functional consequences
Recently Published Documents





Animals ◽  
2022 ◽  
Vol 12 (2) ◽  
pp. 207
Xiaoyun Wu ◽  
Wondossen Ayalew ◽  
Min Chu ◽  
Jie Pei ◽  
Chunnian Liang ◽  

The mammary gland is a complicated organ comprising several types of cells, and it undergoes extensive morphogenetic and metabolic changes during the female reproductive cycle. RNA editing is a posttranscriptional modification event occurring at the RNA nucleotide level, and it drives transcriptomic and proteomic diversities, with potential functional consequences. RNA editing in the mammary gland of yaks, however, remains poorly understood. Here, we used REDItools to identify RNA editing sites in mammary gland tissues in yaks during the lactation period (LP, n = 2) and dry period (DP, n = 3). Totally, 82,872 unique RNA editing sites were identified, most of which were detected in the noncoding regions with a low editing degree. In the coding regions (CDS), we detected 5235 editing sites, among which 1884 caused nonsynonymous amino acid changes. Of these RNA editing sites, 486 were found to generate novel possible miRNA target sites or interfere with the initial miRNA binding sites, indicating that RNA editing was related to gene regulation mediated by miRNA. A total of 14,159 RNA editing sites (involving 3238 common genes) showed a significant differential editing level in the LP when compared with that in the DP through Tukey’s Honest Significant Difference method (p < 0.05). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, genes that showed different RNA editing levels mainly participated in pathways highly related to mammary gland development, including MAPK, PI3K-Akt, FoxO, and GnRH signaling pathways. Collectively, this work demonstrated for the first time the dynamic RNA editome profiles in the mammary gland of yaks and shed more light on the mechanism that regulates lactation together with mammary gland development.

2022 ◽  
Andrea Piserchio ◽  
Eta A Isiroho ◽  
Kimberly Long ◽  
Amanda L Bohanon ◽  
Eric A Kumar ◽  

Translation is a highly energy consumptive process tightly regulated for optimal protein quality and adaptation to energy and nutrient availability. A key facilitator of this process is the α-kinase eEF-2K that specifically phosphorylates the GTP-dependent translocase eEF-2, thereby reducing its affinity for the ribosome and suppressing the elongation phase of protein synthesis. eEF-2K activation requires calmodulin binding and auto-phosphorylation at the primary stimulatory site, T348. Biochemical studies have predicted that calmodulin activates eEF-2K through a unique allosteric process mechanistically distinct from other calmodulin-dependent kinases. Here we resolve the atomic details of this mechanism through a 2.3 Å crystal structure of the heterodimeric complex of calmodulin with the functional core of eEF-2K (eEF-2KTR). This structure, which represents the activated T348-phosphorylated state of eEF-2KTR, highlights how through an intimate association with the calmodulin C-lobe, the kinase creates a spine that extends from its N-terminal calmodulin-targeting motif through a conserved regulatory element to its active site. Modification of key spine residues has deleterious functional consequences.

Insects ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 69
Ferdinand Nanfack-Minkeu ◽  
Laura King Sirot

There is intense interest in controlling insect reproductive output. In many insect species, reproductive output is profoundly influenced by mating, including the receipt of sperm and seminal fluid molecules, through physiological and behavior changes. To understand these changes, many researchers have investigated post-mating gene expression regulation. In this review, we synthesize information from studies both across and within different species about the impact of mating, or components of mating, on female gene expression patterns. We found that genes related to the roles of metabolism, immune-response, and chemosensation are regulated by mating across many different insect species. We highlight the few studies that have taken the important next step of examining the functional consequences of gene expression regulation which is crucial in order to understand the mechanisms underlying the mating-regulated control of female lifespan and reproduction and to make use of such knowledge to propagate or control insect populations. The potential of cross-study comparisons is diminished by different studies using different methods. Thus, we also include a consideration of how future studies could be designed to facilitate cross-study comparisons and a call for collaboration across researchers studying different insect species and different aspects of insect biology.

Open Medicine ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. 119-123
Ruizhi Zheng ◽  
Ting Zhang ◽  
Xianzhu Zeng ◽  
Miao Yu ◽  
Zhao Jin ◽  

Abstract Bilateral medial medullary infarction (BMMI) is an extremely rare type of cerebrovascular accident often resulting in poor functional consequences. “Heart appearance” on diffusion-weighted imaging (DWI) of magnetic resonance imaging (MRI) is the unique presentation of BMMI. In this article, we present an acute ischemic stroke patient whose brain MRI showed the atypical “heart appearance” sign, manifested unusual bilateral central facial paralysis concurrently. For an early diagnosis of BMMI, it is essential to recognize the characteristic clinical and MRI findings of this rare type of stroke. Abnormal small dot or linear DWI signal at the midline of the brainstem should not be ignored at the early stage of stroke.

2022 ◽  
Marina Feric ◽  
Azadeh Sarfallah ◽  
Furqan Dar ◽  
Dmitry Temiakov ◽  
Rohit V Pappu ◽  

Phase separation organizes many membraneless structures in cells. The functional consequences of concentrating cellular machinery into biomolecular condensates, however, is largely unclear. Here, we use in vitro reconstitutions, in vivo studies, and computational modelling to uncover structure-function relationships of mitochondrial (mt-) transcriptional condensates. In vitro, we find that the core mt-transcription machinery — consisting of POLRMT, TFAM, TFB2M, and DNA — forms viscoelastic, multi-phasic condensates. Strikingly, the rates of condensate-mediated transcription are considerably lower than equivalent reactions in bulk solution. Dampened rates are associated with reduced diffusivities of components that become kinetically arrested in non-equilibrium, vesicular condensates. Perturbation of mt-components in vivo and computational simulations recapitulate the transcription-dependent reorganizations observed in vitro. Our findings demonstrate close, bidirectional interdependence between structure and function of transcriptional condensates.

