Conserving large carnivores: dollars and fence.

Conservationists often advocate for landscape approaches to wildlife management while others argue for physical separation between protected species and human communities, but direct empirical comparisons of these alternatives are scarce. We relate African lion population densities and population trends to contrasting management practices across 42 sites in 11 countries. Lion populations in fenced reserves are significantly closer to their estimated carrying capacities than unfenced populations. Whereas fenced reserves can maintain lions at 80% of their potential densities on annual management budgets of $500 km(-2) , unfenced populations require budgets in excess of $2000 km(-2) to attain half their potential densities. Lions in fenced reserves are primarily limited by density dependence, but lions in unfenced reserves are highly sensitive to human population densities in surrounding communities, and unfenced populations are frequently subjected to density-independent factors. Nearly half the unfenced lion populations may decline to near extinction over the next 20-40 years.

Administration of 6-methoxybenzoxazolinone (MBOA) does not augment ovulatory responses in St. Croix White ewes superovulated with PMSG.

The objective of this investigation was to examine the effects of 6-methoxy-benzoxazolinone (MBOA), a plant compound that resembles melatonin and alters ovarian function in rodents, in combination with PMSG on superovulatory responses in the cycling ewe. In Experiment I, St. Croix White ewes (n = 44) were synchronized (intra-vaginal progestin sponge) for 14days followed by hCG (750 IU) at 1 day after sponge removal (day 0). Ewes were assigned to one of six treatments administered on day -1: Control (no PMSG or MBOA; n = 7); PMSG (1000 IU i.m.; n = 7); Low MBOA (0.43 mg/kg i.m.; n = 7); High MBOA (1.15 mg/kg i.m.; n = 7); Low MBOA + PMSG (n = 8); High MBOA + PMSG (n = 8). In Experiment II, St. Croix White ewes (n = 24) were synchronized (progestin CIDR) for 14 days followed by hCG on day 1 after CIDR removal (day 0). Ewes were assigned to one of three treatments administered on day -1: Control (n = 8); PMSG (n = 8); Low MBOA+PMSG (n = 8). Laparoscopy was performed on day 9 to assess numbers of corpora lutea (CL) and visible follicles on each ovary. Blood samples were collected on day -13, -1, 0, 1, and days 6 or 7-12 for analysis of serum progesterone (P4) by RIA. Treatment groups receiving PMSG (alone or with MBOA) exhibited greater (P < 0.05) serum concentrations of P4 post-synchrony than Control and MBOA-only groups. Ovulation rate was lower (P < 0.05) for Control and MBOA-only treated ewes than ewes receiving PMSG. Ovulation rate in ewes treated with MBOA alone was similar (P > 0.10) to Controls, and PMSG treatment alone did not differ (P > 0.10) from MBOA + PMSG treatment. Ewes treated with PMSG alone did not differ (P > 0.10) in follicle number from High MBOA + PMSG treated ewes, however, Low MBOA + PMSG treated ewes had greater numbers of follicles at day 9 (P < 0.05) than the PMSG or High MBOA + PMSG groups in Experiment I; although, this was not replicated in Experiment II with numbers of follicles in the Low MBOA + PMSG group being similar (P > 0.10) to PMSG alone. In summary, the addition of MBOA in combination with PMSG as part of a synchronization-superovuation protocol in the ewe did not increase ovulation rate.

Binge-like acquisition of 3,4-methylenedioxypyrovalerone (MDPV) self-administration and wheel activity in rats.

RATIONALE: Lack of access to conventional sources of reinforcement has been proposed as a risk factor for substance abuse in lower socioeconomic populations. There is laboratory evidence that behavioral alternatives (enrichment or exercise) and alternative reinforcers (e.g., sweetened solutions) can reduce self-administration of a variety of drugs. OBJECTIVES: The objective of this study is to determine if drug self-administration could devalue wheel activity in an animal model. METHODS: Male Wistar rats were trained to self-administer 3,4-methylenedioxypyrovalerone (MDPV; "bath salts"), 0.05 mg/kg/infusion, i.v., with concurrent access to a running wheel that was either locked (LW) or unlocked (UW). RESULTS: MDPV intake steadily increased across the 20-session acquisition interval but did not differ significantly between UW and LW groups. Mean wheel rotations declined significantly across the acquisition interval in the UW group. Of the rats that acquired self-administration, 60 % engaged in a binge-like behavior at the initiation of acquisition; intake was limited only by post-reinforcement time-out. The binge rats had higher post-acquisition levels of drug intake (even after excluding the binge session), and the UW binge rats showed a precipitous post-acquisition drop in wheel activity that was not observed in the UW no-binge rats. CONCLUSIONS: These data confirm that MDPV is a powerful reward/reinforcer and show that a relatively high rate of intake at the onset of drug taking can devalue natural rewards (wheel activity) and can predict higher subsequent drug intake levels. Thus, limiting the intensity of initial drug exposure may attenuate subsequent drug abuse/addiction by preventing the devaluation of natural alternative rewards/reinforcers.

