Data_Sheet_1_Bacterial Nanotubes as Intercellular Linkages in Marine Assemblages.PDF

Several types of bacterial appendages, e.g., pili and fimbriae, are known for their role in promoting interactions and aggregation with particles and bacteria in the ocean. First discovered in Bacillus subtilis and Escherichia coli, but novel to marine bacteria, bacterial nanotubes are hollow tubular structures connecting cell pairs that allow for the internal transport of cytoplasmic metabolites across the connecting structure. While the significance of nanotubes in exchange of cytoplasmic content has been established in non-marine bacteria, their occurrence and potential ecological significance in marine bacteria has not been reported. Using multiple high-resolution microscopy methods (atomic force microscopy, scanning, and transmission electron microscopy), we have determined that marine bacteria isolates and natural assemblages from nearshore upper ocean waters can express bacterial nanotubes. In marine isolates Pseudoalteromonas sp. TW7 and Alteromonas sp. ALTSIO, individual bacterial nanotubes measured 50–160 nm in width and extended 100–600 nm between connected cells. The spatial coupling of different cells via nanotubes can last for at least 90 min, extending the duration of interaction events between marine bacteria within natural assemblages. The nanomechanical properties of bacterial nanotubes vary in adhesion and dissipation properties, which has implication for structural and functional variability of these structures in their ability to stick to surfaces and respond to mechanical forces. Nanotube frequency is low among cells in enriched natural assemblages, where nanotubes form short, intimate connections, <200 nm, between certain neighboring cells. Bacterial nanotubes can form the structural basis for a bacterial ensemble and function as a conduit for cytoplasmic exchange (not explicitly studied here) between members for multicellular coordination and expression. The structural measurements and nanomechanical analyses in this study also extends knowledge about the physical properties of bacterial nanotubes and their consequences for marine microenvironments. The discovery of nanotube expression in marine bacteria has significant potential implications regarding intimate bacterial interactions in spatially correlated marine microbial communities.</p

BVF and Mitral Valve-in-Valve with Surgical Resection of Mitral Prosthetic Valve Leaflets with Mitral SURPLUS

Transcatheter mitral valve-in-valve (ViV) is emerging as an alternative to surgery in patients with degenerated mitral valve bioprosthesis. One of the most common exclusion criteria for mitral ViV is left ventricular outflow tract obstruction (LVOTO) due to displacement of the anterior leaflet of the mitral valve prosthesis towards the septum, thus reducing the LVOT area. LVOTO needs to be prevented, and preoperative transesophageal echocardiography (TEE) and computed tomography angiography (CTA) play a crucial role in identifying the patients at risk. When not recognized on preoperative imaging, LVOT obstruction is a catastrophic complication of transcatheter mitral ViV procedure. Options to avoid LVOT obstruction include laceration of the anterior leaflet of the mitral valve (LAMPOON), septal ablation, or mitral ViV. If none of these techniques are feasible because of excessive calcification of the prosthetic leaflets or absence of a proximal septal branch, redo surgery and mitral valve replacement is the only option available. This is a challenging intervention that requires lysis of the adhesions, explantation of the existing bioprosthesis, and suturing of a new valve.SURPLUS (surgical resection of prosthetic valve leaflets under direct vision) is a hybrid surgical and transcatheter technique that implies just the resection of the bioprosthetic valve leaflets, leaving the stent of the valve intact, and direct implantation of a balloon-expandable valve under direct vision and fluoroscopic guidance. SURPLUS can be performed via a right anterolateral thoracotomy, peripheral cannulation, and fibrillatory arrest. The left atrium is entered through the Sondergaard groove and the bioprosthetic leaflets are resected. In order to implant a larger transcatheter heart valve (THV) prosthesis, a bioprosthetic valve fracture (BVF) can also be performed using a noncompliant balloon. A balloon-expandable valve is then introduced and deployed under direct vision and fluoroscopic guidance in the standard fashion. SURPLUS avoids removal of the whole old mitral valve, thus shortening the duration of cardiopulmonary bypass (CPB) and cardiac ischemia. It is easy and reproducible, and is an option in the hands of surgeons when transcatheter ViV is not feasible because of high risk of LVOTO.Reference(s)Basman C, Kliger C, Kodra A, et al. Transcatheter Mitral Valve-in-Valve With Surgical Resection of Bioprosthetic Valve Leaflets Under Direct Vision (Mitral SURPLUS). J Am Coll Cardiol Intv. 2022 Jun, 15 (12) e145–e146.https://doi.org/10.1016/j.jcin.2022.04.007</p

Comparison of 5 and 10 year outcomes for usual care vs. genomics-based care decisions using individual level probabilities.

