evolution, Meta Intelligence

Being at Home in the World/Universe

The French philosopher Maurice Merleau-Ponty provided an introduction to the problem of being at home when he wrote:

“The world is not what I think, but what I live through. I am open to the world, I have no doubt that I am in communication with it, but I do not possess it; it is inexhaustible. ‘There is a world’, or rather: “There is the world’; I can never completely account for this ever-reiterated assertion in my life.”
Joseph J. Kockelmans (Editor), Phenomenology: The Philosophy of Edmund Husserl and Its Interpretation, Anchor Books Edition, 1967, page 369.

Remy C. Kwant, in his essay “Merleau-Ponty and Phenomenology”, commented:

For, according to him, the original lies buried in a dimension of darkness in such a way that it cannot be brought to light. Our existence is interwoven with the world, is a dialogue with the world. This dialogue reaches its most profound point there where the first and most original meaning arises, a meaning that is pre-conscious and pre-personal. Whatever is in our consciousness, whatever comes to light, becomes lucid, originates also in this darkness. As we have seen, man is able to obtain a measure of knowledge regarding this dark depth. He is able to divine something about the mysterious dialogue between the body-subject and the world. However, according to Merleau-Ponty, an absolute illumination of the phenomenal field is in principle impossible. All man can do is to erect some pointers in a darkness which resists full illumination.
Joseph J. Kockelmans (Editor), Phenomenology: The Philosophy of Edmund Husserl and Its Interpretation, Anchor Books Edition, 1967, page 390-391.

We sense that the interaction between ourselves and the world at every level may not be explainable. Therefore, we seek emotional or psychological shelter. The three levels of shelter are:

hearth and home
a sense of belonging
gods

Think of the song, “A House Is Not a Home”, sung by Dionne Warwick. “A chair is still a chair / Even though there’s no one sitting there … But a room is not a house
/ And a house is not a home” depicts the human longing for shelter via hearth and home. The French philosopher Bruno Latour referred to this as a “parliament of things.”

Consider “Gimme Shelter” by The Rolling Stones, as well as the novel (and later film) The Sheltering Sky by Paul Bowles. Both of these cover the deep issue of shelter.

Heidegger’s essay “Building Dwelling Thinking” (German: Bauen Wohnen Denken) states:

In what follows we shall try to think about dwelling and building. This thinking about building does not presume to discover architectural ideas, let alone to give rules for building. This venture in thought does not view building as an art or as a technique of construction; rather it traces building back into that domain to which everything that is belongs. We ask:

What is it to dwell?

How does building belong to dwelling?

I

We attain to dwelling, so it seems, only by means of building. The latter, building, has the former, dwelling, as its goal. Still, not every building is a dwelling. Bridges and hangars, stadiums and power stations are buildings but not dwellings; railway stations and highways, dams and market halls are built, but they are not dwelling places. Even so, these buildings are in the domain of our dwelling. That domain extends over these buildings and yet is not limited to the dwelling place. The truck driver is at home on the highway, but he does not have his shelter there; the working woman is at home in the spinning mill, but does not have her dwelling place there; the chief engineer is at home in the power station, but he does not dwell there. These buildings house man. He inhabits them and yet does not dwell in them, when to dwell means merely that we take shelter in them. In today’s housing shortage even this much is reassuring and to the good; residential buildings do indeed provide shelter; today’s houses may even be well planned, easy to keep, attractively cheap, open to air, light, and sun, but—do the houses in themselves hold any guarantee that dwelling occurs in them? Yet those buildings that are not dwelling places remain in turn determined by dwelling insofar as they serve man’s dwelling. Thus dwelling would in any case be the end that presides over all building. Dwelling and building are related as end and means. However, as long as this is all we have in mind, we take dwelling and building as two separate activities, an idea that has something correct in it. Yet at the same time by the means-end schema we block our view of the essential relations. For building is not merely a means and a way toward dwelling—to build is in itself already to dwell. Who tells us this? Who gives us a standard at all by which we can take the measure of the nature of dwelling and building?
Martin Heidegger, Poetry, Language, Thought, (translated by Albert Hofstadter), Harper & Row, 1975, pages 145-146.

