Activity

The frequent occurrence of superlinear scaling indicates that biogeochemical activity in large rivers contributes disproportionately to the function of river networks in the Earth system.A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. EZM0414 HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed. Positron emission tomography (PET) imaging is a promising strategy to identify and characterize the tissue-wide burden of HIV. Here, we assess the efficacy of using immunoPET imaging to characterize HIV reservoirs and identify anatomical foci of persistent viral transcriptional activity using a radiolabeled HIV Env-specific broadly neutralizing antibody, 89Zr-VRC01, in HIV-infected individuals with detectable viremia and on suppressive ART compared to uninfected controls (NCT03729752). We also assess the relationship between PET tracer uptake in tissues and timing of ART initiation and direct HIV protein expression in CD4 T cells obtained from lymph node biopsies. We observe significant increases in 89Zr-VRC01 uptake in various tissues (including lymph nodes and gut) in HIV-infected individuals with detectable viremia (N = 5) and on suppressive ART (N = 5) compared to uninfected controls (N = 5). Importantly, PET tracer uptake in inguinal lymph nodes in viremic and ART-suppressed participants significantly and positively correlates with HIV protein expression measured directly in tissue. Our strategy may allow non-invasive longitudinal characterization of residual HIV infection and lays the framework for the development of immunoPET imaging in a variety of other infectious diseases.The 20S proteasome (20S) facilitates turnover of most eukaryotic proteins. Substrate entry into the 20S first requires opening of gating loops through binding of HbYX motifs that are present at the C-termini of certain proteasome activators (PAs). The HbYX motif has been predominantly characterized in the archaeal 20S, whereas little is known about the sequence preferences of the human 20S (h20S). Here, we synthesize and screen ~120 HbYX-like peptides, revealing unexpected differences from the archaeal system and defining the h20S recognition sequence as the Y-F/Y (YФ) motif. To gain further insight, we create a functional chimera of the optimized sequence, NLSYYT, fused to the model activator, PA26E102A. A cryo-EM structure of PA26E102A-h20S is used to identify key interactions, including non-canonical contacts and gate-opening mechanisms. Finally, we demonstrate that the YФ sequence preferences are tuned by valency, allowing multivalent PAs to sample greater sequence space. These results expand the model for termini-mediated gating and provide a template for the design of h20S activators.Male colour patterns of the Trinidadian guppy (Poecilia reticulata) are typified by extreme variation governed by both natural and sexual selection. Since guppy colour patterns are often inherited faithfully from fathers to sons, it has been hypothesised that many of the colour trait genes must be physically linked to sex determining loci as a ‘supergene’ on the sex chromosome. Here, we phenotype and genotype four guppy ‘Iso-Y lines’, where colour was inherited along the patriline for 40 generations. Using an unbiased phenotyping method, we confirm the breeding design was successful in creating four distinct colour patterns. We find that genetic differentiation among the Iso-Y lines is repeatedly associated with a diverse haplotype on an autosome (LG1), not the sex chromosome (LG12). Moreover, the LG1 haplotype exhibits elevated linkage disequilibrium and evidence of sex-specific diversity in the natural source population. We hypothesise that colour pattern polymorphism is driven by Y-autosome epistasis.The sources of isotopically light carbon released during the end-Triassic mass extinction remain in debate. Here, we use mercury (Hg) concentrations and isotopes from a pelagic Triassic-Jurassic boundary section (Katsuyama, Japan) to track changes in Hg cycling. Because of its location in the central Panthalassa, far from terrigenous runoff, Hg enrichments at Katsuyama record atmospheric Hg deposition. These enrichments are characterized by negative mass independent fractionation (MIF) of odd Hg isotopes, providing evidence of their derivation from terrestrial organic-rich sediments (Δ199Hg  less then  0‰) rather than from deep-Earth volcanic gases (Δ199Hg ~ 0‰). Our data thus provide evidence that combustion of sedimentary organic matter by igneous intrusions and/or wildfires played a significant role in the environmental perturbations accompanying the event. This process has a modern analog in anthropogenic combustion of fossil fuels from crustal reservoirs.BACKGROUND This report presents a rare case of a traumatic innominate artery to left innominate vein fistula following a stab wound to the base of the neck. CASE REPORT We report a case of a 23-year-old patient with a traumatic innominate-innominate arteriovenous fistula, after being stabbed in the suprasternal notch area 3 years prior. The patient presented with fatigue, and shortness of breath on exertion. Examination revealed a wide pulse pressure, bounding pulses, and a continuous murmur on the upper sternal area. Chest X-rays, echocardiography, CT angiography, and cardiac catheterization were useful to aid in diagnosis and work-up for fistula repair. A complex 8-mm fistula between the left innominate vein and the proximal innominate artery was noted, with multiple tortuous channels and demonstrating a reversible left-to-right shunt. After medical optimization, successful surgical ligation and division of the fistula was done through median sternotomy without cardiopulmonary bypass. The postoperative recovery was uneventful. CONCLUSIONS Traumatic innominate-innominate arteriovenous fistulas are rare and can pose a diagnostic challenge. High index of suspicion, careful history, examination, and radiologic evaluation usually result in correct diagnosis. Endovascular and surgical approaches are the mainstay treatment.BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is significantly associated with increased mortality. The current study aimed to investigate the predictive ability of the prognostic nutritional index (PNI) in 30-day mortality among AECOPD patients admitted to the ICU. MATERIAL AND METHODS Clinical data were extracted from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Patients were divided into 3 groups according to the tertiles of PNI. Cox proportional hazard regressions were performed to assess the association between PNI and 30-day mortality. Subgroup analyses were performed to identify the consistency of the association. Receiver operator characteristic (ROC) curve analysis was performed to evaluate the predictive accuracy among PNI, serum albumin, neutrophil-to-lymphocyte (NLR), and platelet-to-lymphocyte ratio (PLR). RESULTS A total of 494 AECOPD patients were included in this study. The mean age was 70.8±10.4 years old. Kaplan-Meier analysis showed ongoing divergence in rates of mortality among tertiles (p70 years and with mechanical ventilation. The cut-off value of PNI was 31.8 with sensitivity 62.3% and specificity 64.1%. The area under the ROC of PNI (0.642, 95% CI, 0.560 to 0.717) was better than that of serum albumin, NLR, and PLR. CONCLUSIONS PNI could serve as a simple and reliable prognostic biomarker for AECOPD patients in the ICU.

