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Article: Role of von Willebrand Factor in COVID-19 Associated Coagulopathy.

Mei, Zhen W / van Wijk, Xander M R / Pham, Huy P / Marin, Maximo J

The journal of applied laboratory medicine

2021 Volume 6, Issue 5, Page(s) 1305–1315

Abstract: Background: COVID-19, the disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) can present with symptoms ranging from none to severe. Thrombotic events occur in a significant number of patients with COVID-19, especially in ... ...

Abstract	Background: COVID-19, the disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) can present with symptoms ranging from none to severe. Thrombotic events occur in a significant number of patients with COVID-19, especially in critically ill patients. This apparent novel form of coagulopathy is termed COVID-19-associated coagulopathy (CAC), and endothelial derived von Willebrand factor (vWF) may play an important role in its pathogenesis. Content: vWF is a multimeric glycoprotein molecule that is involved in inflammation, primary and secondary hemostasis. Studies have shown that patients with COVID-19 have significantly elevated levels of vWF antigen and activity, likely contributing to an increased risk of thrombosis seen in CAC. The high levels of both vWF antigen and activity have been clinically correlated with worse outcomes. Furthermore, the severity of a COVID-19 infection appears to reduce molecules that regulate vWF level and activity such as ADAMTS-13 and high-density lipoproteins (HDL). Finally, studies have suggested that patients with group O blood (a blood group with lower baseline levels of vWF) have a lower risk of infection and disease severity compared to other ABO blood groups; however, more studies are needed to elucidate the role of vWF. Summary: CAC is a significant contributor to morbidity and mortality. Endothelial dysfunction with the release of prothrombotic factors, such as vWF, needs further examination as a possible important component in the pathogenesis of CAC.
MeSH term(s)	COVID-19 ; Humans ; SARS-CoV-2 ; Severity of Illness Index ; Thrombosis ; von Willebrand Factor
Chemical Substances	von Willebrand Factor
Language	English
Publishing date	2021-04-30
Publishing country	England
Document type	Journal Article
ISSN	2576-9456
ISSN	2576-9456
DOI	10.1093/jalm/jfab042
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Article ; Online: APOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis.

Long, Xiaoran / Lu, Huaiwu / Cai, Mei-Chun / Zang, Jingyu / Zhang, Zhuqing / Wu, Jie / Liu, Xiaoshi / Cheng, Lin / Cheng, Jiejun / Cheung, Lydia W T / Shen, Zhen / Zhou, Ying / Di, Wen / Zhuang, Guanglei / Yin, Xia

British journal of cancer

2023 Volume 128, Issue 11, Page(s) 2054–2062

Abstract: Background: Ovarian clear cell carcinoma (OCCC) is a challenging disease due to its intrinsic chemoresistance. Immunotherapy is an emerging treatment option but currently impeded by insufficient understanding of OCCC immunophenotypes and their molecular ...

Abstract	Background: Ovarian clear cell carcinoma (OCCC) is a challenging disease due to its intrinsic chemoresistance. Immunotherapy is an emerging treatment option but currently impeded by insufficient understanding of OCCC immunophenotypes and their molecular determinants. Methods: Whole-genome sequencing on 23 pathologically confirmed patients was employed to depict the genomic profile of primary OCCCs. APOBEC3B expression and digital pathology-based Immunoscore were assessed by performing immunohistochemistry and correlated with clinical outcomes. Results: An APOBEC-positive (APOBEC+) subtype was identified based on the characteristic mutational signature and prevalent kataegis events. APOBEC + OCCC displayed favourable prognosis across one internal and two external patient cohorts. The improved outcome was ascribable to increased lymphocytic infiltration. Similar phenomena of APOBEC3B expression and T-cell accumulation were observed in endometriotic tissues, suggesting that APOBEC-induced mutagenesis and immunogenicity could occur early during OCCC pathogenesis. Corroborating these results, a case report was presented for an APOBEC + patient demonstrating inflamed tumour microenvironment and clinical response to immune checkpoint blockade. Conclusions: Our findings implicate APOBEC3B as a novel mechanism of OCCC stratification with prognostic value and as a potential predictive biomarker that may inform immunotherapeutic opportunities.
MeSH term(s)	Female ; Humans ; Ovarian Neoplasms/genetics ; Prognosis ; Mutation ; T-Lymphocytes/pathology ; Carcinoma ; Adenocarcinoma, Clear Cell/genetics ; Tumor Microenvironment ; Cytidine Deaminase ; Minor Histocompatibility Antigens
Chemical Substances	APOBEC3B protein, human (EC 3.5.4.5) ; Cytidine Deaminase (EC 3.5.4.5) ; Minor Histocompatibility Antigens
Language	English
Publishing date	2023-03-30
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02239-5
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Article ; Online: mEMbrain: an interactive deep learning MATLAB tool for connectomic segmentation on commodity desktops.