Stuart Kauffman comes at this from a different angle:

Who are we? Where did we come from? Why are we here? Did Neanderthal, Homo habilis, or Homo erectus ask? Around which fire in the past 3 million years of hominid evolution did these questions first arise? Who knows.

Somewhere along our path, paradise has been lost, lost to the Western mind, and in the spreading world civilization, lost to our collective mind. John Milton must have been the last superb poet of Western civilization who could have sought to justify the ways of God to man in those early years foreshadowing the modern era. Paradise has been lost, not to sin, but to science. Once, a scant few centuries ago, we of the West believed ourselves the chosen of God, made in his image, keeping his word in a creation wrought by his love for us. Now, only 400 years later, we find ourselves on a tiny planet, on the edge of a humdrum galaxy among billions like it scattered across vast megaparsecs, around the curvature of space-time back to the Big Bang. We are but accidents, we’re told. Purpose and value are ours alone to make. Without Satan and God, the universe now appears the neutral home of matter, dark and light, and is utterly indifferent. We bustle, but are no longer at home in the ancient sense.
Stuart Kauffman, At Home in the Universe: The Search for the Laws of Self-Organization and Complexity, Oxford University Press, 1995, page 4.

Kauffman comes to grips with this problem with the final line above. He continues:

In this new view of life, organisms are not merely tinkered-together contraptions, bricolage, in Jacob’s phrase. Evolution is not merely “chance caught on the wing,” in Monod’s evocative image. The history of life captures the natural order, on which selection is privileged to act. If this idea is true, many features of organisms are not merely historical accidents, but also reflections of the profound order that evolution has further molded. If true, we are at home in the universe in ways not imagined since Darwin stood natural theology on is head with his blind watchmaker.
Stuart Kauffman, At Home in the Universe: The Search for the Laws of Self-Organization and Complexity, Oxford University Press, 1995, pages 25-26.

Kauffman wants to complete the Darwinian revolution by adding self-organization and complexity to natural selection. In his vision, this will begin to produce a holistic picture of who we are. This will perhaps allow us to feel “We are all at home in the universe, poised to sanctify by our best, brief, only stay.” [page 30.]

Zooming out from this, we can see a meta-intelligent sense in which science believes it can convert mysteries into problems using math. In contrast to this, philosophers believe the opposite, that the problems are becoming more mysterious.

World-Watching: How Nature Paints With Color

[from Quanta Magazine]

by Yasemin Saplakoglu

When objects interact with light in particular ways — by absorbing or reflecting it — we see in color. A sunset’s orange hues and the ocean’s deep blues inspire artists and dazzle observant admirers. But colors are more than pretty decor; they also play a critical role in life. They attract mates, pollinators and seed-spreaders, and signal danger. And the same color can mean different things to different organisms: A red bird might attract a mate, while a red berry might warn off a hungry human.

For color to communicate meaning, systems to produce it had to evolve, by developing pigments to absorb certain wavelengths of light or structures to reflect them. Organisms also had to produce the machinery to perceive color. When you look out into a forest, you might see lush greenery dappled with yellowish sunlight and pink blooms. But this forest scene would look different if you were a bird or a fly. Color-perception machinery — which include photoreceptors in our eyes that recognize and distinguish light — can differ between species. While humans can’t see ultraviolet light, some birds can. While dogs can’t see red or green, many humans can. Even within species there’s some variation: People who are colorblind have trouble distinguishing some combinations, such as green and red. And many organisms can’t see color at all.

Within one planet, many colorful worlds exist. But how did colors evolve in the first place?

