1
Temperature for Living Things

Temperature is one of the most influential physical parameters in our daily lives. For example, in Tokyo, where the author lives, there are four seasons throughout the year. When it is cold in the winter, people travel to tropical countries to search for warmth. The arrival of spring can be recognized by the warmth of the sunshine filtering through the leaves of trees and the gentle breeze. On the other hand, recent summers have been too hot to relax without an air conditioner. A French chef always pays attention to the temperature of a frying pan and an oven, and a Japanese chef checks the oil temperature in a pot to deep-fry crispy tempura.

In the same way, temperature is intensely involved in the activity of living things from a biological viewpoint (Cossins and Bowler, 1987). Humans sweat in summer and shiver in winter to maintain their body temperature. When we feel ill, we measure the body temperature first. When I was a child, we used an mercury-filled thermometer to measure the body temperature, but now a thermistor has replaced it. Accordingly, it is only natural that there is a long history of comprehending temperature and measuring it. Some intriguing literature is available for the historical background on temperature measurements from the 16th century (Middleton, 1966; Chang, 2004). Here, as the first chapter of this textbook, the relationships between temperature and organisms are summarized. As indicated in Figure 1.1, temperature-related biological phenomena can be categorized into "spontaneous thermogenesis" and "response to environmental temperature" at both an individual body level and a single cell level. Each category will be introduced with relevant examples. Of them all, the spontaneous thermogenesis in single living cells will be highlighted in Chapter 3 as a new outcome brought about by intracellular thermometry.

Figure 1.1 Keywords in biological studies that correlate temperature with physiological events. The original figure is from Okabe and Uchiyama (2021) Commun. Biol., 4, 1377 and is updated here.

1.1 Temperature of Individuals

1.1.1 Spontaneous Heat Generation

1.1.1.1 Human

A human with a body temperature of 36-37 °C is a representative of an endotherm; the body temperature of endotherms is kept higher than that of the environment by spontaneous heat generation (called thermogenesis) (Geneva et al., 2019). Although we were told that humans are homeotherms in our childhood, the actual body temperature of humans considerably varies within a few degrees in relation to circadian rhythms, including ultradian and infradian rhythms (Figure 1.2a) (Zulley et al., 1981). Misconceptions by the use of the terms "endotherm" and "warm-blooded" for mammals have been pointed out for correct comprehension of organismal thermoregulation (Brack Jr. et al., 2022). Women have another circadian rhythm of basal body temperature due to the ovulation cycle (Figure 1.2b) (Lee, 1988; Baker et al., 2020). The menstrual cycle-dependent variability in basal body temperature is affected by aging. However, seasonal variation is slight, and thus, basal body temperature is being proposed as a non-invasive diagnostic indicator of ovulation (Tatsumi et al., 2020). The body temperature of humans is also influenced by race, age, voluntary exercise, and disease (Refinetti and Menaker, 1992).

Figure 1.2 Variation in human body temperature. (a) Rectal temperature (black) and sleep-wake cycle (red) recorded in an isolated subject during internal synchronization (upper) and internal desynchronization (lower). a: wakefulness; q: bedrest. Adapted from Zulley et al. (1981) Pflügers Arch., 391, 314-318. (b) Averaged rectal temperatures of 15 young women (age: 22 ± 4 years) at the mid-follicular and mid-luteal phases in their menstrual cycles. Subjects followed their usual daytime schedules and spent the nights in a sleep laboratory. Adapted from Baker et al. (2020) Temperature, 7, 226-262.

Body temperature is one of the most basic vital signs in clinical diagnosis and routine human health care. To measure human body temperature with high accuracy, actual and predictive measurements using instruments or mathematics, either invasive or non-invasive, are used (Childs, 2018; Chen, 2019). The methods for measuring the human body temperature involve wearable temperature sensors, and information technology-based real-time and long-term recording and expand to the application of life-critical decision-making and mass screening of diseases.

