Daily variation of thermoregulatory costs in laboratory mice selected for high and low basal metabolic rate

Most mammals are known to have clear circadian rhythms of body temperature (T_b) and metabolic rate. Large parts of the rhythms correspond to the oscillation of nonshivering thermogenesis (NST), dependent on visceral organ mass, and, affected by mass of brown adipose tissue (BAT). I tested whether: (1) a different levels of BMR result in respective changes of T_b values and the magnitude of daily RMR oscillations both within and below thermoneutrality; (2) the amplitude of daily variation of RMR depends on ambient temperature (T_a). I studied: (1) daily variation of body temperature at T_a of 23 °C, and (2) the rate of resting metabolism (RMR) within and below thermoneutrality at the time of minimum and increasing T_b (minimum and maximum NST capacity), in two lines of laboratory mice subjected to divergent, artificial selection toward high (HBMR) and low (LBMR) basal rate of metabolism (BMR). All mice had a clear circadian rhythm of T_b with minimum of 36.4±0.2 °C at 7:00 and maximum of 37.8±0.2 °C at 21:00. Their RMR measured below thermoneutrality exhibited significant daily variation, with the maximum between 16:00 and 19:00, when T_b was rising. Within thermoneutral zone (TNZ) I found between-line, but not between-time, differences in RMR. All between-line differences in RMR could be explained by the magnitude of BMR. I did not find any between-line differences of RMR value in temperatures below thermoneutrality. The amplitude of daily variation of RMR measured below TNZ depended neither on the T_a value nor on level of BMR (or visceral organs).     

Estimation of the core temperature control during ambient temperature changes and the influence of circadian rhythm and metabolic conditions in mice

It has been speculated that the control of core temperature is modulated by physiological demands. We could not prove the modulation because we did not have a good method to evaluate the control. In the present study, the control of core temperature in mice was assessed by exposing them to various ambient temperatures (T_a), and the influence of circadian rhythm and feeding condition was evaluated. Male ICR mice (n=20) were placed in a box where T_a was increased or decreased from 27 °C to 40 °C or to −4 °C (0.15 °C/min) at 0800 and 2000 (daytime and nighttime, respectively). Intra-abdominal temperature (T_core) was monitored by telemetry. The relationship between T_core and T_a was assessed. The range of T_a where T_core was relatively stable (range of normothermia, RNT) and T_core corresponding to the RNT median (regulated T_core) were estimated by model analysis. In fed mice, the regression slope within the RNT was smaller in the nighttime than in the daytime (0.02 and 0.06, respectively), and the regulated T_core was higher in the nighttime than in the daytime (37.5 °C and 36.0 °C, respectively). In the fasted mice, the slope remained unchanged, and the regulated T_core decreased in the nighttime (0.05 and 35.9 °C, respectively), while the slopes in the daytime became greater (0.13). Without the estimating individual thermoregulatory response such as metabolic heat production and skin vasodilation, the analysis of the T_a–T_core relationship could describe the character of the core temperature control. The present results show that the character of the system changes depending on time of day and feeding conditions.     

Some like it hot: Mouse temperature preferences in laboratory housing

In standard laboratory environments mice are housed at 20–24 °C. However, their thermoneutral zone ranges between 26 °C and 34 °C. This challenge to homeostasis is by definition stressful, and could therefore affect many aspects of physiology and behavior. We tested the hypothesis that mice under standard laboratory conditions are not housed at a preferred temperature, and predicted that this would be evident in thermotaxis and other behavioral responses to ambient cage temperature. We assessed the temperature preferences of C57BL/6J mice in standard laboratory housing from 4 to 11 weeks of age. Forty-eight mice (24 male and 24 female in groups of three) all born on the same day were randomly assigned to one of eight age treatments. One cage of males and one cage of females were tested each consecutive week. Mice were tested in a set of three connected cages with each cage's temperature set using a water bath. On days 1–3 each group of mice was acclimated to each of the three temperatures (20 °C, 25 °C, or 30 °C) in a random order. Then each group was given free access to all temperatures on days 4–6, and video taped continuously. The location of each mouse and the occurrence of three behavioral categories (Active, Inactive, and Maintenance) were recorded by instantaneous scan samples every 10 min over the 3 days, and time budgets calculated. While both sexes chose warmer temperatures overall (P < 0.001), they preferred warmer temperatures only for maintenance and inactive behavior (P < 0.001). This effect was most pronounced in females (P = 0.017). As temperature selection varied with time of day (P < 0.001), these behavioral differences cannot be due to ambient temperature dictating behavior. We conclude that C57BL/6J mice at 20–24 °C are not housed at their preferred temperature for all behaviors or genders, and that it may not be possible to select a single preferred temperature for all mice.     

