Adaptation and multiplication of bacteria in host tissues

The multiplication of bacteria in the largely undefined and changing environment of host tissues is an essential feature of any infection. Bacterial behaviour is determined both by genetic structures and also by the environment. Little is known about the effect that host factors may have on invading bacteria nor about the way in which alterations in bacterial properties aid proliferation in vivo . Recently our understanding of one feature of this environm ent and of the way in which pathogenic bacteria adapt to it has increased considerably. We now know that the amount of iron that might be readily available to bacteria in body fluids is extremely small. This iron-restricted environment induces phenotypic changes both in the metabolism and in the composition of the outer membrane of bacteria growing in vivo . These and other host-induced changes are now providing a fresh insight into the capability of bacteria to multiply in vivo during infection.

Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 665-675
Author(s):  
J.G. Howard

The following brief survey considers various manoeuvres which can be applied to manipulate the immune response to parasitic infectionsin vivo. The examples quoted largely concern malaria, babesiosis, schistosomiasis and leishmaniasis, predominantly in inbred mouse strains. Since my own relevant research experience has been restricted to leishmaniasis, this will receive undue emphasis, although it does illustrate particularly well points I wish to stress. The types of intervention described do not all provide the precision of interpretation with which they are sometimes credited. Thus, effects of immunosuppression or T-cell depletion alone can usually only implicate the specific immune response (in its broad sense) in shaping the natural history and outcome of an infection or in underlying the effect of prophylactic immunization. Nevertheless, more precise delineation of lymphocyte subset involvement can be obtained by cell replacement studies in some of these models or by exclusion of antibody. The outcomes of these approaches have been (or are) predictable in most cases. More fascinating, however, are the various instances which will be stressed where totally unpredicted and contrary observations have been made which led (or may lead) to fresh insight into the disease. These serendipitous findings illustrate at the same time the value of applying the manoeuvres, even though they imply that the logical immunologist cannot yet always outsmart the parasite by design.


1990 ◽  
Vol 43 (1) ◽  
pp. 99-142 ◽  
Author(s):  
Margarita Mazo

This study presents Stravinsky's well-known ballet Les Noces as seen by an ethnomusicologist familiar with wedding rituals and, particularly, laments of Russian villages. The music of Les Noces, statements made by the composer himself, and the data gleaned from published sources of folk music (those Stravinsky is known to have come in contact with or those accessible to him) are juxtaposed with observations obtained in field interviews with Russian villagers who themselves were participants in wedding rituals and performers of wedding laments. The conceptual and structural ideas of Les Noces are compared to those of the village ritual. The examination of the role of laments and songs in the unfolding of the ritual, the use of ostinato, the analysis of the manner of singing and voice quality in laments, and an inquiry into the polyphonic forms based on polymorphic texture enable a fresh insight into Les Noces and the way Stravinsky handled materials derived from folk practice. The general conceptualization of the composition with its coalescence of high emotional intensity and, at the same time, personal detachment is traced to folk ritual where the episodes, being part of the ritual, embody primarily impersonal responses to the requirements of a ritualized situation, even though they are presented as highly tense and emotionally charged.


2021 ◽  
pp. 110-135
Author(s):  
Lyndsey Jenkins

This chapter shows that Annie Kenney’s suffragette career offers fresh insight into the way that class was represented, understood, and experienced within the WSPU. While WSPU activists frequently claimed that theirs was a classless organization, historians have often been sceptical as to whether this was reflected in their policies and attitudes. Class remained a significant source of tension in the organization even as women attempted to pursue a common goal. This chapter traces how Annie Kenney was first positioned as a representative of, and advocate for, working-class women, and later celebrated for her outstanding commitment to the cause, indicating that the meaning of class was fluid and shifting rather than fixed and static. The chapter raises ideas about the role and representation of working-class women within the WSPU, and demonstrates how women themselves attempted to navigate the complicated terrain of class hierarchies and gendered inequality.


2017 ◽  
Vol 114 (5) ◽  
pp. 1129-1134 ◽  
Author(s):  
Mara H. Sherman ◽  
Ruth T. Yu ◽  
Tiffany W. Tseng ◽  
Cristovao M. Sousa ◽  
Sihao Liu ◽  
...  

A fibroinflammatory stromal reaction cooperates with oncogenic signaling to influence pancreatic ductal adenocarcinoma (PDAC) initiation, progression, and therapeutic outcome, yet the mechanistic underpinning of this crosstalk remains poorly understood. Here we show that stromal cues elicit an adaptive response in the cancer cell including the rapid mobilization of a transcriptional network implicated in accelerated growth, along with anabolic changes of an altered metabolome. The close overlap of stroma-induced changes in vitro with those previously shown to be regulated by oncogenic Kras in vivo suggests that oncogenic Kras signaling—a hallmark and key driver of PDAC—is contingent on stromal inputs. Mechanistically, stroma-activated cancer cells show widespread increases in histone acetylation at transcriptionally enhanced genes, implicating the PDAC epigenome as a presumptive point of convergence between these pathways and a potential therapeutic target. Notably, inhibition of the bromodomain and extraterminal (BET) family of epigenetic readers, and of Bromodomain-containing protein 2 (BRD2) in particular, blocks stroma-inducible transcriptional regulation in vitro and tumor progression in vivo. Our work suggests the existence of a molecular “AND-gate” such that tumor activation is the consequence of mutant Kras and stromal cues, providing insight into the role of the tumor microenvironment in the origin and treatment of Ras-driven tumors.