What’s New and Noteworthy

To pinpoint when different kinds of color signals may have evolved, researchers recently reviewed many papers, covering hundreds of millions of years of evolutionary history, to bring together information from the fossil record and phylogenetic trees (diagrams that depict evolutionary relationships between species). Their analysis across the tree of life suggested that color signals likely evolved much later than color vision. It’s likely that color vision evolved twice, developing independently in arthropods and fish, between 400 million and 500 million years ago. Then plants started using bright colors to attract pollinators and animals to disperse their seeds, and then animals started using colors to warn off predators and eventually to attract mates.

One of the most common colors that we see in nature is green. However, this isn’t a color signal: It’s a result of photosynthesis. Most plants absorb almost all the photons in the red and blue light spectra but only 90% of the green photons. The remaining 10% are reflected, making the plants appear green to our eyes. But why did they evolve to do this? According to a model, this makes photosynthetic machinery more stable, suggesting that sometimes evolution favors stability over efficiency.

The majority of colors in nature are produced by pigments that absorb or reflect different wavelengths of light. While many plants can produce these pigments on their own, most animals can’t; instead, they acquire pigments from their diet. Some pigments, though, are hard to acquire, so some animals instead rely on nanoscale structures that scatter light in particular ways to create “structural colors.” For example, the shell of the blue-rayed limpet has layers of transparent crystals, each of which diffracts and reflects a sliver of the light spectrum. When the layers grow to a precise thickness, around 100 nanometers, the wavelengths in each layer interact with one another, canceling each other out — except for blue. The result is the appearance of a bright blue limpet shell.

Education and the Triple Helix underneath It

We want to restate the basic instinct and intuitions of this education or re-education project.

To get at the “schema” it will help you if you digress for a second and absorb this writeup of Professor Richard Lewontin’s (Harvard biology) 2002 masterpiece, The Triple Helix: Gene, Organism and Environment.

The blurb from Harvard University Press tells us:

“One of our most brilliant evolutionary biologists, Richard Lewontin has also been a leading critic of those—scientists and non-scientists alike—who would misuse the science to which he has contributed so much. In The Triple Helix, Lewontin the scientist and Lewontin the critic come together to provide a concise, accessible account of what his work has taught him about biology and about its relevance to human affairs. In the process, he exposes some of the common and troubling misconceptions that misdirect and stall our understanding of biology and evolution.

The central message of this book is that we will never fully understand living things if we continue to think of genes, organisms, and environments as separate entities, each with its distinct role to play in the history and operation of organic processes. Here Lewontin shows that an organism is a unique consequence of both genes and environment, of both internal and external features. Rejecting the notion that genes determine the organism, which then adapts to the environment, he explains that organisms, influenced in their development by their circumstances, in turn create, modify, and choose the environment in which they live.

The Triple Helix is vintage Lewontin: brilliant, eloquent, passionate and deeply critical. But it is neither a manifesto for a radical new methodology nor a brief for a new theory. It is instead a primer on the complexity of biological processes, a reminder to all of us that living things are never as simple as they may seem.”

Borrow from Lewontin the idea of a “triple helix” and apply it to the ultimate wide-angle view of this process of understanding. The educational triple helix includes and always tries to coordinate:

The student and their life (i.e., every student is first of all a person who is playing the role of a student). Every person is born, lives, and dies.
The student and their field are related to the rest of the campus. (William James: all knowledge is relational.)
The student and the world. (Container ships from Kaohsiung, Taiwan are bringing Lenovo and Acer computers to Bakersfield, California in a world of techno-commerce, exchange rates, insurance, customs, contractual arrangements, etc. In other words, always with some sense of the global political economy.)

The student keeps the triple helix “running” in the back of the mind and tries to create a “notebook of composite sketches” of the world and its workings and oneself and this develops through a life as a kind of portable “homemade” university which stays alive and current and vibrant long after one has forgotten the mean value theorem and the names and sequence for the six wives of Henry VIII).

