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Shi, Dan

Publications and source records attributed to Shi, Dan.

5 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

110 Patients with adenosquamous carcinomas of the pancreas (PASC): imaging differentiation of small (≤ 3 cm) versus large (> 3 cm) tumors

Objective: This study examined radiological imaging features of small (≤ 3 cm) and large (> 3 cm) adenosquamous carcinomas of the pancreas (PASC) lesions to better understand the morphology of these lesions. Methods: Images from 110 patients with pathologically proven PASC (80 males and 30 females, mean age: 62.6 years) were retrospectively reviewed. Two radiologists analyzed images and reached a consensus regarding the following features: location, shape, margins, presence of solid and necrotic components, rim enhancement, density/intensity during the portal venous phase, invasion of surrounding organs, vascular invasion, venous tumor thrombus formation, and enlarged lymph nodes. Differences in the imaging features between the two groups were evaluated with the Chi-square test or Fisher’s exact test. Results: There were 41 small PASC lesions (mean age: 60.59 years) and 69 large PASC lesions (63.74 years). Statistical analysis demonstrated significant differences in the location, shape, adjacent organ and vessel invasion, and venous tumor thrombus formation (P < 0.05). Small PASC lesions were more frequently detected in the pancreatic head and had an ovoid shape. There was no significant difference in the presence of solid and necrotic components (P = 0.090), including approximately 3/4 of the lesions with necrosis and 1/4 purely solid lesions, enlarged lymph nodes (P = 0.068) and other features. Conclusion: Regardless of the tumor size, 75% of PASC lesions present with central necrosis while 25% are purely solid. Small PASC lesions can be associated with lymph node metastasis at a relatively early stage. Large PASC lesions are likely to invade adjacent tissues and be associated with venous tumor thrombus formation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity

hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Using the cryoEM method MicroED, we discover that one segment, 19–29 S20G, forms pairs of β-sheets mated by a dry interface that share structural features with and are similarly cytotoxic to full-length hIAPP fibrils. In contrast, a second segment, 15–25 WT, forms non-toxic labile β-sheets. These segments possess different structures and cytotoxic effects, however, both can seed full-length hIAPP, and cause hIAPP to take on the cytotoxic and structural features of that segment. These results suggest that protein segment structures represent polymorphs of their parent protein and that segment 19–29 S20G may serve as a model for the toxic spine of hIAPP.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Structure of the toxic core of α-synuclein from invisible crystals

We report that the protein α-synuclein is the main component of Lewy bodies, the neuron-associated aggregates seen in Parkinson disease and other neurodegenerative pathologies. An 11-residue segment, which we term NACore, appears to be responsible for amyloid formation and cytotoxicity of human α-synuclein. Here we describe crystals of NACore that have dimensions smaller than the wavelength of visible light and thus are invisible by optical microscopy. As the crystals are thousands of times too small for structure determination by synchrotron X-ray diffraction, we use micro-electron diffraction to determine the structure at atomic resolution. The 1.4 Å resolution structure demonstrates that this method can determine previously unknown protein structures and here yields, to our knowledge, the highest resolution achieved by any cryo-electron microscopy method to date. The structure exhibits protofibrils built of pairs of face-to-face β-sheets. X-ray fibre diffraction patterns show the similarity of NACore to toxic fibrils of full-length α-synuclein. Finally, the NACore structure, together with that of a second segment, inspires a model for most of the ordered portion of the toxic, full-length α-synuclein fibril, presenting opportunities for the design of inhibitors of α-synuclein fibrils.

Lewy bodies↗
DOE OSTI2015

MicroED data collection and processing

The collection and processing of MicroED data are presented. MicroED, a method at the intersection of X-ray crystallography and electron cryo-microscopy, has rapidly progressed by exploiting advances in both fields and has already been successfully employed to determine the atomic structures of several proteins from sub-micron-sized, three-dimensional crystals. A major limiting factor in X-ray crystallography is the requirement for large and well ordered crystals. By permitting electron diffraction patterns to be collected from much smaller crystals, or even single well ordered domains of large crystals composed of several small mosaic blocks, MicroED has the potential to overcome the limiting size requirement and enable structural studies on difficult-to-crystallize samples. This communication details the steps for sample preparation, data collection and reduction necessary to obtain refined, high-resolution, three-dimensional models by MicroED, and presents some of its unique challenges.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