Pavarino, Elisa C / Yang, Emma / Dhanyasi, Nagaraju / Wang, Mona D / Bidel, Flavie / Lu, Xiaotang / Yang, Fuming / Francisco Park, Core / Bangalore Renuka, Mukesh / Drescher, Brandon / Samuel, Aravinthan D T / Hochner, Binyamin / Katz, Paul S / Zhen, Mei / Lichtman, Jeff W / Meirovitch, Yaron

Frontiers in neural circuits

2023 Volume 17, Page(s) 952921

Abstract: Connectomics is fundamental in propelling our understanding of the nervous system's organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited from ...

Abstract	Connectomics is fundamental in propelling our understanding of the nervous system's organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited from ever more precise automatic segmentation methods, which leverage sophisticated deep learning architectures and advanced machine learning algorithms. On the other hand, the field of neuroscience at large, and of image processing in particular, has manifested a need for user-friendly and open source tools which enable the community to carry out advanced analyses. In line with this second vein, here we propose mEMbrain, an interactive MATLAB-based software which wraps algorithms and functions that enable labeling and segmentation of electron microscopy datasets in a user-friendly user interface compatible with Linux and Windows. Through its integration as an API to the volume annotation and segmentation tool VAST, mEMbrain encompasses functions for ground truth generation, image preprocessing, training of deep neural networks, and on-the-fly predictions for proofreading and evaluation. The final goals of our tool are to expedite manual labeling efforts and to harness MATLAB users with an array of semi-automatic approaches for instance segmentation. We tested our tool on a variety of datasets that span different species at various scales, regions of the nervous system and developmental stages. To further expedite research in connectomics, we provide an EM resource of ground truth annotation from four different animals and five datasets, amounting to around 180 h of expert annotations, yielding more than 1.2 GB of annotated EM images. In addition, we provide a set of four pre-trained networks for said datasets. All tools are available from https://lichtman.rc.fas.harvard.edu/mEMbrain/. With our software, our hope is to provide a solution for lab-based neural reconstructions which does not require coding by the user, thus paving the way to affordable connectomics.
MeSH term(s)	Animals ; Connectome/methods ; Deep Learning ; Image Processing, Computer-Assisted/methods ; Software ; Algorithms
Language	English
Publishing date	2023-06-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2452968-0
ISSN	1662-5110 ; 1662-5110
ISSN (online)	1662-5110
ISSN	1662-5110
DOI	10.3389/fncir.2023.952921
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Article: mEMbrain: an interactive deep learning MATLAB tool for connectomic segmentation on commodity desktops.

Pavarino, Elisa C / Yang, Emma / Dhanyasi, Nagaraju / Wang, Mona / Bidel, Flavie / Lu, Xiaotang / Yang, Fuming / Park, Core Francisco / Renuka, Mukesh Bangalore / Drescher, Brandon / Samuel, Aravinthan D T / Hochner, Binyamin / Katz, Paul S / Zhen, Mei / Lichtman, Jeff W / Meirovitch, Yaron

bioRxiv : the preprint server for biology

2023

Abstract: Connectomics is fundamental in propelling our understanding of the nervous systemâ€™s organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited ... ...

Abstract	Connectomics is fundamental in propelling our understanding of the nervous systemâ€™s organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited from ever more precise automatic segmentation methods, which leverage sophisticated deep learning architectures and advanced machine learning algorithms. On the other hand, the field of neuroscience at large, and of image processing in particular, has manifested a need for user-friendly and open source tools which enable the community to carry out advanced analyses. In line with this second vein, here we propose mEMbrain, an interactive MATLAB-based software which wraps algorithms and functions that enable labeling and segmentation of electron microscopy datasets in a user-friendly user interface compatible with Linux and Windows. Through its integration as an API to the volume annotation and segmentation tool VAST, mEMbrain encompasses functions for ground truth generation, image preprocessing, training of deep neural networks, and on-the-fly predictions for proofreading and evaluation. The final goals of our tool are to expedite manual labeling efforts and to harness MATLAB users with an array of semi-automatic approaches for instance segmentation. We tested our tool on a variety of datasets that span different species at various scales, regions of the nervous system and developmental stages. To further expedite research in connectomics, we provide an EM resource of ground truth annotation from 4 different animals and 5 datasets, amounting to around 180 hours of expert annotations, yielding more than 1.2 GB of annotated EM images. In addition, we provide a set of 4 pre-trained networks for said datasets. All tools are available from https://lichtman.rc.fas.harvard.edu/mEMbrain/ . With our software, our hope is to provide a solution for lab-based neural reconstructions which does not require coding by the user, thus paving the way to affordable connectomics.
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.17.537196
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Article ; Online: Retraction Note: Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells.