The immunosuppressant FK506 increases functional recovery and nerve regeneration following peripheral nerve injury.

Regeneration of peripheral nerve fibers over long distances often requires extended periods of convalescence. Loss to society can be measured in terms of increased health care costs, decreased productivity and, in the case of job-related injuries, larger workers' compensation claims. The availability of drugs to increase axonal regeneration would be beneficial not only to patients but also to society in general by decreasing these costs. In the present paper, we present our initial studies on the regenerative effects of the new immunosuppressive agent FK506. Rats given a sciatic nerve crush (axotomy) received daily subcutaneous injections of FK506 (1.0 mg/kg); axotomized control animals received saline. Clinical signs of recovery in the hind feet were manifested two days earlier in FK506-treated than in saline-treated animals; movement in the toes, and walking on the hind feet and toes were observed at 16 and 17 days, respectively, in saline-treated rats and at 14 and 15 days, respectively, in FK506-treated rats. Measurement of interdigit distances in the hind feet at 18 days following axotomy showed a return toward normal position of the toes (increased interdigit distances) during walking in FK506-treated rats. Light and electron microscopy performed at 18 days following axotomy confirmed the clinical appearance of increased functional recovery in FK506-treated rats. Distal to the crush site, the sciatic nerve and its terminal branches from FK506-treated animals contained more myelinated fibers compared to saline-treated animals; in the soleus nerve, the numbers of myelinated axons was increased 2.75-fold. Taken together, the present results suggest that FK506 enhances recovery of function in the rat by increasing the rate of axonal regeneration following a sciatic nerve crush.

Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. IV. Evidence for the involvement of two signals.

Axonal regeneration over long distances is dependent upon events occurring both in the distal stump and in the neuronal cell body. Little is known concerning how events in the distal stump influence the cell body response to injury, or the axon reaction. In the present study, we examined this relationship for one component of the axon reaction (i.e. aberrant neurofilament (NF) phosphorylation) in the C57BL/Ola (Ola) mouse mutant, a model which exhibits delayed Wallerian degeneration (up to 3 weeks) and retarded regeneration of sensory neurons. Non-axotomized normal (C57/6J/BL) and Ola mice demonstrated modest immunostaining to phosphorylated NF (pNF) epitopes (using monoclonal antibody 06-17) in some (11%) L4 dorsal root ganglion (DRG) neuronal cell bodies. In normal mice, modest to intense immunoreactivity was present in 43% of DRG neurons at 1 week following a sciatic nerve crush (axotomy). The intensity and extent of staining declined with reinnervation, being reduced slightly at 2 weeks and more notably by 3 weeks following axotomy. In Ola mice, the intensity and extent (43%) of staining were not different from normal axotomized mice at 1 week following axotomy. However, the intensity was less and the extent of staining reduced by 28% at 2 weeks following axotomy. By 3 weeks, staining levels were again increased, being similar to that observed in Ola and normal mice at 1 week following axotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple signals underlie the axotomy-induced up-regulation of c-JUN in adult sensory neurons.