Spontaneously reduced body temperature and gasping ability as a mechanism of extreme tolerance to asphyxia in neonatal rats

The aim of the investigation was to verify our hypothesis that extreme tolerance of newborn rodents to anoxia is determined by their ability to maintain reduced body temperature and to keep on gasping.Newborn Wistar rats were used. In separate experiments we checked (1) effect of extreme thermal conditions on rectal temperature (T_re) of the newborns in their nests; (2) effect of ambient temperature (T_a) on oxygen consumption; (3) effects of controlled changes in T_re on thermoregulatory and respiratory responses to anoxia and on anoxia tolerance.In their nests rat pups controlled T_re at 32–36 °C while the T_re–T_a difference changed within a range of 1–20 °C. The lowest oxygen consumption of ∼24 ml O₂ kg⁻¹ min⁻¹ was recorded at T_a of 32 °C. Pups, exposed to anoxia at their normal T_re of 33 °C, were able to decrease T_re by another 1.7 °C and they kept on extremely slow and quiescent gasping for scheduled 25 min. In contrast, rats at T_re of 37 °C and 39 °C reached a critical phase of accelerated and shallow gasping after 14.95±0.40 min and 9.25±0.30 min, respectively.In conclusion, reduced T_re and unique gasping ability make newborn rats extremely tolerant to asphyxia.     

Locomotor and energetic consequences of behavioral thermoregulation in the sanguivorous leech Hirudo verbana

Medicinal leeches (Hirudo verbana) thermoregulate with respect to their sanguivorous feeding behavior. Immediate postprandial preferences are for warmer than their initial acclimation temperature (T_a, 21 °C, Petersen et al. 2011), while unfed leeches have a lower preferred temperature (T_pref, 12.5 °C). This may reduce energy expenditure and defer starvation if feeding opportunities are limited. Energetic benefits may have an associated cost if low temperatures reduce mobility and the ability to locate further hosts. These costs could be limited if mobility is unimpaired at low temperatures, or if acclimation can restore locomotor performance to the levels at T_a. The transition from T_a to the unfed T_pref significantly reduced speed and propulsive cycle frequency during swimming, and extension and retraction rates during crawling. Aerobic metabolic rate was also reduced from 0.20±0.03 W kg⁻¹ at T_a to 0.10±0.03 W kg⁻¹ at T_pref. The Q₁₀ values of 1.7–2.9 for energetic and swimming parameters indicate a substantial temperature effect, although part of the decline in swimming performance can be attributed to temperature-related changes in water viscosity. 6 weeks at T_a resulted in no detectable acclimation in locomotor performance or aerobic metabolism. The energetic savings associated with a lower T_pref in unfed leeches effectively doubled the estimated time until depletion of energy reserves. Given that some mobility is still retained at T_pref, and that acclimation is in itself costly, the energetic benefits of selecting cooler temperatures between feedings may outweigh the costs associated with reduced locomotor performance.     

