Existence as Economy and as Charity

Antonio Caso, “La existencia como economía y como caridad” (1916). Translated with Jose G. Rodriguez Jr. as “Existence as Economy and as Charity,” in 20th Century Mexican Philosophy: Essential Readings, eds. Carlos Alberto Sánchez and Robert Eli Sanchez, Jr. (New York: Oxford University Press, 2017)

Existence as Economy and as Charity An Essay on the essence of Christianity (1916) by: Antonio Caso

Antonio Caso rejects the effort of biologists to reduce life to the organic world, a sphere of existence that is defined by economy and egoism, best summarized in the formula: Life = Minimum Effort x Maximum Gain. The problem is that this cannot explain what he calls “disinterested activity,” such as play, art, and self-sacrifice. His primary example of disinterested or selfless activity is the life of Jesus, which Caso also believes is the height of human dignity. In other words, Caso not only argues that there is more than one order of life or existence; he also argues that selfless activity is ultimately what distinguishes human life, whose best expression is found in the essence of Christianity: to give oneself to others “without fear of exhaustion.” To be human is to be willing to sacrifice oneself, best expressed in the following formula: Sacrifice = Maximum Effort x Minimum Gain

Decline of Spectacled Eiders Nesting in Western Alaska

Spectacled eider (Somateria fischeri) populations in western Alaska are now less than 4% of the numbers estimated in the early 1970s. In 1992, an estimated 1721 nesting pairs remained on the Yukon-Kuskokwim Delta. Causes of this rapid and continuing decline of -14% per year are undocumented. Many aspects of spectacled eider biology remain unknown, including their marine foraging habitats, food items, migratory movements, and population ecology. A review of some biological characteristics and possible threats to the species suggests the importance of quantifying potential impacts from parasites and disease, subsistence harvest, predation during brood rearing, and alteration of Bering Sea food resources. Factors causing the population decline of spectacled eiders must be determined and appropriate actions taken to reverse the trend.Key words: Alaska, declining species, Somateria fischeri, spectacled eider, waterfowl, Yukon-Kuskokwim DeltaLes populations d'eider à lunettes (Somateria fischeri) de l'Alaska occidental s'élèvent maintenant à moins de 4 p. cent du total estimé au début des années 70. En 1992, on a estimé à 1721 le nombre de paires nicheuses qui restaient dans le delta du Yukon-Kuskokwim. Les causes de ce déclin rapide et continu de -14 p. cent par an ne sont pas documentées. Bien des aspects de la biologie de l'eider à lunettes restent inconnus, y compris l'habitat marin où il trouve sa nourriture, ses aliments, ses déplacements migratoires et l'écologie de la population. Un examen de certaines caractéristiques biologiques et des menaces dont l'espèce pourrait faire l'objet suggère l'importance qu'il y a à quantifier les retombées potentielles des parasites et des maladies, des récoltes destinées à assurer la subsistance, de la prédation durant l'élevage de la couvée et des changements dans les ressources alimentaires de la mer de Béring. Il faut déterminer les facteurs responsables du déclin de la population de l'eider à lunettes et prendre les mesures qui s'imposent pour renverser la tendance.Mots clés : Alaska, espèce en déclin, Somateria fischeri, eider à lunettes, oiseau aquatique, delta du Yukon-Kuskokwi

Testing and modeling of a traditional timber mortise and tenon joint

The structural safety and behaviour of traditional timber structures depends significantly on the performance of their connections. The behaviour of a traditional mortise and tenon timber joint is addressed using physical testing of full-scale specimens. New chestnut wood and old chestnut wood obtained from structural elements belonging to ancient buildings is used. In addition, the performance of different semi and non-destructive techniques for assessing global strength is also evaluated. For this purpose, ultrasonic testing, micro-drilling and surface penetration are considered, and the possibility of their application is discussed based on the application of simple linear regression models. Finally, nonlinear finite element analysis is used to better understand the behaviour observed in the full-scale experiments, in terms of failure mode and ultimate load. The results show that the ultrasonic pulse velocity through the joint provides a reasonable estimate for the effective- ness of the assembly between the rafter and brace and novel linear regressions are proposed. The failure mechanism and load–displacement diagrams observed in the experiments are well captured by the proposed non-linear finite element analysis, and the parameters that affect mostly the ultimate load of the timber joint are the compressive strength of wood perpendicular to the grain and the normal stiffness of the interface elements representing the contact between rafter and brace

A small molecule inhibitor of tropomyosin dissociates actin binding from tropomyosin-directed regulation of actin dynamics

The tropomyosin family of proteins form end-to-end polymers along the actin filament. Tumour cells rely on specific tropomyosin-containing actin filament populations for growth and survival. To dissect out the role of tropomyosin in actin filament regulation we use the small molecule TR100 directed against the C terminus of the tropomyosin isoform Tpm3.1. TR100 nullifies the effect of Tpm3.1 on actin depolymerisation but surprisingly Tpm3.1 retains the capacity to bind F-actin in a cooperative manner. In vivo analysis also confirms that, in the presence of TR100, fluorescently tagged Tpm3.1 recovers normally into stress fibers. Assembling end-to-end along the actin filament is thereby not sufficient for tropomyosin to fulfil its function. Rather, regulation of F-actin stability by tropomyosin requires fidelity of information communicated at the barbed end of the actin filament. This distinction has significant implications for perturbing tropomyosin-dependent actin filament function in the context of anti-cancer drug development

On-target action of anti-tropomyosin drugs regulates glucose metabolism

The development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets. The impact of the drugs on GSIS was significantly less in Tpm3.1 knock out (KO) mice indicating that the drug action is on-target. Experiments in MIN6 β-cells indicated that the inhibition of GSIS by the drugs was due to disruption to the cortical actin cytoskeleton. The impact of the drugs on insulin-stimulated glucose uptake (ISGU) was also examined in skeletal muscle ex vivo. In the absence of drug, ISGU was decreased in KO compared to WT muscle, confirming a role of Tpm3.1 in glucose uptake. Both compounds suppressed ISGU in WT muscle, but in the KO muscle there was little impact of the drugs. Collectively, this data indicates that the ATM drugs affect glucose metabolism in vivo by inhibiting Tpm3.1's function with few off-target effects

Regulation of cell proliferation by ERK and signal-dependent nuclear translocation of ERK is dependent on Tm5NM1-containing actin filaments

ERK-regulated cell proliferation requires multiple phosphorylation events catalyzed first by MEK and then by casein kinase 2 (CK2), followed by interaction with importin7 and subsequent nuclear translocation of pERK. We report that genetic manipulation of a core component of the actin filaments of cancer cells, the tropomyosin Tm5NM1, regulates the proliferation of normal cells both in vitro and in vivo. Mouse embryo fibroblasts (MEFs) lacking Tm5NM1, which have reduced proliferative capacity, are insensitive to inhibition of ERK by peptide and small-molecule inhibitors, indicating that ERK is unable to regulate proliferation of these knockout (KO) cells. Treatment of wild-type MEFs with a CK2 inhibitor to block phosphorylation of the nuclear translocation signal in pERK resulted in greatly decreased cell proliferation and a significant reduction in the nuclear translocation of pERK. In contrast, Tm5NM1 KO MEFs, which show reduced nuclear translocation of pERK, were unaffected by inhibition of CK2. This suggested that it is nuclear translocation of CK2-phosphorylated pERK that regulates cell proliferation and this capacity is absent in Tm5NM1 KO cells. Proximity ligation assays confirmed a growth factor-stimulated interaction of pERK with Tm5NM1 and that the interaction of pERK with importin7 is greatly reduced in the Tm5NM1 KO cells