Molecular Phylogenetics of Bromus (Poaceae: Pooideae) Based on Chloroplast and Nuclear DNA Sequence Data

We conducted a phylogenetic analysis to characterize relationships among Bromus and test the monophyly of five of the seven morphologically distinct groups within Bromus (Poaceae: Pooideae) that have been treated as sections, subgenera, or genera. We sequenced the chloroplast trnL (UAA) intron, the 3\u27-end of the chloroplast ndhF gene, and the internal transcribed spacers (ITS) of the nuclear ribosomal DNA region for 46 species that represent a large proportion of the morphological and geographical diversity in the genus. Independent analyses of plastid and nuclear ribosomal data identified several lineages in Bromus, but there is some evidence of incongruence between these linkage groups. Nuclear ribosomal trees indicate that two clades comprising some North and South American species of sect. Bromopsis are the successive sister groups of the rest of the genus, and that Old World species of sect. Bromopsis are more closely related to sects. Ceratochloa and Neobromus than they are to the remaining North American species of sect. Bromopsis. In contrast, plastid trees indicate a close relationship between Old World and some North American species of sect. Bromopsis. In the nuclear ribosomal trees, sects. Genea and Bromus (if sect. Triniusia is included within it, as treated by most authors) are monophyletic and not closely related. In the plastid trees, species of these two sections are intermixed, supporting a hybrid origin for B. pectinatus. The monophyly of sect. Ceratochloa is supported in the plastid and nuclear ribosomal trees, and the monophyly of sect. Neobromus is robustly supported in the nuclear ribosomal trees. Current classification schemes do not reflect phylogenetic relationships in Bromus. Tentative evidence of conflict among nuclear and plastid data partitions needs clarification with more robustly supported plastid and nuclear ribosomal gene trees

Cutaneous microvascular reactivity in Charcot neuroarthropathy : a systematic review and meta-analysis

Background: To systematically evaluate the literature investigating the relationship between cutaneous microvascular reactivity in the foot of adults with diabetes-related Charcot neuroarthropathy compared to a non-Charcot adult control group. Methods: A systematic search was conducted to June 2021 using the biomedical databases EBSCO Megafile Ultimate, Cochrane Library and EMBASE. Original research conducting comparative investigation of cutaneous microvascular reactivity in the foot of adults with diabetes and any pattern of acute or chronic Charcot neuroarthropathy and any non-Charcot adult control groups were included. A modified Critical Appraisal Skills Programme tool was used for quality appraisal. Cutaneous microvascular reactivity in diabetes-related Charcot neuroarthropathy data were synthesised and meta-analysis conducted where possible. Results: The search strategy identified 1,684 articles, with seven eligible for inclusion. Included studies used various methodologies and equipment to assess cutaneous microvascular reactivity in 553 participants (162 with Charcot neuroarthropathy). Cutaneous microvascular reactivity in Charcot neuroarthropathy groups was impaired compared to uncomplicated diabetes groups. Meta-analysis investigating the difference in response to thermal hyperaemia demonstrated a significant difference in cutaneous microvascular reactivity between Charcot neuroarthropathy and peripheral neuropathy with a large, pooled effect size (SMD 1.46 95% CI: 0.89– 2.02) and low heterogeneity (I 2 = 4%, T 2 = 0.01) indicating that the cutaneous microvascular response is more impaired in peripheral neuropathy than in Charcot neuroarthropathy. Conclusions: Charcot neuroarthropathy is associated with greater cutaneous microvascular reactivity in the periphery relative to diabetes cohorts with diabetes-related peripheral neuropathy alone. It is unknown if this occurs prior to, or as a result of, Charcot neuroarthropathy

Exome-wide association study of pancreatic cancer risk

We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10(-6); exome-wide statistical significance threshold P<2.5x10(-6)). Cases had more rare inactivating variants in DNA repair genes than controls, even after excluding 13 genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35, P=.045). At the suggestive threshold (P<.001), 6 genes were enriched for rare damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had associations with pancreatic cancer risk, based on the sequence-kernel association test. We confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic cancer and we also identified candidate pancreatic cancer genes. Large collaborations and novel approaches are needed to overcome the genetic heterogeneity of pancreatic cancer predisposition

