Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar ...macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.
The objective was to compare the use of corpus luteum (CL) vascular perfusion to CL diameter and/or echogenicity to diagnose pregnancy at 21 d after timed-AI. Ovaries of Nelore heifers were assessed ...using ultrasonography in B-mode and color Doppler simultaneously 21 d after timed-AI (n = 113). Objective evaluations were performed using an image processing software to extract the number of colored pixels (ColorPix), diameter (mm) and echogenicity/mm² (EchoPix) of the CL. Subjective evaluations of the CL were performed by five evaluators using scores of estimated vascular perfusion area of color Doppler scan videos and estimated CL size and qualitative echogenicity of B-mode scan videos. The reference pregnancy diagnosis was performed 33 d after timed-AI using an ultrasonic device. Corpus luteum ColorPix, diameter and EchoPix were highly correlated (P < 0.001) with pregnancy. Pregnancy diagnosis accuracy, sensitivity, and negative predictive value were not different for CL ColorPix and diameter and was less with use of EchoPix compared to the other parameters. Size and vascular perfusion scores were correlated to the greatest extent (0.88–0.94) with the respective objective values within evaluator. The results from the ROC curve analysis indicated a smaller area under the curve for qualitative echogenicity compared to CL size and vascular perfusion. Corpus luteum vascular perfusion was the only subjective evaluation that when assessed there were no false negative pregnancy diagnoses. In conclusion, the use of the objective CL diameter resulted in the same efficacy as CL vascular perfusion evaluations for early pregnancy diagnosis in Nelore heifers.
Incidence of pneumococcal disease is disproportionally high in infants and elderly. Nasopharyngeal colonisation by Streptococcus pneumoniae is considered a prerequisite for disease but unlike in ...children, carriage in elderly is rarely detected. Here, we tested for S. pneumoniae in nasopharyngeal and saliva samples collected from community-dwelling elderly with influenza-like-illness (ILI). Trans-nasal nasopharyngeal, trans-oral nasopharyngeal and saliva samples (n = 270 per sample type) were collected during winter/spring 2011/2012 from 135 persons aged 60-89 at onset of ILI and 7-9 weeks later following recovery. After samples were tested for pneumococci by conventional culture, all plate growth was collected. DNA extracted from plate harvests was tested by quantitative-PCRs (qPCR) specific for S. pneumoniae and serotypes included in the 13-valent pneumococcal conjugated vaccine (PCV13). Pneumococci were cultured from 14 of 135 (10%) elderly with none of the sampled niches showing superiority in carriage detection. With 76/270 (28%) saliva, 31/270 (11%) trans-oral and 13/270 (5%) trans-nasal samples positive by qPCR, saliva was superior to nasopharyngeal swabs (p<0.001) in qPCR-based carriage detection. Overall, from all methods used in the study, 65 of 135 (48%) elderly carried pneumococci at least once and 26 (19%) at both study time points. The difference between carriage prevalence at ILI (n = 49 or 36%) versus recovery (n = 42 or 31%) was not significant (p = 0.38). At least 23 of 91 (25%) carriage events in 19 of 65 (29%) carriers were associated with PCV13-serotypes. We detected a large reservoir of pneumococci in saliva of elderly, with PCV13-serotype distribution closely resembling the contemporary carriage of serotypes reported in the Netherlands for PCV-vaccinated infants.
The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this ...study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log
reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.
New Representations of the Perturbative S Matrix Baadsgaard, Christian; Bjerrum-Bohr, N E J; Bourjaily, Jacob L ...
Physical review letters,
2016-Feb-12, Letnik:
116, Številka:
6
Journal Article
Recenzirano
We propose a new framework to represent the perturbative S matrix which is well defined for all quantum field theories of massless particles, constructed from tree-level amplitudes and integrable ...term by term. This representation is derived from the Feynman expansion through a series of partial fraction identities, discarding terms that vanish upon integration. Loop integrands are expressed in terms of "Q-cuts" that involve both off-shell and on-shell loop momenta, defined with a precise contour prescription that can be evaluated by ordinary methods. This framework implies recent results found in the scattering equation formalism at one loop, and it has a natural extension to all orders--even nonplanar theories without well-defined forward limits or good ultraviolet behavior.
