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Objective: Circadian rhythms are present almost in all living organisms and synchronized with the zeitgebers (time givers), especially lightdark (LD) cycles. The jetlag and rotating shift work schedules lead to desynchronization of the circadian clock with zeitgebers which may cause various health problems. Studies have shown that withanolide-A (WA) is a potent nootropic and neuroprotective agent found in Withania somnifera. Thus, the objective was to study the effect of WA on the circadian locomotor activity rhythm following the phase inversion of 12:12 h LD cycle in mice and its impact on the spatial memory in mice.Methods: Adult male mice were housed in the chronocubicle and recorded circadian locomotor activity rhythm by using ClockLab setup. The experimental mice were administered with WA (10 μmol/kg/day) for 13 consecutive days at about ZT15 and then evoked an acute phase inversion of 12:12 h light-dark cycle. Further, the Barnes maze test was performed to check the effect of WA on spatial memory following the phase inversion.Results: The results showed that WA-treated group took significantly fewer transient cycles (4.66+0.66) for re-entrainment than the control (9.5+0.43) and vehicle-treated (8.33+1.28) mice following the phase inversion. Similarly, WA-treated mice traveled less distance to reach the target zone in the Barnes maze compared to vehicle and control groups.Conclusion: These results suggest that the WA may act as chronobiotic and neuroprotective agent since it decreased the transient cycles for re-entrainment and retaining spatial memory following the phase inversion.

India had faced a devastating second outbreak of COVID-19 infection, in which a majority of the viral sequences were found to be of the B.1.617.2 lineage (Delta-variant). While India and the world focused on vaccination, reports of vaccine-immunity evasion by the virus, termed "breakthrough cases", emerged worldwide. Our study was focused on the primary objective to identify the mutations associated with breakthrough infections SARS-CoV-2.In our study, we extracted the SARS-CoV-2 RNA (ribonucleic acid) from reverse transcription-polymerase chain reaction (RT-PCR) positive COVID-19 patients, and 150 random samples were sent for sequencing to the Centre for CellularMolecular Biology, Hyderabad. Whole genome sequences of 150 SARS-CoV-2 viral samples were analyzed thoroughly. We mostly found B.1.617 and its sub-lineages in the genomic sequencing results.On further analysis of patient data, it was seen that nine patients had been vaccinated against the SARS-CoV-2 previously. These nine patients had B.1.617/B.1 or A strains, and all of them had similar genomic variations in spike proteins as well as non-structural proteins (NSPs). The mutations seen in these sequences in the Spike (S), NSPs, and open reading frame (ORF) regions would have produced amino acid changes known to improve viral replication, confer drug resistance, influence host-cell interaction, and lead to antigenic drift.Increased virulence culminating in vaccine immunity evasion may be inferred from these specific mutations. Our study adds to the growing body of evidence linking rapidly emerging mutations in the S (Spike) and ORF genes of the SARS-CoV-2 genome to immune evasion.

Fil: Soni, Sanjeev Kumar. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Basu, Priyoneel. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Singaravel, Muniyandi. Banaras Hindu University. Institute of Sciences. Department of Zoology. Chronobiology Laboratory; India Fil: Sharma, Ramaswamy. UT Health San Antonio. Department of Cell Systems and Anatomy; Estados Unidos Fil: Pandi Perumal, Seithikurippu R. Somnogen Canada; Canadá Fil: Cardinali, Daniel Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Abstract: Chronic disruption of circadian rhythms which include intricate molecular transcription-translation feedback loops of evolutionarily conserved clock genes has serious health consequences and negatively affects cardiovascular physiology. Sirtuins (SIRTs) are nuclear, cytoplasmic and mitochondrial histone deacetylases that influence the circadian clock with clock-controlled oscillatory protein, NAMPT, and its metabolite NAD+. Sirtuins are linked to the multi-organ protective role of melatonin, particularly in acute kidney injury and in cardiovascular diseases, where melatonin, via upregulation of SIRT1 expression, inhibits the apoptotic pathway. This review focuses on SIRT1, an NAD+-dependent class III histone deacetylase which counterbalances the intrinsic histone acetyltransferase activity of one of the clock genes, CLOCK. SIRT1 is involved in the development of cardiomyocytes, regulation of voltage-gated cardiac sodium ion channels via deacetylation, prevention of atherosclerotic plaque formation in the cardiovascular system, protection against oxidative damage and anti-thrombotic actions. Overall, SIRT1 has a see-saw effect on cardioprotection, with low levels being cardioprotective and higher levels leading to cardiac hypertrophy.

