PP2ACdc55 dephosphorylates Pds1 and inhibits spindle elongation.

J Cell Sci. 2020 Jun 26;:

Authors: Khondker S, Kajjo S, Chandler-Brown D, Skotheim J, Rudner A, Ikui A

Abstract
PP2ACdc55 regulates cell cycle progression by reversing cyclin-dependent kinase (CDK) and polo-like kinase (Cdc5) dependent phosphorylation events. In S. cerevisiae, Cdk1 phosphorylates securin (Pds1), which facilitates Pds1 binding and inhibiting separase (Esp1). During anaphase, Esp1 cleaves the cohesin subunit Scc1 and promotes spindle elongation. Here, we show that PP2ACdc55 directly dephosphorylates Pds1 both in vivo and in vitro Pds1 hyperphosphorylation in a cdc55 deletion mutant enhanced the Pds1-Esp1 interaction, which played a positive role in Pds1 nuclear accumulation and in spindle elongation. We also show that nuclear PP2ACdc55 played a role during replication stress to inhibit spindle elongation. This pathway acted independently of the known Mec1, Swe1 or Spindle Assembly Checkpoint (SAC) checkpoint pathways. We propose a model where Pds1 dephosphorylation by PP2ACdc55 disrupts the Pds1-Esp1 protein interaction and inhibits Pds1 nuclear accumulation, which prevents spindle elongation, a process that is elevated during replication stress.

PMID: 32591482 [PubMed - as supplied by publisher]

34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/27

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34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/26

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34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/26

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"systems biology"

These pubmed results were generated on 2020/06/25

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48 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/25

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"systems biology"

These pubmed results were generated on 2020/06/24

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43 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/24

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47 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/23

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More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis.

Chem Senses. 2020 Jun 20;:

Authors: Parma V, Ohla K, Veldhuizen MG, Niv MY, Kelly CE, Bakke AJ, Cooper KW, Bouysset C, Pirastu N, Dibattista M, Kaur R, Liuzza MT, Pepino MY, Schöpf V, Pereda-Loth V, Olsson SB, Gerkin RC, Rohlfs Domínguez P, Albayay J, Farruggia MC, Bhutani S, Fjaeldstad AW, Kumar R, Menini A, Bensafi M, Sandell M, Konstantinidis I, Di Pizio A, Genovese F, Öztürk L, Thomas-Danguin T, Frasnelli J, Boesveldt S, Saatci Ö, Saraiva LR, Lin C, Golebiowski J, Dar Hwang L, Ozdener MH, Guàrdia MD, Laudamiel C, Ritchie M, Havlícek J, Pierron D, Roura E, Navarro M, Nolden AA, Lim J, Whitcroft KL, Colquitt LR, Ferdenzi C, Brindha EV, Altundag A, Macchi A, Nunez-Parra A, Patel ZM, Fiorucci S, Philpott CM, Smith BC, Lundström JN, Mucignat C, Parker JK, van den Brink M, Schmuker M, Fischmeister FPS, Heinbockel T, Shields VDC, Faraji F, Santamaría E, Fredborg WEA, Morini G, Olofsson JK, Jalessi M, Karni N, D'Errico A, Alizadeh R, Pellegrino R, Meyer P, Huart C, Chen B, Soler GM, Alwashahi MK, Welge-Lüssen A, Freiherr J, de Groot JHB, Klein H, Okamoto M, Singh PB, Hsieh JW, Reed DR, Hummel T, Munger SD, Hayes JE, GCCR Group Author

Abstract
Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± SD), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.

PMID: 32564071 [PubMed - as supplied by publisher]

From biomechanics to mechanobiology: Xenopus provides direct access to the physical principles that shape the embryo.

Curr Opin Genet Dev. 2020 Jun 18;63:71-77

Authors: Chu CW, Masak G, Yang J, Davidson LA

Abstract
Features of amphibian embryos that have served so well to elucidate the genetics of vertebrate development also enable detailed analysis of the physics that shape morphogenesis and regulate development. Biophysical tools are revealing how genes control mechanical properties of the embryo. The same tools that describe and control mechanical properties are being turned to reveal how dynamic mechanical information and feedback regulate biological programs of development. In this review we outline efforts to explore the various roles of mechanical cues in guiding cilia biology, axonal pathfinding, goblet cell regeneration, epithelial-to-mesenchymal transitions in neural crest, and mesenchymal-to-epithelial transitions in heart progenitors. These case studies reveal the power of Xenopus experimental embryology to expose pathways integrating mechanical cues with programs of development, organogenesis, and regeneration.

