effective-unsupervised-constrained-text-generation-using-perturbed-masking

効果的な教師なし制約付きテキスト生成-擾乱マスキングに基づく手法

효과적인-무감독-제약-텍스트-생성을-위한-교란-마스킹-기반-접근법

improving-out-of-distribution-detection-in-lidar-based-3d-object-detection

lidar搭載3d物体検出におけるアウトオブディストリビューション検出の再検討

lidar-기반-3d-객체-탐지에서-분포-외-객체-탐지-재검토

evaluating-the-feasibility-of-latency-attacks-against-black-box-object-detection-models

物体検出に対するブラックボックス型の敵対的攻撃に対する頑健性の評価-後から攻撃する前に盗む


Ribbon precursors in inner hair cells utilize the polarized microtubule cytoskeleton and the anterograde motor Kif1a for targeted trafficking and structural plasticity to enable proper ribbon synapse assembly and maturation.


coremsg

Sensory synapses are characterized by electron-dense presynaptic specializations, so-called synaptic ribbons. In cochlear inner hair cells (IHCs), ribbons play an essential role as core active zone (AZ) organizers, where they tether synaptic vesicles, cluster calcium channels and facilitate the temporally-precise release of primed vesicles. While a multitude of studies aimed to elucidate the molecular composition and function of IHC ribbon synapses, the developmental formation of these signalling complexes remains largely elusive to date. To address this shortcoming, we performed long-term live-cell imaging of fluorescently-labelled ribbon precursors in young postnatal IHCs to track ribbon precursor motion. We show that ribbon precursors utilize the apico-basal microtubular (MT) cytoskeleton for targeted trafficking to the presynapse, in a process reminiscent of slow axonal transport in neurons. During translocation, precursor volume regulation is achieved by highly dynamic structural plasticity – characterized by regularly-occurring fusion and fission events. Pharmacological MT destabilization negatively impacted on precursor translocation and attenuated structural plasticity, whereas genetic disruption of the anterograde molecular motor Kif1a impaired ribbon volume accumulation during developmental maturation. Combined, our data thus indicate an essential role of the MT cytoskeleton and Kif1a in adequate ribbon synapse formation and structural maintenance.

### Competing Interest Statement

The authors have declared no competing interest.

Slow kinesin-dependent microtubular transport facilitates ribbon synapse assembly in developing cochlear inner hair cells

targeted-microtubule-based-transport-facilitates-ribbon-synapse-assembly-in-developing-cochlear-inner-hair-cells


Targeted Microtubule-Based Transport Facilitates Ribbon Synapse Assembly in Developing Cochlear Inner Hair Cells


title_rewrite


Phosphorylation of the C-terminal serine residues of the α-arrestin Aly3 by the TORC2 pathway inhibits Aly3-mediated ubiquitination and vacuolar transport of the glucose transporter Ght5, thereby ensuring cell-surface localization of Ght5 and enabling cell proliferation under low glucose conditions in fission yeast.


In fission yeast, Schizosaccharomyces pombe , transcriptional upregulation and cell-surface localization of the hexose transporter, Ght5, are required for cell proliferation in low glucose. As the target of rapamycin complex 2 (TORC2) signaling pathway inhibits α-arrestin Aly3-dependent endocytosis of Ght5, we hypothesized that this endocytosis was inhibited by phosphorylation. To identify phosphorylation sites required for cell proliferation in low glucose, serine and threonine residues of Aly3 and Ght5 reportedly phosphorylated were replaced with alanine. We found that C-terminal serine residues of Aly3, but not Ght5, are necessary for proliferation in low glucose. Expression of Aly3 protein unphosphorylated at the C-terminus led to increased ubiquitination and vacuolar accumulation of Ght5 in low glucose, but reversion of one of the alanine residues to serine reduced ubiquitination and vacuolar accumulation of Ght5. Also, Aly3 physically interacted with the HECT-type ubiquitin ligases Pub1 and Pub3, and these interactions were required for surface localization of Ght5 and proliferation in low glucose. This study reveals mechanisms by which Aly3 is regulated so that fission yeast can adapt to nutritional stress.

### Competing Interest Statement

The authors have declared no competing interest.

Phosphorylation of Aly3 C-terminus impedes aberrant endocytosis of S. pombe hexose transporter Ght5

phosphorylation-of-the-c-terminus-of-the-α-arrestin-aly3-regulates-glucose-transporter-ght5-localization-and-cell-proliferation-in-fission-yeast-under-low-glucose-conditions


Phosphorylation of the C-terminus of the α-Arrestin Aly3 Regulates Glucose Transporter Ght5 Localization and Cell Proliferation in Fission Yeast under Low Glucose Conditions



ATG14 is critical for maintaining the structural integrity and cellular plasticity of the oviduct, preventing unscheduled pyroptosis activation, and enabling the timely transport of embryos from the oviduct to the uterus for successful implantation.


