Biosynthesis of Veratrum californicum specialty chemicals in Camelina sativa seed

Megan M. Augustin,Ashutosh K. Shukla,Courtney M. Starks,Mark O’Neil‑Johnson,Linna Han,Cynthia K. Holland,Toni M. Kutchan 한국식물생명공학회 2017 Plant biotechnology reports Vol.11 No.1

Economically feasible systems for heterologous production of complex secondary metabolites originating from difficult to cultivate species are in demand since Escherichia coli and Saccharomyces cerevisiae are not always suitable for expression of plant and animal genes. An emerging oilseed crop, Camelina sativa, has recently been engineered to produce novel oil profiles, jet fuel precursors, and small molecules of industrial interest. To establish C. sativa as a system for the production of medicinally relevant compounds, we introduced four genes from Veratrum californicum involved in steroid alkaloid biosynthesis. Together, these four genes produce verazine, the hypothesized precursor to cyclopamine, a medicinally relevant steroid alkaloid whose analogs are currently being tested for cancer therapy in clinical trials. The future supply of this potential cancer treatment is uncertain as V. californicum is slow-growing and not amendable to cultivation. Moreover, the complex stereochemistry of cyclopamine results in low-yield syntheses. Herein, we successfully engineered C. sativa to synthesize verazine, as well as other V. californicum secondary metabolites, in seed. In addition, we have clarified the stereochemistry of verazine and related V. californicum metabolites.

Preoperative Therapy Regimen Influences the Incidence and Implication of Nodal Downstaging in Patients with Gastric Cancer

Alexander P. Stark,Mariela M. Blum,Yi-Ju Chiang,Prajnan Das,Bruce D. Minsky,Jeannelyn S. Estrella,Jaffer A. Ajani,Brian D. Badgwell,Paul Mansfield,Naruhiko Ikoma 대한위암학회 2020 Journal of gastric cancer Vol.20 No.3

Purpose: Nodal downstaging after preoperative therapy for gastric cancer has been shown to impart excellent prognosis, but this has not been validated in a national cohort. The role of neoadjuvant chemoradiation (NACR) in nodal downstaging remains unclear when compared with that of neoadjuvant chemotherapy alone (NAC). Furthermore, it is unknown whether the prognostic implications of nodal downstaging differ by preoperative regimen. Materials and Methods: Using the National Cancer Database, overall survival (OS) duration was compared among natural N0 (cN0/ypN0), downstaged N0 (cN+/ypN0), and node-positive (ypN+) gastric cancer patients treated with NACR or NAC. Factors associated with nodal downstaging were examined in a propensity score-matched cohort of cN+ patients, matched 1:1 by receipt of NACR or NAC. Results: Of 7,426 patients (natural N0 [n=1,858, 25.4%], downstaged N0 [n=1,813, 24.4%], node-positive [n=3,755, 50.4%]), 58.2% received NACR, and 41.9% received NAC. The median OS durations of downstaged N0 (5.1 years) and natural N0 (5.6 years) patients were similar to one another and longer than that of node-positive patients (2.1 years) (P<0.001). In the matched cohort of cN+ patients, more recent diagnosis (2010–2015 vs. 2004–2009) (odds ratio [OR], 2.57; P<0.001) and NACR (OR, 2.02; P<0.001) were independently associated with nodal downstaging. The 5-year OS rate of downstaged N0 patients was significantly lower after NACR (46.4%) than after NAC (57.7%) (P=0.003). Conclusions: Downstaged N0 patients have the same prognosis as natural N0 patients. Nodal downstaging occurred more frequently after NACR; however, the survival benefit of nodal downstaging after NACR may be less than that when such is achieved by NAC.

Microsurgical Strategies Following Failed Endovascular Treatment with the Pipeline Embolization Device: Case of a Giant Posterior Cerebral Artery Aneurysm

Dale Ding,Robert M. Starke,Kenneth C. Liu 대한뇌혈관외과학회 2014 Journal of Cerebrovascular and Endovascular Neuros Vol.16 No.1

Treatment of giant posterior circulation aneurysms, via endovascular or microsurgical approaches, carries a high risk of morbidity and mortality. While flow-diverting stents (FDSs) represent a potent therapy for endovascular reconstruction of complex aneurysms, they are also associated with novel complications for which effective salvage techniques are lacking. We present a unique complication from failed treatment with a FDS. A 51 year-old male presented with increasing headaches secondary to a giant, fusiform aneurysm of the left posterior cerebral artery, which was largely thrombosed. Due to progressive enlargement of the aneurysm corresponding to worsening clinical symptoms, the lesion was treated with two Pipeline embolization devices (ev3, Plymouth, MN, United States). Three months after Pipeline embolization device treatment, complete posterior cerebral artery occlusion was observed at the origin of the proximal stent. Despite the lack of arterial inflow, the aneurysm dome continued to grow, resulting in obstructive hydrocephalus. Therefore microsurgical intervention was undertaken to trap and excise the aneurysm. The patient's postoperative course was complicated by multiple venous infarcts, ultimately resulting in death. Successful microsurgical obliteration of aneurysms previously treated with FDSs is extremely difficult. A combination of judicious preoperative planning and meticulous intraoperative surgical technique are requisite for effective management of these complicated cases.

