Quantitative Comparison of Abundance Structures of Generalized Communities: From B-Cell Receptor Repertoires to Microbiomes

The \emph{community}, the assemblage of organisms co-existing in a given space and time, has the potential to become one of the unifying concepts of biology, especially with the advent of high-throughput sequencing experiments that reveal genetic diversity exhaustively. In this spirit we show that a tool from community ecology, the Rank Abundance Distribution (RAD), can be turned by the new MaxRank normalization method into a generic, expressive descriptor for quantitative comparison of communities in many areas of biology. To illustrate the versatility of the method, we analyze RADs from various \emph{generalized communities}, i.e.\ assemblages of genetically diverse cells or organisms, including human B cells, gut microbiomes under antibiotic treatment and of different ages and countries of origin, and other human and environmental microbial communities. We show that normalized RADs enable novel quantitative approaches that help to understand structures and dynamics of complex generalize communities

Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Troetschel, C., Hamzeh, H., Alvarez, L., Pascal, R., Lavryk, F., Boenigk, W., Koerschen, H. G., Mueller, A., Poetsch, A., Rennhack, A., Gui, L., Nicastro, D., Struenker, T., Seifert, R., & Kaupp, U. B. Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation. Embo Journal, 39(4), (2020): e102723, doi:10.15252/embj.2019102723.Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca2+ rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin Arbacia punctulata. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H+, and Ca2+. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.We thank Heike Krause for preparing the manuscript. Financial support by the Deutsche Forschungsgemeinschaft (DFG) via the priority program SPP 1726 “Microswimmers” and the Cluster of Excellence 1023 “ImmunoSensation” is gratefully acknowledged. We thank D. Stoddard for management of the UTSW cryo‐electron microscope facility, which is funded in part by a Cancer Prevention and Research Institute of Texas (CPRIT) Core Facility Award (RP170644). This study was supported by HHS|National Institutes of Health (NIH) grant R01 GM083122 and by CPRIT grant RR140082 to D. Nicastro

Yersinia pestis DNA from Skeletal Remains from the 6(th) Century AD Reveals Insights into Justinianic Plague.

Yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. These include the third pandemic of the 19(th) and 20(th) centuries, during which plague was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the Black Death. Previous studies have confirmed that Y. pestis caused these two more recent pandemics. However, a highly spirited debate still continues as to whether Y. pestis caused the so-called Justinianic Plague of the 6(th)-8(th) centuries AD. By analyzing ancient DNA in two independent ancient DNA laboratories, we confirmed unambiguously the presence of Y. pestis DNA in human skeletal remains from an Early Medieval cemetery. In addition, we narrowed the phylogenetic position of the responsible strain down to major branch 0 on the Y. pestis phylogeny, specifically between nodes N03 and N05. Our findings confirm that Y. pestis was responsible for the Justinianic Plague, which should end the controversy regarding the etiology of this pandemic. The first genotype of a Y. pestis strain that caused the Late Antique plague provides important information about the history of the plague bacillus and suggests that the first pandemic also originated in Asia, similar to the other two plague pandemics

Combined sedation with midazolam/propofol for gastrointestinal endoscopy in elderly patients

<p>Abstract</p> <p>Background</p> <p>Although gastrointestinal endoscopy with sedation is increasingly performed in elderly patients, data on combined sedation with midazolam/propofol are very limited for this age group.</p> <p>Methods</p> <p>We retrospectively analyzed 454 endoscopic procedures in 347 hospitalized patients ≥ 70 years who had received combined sedation with midazolam/propofol. 513 endoscopic procedures in 397 hospitalized patients < 70 years during the observation period served as controls. Characteristics of endoscopic procedures, co-morbidity, complications and mortality were compared.</p> <p>Results</p> <p>Elderly patients had a higher level of co-morbidity and needed lower mean propofol doses for sedation. We observed no major complication and no difference in the number of minor complications. The procedure-associated mortality was 0%; the 28-day mortality was significantly higher in the elderly (2.9% vs. 1.0%).</p> <p>Conclusions</p> <p>In this study on elderly patients with high level co-morbidity, a favourable safety profile was observed for a combined sedation with midazolam/propofol with a higher sensitivity to propofol in the elderly.</p

Bilayer-spanning DNA nanopores with voltage-switching between open and closed state.

Membrane-spanning nanopores from folded DNA are a recent example of biomimetic man-made nanostructures that can open up applications in biosensing, drug delivery, and nanofluidics. In this report, we generate a DNA nanopore based on the archetypal six-helix-bundle architecture and systematically characterize it via single-channel current recordings to address several fundamental scientific questions in this emerging field. We establish that the DNA pores exhibit two voltage-dependent conductance states. Low transmembrane voltages favor a stable high-conductance level, which corresponds to an unobstructed DNA pore. The expected inner width of the open channel is confirmed by measuring the conductance change as a function of poly(ethylene glycol) (PEG) size, whereby smaller PEGs are assumed to enter the pore. PEG sizing also clarifies that the main ion-conducting path runs through the membrane-spanning channel lumen as opposed to any proposed gap between the outer pore wall and the lipid bilayer. At higher voltages, the channel shows a main low-conductance state probably caused by electric-field-induced changes of the DNA pore in its conformation or orientation. This voltage-dependent switching between the open and closed states is observed with planar lipid bilayers as well as bilayers mounted on glass nanopipettes. These findings settle a discrepancy between two previously published conductances. By systematically exploring a large space of parameters and answering key questions, our report supports the development of DNA nanopores for nanobiotechnology.The SH lab is supported by the Leverhulme Trust (RPG-170), UCL Chemistry, EPSRC (Institutional Sponsorship Award), the National Physical Laboratory, and Oxford Nanopore Technologies. KG acknowledges funding from the Winton Program of Physics for Sustainability, Gates Cambridge and the Oppenheimer Trust. UFK was supported by an ERC starting grant #261101.This is the final version of the article. It was first published by ACS under the ACS AuthorChoice license at http://dx.doi.org/10.1021/nn5039433 This permits copying and redistribution of the article or any adaptations for non-commercial purposes

