How to Be an Info-Observer and Knowledge Self-Educator: Parachutist Skills

MetaIntelligence is the mental jump where you go from being processed by the system to being the processor of the system.

The U.S. Federal Deposit Insurance Corporation has a “flagship” publication called FDIC Quarterly.

In Volume 15 of this periodical, Number 2, 2021 [PDF] there’s an article called:

The Historic Relationship between Bank Net Interest Margins and Short-Term Interest Rates

(pages 31 to 41)

The authors of this piece have a boxed insert on the first page where they define NIM (Net Interest Margin) which is a phrase and acronym you see in the title above.

The insert begins like this:

Net Interest Margin is a key profitability ratio…

This measure is so popular that banks report it, bank examiners assess it for individual banks, and the FDIC calculates it for the industry every quarter in the “Quarterly Banking Profile.” For a vast majority of banks, net interest income is the primary source of income, and for such banks NIM is a primary component of profitability.

(FDIC Quarterly, 2021, Volume 15, Number 2, page 31)

Such FDIC publications are freely available online and otherwise. Suppose you borrow an issue from the Library or download a copy from their archive and read it attentively. You could begin the process of “parachuting” into something outside of your ken, namely banking and finance.

This learning to become a “parachutist” in knowledge and information is the only way to escape the kind of “house arrest” forced on you by whatever you happened to specialize in in school and if you accept this kind of “knowledge detention” you will always be “stranded on your lonely island” which is not what you want and is potentially a form of “stupidization.” This agility acknowledges the fact that obviously “you can’t major in everything.”

To parachute in and back out of knowledge domains is a profound component of the remedial educational skill we call MetaIntelligence.

European Central Bank’s Macroprudential Bulletin

The European Central Bank’s Macroprudential Bulletin provides insight into the work they are currently doing in the field of macroprudential policy. Their goal is to raise awareness of macroprudential policy issues in the euro area by making their ongoing work and thinking in this field more transparent, and to encourage broader discussion on these key issues.

January 2022, Issue 16

Reforming money market funds

Money market funds perform a key function for the financial system by linking the short-term funding and cash-management needs of various market participants. Proposals to reform the regulation of these funds and enhance the sector’s resilience are assessed in this issue of the Macroprudential Bulletin.

Assessing possible reform proposals

At the onset of the coronavirus pandemic, money market funds proved particularly vulnerable when faced with severe market disruption. This article looks at specific policies to address the liquidity risk of these funds and ensure they can deal with large and unexpected outflows under similar periods of stress.

[Archived PDF of full article]

The impact of a public debt quota on money market funds

Public debt assets tend to be easier to draw down and sell during market stress than private sector debt. Having a minimum public debt quota for private debt money market funds could increase their shock-absorbing capacity. What are the costs and benefits of such a proposal?

[Archived PDF of full article]

Science and Its Discontents: The Case of Natsume Sōseki (夏目 漱石) in Japan

Natsume Sōseki (夏目 漱石) is and was the most prestigious and respected novelist in modern Japan and every student has to engage with such novels of his as Botchan (坊っちゃん, “Young Master”) and Kokoro (こゝろ, or in post-war orthography こころ, “Heart”). Sōseki died in 1916.

Sōseki’s feeling that the modern world is some kind of runaway train with no brakes is expressed clearly in his 1913 novel, Kōjin (行人 , “The Wayfarer”).

One of Sōseki’s dialogues in the novel is about the current science and technology world, which was quite visible already then, and has a very nerve-racking or frightening tempo of a turbulent tsunami.

One character says:

“Now what you call insecurity is the insecurity of the entire human race, and it isn’t peculiar to you alone. Constant motion and flow is our very fate.

“Man’s insecurity stems from the advance of science. Never once has science, which never ceases to move forward, allowed us to pause. From walking to ricksha, from ricksha to carriage, from carriage to train, from train to automobile, from there on to the dirigible, further on to the airplane, and further on and on, no matter how far we may go, it won’t let us take a breath. How far it will sweep us along, nobody knows for sure. It is really frightening.”

Yes, it is frightening, indeed, I agreed.