Balloon Anchor Technique for Pipeline Embolization Device Deployment Across the Neck of a Giant Intracranial Aneurysm

Dale Ding,Robert M. Starke,Avery J. Evans,Mary E. Jensen,Kenneth C. Liu 대한뇌혈관외과학회 2014 Journal of Cerebrovascular and Endovascular Neuros Vol.16 No.2

Treatment of giant intracranial aneurysms, via either surgical or endovascularapproaches, is associated with a high level of technical difficulty aswell as a high rate of treatment-related morbidity and mortality. Flow-divertingstents, such as the Pipeline embolization device (PED), have drasticallyaltered the therapeutic strategies for the treatment of giant aneurysms. Gaining endovascular access using a microcatheter to the portion of theparent artery distal to the aneurysm neck is requisite for safe and effectivestent deployment. Giant aneurysms are often associated with vasculartortuosity, which necessitates significant catheter support systems to enablemaneuvering of PEDs across the aneurysm neck. This is also requiredin order to reduce the probability of stent herniation within giantaneurysms. We report on a case of a giant supraclinoid internal carotidartery (ICA) aneurysm which was treated successfully with a PED utilizinga balloon anchor technique to facilitate direct microcatheter access acrossthe aneurysm neck.

Surgical Approaches for Symptomatic Cerebral Cavernous Malformations of the Thalamus and Brainstem

Dale Ding,Robert M. Starke,R. Webster Crowley,Kenneth C. Liu 대한뇌혈관외과학회 2017 Journal of Cerebrovascular and Endovascular Neuros Vol.19 No.1

Objective:Surgical resection of thalamic and brainstem cerebral cavernous malformations (CCMs) is associated with significant operative morbidity, but it may be outweighed, in some cases, by the neurological damage from recurrent hemorrhage in these eloquent areas. The goals of this retrospective cohort study are to describe the technical nuances of surgical approaches and determine the postoperative outcomes for CCMs of the thalamus and brainstem. Materials and Methods:We reviewed an institutional database of patients harboring thalamic or brainstem CCMs, who underwent surgical resection from 2010 to 2014. The baseline and follow-up neuroimaging and clinical findings of each patient and the operative details of each case were evaluated. Results:A total of eight patients, including two with thalamic and six with brainstem CCMs, were included in the study cohort. All patients had progressive neurological deterioration from recurrent CCM hemorrhage, and the median modified Rankin Scale (mRS) at presentation was 3. The median CCM maximum diameter and volume were 1.7 cm and 1.8 cm3, respectively. The thalamic CCMs were resected using the anterior transcallosal transchoroidal and supracerebellar infratentorial approaches each in one case (13%). The brainstem CCMs were resected using the retrosigmoid and suboccipital trans-cerebellomedullary fissure approaches each in three cases (38%). After a median follow-up of 11.5 months, all patients were neurologically stable or improved, with a median mRS of 2. The rate of functional independence (mRS 0-2) was 63%. Conclusion : Microneurosurgical techniques and approaches can be safely and effectively employed for the management of thalamic and brainstem CCMs in appropriately selected patients.

Plasticity analysis by synchrotron radiation in a Mg₉₇Y₂Zn₁ alloy with bimodal grain structure and containing LPSO phase

Garces, G.,Morris, D.G.,Munoz-Morris, M.A.,Perez, P.,Tolnai, D.,Mendis, C.,Stark, A.,Lim, H.K.,Kim, S.,Shell, N.,Adeva, P. Elsevier Science 2015 Acta materialia Vol.94 No.-

Deformation behaviour has been examined by synchrotron radiation diffraction in an extruded magnesium - long-period-stacking-order phase alloy comprising three components of microstructure. The variation of internal strains and intensities of the important crystallographic planes of the two phases has been examined during compression at several temperatures. The long-period-stacking-order phase remains elastic to stresses beyond the macroscopic yield stress while deformation in the magnesium matrix is dominated by twinning and basal slip, with the coarse-grained regions deforming plastically at stresses well below the macroscopic yield stress while regions with fine grain size deform plastically only at much higher stresses.

