This is an author-produced, peer-reviewed version of this article. © 2016, Elsevier. Licensed under the Creative Commons AttributionNonCommercial-No Derivatives 4.0 License. Details regarding the use of this work can be found at: http://creativecommons.org/licenses/by-nc-nd/ 4.0/ . The final, definitive version of this document can be found online at Physiology & Behavior, doi: 10.1016/j.physbeh.2016 Publication Information Refinetti, Roberto. (2016) E-mail address: refinetti@circadian.org (R. Refinetti). AbstractHuman chronotypes (differences in preference for early or late rising each day) have been extensively studied in recent years, but no attempt has been made to compare human chronotypes with the chronotypes of other animal species. We evaluated behavioral chronotypes in 16 mammalian species along a body size gradient of five orders of magnitude (from mice to cattle). Individuals of all species were studied under a 12L:12D photoperiod in a thermoneutral environment with food and water available at all times. Rhythms of locomotor activity were analyzed for onset time, acrophase, and robustness. Neither of these rhythmic parameters was significantly related to body size, but onset time and acrophase varied considerably from species to species, thus characterizing diurnal and nocturnal species. Chronotype spreads ranged from less than an hour in sheep to almost 24 hours in cats, thus extending both below and above the human chronotype spread of 6 hours. The variability of chronotype (as quantified by the standard deviation of group means) was much larger between species than within species and also larger between individuals of a species than within individuals on consecutive days. These results help situate the matter of human chronotypes within the broader context of variability in the phase angle of entrainment of circadian rhythms in animals.

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Sleep and wake states are regulated by a variety of mechanisms. One such important system is the circadian clock, which provides temporal structure to sleep and wake. Conversely, changes in behavioral state, such as sleep deprivation (SD) or arousal, can phase shift the circadian clock. Here we demonstrate that the level of wakefulness is critical for this arousal resetting of the circadian clock. Specifically, drowsy animals with significant power in the 7-to 9-Hz band of their EEGs do not exhibit phase shifts in response to a mild SD procedure. We then show that treatments that both produce arousal and reset the phase of circadian clock activate (i.e., induce Fos expression in) the basal forebrain. Many of the activated cells are cholinergic. Using retrograde tract tracing, we demonstrate that cholinergic cells activated by these arousal procedures project to the circadian clock in the suprachiasmatic nuclei (SCN). We then demonstrate that arousal-induced phase shifts are blocked when animals are pretreated with atropine injections to the SCN, demonstrating that cholinergic activity at the SCN is necessary for arousal-induced phase shifting. Finally, we demonstrate that electrical stimulation of the substantia innominata of the basal forebrain phase shifts the circadian clock in a manner similar to that of our arousal procedures and that these shifts are also blocked by infusions of atropine to the SCN. These results establish a functional link between the major forebrain arousal center and the circadian system. arousal | phase shift | nonphotic | sleep/wake | brain stimulation T he states of wake and sleep in mammals are regulated by interactions between brainstem and forebrain regions (1, 2), with some areas actively promoting sleep and others promoting wake. The allied circadian clock located in the suprachiasmatic nuclei (SCN) (3) provides temporal structure to behavior and physiology. The sleep/wake systems and circadian systems interact (4), with the circadian system providing temporal input to the sleep and wake systems, thus promoting both states, and ensuring that these behaviors occur at species-specific times of day (5).The activity of the SCN is endogenously regulated and tightly linked to behavioral state. SCN electrical activity is highest during the day, when nocturnal rodents are asleep, with higher activity during rapid-eye-movement (REM) sleep than during slow wave sleep (6). During the waking phase, SCN activity is suppressed by spontaneous behavior (7). Critically, triggering activity or wakefulness, so-called "nonphotic zeitgebers" (time givers), during the sleep phase can reset the phase of the circadian clock (8, 9). There is an inverse relationship between the size of the phase shift due to sleep deprivation (SD) and the amount of effort required to maintain wakefulness during the procedure (8). Specifically, animals that remain awake and alert on their own exhibit large phase shifts, whereas those that require frequent intervention to maintain wakefulness do not shift. These factors su...

Infection born by Coronavirus SARS-CoV-2 has swept the world within a time of a few months. It has created a devastating effect on humanity with social and economic depressions. Europe and America were the hardest hit continents. India has also lost several lives, making the country fourth most deadly worldwide. However, the infection and death rate per million and the case fatality ratio in India were substantially lower than many of the developed nations. Several factors have been proposed including the genetics. One of the important facts is that a large chunk of Indian population is asymptomatic to the SARS-CoV-2 infection. Thus, the real infection in India is much higher than the reported number of cases. Therefore, the majority of people are already immune in the country. To understand the dynamics of real infection as well as level of immunity against SARS-CoV-2, we have performed antibody testing (serosurveillance) in the urban region of fourteen Indian districts encompassing six states. In our survey, the seroprevalence frequency varied between 0.01-0.48, suggesting high variability of viral transmission among states. We also found out that the cases reported by the Government were several fold lower than the real infection. This discrepancy is majorly driven by a higher number of asymptomatic cases. Overall, we suggest that with the high level of immunity developed against SARS-CoV-2 in the majority of the districts, it is less likely to have a second wave in India.

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