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Der konzeptionelle Handlungsrahmen der oeffentlichen Regional- und Arbeitsmarktpolitik in der SaarLorLux-Region

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, D-21400 Kiel A 213072 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Evaluation of metastases in the submandibular gland in head and neck malignancy

BACKGROUND:: Either excision of the submandibular gland during neck dissection or having the submandibular gland in radiation field can result in xerostomia, leading to reduced quality of life. The purpose of this study was to evaluate the prevalence of metastasis to the submandibular gland and to identify potential risk factors leading to the presence of metastases into the gland. PATIENTS AND METHODS:: Of 376 patients with head and neck malignancy who were treated between 1999 and 2008, 130 patients underwent a neck dissection, and in total, 171 submandibular glands were removed. The average age was 61.1 years. RESULTS:: Twenty-three patients (17.7%) revealed some type of pathology in the submandibular gland such as chronic sialadenitis (15), atrophy (5), tumor infiltration (5), and intraglandular lymph node (1). In the group with sialadenitis, the mean age was 57.7 years. Forty-four percent had a pretreatment (radiation, 9%; local resection, 13%; or combined therapy, 22%) before neck dissection. Of the sialadenitis group, 9 of 12 patients had the primary tumor in the lower jaw, floor of mouth, or tongue. CONCLUSIONS:: One needs to be aware of the possibility of occult metastases in level I in oral cavity carcinomas, whereas oropharynx carcinoma constitutes a lower risk for involvement of lymph node metastases at level I. The excision of the submandibular gland should be performed in cases with positive lymph nodes at level I and in tumor sites with a high risk of occult metastasis at level I

Influence of mirrored computed tomograms on decision-making for revising surgically treated orbital floor fractures

PURPOSE This study evaluated whether intraoperative imaging with computer-assisted virtual reconstruction would be advantageous in reconstructions of orbital floor fractures. The surgeon's intention to revise a reconstructed primary orbital floor fracture by evaluating a postoperative mirrored computed tomographic (CT) scan was analyzed intraoperatively before wound closure, during inpatient hospitalization, and after hospitalization. The inter-rater agreement and the match of intention to revise and actual revision were analyzed. MATERIALS AND METHODS Fifty-one anonymized postoperative CT scans of patients with a unilateral orbital floor fracture were mirrored using software. These computer-assisted virtual reconstructions were consecutively examined by 4 examiners. Seven of these patients underwent a revision. In the first part, the inter-rater agreements for all 3 times were analyzed. In the second part, the examiners' intentions to revise were compared with the actual performed revisions. RESULTS The overall inter-rater agreements were 0.69 for the intraoperative phase, 0.55 for the in-hospital phase, and 0.39 for the post-hospital phase. The intraoperative inter-rater agreement for each examiner was 0.58 to 0.80. The Fleiss κ value for the in-hospital and post-hospital phases was lower. The comparison of the examiners' intention to revise and the actual revisions showed that 15 to 24 additional would have been revised. In contrast, 6 of 7 actual revisions would have been revised intraoperatively. The missed actual revision was the same case by all 4 examiners. The accordance of intention to revise with the actual revisions decreased during hospitalization and even more after hospitalization. This study showed strong agreement among examiners for revising anatomically incorrectly reduced orbital floor fractures intraoperatively by evaluating postoperative mirrored CT scans. During the in-hospital and post-hospital phases, the restraints against revision seemed to increase, thus leading to poorer inter-rater agreement. This analysis of postoperative CT scans with computer-assisted virtual reconstructions of the orbit would have led to considerably more revisions intraoperatively, but all actual revisions were detected except for 1 case. This case was the same for all 4 examiners. Operation time would have been prolonged in the additional revised cases, but a better anatomic reconstruction would have been achieved. Furthermore, the intraoperative result of the reconstruction would have been controlled instantly and corrected immediately, if needed. CONCLUSION This study showed that of 6 of 7 actual revisions, implant placement would have been revised intraoperatively by all 4 examiners, if intraoperative imaging with computer-assisted virtual reconstruction of the orbit would have been applied. Therefore, the authors suggest that intraoperative imaging with computer-assisted virtual reconstruction could be advantageous in the prevention of later revisions of orbital floor fractures. In this study, the threshold to revise implant placement intraoperatively seemed to be lower when using intraoperative imaging with virtual reconstructions, because considerably more cases would have been revised intraoperatively by the examiners. In the in-hospital and post-hospital phases, this threshold increased, suggesting the more important role of clinical findings. It is uncertain whether the actual surgeons would have revised the same cases as the examiners if they had used intraoperative imaging with virtual reconstructions for their deliberation. However, the intraoperative inter-rater agreement was good and cost-intensive postoperative revisions might be prevented