The influence of starvation on fast-start performance of Spinibarbus sinensis

Juvenile Spinibarbus sinensis (n = 48, body length, 5.86 ± 0.10 cm, 25 °C) were fasted for 0, 0.5, 1, 2, 4 and 6 weeks. The fast-start performances of the experimental fish were assessed using high-speed video photography and the locomotive kinematics analysis. The morphological parameters including tail height (H₂), tail length (L₂), lateral body area (S₁), median fin area (S₂), dorsal cross section area (S₃) and tail cross section area (S₄) were also measured using TpsDig and the Photoshop. The results showed that 6 week starvation resulted in significant decreases in the escape distance (d), maximum linear velocity (V_max) and maximum linear acceleration (a_max) of center of mass in Stage 1 and Stage 2 of fast-start process (P < 0.05), however there were two relatively sTable phases in the V_max and d, during the week 1–2 (V_max = 0.67 ± 0.06 mm/ms; d = 8.86 ± 0.73 mm) and week 4–6 (V_max = 0.31 ± 0.04 mm/ms; d = 3.70 ± 0.56 mm). When compared with the control group (0 week starvation group), only the 6 week starvation group showed the significantly different response time (t) with average t = 9.20 ± 0.37 ms in week 1–4. There were no significant difference in mass center turning angles at first stage (T_a1) , second stage (T_a2) and the sum of two stages (T_a(1+2)) was also not different (P > 0.05). The fish did not show any directional preference for left or right during escape turning, and all of the related parameters also remained unchanged among treatment group (P > 0.05). The areas of dorsal body cross-section decreased more acutely (P < 0.05) than caudal body cross-section (45.4% vs 38.0%) during the entire starvation period while no significant differences were observed in both the tail height and tail length among all treatment groups (P > 0.05). The results indicated that fast-start performance of juvenile S. sinensis is affected by the starvation; metabolic energy related traits such as the maximum linear velocity and the maximum linear acceleration decreased significantly after starvation; whereas traits with no direct link to metabolic energy such as the response time and turning angle remained unchanged during starvation. The lack of starvation induced change in the maneuverability of the fish suggests that fast-start ability related to escape strategy is relatively well conservative in juvenile S. sinensis.     

Synthesis and biological evaluation of a series of benzoxazole/benzothiazole-containing 2,3-dihydrobenzo[b][1,4]dioxine derivatives as potential antidepressants

A series of benzoxazole/benzothiazole-2,3-dihydrobenzo[b][1,4]dioxine derivatives (5a–5d and 8a–8j) was synthesized. Compounds were evaluated for binding affinities at the 5-HT_1A and 5-HT_2A receptors. Antidepressant activities of the compounds were screened using the forced swimming test (FST) and the tail suspension test (TST). The results indicated that the compounds exhibited high affinities for the 5-HT_1A and 5-HT_2A receptors and showed a marked antidepressant-like activity. Compound 8g exhibited high affinities for the 5-HT_1A (K_i = 17 nM) and 5-HT_2A (K_i = 0.71 nM) receptors; it also produced a decrease of the immobility time and exhibited potent antidepressant-like effects in the FST and TST in mice.     

Reduction in open field-induced hyperthermia in the rat exposed to chlorpyrifos,an anticholinesterase pesticide

Rodents develop a marked elevation in core temperature (T_c) when they are placed in an open field environment (OFE). Open field-induced hyperthermia (OFH) involves activation of thermoregulatory systems that are quiescent under baseline conditions. Cholinergic stimulation arising from exposure to organophosphates (OP) is expected to modulate OFH; subtle effects of OPs may be observed during OFH that would not occur in the absence of stress. We have found that methyl scopolamine (MS), a peripheral muscarinic antagonist, attenuates stress-induced hyperthermia. To this end, we assessed if a low dose of the OP pesticide chlorpyrifos (CHP) would alter OFH with and without administration of MS. T_c and motor activity (MA) of male, Sprague-Dawley rats were monitored by telemetry while housed in their home cage at an ambient temperature of 22°C. At 9 AM the rats were gavaged with corn oil or 10 mg/kg CHP that resulted in a ∼40% inhibition in plasma cholinesterase activity. T_c and MA were the same in the control and CHP groups prior to OFE. The rats were then dosed IP with saline or 1.0 mg/kg MS at 12 noon and subjected to OFE (61×61×61 cm box) for 1 h while T_c and MA were monitored every 2 min. T_c of the corn oil/saline group increased by 1.2°C during OFE, whereas T_c of the CHP/saline group was significantly attenuated. Administration of MS attenuated the OFH in rats treated with corn oil and CHP. Overall, exposure to OFE exacerbated the effects of a relatively low dose of CHP that had no effect in the unstressed animal. In addition, the OFH response to MS suggests a peripheral (i.e., outside of CNS) cholinergic pathway is operative in the control of OFH.     

The thermoregulatory limits of an Australian Passerine,the Silvereye (Zosterops lateralis)

(1) The thermal capabilities of Australian silvereyes (Zosterops lateralis, 11 g) were investigated both at low and high ambient temperatures (T_a) during the photophase and scotophase. (2). The peak metabolic rate (PMR) induced by helium–oxygen (79:21 %, He–O₂) exposure during the photophase was 15.64±1.55 mL O₂ g⁻¹ h⁻¹ at an effective lower survival limit T_a (T_pmr) of −39.7±6.1°C. (3). Above the thermoneutral zone (TNZ), metabolic rate, body temperature (T_b), and thermal conductance increased steeply, but they were able to withstand a T_a of 39°C. (4). Our study shows that silvereyes are able to tolerate an impressive range of T_a from about −42°C to at least +39°C and are able to produce enough heat to maintain a thermal difference between T_b and T_a of up to 80°C.     

