CsrA impacts survival of Yersinia enterocolitica by affecting a myriad of physiological activities.

BackgroundA previous study identified a Yersinia enterocolitica transposon mutant, GY448, that was unable to export the flagellar type three secretion system (T3SS)-dependent phospholipase, YplA. This strain was also deficient for motility and unable to form colonies on Lauria-Bertani agar medium. Preliminary analysis suggested it carried a mutation in csrA. CsrA in Escherichia coli is an RNA-binding protein that is involved in specific post-transcriptional regulation of a myriad of physiological activities. This study investigated how CsrA affects expression of the flagellar regulatory cascade that controls YplA export and motility. It also explored the effect of csrA mutation on Y. enterocolitica in response to conditions that cue physiological changes important for growth in environments found both in nature and the laboratory.ResultsThe precise location of the transposon insertion in GMY448 was mapped within csrA. Genetic complementation restored disruptions in motility and the YplA export phenotype (Yex), which confirmed this mutation disrupted CsrA function. Mutation of csrA affected expression of yplA and flagellar genes involved in flagellar T3SS dependent export and motility by altering expression of the master regulators flhDC. Mutation of csrA also resulted in increased sensitivity of Y. enterocolitica to various osmolytes, temperatures and antibiotics.ConclusionsThe results of this study reveal unique aspects of how CsrA functions in Y. enterocolitica to control its physiology. This provides perspective on how the Csr system is susceptible to adaptation to particular environments and bacterial lifestyles

Fusion-From Stars to Power Sockets

Fusion energy is one of the promising energy sources of the future, with a practically limitless abundance of hydrogen in the universe and earth, it has the potential to replace current energy technologies being theoretically superior in efficiency with minimal environmental impact. A systematic review and meta-analysis of its thermodynamic properties, including the examination of the efficiency of underlying technologies and fusion causing techniques was conducted to examine the potential of this technology as a viable energy source. Through these methods we obtained thermodynamic data relating to to the efficiency of fusion engines, such as the Tokamak, Direct Pulse, Z-Pinch and Fusor style fusion engines, and the underlying technologies relating to conduction and radiation losses in a fusion engine in order to assess current and projected thermodynamic efficiencies and hypothesise potential research requirements to make fusion technology viable. From this research it is concluded that the main flaw in fusion technology is the inability to properly address radiation and conduction losses which minimise the power output of any fusion reactor.Furthermore, while it is necessary to develop these technologies for the development of working fusion technology, their applications to other energy industries, such as solar and nuclear fission, would be more beneficial to the clean energy near future than to the long term goal of fusion technology

Eating attitudes in a group of 11-year-old urban South African girls

No Abstract. South African Journal of Clinical Nutrition Vol. 19(2) 2006: 80-8

RMSE is not enough: Guidelines to robust data-model comparisons for magnetospheric physics

This is a review article of recent data-model comparison methodologies used in magnetospheric physics studies, also presenting a systematic categorization of these metrics for robust usage and augmented scientific output.The magnetospheric physics research community uses a broad array of quantitative data-model comparison methods (metrics) when conducting their research investigations. It is often the case, though, that any particular study will only use one or two metrics, with the two most common being Pearson correlation coefficient and root mean square error (RMSE). Because metrics are designed to test a specific aspect of the data-model relationship, limiting the comparison to only one or two metrics reduces the physical insights that can be gleaned from the analysis, restricting the possible findings from modeling studies. Additional physical insights can be obtained when many types of metrics are applied. We organize metrics into two primary groups: 1) fit performance metrics, often based on the data-model value difference; and 2) event detection metrics, which use a discrete event classification of data and model values determined by a specified threshold. In addition to these groups, there are several major categories of metrics based on the aspect of the data-model relationship that the metric assesses: 1) accuracy; 2) bias; 3) precision; 4) association; 5) and extremes. Another category is skill, which is a measure of any of these metrics against the performance of a reference model. These can be applied to a subset of either the data or the model values, known as reliability and discrimination assessments. In the context of magnetospheric physics examples, we discuss best practices for choosing metrics for particular studies.The authors would like to thank the US government for sponsoring this research, in particular research grants from NASA (NNX17AB87G, NNX16AQ04G, 80NSSC17K0015) and NSF (1663770). This study received partial funding from the European Union Horizon 2020 Research and Innovation Programme under grant agreement 870452 (PAGER). A. Azari’s contributions are based on work supported by the NSF Graduate Research Fellowship Program (DGE 1256260), A. Mukhopadhyay’s contributions are based on work supported by the NASA Future Investigator fellowship 80NSSC18K1120. B. Swiger’s contributions were partially supported by the NASA Future Investigator fellowship number 80NSSC20K1504. Data for Fig. 3 is available at the University of Michigan Deep Blue Data Repository, https://doi. org/10.7302/Z25T3HQC. Figures in section 4 are reused with permission.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171097/1/Liemohn_JASTP_2021_RMSEisnotEnough.pdfDescription of Liemohn_JASTP_2021_RMSEisnotEnough.pdf : Main articleSEL

