87 results
Search Results
2. Paper‐Based Antibody Detection Devices Using Bioluminescent BRET‐Switching Sensor Proteins.
- Author
-
Tenda, Keisuke, van Gerven, Benice, Arts, Remco, Hiruta, Yuki, Merkx, Maarten, and Citterio, Daniel
- Subjects
- *
PROTEINS , *BIOLUMINESCENCE , *FLUORESCENCE resonance energy transfer , *BLOOD plasma , *COLORIMETRIC analysis - Abstract
This work reports on fully integrated "sample‐in‐signal‐out" microfluidic paper‐based analytical devices (μPADs) relying on bioluminescence resonance energy transfer (BRET) switches for analyte recognition and colorimetric signal generation. The devices use BRET‐based antibody sensing proteins integrated into vertically assembled layers of functionalized paper, and their design enables sample volume‐independent and fully reagent‐free operation, including on‐device blood plasma separation. User operation is limited to the application of a single drop (20–30 μL) of sample (serum, whole blood) and the acquisition of a photograph 20 min after sample introduction, with no requirement for precise pipetting, liquid handling, or analytical equipment except for a camera. Simultaneous detection of three different antibodies (anti‐HIV1, anti‐HA, and anti‐DEN1) in whole blood was achieved. Given its simplicity, this type of device is ideally suited for user‐friendly point‐of‐care testing in low‐resource environments. A single drop of blood on paper: Bioluminescent sensing proteins integrated into a multi‐layer paper‐based device allow the user‐friendly and simple quantification of monoclonal antibodies from a single drop of blood by simple color change monitoring. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
3. Sertoli–Leydig tumor and DICER1 gene mutation: A case series and literature review.
- Author
-
Durden, Andrew A, Cass, Gemma K., and Newton, Claire
- Subjects
- *
PROTEINS , *TESTOSTERONE , *PUBLIC health surveillance , *CYSTECTOMY , *HYPERTRICHOSIS , *ADNEXAL diseases , *SALPINGO-oophorectomy , *OVARIAN tumors , *RARE diseases , *ABDOMINAL pain , *GONADS , *COMPUTED tomography , *ABDOMINAL surgery , *ULTRASONIC imaging , *MAGNETIC resonance imaging , *ESTERASES , *IMMUNOHISTOCHEMISTRY , *SEIZURES (Medicine) , *RETENTION of urine , *GENETIC mutation , *ACNE , *TUMORS , *EARLY diagnosis , *COUNSELING , *AMENORRHEA , *GENETIC testing - Abstract
Objective: Sertoli–Leydig cell tumors (SLCTs) are rare neoplasms occurring in young women with 60% associated with DICER1 mutations. This is only the second published case series of patients with SLCTs with associated DICER1 gene alterations. DICER1 syndrome is a rare inherited tumor‐susceptibility syndrome affecting organs such as the ovaries. We use this case series to inform readers on this increasingly important condition in gynecology. Methods and Results: We present three young females presenting with secondary amenorrhoea, hirsutism, acne and in one case tonic–clonic seizures. All cases had high testosterone levels and an adnexal mass on ultrasound. Following surgical removal, pathology confirmed SLCTs and genetic testing followed. All three patients had DICER1 syndrome with two patients subsequently found to be related. Discussion: The prevalence of DICER1 syndrome in the population is estimated to be 1 in 10 000 with a spectrum of sex cord stromal tumors affecting young women. The associated pathological classifications and management. This paper describes the DICER1 gene and the associated tumor predisposition syndrome alongside a surveillance protocol for use in clinical practice. It promotes discussion over the importance of early clinical genetics involvement in sex‐cord stromal tumors and the associated difficulties in counseling in a young patient population. Genetic testing and early detection are imperative for targeted surveillance of at‐risk organs to be performed but despite this there is no international guidance. The cases highlight the psychological impact of tumors in young patients and provokes an ethical discussion over DICER1 gene's inclusion in preimplantation genetics. Conclusions: DICER1 syndrome is a rare but increasingly important condition in pediatric and adolescent gynecology with a paucity of published data and case reports. This makes international consensus on management and surveillance difficult. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Editing the 19 kDa alpha‐zein gene family generates non‐opaque2‐based quality protein maize.
- Author
-
Hurst, J. Preston, Sato, Shirley, Ferris, Tyler, Yobi, Abou, Zhou, You, Angelovici, Ruthie, Clemente, Tom E., and Holding, David R.
- Subjects
- *
GENE families , *AGRICULTURE , *GENOME editing , *PROTEINS , *AMINO acids - Abstract
Summary: Maize grain is deficient in lysine. While the opaque2 mutation increases grain lysine, o2 is a transcription factor that regulates a wide network of genes beyond zeins, which leads to pleiotropic and often negative effects. Additionally, the drastic reduction in 19 kDa and 22 kDa alpha‐zeins causes a floury kernel, unsuitable for agricultural use. Quality protein maize (QPM) overcame the undesirable kernel texture through the introgression of modifying alleles. However, QPM still lacks a functional o2 transcription factor, which has a penalty on non‐lysine amino acids due to the o2 mutation. CRISPR/cas9 gives researchers the ability to directly target genes of interest. In this paper, gene editing was used to specifically target the 19 kDa alpha zein gene family. This allows for proteome rebalancing to occur without an o2 mutation and without a total alpha‐zein knockout. The results showed that editing some, but not all, of the 19 kDa zeins resulted in up to 30% more lysine. An edited line displayed an increase of 30% over the wild type. While not quite the 55% lysine increase displayed by QPM, the line had little collateral impact on other amino acid levels compared to QPM. Additionally, the edited line containing a partially reduced 19 kDa showed an advantage in kernel texture that had a complete 19 kDa knockout. These results serve as proof of concept that editing the 19 kDa alpha‐zein family alone can enhance lysine while retaining vitreous endosperm and a functional O2 transcription factor. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Recent Advancements in Continuous Crystallization of Proteins.
- Author
-
Vikram, M. V. and Yadav, Manishkumar D.
- Subjects
- *
CRYSTALLIZATION , *INSULIN antibodies , *PROTEINS , *MANUFACTURING processes , *BATCH processing , *MONOCLONAL antibodies - Abstract
Recently, there have been many studies and reports on various continuous protein crystallization processes. Due to the increasing demand for pharmaceutical proteins such as insulin and monoclonal antibodies, it has become essential to optimize the current industrial processes to meet these demands. There are various comparisons to be made between current batch crystallization processes and continuous processes for proteins. This review paper aims to review the recent advancements in continuous protein crystallization processes, such as slug flow crystallizers, oscillatory baffled crystallizers, and mixed suspension mixed product removal (MSMPR) crystallizers. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Central markers of neuroinflammation in alcohol use disorder: A meta‐analysis of neuroimaging, cerebral spinal fluid, and postmortem studies.
- Author
-
Adams, Claire, Perry, Nina, Conigrave, James, Hurzeler, Tristan, Stevens, Julia, Yacou Dunbar, Kristiane P., Sweeney, Alicia, Lee, Kylie, Sutherland, Greg, Haber, Paul, and Morley, Kirsten C.
- Subjects
- *
CEREBROSPINAL fluid examination , *COMPLICATIONS of alcoholism , *HIPPOCAMPUS physiology , *BIOMARKERS , *CYTOKINES , *PROTEINS , *ONLINE information services , *META-analysis , *CONFIDENCE intervals , *AUTOPSY , *SYSTEMATIC reviews , *RADIOISOTOPES , *NEUROINFLAMMATION , *COMPARATIVE studies , *POSITRON emission tomography , *DESCRIPTIVE statistics , *CHEMOKINES , *MEDLINE , *NEURORADIOLOGY - Abstract
Introduction and aims: There is emerging evidence that heavy long‐term alcohol consumption may alter the neuroimmune profile. We conducted a meta‐analysis of the association between alcohol use disorder (AUD) and the extent of neuroinflammation using cerebrospinal (CSF), PET (Positron Emission Tomography), and postmortem studies. Design and methods: A comprehensive search of electronic databases was conducted using the Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols (PRISMA‐P) for AUD‐related terms in combination with neuroinflammatory markers and cytokine‐ and chemokine‐related terms for CSF, PET, and postmortem studies. Participants had to meet established criteria for AUD and/or heavy alcohol consumption with dependence features and be compared with healthy controls. Papers retrieved were assessed for inclusion criteria and a critical appraisal was completed using the Newcastle‐Ottawa Scale. A meta‐analysis was conducted on postmortem and PET studies. Results: Eleven papers met the inclusion criteria with CSF, PET, and postmortem studies included in the final analysis. Postmortem studies demonstrate significant heterogeneity (푄 (14) = 62.02, 푝 < 0.001), with the alcohol group showing higher levels of neuroimmune markers than controls (푑 = 1.50 [95% CI 0.56, 2.45]). PET studies demonstrated a lower [11C] PBR28 total volume of distribution (VT) for translocator protein in the hippocampus (g = −1.95 [95% CI −2.72, −1.18], p < 0.001) of the alcohol group compared to controls. Conclusion: There is emerging evidence across multiple diagnostic modalities that alcohol impacts neuroimmune signaling in the human brain. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Pseudo‐pseudo Meigs syndrome in systemic lupus erythematosus misdiagnosed as pseudo‐Meigs' syndrome: A case report.