Studies worldwide have shown that the available vaccines are highly effective against SARS-CoV-2. However, there are growing laboratory reports that the newer variants of concerns (VOCs e.g. Alpha, Beta, Delta etc) may evade vaccine induced defense. In addition to that, there are few ground reports on health workers having breakthrough infections. In order to understand VOC driven breakthrough infection we investigated 14 individuals who tested positive for SARS-CoV-2 after being administered a single or double dose of Covishield (ChAdOx1, Serum Institute of India) from the city of Varanasi, which is located in the Indian state of Uttar Pradesh. Genomic analysis revealed that 78.6% (11/14) of the patients were infected with the B.1.617.2 (Delta) variant. Notably, the frequency (37%) of this variant in the region was significantly lower (p

Chronic jet lag has deleterious effects on many physiological parameters. Most simulations of chronic jet lag consist of repeated advances only, while real-life conditions may differ. We compared n...

Chronic disruption of circadian rhythms which include intricate molecular transcription-translation feedback loops of evolutionarily conserved clock genes has serious health consequences and negatively affects cardiovascular physiology. Sirtuins (SIRTs) are nuclear, cytoplasmic and mitochondrial histone deacetylases that influence the circadian clock with clock-controlled oscillatory protein, NAMPT, and its metabolite NAD

Risperidone is an atypical antipsychotic that is active at multiple dopamine and serotonin receptor subtypes. Based on its high affinity for serotonin receptors, we predicted that it might reset circadian rhythms in a nocturnal rodent. We report temporally differentiated and differential effects of various doses of risperidone on the voluntary locomotor activity rhythm in the Indian field mice, Mus booduga. Risperidone (0.5 mg/kg) elicited phase delays at phases between CT (circadian time) 12 to CT18 and CT0 to CT3, and phase advances at CT6, CT9 and CT21. However, mice injected at CT6 showed maximum advances (1.299 ± 0.286 h), whereas at CT15 showed maximum delays (−1.514 ± 0.312 h). Increasing the dose beyond 0.5 mg/kg at maximally responsive CTs (CT6 and CT15) resulted in progressively smaller but significant shifts. Thus, 0.5 mg/kg is the optimal dose in this species. The fact that risperidone resets the circadian rhythm in a mammal can be extended to clinical studies and used for optimal adju...

Human 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 24h in cats, thus extending both below and above the human chronotype spread of 6h. 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.

Daily exposure to light synchronizes the circadian clock, located in the suprachiasmatic nucleus (SCN), to external day/night cycles. These responses to light can be modified by serotonergic drugs, such as serotonin 5HT1B receptor agonists. Triptans are specific 5HT1B agonists prescribed to treat migraines. Here, we examined the effects of two triptans (zolmitriptan and sumatriptan) on photic phase resetting in Syrian hamsters. Pre-treatment with intra-SCN sumatriptan significantly attenuates, and at higher doses completely blocks, phase advances to light during the late night. Pre-treatment with systemic zolmitriptan significantly attenuates both light-induced phase advances and phase delays. Neither of these drugs, nor their vehicles, causes phase shifts on their own. Pre-treatment with zolmitriptan also significantly reduces the expression of light-induced c-fos in the SCN. Neither zolmitriptan nor vehicle alone induces significant c-fos expression in the SCN. Finally, pre-treatment with zolmitriptan does not attenuate phase shifts to intra-SCN N-methyl-d-aspartate injections, indicating that the mechanism of action for zolmitriptan is likely to be through activation of presynaptic 5HT1B receptors on retinal terminals, thereby decreasing light-induced neurotransmitter release. As triptans are commercially available medications, there is potential for their use in blocking unwanted photic phase shifting during shift-work or jet-lag. Additionally, triptans may also affect the circadian clock in patients receiving them regularly for migraines. Finally, our results may hint at the mechanism by which triptans can alleviate the photophobia that frequently accompanies migraines, namely by activating 5HT1B receptors on retinal terminals elsewhere in the brain, and thereby diminishing visually-evoked neurotransmitter signalling in those areas.