“It is frightening because the fate that the whole of humanity will reach in several centuries, I must go through—in my own lifetime—and at that all alone. That’s why it is frightening. In short, I gather within myself the whole insecurity of the human race, and distill that insecurity down into every moment, that is the fright that I am experiencing.”

(Natsume Sōseki, Kōjin [行人], Charles E. Tuttle Company, 1991, 9th printing, page 285)

Comment: There’s no need to dismiss these feelings as Luddite. They represent a reaction to the vertiginous or dizzying pace of the modern techno-protean change machine with no pause button.

Notice that Sōseki’s life (1867-1916) is basically congruent with Globalization I (i.e., the period of 1870-1913) discussed in the previous essay on Arthur Lewis’s classic Growth and Fluctuations, 1870-1913.

Sōseki has been, like his spokesmen in the citation above, swept up into a change-storm which led to a globalization backlash from 1914-1945, the era of deglobalization. WWI is the beginning bookend of all this.

Notice that the micro world of feelings and moods in the novel are resonant with the macro world though people at a certain time, such as the Sōseki protagonists, are not rigorous or prophetic theoreticians but rather groping in the dark.

What We Mean by “Towards a Composite Understanding of Education”

(MI slogan, motto or catchphrase)

Let’s be concrete and start with the title of the classic 1978 book by the Princeton professor and 1979 Nobel Prize winner, Sir Arthur Lewis, Growth and Fluctuations, 1870-1913 (introduced in the previous essay on “Looking Backwards and Forwards at the Same Time”).

Notice the following other dimensions that have to be included to “compositize” our understanding:

  1. The period 1870-1913/4 is called Globalization I by economic historians. Globalization in this view is not about Marco Polo, but the rise of world prices, such as for wheat.

  2. Paul Kennedy (Yale), who is known for his Rise and Fall of the Great Powers classic, wrote a tighter book called The Rise of the Anglo-German Antagonism, 1860-1914 (1980), described as follows:

    “This book gives an account of the rivalry between Great Britain and Germany in the period leading to the First World War. It gives readers a thorough comparison of the two societies, their political cultures, economies, party politics, courts, the role of the press and pressure groups, and so on. …”

  3. The first treaty between a European power and an Asian country was signed in 1902, “The Anglo-Japanese Alliance.”

    “In this book, Professor Nish deals with one of the most important aspects of far eastern politics in the critical period between 1894 and 1907. His object is to demonstrate how Britain and Japan, at first separately and later jointly, reacted to Russian encroachments in China and east Asia; he is concerned also with the policies of the other European powers and of the U.S., to whose hostility towards the Anglo-Japanese alliance after 1905 Britain showed…”

  4. The first defeat of a European by an Asian nation (i.e., the Russo-Japanese War, 1904-5). The famous Indian writer Pankaj Mishra wrote a recent book on this, showing how this defeat of a European country sent shock waves through the world and especially through the anti-colonial movements of Asia and Africa…

  5. Partition of Africa:

    “Between 1870 and 1914 the whole of Africa, apart from one or two small areas, was partitioned by the European powers.”

    (David Thomson, England in the Nineteenth Century, 1815-1914, 1978, Penguin Books, page 203)

  6. Rise of Suburbia:

    “The 1890s saw the coming of the first electric trams, the first “tubes,” and the first motor-cars. By 1914, almost any provincial city of any size had its electric trams, mostly under municipal control, and London had its buses and underground (i.e., subway). “These changes in urban transport created suburbia.”

    (David Thomson, England in the Nineteenth Century, 1815-1914, 1978, Penguin Books, page 202)

In other words, the world itself is a crisscrossing composite of processes at different scales.

We have growth and fluctuations, the partition of Africa, suburbanization, Anglo-German tensions, techno-revolutions (including those in urban transport), interacting with Globalization I.

All of this culminated in the “guns of August” (i.e., World War I).

We are downstream from World War I, what the Germans call the “Urkatastrophe” (i.e., original calamity), and its reincarnation in World War II and its progeny, the Cold War.