- Author
-
He, Jiaqi, Li, Jinke, Fan, Bao, Yan, Liya, and Ouyang, Ling
- Subjects
- *
SYSTEMIC lupus erythematosus diagnosis , *METHYLPREDNISOLONE , *BOWEL obstructions , *PHYSICAL diagnosis , *BIOMARKERS , *PROTEINS , *HORMONE therapy , *MEIGS syndrome , *OVARIAN tumors , *UREA , *IMMUNOGLOBULINS , *SERUM , *SERODIAGNOSIS , *UTERINE tumors , *DIFFERENTIAL diagnosis , *POSITRON emission tomography computed tomography , *UTERINE fibroids , *ASCITES , *DISEASE relapse , *ABDOMINAL surgery , *SYSTEMIC lupus erythematosus , *DIAGNOSTIC errors , *TUMOR antigens , *RARE diseases , *PELVIS , *CREATININE - Abstract
Symptoms of pelvic masses, elevated serum CA125 levels, massive ascites, and pleural effusion in female patients are usually associated with malignancy. Some benign ovarian tumors or other nonmalignant tumors may also produce similar symptoms, called Meigs syndrome or pseudo‐Meigs' syndrome, which should be one of the differential diagnoses. However, there is an extremely rare form of SLE called pseudo‐pseudo Meigs syndrome (PPMS), which may also present with the above symptoms, but is not associated with any of the tumors. In this paper, we report a case of a 47‐year‐old woman who presented with abdominal distention. The patient was found to have elevated serum CA125 levels to 182.9 U/mL before the operation. Her PET‐CT suggested a large heterogeneous mass in the pelvis measuring 8.2 × 5.8 cm with a large amount of ascites. She was initially diagnosed with ovarian cancer and underwent exploratory laparotomy. Pathology of the surgical specimen revealed a uterine leiomyoma. Two months after discharge, the patient's ascites reappeared along with recurrent intestinal obstruction. After ascites and serological tests, she was eventually diagnosed with systemic lupus erythematosus and received systemic hormonal therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
8. Back Cover: Paper‐Based Antibody Detection Devices Using Bioluminescent BRET‐Switching Sensor Proteins (Angew. Chem. Int. Ed. 47/2018).
- Author
-
Tenda, Keisuke, van Gerven, Benice, Arts, Remco, Hiruta, Yuki, Merkx, Maarten, and Citterio, Daniel
- Subjects
- *
BIOLUMINESCENCE , *PROTEINS , *DETECTORS , *IMMUNOGLOBULINS , *DIGITAL cameras - Abstract
Detecting antibodies in blood is as simple as it can get. In their Communication on page 15369 ff., D. Citterio, M. Merkx et al. integrate antibody‐targeting bioluminescent sensing proteins and other essential assay components into a microfluidic paper‐based analytical device. A drop of blood, a digital camera, and twenty minutes are all that is required to detect the presence and the concentration of multiple antibodies in whole blood based on the color of the emitted light. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
9. Proteotypic peptides of hairs for the identification of common European domestic and wild animal species revealed by in‐sample protein digestion and mass spectrometry analysis.
- Author
-
Kuckova, Stepanka, Smirnova, Tatiana Anatolievna, Straka, David, Meledina, Alena, Santrucek, Jiri, Humpolakova, Karin, Hoskova, Martina, Cejnar, Pavel, and Hynek, Radovan
- Subjects
- *
ANIMAL species , *GOAT breeds , *DOG breeds , *PROTEOLYSIS , *DOMESTIC animals , *MATRIX-assisted laser desorption-ionization , *TIME-of-flight mass spectrometry , *SIKA deer , *AMINO acid sequence - Abstract
The aim of this work is to offer an alternative or complementary analytical tool to the time‐consuming and expensive methods commonly used for the recognition of animal species according to their hair. The paper introduces a simple and fast way for species differentiation of animal hairs called in‐sample digestion. A total of 10 European animal species, including cat, cow, common degu, dog, fallow deer, goat, horse, sika deer, rabbit, roe deer, and 17 different breeds of dogs were examined using specific tryptic cleavage directly in hair followed by matrix‐assisted laser desorption/ionization–time of flight mass spectrometry and liquid chromatography‐electrospray ionization quadrupole time of flight. Principal component analysis was used for the subsequent mass spectrometric data evaluation. This novel approach demonstrates the ability to distinguish among individual animal species, which is supported by finding characteristic m/z values obtained by the mass spectrometry for each animal species. The approach was successfully tested on two "blind" samples. On the other hand, the attempt to distinguish among hairs of different dog breeds has not been successful due to the very similar protein composition and their amino acid sequences. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
10. Biological functions and structural biology of Plasmodium falciparum autophagy‐related proteins: The under‐explored options for novel antimalarial drug design.
- Author
-
Usman, Mohammed Aliyu, Salman, Abdulmalik Abdullahi, Ibrahim, Mohammed Auwal, Furukawa, Koji, and Yamasaki, Kazuhiko
- Subjects
- *
PLASMODIUM falciparum , *DRUG design , *PROTEIN-protein interactions , *PROTEINS , *BIOLOGY , *WORLD health - Abstract
Malaria remains a threat to global public health and the available antimalarial drugs are undermined by side effects and parasite resistance, suggesting an emphasis on new potential targets. Among the novel targets, Plasmodium falciparum autophagy‐related proteins (PfAtg) remain a priority. In this paper, we reviewed the existing knowledge on the functions and structural biology of PfAtg including the compounds with inhibitory activity toward P. falciparum Atg8‐Atg3 protein–protein interaction (PfAtg8‐PfAtg3 PPI). A total of five PfAtg (PfAtg5, PfAtg8, PfAtg12, PfAtg18, and Rab7) were observed to have autophagic and/or non‐autophagic roles. Available data showed that PfAtg8 has conserved hydrophobic pockets, which allows it to interact with PfAtg3 to form PfAtg8‐PfAtg3 PPI. Additionally, 2‐bromo‐N‐(4‐pyridin‐2‐yl‐1,3‐thiazol‐2‐yl) benzamide was identified as the most powerful inhibitor of PfAtg8‐PfAtg3 PPI. Due to the dearth of knowledge in this field, we hope that the article would open an avenue to further research on the remaining PfAtg as possible drug candidates. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
11. Different experimental approaches for Fourier‐transform infrared spectroscopy applications in biology and biotechnology: A selected choice of representative results.
- Author
-
Errico, Sonia, Moggio, Martina, Diano, Nadia, Portaccio, Marianna, and Lepore, Maria
- Subjects
- *
INFRARED spectroscopy , *FOURIER transform infrared spectroscopy , *FOURIER transforms , *BIOLOGY , *DATA analysis - Abstract
Fourier transform infrared (FTIR) spectroscopy is a powerful tool for analyzing the biochemical properties of biological samples such as proteins, cellular materials, and tissues. It provides objective information on samples and has been adopted in many research areas of biomedical and biotechnological interest. FTIR spectroscopy can be performed using different approaches at the macro and micro levels allowing the examination of an incredibly broad class of materials. However, it has become evident that the choice of proper spectra acquisition geometries and the modalities of sample preparation in FTIR spectroscopy analysis require special consideration, especially for certain classes of materials such as cells and tissues. In the present paper, we described the different procedures used for preparing and analyzing different types of biological and biotechnological samples when the more largely available approaches are employed using a commercial FTIR spectrometer. Some basic aspects of data analysis procedures are presented in an Appendix. A certain number of our previous experimental results are reported for demonstrating once more the versatility and the potentiality of FTIR spectroscopy. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
12. Nanopore sensors for single molecular protein detection: Research progress based on computer simulations.
- Author
-
Hu, Gang, Yan, Han, Xi, Guohao, Gao, Zhuwei, Wu, Ziqing, Lu, Zuhong, and Tu, Jing
- Subjects
- *
AMINO acid sequence , *COMPUTER simulation , *CARRIER proteins , *BIOMACROMOLECULES , *PROTEIN structure , *BIOMOLECULES - Abstract
As biological macromolecules, proteins are involved in important cellular functions ranging from DNA replication and biosynthesis to metabolic signalling and environmental sensing. Protein sequencing can help understand the relationship between protein function and structure, and provide key information for disease diagnosis and new drug design. Nanopore sensors are a novel technology to achieve the goal of label‐free and high‐throughput protein sequencing. In recent years, nanopore‐based biosensors have been widely used in the detection and analysis of biomolecules such as DNA, RNA, and proteins. At the same time, computer simulations can describe the transport of proteins through nanopores at the atomic level. This paper reviews the applications of nanopore sensors in protein sequencing over the past decade and the solutions to key problems from a computer simulation perspective, with the aim of pointing the way to the future of nanopore protein sequencing. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
13. Editorial: Adequate protein intake is more crucial than the profile of amino acids intake for sarcopenia prevention during the earlier stages of liver cirrhosis.
- Author
-
Kontogianni, Meropi D.
