Background
Wound complications following resection of a localized soft tissue sarcoma have been associated with lower extremity location, large tumor volume, and use of preoperative radiation. Some ...of these wounds, however, show the potential for healing with local wound care and nonsurgical techniques. We are unaware of any published data establishing factors associated with nonhealing wounds that ultimately are treated with local or free vascularized tissue transfer.
Questions/purposes
The purpose of this study was to determine the variables associated with development of a significant wound complication defined as one that underwent a secondary procedure using local or free tissue transfer after resection of a localized soft tissue sarcoma.
Methods
Using our institution’s cancer center database, we identified 140 patients who underwent resection of a localized extremity soft tissue sarcoma at our institution between 1997 and 2010. Thirty-two patients were excluded who underwent immediate planned vascularized tissue transfer, along with 26 patients who did not receive radiation, and an additional three patients were excluded who were followed for less than 1 month. This left 79 patients, including 18 treated with postoperative external beam radiotherapy and 61 with preoperative external beam radiotherapy. Of patients receiving radiation treatment before surgery, 13 received no additional radiation treatment, 33 underwent intraoperative radiation with electrons (IOERT) to sites considered at high risk for local recurrence, and an additional 15 had perioperative brachytherapy. Univariate and multiple regression analyses were performed using frequency of local or free tissue transfer at 3 weeks or greater postoperatively owing to wound-related complications as a dependent variable.
Results
Lower extremity location and vascular involvement were associated with use of delayed vascularized tissue coverage for wound-healing problems. Patients in this series who underwent preoperative external beam radiotherapy coupled with dose-escalated IOERT or chemotherapy had a similar rate of flap use compared with patients treated with postoperative radiation.
Conclusions
Patients with tumors of the lower extremity involving major neurovascular structures and for whom radiation therapy is planned should be counseled specifically because they appear to be at increased risk for use of delayed local or free vascularized tissue transfer for a nonhealing wound following resection of a localized extremity soft tissue sarcoma.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Human cytomegalovirus (HCMV) enters host by glycoprotein B (gB)-mediated membrane fusion upon receptor-binding to gH/gL-related complexes, causing devastating diseases such as birth defects. Although ...an X-ray crystal structure of the recombinant gB ectodomain at postfusion conformation is available, the structures of prefusion gB and its complex with gH/gL on the viral envelope remain elusive. Here, we demonstrate the utility of cryo electron tomography (cryoET) with energy filtering and the cutting-edge technologies of Volta phase plate (VPP) and direct electron-counting detection to capture metastable prefusion viral fusion proteins and report the structures of glycoproteins in the native environment of HCMV virions. We established the validity of our approach by obtaining cryoET in situ structures of the vesicular stomatitis virus (VSV) glycoprotein G trimer (171 kD) in prefusion and postfusion conformations, which agree with the known crystal structures of purified G trimers in both conformations. The excellent contrast afforded by these technologies has enabled us to identify gB trimers (303kD) in two distinct conformations in HCMV tomograms and obtain their in situ structures at up to 21 Å resolution through subtomographic averaging. The predominant conformation (79%), which we designate as gB prefusion conformation, fashions a globular endodomain and a Christmas tree-shaped ectodomain, while the minority conformation (21%) has a columnar tree-shaped ectodomain that matches the crystal structure of the "postfusion" gB ectodomain. We also observed prefusion gB in complex with an "L"-shaped density attributed to the gH/gL complex. Integration of these structures of HCMV glycoproteins in multiple functional states and oligomeric forms with existing biochemical data and domain organization of other class III viral fusion proteins suggests that gH/gL receptor-binding triggers conformational changes of gB endodomain, which in turn triggers two essential steps to actuate virus-cell membrane fusion: exposure of gB fusion loops and unfurling of gB ectodomain.