The more you can “compositize” the elements of this “historical matrix,” the deeper your MetaIntelligence will be. Hence the catchphrase for the MI site:

“Towards a Composite Understanding of Education”

Looking Backwards and Forwards at the Same Time

Janus and Bi-Directional Smarts

The Roman god Janus looks backwards and forwards at the same time and learning to be somewhat Janus-like is very conducive in the metaintelligence (i.e., larger overview) quest.

There’s a useful French phrase, “reculer pour mieux sauter” which means like a high jumper, you have to take steps backwards to jump higher. In other words, learn to look bi-directionally at the world.

First look back, then forward.

Here’s a concrete example:

W. Arthur Lewis, the “father” of development economics, originally from the Caribbean, taught at Princeton. He won the Nobel in 1979 and wrote various classics such as Growth and Fluctuations, 1870-1913 (1978).

Lewis writes:

In this book we shall not be attempting to give formal or complete explanations of why fluctuations occurred. Like the captain of a ship navigating in stormy seas, we shall need to identify the waves, without needing an exhaustive theory of what causes waves.

When analyzing these fluctuations economists have identified four different cycles, distinguished by length of periodicity, each of which is named after the economist who first wrote about it:

the Kitchin (about three years)
the Juglar (about nine years)
the Kuznets (about twenty years)
the Kondratiev (about fifty years)

(W. Arthur Lewis, Growth and Fluctuations, 1870-1913, 1978, page 19)

Lewis gives us a quick overview of how we got to the era covered by his book:

“The essence of the industrial and agricultural revolutions in the first three quarters of the nineteenth century was in new ways of doing old things—of making iron, textiles and clothes, of growing cereals, and of transporting goods and services. In the last quarter of the nineteenth century the revolution added a new twist—that of making new commodities: telephones, gramophones, typewriters, cameras, automobiles and so on, a seemingly endless process whose twentieth century additions include aeroplanes, radios, refrigerators, washing machines and pleasure boats.”

(Growth and Fluctuations, 1870-1913, page 29)

Professor Norman Stone in his masterpiece on WWI calls this late nineteenth century explosion of material change and inventions the greatest fast quantum leap in world history in transforming the world.

If one reads these lines with a “Janus mind” we wonder, looking forward from the Lewis book and its era:

  1. How does his catchy metaphor of waves in the ocean relate to fluctuations and cycles? When Ben Bernanke (Fed Chair) describes recent decades as “The Great Moderation” does he mean to imply that Lewis-type waves disappeared or got much smaller?
  2. Can computers and mobile phones really match cars and planes in profundity of impact? Or is it only the tremendous spread of mobile or smartphones in the Global South that can?

In fact, the recent economic history classic, Robert Gordon’s The Rise and Fall of American Growth argues against the assumption of endless technical change as a growth accelerator or endless frontier:

In the century after the Civil War, an economic revolution improved the American standard of living in ways previously unimaginable. Electric lighting, indoor plumbing, home appliances, motor vehicles, air travel, air conditioning, and television transformed households and workplaces. With medical advances, life expectancy between 1870 and 1970 grew from 45 to 72 years. Weaving together a vivid narrative, historical anecdotes, and economic analysis, The Rise and Fall of American Growth provides an in-depth account of this momentous era. But has that era of unprecedented growth come to an end?

Gordon challenges the view that economic growth can or will continue unabated, and he demonstrates that the life-altering scale of innovations between 1870 and 1970 can’t be repeated. He contends that the nation’s productivity growth, which has already slowed to a crawl, will be further held back by the vexing headwinds of rising inequality, stagnating education, an aging population, and the rising debt of college students and the federal government. Gordon warns that the younger generation may be the first in American history that fails to exceed their parents’ standard of living, and that rather than depend on the great advances of the past, we must find new solutions to overcome the challenges facing us.

A critical voice in the debates over economic stagnation, The Rise and Fall of American Growth is at once a tribute to a century of radical change and a harbinger of tougher times to come.

  1. Why does one not read of the four cycles mentioned by Lewis (i.e., Kitchin) and the rest listed above in today’s business and financial press? Has there been some great discontinuity?

If you apply a “Janus mind” to the past (described by Lewis) and our sense of the future (described by techno-pessimists like Gordon) you get a more thoughtful sense of “the human prospect.”