We examined the axotomy-induced expression of the immediate-early gene (proto-oncogene) c-jun in the Ola mouse mutant (which exhibits a dramatic delay in Wallerian degeneration) using immunocytochemistry to c-JUN (the protein product of the protooncogene c-jun). c-JUN-like protein immunoreactivity was present in a similar proportion (ca. 60%) of L4 dorsal root ganglion (DRG) neuronal cell bodies from normal (C57/6J/BL) and Ola mice at 1 week following a sciatic nerve crush (axotomy). In normal mice, the intensity and extent of staining declined at 3 weeks, correlating with regeneration. In contrast, Ola mice exhibited a marked reduction (by 77%) in the extent of staining at 2 weeks. At 3 weeks (coinciding to the onset of extensive axonal degeneration in this mutant), staining levels were increased to 1 week levels. Taken together, these findings suggest that multiple signals (both independent and dependent on axonal degeneration) regulate c-jun expression in DRG neuronal cell bodies.

Regulation of the transcription factor c-JUN by nerve growth factor in adult sensory neurons.

We examined the regulation by nerve growth factor (NGF) of the immediate-early gene (proto-oncogene) c-jun in adult dorsal root ganglion (DRG) neurons using immunocytochemistry to c-JUN (the protein product of the proto-oncogene c-jun). Following a sciatic nerve crush, the injury-induced increase in c-JUN-like immunostaining was reduced in DRG neurons by continuous intrathecal infusion of NGF for one week. Conversely, in intact DRG neurons (i.e., without Wallerian degeneration), c-JUN-like immunoreactivity was markedly increased following four weeks of daily NGF antiserum injections (to remove target tissue-derived NGF) into the hindfoot. Taken together, these findings indicate that nerve transection (axotomy) results in a loss of target tissue-derived NGF leading to induction of the transcription factor c-jun which may play a role in axonal regeneration.

The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats.

Recreational use of the cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV; "bath salts") has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions. Minimal information exists on the effects of MDPV in laboratory models. This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity. Male Wistar rats were trained to self-administer MDPV or METH (0.05 mg/kg/infusion, i.v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0-5.6 mg/kg s.c.). METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/h; METH Mean = 0.4 and Max = 1.15; MDPV Mean = 0.9 and Max = 5.8). Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0.01-0.50 mg/kg/inf) showed greater potency and efficacy than METH (0.1-0.25 mg/kg/inf). In addition, both MDPV and METH increased locomotor activity at lower doses (0.5-1.0 mg/kg, s.c.) and transiently decreased activity at the highest dose (5.6 mg/kg, s.c.). Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature. Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (∼1.5 mg/kg/h) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased. Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH.

Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone).

BACKGROUND: The substituted cathinone compound known as mephedrone (4-methylmethcathinone; 4-MMC) has become popular with recreational users of psychomotor-stimulant compounds. Only recently have the first preclinical studies provided information about this drug in the scientific literature; nevertheless, media reports have led to drug control actions in the UK and across several US states. Rodent studies indicate that 4-MMC exhibits neuropharmacological similarity to 3,4-methylenedioxymethamphetamine (MDMA) and prompt investigation of the thermoregulatory, cardiac and locomotor effects of 4-MMC. This study focuses on the role of ambient temperature, which has been shown to shift the effects of MDMA from hyperthermic to hypothermic. METHODS: Male Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1.0-5.6 mg/kg) using an implantable radiotelemetry system under conditions of low (20 °C) and high (30 °C) ambient temperature. RESULTS: A pharmacokinetic study found a T(max) of 0.25 h and a C(max) of 1206 ng/ml after 5.6 mg/kg 4-MMC. A dose-dependent reduction of body temperature was produced by 4-MMC at 20 °C but there was no temperature change at 30 °C. Increased locomotor activity was observed after 4-MMC administration under both ambient temperatures, however, significantly more activity was observed at 30 °C. Heart rate was slowed by 1.0 and 5.6 mg/kg 4-MMC at 20°C, and was slower in the 30 °C vs. 20 °C condition across all treatments. CONCLUSION: These results show that the cathinone analog 4-MMC exhibits in vivo thermoregulatory properties that are distinct from those produced by MDMA.

Mephedrone (4-methylmethcathinone) and d-methamphetamine improve visuospatial associative memory, but not spatial working memory, in rhesus macaques.