Serotonin (5-HT) is an important regulator of the mammalian circadian system, and has been implicated in modulating entrained and free-running rhythms, as well as photic and non-photic phase shifting. In general, 5-HT appears to oppose the actions of light on the circadian system of nocturnal rodents. As well, 5-HT mediates, at least in part, some non-photic responses. The 5-HT1A, 1B and 7 receptors regulate these acute responses to zeitgebers. 5-HT also regulates some entrained and free-running properties of the circadian clock. The receptors that contribute to these phenomena have not been fully examined. Here, we use 5-HT1A receptor knockout (KO) mice to examine the response of the mouse circadian system to a variety of lighting conditions, including a normal light-dark cycle (LD), T-cycles, phase advanced LD cycles, constant darkness (DD), constant light (LL) and a 6 hour dark pulse starting at CT5. Relative to wildtype mice, the 5-HT1A receptor KO mice have lower levels of activity during the first 8h of the night/subjective night in LD and LL, later activity onsets on transient days during re-entrainment, shorter free-running periods in LL when housed with wheels, and smaller phase shifts to dark pulses. No differences were noted in activity levels during DD, alpha under any light condition, free-running period in DD, or phase angle of entrainment in LD. While the 5-HT1A receptor plays an important role in regulating photic and non-photic phase shifting, its contribution to entrained and free-running properties of the circadian clock is relatively minor.

Fisetin, a bioactive flavonoid, found in many fruits, was administered orally (50 mg/kg body weight) to hyperammonemic rats (treated with ammonium chloride (AC) for 8 weeks (i.p. injections, 100 mg/kg body weight). Treatment with AC augmented oxidative stress, levels of ammonia, enzymes (alanine and aspartate transaminases and alkaline phosphatase) in blood, glutamate and glutamine content in brain, caused disturbances in the circadian locomotor rhythm with a reduction in amplitude and period and downregulated the expression of soluble guanylyl cyclase (sGC) and glial fibrillary acidic protein (GFAP) in brain. Co-treatment of fisetin treatment with AC, prevented the AC-induced elevation in oxidative stress, normalized the levels of ammonia, transaminases and alkaline phosphatase in circulation, glutamate and glutamine in brain, upregulated the expression of sGC and GFAP and stabilized the circadian locomotor rhythm. Thus, fisetin assuages AC induced effects through its antioxidant, anti-inflammatory, cytoprotective, neuroprotective and neurotrophic properties.

We quantified motor learning during voluntary wheel-running activity in the Indian pygmy field mouse, Mus terricolor. Wheel running in naive adults was monitored using the Clocklab system. A group of mice having 15 days prior wheel-running experience served as the control. The daily maximum wheel activity for the naive group increased from 21 ± 7 counts/min to 62 ± 4 counts/min in 15 days. The experienced group exhibited 62 ± 1 counts/min throughout the experiment. A significant correlation between days of wheel running and natural log of the highest count/min existed in the experimental group, but not in the experienced group. Thus, improvement in wheel running follows a logarithmic learning curve. Several research applications for this quantification have been discussed. The most important outcome of this quantification is that it primes the mice for a study in which the retention period for this motor learning, i.e. the time taken to “forget” motor learning during wheel running will be elucidated.

The Indian pygmy field mouse, Mus terricolor, is a tiny, yet economically and ecologically important crop pest found throughout South-East Asia. There are no systematic reports exploring its reproductive physiology. We report the presence of distinct periods of annual reproductive activity and quiescence in M. terricolor. Body weight in males and females, relative weights of testis, epididymis and seminal vesicle in males, ovarian and uterine weight in females, gonadal histomorphic changes, testicular and ovarian cholesterol, sialic acid in epididymis, fructose in seminal vesicle, uterine protein content, melatonin in males and females, testosterone in males, estradiol, and progesterone in females were studied over a period of three years in both wild-caught and lab-acclimated mice. The number of Graafian follicles and corpora lutea, and plasma estradiol and progesterone, along with relative weights of ovary and uterus in females exhibited a peak in the months of October–January, compared to June. Based o...

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.

L-5-Hydroxytryptophan (5-HTP), the precursor of serotonin, is known to cause temporally differentiated phase shifts. However, its effects on acceleration of re-entrainment have not been demonstrated before. We report significant acceleration of re-entrainment to a 6-h advanced light dark schedule by 50 mg/kg 5-HTP (∼8 transients reduced to ∼3 transients) injected at ∼ZT 6 in the nocturnal Indian pygmy field mouse, Mus terricolor. The mechanistic explanation is currently unknown, but this probably occurs through serotonergic phase and period modifications. 5-HTP is thus potentially useful as a chronobiotic in circadian rhythm disorders.