PMID: 32563783 [PubMed - as supplied by publisher]

MicroRNA-21 in plasma exosome, but not from whole plasma, as a biomarker for the severe interstitial fibrosis and tubular atrophy (IF/TA) in post-renal transplantation.

Asian Pac J Allergy Immunol. 2020 Jun 21;:

Authors: Saejong S, Townamchai N, Somparn P, Tangtanatakul P, Ondee T, Hirankarn N, Leelahavanichkul A

Abstract
BACKGROUND: Non-invasive diagnosis of interstitial fibrosis and tubular atrophy (IF/TA), a major cause of chronic allograft dysfunction in post-kidney transplantation (post-KT), is needed.
OBJECTIVE: Several candidates of microRNAs (miRs) in plasma exosome or whole plasma were evaluated for IF/TA biomarker.
METHODS: Kidney samples from biopsy and plasma were tested for miRs expression.
RESULTS: Expression of miR-21, miR-142-3p and miR-221 in renal histology with high fibrosis score (Banff classification) was higher than the samples with lesser score (n = 17/group). However, expression of these miRs from plasma exosome or from whole plasma of post-KT patients with different severity of IF/TA as determined by percentage of IF/TA including; grade I (5-25%) (n = 15), grade II (26-50%) (n = 15), grade III (≥ 50%) (n = 6) versus stable graft function (no IF/TA) (n = 15) was not different. However, high expression of miR-21 in exosome, but not from whole plasma, was demonstrated in IF/TA grade II and III compared with IF/TA grade I. In contrast, serum creatinine (Scr) and proteinuria, the current standard biomarkers, could not differentiate IF/TA grade I out of grade II/III. There was no correlation between exosome miR-21 versus the current standard renal injury biomarkers, including Scr, blood urea nitrogen and proteinuria, in IF/TA grade II or grade III.
CONCLUSIONS: High miR-21 in plasma exosome, but not in whole plasma, indicated high grade IF/TA in post-KT patients. This non-invasive monitoring biomarker allows the more frequent evaluation on IF/TA than renal biopsy (a standard but more invasive procedure) resulting in the earlier management. More studies on patients are warrant.

PMID: 32563236 [PubMed - as supplied by publisher]

Recent developments in neoantigen-based cancer vaccines.

Asian Pac J Allergy Immunol. 2020 Jun 21;:

Authors: Hodge K, Supabphol S, Pramod Kumar PK, Poomipak W, Pisitkun T

Abstract
Cynics point out that a cure for cancer has been "around the corner" for the last 50 years. Nevertheless, the recent convergence of deep DNA, RNA, and proteomic technologies with enhanced understanding of the nuances of the adaptive immune system has generated great optimism amongst researchers. The extraordinary heterogeneity of various cancers, once thought to be a major therapeutic hurdle, may now be bypassed via "personalized" vaccine treatments. Specifically, these treatments involve the identification of MHC-bound peptides that are unique to a patient's cancer (neoantigens), followed by immunization with peptides, RNA, or DNA that encodes these neoantigens via various delivery systems, thus amplifying the immune system's response to the particular cancer. Such approaches have shown dramatic results in animal studies. Not surprisingly, then, the field of neoantigen-based immunotherapy has advanced at a spectacular rate, necessitating that interested individuals stay apprised of recent developments. Following an introduction to the subject, we thus focus on aspects that are particularly fast-moving; the cellular sources of neoantigens, which are surprisingly diverse, the tools that are used for their identification, and the status of the numerous clinical trials that are now being conducted.

PMID: 32563235 [PubMed - as supplied by publisher]

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

35 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Exploring molecular evolution of Rubisco in C3 and CAM Orchidaceae and Bromeliaceae.