Metabolic,hygric and ventilatory physiology of the red-tailed phascogale (Phascogale calura; Marsupialia,Dasyuridae): Adaptations to aridity or arboreality?

The red-tailed phascogale is a small arboreal dasyurid marsupial that inhabits semi-arid to arid regions of Western Australia's wheat belt. Its body mass (34.7 g) is only ～15% of that predicted based on its phylogenetic position among other dasyuromorphs; we interpret this as an adaptation to its scansorial and semi-arid/arid lifestyle. The standard physiology of this species at a thermoneutral ambient temperature of 30 °C conforms to that of other dasyurid marsupials; body temperature (34.7 ± 0.37 °C), basal metabolic rate (0.83 ± 0.076 mL O₂ g^?1 h^?1), evaporative water loss (1.68 ± 0.218 mg H₂O g^?1 h^?1) and wet thermal conductance (3.8 ± 0.26 J g^?1 h^?1 °C^?1) all fall within the 95% predication limits for the respective allometric relationships for other dasyurid species. Thermolability confers an energy savings at low T_a and water savings at high T_a. Torpor, observed at low T_a, was found to be more beneficial for energy savings than for water economy. The red-tailed phascogale therefore has a physiology suitable for the challenges of arid environments without any obvious requirement for adaptations to its scansorial lifestyle, other than its considerably lower-than-expected body mass.     

The effect of time left alone at home on dog welfare

The aim of this study was to investigate the effect of time left alone on dog behaviour and cardiac activity. Twelve privately owned dogs, with no history of separation related behaviour problems, were video-recorded on three different occasions when left alone in their home environment. The treatments lasted for 0.5 h (T_0.5); 2 h (T₂) and 4 h (T₄). Video-recording started 10 min before the owner left the house and continued until 10 min after the owner returned, so that interactions between dog and owner as well as behaviour during separation could be studied. Data on heart rate (HR) and heart rate variability (HRV) were collected within the same time period in each treatment. In addition to analysing behaviours separately, behaviours were also grouped together and defined as new variables; physically active, attentive behaviour, vocal, interaction initiated by owner and interaction initiated by dog. There were no differences in behaviour between treatments at equivalent time intervals until the owner returned, although a number of differences were observed at reunion with the owner. Dogs showed a higher frequency of physical activity (P < 0.05) and attentive behaviour (P < 0.01) in T₂ (0.37 ± 0.07; 0.52 ± 0.08, mean frequency of occurrence/15 s ± SE) and T₄ (0.48 ± 0.08; 0.48 ± 0.07) compared to T_0.5 (0.20 ± 0.07; 0.21 ± 0.05). They also showed more tail wagging (P < 0.01) and interacted more with their owners (P < 0.01) in T₂ (0.27 ± 0.08; 0.47 ± 0.09) and T₄ (0.26 ± 0.04; 0.42 ± 0.09) compared to T_0.5 (0.09 ± 0.04; 0.14 ± 0.03). After a longer time of separation, the dogs also showed higher frequencies of lip licking (P < 0.05) and body shaking (P < 0.05) at the owner's return (T_0.5 = 0.09 ± 0.05; T₂ = 0.24 ± 0.08; T₄ = 0.27 ± 0.06 and T_0.5 = 0.03 ± 0.01; T₂ = 0.08 ± 0.03; T₄ = 0.07 ± 0.01, respectively). There was a tendency for higher HR (P < 0.1) during the first and second minute after reunion in T₂ (127.6 ± 1.25, mean bpm ± SE; 111.3 ± 1.24) compared to T_0.5 (106.2 ± 1.06; 87.5 ± 1.02). According to the results of this study, the effect of time left alone was shown by a more intense greeting behaviour by the dog towards their owner as well as by a higher frequency of physical activity and attentive behaviour when the owner returned, already after 2 h of separation. Although this study cannot distinguish between whether dogs were aware of the length of time they were alone (but did not signal it) or whether they were unaware until reminded of it by the return of their owner, it does confirm that dogs are affected by the duration of time at home alone.     

