology of the true lumen with respect to the whole aorta. The true lumen region covered by the endograft was defined based on fiducial markers before and after TEVAR. The helical angle, average helical twist, peak helical twist, and cross-sectional eccentricity, area, and circumference were quantified in this region for pre- and post-TEVAR geometries. Results: Sixteen patients (61.3 \ub1 8.0 years; 12.5% female) were treated successfully for type B dissection (5 acute and 11 chronic) with TEVAR and scans before and after TEVAR were retrospectively obtained (follow-up interval 52 \ub1 91 days). From before to after TEVAR, the true lumen helical angle (–70.0 \ub1 71.1 to –64.9 \ub1 75.4\ub0; P =.782), average helical twist (–4.1 \ub1 4.0 to –3.7 \ub1 3.8\ub0/cm; P =.674), and peak helical twist (–13.2 \ub1 15.2 to –15.4 \ub1 14.2\ub0/cm; P =.629) did not change. However, the true lumen helical radius (1.4 \ub1 0.5 to 1.0 \ub1 0.6 cm; P <.05) and eccentricity (0.9 \ub1 0.1 to 0.7 \ub1 0.1; P <.05) decreased, and the cross-sectional area (3.0 \ub1 1.1 to 5.0 \ub1 2.0 cm2; P <.05) and circumference (7.1 \ub1 1.0 to 8.0 \ub1 1.4 cm; P <.05) increased significantly from before to after TEVAR. The distinct bimodal distribution of chiral and achiral native dissections disappeared after TEVAR, and subgroup analyses showed that the true lumen circumference of acute dissections increased with TEVAR, although it did not for chronic dissections. Conclusions: The unchanged helical angle and average and peak helical twists as a result of TEVAR suggest that the angular positions of the true lumen are constrained and that the endografts were helically conformable in the angular direction. The decrease of helical radius indicated a straightening of the corkscrew shape of the true lumen, and in combination with more circular and expanded lumen cross-sections, TEVAR produced luminal morphology that theoretically allows for lower flow resistance through the endografted portion. The impact of TEVAR on dissection flow lumen morphology and the interaction between endografts and aortic tissue can provide insight for improving device design, implantation technique, and long-term clinical outcomes

Tetra­aqua­bis{μ2-2,7-bis­[(2,6-diisopropyl­phen­yl)imino­meth­yl]naphthalene-1,8-diolato}di-μ3-hydroxido-di-μ2-hydroxido-bis­(trimethyl­phosphine oxide)tetra­nickel(II)–trimethyl­phosphine oxide–diethyl ether–water (1/2/2/2)

The title complex, [Ni4(C36H40N2O2)2(OH)4(C3H9OP)2(H2O)4]·2C4H10O·2C3H9OP·2H2O, is centrosymmetric with a central core that can be described as a defect double cubane. The four metal ions in the cluster are held together by four bridging hydroxide groups. Each NiII atom adopts a distorted octa­hedral geometry

Uranium(III) coordination chemistry and oxidation in a flexible small-cavity macrocycle

U(III) complexes of the conformationally flexible, small-cavity macrocycle trans-calix[2]benzene[2]pyrrolide (L)2–, [U(L)X] (X = O-2,6-tBu2C6H3, N(SiMe3)2), have been synthesized from [U(L)BH4] and structurally characterized. These complexes show binding of the U(III) center in the bis(arene) pocket of the macrocycle, which flexes to accommodate the increase in the steric bulk of X, resulting in long U–X bonds to the ancillary ligands. Oxidation to the cationic U(IV) complex [U(L)X][B(C6F5)4] (X = BH4) results in ligand rearrangement to bind the smaller, harder cation in the bis(pyrrolide) pocket, in a conformation that has not been previously observed for (L)2–, with X located between the two ligand arene rings

Patients with serious injection drug use-related infections who experience patient-directed discharges on oral antibiotics have high rates of antibiotic adherence but require multidisciplinary outpatient support for retention in care

Background: Persons who inject drugs (PWID) are frequently admitted for serious injection-related infections (SIRIs). Outcomes and adherence to oral antibiotics for PWID with patient-directed discharge (PDD) remain understudied. Methods: We conducted a prospective multicenter bundled quality improvement project of PWID with SIRI at 3 hospitals in Missouri. All PWID with SIRI were offered multidisciplinary care while inpatient, including the option of addiction medicine consultation and medications for opioid use disorder (MOUD). All patients were offered oral antibiotics in the event of a PDD either at discharge or immediately after discharge through an infectious diseases telemedicine clinic. Additional support services included health coaches, a therapist, a case manager, free clinic follow-up, and medications in an outpatient bridge program. Patient demographics, comorbidities, 90-day readmissions, and substance use disorder clinic follow-up were compared between PWID with PDD on oral antibiotics and those who completed intravenous (IV) antibiotics using an as-treated approach. Results: Of 166 PWID with SIRI, 61 completed IV antibiotics inpatient (37%), while 105 had a PDD on oral antibiotics (63%). There was no significant difference in 90-day readmission rates between groups ( Conclusions: PWID with SIRI who experience a PDD should be provided with oral antibiotics. Multidisciplinary outpatient support services are needed for PWID with PDD on oral antibiotics

A New Species of Boubou (Malaconotidae: Laniarius) from the Albertine Rift

We describe Laniarius willardi, a new species of boubou shrike (Malaconotidae) from the Albertine Rift of Africa. The most conspicuous, distinguishing morphological feature of the species is a gray to blue-gray iris. This and external morphometric data indicate that L. willardi is diagnosable from other black or sooty boubous. Further, L. willardi is genetically diagnosable, and its closest relative is the Mountain Sooty Boubou (L. poensis camerunensis) from Cameroon. The Crimson-breasted Bush-shrike (L. atrococcineus) and the Lowland Sooty Boubou (L. leucorhynchus) are together the sister clade to L. willardi—L.p. camerunensis. Laniarius willardi and the geographically codistributed L. p. holomelas differ by 11.5% in uncorrected sequence divergence, and elevational data taken from museum specimens suggest the possibility of elevational segregation of the species at ∼2,000 m, withL. willardi occurring at lower elevations. Our broad sampling of black and sooty boubou taxa indicate that (1) races of Mountain Sooty Boubou (L. poensis) do not form a monophyletic clade; (2) L. p. camerunensismay represent multiple, nonsister lineages; and (3) at least one race of Fülleborn\u27s Black Boubou (L. fuelleborni usambaricus) is genetically distinct from other races of that species