| 1. |
- Martins, Leila R., et al.
(author)
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Stk33 is required for spermatid differentiation and male fertility in mice
- 2018
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In: Developmental Biology. - : Academic Press. - 0012-1606 .- 1095-564X. ; 433:1, s. 84-93
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Journal article (peer-reviewed)abstract
- Spermiogenesis is the final phase during sperm cell development in which round spermatids undergo dramatic morphological changes to generate spermatozoa. Here we report that the serine/threonine kinase Stk33 is essential for the differentiation of round spermatids into functional sperm cells and male fertility. Constitutive Stk33 deletion in mice results in severely malformed and immotile spermatozoa that are particularly characterized by disordered structural tail elements. Stk33 expression first appears in primary spermatocytes, and targeted deletion of Stk33 in these cells recapitulates the defects observed in constitutive knockout mice, confirming a germ cell-intrinsic function. Stk33 protein resides in the cytoplasm and partially co-localizes with the caudal end of the manchette, a transient structure that guides tail elongation, in elongating spermatids, and loss of Stk33 leads to the appearance of a tight, straight and elongated manchette. Together, these results identify Stk33 as an essential regulator of spermatid differentiation and male fertility.
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| 2. |
- Dejonghe, Wim, et al.
(author)
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Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane.
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| 3. |
- Elf, Stefan, et al.
(author)
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Applying user-behavior to bandwidth adaptations in collaborative workspace applications and video conferencing
- 2003
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Reports (other academic/artistic)abstract
- A bandwidth-sharing scheme for group video conferencing is presented in this paper. The key features of the scheme are the monitoring of user behavior and message passing, which are used by each client in order to identify and report their interest in other group members. Each video sender operates on the information about other users ' interest in order to adjust the sender's own frame rate, resolution, and ultimately bandwidth consumption in an attempt to satisfy the current interests of the receivers as well as the overall bandwidth constraints of the session. A general framework, an initial prototype, and a bandwidth allocation algorithm are presented together with experimental results. The experiences from the prototype have prompted refinements to the bandwidth-allocation algorithm that will be important for future implementations. We also conclude that the necessary messaging will not add a significant amount of bandwidth.
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| 4. |
- Elf, Stefan, et al.
(author)
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Schemes for user-interest controlled video bandwidth adaptation in a collaborative workspace environment
- 2004
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In: 2004 IEEE International Conference on Multimedia and Expo. - Piscataway, NJ : IEEE Communications Society. - 0780386035 ; , s. 197-200
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Conference paper (peer-reviewed)abstract
- In this paper, bandwidth-sharing schemes, controlled by user-interest, are presented as an approach to efficient use of resources in a collaborative workspace environment. Two schemes for group videoconferencing are presented and evaluated. Monitoring of user-behavior and message passing to adapt video bandwidth allocation to user needs are key features of both schemes, in which each user's client reports interest in other users to enable them to determine their relative importance. Experimental results using a prototype implementation to sample user-behavior show that one scheme is better suited for high, and the other for low bandwidth-limit scenarios. Measurements also show that the message passing does not add a substantial amount of bandwidth.
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| 5. |
- Scholl, Jeremiah, et al.
(author)
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Efficient workspaces through semantic reliability
- 2003
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In: 10th International Conference on Telecommunications. - Piscataway, NJ : IEEE Communications Society. - 0780376617 ; , s. 1099-1104
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Conference paper (peer-reviewed)abstract
- Transport level protocols typically provide “best-effort” data delivery where no attempts are made to recover lost packets, or “reliable” data delivery where techniques are used to ensure that all data sent out eventually reaches the receiver(s). However, it has been suggested that some applications will perform better when using dynamically configurable reliability based on application level semantics. A general framework has been created with the intent of delivering this type of semantic reliability to a wide variety of applications, but to date little research has been done to demonstrate how any applications can benefit from the use of such a framework. This paper addresses this problem in that it discusses semantic reliability in the context of collaborative workspaces.
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| 6. |
- Scholl, Jeremiah, et al.
(author)
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User-interest driven video adaptation for collaborative workspace applications
- 2003
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In: Group Communications and Charges. - Berlin : Encyclopedia of Global Archaeology/Springer Verlag. - 9783540200512 ; , s. 3-12
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Conference paper (peer-reviewed)abstract
- This paper presents a bandwidth sharing scheme for group video conferencing. The key features of the scheme are the monitoring of implicit user-hints and message passing, which are used by each client in order to identify and report their interest in other group members. Information about user interest is then used by each video sender in order to adjust their frame-rate, resolution, and ultimately bandwidth consumption in an attempt to satisfy the current interests of the receivers. A general framework and initial prototype are presented together with experimental results.
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| 7. |
- Schöpf, Julia, et al.
(author)
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Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions
- 2024
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In: Nature Communications. - 2041-1723. ; 15, s. 1-17
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Journal article (peer-reviewed)abstract
- Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a rationale for PRMT5-targeted therapies. Functional studies show that FUS-TFCP2 blocks myogenic differentiation, induces transcription of ALK and truncated TERT, and inhibits DNA repair. Unlike other fusion-driven sarcomas, TFCP2-rearranged tumors exhibit genomic instability and signs of defective homologous recombination. DNA methylation profiling demonstrates a close relationship with undifferentiated sarcomas. In two patients, sarcoma was preceded by benign lesions carrying FUS-TFCP2, indicating stepwise sarcomagenesis. This study illustrates the potential of linking precision oncology with preclinical research to gain insight into the classification, pathogenesis, and therapeutic vulnerabilities of rare cancers.
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| 8. |
- Trautmann, Marcel, et al.
(author)
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Requirement for YAP1 signaling in myxoid liposarcoma.
- 2019
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In: EMBO molecular medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 11:5
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Journal article (peer-reviewed)abstract
- Myxoid liposarcomas (MLS), malignant tumors of adipocyte origin, are driven by the FUS-DDIT3 fusion gene encoding an aberrant transcription factor. The mechanisms whereby FUS-DDIT3 mediates sarcomagenesis are incompletely understood, and strategies to selectively target MLS cells remain elusive. Here we show, using an unbiased functional genomic approach, that FUS-DDIT3-expressing mesenchymal stem cells and MLS cell lines are dependent on YAP1, a transcriptional co-activator and central effector of the Hippo pathway involved in tissue growth and tumorigenesis, and that increased YAP1 activity is a hallmark of human MLS Mechanistically, FUS-DDIT3 promotes YAP1 expression, nuclear localization, and transcriptional activity and physically associates with YAP1 in the nucleus of MLS cells. Pharmacologic inhibition of YAP1 activity impairs the growth of MLS cells invitro and invivo These findings identify overactive YAP1 signaling as unifying feature of MLS development that could represent a novel target for therapeutic intervention.
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