Neuromuscular fatigue during a prolonged intermittent exercise: Application to tennis

The time course of alteration in neuromuscular function of the knee extensor muscles was characterized during a prolonged intermittent exercise. Maximal voluntary contraction (MVC) and surface EMG activity of both vastii were measured during brief interruptions before (T₀), during (30, 60, 90, 120, 150 and 180 min: T₃₀, T₆₀, T₉₀, T₁₂₀, T₁₅₀, T₁₈₀) and 30 min after (T₊₃₀) a 3 h tennis match in 12 trained players. M-wave and twitch contractile properties were analyzed following single stimuli. Short tetani at 20 Hz and 80 Hz were also applied to six subjects at T₀ and T₁₈₀. Significant reductions in MVC (P < 0.05; −9%) and electromyographic activity normalized to the M wave for both vastii (P < 0.01) occurred with fatigue at T₁₈₀. No significant changes in M-wave duration and amplitude nor in twitch contractile properties were observed. The ratio between the torques evoked by 20 Hz and 80 Hz stimulation declined significantly (P < 0.001; −12%) after exercise. Central activation failure and alterations in excitation–contraction coupling are probable mechanisms contributing to the moderate impairment of the neuromuscular function during prolonged tennis playing.     

Benzyl 1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3′,4′:1,2]pyridin[3,4-b]indole-2-substituted acetates: One-pot-preparation,anti-tumor activity,docking toward DNA and 3D QSAR analysis

To discover the anti-tumoral indoles a series of benzyl 1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3′,4′:1,2]pyridin[3,4-b]indole-2-substituted acetates (2a–n) are prepared via one-pot-preparation. The IC₅₀ values of 2a–n in vitro against human lung carcinoma, prostate cancer, nasopharyngeal carcinoma, vincristine-resistant KB subline and human breast carcinoma cells range from 40 nM to 60 μM. On Sarcoma 180 (S180) tumor-bearing mouse model four of them (2e,g,h,i) significantly inhibited the tumor growth. At the dose of 0.1 mg/kg the efficacy of the most potent 2h was equal to that of 1.0 mg/kg of doxorubicin. In contrast to doxorubicin, at 1.0 mg/kg of dose 2e,g,h,i did not induce the treated S180 mice to have organ atrophy and body emaciation. The healthy mice receiving 10, 100 and 500 mg/kg of 2e,g,h,i gave no any neurotoxic response. Even up to the dose of 500 mg/kg the healthy mice occurred no death. The interaction of 2a–n with DNA was confirmed by the fluorescence quenching experiments and automated flexible ligand docking. By 3D QSAR analysis the IC₅₀ values of 2a–n against prostate cancer cells were correlated with the structures and conformations of their side chains. To increase the data related to their physical-chemical properties the experimental Log P values were also provided.     

Climate change and animals in Saudi Arabia

Global warming is occurring at an alarming rate and predictions are that air temperature (T_a) will continue to increase during this century. Increases in T_a as a result of unabated production of greenhouse gases in our atmosphere pose a threat to the distribution and abundance of wildlife populations worldwide. Although all the animals worldwide will likely be affected by global warming, diurnal animals in the deserts will be particularly threatened in the future because T_as are already high, and animals have limited access to water. It is expected that Saudi Arabia will experience a 3–5 °C in T_a over the next century. For predicting the consequences of global warming for animals, it is important to understand how individual species will respond to higher air temperatures. We think that populations will not have sufficient time to make evolutionary adjustments to higher T_a, and therefore they will be forced to alter their distribution patterns, or make phenotypic adjustments in their ability to cope with high T_a. This report examines how increases in T_a might affect body temperature (T_b) in the animals of arid regions. We chose three taxonomic groups, mammals, birds, and reptiles (Arabian oryx, Arabian spiny-tailed lizard, vultures, and hoopoe larks) from Saudi Arabia, an area in which T_a often reaches 45 °C during midday in summer. When T_a exceeds T_b, animals must resort to behavioral and physiological methods to control their T_b; failure to do so results in death. The observations of this study show that in many cases T_b is already close to the upper lethal limit of around 47° C in these species and therefore allowing their T_b to increase as T_a increases are not an option. We conclude that global warming will have a detrimental impact on a wide range of desert animals, but in reality we know little about the ability of most animals to cope with change in T_a. The data presented should serve as base-line information on T_b of animals in the Kingdom for future scientists in Saudi Arabia as they explore the impact of global warming on animal species.     