Recurrent pregnancy loss (RPL), characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, the precise cellular mechanisms that maintain the structural and functional integrity of the oviduct are not studied yet. Here, we report that autophagy is critical for maintaining the oviduct homeostasis and keeping the inflammation under check to enable embryo transport. Specifically, the loss of the autophagy-related gene, Atg14 in the oviduct causes severe structural abnormalities compromising its cellular plasticity and integrity leading to the retention of embryos. Interestingly, the selective loss of Atg14 in oviduct ciliary epithelial cells did not impact female fertility, highlighting the specificity of ATG14 function in distinct cell types within the oviduct. Mechanistically, loss of Atg14 triggered unscheduled pyroptosis leading to inappropriate embryo retention and impeded embryo transport in the oviduct. Finally, pharmacological activation of pyroptosis in pregnant mice led to an impairment in embryo transport. Together, we found that ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport from the oviduct to uterus for the successful implantation. Of clinical significance, these findings provide possible insights on the underlying mechanism(s) of early pregnancy loss and might aid in developing novel prevention strategies using autophagy modulators.

### Competing Interest Statement

The authors have declared no competing interest.

*   WT
    :   Wild Type
    HESCs
    :   Human Endometrial stromal cells
    dpc
    :   Days post coitum
    E2
    :   Estrogen
    P4
    :   Progesterone
    cKO
    :   conditional knockout

The autophagy protein, ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy

autophagy-protein-atg14-safeguards-oviduct-function-to-enable-embryo-transport-during-early-pregnancy


Autophagy Protein ATG14 Safeguards Oviduct Function to Enable Embryo Transport During Early Pregnancy



Microtubules organize the pericentrosomal nest from which procentrioles emerge, retain deuterosomes in a focused area, promote their maturation, and assist in the collective migration of centrioles to the apical membrane during multiciliated cell differentiation.


Centriole number must be restricted to two in cycling cells to avoid pathological cell divisions. Multiciliated cells (MCC), however, need to produce a hundred or more centrioles to nucleate the same number of motile cilia required for fluid flow circulation. These centrioles are produced by highjacking cell cycle and centriole duplication programs. However, how the MCC progenitor handles such a massive number of centrioles to finally organize them in an apical basal body patch is unclear. Here, using new cellular models and high-resolution imaging techniques, we identify the microtubule network as the bandleader, and show how it orchestrates the process in space and in time. Organized by the pre-existing centrosome at the start of amplification, microtubules build a nest of centriolar components from which procentrioles emerge. When amplification is over, the centrosome’s dominance is lost as new centrioles mature and become microtubule nucleators. Microtubules then drag all the centrioles to the nuclear membrane, assist their isotropic perinuclear disengagement and their subsequent collective apical migration. These results reveal that in brain MCC as in cycling cells, the same dynamics - from the centrosome to the cell pole via the nucleus-exists, is the result of a reflexive link between microtubules and the progressive maturation of new centrioles, and participates in the organized reshaping of the entire cytoplasm. On the other hand, new elements described in this work such as microtubule-driven organization of a nest, identification of a spatio-temporal progression of centriole growth and microtubule-assisted disengagement, may shed new light on the centriole duplication program.

![Figure][1]</img>

### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

Microtubule-dependent orchestration of centriole amplification in brain multiciliated cells

microtubule-dependent-orchestration-of-centriole-amplification-in-brain-multiciliated-cells


Microtubule-Dependent Orchestration of Centriole Amplification in Brain Multiciliated Cells



USP8 is recruited to Rab5-positive early endosomes through its interaction with the Rab5 guanine nucleotide exchange factor Rabex5, and this recruitment dissociates Rabex5 from endosomes while promoting the recruitment of the Rab7 guanine nucleotide exchange factor SAND-1/Mon1, thereby facilitating the transition from Rab5-positive early endosomes to Rab7-positive late endosomes and lysosomes.


The spatiotemporal transition of small GTPase Rab5 to Rab7 is crucial for early-to-late endosome maturation, yet the precise mechanism governing Rab5-to-Rab7 switching remains elusive. USP8, a ubiquitin-specific protease, plays a prominent role in the endosomal sorting of a wide range of transmembrane receptors and is a promising target in cancer therapy. Here, we identified that USP8 is recruited to Rab5-positive carriers by Rabex5, a guanine nucleotide exchange factor (GEF) for Rab5. The recruitment of USP8 dissociates Rabex5 from early endosomes (EEs) and meanwhile promotes the recruitment of the Rab7 GEF SAND-1/Mon1. In USP8-deficient cells, the level of active Rab5 is increased, while the Rab7 signal is decreased. As a result, enlarged EEs with abundant intraluminal vesicles (ILVs) accumulate and digestive lysosomes are rudimentary. Together, our results reveal an important and unexpected role of a deubiquitinating enzyme in endosome maturation.