The reader should think of Emerson’s point from his Journals of Ralph Waldo Emerson: 1824–1832—“The things taught in schools and colleges are not an education, but the means to an education.”

Education: Holding On to the Adventure Part of It

Education must hold on to learning-as-adventure or it goes stale.

Here’s a real example:

A man goes to his American Heritage Dictionary, to look up the word “vinaigrette” which he seems to remember as a salad dressing but finds there are as so often happens, other meanings.

The man’s eye looks down and comes across medicinal words close by like “vinblastine” and “vincristine” which have anti-tumor properties and are used in cancer medicine.

If you read the dictionary definitions receptively and thoughtfully you enter a world of tremendous complexity and interest (e.g., alkaloids, plant chemistry, phytochemistry, medicine, etc.). The Madagascar periwinkle plant is mentioned as a source for these alkaloids that become anti-neoplastic drugs. You wonder: why Madagascar? Why periwinkle plants? Why plants? These questions have “nontrivial” answers.

You also wonder about the nature of alkaloids and whether there are some evolutionary reasons why some plants produce food, some poisons (poison ivy, say), and others “good poisons” (i.e., alkaloids that can be made therapeutic through pharmacology).

You perhaps remember the PBS program of years ago about the black genius who did deep work in these and other “phytochemical” fields:

Percy Lavon Julian (April 11, 1899 – April 19, 1975) was a research chemist and a pioneer in the chemical synthesis of medicinal drugs from plants. He later started his own company to synthesize steroid intermediates from the wild Mexican yam. Julian received more than 130 chemical patents.

You can be dismissive and dismiss this “spontaneous questing” as a kind of woolgathering or “lolling about” mentally but the truth is often the opposite: it is only such “productive daydreams” that allow you to penetrate fields and topics and questions and problems by finding a “surprise window” or “backdoor” into them. Serendipity is very related to education, which has both formal or “do your homework” components to it and also a “wander about” one when you’re quite relaxed and mentally receptive.

Going from your “vinaigrette” definition quest, where you started, to wandering off into a deep look at vinblastine, vincristine, cancer, alkaloids and phytochemicals opens up “worlds” to you which is of course at the very basis of real education.

Pathogens-Watching

New Articles in PLOS Pathogens

Insertive Condom-Protected and Condomless Vaginal Sex Both Have a Profound Impact on the Penile Immune Correlates of HIV Susceptibility

by Avid Mohammadi, Sareh Bagherichimeh, Yoojin Choi, Azadeh Fazel, Elizabeth Tevlin, Sanja Huibner, Zhongtian Shao, David Zuanazzi, Jessica L. Prodger, Sara V. Good, Wangari Tharao & Rupert Kaul

Summary: In heterosexual men, the penis is the primary site of Human Immunodeficiency Virus (HIV) acquisition. Levels of inflammatory cytokines in the coronal sulcus are associated with an increased HIV risk, and we hypothesized that these may be altered after insertive penile sex. Therefore, we designed the Sex, Couples and Science Study (SECS study) to define the impact of penile–vaginal sex on the penile immune correlates of HIV susceptibility. We found that multiple coronal sulcus cytokines increased dramatically and rapidly after sex, regardless of condom use, with a return to baseline levels by 72 hours. The changes observed after condomless sex were strongly predicted by cytokine concentrations in the vaginal secretions of the female partner, and were similar in circumcised and uncircumcised men. We believe that these findings have important implications for understanding the immunopathogenesis of penile HIV acquisition; in addition, they have important implications for the design of clinical studies of penile HIV acquisition and prevention.