The purposes of this study were to estimate the eye lens dose during the handling of radiopharmaceuticals and to validate the requirement of X-ray protective goggles in nuclear medicine.

Simulated eye lens radiation exposure (3-mm dose equivalent rate) was measured using a radiophotoluminescent glass dosimeter (RPLD) positioned at distances of 30 and 60 cm from

Tc,

In, and

I radiation sources. Reduction rates were evaluated for the following means of radiation protection X-ray protective goggles (0.07-, 0.50-, and 0.75-mm lead equivalent), a syringe shield, and a lead glass plate.

3-mm dose equivalent rates without protection were obtained at 6.13±0.13 µSv/min/GBq for

Tc, 23.08±0.19 µSv/min/GBq for

In, and 11.07±0.11 µSv/min/GBq for

I. Reduction rates for each source were over 90% for the syringe shield and the lead glass plate. The 0.75-mm lead equivalent X-ray protective goggles decreased the 3-mm dose equivalent rate by 68.8% for

Tc, 60.6% for

In, and 68.1% for

I.

Although the estimated eye lens equivalent dose during the handling of radiopharmaceuticals did not exceed the threshold dose, our results suggest that 0.75-mm lead equivalent X-ray protective goggles are needed to reduce the exposure of the lens while handling

Tc,

In, and

I radiation sources.

Although the estimated eye lens equivalent dose during the handling of radiopharmaceuticals did not exceed the threshold dose, our results suggest that 0.75-mm lead equivalent X-ray protective goggles are needed to reduce the exposure of the lens while handling 99mTc, 111In, and 123I radiation sources.

The structural integrity of the resin cement layer, the bond strength, and the biomechanical behavior of different fiberglass post cementation techniques were evaluated.

Thirty-three bovine incisors were divided into three groups (n = 11) conventional fiberglass post (CFP), conventional fiberglass post in flared root canals (CFL), and relined fiberglass post (RFP). Six specimens from each group were submitted for high-resolution microcomputed tomography (μCT) to evaluate the integrity and presence/volume of voids at the resin cement layer. Finite element analysis (FEA) of two three-dimensional (3D) models of each group were conducted, one considered ideal (without interface defects) and another containing the conditions identified in the μCT analysis. Push-out bond strength tests were conducted for all specimens.

The CFL group had the greatest mean values of void (Thirds cervical 73.67; middle 95.67; apical 47.33) and gap concentration (Thirds cervical 14.67; middle 15.83; apical 8.33) compared with CFP and RFP. A significant difference in bond strength was observed between the cervical (1.33 MPa) and middle thirds (1.85 MPa) compared with the apical third (4.85 MPa) of the CFL. A significant difference was observed in the bond strength in the CFL (1.33 MPa) and RFP (3.29 MPa) in the cervical third, which were statistically similar to the bond strength of the CFP. The tensile stress distributions were similar in most structures, localized in the cervical region on the lingual surface.

Structural defects in the interface layer might influence the bond strength and biomechanical behavior under the different fiberglass post cementations.

Structural defects in the interface layer might influence the bond strength and biomechanical behavior under the different fiberglass post cementations.Advancements in dental cements have considerably improved their bond strengths. However, high bond strength often makes the removal of restorations difficult. Thus, smart dental cements that show controllable bond strength are required. A conventional resin-modified glass-ionomer-cement demonstrated a significant reduction in the bond strength after current application. However, for this system, the ions in the cement are released into the oral cavity, resulting in a reduction of the electrical conductivity and in losses of the expected on-demand debonding property. Herein, the effects of immersion in 0.9 and 15% NaCl solutions on the electrical conductivity and debonding properties were investigated. The cement immersed in 0.9% NaCl solution from 1 to 28 days maintained similar bond strength reductions after current application, whereas that in 15% NaCl solution initially showed no bond strength reduction after 1 day but exhibited an increase in the bond strength reduction after immersion for 28 days.