The complex relationship between pediatric cardiac surgical case volumes and mortality rates in a national clinical database

ObjectiveWe sought to determine the association between pediatric cardiac surgical volume and mortality using sophisticated case-mix adjustment and a national clinical database.MethodsPatients 18 years of age or less who had a cardiac operation between 2002 and 2006 were identified in the Society of Thoracic Surgeons Congenital Heart Surgery Database (32,413 patients from 48 programs). Programs were grouped by yearly pediatric cardiac surgical volume (small, <150; medium, 150–249; large, 250–349; and very large, ≥350 cases per year). Logistic regression was used to adjust mortality rates for volume, surgical case mix (Aristotle Basic Complexity and Risk Adjustment for Congenital Heart Surgery, Version 1 categories), patient risk factors, and year of operation.ResultsWith adjustment for patient-level risk factors and surgical case mix, there was an inverse relationship between overall surgical volume as a continuous variable and mortality (P = .002). When the data were displayed graphically, there appeared to be an inflection point between 200 and 300 cases per year. When volume was analyzed as a categorical variable, the relationship was most apparent for difficult operations (Aristotle technical difficulty component score, >3.0), for which mortality decreased from 14.8% (60/406) at small programs to 8.4% (157/1858) at very large programs (P = .02). The same was true for the subgroup of patients who underwent Norwood procedures (36.5% [23/63] vs 16.9% [81/479], P < .0001). After risk adjustment, all groups performed similarly for low-difficulty operations. Conversely, for difficult procedures, small programs performed significantly worse. For Norwood procedures, very large programs outperformed all other groups.ConclusionThere was an inverse association between pediatric cardiac surgical volume and mortality that became increasingly important as case complexity increased. Although volume was not associated with mortality for low-complexity cases, lower-volume programs underperformed larger programs as case complexity increased

Physical Conditions of Accreting Gas in T Tauri Star Systems

We present results from a low resolution (R~300) near-infrared spectroscopic variability survey of actively accreting T Tauri stars (TTS) in the Taurus-Auriga star forming region. Paschen and Brackett series H I recombination lines were detected in 73 spectra of 15 classical T Tauri systems. The values of the Pan/PaB, Brn/BrG, and BrG/Pan H I line ratios for all observations exhibit a scatter of < 20% about the weighted mean, not only from source to source, but also for epoch-to-epoch variations in the same source. A representative or `global' value was determined for each ratio in both the Paschen and Brackett series as well as the BrG/Pan line ratios. A comparison of observed line ratio values was made to those predicted by the temperature and electron density dependent models of Case B hydrogen recombination line theory. The measured line ratios are statistically well-fit by a tightly constrained range of temperatures (T < 2000 K) and electron densities 1e9 < n_e < 1e10 cm^-3. A comparison of the observed line ratio values to the values predicted by the optically thick and thin local thermodynamic equilibrium cases rules out these conditions for the emitting H I gas. Therefore, the emission is consistent with having an origin in a non-LTE recombining gas. While the range of electron densities is consistent with the gas densities predicted by existing magnetospheric accretion models, the temperature range constrained by the Case B comparison is considerably lower than that expected for accreting gas. The cooler gas temperatures will require a non-thermal excitation process (e.g., coronal/accretion-related X-rays and UV photons) to power the observed line emission.Comment: 12 pages, emulateapj format, Accepted for publication in Ap

Using open records laws for research purposes

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Direct measurement and modeling of intraglottal, subglottal, and vocal fold collision pressures during phonation in an individual with a hemilaryngectomy