[Archived PDF]

Engineering, Decoding and Systems-Level Characterization of Chimpanzee Cytomegalovirus

by Quang Vinh Phan, Boris Bogdanow, Emanuel Wyler, Markus Landthaler, Fan Liu, Christian Hagemeier & Lüder Wiebusch

Summary: Human cytomegalovirus (HCMV) infection is associated with systemic disease in immunocompromised individuals and congenitally infected neonates. Animal CMVs and their bacterial artificial chromosome (BAC) clones have been utilized as models for CMV infection and thereby contributed immensely to the understanding of pathogenesis, host immune response and underlying molecular mechanism of CMV infections. As the closest relative to HCMV, the chimpanzee CMV (CCMV) holds a great potential as a model system for HCMV infection but its application was limited due to the lack of tools and data for functional genomic analyses. Here, the cloning of the CCMV as a BAC vector made its viral genome available to gene targeting techniques that allow the efficient application of reverse genetic strategies. Furthermore, the multi-omic datasets created in this study provide an in-depth view of the viral gene repertoire and the host cell responses to infection, confirming the close phylogenetic relationship between HCMV and CCMV on a system level. Taken together, the newly established CCMV–BAC system presents a framework for HCMV modeling and comparative studies to address key questions in evolutionary processes and infection mechanisms.

[Archived PDF]

RplI Interacts with 5′ UTR of exsA to Repress Its Translation and Type III Secretion System in Pseudomonas aeruginosa

by Dan Wang, Xinxin Zhang, Liwen Yin, Qi Liu, Zhaoli Yu, Congjuan Xu, Zhenzhen Ma, Yushan Xia, Jing Shi, Yuehua Gong, Fang Bai, Zhihui Cheng, Weihui Wu, Jinzhong Lin & Yongxin Jin

Summary: Ribosomes provide all living organisms the capacity to synthesize proteins. The production of many ribosomal proteins is often controlled by an autoregulatory feedback mechanism. P. aeruginosa is an opportunistic human pathogen and its type III secretion system (T3SS) is a critical virulence determinant in host infections. In this study, by screening a Tn5 mutant library, we identified rplI, encoding ribosomal large subunit protein L9, as a novel repressor for the T3SS. Further exploring the regulatory mechanism, we found that the RplI protein interacts with the 5’ UTR (5’ untranslated region) of exsA, a gene coding for transcriptional activator of the T3SS. Such an interaction likely blocks ribosome loading on the exsA 5’ UTR, inhibiting the initiation of exsA translation. The significance of this work is in the identification of a novel repressor for the T3SS and elucidation of its molecular mechanism. Furthermore, this work provides evidence for individual ribosomal protein regulating mRNA translation beyond its autogenous feedback control.

[Archived PDF]

Structure of a Bacterial Rhs Effector Exported by the Type VI Secretion System

by Patrick Günther, Dennis Quentin, Shehryar Ahmad, Kartik Sachar, Christos Gatsogiannis, John C. Whitney & Stefan Raunser

Summary: Bacteria have developed a variety of strategies to compete for nutrients and limited resources. One system widely used by Gram-negative bacteria is the T6 secretion system which delivers a plethora of effectors into competing bacterial cells. Known functions of effectors are degradation of the cell wall, the depletion of essential metabolites such as NAD⁺ or the cleavage of DNA. RhsA is an effector from the widespread plant-protecting bacteria Pseudomonas protegens. We found that RhsA forms a closed cocoon similar to that found in bacterial Tc toxins and metazoan teneurin proteins. The effector cleaves its polypeptide chain by itself in three pieces, namely the N-terminal domain including a seal, the cocoon and the actual toxic component which potentially cleaves DNA. The toxic component is encapsulated in the large cocoon, so that the effector producing bacterium is protected from the toxin. In order for the toxin to exit the cocoon, we propose that the seal, which closes the cocoon at one end, is removed by mechanical forces during injection of the effector by the T6 secretion system. We further hypothesize about different scenarios for the delivery of the toxin into the cytoplasm of the host cell. Together, our findings expand the knowledge of the mechanism of action of the T6 secretion system and its essential role in interbacterial competition.