Martinez, Jennifer / Cunha, Larissa D / Park, Sunmin / Yang, Mao / Lu, Qun / Orchard, Robert / Li, Quan-Zhen / Yan, Mei / Janke, Laura / Guy, Cliff / Linkermann, Andreas / Virgin, Herbert W / Green, Douglas R

Nature

2022 Volume 609, Issue 7927, Page(s) 640

Language	English
Publishing date	2022-08-31
Publishing country	England
Document type	Retraction of Publication
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-05201-2
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Article ; Online: Post-embryonic remodeling of the C. elegans motor circuit.

Mulcahy, Ben / Witvliet, Daniel K / Mitchell, James / Schalek, Richard / Berger, Daniel R / Wu, Yuelong / Holmyard, Doug / Lu, Yangning / Ahamed, Tosif / Samuel, Aravinthan D T / Chisholm, Andrew D / Lichtman, Jeff W / Zhen, Mei

Current biology : CB

2022 Volume 32, Issue 21, Page(s) 4645–4659.e3

Abstract: During development, animals can maintain behavioral output even as underlying circuitry structurally remodels. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse rewiring while the animal continuously moves with an ... ...

Abstract	During development, animals can maintain behavioral output even as underlying circuitry structurally remodels. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse rewiring while the animal continuously moves with an undulatory pattern. To understand how the circuit transitions from its juvenile to mature configuration without interrupting functional output, we reconstructed the C. elegans motor circuit by electron microscopy across larval development. We observed the following: First, embryonic motor neurons transiently interact with the developing post-embryonic motor neurons prior to remodeling of their juvenile wiring. Second, post-embryonic neurons initiate synapse development with their future partners as their neurites navigate through the juvenile nerve cords. Third, embryonic and post-embryonic neurons sequentially build structural machinery needed for the adult circuit before the embryonic neurons relinquish their roles to post-embryonic neurons. Fourth, this transition is repeated region by region along the body in an anterior-to-posterior sequence, following the birth order of neurons. Through this orchestrated and programmed rewiring, the motor circuit gradually transforms from asymmetric to symmetric wiring. These maturation strategies support the continuous maintenance of motor patterns as the juvenile circuit develops into the adult configuration.
MeSH term(s)	Animals ; Caenorhabditis elegans/physiology ; Motor Neurons/physiology ; Synapses/physiology ; Neurites ; Caenorhabditis elegans Proteins/genetics
Chemical Substances	Caenorhabditis elegans Proteins
Language	English
Publishing date	2022-10-24
Publishing country	England
Document type	Journal Article
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2022.09.065
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Article ; Online: Test Strategy Optimization Based on Soft Sensing and Ensemble Belief Measurement.

Mei, Wenjuan / Liu, Zhen / Tang, Lei / Su, Yuanzhang

Sensors (Basel, Switzerland)

2022 Volume 22, Issue 6

Abstract: Resulting from the short production cycle and rapid design technology development, traditional prognostic and health management (PHM) approaches become impractical and fail to match the requirement of systems with structural and functional complexity. ... ...

Abstract	Resulting from the short production cycle and rapid design technology development, traditional prognostic and health management (PHM) approaches become impractical and fail to match the requirement of systems with structural and functional complexity. Among all PHM designs, testability design and maintainability design face critical difficulties. First, testability design requires much labor and knowledge preparation, and wastes the sensor recording information. Second, maintainability design suffers bad influences by improper testability design. We proposed a test strategy optimization based on soft-sensing and ensemble belief measurements to overcome these problems. Instead of serial PHM design, the proposed method constructs a closed loop between testability and maintenance to generate an adaptive fault diagnostic tree with soft-sensor nodes. The diagnostic tree generated ensures high efficiency and flexibility, taking advantage of extreme learning machine (ELM) and affinity propagation (AP). The experiment results show that our method receives the highest performance with state-of-art methods. Additionally, the proposed method enlarges the diagnostic flexibility and saves much human labor on testability design.
MeSH term(s)	Humans ; Learning ; Machine Learning ; Prognosis
Language	English
Publishing date	2022-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s22062138
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Article ; Online: Callose wall and sporoderm characteristics during the anther development stage of Dendrobium officinale

Deng, Wei / Lin, Mei Zhen / Tian, Hui Qiao

Flora. 2023 Apr. 13, p.152278-

2023 , Page(s) 152278–

Abstract: The pollen developmental characteristics in plants with pollinia remain unknown. In this study, Dendrobium officinale (Orchidaceae) pollinium development was investigated on the basis of a histochemical examination of polysaccharides and lipids. The D. ... ...