<p>Results are presented for the Mayo Clinic and TJU cohorts. McNemar’s test was used to test for significant differences between usual care and GC-based treatment outcomes for each cohort.</p><p>BCR = biochemical recurrence; MET = metastasis; GC = genomic classifier.</p><p>Comparison of 5 and 10 year outcomes for usual care vs. genomics-based care decisions using individual level probabilities.</p

Descriptions of patient characteristics for each cohort.

<p>SD = standard deviation; ECE = extracapsular extension; SVI = seminal vesicle invasion; PSM = positive surgical margin; LNI = lymph node involvement; GC = genomic classifier; TJU = Thomas Jefferson University; Ref. = reference</p><p>*Note, three patients were excluded from this original cohort due to unknown ECE status; Overall cohort metastatic risk, range of risks for cohort, and proportion classified as high risk according to GC was based on the reweighted cohort of 808 patients from the original cohort of 216 patients.</p><p>Descriptions of patient characteristics for each cohort.</p

Simplified state transition diagram representing the treatment decisions and health state transitions post radical prostatectomy.

<p>NED represents patients with no evidence of disease.</p

Comparison of 5 and 10 year outcomes for population level probabilities vs. individual level probabilities using usual care treatment.

<p>Results are presented for the Mayo Clinic and TJU cohorts.</p><p>Comparison of 5 and 10 year outcomes for population level probabilities vs. individual level probabilities using usual care treatment.</p

Time in life years (LYs) in states (Subfigure A), and quality-adjusted life years (QALYs) in states (Subfigure B) for the Mayo Clinic Cohort. GC-based treatment refers to treatment decisions made based upon the genomic risk classifier assay.

<p>BCR = biochemical recurrence; NED = no evidence of disease; GC = genomic classifier.</p

Intact Type I Interferon Production and IRF7 Function in Sooty Mangabeys

<div><p>In contrast to pathogenic HIV/SIV infections of humans and rhesus macaques (RMs), natural SIV infection of sooty mangabeys (SMs) is typically non-pathogenic despite high viremia. Several studies suggested that low immune activation and relative resistance of CD4+ central memory T-cells from virus infection are mechanisms that protect SMs from AIDS. In 2008 it was reported that plasmacytoid dendritic cells (pDCs) of SMs exhibit attenuated interferon-alpha (IFN-α) responses to TLR7/9 ligands <i>in vitro</i>, and that species-specific amino acid substitutions in SM Interferon Regulatory Factor-7 (IRF7) are responsible for this observation. Based on these findings, these authors proposed that “muted” IFN-α responses are responsible for the benign nature of SIV infection in SMs. However, other studies indicated that acutely SIV-infected SMs show robust IFN-α responses and marked upregulation of Interferon Stimulated Genes (ISGs). To investigate this apparent disparity, we first examined the role of the reported IRF7 amino acid substitutions in SMs. To this end, we sequenced all IRF7 exons in 16 breeders, and exons displaying variability (exons 2,3,5,6,7,8) in the remainder of the colony (177 animals). We found that the reported Ser-Gly substitution at position 191 was a sequencing error, and that several of the remaining substitutions represent only minor alleles. In addition, functional assays using recombinant SM IRF7 showed no defect in its ability to translocate in the nucleus and drive transcription from an IFN-α promoter. Furthermore, <i>in vitro</i> stimulation of SM peripheral blood mononuclear cells with either the TLR7 agonist CL097 or SIV_mac239 induced an 500–800-fold induction of IFN-α and IFN-β mRNA, and levels of IFN-α production by pDCs similar to those of RMs or humans. These data establish that IFN-α and IRF7 signaling in SMs are largely intact, with differences with RMs that are minor and unlikely to play any role in the AIDS resistance of SIV-infected SMs.</p></div

Clustered ranking plot of the stroke prophylaxis network.

This plot is based on cluster analysis of SUCRA values for efficacy and safety. Each color represents a group of treatments that belong to the same cluster. Treatments lying in the upper right corner are more effective and safe than the other treatments. VKA = Dose-adjusted vitamin K antagonists.</p

Additional file 7: of BALDR: a computational pipeline for paired heavy and light chain immunoglobulin reconstruction in single-cell RNA-seq data

Sequences from nested RT-PCR. The Ig chains obtained from Sanger sequencing of nested RT-PCR. (XLSX 62 kb