L-5-Hydroxytryptophan (5-HTP), the precursor of serotonin, has phase-resetting ability under constant conditions in mammals. However, it is not known whether it can entrain a free-running rhythm. We report that 5-HTP (50 mg/kg) entrains the free-running rhythm of Mus terricolor to 24 h, when presented once in 24 h at zeitgeber time (ZT) 6, corresponding to its previously known circadian time (CT) of maximum advance in complete darkness (CT 6), on the last pre-intervention day. This entrainment is accompanied by shortening of the period and visible after withdrawal of injections. After-effects may persist for a few days. The mechanistic explanation is currently unknown, but this probably occurs through serotonergic phase and period modifications. 5-HTP is thus potentially useful as a chronobiotic in circadian rhythm disorders.

We report the presence of variations in the rate and direction of re-entrainment to acute simulated jet lag in wild-caught North Indian palm squirrels (Funambulus pennanti). Adult laboratory and wheel-acclimated (Lafayette, USA) males (N = 30) were entrained to a 12:12 h light/dark (LD) schedule, followed by a 9 h advance of the LD schedule to simulate acute jet lag. The direction and rate of re-entrainment, i.e. the number of orthodromic (advancing) and antidromic (delaying) transients, the acrophases of daily rhythms in each case, duration of activity (α) and phase angle relationship (ψ) were noted using Clocklab (Coulbourn, USA). The squirrels exhibited distinct variations in their response to simulated acute jet lag, re-entraining either slowly (14/30) or rapidly (10/30) by advancing transients, or undergoing antidromic re-entrainment slowly (5/30), and, in only one individual, rapidly. Acrophases re-entrained slower than onsets. α underwent compression during re-entrainment, particularly during fast ...

We report some basic circadian characteristics in Mus terricolor, the nocturnal pygmy field mouse. Both male and female M. terricolor entrain well to a 12:12 light:dark schedule. Activity is completely nocturnal in distribution in LD. ρ and α in LD differ significantly between males and females. Free-running circadian locomotor activity rhythm in DD was 23.69 h (males) and 23.46 h (females). In LD, ψ was −0.20 h and −0.15 h in males and females, respectively. Rhythms were accurate (6.02 in males/7.30 in females [h−1]) and precise (4.83 in males /4.74 in females [h−1]). Fifteen-minute perturbations with ∼70 lux white light in DD led to predictable phase advances and delays. Mus terricolor took ∼7 days to re-entrain to a 6 h advance in the ambient light schedule, with rapid resynchronization to a 6 h phase delay. These results indicate that M. terricolor is a good model animal for in-depth research in circadian biology.

Serotonergic agents usually attenuate light-induced phase shifts in nocturnal species. L-5-Hydroytrytptophan (5-HTP) is a non-specific serotonergic agonist and the natural precursor of serotonin. We investigated the ability of 5-HTP to potentiate or attenuate light-induced phase shifts using a comparatively lower intensity of light (∼70 lux). Mice free-running in DD were given either light exposure at circadian times (CTs) 15 and 21 with saline (light-exposed control) or 50 mg/kg of 5-HTP (Himedia) at 0.5 circadian h prior to light exposure. L-5-Hydroytrytptophan potentiated the phase advance of the rhythm caused by light at CT 21; however, 5-HTP fails to significantly attenuate/potentiate phase delays. Total activity increased during phase advance potentiation, compared to control, indicating that this phenomenon may possibly be at least partially behavioral arousal-dependent. These preliminary findings are interesting and unexpected; further experimentation is necessary, and the results indicate possibl...

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is a heterogeneous structure. Two key populations of cells that receive retinal input and are believed to participate in circadian responses to light are cells that contain vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP). VIP acts primarily through the VPAC2 receptor, while GRP works primarily through the BB2 receptor. Both VIP and GRP phase shift the circadian clock in a manner similar to light when applied to the SCN, both in vivo and in vitro, indicating that they are sufficient to elicit photic-like phase shifts. However, it is not known if they are necessary signals for light to elicit phase shifts. Here we test the hypothesis that GRP and VIP are necessary signaling components for the photic phase shifting of the hamster circadian clock by examining two antagonists for each of these neuropeptides. The BB2 antagonist PD176252 had no effect on light-induced delays on its own, while the BB2 antagonist RC-3095 had the unexpected effect of significantly potentiating both phase delays and advances. Neither of the VIP antagonists ([d-p-Cl-Phe6, Leu17]-VIP, or PG99-465) altered phase shifting responses to light on their own. When the BB2 antagonist PD176252 and the VPAC2 antagonist PG99-465 were delivered together to the SCN, phase delays were significantly attenuated. These results indicate that photic phase shifting requires participation of either VIP or GRP; phase shifts to light are only impaired when signalling in both pathways are inhibited. Additionally, the unexpected potentiation of light-induced phase shifts by RC-3095 should be investigated further for potential chronobiotic applications.