- Subjects
- *
CIRRHOSIS of the liver , *AMINO acids , *PROTEINS , *MUSCLE mass , *SARCOPENIA , *LIVER - Abstract
LINKED CONTENT: This article is linked to Hey et al paper. To view this article, visit https://doi.org/10.1111/apt.17917 [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
14. In Vitro Selection of a DNA Aptamer Targeting Degraded Protein Fragments for Biosensing.
- Author
-
Liu, Meng, Wang, Jiayi, Chang, Yangyang, Zhang, Qiang, Chang, Dingran, Hui, Christy Y., Brennan, John D., and Li, Yingfu
- Subjects
- *
APTAMERS , *DEOXYRIBOZYMES , *CLOSTRIDIOIDES difficile , *DNA , *PROTEINS , *BIODEGRADATION - Abstract
Protein biomarkers often exist as degradation fragments in biological samples, and affinity agents derived using a purified protein may not recognize them, limiting their value for clinical diagnosis. Herein, we present a method to overcome this issue, by selecting aptamers against a degraded form of the toxin B protein, which is a marker for diagnosing toxigenic Clostridium difficile infections. This approach has led to isolation of a DNA aptamer that recognizes degraded toxin B, fresh toxin B, and toxin B spiked into human stool samples. DNA aptamers selected using intact recombinant toxin B failed to recognize degraded toxin B, which is the form present in stored stool samples. Using this new aptamer, we produced a simple paper‐based analytical device for colorimetric detection of toxin B in stool samples, or in the NAP1 strain of Clostridium difficile. The combined aptamer‐selection and paper‐sensing strategy can expand the practical utility of DNA aptamers in clinical diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
15. In Vitro Selection of a DNA Aptamer Targeting Degraded Protein Fragments for Biosensing.
- Author
-
Liu, Meng, Wang, Jiayi, Chang, Yangyang, Zhang, Qiang, Chang, Dingran, Hui, Christy Y., Brennan, John D., and Li, Yingfu
- Subjects
- *
APTAMERS , *DEOXYRIBOZYMES , *CLOSTRIDIOIDES difficile , *DNA , *PROTEINS , *BIODEGRADATION - Abstract
Protein biomarkers often exist as degradation fragments in biological samples, and affinity agents derived using a purified protein may not recognize them, limiting their value for clinical diagnosis. Herein, we present a method to overcome this issue, by selecting aptamers against a degraded form of the toxin B protein, which is a marker for diagnosing toxigenic Clostridium difficile infections. This approach has led to isolation of a DNA aptamer that recognizes degraded toxin B, fresh toxin B, and toxin B spiked into human stool samples. DNA aptamers selected using intact recombinant toxin B failed to recognize degraded toxin B, which is the form present in stored stool samples. Using this new aptamer, we produced a simple paper‐based analytical device for colorimetric detection of toxin B in stool samples, or in the NAP1 strain of Clostridium difficile. The combined aptamer‐selection and paper‐sensing strategy can expand the practical utility of DNA aptamers in clinical diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
16. Role of FOXO protein's abnormal activation through PI3K/AKT pathway in platinum resistance of ovarian cancer.
- Author
-
Shi, Yun‐Yue, Meng, Xiang‐Tian, Xu, Ya‐Nan, and Tian, Xiu‐Juan
- Subjects
- *
PROTEINS , *OVARIAN tumors , *APOPTOSIS , *PLATINUM , *GENE expression , *TRANSFERASES , *DNA damage , *TRANSCRIPTION factors , *DRUG resistance in cancer cells - Abstract
Aim: Platinum‐based chemotherapy is the standard treatment for ovarian cancer. However, tumor cells' resistance to platinum drugs often occurs. This paper provides a review of Forkhead box O (FOXO) protein's role in platinum resistance of ovarian cancer which hopefully may provide some further guidance for the treatment of platinum‐resistant ovarian cancer. Methods: We reviewed a 128 published papers from authoritative and professional journals on FOXO and platinum‐resistant ovarian cancer, and adopts qualitative analyses and interpretation based on the literature. Results: Ovarian cancer often has abnormal activation of cellular pathways, the most important of which is the PI3K/AKT pathway. FOXOs act as crucial downstream factor of the PI3K/Akt pathway and are negatively regulated by it. DNA damage response and apoptosis including the relationship between FOXOs and ATM‐Chk2‐p53 are essential for platinum resistance of ovarian cancer. Through gene expression analysis in platinum‐resistant ovarian cancer cell model, it was found that FoxO‐1 is decreased in platinum‐resistant ovarian cancer, so studying the role of FOXO in the pathway on platinum‐induced apoptosis may further guide the treatment of platinum‐resistant ovarian cancer. Conclusions: There are many drug resistance mechanisms in ovarian cancer, wherein the decrease in cancer cells apoptosis is one of the important causes. Constituted by a series of transcription factors evolving conservatively and mainly working in inhibiting cancer, FOXO proteins play various roles in cells' antitumor response. More and more evidence suggests that we need to re‐understand the role that FOXOs have played in cancer development and treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
17. Single‐Step N‐Terminal Modification of Proteins via a Bio‐Inspired Copper(II)‐Mediated Aldol Reaction.
- Author
-
Hanaya, Kengo, Yamoto, Kaho, Taguchi, Kazuaki, Matsumoto, Kazuaki, Higashibayashi, Shuhei, and Sugai, Takeshi
- Subjects
- *
EPIDERMAL growth factor receptors , *CHEMICAL modification of proteins , *PROTEINS , *COPPER , *PROTEIN structure - Abstract
The chemical modification of proteins is an effective technique for manipulating the properties and functions of proteins, and for creating protein‐based materials. The N‐terminus is a promising target for single‐site modification that provides modified proteins with uniform structures and properties. In this paper, a copper(II)‐mediated aldol reaction with 2‐pyridinecarboxaldehyde (2‐PC) derivatives is proposed as an operationally simple method to selectively modify the N‐terminus of peptides and proteins at room temperature and physiological pH. The copper(II) ion activates the N‐terminal amino acids by complexation with an imine of the N‐terminal amino acid and 2‐PCs, realizing the selective formation of the nucleophilic intermediate at the N‐terminus. This results in a stable carbon‐carbon bond between the 2‐PCs and the α‐carbon of various N‐terminal amino acids. The reaction is applied to four different proteins, including biopharmaceuticals such as filgrastim and trastuzumab. The modified trastuzumab retains the human epidermal growth factor receptor 2 recognition activity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
18. Ultrasound and effect on the surface hydrophobicity of proteins: a meta‐analysis.
- Author
-
Bezerra, Jaqueline de Araújo, Sanches, Edgar Aparecido, Lamarão, Carlos Victor, and Campelo, Pedro Henrique
- Subjects
- *
ULTRASONIC imaging , *PROTEINS - Abstract
Summary: This review aims to investigate and evaluate the effect of ultrasound process parameters on the interfacial properties (surface hydrophobicity) of food proteins. The data obtained from English published papers accessed on Web of Science, PubMed and Wiley published from 2013 to 2021 allowed a table overview construction and a meta‐analysis. Study selection was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses method. A total of 40 relevant reports and 185 data used for meta‐analysis were considered. In general, the results revealed that the use of the ultrasound process increased the surface hydrophobicity of proteins. Processing time, power, amplitude and ultrasound frequency were significant in protein modification. The findings showed that the ultrasound process parameters should be considered to assess the effect on the modification and improvement of the interfacial properties of proteins. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
19. A Review on Biodegradable Packaging Films from Vegetative and Food Waste.
- Author
-
Gupta, Prashant, Toksha, Bhagwan, and Rahaman, Mostafizur
- Subjects
- *
PACKAGING film , *FOOD waste , *SCIENTIFIC literature , *BIODEGRADABLE plastics , *FOOD industrial waste , *PLASTIC scrap , *PLASTICS in packaging , *PLASTIC scrap recycling - Abstract
Plastics around the globe have been a matter of grave concern due to the unavoidable habits of human mankind. Taking waste statistics in India for the year 2019–20 into account, the data of 60 major cities show that the generation of plastic waste stands tall at around 26,000 tonnes/day, of which only about 60 % is recycled. A majority of the non‐recycled plastic waste is petrochemical‐based packaging materials that are non‐biodegradable in nature. Vegetative/food waste is another global issue, evidenced by vastly populated countries such as China and India accounting for 91 and 69 tonnes of food wastage, respectively in 2019. The mitigation of plastic packaging issues has led to key scientific developments, one of which is biodegradable materials. However, there is a way that these two waste‐related issues can be fronted as the analogy of "taking two shots with the same arrow". The presence of various bio‐compounds such as proteins, cellulose, starch, lipids, and waxes, etc., in food and vegetative waste, creates an opportunity for the development of biodegradable packaging films. Although these flexible packaging films have limitations in terms of mechanical, permeation, and moisture absorption characteristics, they can be fine‐tuned in order to convert the biobased raw material into a realizable packaging product. These strategies could work in replacing petrochemical‐based non‐biodegradable packaging plastics which are used in enormous quantities for various household and commercial packaging applications to combat the ever‐increasing pollution in highly populated countries. This paper presents a systematic review based on modern scientific tools of the literature available with a major emphasis on the past decade and aims to serve as a standard resource for the development of biodegradable packaging films from food/vegetative waste. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
20. Most promising alternative protein sources possible to use in sports nutrition – A review.
- Author
-
Grdeń, Adam and Sołowiej, Bartosz G.