The Myriapoda, composed of millipedes and centipedes, is a fascinating but poorly understood branch of life, including species with a highly unusual body plan and a range of unique adaptations to ...their environment. Here, we sequenced and assembled 2 chromosomal-level genomes of the millipedes Helicorthomorpha holstii (assembly size = 182 Mb; shortest scaffold/contig length needed to cover 50% of the genome N50 = 18.11 Mb mainly on 8 pseudomolecules) and Trigoniulus corallinus (assembly size = 449 Mb, N50 = 26.78 Mb mainly on 17 pseudomolecules). Unique genomic features, patterns of gene regulation, and defence systems in millipedes, not observed in other arthropods, are revealed. Both repeat content and intron size are major contributors to the observed differences in millipede genome size. Tight Hox and the first loose ecdysozoan ParaHox homeobox clusters are identified, and a myriapod-specific genomic rearrangement including Hox3 is also observed. The Argonaute (AGO) proteins for loading small RNAs are duplicated in both millipedes, but unlike in insects, an AGO duplicate has become a pseudogene. Evidence of post-transcriptional modification in small RNAs—including species-specific microRNA arm switching—providing differential gene regulation is also obtained. Millipedes possesses a unique ozadene defensive gland unlike the venomous forcipules found in centipedes. We identify sets of genes associated with the ozadene that play roles in chemical defence as well as antimicrobial activity. Macro-synteny analyses revealed highly conserved genomic blocks between the 2 millipedes and deuterostomes. Collectively, our analyses of millipede genomes reveal that a series of unique adaptations have occurred in this major lineage of arthropod diversity. The 2 high-quality millipede genomes provided here shed new light on the conserved and lineage-specific features of millipedes and centipedes. These findings demonstrate the importance of the consideration of both centipede and millipede genomes—and in particular the reconstruction of the myriapod ancestral situation—for future research to improve understanding of arthropod evolution, and animal evolutionary genomics more widely.
Salphen the puzzle: Zn(salphen) complexes such as that shown organize into nanofibrils in the solid state. This assembly involves an intermolecular Zn⋅⋅⋅O interaction that stabilizes a polymeric ...structure with a (ZnO)n backbone. By tuning the peripheral substituents, luminescent gels may be prepared and the diameters of the fibers can be controlled.
We present results from an analysis of all data taken by the BICEP2 and Keck Array cosmic microwave background (CMB) polarization experiments up to and including the 2014 observing season. This ...includes the first Keck Array observations at 95 GHz. The maps reach a depth of 50 nK deg in Stokes Q and U in the 150 GHz band and 127 nK deg in the 95 GHz band. We take auto- and cross-spectra between these maps and publicly available maps from WMAP and Planck at frequencies from 23 to 353 GHz. An excess over lensed ΛCDM is detected at modest significance in the 95×150 BB spectrum, and is consistent with the dust contribution expected from our previous work. No significant evidence for synchrotron emission is found in spectra such as 23×95, or for correlation between the dust and synchrotron sky patterns in spectra such as 23×353. We take the likelihood of all the spectra for a multicomponent model including lensed ΛCDM, dust, synchrotron, and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r) using priors on the frequency spectral behaviors of dust and synchrotron emission from previous analyses of WMAP and Planck data in other regions of the sky. This analysis yields an upper limit r_{0.05}<0.09 at 95% confidence, which is robust to variations explored in analysis and priors. Combining these B-mode results with the (more model-dependent) constraints from Planck analysis of CMB temperature plus baryon acoustic oscillations and other data yields a combined limit r_{0.05}<0.07 at 95% confidence. These are the strongest constraints to date on inflationary gravitational waves.
Whole-genome duplication (WGD) results in new genomic resources that can be exploited by evolution for rewiring genetic regulatory networks in organisms. In metazoans, WGD occurred before the last ...common ancestor of vertebrates, and has been postulated as a major evolutionary force that contributed to their speciation and diversification of morphological structures. Here, we have sequenced genomes from three of the four extant species of horseshoe crabs-Carcinoscorpius rotundicauda, Limulus polyphemus and Tachypleus tridentatus. Phylogenetic and sequence analyses of their Hox and other homeobox genes, which encode crucial transcription factors and have been used as indicators of WGD in animals, strongly suggests that WGD happened before the last common ancestor of these marine chelicerates >135 million years ago. Signatures of subfunctionalisation of paralogues of Hox genes are revealed in the appendages of two species of horseshoe crabs. Further, residual homeobox pseudogenes are observed in the three lineages. The existence of WGD in the horseshoe crabs, noted for relative morphological stasis over geological time, suggests that genomic diversity need not always be reflected phenotypically, in contrast to the suggested situation in vertebrates. This study provides evidence of ancient WGD in the ecdysozoan lineage, and reveals new opportunities for studying genomic and regulatory evolution after WGD in the Metazoa.
Small RNAs in Cnidaria: A review Li, Yiqian; Hui, Jerome H. L.
Evolutionary applications,
February 2023, Letnik:
16, Številka:
2
Journal Article
Recenzirano
Odprti dostop
As fundamental components of RNA silencing, small RNA (sRNA) molecules ranging from 20 to 32 nucleotides in length have been found as potent regulators of gene expression and genome stability in many ...biological processes of eukaryotes. Three major small RNAs are active in animals, including the microRNA (miRNA), short interfering RNA (siRNA), and PIWI‐interacting RNA (piRNA). Cnidarians, the sister group to bilaterians, are at a critical phylogenetic node to better model eukaryotic small RNA pathway evolution. To date, most of our understanding of sRNA regulation and its potential contribution to evolution has been limited to a few triploblastic bilaterian and plant models. The diploblastic nonbilaterians, including the cnidarians, are understudied in this regard. Therefore, this review will present the current‐known small RNA information in cnidarians to enhance our understanding of the development of the small RNA pathways in early branch animals.