### Competing Interest Statement

The authors have declared no competing interest.

Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturation

ubiquitin-specific-protease-usp8-regulates-endosome-maturation-by-coordinating-rab5-and-rab7-gtpase-activation


Ubiquitin-Specific Protease USP8 Regulates Endosome Maturation by Coordinating Rab5 and Rab7 GTPase Activation



Disruption of ESCRT machinery leads to accumulation of exosome cargoes within presynaptic terminals, without depleting their signaling activities, suggesting synaptic exosomes primarily serve proteostatic functions rather than intercellular signaling.


Exosomes are membrane-bound vesicles released by many cells including neurons, carrying cargoes involved in signaling and disease. It has been unclear whether exosomes promote intercellular signaling in vivo or serve primarily to dispose of unwanted cargo. This is because manipulations of exosome cargo expression or traffic often result in their depletion from the donor cell, making it difficult to distinguish whether these cargoes act cell-autonomously or through transcellular transfer. Exosomes arise when multivesicular endosomes fuse with the plasma membrane, releasing their intralumenal vesicles outside the cell. We show that loss of multivesicular endosome-generating ESCRT (endosomal sorting complex required for transport) machinery disrupts release of exosome cargoes from Drosophila motor neurons, without depleting them from the donor presynaptic terminal. Cargoes and autophagic vacuoles accumulate in presynaptic terminals, suggesting that compensatory autophagy follows endosome dysfunction. Surprisingly, exosome cargoes Synaptotagmin-4 (Syt4) and Evenness Interrupted (Evi) retain many of their signaling activities upon ESCRT depletion, despite being trapped in presynaptic terminals. Thus, these cargoes may not require intercellular transfer, and instead are likely to function cell autonomously in the motor neuron. Our results indicate that synaptic exosome release depends on ESCRT, and serves primarily as a proteostatic mechanism for at least some cargoes.

### Competing Interest Statement

The authors have declared no competing interest.

ESCRT disruption provides evidence against signaling functions for synaptic exosomes

escrt-disruption-reveals-synaptic-exosomes-primarily-serve-proteostatic-functions-not-intercellular-signaling


ESCRT Disruption Reveals Synaptic Exosomes Primarily Serve Proteostatic Functions, Not Intercellular Signaling



The actomyosin system, consisting of actin and the class I myosin TbMyo1, is essential for maintaining the complex three-dimensional architecture of the endosomal system in bloodstream form Trypanosoma brucei.


The actin cytoskeleton is a ubiquitous feature of eukaryotic cells, yet its complexity varies across different taxa. In the parasitic protist Trypanosoma brucei , a rudimentary actomyosin system consisting of one actin gene and two myosin genes has been retained despite significant investment in the microtubule cytoskeleton. The functions of this highly simplified actomyosin system remain unclear, but appear to centre on the endomembrane system. Here, advanced light and electron microscopy imaging techniques together with biochemical and biophysical assays were used to explore the relationship between the actomyosin and endomembrane systems. The class I myosin (TbMyo1) had a large cytosolic pool and its ability to translocate actin filaments in vitro was shown here for the first time. TbMyo1 exhibited strong association with the endosomal system and was additionally found on glycosomes. At the endosomal membranes, TbMyo1 colocalised with markers for early and late endosomes (TbRab5A and TbRab7, respectively), but not with the marker associated with recycling endosomes (TbRab11). Actin and myosin were simultaneously visualised for the first time in trypanosomes using an anti-actin chromobody. Disruption of the actomyosin system using the actin-depolymerising drug latrunculin A resulted in a delocalisation of both the actin chromobody signal and an endosomal marker, and was accompanied by a specific loss of endosomal structure. This suggests that the actomyosin system is required for maintaining endosomal integrity in T. brucei .

### Competing Interest Statement

The authors have declared no competing interest.

The actomyosin system is essential for the integrity of the endosomal system in bloodstream form Trypanosoma brucei

the-actomyosin-system-is-essential-for-maintaining-the-complex-endosomal-architecture-in-bloodstream-form-trypanosoma-brucei


The Actomyosin System is Essential for Maintaining the Complex Endosomal Architecture in Bloodstream Form Trypanosoma brucei