The purpose of this paper is to report on the first in vivo application of a recently developed transoral, dual-sensor pressure probe that directly measures intraglottal, subglottal, and vocal fold collision pressures during phonation. Synchronous measurement of intraglottal and subglottal pressures was accomplished using two miniature pressure sensors mounted on the end of the probe and inserted transorally in a 78-year-old male who had previously undergone surgical removal of his right vocal fold for treatment of laryngeal cancer. The endoscopist used one hand to position the custom probe against the surgically medialized scar band that replaced the right vocal fold and used the other hand to position a transoral endoscope to record laryngeal high-speed videoendoscopy of the vibrating left vocal fold contacting the pressure probe. Visualization of the larynx during sustained phonation allowed the endoscopist to place the dual-sensor pressure probe such that the proximal sensor was positioned intraglottally and the distal sensor subglottally. The proximal pressure sensor was verified to be in the strike zone of vocal fold collision during phonation when the intraglottal pressure signal exhibited three characteristics: an impulsive peak at the start of the closed phase, a rounded peak during the open phase, and a minimum value around zero immediately preceding the impulsive peak of the subsequent phonatory cycle. Numerical voice production modeling was applied to validate model-based predictions of vocal fold collision pressure using kinematic vocal fold measures. The results successfully demonstrated feasibility of in vivo measurement of vocal fold collision pressure in an individual with a hemilaryngectomy, motivating ongoing data collection that is designed to aid in the development of vocal dose measures that incorporate vocal fold impact collision and stresses.Fil: Mehta, Daryush D.. Massachusetts General Hospital; Estados UnidosFil: Kobler, James B.. Massachusetts General Hospital; Estados UnidosFil: Zeitels, Steven M.. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados UnidosFil: Zañartu, Matías. Universidad Técnica Federico Santa María; ChileFil: Ibarra, Emiro J.. Universidad Técnica Federico Santa María; ChileFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Manriquez, Rodrigo. Universidad Técnica Federico Santa María; ChileFil: Erath, Byron D.. Clarkson University; Estados UnidosFil: Peterson, Sean D.. University of Waterloo; CanadáFil: Petrillo, Robert H.. Center For Laryngeal Surgery and Voice Rehabilitation; Estados UnidosFil: Hillman, Robert E.. Center For Laryngeal Surgery and Voice Rehabilitation; Estados Unidos. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados Unido

Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies

Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated ‘regulatory hotspots’ around genes closely associated with progenitor programs. To examine their functional significance, we deleted ‘hotspot’ enhancer elements for Six2 and Wnt4. Removal of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression. When combined with a Six2 null allele, progeny display a premature depletion of nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype also enhanced in combination with a Wnt4 null mutation. To explore the regulatory landscape that supports proper target gene expression, we performed CTCF ChIP-seq to identify insulator-boundary regions. One such putative boundary lies between the Six2 and Six3 loci. Evidence for the functional significance of this boundary was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound boundary, removing Six2 from its distal enhancer regulation, but placed next to Six3 enhancer elements which support ectopic Six2 expression in the lens where Six3 is normally expressed. Six3 is now predicted to fall under control of the Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in nephron progenitors. 4C-seq supports the model for Six2 distal enhancer interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our view of the regulatory genome and regulatory landscape underpinning mammalian nephrogenesis

Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies.

Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated \u27regulatory hotspots\u27 around genes closely associated with progenitor programs. To examine their functional significance, we deleted \u27hotspot\u27 enhancer elements for Six2 and Wnt4. Removal of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression. When combined with a Six2 null allele, progeny display a premature depletion of nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype also enhanced in combination with a Wnt4 null mutation. To explore the regulatory landscape that supports proper target gene expression, we performed CTCF ChIP-seq to identify insulator-boundary regions. One such putative boundary lies between the Six2 and Six3 loci. Evidence for the functional significance of this boundary was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound boundary, removing Six2 from its distal enhancer regulation, but placed next to Six3 enhancer elements which support ectopic Six2 expression in the lens where Six3 is normally expressed. Six3 is now predicted to fall under control of the Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in nephron progenitors. 4C-seq supports the model for Six2 distal enhancer interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our view of the regulatory genome and regulatory landscape underpinning mammalian nephrogenesis