scholarly journals The Secrets of Alternative Autophagy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3241
Author(s):  
Kaja Urbańska ◽  
Arkadiusz Orzechowski

For many years, it was thought that ATG5 and ATG7 played a pivotal role in autophagy, and that the knockdown of one of these genes would result in its inhibition. However, cells with ATG5 or ATG7 depletion still generate autophagic vacuoles with mainly trans-Golgi-originated isolation membranes and do not die. This indicates that autophagy can occur via ATG5/ATG7-independent alternative autophagy. Its molecular mechanism differs from that of the canonical pathway, including inter alia the phosphorylation of ULK1, and lack of LC3 modifications. As the alternative autophagy pathway has only recently been described, little is known of its precise role; however, a considerable body of evidence suggests that alternative autophagy participates in mitochondrion removal. This review summarizes the latest progress made in research on alternative autophagy and describes its possible molecular mechanism, roles and methods of detection, and possible modulators. There is a need for further research focused on types of autophagy, as this can elucidate the functioning of various cell types and the pathogenesis of human and animal diseases.

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 284
Author(s):  
Yu-Hao Liu ◽  
Chien-Chang Chen ◽  
Yi-Jen Hsueh ◽  
Li-Man Hung ◽  
David Hui-Kang Ma ◽  
...  

Although several modes of reprogramming have been reported in different cell types during iPSC induction, the molecular mechanism regarding the selection of different modes of action is still mostly unknown. The present study examined the molecular events that participate in the selection of such processes at the onset of somatic reprogramming. The activity of STAT3 versus that of Erk1/2 reversibly determines the reprogramming mode entered; a lower activity ratio favors the deterministic process and vice versa. Additionally, extraneous E-cadherin facilitates the early events of somatic reprogramming, potentially by stabilizing the LIF/gp130 and EGFR/ErbB2 complexes to promote entry into the deterministic process. Our current findings demonstrated that manipulating the pSTAT3/pErk1/2 activity ratio in the surrounding milieu can drive different modes of action toward either the deterministic or the stochastic process in the context of OSKM-mediated somatic reprogramming.


2021 ◽  
Author(s):  
Zhengyan Guo ◽  
Yue Tang ◽  
Wei Tang ◽  
Yihua Chen

Heptose-containing natural products hold great potential as drugs for the treatment of human and animal diseases.


Insects ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 366
Author(s):  
Raisa Rodrigues Santos Rios ◽  
Maria Clara Alves Santarém ◽  
Karlos Antônio Lisboa Ribeiro Júnior ◽  
Breno Araujo de Melo ◽  
Sybelle Georgia Mesquita da Silva ◽  
...  

The species of the Culicoides genus are hematophagous, and some of them are vectors of important human and animal diseases. This group of insects is distributed worldwide, varying according to local species. Knowledge of the geographic distribution of specific species is crucial for the development and implementation of control strategies. The aim of this work was to investigate the occurrence of Culicoides in the state of Alagoas in northeast Brazil. Midges were captured with CDC light traps, and their identification and morphological analyses were performed by the Ceratopogonidae Collection of the Oswaldo Cruz Foundation (FIOCRUZ/CCER) in Rio de Janeiro, Brazil. Morphological analyses were performed using the key to Culicoides from the guttatus group and comparison with other deposited specimens. DNA sequencing, genetic analysis and comparison with sequences in the Genbank database, confirmed the identification of the flies as Culicoides insignis. This was the first formal report of C. insignis being found in Alagoas.


2017 ◽  
Vol 8 (2) ◽  
pp. e2608-e2608 ◽  
Author(s):  
Hongfeng Yuan ◽  
Brandon Tan ◽  
Shou-Jiang Gao

Abstract Tenovin-6 has attracted significant interest because it activates p53 and inhibits sirtuins. It has anti-neoplastic effects on multiple hematopoietic malignancies and solid tumors in both in vitro and in vivo studies. Tenovin-6 was recently shown to impair the autophagy pathway in chronic lymphocytic leukemia cells and pediatric soft tissue sarcoma cells. However, whether tenovin-6 has a general inhibitory effect on autophagy and whether there is any involvement with SIRT1 and p53, both of which are regulators of the autophagy pathway, remain unclear. In this study, we have demonstrated that tenovin-6 increases microtubule-associated protein 1 light chain 3 (LC3-II) level in diverse cell types in a time- and dose-dependent manner. Mechanistically, the increase of LC3-II by tenovin-6 is caused by inhibition of the classical autophagy pathway via impairing lysosomal function without affecting the fusion between autophagosomes and lysosomes. Furthermore, we have revealed that tenovin-6 activation of p53 is cell type dependent, and tenovin-6 inhibition of autophagy is not dependent on its regulatory functions on p53 and SIRT1. Our results have shown that tenovin-6 is a potent autophagy inhibitor, and raised the precaution in interpreting results where tenovin-6 is used as an inhibitor of SIRT1.


