Cities and methods from complexity science

The dynamics of human society is now been studying in the context of the artificial environment created by cities. In this work, the authors describe some of the formal methods used in complexity science to study urban systems. The authors discuss some of the important quantitative approaches on cities paying attention to some of the deepest controversies in present scientific studies. The authors will stress the importance of a transdisciplinary approach when studying this type of cooperative social environments.     

Copernicus and Fracastoro: the dedicatory letters to Pope Paul III, the history of astronomy, and the quest for patronage

Copernicus’s De revolutionibus (1543) and Girolamo Fracastoro’s Homocentrica (1538) were both addressed to Pope Paul III (1534-1549). Their dedicatory letters represent a rhetorical exercise in advocating an astronomical reform and an attempt to obtain the papal favour. Following on from studies carried out by Westman (1990) and Barker & Goldstein (2003), this paper deals with cultural, intellectual and scientific motives of both texts, and aims at underlining possible relations between them, such as that Copernicus knew of Fracastoro’s Homocentrica, and that at least part of the rhetorical strategy laid out in De revolutionibus’s dedicatory letter can be read as a sophisticated response to Fracastoro’s arguments.     

Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures

Sensory acuity and motor dexterity deteriorate when human limbs cool down, but pain perception persists and cold-induced pain can become excruciating. Evolutionary pressure to enforce protective behaviour requires that damage-sensing neurons (nociceptors) continue to function at low temperatures. Here we show that this goal is achieved by endowing superficial endings of slowly conducting nociceptive fibres with the tetrodotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 (ref. 2). This channel is essential for sustained excitability of nociceptors when the skin is cooled. We show that cooling excitable membranes progressively enhances the voltage-dependent slow inactivation of tetrodotoxin-sensitive VGSCs. In contrast, the inactivation properties of Na(v)1.8 are entirely cold-resistant. Moreover, low temperatures decrease the activation threshold of the sodium currents and increase the membrane resistance, augmenting the voltage change caused by any membrane current. Thus, in the cold, Na(v)1.8 remains available as the sole electrical impulse generator in nociceptors that transmits nociceptive information to the central nervous system. Consistent with this concept is the observation that Na(v)1.8-null mutant mice show negligible responses to noxious cold and mechanical stimulation at low temperatures. Our data present strong evidence for a specialized role of Na(v)1.8 in nociceptors as the critical molecule for the perception of cold pain and pain in the cold.     

Intracellular protein degradation in mammalian cells: recent developments

In higher organisms, dietary proteins are broken down into amino acids within the digestive tract but outside the cells, which incorporate the resulting amino acids into their metabolism. However, under certain conditions, an organism loses more nitrogen than is assimilated in the diet. This additional loss was found in the past century to come from intracellular proteins and started an intensive research that produced an enormous expansion of the field and a dispersed literature. Therefore, our purpose is to provide an updated summary of the current knowledge on the proteolytic machinery involved in intracellular protein degradation and its physiological and pathological relevance, especially addressed to newcomers in the field who may find further details in more specialized reviews. However, even providing a general overview, this is an extremely wide field and, therefore, we mainly focus on mammalian cells, while other cells will be mentioned only for comparison purposes.     

A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition

Disruption of histone acetylation patterns is a common feature of cancer cells, but very little is known about its genetic basis. We have identified truncating mutations in one of the primary human histone deacetylases, HDAC2, in sporadic carcinomas with microsatellite instability and in tumors arising in individuals with hereditary nonpolyposis colorectal cancer syndrome. The presence of the HDAC2 frameshift mutation causes a loss of HDAC2 protein expression and enzymatic activity and renders these cells more resistant to the usual antiproliferative and proapoptotic effects of histone deacetylase inhibitors. As such drugs may serve as therapeutic agents for cancer, our findings support the use of HDAC2 mutational status in future pharmacogenetic treatment of these individuals.     

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma.     

Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis

Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC.     

Are plants cognitive? A reply to Adams

According to F. Adams [this journal, vol. 68, 2018] cognition cannot be realized in plants or bacteria. In his view, plants and bacteria respond to the here-and-now in a hardwired, inflexible manner, and are therefore incapable of cognitive activity. This article takes issue with the pursuit of plant cognition from the perspective of an empirically informed philosophy of plant neurobiology. As we argue, empirical evidence shows, contra Adams, that plant behavior is in many ways analogous to animal behavior. This renders plants suitable to be described as cognitive agents in a non-metaphorical way. Sections two to four review the arguments offered by Adams in light of scientific evidence on plant adaptive behavior, decision-making, anticipation, as well as learning and memory. Section five introduces the ‘phyto-nervous’ system of plants. To conclude, section six resituates the quest for plant cognition into a broader approach in cognitive science, as represented by enactive and ecological schools of thought. Overall, we aim to motivate the idea that plants may be considered genuine cognitive agents. Our hope is to help propel public awareness and discussion of plant intelligence once appropriately stripped of anthropocentric preconceptions of the sort that Adams' position appears to exemplify.     

Myosin II in mechanotransduction: master and commander of cell migration, morphogenesis, and cancer

Mechanotransduction encompasses the role of mechanical forces in controlling cell behavior by activating signal transduction pathways. Most forces at a cellular level are caused by myosin II, which contracts and cross-links actin. Myosin II-dependent forces are transmitted through the actin cytoskeleton to molecular endpoints that promote specific cellular outcomes, e.g., cell proliferation, adhesion, or migration. For example, most adhesive and migratory phenomena are mechanically linked by a molecular clutch comprised of mechanosensitive scaffolds. Myosin II activation and mechanosensitive molecular mechanisms are finely tuned and spatiotemporally integrated to coordinate morphogenetic events during development. Mechanical events dependent on myosin II also participate in tumor cell proliferation, invasion, and metastatic dissemination. Specifically, tumor cells alter the mechanical properties of the microenvironment to create favorable conditions for proliferation and/or dissemination. These observations position myosin II-dependent force generation and mechanotransduction at the crossroads between normal development and cancer.