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) can be reset by the cholinergic agonist carbachol. In hamsters, intraSCN carbachol produces phase advances during the day. This phenomenon has previously been attributed to the muscarinic receptors, as carbachol-induced phase shifts are blocked by pretreatment with the muscarinic antagonist atropine. The SCN contains all five muscarinic receptors, leaving open the question as to which muscarinic receptors mediate these shifts. Here we test two selective muscarinic agonists, the M1/4 agonist McN-A-343 and the M2/3 agonist bethanechol, in addition to the non-selective cholinergic agonist carbachol. Consistent with previous reports, carbachol produced significant phase advances when injected to the SCN during the mid-subjective day. At the doses used here, McN-A-343, but not bethanechol, also produced significant phase shifts when injected to the SCN during the mid-subjective day. Phase shifts to McN-A-343 were as large as those produced by carbachol, suggesting that activation of the M1/4 receptors alone can fully account for the daytime phase advances produced by cholinergic agonists. Given acetylcholine's role in arousal, and the similarity between phase advances to carbachol/McN-A-343 and to exercise and arousal manipulations, it is possible that acetylcholine may contribute to non-photic resetting of the circadian clock.

Biological rhythms are ubiquitous phenomena that enable an organism to temporally adapt to the environment. Jet lag occurs during rapid transmeridial transport and disrupts the normal biological rhythm. Disruption of the biological rhythm is known to reduce survival and hasten tumorigenesis in male mice. Dalton's lymphoma (DL) is a spontaneous and highly invasive T-cell lymphoma that develops as an ascitic tumor in murines. DL was induced by serial implantation of live ascite cells in laboratory-acclimated age-matched male and female AKR mice. The mice were then subjected to simulated chronic jet lag (CJL) by rapidly and alternately advancing and delaying the ambient light dark cycle by 8 h every 2 days. Females, but not males, with DL became arrhythmic after exposure to simulated CJL. Survival was significantly curtailed in both male and female mice with DL + CJL compared to survival in mice with DL alone or CJL alone (∼16 days after DL induction in mice and facing jet lag, and ∼28 days after DL inductio...

Dalton's lymphoma (DL) is a spontaneous and highly invasive T-cell lymphoma that develops as an ascitic tumor in murines. DL was induced by serial implantation of live ascite cells in laboratory-acclimated age-matched male AKR mice. The effects of DL on the locomotor activity rhythm were studied under 12:12 h light:dark (LD) cycle. A significant decrease in the total and peak wheel-running activity was seen after the induction of DL, in comparison with the vehicle-injected control group. Durations of activity and rest were altered in DL mice, with a sharp daily increase in the duration of rest in the DL group. Circadian time period and acrophase of the rhythm remained similar in both control and DL mice. The mean estimate of statistic of rhythmicity (MESOR) and the amplitude of the locomotor activity rhythm were significantly lesser in post-DL-induced mice. A reduction in the span of the M1 and M2 motor cortex regions in DL mice and anatomical changes in the dentate gyrus were also seen. Thus, the effects...

Present study examines biological efiects of 2.45GHz microwave radiation in Parkes strain mice. Forty-day-old mice were exposed to CW (continuous wave) microwave radiation (2h/day for 30 days). Locomotor activity was recorded on running wheel for 12 days prior to microwave exposure (pre-exposure), 7 days during the flrst week of exposure (short-term exposure) and another 7-day spell during the last week of the 30-day exposure period (long-term exposure). Morris water maze test was performed from 17th to 22nd day of exposure. At the termination of the exposure, blood was processed for hematological parameters, brain for comet assay, epididymis for sperm count and motility and serum for SGOT (serum glutamate oxaloacetate transaminase) and SGPT (serum glutamate

Daily variation in circulatory melatonin level, during different seasons, has been reported to influence immune system and free-radical scavenging capacity in mammals, including human beings. Similar studies have not been carried out on small ruminant viz. goats that are susceptible to opportunistic infections, increased oxidative load and sickness during free-grazing activity and frequent exposure to agro-chemicals. Therefore, daily variation in immune status, antioxidant enzyme activity and its possible correlation with circulatory melatonin level during two different seasons, summer (long day) and winter (short day) were studied in the Indian goat, Capra hircus. The clinically important immune parameters, such as total leukocyte count, % lymphocyte count and % stimulation ratio of T-lymphocytes presented a day/night rhythm prominently in the winter. The oxidative load in terms of malonedialdehyde was always low during night while antioxidant enzymes superoxide dismutase, catalase and total antioxidant status were high during nighttime (1800 to 0600 hrs). Interestingly, the studied parameters were significantly higher during the winter in both the sexes. Rhythmometric analyses showed prominent rhythmicity in above parameters. The data presented strong positive correlation between high levels of nighttime melatonin levels and immune parameters during winter. It suggests that melatonin possesses immunoenhacing as well as antioxidative property during winter. This might be a necessity for maintenance of physiological harmony in goats to protect them from winter stress.