2022 ◽  
Vol 162 ◽  
pp. 105577
Maham Rais ◽  
Jonathan W. Lovelace ◽  
Xinghao S. Shuai ◽  
Walker Woodard ◽  
Steven Bishay ◽  

2021 ◽  
pp. 108886832110659
Garriy Shteynberg ◽  
Jacob B. Hirsh ◽  
Jon Garthoff ◽  
R. Alexander Bentley

Contemporary research on human sociality is heavily influenced by the social identity approach, positioning social categorization as the primary mechanism governing social life. Building on the distinction between agency and identity in the individual self (“I” vs. “Me”), we emphasize the analogous importance of distinguishing collective agency from collective identity (“We” vs. “Us”). While collective identity is anchored in the unique characteristics of group members, collective agency involves the adoption of a shared subjectivity that is directed toward some object of our attention, desire, emotion, belief, or action. These distinct components of the collective self are differentiated in terms of their mental representations, neurocognitive underpinnings, conditions of emergence, mechanisms of social convergence, and functional consequences. Overall, we show that collective agency provides a useful complement to the social categorization approach, with unique implications for multiple domains of human social life, including collective action, responsibility, dignity, violence, dominance, ritual, and morality.

2021 ◽  
Oksana Stepinska ◽  
Dorota Dymkowska ◽  
Lukasz Mateuszuk ◽  
Krzysztof Olaf Zablocki

Treatment of endothelial cells with bacterial lipopolysaccharide (LPS) evokes a number of metabolic and functional consequences which built a multifaceted physiological response of endothelium to bacterial infection. Here effects of LPS on human aortic endothelial cells (HAEC) have been investigated. Among the spectrum of biochemical changes substantially elevated N-nicotinamide methyltransferase (NNMT) protein level was particularly intriguing. It has been shown that silencing of the NNMT-encoding gene prevented several changes which are observed in control HAECs due to treatment with LPS. They include significantly increased cytosolic Ca2+ concentration and abnormally strong calcium response to thapsigargin, altered energy metabolism which is switched to anaerobic glycolysis and rearrangement of the mitochondrial network organization. Biochemical mechanisms behind protecting effect of partial NNMT deficiency remains unknown but we speculate that the primary role in this phenomenon is attributed to normalized Ca2+ response in cells partially deprived of the NNMT gene. However, this assumption needs to be verified experimentally. Nevertheless, this paper focuses the reader attention on NNMT, which is an important enzyme that potentially may affect cellular metabolism by two means: direct influence based on a regulation of NAD+ synthesis through modulation of nicotinamide availability, and a regulation of S-adenosylmethionine concentration and therefore controlling of methylation processes including modification of chromatin and epigenetic effects

Sang-Eun Lee ◽  
Eunji Cho ◽  
Soomin Jeong ◽  
Yejij Song ◽  
Seokjo Kang ◽  

Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1 (SGIP1), originally known as a regulator of energy homeostasis, was later found to be an ortholog of Fer/Cip4 homology domain-only (FCHo) proteins and to function during endocytosis. SGIP1α is a longer splicing variant in mouse brains that contains additional regions in the membrane phospholipid-binding domain (MP) and C-terminal region, but functional consequences with or without additional regions between SGIP1 and SGIP1α remain elusive. Moreover, many previous studies have either inadvertently used SGIP1 instead of SGIP1α or used the different isoforms with or without additional regions indiscriminately, resulting in further confusion. Here, we report that the additional region in the MP is essential for SGIP1α to deform membrane into tubules and for homo-oligomerization, and SGIP1, which lacks this region, fails to perform these functions. Moreover, only SGIP1α rescued endocytic defects caused by FCHo knock-down. Thus, our results indicate that SGIP1α, but not SGIP1, is the functional ortholog of FCHos, and SGIP1 and SGIP1α are not functionally redundant. These findings suggest that caution should be taken in interpreting the role of SGIP1 in endocytosis.

2021 ◽  
Juan Luis Riquelme ◽  
Mike Hemberger ◽  
Gilles Laurent ◽  
Julijana Gjorgjieva

Single spikes can trigger repeatable sequences of spikes in cortical networks. The mechanisms that support reliable propagation from such small events and their functional consequences for network computations remain unclear. We investigated the conditions in which single spikes trigger reliable and temporally precise sequences in a network model constrained by experimental measurements from turtle cortex. We examined the roles of connectivity, synaptic strength, and spontaneous activity in the generation of sequences. Sparse but strong connections support sequence propagation, while dense but weak connections modulate propagation reliability. Unsupervised clustering reveals that sequences can be decomposed into sub-sequences corresponding to divergent branches of strongly connected neurons. The sparse backbone of strong connections defines few failure points where activity can be selectively gated, enabling the controlled routing of activity. These results reveal how repeatable sequences of activity can be triggered, sustained, and controlled, with significant implications for cortical computations.

Sign in / Sign up

Export Citation Format

Share Document