Molecular Pathogenesis of Vibrio vulnificus

Gulig Paul A.,Bourdage Keri L.,Starks Angela M. The Microbiological Society of Korea 2005 The journal of microbiology Vol.43 No.1

Vibrio vulnificus is an opportunistic pathogen of humans that has the capability of causing rare, yet devastating disease. The bacteria are naturally present in estuarine environments and frequently contaminate seafoods. Within days of consuming uncooked, contaminated seafood, predisposed individuals can succumb to sepsis. Additionally, in otherwise healthy people, V. vulnificus causes wound infection that can require amputation or lead to sepsis. These diseases share the characteristics that the bacteria multiply extremely rapidly in host tissues and cause extensive damage. Despite the analysis of virulence for over 20 years using a combination of animal and cell culture models, surprisingly little is known about the mechanisms by which V. vulnificus causes disease. This is in part because of differences observed using animal models that involve infection with bacteria versus injection of toxins. However, the increasing use of genetic analysis coupled with detailed animal models is revealing new insight into the pathogenesis of V. vulnificus disease.

Eyebrow Incision for Surgical Evacuation of a Lobar Intracerebral Hematoma with a Novel Endoport System

Dale Ding,Colin J. Przybylowski,Robert M. Starke,R. Webster Crowley,Kenneth C. Liu 대한뇌혈관외과학회 2017 Journal of Cerebrovascular and Endovascular Neuros Vol.19 No.2

Large lobar intracerebral hemorrhages (ICHs) can cause rapid neurological deterioration, and affected patients have low rates of survival and functional independence. Currently, the role of surgical intervention in the management patients with lobar ICHs is controversial. Minimally invasive technologies have been developed which may potentially decrease the operative morbidity of ICH surgery. The aim of this case report is to describe the technical aspects of the use of a novel minimally invasive endoport system, the BrainPath (NICO, Indianapolis, IN, USA), through an eyebrow incision for evacuation of a large lobar hematoma. An 84-year-old female presented with a left frontal ICH, measuring 7.5 cm in maximal diameter and 81 cm3 in volume, secondary to cerebral amyloid angiopathy. Through a left eyebrow incision, a miniature modified orbitozygomatic craniotomy was performed, which allowed endoport cannulation of the hematoma from a lateral subfrontal cortical entry point. Endoport-assisted hematoma evacuation resulted in nearly 90% volume reduction and improvement of the patient's functional status at clinical follow-up. We found that minimally invasive endoport technology can be employed in conjunction with conventional neurosurgical skull base principles to achieve safe and effective evacuation of large lobar hematomas in carefully selected patients.

TORSIONAL RESONANCE MODE ATOMIC FORCE MICROSCOPY OF A PROTEIN–DNA COMPLEX

GILBERTO WEISSMÜLLER,AYHAN YURTSEVER,LILIAN T. COSTA,ANA B. F. PACHECO,PAULO M. BISCH,WOLFGANG M. HECKL,ROBERT W. STARK 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2008 NANO Vol.3 No.6

Precise mapping of protein-binding sites on DNA is an important application of atomic force microscope (AFM) imaging. For a reliable measurement of distances on curved DNA molecules, an image-processing algorithm is required, which extracts the DNA contour from topographic AFM data. To this end we implemented an image analysis method providing an efficient way to obtain the contour together with a physical map of single and multiple protein-binding sites. This method relies on a calculation of the height profile along the DNA fragment, allowing one to determine the DNA length and the relative position of the binding site occupied by a protein. As a first test, complexes of the LexA repressor protein from the Escherichia coli SOS system and DNA fragments containing a specific LexA binding site (recA operator) were imaged by the torsional resonance mode (TR mode) and analyzed using the specialized algorithm. A topographic height of less than 0.5 nm of the DNA molecules indicates repulsive imaging conditions.

CdSe Single-Nanocrystal-Based Active Optical Tips for Near-Field Optics: Towards a Nanosource of Light

N. Chevalier,F. Chandezon,J. Bleuse,J.C. Woehl,J.F. Motte,M. Stark,M.J. Nasse,P. Reiss,S. Huant 한국물리학회 2005 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.47 No.1

We present a method to realize active optical tips for use in near-field optics that can operate at room temperature. A metal-coated optical tip is covered with a thin polymer layer stained with CdSe nanocrystals at low density. The time analysis of the emission rate of the active tip and the analysis of its emission spectra reveal that a very small number of particles - possibly down to only one nanocrystal - can be made active at the tip apex. This opens the way to optics with a single nanocrystal as a light source.