BMC Evol Biol. 2020 01 22;20(1):11

Authors: Hermida-Carrera C, Fares MA, Font-Carrascosa M, Kapralov MV, Koch MA, Mir A, Molins A, Ribas-Carbó M, Rocha J, Galmés J

Abstract
BACKGROUND: The CO2-concentrating mechanism associated to Crassulacean acid metabolism (CAM) alters the catalytic context for Rubisco by increasing CO2 availability and provides an advantage in particular ecological conditions. We hypothesized about the existence of molecular changes linked to these particular adaptations in CAM Rubisco. We investigated molecular evolution of the Rubisco large (L-) subunit in 78 orchids and 144 bromeliads with C3 and CAM photosynthetic pathways. The sequence analyses were complemented with measurements of Rubisco kinetics in some species with contrasting photosynthetic mechanism and differing in the L-subunit sequence.
RESULTS: We identified potential positively selected sites and residues with signatures of co-adaptation. The implementation of a decision tree model related Rubisco specific variable sites to the leaf carbon isotopic composition of the species. Differences in the Rubisco catalytic traits found among C3 orchids and between strong CAM and C3 bromeliads suggested Rubisco had evolved in response to differing CO2 concentration.
CONCLUSIONS: The results revealed that the variability in the Rubisco L-subunit sequence in orchids and bromeliads is composed of coevolving sites under potential positive adaptive signal. The sequence variability was related to δ13C in orchids and bromeliads, however it could not be linked to the variability found in the kinetic properties of the studied species.

PMID: 31969115 [PubMed - indexed for MEDLINE]

Usefulness of milk mid-infrared spectroscopy for predicting lameness score in dairy cows.

J Dairy Sci. 2020 Mar;103(3):2534-2544

Authors: Bonfatti V, Ho PN, Pryce JE

Abstract
The objective of this study was to evaluate the ability of milk infrared spectra to predict cow lameness score (LMS) for use as an indicator of cow health on Australian dairy farms, or as an indicator trait for genetic evaluation purposes. The study involved 3,771 cows from 10 farms in Australia. Milk infrared spectra collected during the monthly herd testing were available in all the farms involved in the study. Lameness score was measured once in each herd, within 72 h from a test day, and merged to the closest spectra records. Lameness score was expressed on a scale from 0 to 3, where 0 is assigned to sound cows and scores 1 to 3 are assigned to cows with increased lameness severity. Partial least squares discriminant analysis was used to develop prediction models for classifying sound (score 0) and not-sound cows (i.e., cows walking unevenly, score greater than 0). Discriminant models were tested in a 10-fold random cross-validation process. Milk infrared spectra correctly classified only 57% of the cows walking unevenly and only 59% of the sound cows. When additional predictors (parity, age at calving, days in milk, and milk yield) were included in the prediction model, the model correctly classified 57% of the cows walking unevenly and 62% of the sound cows. The same model applied only to the cows in the first third of lactation correctly classified 66% of the cows walking unevenly and 57% of the sound cows. When the prediction model was used to identify lame cows (scores 2 and 3), only 49% of them were classified as such. These results are considered to be too poor to envisage a practical application of these models in the near future as on-farm tools to provide an indication of LMS. To investigate whether, at this stage, predictions of the LMS could be useful as large-scale phenotypes for animal breeding purposes, we estimated (co)variance components for actual and predicted LMS using 2,670 and 24,560 records, respectively. As the genetic correlation between actual and predicted LMS was not significantly different from zero, predictions of lameness from milk spectra and additional on-farm variables cannot be used, at this stage, as an indicator trait for actual LMS. More research is needed to find better strategies to predict lameness.

PMID: 31882209 [PubMed - indexed for MEDLINE]

Lipid-dependent coupling of secretory cargo sorting and trafficking at the trans-Golgi network.

FEBS Lett. 2019 09;593(17):2412-2427

Authors: von Blume J, Hausser A

Abstract
In eukaryotic cells, the trans-Golgi network (TGN) serves as a platform for secretory cargo sorting and trafficking. In recent years, it has become evident that a complex network of lipid-lipid and lipid-protein interactions contributes to these key functions. This review addresses the role of lipids at the TGN with a particular emphasis on sphingolipids and diacylglycerol. We further highlight how these lipids couple secretory cargo sorting and trafficking for spatiotemporal coordination of protein transport to the plasma membrane.

PMID: 31344259 [PubMed - indexed for MEDLINE]