A gene for all seasons: The evolutionary consequences of HIF-1 in carcinogenesis, tumor growth and metastasis.

Oxygen played a pivotal role in the evolution of multicellularity during the Cambrian Explosion. Not surprisingly, responses to fluctuating oxygen concentrations are integral to the evolution of cancer-a disease characterized by the breakdown of multicellularity. Poorly organized tumor vasculature results in chaotic patterns of blood flow characterized by large spatial and temporal variations in intra-tumoral oxygen concentrations. Hypoxia-inducible growth factor (HIF-1) plays a pivotal role in enabling cells to adapt, metabolize, and proliferate in low oxygen conditions. HIF-1 is often constitutively activated in cancers, underscoring its importance in cancer progression. Here, we argue that the phenotypic changes mediated by HIF-1, in addition to adapting the cancer cells to their local environment, also "pre-adapt" them for proliferation at distant, metastatic sites. HIF-1-mediated adaptations include a metabolic shift towards anaerobic respiration or glycolysis, activation of cell survival mechanisms like phenotypic plasticity and epigenetic reprogramming, and formation of tumor vasculature through angiogenesis. Hypoxia induced epigenetic reprogramming can trigger epithelial to mesenchymal transition in cancer cells-the first step in the metastatic cascade. Highly glycolytic cells facilitate local invasion by acidifying the tumor microenvironment. New blood vessels, formed due to angiogenesis, provide cancer cells a conduit to the circulatory system. Moreover, survival mechanisms acquired by cancer cells in the primary site allow them to remodel tissue at the metastatic site generating tumor promoting microenvironment. Thus, hypoxia in the primary tumor promoted adaptations conducive to all stages of the metastatic cascade from the initial escape entry into a blood vessel, intravascular survival, extravasation into distant tissues, and establishment of secondary tumors.

Comparative study between charge and spin thermoelectric figure of merits in an antiferromagnetic ring.

Considering the unique and diverse characteristic features of antiferromagnetic (AFM) systems, here in our work, we explore spin-dependent thermoelectric behavior in an AFM ring geometry. A reasonably large (≫1) spin figure of merit, referred to asZST, is obtained under suitable input conditions. Two important prerequisites are (i) breaking the symmetry among up and down spin sub-Hamiltonians and (ii) generating different asymmetric transmission line shapes across a Fermi energy for two opposite spin electrons. Describing the physical system within a tight-binding framework, where spin-dependent scattering occurs due to the interaction of itinerant electrons with local magnetic moments via the usual spin-moment exchange interaction, we compute all the thermoelectric quantities based on Landauer integrals following the Green's function technique. The behavior of charge figure of merit, denoted asZCT, is also discussed along withZST. ThoughZCTreaches above unity, it is much smaller compared toZST. This is the key finding of our investigation. To make the present communication a self-contained one, we compare the results with another arrangement of magnetic moments in a ring-like geometry and in a chain-like one. Our analysis gives a suitable hint that in the presence of spin-dependent scattering, much more favorable energy conversion can be substantiated.

Digest: Natural selection fluctuates at an extremely fine spatial scale inside a wild population of snapdragon plants.

Marrot et al. used snapdragon plants on a small island to experimentally investigate how spatial structure influences the evolution of biological communities. Using a spline-based fitness function, they studied the varying relationships between traits under selection and driving environmental factors in snapdragons. The authors found that environmental heterogeneity, even on a small spatial scale, may provide several fitness optima on the fitness landscape, paving the way for coexistence of diverse phenotypes. In the absence of sufficient gene flow, this could also lead to microgeographic adaptations.

Role of inter-electrode coupling on thermoelectricity in an interferometric geometry: a new proposition.

Efficient thermoelectric (TE) energy conversion is one of the most desirable solutions of our current day energy crisis. Exploiting the effect of quantum interference among electronic waves, in this work we propose a prescription of getting high TE efficiency, the so-calledfigure of merit(ZT), considering an interferometric geometry where a loop conductor is clamped between two heat baths. Unlike conventional junction configurations, we introduce an additional path for electron transfer directly from source to drain, due to their close proximity. The interplay between different paths leads to an enhancedZT(ZT > 1). Moreover, the efficiency can be further regulated by tuning the inter-electrode coupling. The effects of magnetic flux threaded by the ring and disorder are also discussed. Our proposed prescription may lead to a new route of designing tunable TE devices at nanoscale level.

Senescence-Induced Chemoresistance in Triple Negative Breast Cancer and Evolution-Based Treatment Strategies.

Triple negative breast cancer (TNBC) is classically treated with combination chemotherapies. Although, initially responsive to chemotherapies, TNBC patients frequently develop drug-resistant, metastatic disease. Chemotherapy resistance can develop through many mechanisms, including induction of a transient growth-arrested state, known as the therapy-induced senescence (TIS). In this paper, we will focus on chemoresistance in TNBC due to TIS. One of the key characteristics of senescent cells is a complex secretory phenotype, known as the senescence-associated secretory proteome (SASP), which by prompting immune-mediated clearance of senescent cells maintains tissue homeostasis and suppresses tumorigenesis. However, in cancer, particularly with TIS, senescent cells themselves as well as SASP promote cellular reprograming into a stem-like state responsible for the emergence of drug-resistant, aggressive clones. In addition to chemotherapies, outcomes of recently approved immune and DNA damage-response (DDR)-directed therapies are also affected by TIS, implying that this a common strategy used by cancer cells for evading treatment. Although there has been an explosion of scientific research for manipulating TIS for prevention of drug resistance, much of it is still at the pre-clinical stage. From an evolutionary perspective, cancer is driven by natural selection, wherein the fittest tumor cells survive and proliferate while the tumor microenvironment influences tumor cell fitness. As TIS seems to be preferred for increasing the fitness of drug-challenged cancer cells, we will propose a few tactics to control it by using the principles of evolutionary biology. We hope that with appropriate therapeutic intervention, this detrimental cellular fate could be diverted in favor of TNBC patients.