Biological clocks help organism to adapt temporally to a variety of rhythmic environmental cues. Acute changes in the rhythmicity of entraining cues causes short- to long-term physiological distress in individuals, for example, those occurring during jet-lag after long-haul transmeridial flights, or shift work. Variations in the rate of re-entrainment to a 9 h advanced schedule (simulation of acute Jet-lag/shift work) in the Indian pygmy field mouse, Mus terricolor are reported. Wheel- and lab-acclimated adult male mice were entrained to a 12:12 h light:dark (LD) cycles, followed by a 9 h advance in the LD cycle. In response, these mice either advanced or delayed their activity onsets, with individual variation in the rate and direction. Rapid orthodromic (advancing) re-entrainers exhibited a coincidence of activity onsets with the new dark onset in= 3 days, while gradually advancing re-entrainers took -9 days or more. Delayers (antidromic) also either re-entrained very rapidly (= 2 days), or gradually (-9 days). Acrophase measurement confirmed the direction of the transients, which did not depend on the free-running period. Such different patterns might determine the differential survival of individuals under the pressure of re-entrainment schedules seen in jet-lag and shift work.

We report that l-5-hydroxytryptophan (5-HTP), a serotonin precursor, resets the overt circadian rhythm in the Indian pygmy field mouse, Mus terricolor, in a phase- and dose-dependent manner. We used wheel running to assess phase shifts in the free-running locomotor activity rhythm. Following entrainment to a 12:12 h light–dark cycle, 5-HTP (100 mg/kg in saline) was intraperitoneally administered in complete darkness at circadian time (CT)s 0, 3, 6, 9, 12, 15, 18, and 21, and the ensuing phase shifts in the locomotor activity rhythm were calculated. The results show that 5-HTP differentially shifts the phase of the rhythm, causing phase advances from CT 0 to CT 12 and phase delays from CT 12 to CT 21. Maximum advance phase shift was at CT 6 (1.18 ± 0.37 h) and maximum delay was at CT 18 (−2.36 ± 0.56 h). No extended dead zone is apparent. Vehicle (saline) at any CT did not evoke a significant phase shift. Investigations with different doses (10, 50, 100, and 200 mg/kg) of 5-HTP revealed that the phase resetting effect is dose-dependent. The shape of the phase–response curve (PRC) has a strong similarity to PRCs obtained using some serotonergic agents. There was no significant increase in wheel-running activity after 5-HTP injection, ruling out behavioral arousal-dependent shifts. This suggests that this phase resetting does not completely depend on feedback of the overt rhythmic behavior on the circadian clock. A mechanistic explanation of these shifts is currently lacking.

Priyoneel Basu, Muniyandi SingaravelChronobiology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, IndiaRecently, an editorial in Nature Neuroscience pointed out the need for exercising caution in the use of over-the-counter drinks purporting to promote relaxation and containing, among other substances with chronobiotic activity, L-5-Hydroxytryptophan (5-HTP).1 This reality-check certainly raises an issue worth the attention of scientists who deal with, and laymen who dabble in, biological rhythms. Proprietary and patented formulations often project an image of safety, which is augmented by their over-the-counter availability as attractively packaged nutritional supplements. The allure of these bottled shots of bliss may seem undeniable to the general public. An online search of the words "5-HTP relaxation drink" returns > 7 million websites. Websites promoting these drinks do carry limited warnings or disclaimers (in fine print). The actual concentration of constituents is sometimes not provided in the online information leaflets. Certain websites provide a Natural Standard Editorial Board blinded review,2,3 which summarizes known scientific literature (exhaustively) and mentions likely safe doses. In view of the rising popularity and wide availability of 5-HTP containing drinks, we feel that scientists and the general public alike would profit from an additional nugget of information regarding a previously unforeseen effect of 5-HTP consumption at an inappropriate time, as brought to light by recent literature in the area.View orignal paper by Narsimhan