The connectivity amongst photoreceptors is critical to their function, as it underpins lateral inhibition and effective translation of stimuli into neural signals. Despite much work characterizing ...second‐order interneurons in the outer retina, the synapses directly connecting photoreceptors have often been overlooked. Telodendria are fine processes that connect photoreceptor pedicles. They have been observed in diverse vertebrate groups, yet their roles in vision remain speculative. Here, we visualize telodendria via fluorescent protein expression in photoreceptor subtypes. We characterized short wavelength cone telodendria in adult and larval zebrafish retina. Additionally, in the larval retina, we investigated rod telodendria and UV cone telodendria in mutant and transgenic retinas with altered complements of cone types. In the adult retina, telodendria are twice as abundant and branch almost twice as often on blue cones compared to UV cones. Pedicles of neighboring UV and blue cones typically converge into contiguous pairs, despite the regular spacing of their cell bodies. In contrast to adults, larval UV cone telodendria are more numerous (1.3 times) than blue cone telodendria. UV cone telodendria are not detectably affected by ablation of blue cones, and are reduced twofold in mutant larval retina with few UV cones. We thus saw no evidence that telodendria increase in number in the absence of their typical cellular neighbors. We also found that larval rod telodendria are less abundant than short wavelength cone telodendria. In summary, we describe the development and morphology of zebrafish photoreceptor synaptic connectivity toward appreciating the function of telodendria in visual signal processing.
Telodendria and their connectivity patterns were characterized in the zebrafish retina. Telodendria are fine projections connecting adjacent photoreceptor pedicles. Telodendria are enigmatic in their function, and detailing their morphology within the crystalline zebrafish cone mosaic lays groundwork for appreciating their role in signal processing at the visual system's first synapse.
Alternative lengthening of telomeres (ALT) is a telomerase-independent but recombination-dependent pathway that maintains telomeres. Here, we describe an assay to visualize ALT-mediated telomeric DNA ...synthesis in ALT-associated PML bodies (APBs) without DNA-damaging agents or replication inhibitors. Using this assay, we find that ALT occurs through two distinct mechanisms. One of the ALT mechanisms requires RAD52, a protein implicated in break-induced DNA replication (BIR). We demonstrate that RAD52 directly promotes telomeric D-loop formation in vitro and is required for maintaining telomeres in ALT-positive cells. Unexpectedly, however, RAD52 is dispensable for C-circle formation, a hallmark of ALT. In RAD52-knockout ALT cells, C-circle formation and RAD52-independent ALT DNA synthesis gradually increase as telomeres are shortened, and these activities are dependent on BLM and BIR proteins POLD3 and POLD4. These results suggest that ALT occurs through a RAD52-dependent and a RAD52-independent BIR pathway, revealing the bifurcated framework and dynamic nature of this process.
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•An assay to visualize ALT telomere DNA synthesis in APBs•APBs are functionally important for ALT DNA synthesis•RAD52 promotes telomere D-loops in vitro and ALT DNA synthesis in APBs•A RAD52-independent BIR pathway is responsible for C-circle formation
Alternative lengthening of telomeres (ALT) is a telomerase-independent but recombination-dependent process that extends telomeres. Zhang et al. show that ALT is in fact a bifurcated pathway involving both RAD52-dependent and RAD52-independent break-induced DNA replication (BIR) in ALT-associated PML bodies (APBs), revealing an unexpected framework of the ALT pathway.
What was the ‘alt’ in alt-right, alt-lite, and alt-left? Tracing these controversial terms’ development over the 2010s, this article interrogates the construction, meaning, and utility of the ‘alt’ ...modifier in US politics. Contextualizing the emergence of ‘alt’ among wider debates about how to spatially conceptualize anti-system politics beyond the left-right spectrum, it argues that ‘alt’ was used to name a tendency that moved beyond traditional ideological questions about what society should look like, and instead signified a preference about how politics should be done: namely, a rejection of the mainstream norms of political conduct, and an embrace of vulgarity, incivility and an extremely adversarial approach to political opposition. It shows how a popular-cultural understanding of ‘alternative’ was used to give this approach a countercultural sheen, and maps out the cleavages between groups that the alt/mainstream binary opened up. Finally, it considers the legacy of the ‘alt’ modifier in contemporary politics.
Online media sites such as Breitbart News in the United States and The Canary in the United Kingdom have come to prominence as powerful new agents. Their reach and influence in the contemporary ...digital media ecology have been widely highlighted, yet there has been little scholarship to situate these important new players in the field of political communication. This article argues that, first, these ‘interlopers’ known as the ‘alt-right’ and ‘alt-left’ need to be understood as embedded in the context of populist politics. Second, ‘hyperpartisan’ describes these sites better than the framework of alternative media as it mirrors populism’s ideological pillar of ‘us’ versus ‘them’. Finally, a deliberate provocation is argued to name these digital start-ups as news to create a starting point for conceptualising these disruptive new media forces.