Tensiomyography of selected lower-limb muscles in professional soccer players

Tensiomyography is a non-invasive method of neuromuscular assessment used to measure muscle action characteristics, muscle tone, and muscle fiber type, and provides information on acute and chronic responses of muscle to different training loads. The aims of the present study were: to analyse differences in muscle response and mechanical characteristics of two major muscles of the lower extremity in a large group of Spanish soccer players according to playing position, and to provide group norms against which clinical findings may be compared. Data were collected from 78 professional soccer players (age 26.6 ± 4.4 years; height: 179.2 ± 5.3 cm; body mass: 75.8 ± 5.3 kg). Tensiomyography was recorded from the rectus femoris (RF) and biceps femoris (BF) muscles after 2 days without take part in any strenuous exercise or training. Five tensiomyographic parameters were analyzed: maximal displacement (D_m), contraction time (T_c), sustain time (T_s), delay time (T_d), and half-relaxation time (T_r). A good to excellent intra-session reliability was found for all contractile parameters (ICC ranged from 0.78 to 0.95). No significant differences between players of any position were observed in absolute values of BF. However, significant differences were observed for T_c, T_r and T_s between the different playing positions on RF (P < 0.05, effect size ranged from 1.3 to 1.6). Professional soccer players showed muscles with ability to rapidly generate force during contractions. The neuromuscular profile provided could help in identifying the normative data that are important for the different positions in order to optimize the training and recovery process of each individual player.     

Environmental stress and elicitors enhance taxol production by endophytic strains of Paraconiothyrium variabile and Epicoccum nigrum

This study examined the effect of different elicitors (seven, different concentrations) and environmental factors (water activity (a_w), pH) on taxol production by strains of two endophytic fungi, Paraconiothyrium variabile and Epicoccum nigrum, isolated from temperate yew trees. A defined liquid broth medium was modified with elicitors, solute a_w depressors at different pH values. For P. variabile, the best elicitor was salicylic acid at 50 mg/l which gave a taxol yield of 14.7 ± 4.8 μg/l. The study of synergistic effects between elicitor, a_w and pH on taxol production showed that the highest yield of taxol (68.9 ± 11.9 μg/l) was produced under modified ionic stress of 0.98 a_w (KCl) at pH 5 when supplemented with 20 mg/l of salicylic acid. For E. nigrum, serine was the best elicitor which increased yield significantly (29.6 fold) when KCL was used as the a_w depressor (0.98 a_w) at pH 5.0 with 30 mg/l of serine. The maximum taxol yield produced by E. nigrum was 57.1 ± 11.8 μg/l. Surface response models were used to build contour maps to determine the conditions for maximum and marginal conditions for taxol yield in relation to the best elicitor and a_w, and the best pH for the first time. This will be beneficial for identifying key parameters for improvement of taxol yields by endophytic fungi.     

The effects of cage volume and cage shape on the condition and behaviour of captive European starlings (Sturnus vulgaris)

Cage size is widely recognised as an important determinant of captive animal welfare, but in contrast, cage shape has received far less attention. Husbandry recommendations for flying birds state that cages should be long in shape because this allows greater potential for flight. However, so far no studies have investigated the impact of cage shape on the behaviour or welfare of captive flying birds. We measured the effects of cage size and shape on the condition and behaviour of captive wild-caught European starlings (Sturnus vulgaris) using a 2 × 3 factorial design in which birds were individually housed for 1 week in cages of one of two volumes (either medium at 0.3 m³ or large at 1 m³), and one of three shapes (long with an aspect ratio (i.e. length/height) of 3.43), standard with an aspect ratio of 1.72 or tall with an aspect ratio of 0.86). We found effects of cage size and the interaction of cage size and shape on the behaviour and condition of birds. In interpreting the welfare implications of our results we focused on stereotypic behaviour as measured by incidence of somersaulting and a novel statistic that quantifies sequential dependencies in the birds’ locations within the cage. The lowest measures of stereotypic behaviour were recorded in the large cages and the medium long cage. Cage shape was more important in determining the quantity of stereotypic behaviour in the medium cages than the large cages. Our findings support the recommendation that starlings be housed in long-shaped cages.     

