Digitization workflows for flat sheets and packets of plants, algae, and fungi

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141708/1/aps31500065.pd

Development of a Tumor-Selective Approach to Treat Metastatic Cancer

BACKGROUND: Patients diagnosed with metastatic cancer have almost uniformly poor prognoses. The treatments available for patients with disseminated disease are usually not curative and have side effects that limit the therapy that can be given. A treatment that is selectively toxic to tumors would maximize the beneficial effects of therapy and minimize side effects, potentially enabling effective treatment to be administered. METHODS AND FINDINGS: We postulated that the tumor-tropic property of stem cells or progenitor cells could be exploited to selectively deliver a therapeutic gene to metastatic solid tumors, and that expression of an appropriate transgene at tumor loci might mediate cures of metastatic disease. To test this hypothesis, we injected HB1.F3.C1 cells transduced to express an enzyme that efficiently activates the anti-cancer prodrug CPT-11 intravenously into mice bearing disseminated neuroblastoma tumors. The HB1.F3.C1 cells migrated selectively to tumor sites regardless of the size or anatomical location of the tumors. Mice were then treated systemically with CPT-11, and the efficacy of treatment was monitored. Mice treated with the combination of HB1.F3.C1 cells expressing the CPT-11-activating enzyme and this prodrug produced tumor-free survival of 100% of the mice for >6 months (P<0.001 compared to control groups). CONCLUSIONS: The novel and significant finding of this study is that it may be possible to exploit the tumor-tropic property of stem or progenitor cells to mediate effective, tumor-selective therapy for metastatic tumors, for which no tolerated curative treatments are currently available

Digitization Workflows for Flat Sheets and Packets of Plants, Algae, and Fungi

Effective workflows are essential components in the digitization of biodiversity specimen collections. To date, no comprehensive, community-vetted workflows have been published for digitizing flat sheets and packets of plants, algae, and fungi, even though latest estimates suggest that only 33% of herbarium specimens have been digitally transcribed, 54% of herbaria use a specimen database, and 24% are imaging specimens. In 2012, iDigBio, the U.S. National Science Foundation’s (NSF) coordinating center and national resource for the digitization of public, nonfederal U.S. collections, launched several working groups to address this deficiency. Here, we report the development of 14 workflow modules with 7–36 tasks each. These workflows represent the combined work of approximately 35 curators, directors, and collections managers representing more than 30 herbaria, including 15 NSF-supported plant-related Thematic Collections Networks and collaboratives. The workflows are provided for download as Portable Document Format (PDF) and Microsoft Word files. Customization of these workflows for specific institutional implementation is encouraged

Saddle-Shaped Annuloplasty Improves Leaflet Coaptation in Repair for Ischemic Mitral Regurgitation

Background. Current repair results for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings are characterized by high IMR recurrence rates. Current annuloplasty rings treat annular dilatation, but they do little to improve (and may actually exacerbate) leaflet tethering. New saddle-shaped annuloplasty rings have been shown to maintain or restore a more physiologic annular and leaflet geometry and function. Using a porcine IMR model, we sought to demonstrate the influence of annuloplasty ring shape on leaflet coaptation. Methods. Eight weeks after posterolateral infarct, eight pigs with grade 2D or higher IMR were randomized to undergo either a 28-mm flat ring annuloplasty (n=4) or a 28-mm saddle-shaped ring annuloplasty (n=4). Realtime three-dimensional echocardiography and a customized image analysis protocol allowed three-dimensional assessment of leaflet coaptation before and after annuloplasty. Results. Total leaflet coaptation area was significantly higher after saddle-shaped ring annuloplasty (109.6 +/- 26.9 mm(2)) compared with flat ring annuloplasty (46.2 +/- 7.7 mm(2), p <0.01). After annuloplasty, total coaptation area decreased by 87.5 mm(2) (or 65%) in the flat annuloplasty group (p = 0.01), whereas total coaptation area increased by 22.2 mm(2) (or 25%) in the saddle-shaped annuloplasty group (p = 0.28). Conclusions. This study shows that the use of undersized saddle-shaped annuloplasty rings in mitral valve repair for IMR improves leaflet coaptation, whereas the use of undersized flat annuloplasty rings worsens leaflet coaptation. Because one of Carpentier's fundamental principles of mitral valve repair (durability) is to create a large surface of coaptation, saddle-shaped annuloplasty may increase repair durability. (C) 2015 by The Society of Thoracic Surgeon

Saddle-Shaped Annuloplasty Improves Leaflet Coaptation in Repair for Ischemic Mitral Regurgitation.