MicroRNA evolution by arm switching Griffiths-Jones, Sam; Hui, Jerome H L; Marco, Antonio ...
EMBO reports,
February 2011, Letnik:
12, Številka:
2
Journal Article
Recenzirano
Odprti dostop
MicroRNAs (miRNAs) modulate transcript stability and translation. Functional mature miRNAs are processed from one or both arms of the hairpin precursor. The miR‐100/10 family has undergone three ...independent evolutionary events that have switched the arm from which the functional miRNA is processed. The dominant miR‐10 sequences in the insects Drosophila melanogaster and Tribolium castaneum are processed from opposite arms. However, the duplex produced by Dicer cleavage has an identical sequence in fly and beetle. Expression of the Tribolium miR‐10 sequence in Drosophila S2 cells recapitulates the native beetle pattern. Thus, arm usage is encoded in the primary miRNA sequence, but outside the mature miRNA duplex. We show that the predicted messenger RNA targets and inferred function of sequences from opposite arms differ significantly. Arm switching is likely to be general, and provides a fundamental mechanism to evolve the function of a miRNA locus and target gene network.
In the miR‐100/10 miRNA family, the arm of the hairpin precursor from which the dominant functional miRNA is processed has switched at least three times during evolution. Arm choice is encoded in the sequence of the primary transcript, and has profound effects on the function of orthologous miRNAs.
The tumor immune microenvironment impacts the biological behavior of the tumor, but its effect on clinical outcomes in head and neck cutaneous squamous cell carcinomas (HNcSCC) is largely unknown.
We ...compared the immune milieu of high-risk HNcSCC that never progressed to metastasis with those that metastasized using multiparameter imaging mass cytometry. The cohort included both immunosuppressed patients (IS) and patients with an absence of clinical immune-suppression (ACIS). Spatial analyses were used to identify cellular interactions that were associated with tumor behavior.
Nonprogressing primary HNcSCC were characterized by higher CD8+ and CD4+ T-cell responses, including numerically increased regulatory T cells. In contrast, primary lesions from HNcSCC patients who progressed were largely devoid of T cells with lower numbers of innate immune cells and increased expression of checkpoint receptors and in the metastatic lesions were characterized by an accumulation of B cells. Spatial analysis reveals multiple cellular interactions associated with nonprogressing primary tumors that were distinct in primary tumors of disease-progressing patients. Cellular regional analysis of the tumor microenvironment also shows squamous cell-enriched tumor regions associated with primary nonprogressing tumors.
Effective responses from both CD8+ and CD4+ T cells in the tumor microenvironment are essential for immune control of primary HNcSCC. Our findings indicate that the early events that shape the immune responses in primary tumors dictate progression and disease outcomes in HNcSCC.
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•A novel rotating UVC-LED device was invented to improve air quality.•Efficacy of static irradiation was 53–79 % lower in poorly- than well-mixed rooms.•Using moving irradiation in a ...poorly-mixed room could enhance efficacy by 22–50 %.•A more compact and safe disinfection system is possible with UVC-LED.
The potential of inactivating indoor bacteria aerosols using a novel rotating ultraviolet-C (UV-C) light-emitting-diode (LED) system was investigated. The system was installed in the upper level of a full scale chamber and its effectiveness against aerosolized E. coli, S. marcescens, and S. epidermidis under the well-mixed with stationary UV-LED scenario was initially tested. The estimated susceptibility values were 1.068, 1.148, and 0.156 m2/J for E. coli, S. marcescens, and S. epidermidis, respectively. Three additional scenarios of experiments were conducted, in which E. coli was aerosolized into the test chamber and then allowed to decay under (i) poorly-mixed condition with stationary system, (ii) well-mixed with rotating system, and (iii) poorly-mixed conditions with rotating system. Our results showed no significant difference between the performance of stationary and rotating UR-UVGI-LED systems under a well-mixed condition. While the performance of the stationary UR-UVGI-LED system under a poorly-mixed condition decreased by 52.90–79.38 % compared to a well-mixed condition, rotating the UR-UVGI-LED system under a poorly-mixed condition, compared to the stationary system, enhanced its performance by 22.36–49.86 %. Thus, our proposed rotating irradiation offers great potential for application in environments where bioaerosols are unevenly distributed in a built environment.
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