BACKGROUND AND PURPOSE: The novel cathinone derivative 4-methylmethcathinone (4-MMC; mephedrone) is increasingly popular with recreational users. Little scientific information is available but users report both entactogen-like and classic stimulant-like subjective properties. A recent study in humans reported psychomotor speed improvement after intranasal 4-MMC suggesting classic stimulant properties. Limitations of the user group (which was impaired on some tasks) prompt controlled laboratory investigation. EXPERIMENTAL APPROACH: Adult male rhesus monkeys were trained to perform tasks from the non-human primate Cambridge Neuropsychological Test Automated Battery, which assess spatial working memory, visuospatial associative memory, learning and motivation for food reward. Test of bimanual motor coordination and manual tracking were also included. The subjects were challenged with 0.178-0.56 mg·kg(-1) 4-MMC and 0.056-0.56 mg·kg(-1) d-methamphetamine (MA), i.m., in randomized order for behavioural evaluation. KEY RESULTS: A pronounced improvement in visuospatial memory and learning was observed after the 0.32 mg·kg(-1) dose of each compound, this effect was confirmed with subsequent repetition of these conditions. Spatial working memory was not improved by either drug, and the progressive ratio, bimanual motor and rotating turntable tasks were all disrupted in a dose-dependent manner. CONCLUSIONS AND IMPLICATIONS: These studies show that 4-MMC produces behavioural effects, including improvements in complex spatial memory and learning that are in large part similar to those of MA in non-human primates. Thus, the data suggest that the effects of 4-MMC in monkeys can be classified with classical psychomotor stimulants.

The role of coaching in the business of dentistry.

Coaching is a subject dentistry appears to have let slip by, yet as this article outlines, it has so much to offer in many different aspects of dentistry, but particularly in fulfilling the Standards for dental professionals determined by the General Dental Council (GDC). Evidence suggests that coaching has produced tremendous benefits to business, and dentistry is a business.

Gestational, periparturient and preweaning growth traits of Holstein versus Gir x Holstein F1 crossbred dairy calves born to Holstein dams.

The objectives of this study were to assess the gestational, periparturient and preweaning growth traits of Holstein vs Gir x Holstein (G x H F1) cross-bred dairy calves. Holstein cows (n=64) pregnant with Holstein (H x H) calves (bulls, n=16; heifers, n=18) or G x H (bulls, n=8; heifers, n=22) calves were sampled from 60 days of gestation through calving for serum progesterone (P4) and in utero placentome sizes, and at parturition for calving ease scores (CES), calf vigour scores (CVS), and placental characteristics. Post-calving calf measures included birth weight (day 0) and body weight (kg), hip width (HW), body length (BL), wither height (WH), hip height (HH) and heart girth (HG) through 42 days of age. Serum IgG and calf vital function tests (respiration rate (RR), heart rate (HR), rectal temperature (RT) and fecal scores) were recorded on days 1, 3, 7 and 14 of age (a.m. and p.m.). Serum gestational P4 was higher (p < 0.05) for cows with H x H than G x H calves. Placentome measurements in utero were greater (p < 0.01) for H x H calves than for G x H calves, while at parturition placental characteristics did not differ (p > 0.10). Gestation length, CES and CVS also did not differ (p > 0.10) between H x H and G x H calves. Calf RR and HR were higher (p < 0.05) for H x H than G x H calves at both a.m. and p.m., while RT, fecal scores and serum IgG did not differ (p > 0.10) between H x H and G x H calves. Birth weight did not differ (p > 0.10) between H x H and G x H calves within sex. Moreover, bulls did not differ (p > 0.10) in any of the growth measures between H x H and G x H calves, whereas H x H heifers at days 28 and 42 of age were greater (p < 0.05) in all growth traits than G x H heifers. Nevertheless, the relative change in growth measures over time (days 0 to 42) did not differ (p > 0.10) between H x H and G x H calves. While subtle differences in gestational, early growth and vital function characteristics were observed, these data suggest very similar developmental profiles between H x H and G x H calves.

Two techniques to make the lymphocytotoxic crossmatch more sensitive: prolonged incubation and the antiglobulin test.

Two techniques capable of increasing the sensitivity of the lymphocytotoxic crossmatch test were compared for sensitivity and practically using the fluorochromasia modification of the cytotoxicity test. Prolonging the incubation period after addition of complement in the standard test resulted in further positive reactions. Modification of the test by addition of antiglobulin reagent increased the reactivity more than prolonged incubation of the standard test. The fluorochromasia adaptation of the antiglobulin test had sensitivity equivalent to the original antiglobulin method. The antiglobulin technique had a number of disadvantages, and neither the prolonged incubation nor the antiglobulin procedure meet the requirements of a busy histocompatibility testing service in view of the time consumed for the first and the complexity of the second.