With large social media platforms coming under increasing pressure to deplatform far-right users, the Alternative Technology movement (Alt-Tech) emerged as a new digital support infrastructure for ...the far right. We conduct a qualitative analysis of the prominent Alt-Tech platform Gab, a social networking service primarily modelled on Twitter, to assess the far-right virtual community on the platform. We find Gab’s technological affordances – including its lack of content moderation, culture of anonymity, microblogging architecture and funding model – have fostered an ideologically eclectic far-right community united by fears of persecution at the hands of ‘Big Tech’. We argue that this points to the emergence of a novel techno-social victimology as an axis of far-right virtual community, wherein shared experiences or fears of being deplatformed facilitate a coalescing of assorted far-right tendencies online.
Abstract
Anterolateral thigh (ALT) flap is the workhorse for reconstruction in head and neck post cancer excision. Chimeric multi-paddle flaps are useful for composite defects involving skin, mucosa, ...and soft tissue. The nerve to vastus lateralis (VL) runs along the pedicle, frequently interdigitating with it or the perforators. Sometimes, the nerve may be preserved during harvest but needs to be sacrificed frequently, leading to increased donor site morbidity.
We recommend a simple technique to preserve the nerve, wherein the skin paddles or chimeric components are divided in-situ and manipulated around it without causing injury.
This technique was used in 27 cases over 5 years. All involved nerves, perforators and pedicles were preserved.
The technique can be extended to any flap harvest with multiple perforators with nerves in proximity, when multiple skin islands are desired.
A promising strategy to improve the effectivity of anticancer treatment and decrease its side effects is to modulate drug release by using nanoparticulates (NPs) as carriers. In this study, ...methotrexate-loaded chitosan-polyanion nanoparticles were produced by polyelectrolyte complexation assisted by high-intensity sonication, using several anionic polymers, such as the sodium and potassium salts of poly(maleic acid-
-ethylene) and poly(maleic acid-
-octadecene), here named PAM-2 and PAM-18, respectively. Such NPs were analyzed and characterized according to particle size, polydispersity index, zeta potential and encapsulation efficiency. Likewise, their physical stability was tested at 4 °C and 40 °C in order to evaluate any change in the previously mentioned particle parameters. The in vitro methotrexate release was assessed at a pH of 7.4, which simulated physiological conditions, and the data were fitted to the heuristic models of order one, Higuchi, Peppas-Sahlin and Korsmeyer-Peppas. The results revealed that most of the MTX-chitosan-polyanion NPs have positive zeta potential values, sizes <280 nm and monodisperse populations, except for the NPs formed with PAM-18 polyanions. Further, the NPs showed adequate physical stability, preventing NP-NP aggregation. Likewise, these carriers modified the MTX release by an anomalous mechanism, where the NPs formed with PAM-2 polymer led to a release mechanism controlled by diffusion and relaxation, whereas the NPs formed with PAM-18 led to a mainly diffusion-controlled release mechanism.
Background
The epithelial cell‐derived danger signal mediators thymic stromal lymphopoietin (TSLP) and IL‐33 are consistently associated with adaptive Th2 immune responses in asthma. In addition, ...TSLP and IL‐33 synergistically promoted group 2 innate lymphoid cell (ILC2) activation to induce innate allergic inflammation. However, the mechanism of this synergistic ILC2 activation is unknown.
Methods
BALB/c WT and TSLP receptor‐deficient (TSLPR−/−) mice were challenged intranasally with Alternaria extract (Alt‐Ext) or PBS for 4 consecutive days to evaluate innate airway allergic inflammation. WT mice pre‐administered with rTSLP or vehicle, TSLPR−/− mice, and IL‐33 receptor‐deficient (ST2−/−) mice were challenged intranasally with Alt‐Ext or vehicle once or twice to evaluate IL‐33 release and TSLP expression in the lung. TSLPR and ST2 expression on lung ILC2 were measured by flow cytometry after treatment of rTSLP, rIL‐33, rTSLP + rIL‐33, or vehicle.
Results
Thymic stromal lymphopoietin receptor deficient mice had significantly decreased the number of lung ILC2 expressing IL‐5 and IL‐13 following Alt‐Ext‐challenge compared to WT mice. Further, eosinophilia, protein level of lung IL‐4, IL‐5, and IL‐13, and airway mucus score were also significantly decreased in TSLPR−/− mice compared to WT mice. Endogenous and exogenous TSLP increased Alt‐Ext‐induced IL‐33 release into BALF, and ST2 deficiency decreased Alt‐Ext‐induced TSLP expression in the lung. Further, rTSLP and rIL‐33 treatment reciprocally increased each other's receptor expression on lung ILC2 in vivo and in vitro.
Conclusion
Thymic stromal lymphopoietin and IL‐33 signaling reciprocally enhanced each other's protein release and expression in the lung following Alt‐Ext‐challenge and each other's receptor expression on lung ILC2 to enhance ILC2 activation.
We found that TSLPR deficiency significantly decrease the number of lung ILC2, airway eosinophils, and mucus production in mouse challenged with Alternaria extract. TSLP‐TSLPR and IL‐33‐ST2 signaling augments each other's protein release and expression in the lung epithelial cells after aeroallergen challenge. TSLP and IL‐33 signaling increases each other's receptor expression on lung ILC2, and the IL‐33‐augmented TSLPR expression enhances pSTAT5 in the ILC2.
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