scholarly journals The nucleation of protein crystals as a race against time with on- and off-pathways

2017 ◽  
Vol 50 (4) ◽  
pp. 1056-1065 ◽  
Author(s):  
Cecilia Ferreira ◽  
Silvia Barbosa ◽  
Pablo Taboada ◽  
Fernando A. Rocha ◽  
Ana M. Damas ◽  
...  

High supersaturation levels are a necessary but insufficient condition for the crystallization of purified proteins. Unlike most small molecules, proteins can take diverse aggregation pathways that make the outcome of crystallization assays quite unpredictable. Here, dynamic light scattering and optical microscopy were used to show that the nucleation of lysozyme crystals is preceded by an initial step of protein oligomerization and by the progressive formation of metastable clusters. Because these steps deplete the concentration of soluble monomers, the probability of obtaining protein crystals decreases as time progresses. Stochastic variations of the induction time are thus amplified to a point where fast crystallization can coexist with unyielding regimes in the same conditions. With an initial hydrodynamic radius of ∼100 nm, the metastable clusters also promote the formation of protein crystals through a mechanism of heterogeneous nucleation. Crystal growth (on-pathway) takes place in parallel with cluster growth (off-pathway). The Janus-faced influence of the mesoscopic clusters is beneficial when it accelerates the formation of the first precrystalline nuclei and is detrimental as it depletes the solution of protein ready to crystallize. Choosing the right balance between the two effects is critical for determining the success of protein crystallization trials. The results presented here suggest that a mild oligomerization degree promotes the formation of a small number of metastable clusters which then catalyze the nucleation of well differentiated crystals.

Crystals ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 400 ◽  
Author(s):  
Yong Yu ◽  
Kai Li ◽  
Hai Lin ◽  
Ji-Cheng Li

Space is expected to be a convection-free, quiescent environment for the production of large-size and high-quality protein crystals. However, the mechanisms by which the diffusion environment in space improves the quality of the protein crystals are not fully understood. The interior of a microfluidic device can be used to simulate a microgravity environment to investigate the protein crystallization mechanism that occurs in space. In the present study, lysozyme crystals were grown in a prototype microchannel device with a height of 50 μm in a glass-polydimethylsiloxane (PDMS)-glass sandwich structure. Comparative experiments were also conducted in a sample pool with a height of 2 mm under the same growth conditions. We compared the crystal morphologies and growth rates of the grown crystals in the two sample pools. The experimental results showed that at very low initial supersaturation, the morphology and growth rates of lysozyme crystals under the simulated microgravity conditions is similar to that on Earth. With increasing initial supersaturation, a convection-free, quiescent environment is better for lysozyme crystal growth. When the initial supersaturation exceeded a threshold, the growth of the lysozyme crystal surface under the simulated microgravity conditions never completely transform from isotropic to anisotropic. The experimental results showed that the convection may have a dual effect on the crystal morphology. Convection can increase the roughness of the crystal surface and promote the transformation of the crystal form from circular to tetragonal during the crystallization process.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098668
Author(s):  
Bo Pang ◽  
Cong Hu ◽  
Qian Liu ◽  
Jinyu Yu ◽  
Zhentong Wei ◽  
...  

Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial tumor. The lesions may be single or multiple and usually behave in a benign or indolent fashion, sometimes persisting for many years. In the present case, a 37-year-old woman had experienced primary infertility for 12 years, and a diagnostic laparoscopy was performed. Approximately 200 mL of dark red, free fluid in the pelvis and more than 10 yellow-white nodules on the surface of the right round ligament, sacrum ligament, right fallopian tube, and both sides of the uterus were found. A lesionectomy was performed and immunohistochemical markers indicated WDPM with adenomatoid tumor. The patient was monitored by computed tomography and serum CA125 (cancer antigen 125) levels for 49 months with no recurrence. WDPM and adenomatoid tumor are both benign tumors of mesothelial origin. Because of the lack of effective radical treatment, regular follow-up is sufficient. However, the effects of estrogen and progesterone on WDPM and adenomatoid tumors during ovulation or pregnancy remains unclear. Although WDPM is not life threatening, a strategy to fulfill the fertility requirements of women with this condition is a new challenge for infertility doctors.


2020 ◽  
Author(s):  
Mirela Danila ◽  
Roxana Sirli ◽  
Alina Popescu ◽  
Nicoleta Iacob ◽  
Ana-Maria Ghiuchici

Primary biliary tract neuroendocrine tumors (NETs) are extremely rare tumors that account for 0.2-2% of all gastrointestinal neuroendocrine tumors. The typical presentation is with jaundice and other symptoms related to biliary obstruction.We present a case of right hepatic duct NET in a 27-year-old female patient, asymptomatic, presented for a routine ultrasound examination that revealed moderate dilatation of the intrahepatic biliary ducts and a 20 mm hyperechoic lesion in the right hepatic biliary duct. Additional imaging was performed with the presumptive diagnosis of cholangiocarcinoma. After surgery, the histopathological and immunohistochemical report was conclusive for the diagnosis of G2 well-differentiated NET