Regio-reactive resin: a platform for orthogonal loading using the polymer backbone and cross-linker.

A new support for solid-phase combinatorial organic synthesis has been developed, which we term a regio-reactive resin (R(3)-resin). The resin is based on a unique hydroxyl-functionalized cross-linker readily synthesized in two steps starting from 4-hydroxybenzaldehyde. The cross-linker's ease of synthesis and high purity enables the preparation of gel-type resins with regio-reactive orthogonal loading sites. The resin's swelling properties were investigated, and its potential utility was demonstrated via orthogonal reactivity of the pendant and cross-linker sites.

Bradykinin and angiotensin II: activation of protein kinase C in arterial smooth muscle.

The effects of bradykinin (BK) and angiotensin II (ANG II) were compared in cultured rat mesenteric arterial smooth muscle cells. BK and ANG II activated a phosphoinositide-specific phospholipase C, leading to the rapid release of [3H]inositol phosphates, an increase in intracellular calcium, and formation of sn-1,2-diacylglycerol (DAG). DAG formation was biphasic with a transient peak at 5 s followed by a sustained increase from 60 to 600 s. The BK-mediated increases in inositol triphosphate and DAG were dose dependent with half-maximal increases at concentrations of 5 and 2 nM, respectively. Both hormones were found to activate protein kinase C (PKC) as assessed by phosphorylation of the 68- to 72-kDa intracellular PKC substrate myristoylated alanine-rich C kinase substrate. However, despite similar phosphorylation of this substrate, only ANG II produced a significant increase in membrane-bound PKC activity. The mechanism accounting for the inability of BK to increase membrane-bound PKC activity is unclear. Our studies excluded differential translocation of PKC to the nuclear membrane, production of an inhibitor of membrane-bound PKC activity, and expression of BK and ANG II receptors on different cells as the mechanism. Vascular smooth muscle cells were found to express at least four different PKC isozymes: alpha, delta, zeta, and a faint band for epsilon. All of the isozymes except zeta-PKC were translocated by treatment with the phorbol ester 4 beta-phorbol 12-myristate 13-acetate. However, neither ANG II nor BK produced significant translocation of any measured isozyme; therefore, we could not exclude the possibility that ANG II and BK activate different isozymes of PKC. Both hormones were found to have a similar small and inconsistent effect in stimulating [3H]thymidine incorporation. These observations demonstrate that BK and ANG II have similar biochemical effects on vascular smooth muscle cells and imply that, in selected vessels, the vasodilatory effects of BK mediated by the endothelium may be partially counterbalanced by a vasoconstrictor effect on the underlying vascular smooth muscle cells.

Quadriceps-hamstring EMG activity during functional, closed kinetic chain exercise to fatigue.

It has been hypothesized that the ability of the neuromuscular system to co-contract muscles for joint stabilization may be impaired during the development of fatigue. The purpose of this study was to examine muscle activation of the quadriceps and hamstring muscles during a prolonged closed kinetic chain exercise, the forward lunge. Eight males and two females [mean (SD) age 26.0 (2.3) years, height 177.2 (13.6) cm, body mass 82.8 (17.1) kg] with no prior knee pathology volunteered for this study. Subjects performed repeated forward lunges onto their dominant leg at the cadence of one full lunge cycle every 2 s, until the point of volitional failure. Digital switches were positioned to record foot-strike and knee-strike of the lunge leg at the midpoint of the lunge, as well as heel-strike upon return to stance. During the lunge performance, surface electromyographic (EMG) signals of the vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), and semitendinosus (ST) muscles of the supporting leg were measured. Heart rate was also monitored every 30 s during the performance. All EMG data were full-wave rectified, partitioned into up and down phases, and integrated over the entire exercise period. The results demonstrated a significant increase in activation of the VL, VM, and BF during performance of the forward lunge to volitional failure (P < 0.05). No significant increase was shown for the ST. Heart rate increased significantly over the course of the lunge. These findings suggest that activation of the VL, VM, and BF muscles occurs as a unit during performance of the forward lunge during both concentric and eccentric lunge phases.