Globalization and Its Nuances

The PBS TV program History Detectives had an episode entitled “Atocha Spanish Silver” where the wreck of the Spanish ship Atocha was described like this:

“In 1985, one of the greatest treasure discoveries was made off the Florida Keys, when the wreck of the Spanish ship Atocha was found. On board were some forty tons of silver and gold, which in 1622 had been heading from the New World to the Spanish treasury as the means to fund the Thirty Years’ War.”

Is this an obvious case of globalization? What about Marco Polo? RomeHan dynasty China trade in silks? Silk Road and Samarkand? Colombus? Magellan? Vasco da Gama?

All of these cases constitute a kind of harmless kind of “pop globalization” based on exotic voyages and travels.

Consider another such example, perhaps more academic:

“About the middle of the sixteenth century Antwerp reached its apogee. For the first time in history there existed both a European and a world market; the economies of different parts of Europe had become interdependent and were linked through the Antwerp market, not only with each other but also with the economies of large parts of the rest of the world. Perhaps no other city has ever again played such a dominant role as did Antwerp in the second quarter of the sixteenth century.”

(Europe in the Sixteenth Century, Koenigsberger and Mosse, Holt Rinehart Publishers, 1968, page 50)

Debt repudiations in several places in the 1550s are described like this:

“This caused the first big international bank crash, for the Antwerp bankers now could not meet their own obligations.”

(Europe in the Sixteenth Century, Koenigsberger and Mosse, Holt Rinehart Publishers, 1968, page 51)

This sounds like some kind of identifiably global period.

Actually, modern historians define globalization as “price convergence” (i.e., wheat has now a unified “world price,” implying a world market). This rigorous definition is confirmed by and also shows up in the data in the 1820s and may or may not be prefigured by all the Marco Polo and Atocha silver stories, mentioned above.

These episodes in history are not there yet.

One sees wheat prices and other commodity prices converging in the 1820s and thereafter based on railroads, steamships and telegrams.

The classic in this kind of analysis is:

Globalization and History: The Evolution of a Nineteenth-Century Atlantic Economy, by Kevin O’Rourke and Jeffrey Williamson.

Kevin O’Rourke and Jeffrey Williamson present a coherent picture of In Globalization and History, Kevin O’Rourke and Jeffrey Williamson present a coherent picture of trade, migration, and international capital flows in the Atlantic economy in the century prior to 1914—the first great globalization boom, which anticipated the experience of the last fifty years. The authors estimate the extent of globalization and its impact on the participating countries, and discuss the political reactions that it provoked. The book’s originality lies in its application of the tools of open-economy economics to this critical historical period—differentiating it from most previous work, which has been based on closed-economy or single-sector models. The authors also keep a close eye on globalization debates of the 1990s, using history to inform the present and vice versa. The book brings together research conducted by the authors over the past decade—work that has profoundly influenced how economic history is now written and that has found audiences in economics and history, as well as in the popular press.

(book summary)

In everyday language, we associate the word globalization with some ever-increasing Marco Polo phenomena. While that’s not entirely wrong, globalization in the more technical sense begins to show up in the data only from the 1820s. At this point, we begin to see the convergence of worldwide wheat prices, for example. This makes the world, for the first time, a global “store” with unified prices. Here is the technical beginning of globalization. The years 1870-1914 are subsequently the first real era of modern globalization and represent a kind of “take-off” from the first stirrings of the 1820s. World Wars I & II might be seen as globalization backlash.

At this moment in world history, whether Putin’s invasion of Ukraine will constitute a new wave of deglobalization remains to be seen.

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


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 penilevaginal 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 CCMVBAC 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. Paeruginosa 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 Pnodorum 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 Aeaegypti 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]

Essay 110: Education and Famine Analysis

The great historian Élie Halévy’s (died in 1937) History of the English People in the Nineteenth Century, a multi-volume classic, gives us a sense of nineteenth century famine dynamics for the 1840s, which combines failed harvests and failed incomes and failed speculations together:

“It was a ‘dearth’ (i.e., scarcity)—a crisis belonging to the old order—the last ‘dearth,’ in fact, Europe had known up to the present day (i.e., before 1937). The unsatisfactory harvest of 1845 was followed by the disastrous autumn of 1846. The potato disease was worse than it had been the year before. The cereal harvest, moderately good in 1845, was a failure not only in the United Kingdom, but in France and throughout Western Europe. In 1845, Great Britain could still purchase corn even in Ireland, while the Irish poor were starving to death. Nothing of the kind was possible at the end of 1846.

Britain could not obtain wheat from France or Germany. In short, it was no longer Ireland alone, but the whole of Western Europe that had to be saved from famine.

“The United Kingdom, France, and Germany must import Russian and American wheat, the only sources available to supply the deficit.

“In consequence the price of wheat rose from 50 shillings and 2d. on August 22 to 65 shillings and 7d. on November 18. The price of wheat rose once more. It exceeded 78 shillings in March.

“In Germany and France, where another ‘jacquerie’ seemed to have begun, hunger caused an outbreak of rioting. The same happened in Scotland and the south of England…but England suffered in common with Ireland and Continental Europe, and a drain on English gold began, to pay for the Russian and American wheat.

“Later there was a fall of 50% in four months. The corn factors (i.e., corn dealers) who for months had been gambling on a rise had no time to retrace their steps and were ruined at a single blow.” (“Commerical Failures in 1847,” Eclectic Review, December 1847)

(Élie Halévy, “Victorian Years (1841-1895),” Halévy’s History of the English People in the Nineteenth Century, Volume 4, pages 191-193, Ernest Benn Ltd., 1970)

Note that in British usage, “corn” refers to all feed grains (primarily wheat), not corn (in the American sense) or maize. For example, see the Corn Laws.

We sense from Halévy’s description of the “food insecurity” of the nineteenth century in Europe, why the Revolutions of 1848 were to a large extent severe food riots and how food poverty and speculation interacted with risk and uncertainty prevailing.

This should be read and pondered in connection with Prof. Amartya Sen’s classic from 1981, Poverty and Famines, which highlights the famine of income and buying power, as opposed to famines based on outright crop failures. Pearl Buck’s classic novel, The Good Earth (1931), fits this topic set, as it analyzes in human terms the pattern of Chinese famines. It is interesting to note, parenthetically, that the movie of The Good Earth could not feature Chinese actors in lead roles due to racial craziness at the time. Stepping back, we see a world of food insecurity aggravated by the spectre of racism further poisoning social relations worldwide.

Halévy states: “It was a ‘dearth’ (i.e., scarcity)—a crisis belonging to the old order—the last ‘dearth,’ in fact, Europe had known up to the present day…”.

It would be instructive to ponder whether this really was “a crisis belonging to the old order” given the catastrophes and food crises that could come with climate change from 2019 on out. Will we have “global ‘dearths’”?