- Subjects
- *
SINGLE cell proteins , *SPORTS nutrition , *EDIBLE insects , *PROTEINS , *LIVESTOCK productivity , *GLYCOALKALOIDS - Abstract
Summary: A growing world population and ongoing climate change have created a need to find new sources of high‐quality food, especially protein, that are sustainable and environmentally friendly and help to reduce unsustainable livestock production. Therefore, it is necessary to look for sources of protein from new raw materials or to use existing materials that have not been used on a large scale. The highest protein intake characterises athletes; thus, the market for high‐protein products should be targeted for them. This paper outlines the main problems associated with protein production to date, mainly from animal sources and some known plant sources such as pulses, which can cause gastrointestinal problems in athletes. This review aimed to propose several new/alternative protein sources (Single Cell Protein, edible insects, algae, and potato protein) that may have the potential for use in food, including food for athletes while solving the described problems associated with existing protein sources. Insects have the best amino acid composition; microbial and algal proteins have great potential but require further development of technology for application to food products. Potato proteins are of high value and quality but also contain glycoalkaloids. However, using them brings additional economic and environmental benefits. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
21. Constructing a PPI Network Based on Deep Transfer Learning for Protein Complex Detection.
- Author
-
Yuan, Xin, Deng, Hangyu, and Hu, Jinglu
- Subjects
- *
DEEP learning , *CONVOLUTIONAL neural networks , *PROTEIN-protein interactions , *PROTEINS , *ELECTRICAL engineers - Abstract
In the detection of protein complexes, the completeness of a protein–protein interaction (PPI) network is crucial. Complete PPI networks, however, are not available for most species because experimentally identified PPIs are usually very limited. This paper proposes a deep learning based PPI predictor to construct a complete PPI network, from which protein complexes are detected using a spectral clustering method. For this purpose, the unknown PPIs are estimated by using a deep PPI predictor consisting of a semi‐supervised SVM classifier and a deep feature extractor of the convolutional neural network (CNN). Meanwhile, the similarities of gene ontology (GO) annotations contribute to protein interactions, and the differences of subcellular localizations contribute to negative interactions. Considering that, we pretrain the deep CNN feature extractor in a class of deep GO annotation and subcellular localization predictors using datasets from the type species, then transfer it to the PPI prediction model for fine‐tuning. In this way, we have a deep PPI detector enhanced with transfer learning of GO annotation and subcellular localization prediction. Experimental results on benchmark datasets show that the proposed method outperforms the state‐of‐the‐art methods. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
22. Contribution of a ZIP-family protein to manganese uptake and infective endocarditis virulence in Streptococcus sanguinis.
- Author
-
Puccio, Tanya, Kunka, Karina S., Seon-Sook An, and Kitten, Todd
- Subjects
- *
STREPTOCOCCUS sanguis , *INFECTIVE endocarditis , *MANGANESE , *IRON , *PROTEINS - Abstract
Streptococcus sanguinis is an important cause of infective endocarditis. In strain SK36, the ABC-family manganese transporter, SsaACB, is essential for virulence. We have now identified a ZIP-family protein, TmpA, as a secondary manganese transporter. A tmpA mutant had no phenotype, but a ΔssaACB ΔtmpA mutant was more attenuated for serum growth and for virulence in a rabbit model than its ΔssaACB parent. The growth of both mutants was restored by supplemental manganese, but the ΔssaACB ΔtmpA mutant required twenty-fold more and accumulated less. Although ZIP-family proteins are known for zinc and iron transport, TmpA-mediated transport of either metal was minimal. While ssaACB appears ubiquitous in St. sanguinis, tmpA was present in a majority of strains and a mntH gene encoding an NRAMP-family transporter was identified in relatively few, including VMC66. As in SK36, deletion of ssaACB greatly diminished VMC66 endocarditis virulence and serum growth, and deletion of tmpA from this mutant diminished virulence further. Virulence was not significantly altered by deletion of mntH from either VMC66 or its ΔssaACB mutant. This and the accompanying paper together suggest that SsaACB is of primary importance for endocarditis virulence while secondary transporters TmpA and MntH contribute to growth under differing conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
23. Revelation of point mutations effect in Mycobacterium tuberculosis MfpA protein that involved in mycobacterial DNA supercoiling and fluoroquinolone resistance.
- Author
-
Gautam, Princy, Shivangi, and Meena, Laxman S.
- Subjects
- *
MYCOBACTERIUM tuberculosis , *DNA topoisomerase II , *PROTEIN stability , *PYRAZINAMIDE , *PROTEINS , *DNA , *DNA replication , *ANTIBIOTICS - Abstract
MfpA protein is encoded by Mycobacterium tuberculosis (Mtb) and stands for Mycobacterium fluoroquinolone resistance protein A. This protein provides Mtb intrinsic resistant property from fluoroquinolone antibiotics by inhibiting DNA gyrase that are known to be the primary target of fluoroquinolone drugs. DNA gyrases are important for bacterial chromosomal genesis as they are majorly involved in DNA replication, transcription, and bacterial stress response to several external stimulus. Therefore, in Mtb, it forms an essential integrity and also a desirable target for drug development approaches. This paper implies on determining the essential facts about mfpA including its interaction study, epitope prediction, modeling, and validation, and most importantly it deals with the mutation. Mutational analysis was carried out on the basis of sequential information and there were several mutations that cause a large decrease in the stability of the protein. Total 24 mutations were shortlisted based on ΔΔG value: W154G, F54G, L84G, F9G, W4G, F74G, F64G, F49G, L104G, L94G, L124G, F29G, L39G, L59G, W60G, L114G, , W154S, L19G, L144G, L129G, F34G, W154D, W154A, and W4S. Separate mutation on DXXG GTPase motif was examined to check any effect on protein stability and we found that D33A, D98A, D128A, G36A, G101A, G131A, D33G, D98G, D128G, G36W, G101W, G131W, D33K, D98K, and D128K decrease protein stability the most. Further stress‐dependent analysis on selected residues showed that lower temperature and pH destabilize the protein. The reason behind this increase in protein destability was drastic decrease and disruption of interatomic interactions in mutant MfpA. These analysis provides essential information about the residues that are important for MfpA stability and also enlightens protein vulnerability after mutation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
24. Glucose‐Induced Disintegrated Hydrogel for the Glucose‐Responsive Delivery of Insulin.
- Author
-
Lu, Yangyang, Yu, Haojie, Wang, Li, Shen, Di, and Liu, Jian
- Subjects
- *
INSULIN , *POLYMERS , *BIOCOMPATIBILITY , *GLUCOSE , *ESTERS - Abstract
Stimulus‐sensitive drug delivery materials are of vital significance to modern therapeutic technology. In particular, glucose‐responsive hydrogels capable of biomimetic release of hypoglycemic drugs according to glucose concentrations are one of the current research hotspots. In this paper, an injectable, glucose‐induced disintegrated natural‐polysaccharide‐based hydrogel with good self‐healing ability and biocompatibility is reported. The glucose‐responsiveness of the hydrogel stems from the reversible phenylborate ester bonds. The glucose‐triggered disintegration and insulin release are demonstrated in the hydrogel in a physiological environment. The two polymers produced by the disintegration of the hydrogel have good biocompatibility and biodegradability. Therefore, the hydrogel is considered to result in the development of smart insulin delivery systems. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
25. ESCASA: Analytical estimation of atomic coordinates from coarse‐grained geometry for nuclear‐magnetic‐resonance‐assisted protein structure modeling. I. Backbone and Hβ protons.
- Author
-
Lubecka, Emilia A. and Liwo, Adam
- Subjects
- *
PROTEIN structure , *PROTEIN models , *PROTONS , *SPINE , *MOLECULAR dynamics - Abstract
A method for the estimation of coordinates of atoms in proteins from coarse‐grained geometry by simple analytical formulas (ESCASA), for use in nuclear‐magnetic‐resonance (NMR) data‐assisted coarse‐grained simulations of proteins is proposed. In this paper, the formulas for the backbone Hα and amide (HN) protons, and the side‐chain Hβ protons, given the Cα‐trace, have been derived and parameterized, by using the interproton distances calculated from a set of 140 high‐resolution non‐homologous protein structures. The mean standard deviation over all types of proton pairs in the set was 0.44 Å after fitting. Validation against a set of 41 proteins with NMR‐determined structures, which were not considered in parameterization, resulted in average standard deviation from average proton–proton distances of the NMR‐determined structures of 0.25 Å, compared to 0.21 Å obtained with the PULCHRA all‐atom‐chain reconstruction algorithm and to the 0.12 Å standard deviation of the average‐structure proton–proton distance of NMR‐determined ensembles. The formulas provide analytical forces and can, therefore, be used in coarse‐grained molecular dynamics. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
26. Regulation of polyamine homeostasis through an antizyme citrullination pathway.
- Author
-
Yang, Yi‐Fang, Lee, Chien‐Yun, Hsieh, Ju‐Yi, Liu, Yi‐Liang, Lin, Chi‐Li, Liu, Guang‐Yaw, and Hung, Hui‐Chih
- Subjects
- *
POLYAMINES , *ORNITHINE decarboxylase , *HOMEOSTASIS , *PUTRESCINE , *PROTEINS , *DIMERS - Abstract
This study reveals an uncovered mechanism for the regulation of polyamine homeostasis through protein arginyl citrullination of antizyme (AZ), a natural inhibitor of ornithine decarboxylase (ODC). ODC is critical for the cellular production of polyamines. AZ binds to ODC dimers and promotes the degradation of ODC via the 26S proteasome. This study demonstrates the protein citrullination of AZ catalyzed by peptidylarginine deiminase type 4 (PAD4) both in vitro and in cells. Upon PAD4 activation, the AZ protein was citrullinated and accumulated, leading to higher levels of ODC proteins in the cell. In the PAD4‐overexpressing and activating cells, the levels of ODC enzyme activity and the product putrescine increased with the level of citrullinated AZ proteins and PAD4 activity. Suppressing cellular PAD4 activity reduces the cellular levels of ODC and downregulates cellular polyamines. Furthermore, citrullination of AZ in the C‐terminus attenuates AZ function in the inhibition, binding, and degradation of ODC. This paper provides evidence to illustrate that PAD4‐mediated AZ citrullination upregulates cellular ODC and polyamines by retarding ODC degradation, thus interfering with the homeostasis of cellular polyamines, which may be an important pathway regulating AZ functions that is relevant to cancer biology. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