[Archived PDF]

Non-Neutralizing Antibodies Targeting the Immunogenic Regions of HIV-1 Envelope Reduce Mucosal Infection and Virus Burden in Humanized Mice

by Catarina E. Hioe, Guangming Li, Xiaomei Liu, Ourania Tsahouridis, Xiuting He, Masaya Funaki, Jéromine Klingler, Alex F. Tang, Roya Feyznezhad, Daniel W. Heindel, Xiao-Hong Wang, David A. Spencer, Guangnan Hu, Namita Satija, Jérémie Prévost, Andrés Finzi, Ann J. Hessell, Shixia Wang, Shan Lu, Benjamin K. Chen, Susan Zolla-Pazner, Chitra Upadhyay, Raymond Alvarez & Lishan Su

Summary: In the past decade, HIV-1 has infected an estimated 1.5 to 2 million people every year, but vaccines needed to control this pandemic are unavailable. Among vaccines tested in the human efficacy trials, the RV144 vaccine regimen showed a modest efficacy and revealed non-neutralizing antibodies against the virus envelope glycoproteins as a correlate of reduced virus acquisition. To design more efficacious HIV-1 vaccines, a better understanding about antiviral mechanisms of these antibodies is needed. Here non-neutralizing monoclonal antibodies against two immunogenic sites on the virus envelope were evaluated for passive administration to humanized mice that were subsequently challenged with HIV-1. The antibodies did not block mucosal HIV-1 infection but reduced virus burden. The level of virus reduction correlated with the antibody binding potency and the effector functions mediated through their Fc fragments, which included antibody-dependent phagocytosis and complement activation, but not the commonly studied antibody-dependent cellular cytotoxicity. The importance of the Fc functions was further demonstrated by reduced virus control when mutations were introduced to decrease Fc activities. This study provides new evidence for the important contribution of multiple Fc-dependent antibody functions in immune control against HIV-1.

[Archived PDF]

Variability in an Effector Gene Promoter of a Necrotrophic Fungal Pathogen Dictates Epistasis and Effector-Triggered Susceptibility in Wheat

by Evan John, Silke Jacques, Huyen T. T. Phan, Lifang Liu, Danilo Pereira, Daniel Croll, Karam B. Singh, Richard P. Oliver & Kar-Chun Tan

Summary: Breeding for durable resistance to fungal diseases in crops is a continual challenge for crop breeders. Fungal pathogens evolve ways to overcome host resistance by masking themselves through effector evolution and evasion of broad-spectrum defense responses. Association studies on mapping populations infected by isolate mixtures are often used by researchers to seek out novel sources of genetic resistance. Disease resistance quantitative trait loci (QTL) are often minor or inconsistent across environments. This is a particular problem with septoria diseases of cereals such as septoria nodorum blotch (SNB) of wheat caused by Parastagonospora nodorum. The fungus uses a suite of necrotrophic effectors (NEs) to cause SNB. We characterized a genetic element, called PE401, in the promoter of the major NE gene Tox1, which is present in some P. nodorum isolates. PE401 functions as a transcriptional repressor of Tox1 and exerts epistatic control on another major SNB resistance QTL in the host. In the context of crop protection, constant surveillance of the pathogen population for the frequency of PE401 in conjunction with NE diversity will enable agronomists to provide the best advice to growers on which wheat varieties can be tailored to provide optimal SNB resistance to regional pathogen population genotypes.

[Archived PDF]

Mutational Analysis of Aedes aegypti Dicer 2 Provides Insights into the Biogenesis of Antiviral Exogenous Small Interfering RNAs

by Rommel J. Gestuveo, Rhys Parry, Laura B. Dickson, Sebastian Lequime, Vattipally B. Sreenu, Matthew J. Arnold, Alexander A. Khromykh, Esther Schnettler, Louis Lambrechts, Margus Varjak & Alain Kohl