2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Haider Alyousef ◽  
Elsawi M. Osman ◽  
Mohamed A. Gomha

Introduction. Liposarcoma is a rare pathological entity. By far it is the most common histological subtype of genitourinary sarcomas in adults. Approximately two hundred cases were reported in the literature. We are hereby presenting a case with a typical clinical scenario of paratesticular liposarcoma.Case report. A 75-year-old gentleman presented with a painless right hemiscrotal swelling that was progressively increasing in size over the last 6 years. Testicular tumour markers were negative. Imaging showed a heterogenous mass with fat component. Subsequently he underwent wide local excision that included the paratesticular mass along with the right testicle and all right inguinal canal contents up to the deep inguinal ring with the sparing of right illioinguinal nerve. Histopathological examination showed a well differentiated liposarcoma of the spermatic cord. He remained recurrence-free so far after 18 months of followup.Conclusion. Radical orchidectomy with wide local excision comprises the cornerstone of treatment of paratesticular liposarcoma. Due to the rarity of the disease there is no definite universal consensus of opinion as regards the role of radiotherapy and chemotherapy.


2003 ◽  
Vol 127 (1) ◽  
pp. 81-84 ◽  
Author(s):  
Hwei-Yee Lee ◽  
Qasim Ahmed

Abstract We report the case of a 69-year-old woman who presented with postmenopausal bleeding. Endometrial curettings showed complex atypical hyperplasia with focal well-differentiated adenocarcinoma. A computed tomographic scan of the abdomen revealed a right ovarian mass. Histologically, the right ovarian tumor was a fibrothecoma with minor sex cord elements showing focal fibrosarcomatous change. Fibrosarcoma of the ovary is a rare tumor that is considered to arise de novo or secondary to benign fibromatous tumors. Fibrothecoma of the ovary with minor sex cord elements is also a rare entity. To the best of our knowledge, this is the first reported case of a fibrosarcoma arising in a fibrothecoma with minor sex cord elements.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Honoka Fuse ◽  
Masaya Ito ◽  
Kosuke Takemura ◽  
Shuzo Ikuta ◽  
Toru Motoi ◽  
...  

A 37-year-old Burmese woman presented with an incidentally found retroperitoneal fat-containing tumor. The tumor was 9 cm in the longest diameter, surrounding the right kidney, and composed of homogenous adipose tissue with thickened septum-like structures and spotty nonadipose structures, which were enhanced on contrast-enhanced computed tomography and magnetic resonance imaging. The tumor did not show either a beak sign or synchronous angiomyolipoma-like lesion in the kidneys. The tumor had irregular septa, thin blood vessels, and spotty small soft-tissue nodules. The tumor did not contain any heterogeneously enhanced solid lesions suspicious for dedifferentiated liposarcomas. Based on these imaging findings, a clinical diagnosis of a well-differentiated liposarcoma was made. Under the consensus of a multidisciplinary cancer board, she was recommended to undergo core-needle biopsy to confirm the clinical diagnosis. However, she declined to undergo biopsy for financial reasons. She underwent kidney-sparing retroperitoneal tumor resection. Histopathologically, the tumor was an angiomyolipoma with positive immunostaining for HMB45 and Melan A. The present case suggests the importance of core-needle biopsy prior to surgical intervention for retroperitoneal fat-containing tumors.


2009 ◽  
Vol 54 (No. 11) ◽  
pp. 543-546 ◽  
Author(s):  
G. Serin ◽  
A. Aydogan

This report describes the clinical and histopathological findings associated with a mammary chondrosarcoma in a mongrel bitch. The tumour was located in the right caudo-abdominal mammary gland, and was 6 × 8 × 4 cm in size, weighed 200 g and was very firm to the touch. Microscopically, a well differentiated chondrosarcoma, rarely observed in canine mammary gland tumours, was diagnosed.


2016 ◽  
Vol 21 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Daniel L. Ericson ◽  
Xingyu Yin ◽  
Alexander Scalia ◽  
Yasmin N. Samara ◽  
Richard Stearns ◽  
...  

Soft Matter ◽  
2020 ◽  
Vol 16 (8) ◽  
pp. 1955-1960 ◽  
Author(s):  
Tomoya Yamazaki ◽  
Alexander E. S. Van Driessche ◽  
Yuki Kimura

Dynamic behavior of defects in lysozyme protein crystals reveals that the lattice molecules are mobile throughout the crystal.


Crystals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 78
Author(s):  
Yoshinobu Hashizume ◽  
Koji Inaka ◽  
Naoki Furubayashi ◽  
Masayuki Kamo ◽  
Sachiko Takahashi ◽  
...  

In this paper, we present a summary on how to obtain protein crystals from which better diffraction images can be produced. In particular, we describe, in detail, quality evaluation of the protein sample, the crystallization conditions and methods, flash-cooling protection of the crystal, and crystallization under a microgravity environment. Our approach to protein crystallization relies on a theoretical understanding of the mechanisms of crystal growth. They are useful not only for space experiments, but also for crystallization in the laboratory.


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