27. Salivary proteins and peptides in the aetiology of caries in children: Systematic literature review.
- Author
-
Piekoszewska‐Ziętek, Paula, Turska‐Szybka, Anna, and Olczak‐Kowalczyk, Dorota
- Subjects
- *
SALIVA analysis , *DENTAL caries , *ENZYMES , *GLYCOPROTEINS , *MEDICAL information storage & retrieval systems , *LACTOBACILLUS , *MEDLINE , *ONLINE information services , *PEPTIDES , *PROTEINS , *RISK assessment , *STREPTOCOCCUS mutans , *SYSTEMATIC reviews , *CHILDREN - Abstract
Background: To assess the relationship of chosen salivary proteins and peptides levels with the occurrence of caries in children. Methods: PubMed, MEDLINE and EMBASE databases from 2000 to 2018 were researched for original observational studies published in English. The risk of bias and quality of the included papers were assessed regarding the guidelines by Fowkes and Fulton. Results: Twenty‐two studies were included in the review, from which the issue of glycoproteins (including immunoglobulins), AMPs and salivary enzymes was discussed. The research involved primary dentition (13 papers), as well as mixed (7) and permanent dentition (5). Caries assessment included visual inspection, dmft/s and DMFT/S indexed; quantity of Streptococcus mutans and Lactobacillus spp. bacteria; and caries risk assessment. Discussion: The results of studies regarding the connection between salivary peptides and proteins and caries development in children are promising; however, further investigations should be undertaken. The majority of studies included are case–control and cross‐sectional; however, it is necessary to conduct more cohort studies with adequate follow‐up prior to considering this as markers for caries risk assessment. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
28. Deep Protein Subcellular Localization Predictor Enhanced with Transfer Learning of GO Annotation.
- Author
-
Yuan, Xin, Pang, Erli, Lin, Kui, and Hu, Jinglu
- Subjects
- *
CONVOLUTIONAL neural networks , *DEEP learning , *AMINO acid sequence , *PROTEINS , *ANNOTATIONS - Abstract
Since the large‐scale protein sequence data is available, applying deep neural networks to mine better features from the sequences becomes possible. Eukaryotic protein subcellular localization prediction which makes a contribution in many biology process, has used protein sequences in many automatic predicting methods. Moreover, gene ontology (GO) annotation has been shown to be helpful in improving the prediction accuracy of subcellular localization. However, experimentally annotated proteins are not always available. On the other hand, experimentally annotated proteins are available for certain species such as human, mouse, Arabidopsis thaliana, etc. It is highly motivated to perform deep learning of GO annotations on the available experimentally annotated proteins and to transfer it to subcellular localization prediction on other species. In this paper, we propose a deep protein subcellular localization predictor, consisting of a linear classifier and a deep feature extractor of convolution neural network (CNN). The deep CNN feature extractor is first shared and pre‐trained in a deep GO annotation predictor, and then is transferred to the subcellular localization predictor with fine‐tuning using protein localization samples. In this way, we have a deep protein subcellular localization predictor enhanced with transfer learning of GO annotation. The proposed method has good performances on the Swiss‐Prot datasets, when transfer learning using the protein samples both within and out species. Moreover, it outperforms the state‐of‐the‐art traditional methods on benchmark datasets. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
29. Physicochemical and functional characteristics of proteins treated by a pH‐shift process: a review.
- Author
-
Tang, Zhen‐Xing, Ying, Rui‐Feng, and Shi, Lu‐E
- Subjects
- *
PROTEINS , *PROTEIN structure , *ISOELECTRIC point , *ELECTROSTATIC interaction , *MEAT - Abstract
Summary: Advanced structures of food proteins are maintained by many forces such as hydrophobic activities, electrostatic interaction, and disulphide bond interaction, which can affect their functional characteristics to a certain extent. Therefore, many approaches have been utilised to improve functional characteristics of food proteins. pH‐shift process refers to the method that food proteins are treated under extreme alkaline or acid conditions followed by adjusting pH to isoelectric point or neutral pH. Many studies have showed that pH‐shift process can significantly affect the functional characteristics of food proteins, for example emulsifying activities, forming property, solubility and water/oil adsorption ability. pH‐shift process has been utilised to recover protein isolates from many sources including fish, fish by‐products, meat processing products. Many researches have indicated that the functional and physicochemical characteristics of recovered protein isolates are significantly influenced by pH‐shift process. In this paper, the latest studies regarding the functional and physicochemical characteristics of proteins treated or recovered through pH‐shift process, and potential applications of obtained protein isolates in the production of the hydrolysates or used as a delivery system were reviewed. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
30. Nanomaterials‐Based Surface Protein Imprinted Polymers: Synthesis and Medical Applications.
- Author
-
Pan, Mingfei, Hong, Liping, Xie, Xiaoqian, Liu, Kaixin, Yang, Jingying, and Wang, Shuo
- Subjects
- *
IMPRINTED polymers , *POLYMERIZATION , *MOLECULAR imprinting , *MEDICAL polymers , *NANOTECHNOLOGY , *SOLID phase extraction - Abstract
Proteins are an essential part of organisms and play a very important role in life activities. Molecular imprinting technology (MIT) can prepare functional materials with specific identification abilities. In recent years, various molecularly imprinted materials have been widely used in the fields of solid‐phase extraction, bionic sensing, and on‐line analysis. Due to the limit of the properties of protein macromolecules, the development of MIT for protein molecules is relatively slow. With the continuous deepening on the research of nanomaterials and surface molecular imprinting technology, a large numbers of interesting and successful strategies appear on imprinted protein. Some surface protein imprinting materials with excellent properties and unique functions are applied in proteomics, biological imaging, medical diagnosis, and other fields, showing great potential application value. This paper summarizes the latest preparation and analysis strategies of surface protein imprinting based on nanomaterials, introduces medical application of protein imprinting materials in sample separation and purification, proteomics, biomedical and other aspects in recent years, and looks forward to the development opportunities and challenges in protein imprinting field. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
31. Biodevices using microwells sealed with artificial lipid bilayers: Improvement of sealing performance by protein coating.
- Author
-
Kashimura, Yoshiaki, Sumitomo, Koji, and Nakashima, Hiroshi
- Subjects
- *
BILAYER lipid membranes , *SIGNAL detection , *ION transport (Biology) , *SERUM albumin , *PROTEINS , *LEAKAGE - Abstract
The use of microwells sealed with lipid bilayers is promising for biodevices that utilize protein functions. We have fabricated microwell structures on a Si substrate sealed with lipid bilayers. We have investigated Ca2+ ion transport through α‐hemolysin channels with fluorescent microscopy. However, problems remain as regards achieving the detection of smaller signal such as receptor channels. Ion leakage through the interfacial water layer between the lipid bilayer and the substrate is one of the major hurdles to be overcome. In this paper, we present the mechanism of the ion leakage behavior and then an improved microwell structure that uses bovine serum albumin coating on the device surface to prevent ion leakage from/into the microwells. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
32. Clathrin‐dependent endocytosis predominantly mediates protein absorption by fat body from the hemolymph in Bombyx mori.
- Author
-
Wang, Yu‐Jie, Li, Shu‐Yan, Zhao, Jia‐Ye, Li, Kang, Xu, Jing, Xu, Xian‐Ying, Wu, Wen‐Mei, Yang, Rong, Xiao, Yang, Ye, Ming‐Qiang, Liu, Ji‐Ping, Zhong, Yang‐Jin, Cao, Yang, Yi, Hui‐Yu, and Tian, Ling
- Subjects
- *
ENDOCYTOSIS , *BODY composition , *SILKWORMS , *HEMOLYMPH , *INSECT metamorphosis , *PROTEINS - Abstract
During insect larval–pupal metamorphosis, proteins in the hemolymph are absorbed by the fat body for the maintenance of intracellular homeostasis; however, the type of proteins and how these proteins are internalized into the fat body are unclear. In Bombyx mori, the developmental profiles of total proteins in the hemolymph and fat body showed that hemolymph‐decreased protein bands (55–100 kDa) were in accordance with those protein bands that increased in the fat body. Inhibition of clathrin‐dependent endocytosis predominantly blocked the transportation of 55–100 kDa proteins from the hemolymph into the fat body, which was further verified by RNA interference treatment of Bmclathrin. Six hexamerins were shown to comprise ∼90% of the total identified proteins in both the hemolymph and fat body by mass spectrum (MS) analysis. In addition, hemolymph‐specific proteins were mainly involved in material transportation, while fat body‐specific proteins particularly participated in metabolism. In this paper, four hexamerins were found for the first time, and potential proteins absorbed by the fat body from the hemolymph through clathrin‐dependent endocytosis were identified. This study sheds light on the protein absorption mechanism during insect metamorphosis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
