Spatiotemporal heterogeneity and patterning of developing renal blood vessels

Abstract

The kidney vasculature facilitates the excretion of wastes, the dissemination of hormones, and the regulation of blood chemistry. To carry out these diverse functions, the vasculature is regionalized within the kidney and along the nephron. However, when and how endothelial regionalization occurs remains unknown. Here, we examine the developing kidney vasculature to assess its 3-dimensional structure and transcriptional heterogeneity. First, we observe that endothelial cells (ECs) grow coordinately with the kidney bud as early as E10.5, and begin to show signs of specification by E13.5 when the first arteries can be identified. We then focus on how ECs pattern and remodel with respect to the developing nephron and collecting duct epithelia. ECs circumscribe nephron progenitor populations at the distal tips of the ureteric bud (UB) tree and form stereotyped cruciform structures around each tip. Beginning at the renal vesicle (RV) stage, ECs form a continuous plexus around developing nephrons. The endothelial plexus envelops and elaborates with the maturing nephron, becoming preferentially enriched along the early distal tubule. Lastly, we perform transcriptional and immunofluorescent screens to characterize spatiotemporal heterogeneity in the kidney vasculature and identify novel regionally enriched genes. A better understanding of development of the kidney vasculature will help instruct engineering of properly vascularized ex vivo kidneys and evaluate diseased kidneys.

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Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects

Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects

Cancers doi: 10.3390/cancers10040111

Authors: Valentina Ovalle Eric A. Strom Simona Shaitelman Karen Hoffman Richard Amos George Perkins Welela Tereffe Benjamin D. Smith Michael Stauder Wendy Woodward

Introduction: Accelerated partial breast irradiation (APBI) with protons results in a very different acute effect profile than standard whole breast irradiation. We reviewed our initial experience with proton APBI and felt that a detailed description of these effects were needed to permit a common tool to compare experience with this developing technology. Methods: Sixty sequential patients treated with proton APBI on a prospective protocol were evaluated and 43 patients with a minimum six-month follow-up underwent detailed photographic and radiologic analysis. The tumorectomy cavity plus an additional 1.5 cm clinical target volume (CTV) was treated with two or three passively-scattered proton beams to a dose of 34 Gy in 10 fractions in one week. Photographs were taken at the end of radiation, at two weeks, six weeks, and every six months thereafter. Mammography was obtained at six months after radiation and annually thereafter. All visual changes were categorized using the smallest meaningful gradations in findings and are demonstrated herein. All treatment-related mammographic findings are reported. Findings: Visual and mammographic findings showed a clear time-dependent relationship and significant variation between individuals. Peak skin reaction occurred at two to six weeks after completion of therapy. At two weeks most patients had either no visible effects and patchy erythema involving <50% of the treated skin (60%). At six weeks most patients had either patchy erythema involving <50% of the overlying skin (33%) or patchy erythema involving >50% of the treated skin (28%). Only one patient developed any moist desquamation. At six months most patients had no visible skin changes (57%) or a small, circular area of mild hyperpigmentation (33%). Mammographic changes seen at six months were regional skin thickening (40%), residual seroma (14%), localized retraction (26%), and fat necrosis (2%). A subcategorized variant on the CTCAE 4.0 was developed to foster granular recording of these findings.

https://ift.tt/2JrMFfV

Sarcomatoid Adenocarcinoma of the Ampulla of Vater

Abstract

Sarcomatoid adenocarcinoma of ampulla of Vater is an extremely rare malignant neoplasm that displays both carcinomatous and sarcomatous component. A 58-year-old woman was admitted to our hospital under the suspicion of an ampulla of Vater cancer. Abdominal computed tomography and endoscopy demonstrated a bulging of ampulla and the biopsy specimen revealed an adenocarcinoma, well differentiated in the background of tubulovillous adenoma. So we performed the pylorus preserving pancreaticoduodenectomy. At postoperative biopsy, the tumor was composed of adenocarcinoma component and sarcomatoid component. Thus, a diagnosis of sarcomatoid adenocarcinoma of ampulla of Vater could be made. Here, we present a case of sarcomatoid adenocarcinoma of ampulla of Vater.

https://ift.tt/2GGxguB

GntR is involved in the expression of virulence in strain Streptococcus suis P1/7

Abstract

Streptococcus suis is a severe zoonotic pathogen, responsible for acute diseases in pigs and human. GntR proteins widely distribute in various bacteria species. In previous study, GntR proteins were reported to be involved in virulence in many pathogens. To investigate the relationship between GntR and S. suis serotype 2, we constructed an isogenic deletion mutant P1/7ΔgntR and an isogenic single-nucleotide substitution mutant P1/7gntR^(SC070731), which took strain P1/7 as parent. The results show that the mutants P1/7ΔgntR and P1/7gntR^(SC070731) have a stronger ability to tolerate the oxidative stress and reproduce in blood. Moreover, higher fatality rate observed in mice when challenged with P1/7ΔgntR or P1/7gntR^(SC070731) compared with that of P1/7. Overall, all results suggest that GntR greatly impacts the virulence of S. suis serotype 2 strain P1/7 and give a new perspective of virulence generation in S. suis.

https://ift.tt/2qbPERp

Neisseria meningitidis disease-associated clones in Amazonas State, Brazil

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https://ift.tt/2uTyE7j

Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers doi: 10.3390/cancers10040110

Authors: Adrián Montaño Maribel Forero-Castro Darnel Marchena-Mendoza Rocío Benito Jesús María Hernández-Rivas

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease.

https://ift.tt/2Iz2Wyd

Retinal detachment in albinism

https://ift.tt/2H4jTDK