2019 ◽  
Vol 11 (4) ◽  
pp. 703-723
Author(s):  
V. V. Naumkin

The article provides a fresh insight into the little known peacemaking initiative in the history of the Soviet diplomacy launched and planned by the head of the first Soviet diplomatic mission in the Arab world – in the Kingdom of Hejaz – Consul General Kerim Hakimov. As the troops commanded by Abdel Aziz bin Saud, the then ruler of Nejd, were rapidly approaching the Hejaz, and by the early 1925 had captured its capital Jeddah, Moscow, mindful of the future, gave its approval for Hakimov to get along with forging contacts with the Nejd representatives. The author reviews the motives underlying the decision to make an attempt at reconciliation between Ibn Saud and Sharif Hussein that would allow a possibility to establish a direct contact with the would-be founder of Saudi Arabia located in Mecca. Eventually, the Soviet Consul General managed to procure the vital information about the situation in Arabia and make a realistic assessment of Ibn Saud’s chances to gain victory. The trip made by the Consul General had an impact on Moscow’s determination to move forward along the way of supporting Ibn Saud in his efforts to unify the Arab lands, as a result, the USSR was the first nation to recognize the new state in Arabia.


2021 ◽  
Author(s):  
Joann Diray-Arce ◽  
Asimenia Angelidou ◽  
Kristoffer Jarlov Jensen ◽  
Maria Giulia Conti ◽  
Rachel S. Kelly ◽  
...  

SummaryVaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology, including metabolomics, enables new characterization of vaccine mechanisms of action, these tools have yet to be applied to infants at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employed mass spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea Bissau in vivo and the U.S. in vitro. BCG selectively altered plasma lipid pathways, including lysophospholipids. BCG-induced lysophosphatidylcholines (LPCs) correlated with both TLR agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising the possibility that LPCs contribute to BCG immunogenicity. Analysis of an independent newborn cohort from The Gambia demonstrated shared vaccine-induced metabolites such as phospholipids and sphingolipids. BCG-induced changes to the plasma lipidome and LPCs may contribute to its immunogenicity and inform the discovery and development of early life vaccines.HighlightsNeonatal BCG immunization generates distinct metabolic shifts in vivo and in vitro across multiple independent cohorts.BCG induces prominent changes in concentrations of plasma lysophospholipids (LPLs)BCG induced changes in plasma lysophosphatidylcholines (LPCs) correlate with BCG effects on TLR agonist- and mycobacterial antigen-induced cytokine responses.Characterization of vaccine-induced changes in metabolism may define predictive signatures of vaccine responses and inform early life vaccine development.Abstract FigureGraphical abstract:BCG vaccination perturbs metabolic pathways in vivo and in vitro.Vaccines have traditionally been developed empirically, with limited insight into their impact on molecular pathways. Metabolomics provides a new approach to characterizing vaccine mechanisms but has not yet been applied to human newborns, who are at the highest risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) prevents disseminated mycobacterial disease in children and can induce broad protection to reduce mortality due to non-TB infections. Underlying mechanisms are incompletely characterized. Employing mass spectrometry-based metabolomics, we demonstrate that early BCG administration alters the human neonatal plasma metabolome, especially lipid metabolic pathways such as lysophosphatidylcholines (LPCs), both in vivo and in vitro. Plasma LPCs correlated with both innate TLR-mediated and PPD antigen-induced cytokine responses suggesting that BCG-induced lipids might contribute to the immunogenicity of this vaccine. Vaccine-induced metabolic changes may provide fresh insights into vaccine immunogenicity and inform the discovery and development of early life vaccines.


1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.


2014 ◽  
Vol 1 (3) ◽  
pp. 3-7
Author(s):  
O. Zhukorskyy ◽  
O. Hulay

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.


2020 ◽  
Vol 11 (1) ◽  
pp. 22-26
Author(s):  
S.V. Tsymbal ◽  

The digital revolution has transformed the way people access information, communicate and learn. It is teachers' responsibility to set up environments and opportunities for deep learning experiences that can uncover and boost learners’ capacities. Twentyfirst century competences can be seen as necessary to navigate contemporary and future life, shaped by technology that changes workplaces and lifestyles. This study explores the concept of digital competence and provide insight into the European Framework for the Digital Competence of Educators.


Author(s):  
Andrew Erskine

Plutarch wrote twenty-three Greek Lives in his series of Parallel Lives—of these, ten were devoted to Athenians. Since Plutarch shared the hostile view of democracy of Polybius and other Hellenistic Greeks, this Athenian preponderance could have been a problem for him. But Plutarch uses these men’s handling of the democracy and especially the demos as a way of gaining insight into the character and capability of his protagonists. This chapter reviews Plutarch’s attitude to Athenian democracy and examines the way a statesman’s character is illuminated by his interaction with the demos. It also considers what it was about Phocion that so appealed to Plutarch, first by looking at his relationship with the democracy and then at the way he evokes the memory of Socrates. For him this was not a minor figure, but a man whose life was representative of the problems of Athenian democracy.


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