IMF, ECB and Others Give 2022 Economic Outlook Today

from the World Economic Forum Davos Agenda:

Today the IMF, European Central Bank, and global economic leaders discussed the future of the economy at the “Global Economic Outlook” session at Davos Agenda 2022.

Inflation, global economic recovery and COVID-19 impacts are discussed.

Please find selected quotes below. View the full session here.

Christine Lagarde, President, European Central Bank:

“In Europe, we are not seeing inflation spiral out of control. We assume energy prices will stabilize from the middle of 2022, bottlenecks will also stabilize in 2022 and gradually, inflation numbers will decline.”

“When I look at the labor market, we are not experiencing anything like The Great Resignation, and our employment participation numbers are getting very close to the pre-pandemic level.”

“In Europe we are unlikely to face the kind of inflation increases that the U.S. market has faced.”

“More recently, we have learnt the lesson of humility–the ECB, IMF, OECD and others all underestimated the recovery, the employment participation and, obviously, inflation.”

Kristalina Georgieva, Managing Director, International Monetary Fund (IMF):

“The response to the pandemic crisis has been anything but orthodox— in a highly coordinated manner both central banks and finance authorities have prevented the world falling into yet another great depression.”

“If I were to offer policy makers a new year’s resolution, it would policy flexibility.”

“In low-income countries, 60% are in either debt distress or in danger of debt distress–more than twice as many as in 2015.”

Haruhiko Kuroda (黒田 東彦), Governor, Bank of Japan:

“Japan response to the pandemic has been relatively successful, however, the pandemic has had a significant, negative impact on Japan’s economy.”

“Unlike U.S. or Europe, we have to continue extremely accommodative, easy monetary policy for the time being. We expect the inflation rate in 2022 and 2023 to be around 1 percent still.”

Paulo Guedes, Minister of Economy, Ministry of Economy of Brazil:

“Central banks are sleeping at the wheel–inflation will be a real problem very soon for the western world.”

“More than 3 million new jobs were created in 2021 and the government has assisted 68 million Brazilians with direct income transfers.”

Sri Mulyani Indrawati, Minister of Finance, Ministry of Finance of Indonesia: 

“We see a strong recovery in the Indonesian economy in 2022, and to build on this we are expecting more than 1% of additional GDP growth from a series of recent reforms.”

“Indonesia is the largest economy in the ASEAN region, but it is vulnerable to a dependence on commodities–the emphasis now is on value-added activities.”

About the Davos Agenda 2022

For over 50 years, the World Economic Forum has been the international organization for public-private cooperation. The Davos Agenda 2022 is the focal point at the start of the year for leaders to share their outlook, insights and plans relating to the most urgent global issues. The meeting will provide a platform to accelerate the partnerships needed to tackle shared challenges and shape a more sustainable and inclusive future. Learn more about the program and view sessions live and on demand.

Interesting Intuition from Marx

There’s an intriguing and puzzling quote from Marx which is very informative in a completely unexpected way, when Marx says:

“Life is not determined by consciousness, but consciousness by life.”
(The German Ideology, International Publishers, 1970, page 47)

This seems to fit Marx’s obsession with practical circumstances as the “driver” and ideas and subjective states of mind as secondary or even derivative. For Marx, culture and consciousness are “epiphenomena” like the foam on a wave.

In a different way, modern philosophers have their own versions of this:

  1. For Wittgenstein, “forms of life” come first before all else.
  2. For Husserl, “the life-world” comes before theory.
  3. For Heidegger, “being-in-the-world” comes before theory.

Marx’s reduction of everything to material circumstances as primary causes of everything would seem to these other philosophers as a kind of extremist monomania on Marx’s part, as when he says:

We do not set out from what men say, imagine, conceive, nor from men as narrated, thought of, imagined, conceived, in order to arrive at men in the flesh. We set out from real, active men, and on the basis of their real life-process we demonstrate the development of the ideological reflexes and echoes of this life-process. Their material life-process dominates.

The phantoms formed in the human brain are also, necessarily, sublimates of their material life-process which is empirically verifiable and bound to material premises. Morality, religion, metaphysics, all the rest of ideology and their corresponding forms of consciousness, thus no longer retain the semblance of independence.