33. Peptidylprolylisomerases, Protein Folders, or Scaffolders? The Example of FKBP51 and FKBP52.
- Author
-
Rein, Theo
- Subjects
- *
CARRIER proteins , *PROTEINS , *CYCLOPHILINS , *PROTEIN folding , *COMPLEX organizations - Abstract
Peptidylprolyl‐isomerases (PPIases) comprise of the protein families of FK506 binding proteins (FKBPs), cyclophilins, and parvulins. Their common feature is their ability to expedite the transition of peptidylprolyl bonds between the cis and the trans conformation. Thus, it seemed highly plausible that PPIase enzymatic activity is crucial for protein folding. However, this has been difficult to prove over the decades since their discovery. In parallel, more and more studies have discovered scaffolding functions of PPIases. This essay discusses the hypothesis that PPIase enzymatic activity might be the consequence of binding to peptidylprolyl protein motifs. The main focus of this paper is the large immunophilins FKBP51 and FKBP52, but other PPIases such as cyclophilin A and Pin1 are also described. From the hypothesis, it follows that the PPIase activity of these proteins might be less relevant, if at all, than the organization of protein complexes through versatile protein binding. Also see the video abstract here https://youtu.be/A33la0dx5LE. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
34. On the evolution of the quality of macromolecular models in the PDB.
- Author
-
Brzezinski, Dariusz, Dauter, Zbigniew, Minor, Wladek, and Jaskolski, Mariusz
- Subjects
- *
BIOMACROMOLECULES , *STRUCTURAL models , *DATABASES , *BIOLOGICAL models , *MACROMOLECULAR dynamics , *X-ray crystallography - Abstract
Crystallographic models of biological macromolecules have been ranked using the quality criteria associated with them in the Protein Data Bank (PDB). The outcomes of this quality analysis have been correlated with time and with the journals that published papers based on those models. The results show that the overall quality of PDB structures has substantially improved over the last ten years, but this period of progress was preceded by several years of stagnation or even depression. Moreover, the study shows that the historically observed negative correlation between journal impact and the quality of structural models presented therein seems to disappear as time progresses. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
35. Ancient dental pulp: Masterpiece tissue for paleomicrobiology.
- Author
-
Mai, Ba Hoang Anh, Drancourt, Michel, and Aboudharam, Gérard
- Subjects
- *
DENTAL pulp , *SALMONELLA enterica serovar Typhi , *RICKETTSIA , *STAPHYLOCOCCUS aureus , *BLOODBORNE infections , *YERSINIA pestis , *PROTEOMICS - Abstract
Introduction: Dental pulp with special structure has become a good reference sample in paleomicrobiology‐related blood‐borne diseases, many pathogens were detected by different methods based on the diagnosis of nucleic acids and proteins. Objectives: This review aims to propose the preparation process from ancient teeth collection to organic molecule extraction of dental pulp and summary, analyze the methods that have been applied to detect septicemic pathogens through ancient dental pulps during the past 20 years following the first detection of an ancient microbe. Methods: The papers used in this review with two main objectives were obtained from PubMed and Google scholar with combining keywords: "ancient," "dental pulp," "teeth," "anatomy," "structure," "collection," "preservation," "selection," "photography," "radiography," "contamination," "decontamination," "DNA," "protein," "extraction," "bone," "paleomicrobiology," "bacteria," "virus," "pathogen," "molecular biology," "proteomics," "PCR," "MALDI‐TOF," "LC/MS," "ELISA," "immunology," "immunochromatography," "genome," "microbiome," "metagenomics." Results: The analysis of ancient dental pulp should have a careful preparation process with many different steps to give highly accurate results, each step complies with the rules in archaeology and paleomicrobiology. After the collection of organic molecules from dental pulp, they were investigated for pathogen identification based on the analysis of DNA and protein. Actually, DNA approach takes a principal role in diagnosis while the protein approach is more and more used. A total of seven techniques was used and ten bacteria (Yersinia pestis, Bartonella quintana, Salmonella enterica serovar Typhi, Salmonella enterica serovar Paratyphi C, Mycobacterium leprae, Mycobacterium tuberculosis, Rickettsia prowazeki, Staphylococcus aureus, Borrelia recurrentis, Bartonella henselae) and one virus (Anelloviridae) were identified. Y. pestis had the most published in quantity and all methods were investigated for this pathogen, S. aureus and B. recurrentis were identified by three different methods and others only by one. The combining methods interestingly increase the positive rate with ELISA, PCR and iPCR in Yersinia pestis diagnosis. Twenty‐seven ancient genomes of Y. pestis and one ancient genome of B. recurrentis were reconstructed. Comparing to the ancient bone, ancient teeth showed more advantage in septicemic diagnosis. Beside pathogen identification, ancient pulp help to distinguish species. Conclusions: Dental pulp with specific tissue is a suitable sample for detection of the blood infection in the past through DNA and protein identification with the correct preparation process, furthermore, it helps to more understand the pathogens of historic diseases and epidemics. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
36. Phenethylamine@Pillar[5]arene Biointerface for Highly Enantioselective Adsorption of Protein.
- Author
-
Yan, Hewei, Ma, Junkai, Zhu, Fei, Quan, Jiaxin, Dhinakaran, Manivannan Kalavathi, and Li, Haibing
- Subjects
- *
ADSORPTION capacity , *ADSORPTION (Chemistry) , *LYSOZYMES , *PROTEINS , *BLOOD platelet activation , *CONSTRUCTION materials , *ENZYMES - Abstract
In the life system, the biointerface plays an important role in cell adsorption, platelet adsorption and activation. Therefore, the study of protein adsorption on the biointerface is of great significance for understanding life phenomena and treatment in vitro. In this paper, a chiral biointerface was constructed by the virtue of host‐guest interaction between a water‐soluble pillar[5]arene (WP5) and phenethylamine (PEA) over a gold surface for adsorption of lysozyme proteins. From the experimental results it was identified that the host‐guest biointerface has a high adsorption capacity and strong chiral selectivity. Furthermotre, it was identified that the host‐guest interaction plays the decisive role in the enhancement of chirality of the interface, which was much beneficial for increasing protein adsorption and amplifying the capacity of chiral discrimination. Therefore, this work provides a new idea for the construction of biointerface materials with high protein adsorption capacity and high chiral selectivity through supramolecular interaction, which will have potential applications in the fields of biosensors, biocatalysts, biomaterials. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
37. Clinical and genetic features in pyridoxine-dependent epilepsy: a Chinese cohort study.
- Author
-
Jiao, Xianru, Xue, Jiao, Gong, Pan, Wu, Ye, Zhang, Yuehua, Jiang, Yuwu, and Yang, Zhixian
- Subjects
- *
EPILEPSY , *CHINA studies , *COHORT analysis , *VITAMIN B6 , *SEIZURES (Medicine) , *DIAGNOSIS of epilepsy , *PROTEINS , *BRAIN , *RESEARCH , *SEQUENCE analysis , *GENETIC mutation , *ELECTROENCEPHALOGRAPHY , *RESEARCH methodology , *RETROSPECTIVE studies , *EVALUATION research , *MEDICAL cooperation , *COMPARATIVE studies , *RESEARCH funding , *OXIDOREDUCTASES ,SIDE effects of anticonvulsants - Abstract
Aim: To characterize the clinical and genetic characteristics of a large cohort of patients with pyridoxine-dependent epilepsy (PDE).Method: We retrospectively collected clinical and genetic information of 33 (15 males, 18 females; mean [SD] age 4y 11mo [2y 5mo]; 1y 3mo-10y 4mo) patients with PDE from 31 unrelated families at a single centre.Results: There were many types of seizures, with focal seizures in 32 cases. Dravet syndrome was suspected clinically in two patients. Electroencephalogram (EEG) was normal in seven patients at the initial stage and then in 17 patients during pyridoxine maintenance therapy. Genetic studies revealed 26 kinds of variants in ALDH7A1 and four in PLPBP with 18 variants unreported previously, and 48 ALDH7A1 variants were located in exon 11, 12, 14, and 17 or intron 9 and 11. In addition, three patients carried different exons deletion. Among these, seizures could be controlled for several years in one patient by levetiracetam monotherapy. Another patient remained seizure free for up to 7 months without therapy. All patients received oral pyridoxine treatment, with only one case (with exon 8-13 deletion) showing poor control.Interpretation: This study illustrates the range of clinical presentations and genetic causes in PDE, as well as responsiveness to antiepileptic drugs. A relationship between EEG and pyridoxine therapy could be seen in many cases. Seizure control was seen in all with pyridoxine monotherapy except for one patient.What This Paper Adds: There is a parallel relationship between electroencephalogram and pyridoxine therapy in many patients. Patients with pyridoxine-dependent epilepsy may respond well to low-dose pyridoxine. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
38. Methanethiosulfonate Derivative of OX063 Trityl: A Promising and Efficient Reagent for Side‐Directed Spin Labeling of Proteins.
- Author
-
Tormyshev, Victor M., Chubarov, Alexey S., Krumkacheva, Olesya A., Trukhin, Dmitry V., Rogozhnikova, Olga Yu., Spitsyna, Anna S., Kuzhelev, Andrey A., Koval, Vladimir V., Fedin, Matvey V., Godovikova, Tatyana S., Bowman, Michael K., and Bagryanskaya, Elena G.
