Bacterial EPIYA effectors – Where do they come from? What are they? Where are they going?

Recent studies have revealed a distinct class of bacterial effectors defined by the presence of EPIYA or EPIYA‐related motif. These bacterial EPIYA effectors are delivered into host cells via type III or IV secretion, where they undergo tyrosine phosphorylation at the EPIYA motif and thereby manipulate host signalling by promiscuously interacting with multiple SH2 domain‐containing proteins. Up to now, nine EPIYA effectors have been identified from various bacteria. These effectors do not share sequence homology outside the EPIYA motif, arguing against the idea that they have common ancestors. A search of mammalian proteomes revealed the presence of a mammalian EPIYA‐containing protein, Pragmin, which potentiates Src family kinase (SFK) activity by binding and sequestrating the SFK inhibitor Csk upon EPIYA phosphorylation. As several bacterial EPIYA effectors also target Csk, they may have evolved through generation of sequences that mimic the Pragmin EPIYA motif. EPIYA motifs are often diverged through multiple duplications in each bacterial effector. Such a structural plasticity appears to be due to intrinsic disorder of the EPIYA‐containing region, which enables the bacterial effectors to undergo efficient phosphorylation and mediate promiscuous interaction with multiple host proteins. Given the functional versatility of the EPIYA motif, many more bacterial EPIYA effectors will soon be emerging.     

Where are we going?

The foregoing study attempts to document the course of the American Society of Plastic and Reconstructive Surgeons, Inc. during the period 1964-1973, inclusive. A special attempt has been made to delineate the current trends. Trends, when recognized, may be enhanced, modified, or prevented-as deemed appropriate by the membership.     

Free centrosomes: Where do they all come from?

Centrosomes act as major microtubule-organizing centers in most cell types. Their functions in interphase and mitosis are usually facilitated by their association with the nucleus. This may be particularly true in very large cells. Several papers report free centrosomes in syncytial Drosophila embryos. However, this phenotype often remains little explored. Yet, free centrosomes can occur by multiple mechanisms, including functional defects of the mitotic spindle, detachment of centrosomes from the nuclear envelope, centrosome inactivation upon DNA damage, and de novo centrosome genesis. Deciphering the cellular mechanism leading to free centrosomes upon a given perturbation such as a mutation or injection of a drug, can provide valuable clues regarding the nature of the molecular pathway affected. To this end, genetic and cytological tests, as well as time-lapse imaging are available. These studies can inform on the biology of centrosomes, cell cycle regulation and cytoskeletal dynamics. Here we briefly discuss what to make of free centrosomes in the fly embryo.     

50 Years of Women in Cell Biology: Where have we been? Where are we going?

It’s been 50 years since Women in Cell Biology (WICB) was founded by junior women cell biologists who found themselves neither represented at the American Society for Cell Biology (ASCB) presentations nor receiving the information, mentoring, and sponsorship they needed to advance their careers. Since then, gender parity at ASCB has made significant strides: WICB has become a standing ASCB committee, women are regularly elected president of the ASCB, and half the symposia speakers are women. Many of WICB’s pioneering initiatives for professional development, including career panels, workshops, awards for accomplishments in science and mentoring, and career mentoring roundtables, have been incorporated and adapted into broader “professional development” that benefits all members of ASCB. The time has passed when we can assume that all women benefit equally from progress. By strategically, thoughtfully, and honestly recognizing the challenges to women of the past and today, we may anticipate those new challenges that will arise in the next 50 years. WICB, in collaboration with the ASCB, can lead in data collection and access and can promote diversity, equity, and inclusion. This work will be a fitting homage to the women who, half a century ago, posted bathroom stall invitations to the first Women in Cell Biology meetup.     

Sexual dimorphism in primates: Where are we and where do we go from here?