Karl Marx with Friedrich Engels, The German Ideology, page 47

This idea from Marx is both suggestive and obsessive and maniacal at the same time, what the French call an “idée fixe” or fixation.

It is more accurate to say perhaps that life and consciousness are a “double helix.”

How to See Fundamental Tension in the World Easily

People-Class Part II

A few years ago, in 2006, there was a first rate movie called The Last King of Scotland with the great black American actor, Forest Whitaker, playing barbaric Idi Amin Dada Oumee who destroyed the life of the Asian community in Uganda in the 1970s.

This great actor later appeared on the TV talk show, The Charlie Rose Show. Charlie Rose and Whitaker were discussing the movie and Rose denounces Idi Amin as the mad barbarian he was.

But Whitaker objects and says, “You gotta keep in mind, Charlie, that more than 90% of Ugandan commerce was in Asian hands and the situation was not viable.”

We have here a simple way of seeing our world more clearly since commerce is a cosmopolitan activity of business people whereas “ethnonational” considerations (expressed by Whitaker) are tribal and backward or inward looking and not conducive to cosmopolitanism.

Somebody once made the quip that the world, country by country, is divided into the tribal “ethnonational” Serbs (so to speak) in conflict with the “cosmopolitans.”

In this vocabulary Trump and Trumpism are “Serbian.” He will decide who is and who is not a “real American.”

Go back to our essay on the concept of “people–class” and all the attendant genocidal murders. (Uganda under Amin being the example we’re mindful of here).

Ethnonationalism (e.g., “Serbian” style anti-cosmopolitanism) is of course exactly what is at war with cosmopolitan or internationalist global trends and commercial chains which makes it nativist. Populism refers to that connected sense that the elites (in the worst case, “The Davos Crowd”) are trying to destroy the real people (e.g., “Trump’s America”) via their internationalist or cosmopolitan attitudes and behaviors.

Thus the movie The Last King of Scotland and the discussions it engendered are very “canonical” or educational in laying forth this “civil war” everywhere.

Thinking of a group as a “people–class” tells you that Idi Amin or Rwanda 1994 belligerence (i.e., ethnonationalism) is being stoked by politicians to create “hatred opportunities” like Trump did. Trump’s idea was to use hatred as a “wave maker” that he could ride. The Trump voters created a nativist/populist cult figure in Trump. He would protect them from the outside world and globalism by ethnonationalism.

Forest Steven Whitaker (born July 15, 1961) is an American actor, producer, director, and activist. He is the recipient of such accolades as an Academy Award, a Golden Globe Award, a British Academy Film Award, and two Screen Actors Guild Awards.

After making his film debut in Fast Times at Ridgemont High (1982), Whitaker went on to earn a reputation for intensive character study work for films such as Bird; Good Morning, Vietnam; The Crying Game; Platoon; Ghost Dog: The Way of the Samurai; The Great Debaters; The Butler; Arrival; and Respect. He has also appeared in blockbusters such as Panic Room, Rogue One: A Star Wars Story as Saw Gerrera and Black Panther as Zuri. For his portrayal of Ugandan dictator Idi Amin in the British historical drama film The Last King of Scotland (2006), Whitaker won the Academy Award for Best Actor.

Wikipedia

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.

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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.

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Is the Concept of “People-Class” Illuminating?

Abram Leon was a tragic Belgian/Polish Jewish sociologist who was murdered by the Nazis in 1944. He fused the concept of people (e.g., the French people, or the Japanese people) with the concept of class (e.g. “the working class”) to make a hybridized concept of people–class.

Can we say that the Rwandan genocide in 1994, say, was the murder of a people–class (i.e., the Tutsi)?

Were the Armenian victims in 1915 an analogous phenomenon for the Ottoman Empire?

One immediately thinks of the Jews of Europe in WWII and the Chinese in 1965 Indonesia. (Think of the movie, The Year of Living Dangerously with Mel Gibson, which gives some “atmospherics” for this time in Indonesia.)

Is the Abram Leon notion of a people–class helpful in understanding these modern genocidal phenomena as an ensemble?

Meta intelligence is defined as working towards a “Composite Understanding of Education,” as you see in the masthead for this site.

Is people–class such a composite?