- Subjects
- *
SPIN labels , *LABELS , *SERUM albumin , *PROTEINS , *BIOLOGICAL systems - Abstract
Trityl radicals (TAMs) have recently appeared as an alternative source of spin labels for measuring long distances in biological systems. Finland trityl radical (FTAM) served as the basis for this new generation of spin labels, but FTAM is rather lipophilic and susceptible to self‐aggregation, noncovalent binding with lipophilic sites of proteins, and noncovalent docking at the termini of duplex DNA. In this paper the very hydrophilic OX063 TAM with very low toxicity and little tendency for aggregation is used as the basis for a spin label. Human serum albumin (HSA) labeled with OX063 has an intense narrow line typical of TAM radicals in solution, whereas HSA labeled with FTAM shows broad lines and extensive aggregation. In pulse EPR measurements, the measured phase memory time TM for HSA labeled with OX063 is 6.3 μs at 50 K, the longest yet obtained with a TAM‐based spin label. The lowered lipophilicity also decreases side products in the labeling reaction. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
39. Nitrogen storage regulation by PII protein: lessons learned from taxonomic outliers.
- Author
-
Rubio, Vicente, Marco‐Marín, Clara, and Llácer, José Luis
- Subjects
- *
NITROGEN , *PROTEINS , *MULTIENZYME complexes , *GLUTAMINE synthetase , *GOVERNMENT regulation , *COEVOLUTION - Abstract
The paper 'Interaction of N‐acetyl‐l‐glutamate kinase with the PII signal transducer in the non‐photosynthetic alga Polytomella parva: Co‐evolution towards a hetero‐oligomeric enzyme' by Selim et al. highlights how the study of a true taxonomic oddity, the heterotrophic unicellular alga P. parva, has been instrumental in uncovering the large potential for adaptive variation in the signaling complex of PII with the enzyme N‐acetylglutamate kinase (NAGK). This complex modifies the regulatory properties of NAGK, allowing nitrogen stockpiling as arginine. In P. parva, a stable PII‐NAGK complex is formed which lacks regulation by canonical PII effectors but which exhibits novel adaptive responses to nitrogen abundance mediated by glutamine, a neo‐effector of PII proteins of photosynthetic eukaryotes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
40. Nonbubble‐Propelled Biodegradable Microtube Motors Consisting Only of Protein.
- Author
-
Sugai, Natsuho, Morita, Yoshitsugu, and Komatsu, Teruyuki
- Subjects
- *
MOLECULAR motor proteins , *PROTEINS , *UREASE , *PROTEIN synthesis , *MOTORS - Abstract
This paper describes the synthesis of protein microtube motors having a urease interior surface and highlights their nonbubble‐propelled behavior driven by enzymatic reaction (urea→NH3 and CO2). The precursor microtubes were prepared by layer‐by‐layer assembly using a track‐etched microporous polycarbonate membrane. Immobilization of a urease on the internal wall was accomplished using avidin–biotin interaction. The tubules swam smoothly in an aqueous media containing a physiological concentration of urea. Each tubule was rotating laterally while moving forward. It is remarkable that the microtubes were digested completely by proteases, demonstrating perfect biodegradability. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
41. Improving pulse crops as a source of protein, starch and micronutrients.
- Author
-
Robinson, G. H. J., Balk, J., and Domoney, C.
- Subjects
- *
GLUCANS , *LEGUMES , *EDIBLE plants , *PROTEINS , *MICRONUTRIENTS , *SUSTAINABILITY , *NUTRITIONAL value , *BIOFORTIFICATION - Abstract
Pulse crops have been known for a long time to have beneficial nutritional profiles for human diets but have been neglected in terms of cultivation, consumption and scientific research in many parts of the world. Broad dietary shifts will be required if anthropogenic climate change is to be mitigated in the future, and pulse crops should be an important component of this change by providing an environmentally sustainable source of protein, resistant starch and micronutrients. Further enhancement of the nutritional composition of pulse crops could benefit human health, helping to alleviate micronutrient deficiencies and reduce risk of chronic diseases such as type 2 diabetes. This paper reviews current knowledge regarding the nutritional content of pea (Pisum sativum L.) and faba bean (Vicia faba L.), two major UK pulse crops, and discusses the potential for their genetic improvement. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
42. An Arabidopsis berberine bridge enzyme‐like protein specifically oxidizes cellulose oligomers and plays a role in immunity.
- Author
-
Locci, Federica, Benedetti, Manuel, Pontiggia, Daniela, Citterico, Matteo, Caprari, Claudio, Mattei, Benedetta, Cervone, Felice, and De Lorenzo, Giulia
- Subjects
- *
ARABIDOPSIS proteins , *PLANT cell walls , *OLIGOSACCHARIDES , *OLIGOMERS , *CELLULOSE , *PROTEINS - Abstract
Summary: The plant cell wall is the barrier that pathogens must overcome to cause a disease, and to this end they secrete enzymes that degrade the various cell wall components. Due to the complexity of these components, several types of oligosaccharide fragments may be released during pathogenesis and some of these can act as damage‐associated molecular patterns (DAMPs). Well‐known DAMPs are the oligogalacturonides (OGs) released upon degradation of homogalacturonan and the products of cellulose breakdown, i.e. the cellodextrins (CDs). We have previously reported that four Arabidopsis berberine bridge enzyme‐like (BBE‐like) proteins (OGOX1–4) oxidize OGs and impair their elicitor activity. We show here that another Arabidopsis BBE‐like protein, which is expressed coordinately with OGOX1 during immunity, specifically oxidizes CDs with a preference for cellotriose (CD3) and longer fragments (CD4–CD6). Oxidized CDs show a negligible elicitor activity and are less easily utilized as a carbon source by the fungus Botrytis cinerea. The enzyme, named CELLOX (cellodextrin oxidase), is encoded by the gene At4 g20860. Plants overexpressing CELLOX display an enhanced resistance to B. cinerea, probably because oxidized CDs are a less valuable carbon source. Thus, the capacity to oxidize and impair the biological activity of cell wall‐derived oligosaccharides seems to be a general trait of the family of BBE‐like proteins, which may serve to homeostatically control the level of DAMPs to prevent their hyperaccumulation. Significance Statement: This paper uncovers the activity of a member of the gene family encoding the berberine bridge enzyme‐like (BBE‐like) proteins. It encodes a specific oxidase that impairs the damage‐associated molecular pattern (DAMP) activity of cellodextrins and plays a role in immunity. The oxidation and inactivation of DAMPs seem to be general and important functions of several BBE‐like proteins and this work opens up avenues for the study of the physiological role and evolution of this family. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
43. Role of dietary phosphate restriction in chronic kidney disease.
- Author
-
Elder, Grahame J, Malik, Avya, and Lambert, Kelly
- Subjects
- *
CHRONIC kidney failure , *PHOSPHATES , *CARDIOVASCULAR diseases risk factors , *PROTEINS , *MOBILE apps - Abstract
Aim: Patients with progressive chronic kidney disease (CKD) develop positive phosphate balance that is associated with increased cardiovascular risk and mortality. Modification of dietary phosphate is a commonly used strategy to improve outcomes but is complicated by the need for adequate dietary protein. Surprisingly, the evidence for patient‐level benefits from phosphate restriction is tenuous, and the justification for using any phosphate binder for pre‐dialysis patients is questionable. Methods: The evidence for dietary phosphate modification was reviewed, along with the possible role of a smart phone application (app) that provides information on phosphate, sodium, potassium and nutrients in over 50 000 Australian foods. A pilot study of healthy participants assigned to dietetic advice and standard diet sheets, or dietetic advice, diet sheets and use of the smart phone app was performed. Results: Following baseline studies, 25 participants commenced the sodium and phosphate restricted diet. After 2 weeks, both groups showed non‐significant trends to reduction in urinary phosphate and sodium. App users referred to information on the app more frequently than the control group participants referred to written instructions, found referring to the app more convenient, felt they learned more new information, were more motivated to maintain the diet and were more likely to recommend their information source to family or friends (all P < 0.05). Conclusions: Maintaining phosphate balance remains an important goal of CKD management, although diets incorporating very low phosphate and protein contents may worsen patient outcomes. For selected patients, a smart phone app may improve dietary acceptance and compliance. Summary at a Glance: Abnormalities of phosphate metabolism are ubiquitous with chronic kidney disease, and management for hyperphosphataemia predominantly involves dietary phosphate restriction and the use of phosphate binders. This paper describes the evidence, or lack thereof, for dietary phosphate restriction, and also discusses a possible user‐friendly tool, in the form of a smart phone app, which may potentially be beneficial to patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
44. Stratiform Protein Microtube Reactors Containing Glucose Oxidase Layer.
- Author
-
Adachi, Ryo, Akiyama, Motofusa, Morita, Yoshitsugu, and Komatsu, Teruyuki
- Subjects
- *
GLUCOSE oxidase , *CATALYTIC activity , *POLYCARBONATES , *INTERMEDIATES (Chemistry) , *SERUM albumin , *POROUS materials - Abstract
Abstract: This paper describes the synthesis and catalytic activities of stratiform protein microtube reactors containing a glucose oxidase (GOD) enzyme layer. The microtubes were fabricated by layer‐by‐layer assembly using a microporous polycarbonate membrane with human serum albumin (HSA), poly( l‐arginine) (PLA), and GOD. The GOD component was introduced into the tube wall as the innermost layer, the intermediate layer, or all internal protein layers. SEM observations revealed the formation of uniform hollow cylinders with ca. 1.17 μm outer diameter and ca. 135 nm wall thickness. In aqueous medium, each microtube catalyzed β‐ d‐glucose oxidation with high efficiency. We first ascertained the enzyme parameters (Km and kcat) of these microtube reactors. Different catalytic activities that have dependent on the GOD layer position in the cylindrical wall have been elucidated. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
45. Development and validation of a liquid chromatography/tandem mass spectrometry method for determination of caspofungin in dried blood spots.