Summary: Aedes aegypti mosquitoes that transmit human-pathogenic viruses rely on the exogenous small interfering RNA (exo-siRNA) pathway as part of antiviral responses. This pathway is triggered by virus-derived double-stranded RNA (dsRNA) produced during viral replication that is then cleaved by Dicer 2 (Dcr2) into virus-derived small interfering RNAs (vsiRNAs). These vsiRNAs target viral RNA, leading to suppression of viral replication. The importance of Dcr2 in this pathway has been intensely studied in the Drosophila melanogaster model but is largely lacking in mosquitoes. Here, we have identified conserved and functionally relevant amino acids in the helicase and RNase III domains of Ae. aegypti Dcr2 that are important in its silencing activity and antiviral responses against Semliki Forest virus (SFV). Small RNA sequencing of SFV-infected mosquito cells with functional or mutated Dcr2 gave new insights into the nature and origin of vsiRNAs. The findings of this study, together with the different molecular tools we have previously developed to investigate the exo-siRNA pathway of mosquito cells, have started to uncover important properties of Dcr2 that could be valuable in understanding mosquito-arbovirus interactions and potentially in developing or assisting vector control strategies.

[Archived PDF]

Probing the Structure and Function of the Protease Domain of Botulinum Neurotoxins Using Single-Domain Antibodies

by Kwok-ho Lam, Jacqueline M. Tremblay, Kay Perry, Konstantin Ichtchenko, Charles B. Shoemaker & Rongsheng Jin

Summary: Botulinum neurotoxins (BoNTs) are extremely toxic to humans by causing flaccid paralysis of botulism. The catalytic light chain (LC) of BoNTs is the warhead of the toxin, which is mainly responsible for BoNT’s neurotoxic effects. As an endopeptidase, LC is delivered by the toxin to inside neurons where it specifically cleaves neuronal SNARE proteins and causes muscle paralysis. While the currently available equine and human antitoxin sera can prevent further intoxication, they do not promote recovery from paralysis that has already occurred. We strike to develop single-domain variable heavy-chain (VHH) antibodies targeting the LC of BoNT/A (LC/A) and BoNT/B (LC/B) as antidotes to inhibit or eliminate the intraneuronal LC protease. Here, we report the identification and characterization of large panels of new and unique VHHs that bind to LC/A or LC/B. Using a combination of X-ray crystallography and biochemical assays, we reveal that VHHs exploit diverse mechanisms to interact with LC/A and LC/B and inhibit their protease activity, and such knowledge can be harnessed to predict their specificity towards different toxin subtypes within each serotype. We anticipate that the new VHHs and their characterization reported here will contribute to the development of improved botulism therapeutics having high potencies and broad specificities.

[Archived PDF]

B Cell Overexpression of FCRL5 and PD-1 Is Associated with Low Antibody Titers in HCV Infection

by Clinton O. Ogega, Nicole E. Skinner, Andrew I. Flyak, Kaitlyn E. Clark, Nathan L. Board, Pamela J. Bjorkman, James E. Crowe Jr., Andrea L. Cox, Stuart C. Ray & Justin R. Bailey

Summary: Antiviral immunity relies on production of protective immunoglobulin G (IgG) by B cells, but many hepatitis C virus (HCV)-infected individuals have very low levels of HCV-specific IgG in their serum. Elucidating mechanisms underlying this suboptimal IgG expression remains paramount in guiding therapeutic and vaccine strategies. In this study, we developed a highly specific method to capture HCV-specific B cells and characterized their surface protein expression. Two proteins analyzed were Fc receptor-like protein 5 (FCRL5), a cell surface receptor for IgG, and programmed cell death protein-1 (PD-1), a marker of lymphocyte activation and exhaustion. We measured serum levels of anti-HCV IgG in these subjects and demonstrated that overexpression of FCRL5 and PD-1 on memory B cells was associated with reduced anti-E2 IgG levels. This study uses HCV as a viral model, but the findings may be applicable to many viral infections, and they offer new potential targets to enhance antiviral IgG production.

[Archived PDF]