There are currently several debates taking place in palaeoanthropological circles in which the issue of sexual dimorphism is crucial. During the 60th Jubilee of the discovery of the TaungAustralopithecus skull, the authors concurred that much of the debate was due to differences in perception concerning dimorphism, and it was suggested that a study session dealing principally with sexual dimorphism in Primates should be organised with a view to determining what, if anything, could be observed in extant primates that might be utilised for determining the existence of dimorphism in fossil species. An advertisement was placed in the Journal of Human Evolution, calling for papers. Response was encouraging, suggesting that there was indeed a need for such a meeting, which was organised to take place late in November in Italy. Seventeen scientists sent abstracts, but due to the rather short notice, several were unable to attend the meeting. Nevertheless, papers were received and read at the meeting which form the basis for this issue of the Journal of Human Evolution. What remains to be done now, is for a second meeting to be organised at which the findings of the first meeting can be extended backwards in time into the fossil record.     

Physician prescribing practices: What do we know? Where do we go? How do we get there?

Although drug prescribing is one of the most important components of medical care, little is known about how prescribing practices are determined and how they can be influenced. Enhancing the quality and effectiveness of drug prescribing requires research and better dissemination of information to physicians and other decision-makers. This requires a collaborative effort and a coordinated action plan. Participants at the Physician Prescribing Practices Workshop, held in Ottawa in October 1995, addressed issues and made recommendations in three areas: current knowledge and issues for research in the field of prescribing practices, and the capacity of Canadian databases to study these issues, strategies for disseminating and implementing knowledge and research findings to enhance the quality of prescribing; and the formation of a network to foster collaboration among stakeholders.     

Variation of bar-press duration: Where do new responses come from?

Instrumental learning involves both variation and selection: variation of what the animal does, and selection by reward from among the variation. Four experiments with rats suggested a rule about how variation is controlled by recent events. Experiment 1 used the peak procedure. Measurements of bar-press durations showed a sharp increase in mean duration after the time that food was sometimes given. The increase was triggered by the omission of expected food. Our first explanation of the increase was that it was a frustration effect. Experiment 2 tested this explanation with a procedure in which the first response of a trial usually produced food, ending the trial. In Experiment 2, unlike Experiment 1, omission of expected food did not produce a large increase in bar-press duration, which cast doubt on the frustration explanation. Experiments 3 and 4 tested an alternative explanation: a decrease in expectation of reward increases variation. Both used two signals associated with different probabilities of reward. Bar presses were more variable in duration during the signal with the lower probability of reward, supporting this alternative. These experiments show how variation can be studied with ordinary equipment and responses.     

Where do they come from? Insights into autophagosome formation

Autophagosomes (APs) are unique organelles that enwrap cytoplasmic components when necessary. APs then fuse with lysosomes and enclosed materials are degraded. Although approximately 30 autophagy-related genes (ATG) required for AP formation have been identified, fundamental questions on the membrane source or dynamics during the formation remain unresolved. Here, we present a comprehensive overview of the putative membrane sources identified to date.     

Where do human schistosomes come from? An evolutionary approach

Schistosomiases affect between 200 and 400 million people, mainly in the tropical and poorly developed zones of the globe. They are often considered as the 'second' disease of mankind, just after malaria. One important question regarding human parasites is: are they the descendants of parasites that used to infect our primate ancestors and have had an evolution parallel to that of the human lineage, or are they the result of lateral transfers of parasites that evolved in different hosts? Recently, knowledge of the biology of schistosomes has dramatically increased, and answers to this and other questions are beginning to emerge.     

Where do animal alpha-amylases come from? An interkingdom trip

Alpha-amylases are widely found in eukaryotes and prokaryotes. Few amino acids are conserved among these organisms, but at an intra-kingdom level, conserved protein domains exist. In animals, numerous conserved stretches are considered as typical of animal alpha-amylases. Searching databases, we found no animal-type alpha-amylases outside the Bilateria. Instead, we found in the sponge Reniera sp. and in the sea anemone Nematostella vectensis, alpha-amylases whose most similar cognate was that of the amoeba Dictyostelium discoideum. We found that this "Dictyo-type" alpha-amylase was shared not only by these non-Bilaterian animals, but also by other Amoebozoa, Choanoflagellates, and Fungi. This suggested that the Dictyo-type alpha-amylase was present in the last common ancestor of Unikonts. The additional presence of the Dictyo-type in some Ciliates and Excavates, suggests that horizontal gene transfers may have occurred among Eukaryotes. We have also detected putative interkingdom transfers of amylase genes, which obscured the historical reconstitution. Several alternative scenarii are discussed.