Synthesis and antiprotozoal activity of 2,5-bis[amidinoaryl]thiazoles

Seven novel diamidino 2,5-bis(aryl)thiazoles (5a–g) were synthesized and evaluated against Trypanosoma brucei rhodensiense (T. b. r.) and Plasmodium falciparum (P. f.). The diamidines were obtained directly from the corresponding bis-nitriles (4a–g) by the action of lithium bis(trimethylsilyl)amide. The bis-nitriles 4a–f were synthesized in four steps starting with the Stille coupling of 2-tributyltinthiazole with the appropriate cyanoaryl halide. The bis-nitrile 5g was obtained by the palladium facilitated coupling of the mixed tin-silyl reagent 2-trimethylsilyl-5-trimethyltinthiazole with 2-bromo-5-cyanopyridine. The amidoxime potential prodrugs 6a–e, 6g were obtained by the reaction of hydroxylamine with the bis-nitriles. O-Methylation of the amidoximes gave the corresponding N-methoxyamidines 7a–c, 7e, 7g. The diamidines showed strong DNA binding affinity as reflected by ΔT_m measurements. Four of the diamidines 5a, 5b, 5d and 5e were highly active in vitro against P. f. giving IC₅₀ values between 1.1 and 2.5 nM. The same four diamidines showed IC₅₀ values between 4 and 6 nM against T. b. r. The selectivity indices ranged from 233 to 9175. One diamidine 5a produced one of four cures at an ip dose of 4 × 5 mg/kg in the STIB900 mouse model for acute African trypanosomiasis. The amidoxime and N-methoxyamidine of 5a were the only produgs to provide cures (1/4 cures) in the same mouse model on oral dosage at 4 × 25 mg/kg.     

Synthesis and discovery of 2,3-dihydro-3,8-diphenylbenzo[1,4]oxazines as a novel class of potent cholesteryl ester transfer protein inhibitors

2,3-Dihydro-3,8-diphenylbenzo[1,4]oxazines were identified as a new class of potent cholesteryl ester transfer protein inhibitors. The most potent compound 6a (IC₅₀ = 26 nM) possessed a favorable pharmacokinetic profile with good oral bioavailability in rat (F = 53%) and long human liver microsome stability (t_1/2 = 62 min). It increased HDL-C in human CETP transgenic mice and high-fat fed hamsters. The structure and activity relationship of this series will be described in this Letter.     

Energy metabolism and thermoregulation in pygmy lorises (Nycticebus pygmaeus) from Yunnan Daweishan Nature Reserve

The pygmy loris (Nycticebus pygmaeus) is a small prosimian living in Vietnam, Laos, eastern Cambodia and the south part of China. In China it is only found in Pingbian, Hekou, Jinping, Luchun of Yunnan. As N. pygmaeus is seriously threatened by hunting, trade and habitat destruction, it is listed in Appendix II of CITES, and in 2006 the IUCN classified it as “vulnerable”. In order to understand the characteristics of energy metabolism and thermoregulation of N. pygmaeus, the resting metabolic rate (RMR) and body temperature (T_b) at different ambient temperature (T_a) of pygmy lorises, as well as body mass, energy intake, digestable energy intake, digestability and the thermal conductance were measured in captivity. The results obtained mainly are as follows: (1) Pygmy loris feed dry food averaged 12.90 ± 1.02 g/d. They could gain 214.87 ± 16.65 kJ/d from food intake, and earned 200.15 ± 16.36 kJ digestable energy intake per day with 90.13 ± 1.34% of the digestability. (2) The T_b at room temperatures was a little low (35.23 ± 0.16 °C) and varied with T_a from 25 °C to 35 °C. There was a positive relationship between T_b and T_a, which was described as: T_b = 27.22 + 0.34T_a (r = 0.880). (3) The resting metabolic rate (RMR) of the pygmy loris was 0.3844 ± 0.0162 mlO₂/g/h, which was 51.91 ± 1.90% of the previous predicted rate by Kleiber (1961) [21]. (4) The average thermal conductance of the pygmy loris (N. pygmaeus) was 0.0449 ± 0.0031 mlO₂/g/h/°C. These characteristics of energy metabolism and thermoregulation of N. pygmaeus in Yunnan Daweishan Nature Reserve might be considered as the adaptive characteristics to their environment in tropical semi-evergreen forests and secondary forests.