The human nasopharynx is the main reservoir for Streptococcus pneumoniae. We applied conventional and molecular methods to determine the prevalence of S. pneumoniae nasopharyngeal colonization in ...adults. Paired trans-orally and trans-nasally obtained nasopharyngeal samples from 268 parents of 24-month-old children were assessed for pneumococcal presence. Parents were classified as colonized when live pneumococci were recovered from either sample cultured on medium selective for S. pneumoniae. Of the 52 (19%) colonized parents 49 (18%) were culture-positive in trans-nasal and 10 (4%) in trans-oral samples. Bacterial growth was harvested from these cultures, DNA isolated and tested by quantitative-PCR (qPCR) targeting lytA and piaA genes specific for S. pneumoniae. A sample was considered positive if signals for both genes were detected. Altogether 105 (39%) individuals were classified as positive for pneumococcus by qPCR including 50 (19%) in trans-nasal and 94 (35%) in trans-oral settings. Although significantly more trans-nasal compared to trans-oral samples were culture-positive for S. pneumoniae at the primary diagnostic step (p<0.001) the opposite was observed in qPCR results (p<0.001). To confirm the presence of live pneumococcus in samples positive by qPCR but negative at the initial diagnostic step, we serially-diluted cell harvests, re-cultured and carefully examined for S. pneumoniae presence. Live pneumococci were recovered from an additional 43 parents including 42 positive in trans-oral and 4 in trans-nasal samples increasing the number of individuals culture- and qPCR-positive to 93 (35%) and positive by either of two methods to 107 (40%). There were significantly more trans-oral than trans-nasal samples positive for pneumococcus by both culture and qPCR (n = 71; 27%; vs. n = 50; 19%; p<0.05). Our data suggest that pneumococcal colonization is more common in adults than previously estimated and point towards the superiority of a trans-oral over a trans-nasal approach when testing adults for colonization with S. pneumoniae.
Postoperative pancreatic fistula (POPF) with reported incidence rates up to 45% contributes substantially to overall morbidity. In this study, we conducted a retrospective evaluation of POPF along ...with its potential perioperative clinical risk factors and its effect on tumor recurrence. Clinical data on patients who had received pancreatoduodenectomy (PD), distal pancreatectomy (DP), or duodenum-preserving pancreatic head resection (DPPHR) were prospectively collected between 2007 and 2016. A Picrosirius red staining score was developed to enable morphological classification of the resection margin of the pancreatic stump. The primary end point was the development of major complications. The secondary end points were overall and recurrence-free survival. 340 patients underwent pancreatic resection including 222 (65.3%) PD, 87 (25.6%) DP, and 31 (9.1%) DPPHR. Postoperative major complications were observed in 74 patients (21.8%). In multivariable logistic regression analysis, POPF correlated with body mass index (BMI) (p = 0.025), prolonged stay in hospital (p<0.001), high Picrosirius red staining score (p = 0.049), and elevated postoperative levels of amylase or lipase in drain fluid (pless than or equal to0.001). Multivariable Cox regression analysis identified UICC stage (p<0.001), tumor differentiation (p<0.001), depth of invasion (p = 0.001), nodal invasion (p = 0.001), and the incidence of POPF grades B and C (p = 0.006) as independent prognostic markers of recurrence-free survival. Besides the known clinicopathological risk factors BMI and amylase in the drain fluid, the incidence of POPF correlates with high Picrosirius red staining score in the resection margins of the pancreatic stumps of curatively resected pancreatic ductal adenocarcinoma (PDAC). Furthermore, clinically relevant POPF seems to be a prognostic factor for tumor recurrence in PDAC.
Trilayer nickelates, which exhibit a high degree of orbital polarization combined with an electron count (d^{8.67}) corresponding to overdoped cuprates, have been identified as a promising candidate ...platform for achieving high-T_{c} superconductivity. One such material, La_{4}Ni_{3}O_{8}, undergoes a semiconductor-insulator transition at ∼105 K, which was recently shown to arise from the formation of charge stripes. However, an outstanding issue has been the origin of an anomaly in the magnetic susceptibility at the transition and whether it signifies the formation of spin stripes akin to single layer nickelates. Here we report single crystal neutron diffraction measurements (both polarized and unpolarized) that establish that the ground state is indeed magnetic. The ordering is modeled as antiferromagnetic spin stripes that are commensurate with the charge stripes, the magnetic ordering occurring in individual trilayers that are essentially uncorrelated along the crystallographic c axis. A comparison of the charge and spin stripe order parameters reveals that, in contrast to single-layer nickelates such as La_{2-x}Sr_{x}NiO_{4} as well as related quasi-2D oxides including manganites, cobaltates, and cuprates, these orders uniquely appear simultaneously, thus demonstrating a stronger coupling between spin and charge than in these related low-dimensional correlated oxides.