Class Frizzled GPCRs in GtoPdb v.2021.3

Receptors of the Class Frizzled (FZD, nomenclature as agreed by the NC-IUPHAR subcommittee on the Class Frizzled GPCRs [175]), are GPCRs originally identified in Drosophila [19], which are highly conserved across species. While SMO shows structural resemblance to the 10 FZDs, it is functionally separated as it mediates effects in the Hedgehog signaling pathway [175]. FZDs are activated by WNTs, which are cysteine-rich lipoglycoproteins with fundamental functions in ontogeny and tissue homeostasis. FZD signalling was initially divided into two pathways, being either dependent on the accumulation of the transcription regulator β-catenin or being β-catenin-independent (often referred to as canonical vs. non-canonical WNT/FZD signalling, respectively). WNT stimulation of FZDs can, in cooperation with the low density lipoprotein receptors LRP5 (O75197) and LRP6 (O75581), lead to the inhibition of a constitutively active destruction complex, which results in the accumulation of β-catenin and subsequently its translocation to the nucleus. β-catenin, in turn, modifies gene transcription by interacting with TCF/LEF transcription factors. WNT/β-catenin-independent signalling can also be activated by FZD subtype-specific WNT surrogates [133]. β-catenin-independent FZD signalling is far more complex with regard to the diversity of the activated pathways. WNT/FZD signalling can lead to the activation of heterotrimeric G proteins [33, 178, 150], the elevation of intracellular calcium [184], activation of cGMP-specific PDE6 [2] and elevation of cAMP as well as RAC-1, JNK, Rho and Rho kinase signalling [56]. Novel resonance energy transfer-based tools have allowed the study of the GPCR-like nature of FZDs in greater detail. Upon ligand stimulation, FZDs undergo conformational changes and signal via heterotrimeric G proteins [239, 240, 102, 174]. Furthermore, the phosphoprotein Dishevelled constitutes a key player in WNT/FZD signalling towards planar-cell-polarity-like pathways. Importantly, FZDs exist in at least two distinct conformational states that regulate pathway selection [240]. As with other GPCRs, members of the Frizzled family are functionally dependent on the arrestin scaffolding protein for internalization [22], as well as for β-catenin-dependent [13] and -independent [89, 14] signalling. The pattern of cell signalling is complicated by the presence of additional ligands, which can enhance or inhibit FZD signalling (secreted Frizzled-related proteins (sFRP), Wnt-inhibitory factor (WIF), sclerostin or Dickkopf (DKK)), as well as modulatory (co)-receptors with Ryk, ROR1, ROR2 and Kremen, which may also function as independent signalling proteins

Class Frizzled GPCRs (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Receptors of the Class Frizzled (FZD, nomenclature as agreed by the NC-IUPHAR subcommittee on the Class Frizzled GPCRs [156]), are GPCRs originally identified in Drosophila [17], which are highly conserved across species. While SMO shows structural resemblance to the 10 FZDs, it is functionally separated as it mediates effects in the Hedgehog signaling pathway [156]. FZDs are activated by WNTs, which are cysteine-rich lipoglycoproteins with fundamental functions in ontogeny and tissue homeostasis. FZD signalling was initially divided into two pathways, being either dependent on the accumulation of the transcription regulator β-catenin or being β-catenin-independent (often referred to as canonical vs. non-canonical WNT/FZD signalling, respectively). WNT stimulation of FZDs can, in cooperation with the low density lipoprotein receptors LRP5 (O75197) and LRP6 (O75581), lead to the inhibition of a constitutively active destruction complex, which results in the accumulation of β-catenin and subsequently its translocation to the nucleus. β-Catenin, in turn, modifies gene transcription by interacting with TCF/LEF transcription factors. β-Catenin-independent FZD signalling is far more complex with regard to the diversity of the activated pathways. WNT/FZD signalling can lead to the activation of heterotrimeric G proteins [28, 159, 135], the elevation of intracellular calcium [164], activation of cGMP-specific PDE6 [2] and elevation of cAMP as well as RAC-1, JNK, Rho and Rho kinase signalling [48]. Novel resonance energy transfer-based tools have allowed the study of the GPCR-like nature of FZDs in greater detail. Upon ligand stimulation, FZDs undergo conformational changes and signal via heterotrimeric G proteins [213, 214]. Furthermore, the phosphoprotein Dishevelled constitutes a key player in WNT/FZD signalling. Importantly, FZDs exist in at least two distinct conformational states that regulate the pathway selection [214]. As with other GPCRs, members of the Frizzled family are functionally dependent on the arrestin scaffolding protein for internalization [19], as well as for β-catenin-dependent [12] and -independent [80, 13] signalling. The pattern of cell signalling is complicated by the presence of additional ligands, which can enhance or inhibit FZD signalling (secreted Frizzled-related proteins (sFRP), Wnt-inhibitory factor (WIF), sclerostin or Dickkopf (DKK)), as well as modulatory (co)-receptors with Ryk, ROR1, ROR2 and Kremen, which may also function as independent signalling proteins