Abstract	The pollen developmental characteristics in plants with pollinia remain unknown. In this study, Dendrobium officinale (Orchidaceae) pollinium development was investigated on the basis of a histochemical examination of polysaccharides and lipids. The D. officinale anther wall is composed of one layer of epidermal cells, two layers of endothecial cells, one layer of middle layer cells, and one layer of tapetal cells. The microspore mother cells, which have no obvious callose wall structure before meiosis, undergo simultaneous microsporogenesis. After meiosis, four microspores in a tetrad do not separate and subsequently develop as pollen tetrads, which ultimately form two pollinia. During microspore development, sporopollenin covers the pollinium surface and forms the exine of the pollinium, but the pollen tetrads inside the pollinium lack the exine structure. A pollen germinal pore was not detected in the pollinium exine. An in vitro analysis of pollen germination revealed that pollen grains at the surface of pollinia covered with an exine layer do not germinate. Furthermore, pollen tubes are mainly produced by the pollen grains inside the pollinium.
Keywords	Dendrobium officinale ; callose ; exine ; flora ; meiosis ; microsporogenesis ; pollen germination ; pollen tetrad ; pollinia (pollen) ; sporopollenin ; Lipids ; Pollen development ; Pollinium ; Polysaccharides
Language	English
Dates of publication	2023-0413
Publishing place	Elsevier GmbH
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	5580-3
ISSN	0367-2530 ; 0373-6490
ISSN	0367-2530 ; 0373-6490
DOI	10.1016/j.flora.2023.152278
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A protocol for high-throughput screening of histone lysine demethylase 4 inhibitors using TR-FRET assay.

Wu, Qiong / Lin, Wenwei / Li, Zhen-Mei / Rankovic, Zoran / White, Stephen W / Chen, Taosheng / Yang, Jun

STAR protocols

2021 Volume 2, Issue 3, Page(s) 100702

Abstract: Identification of diverse chemotypes of selective KDM4 inhibitors is important for exploring and validating the roles of KDM4s in the pathogenesis of human disease and for developing therapies. Here, we report a protocol for high-throughput screening of ... ...

Abstract	Identification of diverse chemotypes of selective KDM4 inhibitors is important for exploring and validating the roles of KDM4s in the pathogenesis of human disease and for developing therapies. Here, we report a protocol for high-throughput screening of KDM4 inhibitors using TR-FRET demethylation functional assay. We describe this protocol for screen of KDM4B inhibitors, which can be modified to screen inhibitors of other JmjC-domain-containing KDMs. For complete details on the use and execution of this protocol, please refer to Singh et al. (2021).
MeSH term(s)	Drug Evaluation, Preclinical/methods ; Fluorescence Resonance Energy Transfer/methods ; High-Throughput Screening Assays/methods ; Histone Demethylases/antagonists & inhibitors ; Histones/metabolism ; Humans ; Jumonji Domain-Containing Histone Demethylases/antagonists & inhibitors ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Lysine ; Substrate Specificity
Chemical Substances	Histones ; Histone Demethylases (EC 1.14.11.-) ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; KDM4B protein, human (EC 1.14.11.-) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2021-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2021.100702
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Article ; Online: A protocol for high-throughput screening of histone lysine demethylase 4 inhibitors using TR-FRET assay

Qiong Wu / Wenwei Lin / Zhen-Mei Li / Zoran Rankovic / Stephen W. White / Taosheng Chen / Jun Yang

STAR Protocols, Vol 2, Iss 3, Pp 100702- (2021)

2021

Abstract: Summary: Identification of diverse chemotypes of selective KDM4 inhibitors is important for exploring and validating the roles of KDM4s in the pathogenesis of human disease and for developing therapies. Here, we report a protocol for high-throughput ... ...

Abstract	Summary: Identification of diverse chemotypes of selective KDM4 inhibitors is important for exploring and validating the roles of KDM4s in the pathogenesis of human disease and for developing therapies. Here, we report a protocol for high-throughput screening of KDM4 inhibitors using TR-FRET demethylation functional assay. We describe this protocol for screen of KDM4B inhibitors, which can be modified to screen inhibitors of other JmjC-domain-containing KDMs.For complete details on the use and execution of this protocol, please refer to Singh et al. (2021).
Keywords	Cancer ; High Throughput Screening ; Molecular/Chemical Probes ; Protein Biochemistry ; Protein expression and purification ; Structural Biology ; Science (General) ; Q1-390
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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