For more than 20 years, the reported occurrence of diamonds in the chromites and peridotites of the Luobusa massif in Tibet (a complex described as an ophiolite) has been widely ignored by the ...diamond research community. This skepticism has persisted because the diamonds are similar in many respects to high-pressure high-temperature (HPHT) synthetic/industrial diamonds (grown from metal solvents), and the finding previously has not been independently replicated. We present a detailed examination of the Luobusa diamonds (recovered from both peridotites and chromitites), including morphology, size, color, impurity characteristics (by infrared spectroscopy), internal growth structures, trace-element patterns, and C and N isotopes. A detailed comparison with synthetic industrial diamonds shows many similarities. Cubo-octahedral morphology, yellow color due to unaggregated nitrogen (C centres only, Type Ib), metal–alloy inclusions and highly negative δC13 values are present in both sets of diamonds. The Tibetan diamonds (n=3) show an exceptionally large range in δN15 (−5.6 to +28.7‰) within individual crystals, and inconsistent fractionation between {111} and {100} growth sectors. This in contrast to large synthetic HPHT diamonds grown by the temperature gradient method, which have with δN15=0‰ in {111} sectors and +30‰ in {100} sectors, as reported in the literature. This comparison is limited by the small sample set combined with the fact the diamonds probably grew by different processes. However, the Tibetan diamonds do have generally higher concentrations and different ratios of trace elements; most inclusions are a NiMnCo alloy, but there are also some small REE-rich phases never seen in HPHT synthetics. These characteristics indicate that the Tibetan diamonds grew in contact with a C-saturated Ni–Mn–Co-rich melt in a highly reduced environment. The stable isotopes indicate a major subduction-related contribution to the chemical environment. The unaggregated nitrogen, combined with the lack of evidence for resorption or plastic deformation, suggests a short (geologically speaking) residence in the mantle. Previously published models to explain the occurrence of the diamonds, and other phases indicative of highly reduced conditions and very high pressures, have failed to take into account the characteristics of the diamonds and the implications for their formation. For these diamonds to be seriously considered as the result of a natural growth environment requires a new understanding of mantle conditions that could produce them.
•The occurrence of diamonds in the Luobusa massif have been independently verified.•“Ophiolite” diamonds have many similarities with HPHT synthetic diamonds.•Growth from metallic-rich melts under reduced conditions account for their features.•Current models for their formation do not account for the diamonds' characteristics.
Supported lipid bilayers (SLBs) are a useful tool for studying the interactions between lipids and other biomolecules that make up a cell membrane. SLBs are typically formed by the adsorption and ...rupture of vesicles from solution. Although it is known that many experimental factors can affect whether SLB formation is successful, there is no comprehensive understanding of the mechanism. In this work, we have used a quartz crystal microbalance (QCM) to investigate the role of the salt in the buffer on the formation of phosphatidylcholine SLBs on a silicon dioxide (SiO2) surface. We varied the concentration of sodium chloride in the buffer, from 5 to 150 mM, to find the minimum concentration of NaCl that was required for the successful formation of an SLB. We then repeated the experiments with other group I chloride salts (LiCl, KCl, and CsCl) and found that at higher salt concentrations (150 mM) SLB formation was successful for all of the salts used, and the degree of deformation of the adsorbed vesicles at the critical vesicle coverage was cation-dependent. The results showed that at an intermediate salt concentration (50 mM) the critical vesicle coverage was cation-dependent and at low salt concentrations (12.5 mM) the cation used determined whether SLB formation was successful. We found that the successful formation of SLBs could occur at lower electrolyte concentrations for KCl and CsCl than it did for NaCl. To understand these results, we calculated the magnitude of the vesicle–surface interaction energy using the Derjaguin–Landau–Verwey–Overbeek (DLVO) and extended-DLVO theory. We managed to explain the results obtained at higher salt concentrations by including cation-dependent surface potentials in the calculations and at lower salt concentrations by the addition of a cation-dependent hydration force. These results showed that the way that different cations in solution affect the 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)–SiO2 surface interaction energy depends on the ionic strength of the solution.
PDF