2008 ◽  
pp. 465-471
Author(s):  
E. M. Alkhalifa

The rich contributions made in the field of human computer interaction (HCI) have played a pivotal role in shifting the attention of the industry to the interaction between users and computers (Myers, 1998). However, technologies that include hypertext, multimedia, and manipulation of graphical objects were designed and presented to the users without referring to critical findings made in the field of cognitive psychology. These findings allow designers of multimedia educational systems to present knowledge in a fashion that would optimize learning.


Zygote ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 49-53
Author(s):  
Yuki Maruyama ◽  
Atsushi P. Kimura

SummaryIn eutherian mammals, the placenta plays a critical role in embryo development by supplying nutrients and hormones and mediating interaction with the mother. To establish the fine connection between mother and embryo, the placenta needs to be formed normally, but the mechanism of placental differentiation is not fully understood. We previously revealed that mouse prolyl oligopeptidase (POP) plays a role in trophoblast stem cell (TSC) differentiation into two placental cell types, spongiotrophoblasts (SpT) and trophoblast giant cells. Here, we focused on SpT differentiation and attempted to elucidate a molecular mechanism. ForAscl2,Arnt, andEgfrgenes that are indispensable for SpT formation, we found that a POP-specific inhibitor, SUAM-14746, significantly decreasedAscl2expression, which was consistent with a significant decrease in expression ofFlt1, a gene downstream ofAscl2. Although this downregulation was unlikely to be mediated by the PI3K-Akt pathway, our results indicated that POP controls TSC differentiation into SpT by regulating theAscl2gene.


2002 ◽  
Vol 175 (1) ◽  
pp. 61-73 ◽  
Author(s):  
G Schreiber

In larger mammals, thyroid hormone-binding plasma proteins are albumin, transthyretin (TTR) and thyroxine (T4)-binding globulin. They differ characteristically in affinities and release rates for T4 and triiodothyronine (T3). Together, they form a 'buffering' system counteracting thyroid hormone permeation from aqueous to lipid phases. Evolution led to important differences in the expression pattern of these three proteins in tissues. In adult liver, TTR is only made in eutherians and herbivorous marsupials. During development, it is also made in tadpole and fish liver. More intense TTR synthesis than in liver is found in the choroid plexus of reptilians, birds and mammals, but none in the choroid plexus of amphibians and fish, i.e. species without a neocortex. All brain-made TTR is secreted into the cerebrospinal fluid, where it becomes the major thyroid hormone-binding protein. During ontogeny, the maximum TTR synthesis in the choroid plexus precedes that of the growth rate of the brain and occurs during the period of maximum neuroblast replication. TTR is only one component in a network of factors determining thyroid hormone distribution. This explains why, under laboratory conditions, TTR-knockout mice show no major abnormalities. The ratio of TTR affinity for T4 over affinity for T3 is higher in eutherians than in reptiles and birds. This favors T4 transport from blood to brain providing more substrate for conversion of the biologically less active T4 into the biologically more active T3 by the tissue-specific brain deiodinases. The change in affinity of TTR during evolution involves a shortening and an increase in the hydrophilicity of the N-terminal regions of the TTR subunits. The molecular mechanism for this change is a stepwise shift of the splice site at the intron 1/exon 2 border of the TTR gene. The shift probably results from a sequence of single base mutations. Thus, TTR evolution provides an example for a molecular mechanism of positive Darwinian evolution. The amino acid sequences of fish and amphibian TTRs are very similar to those in mammals, suggesting that substantial TTR evolution occurred before the vertebrate stage. Open reading frames for TTR-like sequences already exist in Caenorhabditis elegans, yeast and Escherichia coli genomes.


Sign in / Sign up

Export Citation Format

Share Document