The regulation of human body temperature has been the central subject of physiology (Houdas and Ring, 1982; Jessen, 2001). It functions with the nervous system. Some molecules involved in temperature sensing in the periphery and the neural circuits that transmit temperature information to the brain, as well as the central circuits for maintaining body temperature homeostasis, have been identified, whereas the detailed thermoregulatory mechanisms are still unclear (Tan and Knight, 2018). Fever is an uncomfortable, ill status for us, but it is even controlled under a thermoregulation system with identified neural circuits. In addition to the inflammatory response induced by pathogen infection (Roth et al., 2006), fever can also be caused by social stress (Kataoka et al., 2020).

In contrast to heat generation for a healthy life, cancers and tumors significantly increase the focus temperature, which has been empirically accepted since the 1960s (Lawson and Chughtai, 1963). Now, infrared thermography of skin temperature is considered adequate for the diagnosis of malignant soft-tissue tumors (Figure 1.3a, 1.3b) (Shimatani et al., 2022). Microcalorimetric investigation using a mass of cells confirmed that the heat production rate of tumor cells depends on their malignancy (Figure 1.3c) (Monti et al., 1986).

Figure 1.3 Heat production in tumors. (a,b) Representative case of myxofibrosarcoma. (a) Skin temperature map by infrared thermography. A malignant soft-tissue tumor in the right thigh was diagnosed as myxofibrosarcoma. The skin temperature on the affected part is higher than the surrounding areas. (b) Sections of the myxofibrosarcoma stained with hematoxylin and eosin (magnification: ×200). Panels (a,b) are adapted from Shimatani et al. (2022) Int. J. Clin. Oncol., 27, 234-243. (c) Heat production rate per lymphoma cell from non-Hodgkin lymphoma patients. The left group of 13 patients died within two years, while the right group of 17 patients survived two years or longer. Horizontal bars indicate median values. Panel (c) Monti et al. (1986) Scand. J. Haematol., 36, 353-357 / John Wiley & Sons.

1.1.1.2 Bear

An extreme case of animal spontaneous thermogenesis is found in hibernation (Kosara, 2011), especially in bears (Harlow et al., 2004). The body temperature of a hibernating black bear (Ursus americanus) is displayed in Figure 1.4 (Tøien et al., 2011). During hibernation in winter, even in cold environments (-40-0 °C) where metabolic activity is markedly suppressed, Ursus americanus maintains a body temperature of 32-38 °C by performing regular muscular exercises without waking up from sleep.

Figure 1.4 Thermogenesis of a hibernating bear. (a) A black bear, Ursus americanus (© Meunierd). (b) Hibernation of Ursus americanus in an artificial den. (c) Temperature patterns of the core body temperature of a hibernating Ursus americanus (Tb, black) and the outside of a cave (Ta, dark blue). Purple lines indicate the movements of the black bear. Panels (b,c) Tøien et al. (2011) Science, 331, 906-909 / American Association for the Advancement of Science.

1.1.1.3 Oceanic Lives

Due to the high thermal conductivity of water, it is harder for marine creatures to keep their body temperature higher than their surroundings compared to animals living on land. Nevertheless, various fish maintain their body temperature higher than the surrounding sea. Figure 1.5 shows the relationship between the ambient temperature and the body temperature of bigeye tuna (Thunnus obesus) (Holland et al., 1992). The ambient temperature fluctuations were due to vertical excursions of Thunnus obesus of more than 100 meters. Analyzing these temperature data suggested that the whole-body thermal conductivity of Thunnus obesus was altered by two orders of magnitude between the warming and cooling phases. A mesopelagic fish, opah (Lampris guttatus), also shows temperature elevations above ambient by 3.2-6.0 °C in its heart, viscera, cranial region, and pectoral muscle (Wegner et al., 2015). It has been assumed that the endothermic properties of these living things are beneficial for enhancing physiological performance in cold oceans. Temperature regulation to keep the body temperatures higher, or occasionally lower, than their environment has also been observed in king penguins (Handrich et al., 1997) and sea turtles (Sato, 2014).

Figure 1.5 Thermoregulation of a tuna. (a) A bigeye tuna, Thunnus obesus (© MikeCloud). (b) The body temperature of a swimming Thunnus obesus (TB) and ambient temperature (TA). Panel (b) is adapted from Holland et al. (1992)...