- Author
-
Cheng, Xiaoliang, Liu, Kunhong, Liu, Yong, Wang, Maoyi, and Ma, Ying
- Subjects
- *
DRIED blood spot testing , *LIQUID chromatography-mass spectrometry , *HEMATOCRIT , *PHARMACOKINETICS , *PROTEINS - Abstract
Rationale: A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantification of caspofungin in dried blood spots (DBS) was developed and validated. Methods: The DBS samples were prepared by spotting whole blood onto Whatman 903 filter paper, drying at room temperature and extracting with 50% methanol and further cleaned by protein precipitation with acetonitrile. Roxithromycin was selected as internal standard, and the separation of the analytes with endogenous ingredients was accomplished on a Hypersil GOLD aQ column with a mobile phase composed of 0.1% formic acid (v/v) and methanol in gradient mode. The detection of the analytes was performed on a triple quadrupole mass spectrometer in positive electrospray ionization mode, and the following selective reaction monitoring (SRM) transitions were monitored: m/z 547.6 → 538.7 and 837.4→ 679.4 for quantification of caspofungin and the internal standard, respectively. Results: The total analytical time was 8 min for each run. The calibration curve exhibited a good linearity over the range from 0.2 to 20 μg/mL and the lower limit of quantification (LLOQ) was 0.2 μg/mL for caspofungin in DBS. The recoveries of caspofungin ranged from 62.64% to 76.69%, and no obvious matrix effect was observed. The intra‐ and inter‐day precision and accuracy were within acceptable limits, and caspofungin in DBS was stable after storage at room temperature for 24 h and at −80°C for 30 days. There was no evident effect of the hematocrit value on the analysis of caspofungin. Conclusions: The proposed method presents an alternative to the conventional venous sampling method, and was successfully utilized for pharmacokinetics study of caspofungin in ICU patients. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
46. Mapping the tandem mass spectrometric characteristics of citrulline-containing peptides.
- Author
-
Steckel, Arnold, Uray, Katalin, Turiák, Lilla, Gömöry, Ágnes, Drahos, László, Hudecz, Ferenc, and Schlosser, Gitta
- Subjects
- *
PEPTIDES , *CITRULLINE , *ARGININE , *OLIGOPEPTIDES , *PROTEINS - Abstract
Rationale: Protein citrullination (deimination) is a post-translational modification of proteins converting arginine(s) into citrulline(s). "Overcitrullination" could be associated with severe pathological conditions. Mass spectrometric analysis of modified proteins is hindered by several problems. A comprehensive study of the fragmentation of deiminated peptides is not yet available. In this paper we have made an attempt to describe the characteristics of these processes, based on the studies of epitope model oligopeptides derived from clinically relevant proteins. Methods: Solutions of purified model peptides containing either one or two citrulline residues as well as their native variants were injected directly into the electrospray source of a high accuracy and resolution quadrupole-time-of-flight instrument and were analysed by tandem mass spectrometry using low-energy collision-induced dissociation. Results: Loss of isocyanic acid from citrulline residues is a preferred fragmentation route for deiminated peptides, which yields ornithine residues in the sequence. However, simultaneous detection of both the isocyanic acid loss and sequence fragments is often compromised. A preferential cleavage site was observed between citrulline and any other following amino acids yielding intensive complementary b- and y-type ions. Also, citrulline positioned at the C-termini displays a preferential cleavage N-terminal to this residue yielding characteristic y1 ions. These phenomena are described here for the first time and are referred to as the "citrulline effect". Conclusions: We found that the citrulline effect is very pronounced and could be used as a complementary tool for the confirmation of modification sites in addition to losses of isocyanic acids from the protonated molecules or from fragment ions. Low collision energy applied to peptide ions having partially mobile protons reveals the site of modification by generating specific and intensive fragments of the sequence. On the other hand, fragmenting precursor ions with mobile protons usually allows full sequence coverage, although citrulline-specific fragments may exhibit lower intensities compared to other fragments. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
47. Historical aspects of studies on roles of the inflammasome in the pathogenesis of periodontal diseases.
- Author
-
Shibata, K.
- Subjects
- *
CYTOKINES , *INTERLEUKIN-1 , *CARCINOGENESIS , *INFLAMMASOMES , *PERIODONTAL disease , *ANIMALS , *CHRONIC diseases , *MACROPHAGES , *MICE , *PERIODONTITIS , *PROTEINS , *PROTEOLYTIC enzymes , *GRAM-negative anaerobic bacteria - Abstract
The proinflammatory cytokine interleukin-1β (IL-1β) is produced as inactive proIL-1β and then processed by caspase-1 to become active. In 2002, it was demonstrated that the intracellular multiprotein complex known as the inflammasome functions as a molecular platform to trigger activation of caspase-1. Inflammasomes are known to function as intracellular sensors for a broad spectrum of various pathogen-associated and damage-associated molecular patterns. In 1985, it was demonstrated that Porphyromonas gingivalis, a representative bacterium causing chronic periodontitis, induces IL-1 production by murine peritoneal macrophages. Since then, many studies have suggested that IL-1, particularly IL-1β plays key roles in the pathogenesis of periodontal diseases. However, the term "inflammasome" was not used until the involvement of inflammasomes in periodontal disease was suggested in 2009. Several subsequent studies on the roles of the inflammasome in the pathogenesis of periodontal diseases have been published. Interestingly, two contradictory reports on the modulation of inflammasomes by P. gingivalis have been published. Some papers have described how P. gingivalis activates the inflammasome to produce IL-1β whereas some stated that P. gingivalis inhibits inflammasome activation to subvert immune responses. Several lines of evidence have suggested that the inflammasome activation is modulated by periodontopathic bacteria other than P. gingivalis. Hence, studies on the roles of inflammasomes in the pathogenesis of periodontal diseases began only 8 years ago and many pathological roles of inflammasomes remain to be clarified. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
48. <italic>Fragon</italic>: rapid high‐resolution structure determination from ideal protein fragments.
- Author
-
Jenkins, Huw T.
- Subjects
- *
PROTEINS , *MOLECULAR structure , *DENSITY - Abstract
Correctly positioning ideal protein fragments by molecular replacement presents an attractive method for obtaining preliminary phases when no template structure for molecular replacement is available. This has been exploited in several existing pipelines. This paper presents a new pipeline, named
Fragon , in which fragments (ideal α‐helices or β‐strands) are placed usingPhaser and the phases calculated from these coordinates are then improved by the density‐modification methods provided byACORN . The reliable scoring algorithm provided byACORN identifies success. In these cases, the resulting phases are usually of sufficient quality to enable automated model building of the entire structure.Fragon was evaluated against two test sets comprising mixed α/β folds and all‐β folds at resolutions between 1.0 and 1.7 Å. Success rates of 61% for the mixed α/β test set and 30% for the all‐β test set were achieved. In almost 70% of successful runs, fragment placement and density modification took less than 30 min on relatively modest four‐core desktop computers. In all successful runs the best set of phases enabled automated model building withARP /wARP to complete the structure. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
49. Synergy among phase-refinement techniques in macromolecular crystallography.
- Author
-
Burla, Maria Cristina, Cascarano, Giovanni Luca, Giacovazzo, Carmelo, and Polidori, Giampiero
- Subjects
- *
CRYSTALLOGRAPHY , *ELECTRON density , *CRYSTAL structure - Abstract
Ab initio and non- ab initio phasing methods are often unable to provide phases of sufficient quality to allow the molecular interpretation of the resulting electron-density maps. Phase extension and refinement is therefore a necessary step: its success or failure can make the difference between solution and nonsolution of the crystal structure. Today phase refinement is trusted to electron-density modification (EDM) techniques, and in practice to dual-space methods which try, via suitable constraints in direct and in reciprocal space, to generate higher quality electron-density maps. The most popular EDM approaches, denoted here as mainstream methods, are usually part of packages which assist crystallographers in all of the structure-solution steps from initial phasing to the point where the molecular model perfectly fits the known features of protein chemistry. Other phase-refinement approaches that are based on different sources of information, denoted here as out-of-mainstream methods, are not frequently employed. This paper aims to show that mainstream and out-of-mainstream methods may be combined and may lead to dramatic advances in the present state of the art. The statement is confirmed by experimental tests using molecular-replacement, SAD-MAD and ab initio techniques. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
50. Pattern mixture models for clinical validation of biomarkers in the presence of missing data.
- Author
-
Gao, Fei, Dong, Jun, Zeng, Donglin, Rong, Alan, and Ibrahim, Joseph G.
- Subjects
- *
ANTINEOPLASTIC agents , *ALGORITHMS , *BIOMETRY , *CLINICAL trials , *COLON tumors , *COMPUTER simulation , *PROTEINS , *REGRESSION analysis , *RESEARCH funding , *PROPORTIONAL hazards models ,RECTUM tumors - Abstract
Targeted therapies for cancers are sometimes only effective in a subset of patients with a particular biomarker status. In clinical development, the biomarker status is typically determined by an investigational-use-only/laboratory-developed test. A market ready test (MRT) is developed later to meet regulatory requirements and for future commercial use. In the USA, the clinical validation of MRT showing efficacy and safety profile of the targeted therapy in the biomarker subgroups determined by MRT is needed for pre-market approval. One of the major challenges in carrying out clinical validation is that the biomarker status per MRT is often missing for many subjects. In this paper, we treat biomarker status as a missing covariate and develop a novel pattern mixture model in the setting of a proportional hazards model for the time-to-event outcome variable. We specify a multinomial regression model for the missing biomarker statuses, and develop an expectation-maximization algorithm by the Method of Weights (Ibrahim, Journal of the American Statistical Association, 1990) to estimate the parameters in the regression model. We use Louis' formula (Louis, Journal of the Royal Statistical Society. Series B, 1982) to obtain standard errors estimates. We examine the performance of our method in extensive simulation studies and apply our method to a clinical trial in metastatic colorectal cancer. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.