Class Frizzled GPCRs in GtoPdb v.2023.1

Receptors of the Class Frizzled (FZD, nomenclature as agreed by the NC-IUPHAR subcommittee on the Class Frizzled GPCRs [180]), are GPCRs originally identified in Drosophila [20], which are highly conserved across species. While SMO shows structural resemblance to the 10 FZDs, it is functionally separated as it is involved in the Hedgehog signaling pathway [180]. SMO exerts its effects by activating heterotrimeric G proteins or stabilization of GLI by sequestering catalytic PKA subunits [186, 6, 58]. While SMO itself is bound by sterols and oxysterols [27, 94], FZDs are activated by WNTs, which are cysteine-rich lipoglycoproteins with fundamental functions in ontogeny and tissue homeostasis. FZD signalling was initially divided into two pathways, being either dependent on the accumulation of the transcription regulator β-catenin or being β-catenin-independent (often referred to as canonical vs. non-canonical WNT/FZD signalling, respectively). WNT stimulation of FZDs can, in cooperation with the low density lipoprotein receptors LRP5 (O75197) and LRP6 (O75581), lead to the inhibition of a constitutively active destruction complex, which results in the accumulation of β-catenin and subsequently its translocation to the nucleus. β-catenin, in turn, modifies gene transcription by interacting with TCF/LEF transcription factors. WNT/β-catenin-dependent signalling can also be activated by FZD subtype-specific WNT surrogates [138]. β-catenin-independent FZD signalling is far more complex with regard to the diversity of the activated pathways. WNT/FZD signalling can lead to the activation of heterotrimeric G proteins [34, 183, 155], the elevation of intracellular calcium [189], activation of cGMP-specific PDE6 [2] and elevation of cAMP as well as RAC-1, JNK, Rho and Rho kinase signalling [57]. Novel resonance energy transfer-based tools have allowed the study of the GPCR-like nature of FZDs in greater detail. Upon ligand stimulation, FZDs undergo conformational changes and signal via heterotrimeric G proteins [244, 245, 107, 179, 104]. Furthermore, the phosphoprotein Dishevelled constitutes a key player in WNT/FZD signalling towards planar-cell-polarity-like pathways. Importantly, FZDs exist in at least two distinct conformational states that regulate pathway selection [245]. As with other GPCRs, members of the Frizzled family are functionally dependent on the arrestin scaffolding protein for internalization [23], as well as for β-catenin-dependent [14] and -independent [91, 15] signalling. The pattern of cell signalling is complicated by the presence of additional ligands, which can enhance or inhibit FZD signalling (secreted Frizzled-related proteins (sFRP), Wnt-inhibitory factor (WIF), sclerostin or Dickkopf (DKK)), as well as modulatory (co)-receptors with Ryk, ROR1, ROR2 and Kremen, which may also function as independent signalling proteins

Method for bacteriophage isolation against target Campylobacter strains

Aims: Poultry meat is considered a major source of Campylobacter. This micro-aerobic bacterium is commonly responsible for foodborne illness. This work focuses on the isolation of Campylobacter coli lytic bacteriophages (phages) against target C. coli strains. Methods and Results: A method involving the enrichment of free-range chicken samples in a broth containing the target C. coli strains and salts (CaCl2 and MgSO4) was used for phage isolation. This method allowed the isolation of 43 phages that were active against 83% of the C. coli strains used in the isolation procedure. Approximately 65% of the phages were also effective against Campylobacter jejuni strains. Conclusions: The use of target pathogens in the phage isolation step improves the likelihood of detecting and isolating phages for the control of these specific strains. Significance and Impact of the Study: This technique will be valuable in the context of phage therapy for enriching for phages that are active against specifically identified strains of bacteria, for example from a food poisoning outbreak or epidemic strains resistant to multiple antibiotics. In these situations, using the conventional methods for searching for bacteriophages active for these particular strains can be a time-consuming, if not an unsuccessful process. Using the isolation method described in this manuscript, the particular strains can be added to the enrichment broth increasing the probability of finding phages against them. Therefore, it will shorten the time needed for seeking phages able to lyse target strains, which in most of the cases, because of the rapid increase in antimicrobial-resistant bacteria, is of crucial importance.Fundação para a Ciência e a Tecnologia (FCT

Knowledge acquisition for the internationalization of the smaller firm: content and sources

Internationalization process research emphasizes accumulated experience and networks as sources of knowledge for internationalization. Our understanding, however, as to what this knowledge is in practice for smaller firms, the challenges they face in acquiring it, and how they address those challenges is limited. Integrating organizational learning concepts with our theoretical understanding of the small firm internationalization process, we develop a new framework for understanding knowledge acquisition processes, which are examined with a case study of 10 Scottish internationalizing firms. We find smaller firms may not have relevant experience or useful networks, and rely on sources rarely recognised before. Firms used recruitment, government advisors and consultants to acquire indirect experience. Recruitment is a source of market and technological knowledge and government advisors and consultants a source of internationalization knowledge. Accessing internal information is important for firms that have internationalized. Our integrated theoretical framework identifies knowledge content and sources that are critical for internationalization, but that may be absent