BACKGROUND: Current repair results for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings are characterized by high IMR recurrence rates. Current annuloplasty rings treat annular dilatation, but they do little to improve (and may actually exacerbate) leaflet tethering. New saddle-shaped annuloplasty rings have been shown to maintain or restore a more physiologic annular and leaflet geometry and function. Using a porcine IMR model, we sought to demonstrate the influence of annuloplasty ring shape on leaflet coaptation. METHODS: Eight weeks after posterolateral infarct, eight pigs with grade 2+ or higher IMR were randomized to undergo either a 28-mm flat ring annuloplasty (n = 4) or a 28-mm saddle-shaped ring annuloplasty (n = 4). Real-time three-dimensional echocardiography and a customized image analysis protocol allowed three-dimensional assessment of leaflet coaptation before and after annuloplasty. RESULTS: Total leaflet coaptation area was significantly higher after saddle-shaped ring annuloplasty (109.6 ± 26.9 mm(2)) compared with flat ring annuloplasty (46.2 ± 7.7 mm(2), p CONCLUSIONS: This study shows that the use of undersized saddle-shaped annuloplasty rings in mitral valve repair for IMR improves leaflet coaptation, whereas the use of undersized flat annuloplasty rings worsens leaflet coaptation. Because one of Carpentier\u27s fundamental principles of mitral valve repair (durability) is to create a large surface of coaptation, saddle-shaped annuloplasty may increase repair durability

Germline deletion of AMP-activated protein kinase β subunits reduces bone mass without altering osteoclast differentiation or function

Since AMP-activated protein kinase (AMPK) plays important roles in modulating metabolism in response to diet and exercise, both of which influence bone mass, we examined the influence of AMPK on bone mass in mice. AMPK is an αβγ heterotrimer where the β subunit anchors the α catalytic and γ regulatory subunits. Germline deletion of either AMPK β1 or β2 subunit isoforms resulted in reduced trabecular bone density and mass, but without effects on osteoclast (OC) or osteoblast (OB) numbers, as compared to wild-type littermate controls. We tested whether activating AMPK in vivo would enhance bone density but found AICA-riboside treatment caused a profound loss of trabecular bone volume (49.5%) and density and associated increased OC numbers. Consistent with this, AICA-riboside strongly stimulated OC differentiation in vitro, in an adenosine kinase-dependent manner. OCs and macrophages (unlike OBs) lacked AMPK β2 subunit expression, and when generated from AMPK β1−/− mice displayed no detectable AMPK activity. Nevertheless, AICA-riboside was equally effective at stimulating OC differentiation from wild-type or β1−/− progenitors, indicating that AMPK is not essential for OC differentiation or the stimulatory action of AICA-riboside. These results show that AMPK is required to maintain normal bone density, but not through bone cell differentiation, and does not mediate powerful osteolytic effects of AICA-riboside.—Quinn, J. M. W., Tam, S., Sims, N. A., Saleh, H., McGregor, N. E., Poulton, I. J., Scott, J. W., Gillespie, M. T., Kemp, B. E., van Denderen, B. J. W. Germline deletion of AMP-activated protein kinase β subunits reduces bone mass without altering osteoclast differentiation or function

HB1.F3.C1 cells injected intravenously localized to microscopic bone marrow disease.

<div><p>Concordant detection of v-<i>myc</i> (HB1.F3.C1 cells) by PCR and TH expression (neuroblastoma cells) by RT-PCR in bone marrow specimens.</p> <p>Bone marrow samples isolated from animals injected with HB1.F3.C1 cells were analyzed for the presence of v-<i>myc</i> (HB1.F3.C1 cells) or the expression of TH (NB-1643 cells).</p> <p>HB1.F3.C1 cells were present in the bone marrow only when tumor cells were also present.</p> <p>HB1.F3.C1 cells were not detected in the bone marrow of non-tumor-bearing animals.</p> <p>The positive controls (+) were DNA extracted from HB1.F3.C1 cells for v-<i>myc</i>, and RNA extracted from NB-1691 cells for TH.</p> <p>The negative controls (−) contained no DNA or RNA template, respectively.</p></div

HB1.F3.C1 cells transduced with an adenoviral multiplicity of infection of 5, 10, or 20 retain their tumor-tropism toward conditioned medium from SK-N-AS neuroblastoma cells.

<p>Bars represent the average number of migrated cells±SEM of triplicate wells in modified Boyden chamber assays.</p

Es1^e SCID mice injected intravenously with neuroblastoma cells develop multiple disseminated tumors.

<div><p>SK-N-AS cells (5×10⁵) transduced to express luciferase were injected into tail veins.</p> <p>One month following injection of tumor cells, mice were injected intraperitoneally with luciferin and imaged using a Xenogen IVIS imaging system, according the directions of the manufacturer.</p> <p>Multiple tumors were present in 100% of mice.</p> <p>Two representative mice are shown.</p></div