ER cargo properties specify a requirement for COPII coat rigidity mediated by Sec13p

Eukaryotic secretory proteins exit the endoplasmic reticulum (ER) via transport vesicles generated by the essential coat protein complex II (COPII) proteins. The outer coat complex, Sec13-Sec31, forms a scaffold that is thought to enforce curvature. By exploiting yeast bypass-of-sec-thirteen (bst) mutants, where Sec13p is dispensable, we probed the relationship between a compromised COPII coat and the cellular context in which it could still function. Genetic and biochemical analyses suggested that Sec13p was required to generate vesicles from membranes that contained asymmetrically distributed cargoes that were likely to confer opposing curvature. Thus, Sec13p may rigidify the COPII cage and increase its membrane-bending capacity; this function could be bypassed when a bst mutation renders the membrane more deformable.     

Temperament influences mitochondrial capacity in skeletal muscle from 8 through 18 mo of age in Brahman heifers

Temperamental cattle tend to yield carcasses of poorer quality, and Brahman cattle are reportedly more temperamental than non-indicus cattle breeds. A potential link between temperament and product quality may be mitochondrial activity. We hypothesized that mitochondrial measures would be greater in temperamental compared with calm heifers and that the relationships between temperament and mitochondria would persist as heifers age. Serum cortisol and skeletal muscle (longissimus thoracis [LT] and trapezius [TRAP]) mitochondrial profiles and antioxidant activities were quantified from the same calm (n = 6) and temperamental (n = 6) Brahman heifers at 8, 12, and 18 mo of age. Data were analyzed using a mixed model ANOVA in SAS (9.4) with repeated measures. Serum cortisol was greater in temperamental compared with calm heifers throughout the study (P = 0.02). Mitochondrial volume density (citrate synthase [CS] activity) increased over time (P < 0.0001) but was similar between temperament and muscle groups. Mitochondrial function (cytochrome c oxidase activity) was greatest in the temperamental LT at 8 mo of age (P ≤ 0.0006), greatest in the temperamental TRAP at 18 mo of age (P ≤ 0.003), and did not differ by temperament at 12 mo of age. Integrative (relative to tissue wet weight) mitochondrial oxidative phosphorylation capacity with complex I substrates (P_CI), P_CI plus complex II substrate (P_CI+II), noncoupled electron transfer system capacity (E_CI+II), and E with functional complex II only (E_CII) were greater in the TRAP than LT for calm heifers at all ages (P ≤ 0.002), but were similar between muscle groups in temperamental heifers. Overall, calm heifers tended to have greater intrinsic (relative to CS activity) P_CI and flux control of P_CI+II (P ≤ 0.1) than temperamental heifers, indicating greater utilization of complex I paired with greater coupling efficiency in calm heifers. Within the LT, integrative P_CI+II was greater (P = 0.05) and E_CI+II tended to be greater (P = 0.06) in temperamental compared with calm heifers. From 8- to 18-mo old, glutathione peroxidase (GPx) activity decreased (P < 0.0001) and superoxide dismutase activity increased (P = 0.02), and both were similar between muscle groups. The activity of GPx was greater in temperamental compared with calm heifers at 8 (P = 0.004) but not at 12 or 18 mo of age. These results detail divergent skeletal muscle mitochondrial characteristics of live Brahman heifers according to temperament, which should be further investigated as a potential link between temperament and product quality.     

Moonquakes

Although the average rate of seismic energy release within the moon appears to be far below that of the earth, over 100 events believed to be moonquakes have been recorded by the two seismic stations installed on the lunar surface during Apollo missions 12 and 14. With few exceptions, the moonquakes occur at monthly intervals near times of perigee and apogee and show correlations with the longer-term (7-month) lunar gravity variations. The repeating moonquakes are believed to occur at not less than 10 different locations. However, a single focal zone accounts for 80 percent of the total seismic energy detected. This active zone appears to be 600 kilometers south-southwest of the Apollo 12 and 14 sites and deep within the moon. Each focal zone must be small (less than 10 kilometers in linear dimension) and fixed in location over a 14-month period. Cumulative strain at each location is inferred. Thus, the moonquakes appear to be releasing internal strain of unknown origin, the release being triggered by tidal stresses.     

Missile inpacts as sources of seismic energy on the moon

Seismic signals recorded from impacts of missiles at the White Sands Missile Range are radically different from the signal recorded from the Apollo 12 lunar module impact. This implies that lunar structure to depths of at least 10 to 20 kilometers is quite different from the typical structure of the earth's crust. Results obtained from this study can be used to predict seismic wave amplitudes from future man-made lunar impacts. Seismic energy and crater dimensions from impacts are compared with measurements from chemical explosions.     

The viking seismic experiment

A three-axis short-period seismometer is now operating on Mars in the Utopia Planitia region. The noise background correlates well with wind gusts. Although no quakes have been detected in the first 60 days of observation, it is premature to draw any conclusions about the seismicity of Mars. The instrument is expected to return data for at least 2 years.     

Continuous infusion of propofol in dogs premedicated with methotrimeprazine

Objective To evaluate the cardiopulmonary and clinical effects of three different infusion rates of propofol in dogs premedicated with methotrimeprazine. Study design Randomized experimental trial. Animals Ten healthy adult mixed‐breed male and female dogs, weighing from 14 to 20 kg. Methods Dogs were premedicated with methotrimeprazine [1 mg kg^?1 intravenously (IV)] followed by induction of anesthesia with 4.5 mg kg^?1 of propofol IV and maintenance with propofol for 60 minutes as follows: T1, 0.2 mg kg^?1 minute^?1; T2, 0.3 mg kg^?1minute^?1; and T3, 0.4 mg kg^?1minute^?1. Heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), end‐tidal CO₂ (P_ETCO₂), arterial hemoglobin O₂ saturation, arterial blood gases, and pedal and cutaneous reflexes were measured before and 5, 10, 20, 30, 45 and 60 minutes after the beginning of the propofol infusion. Statistical analysis was performed using an anova . Results Heart rate increased during anesthesia in all cases and arterial blood pressure decreased only in dogs in the T3 category. Respiratory depression was proportional to the infusion rate of propofol. Muscle relaxation was satisfactory, but analgesia was inadequate in the three treatments. Conclusions The infusion of 0.2–0.4 mg kg^?1 minute^?1 of propofol produced a dose‐dependent respiratory depression. The presence of a pedal withdrawal reflex and marked cardiovascular responses to this noxious stimulus suggests that anesthesia may not be of sufficient depth for surgery to be carried out. Clinical relevance Although several studies have been performed using propofol in animals, few studies have investigated the cardiopulmonary and analgesic effects with different doses. The determination of an adequate propofol infusion rate is necessary for the routine use of this intravenous anesthetic for the maintenance of anesthesia during major surgical procedures in dogs.     

Small ruminant lentivirus genetic subgroups associate with sheep TMEM154 genotypes

Small ruminant lentiviruses (SRLVs) are prevalent in North American sheep and a major cause of production losses for the U.S. sheep industry. Sheep susceptibility to SRLV infection is influenced by genetic variation within the ovine transmembrane 154 gene (TMEM154). Animals with either of two distinct TMEM154 haplotypes that both encode glutamate at position 35 of the protein (E35) are at greater risk of SRLV infection than those homozygous with a lysine (K35) haplotype. Prior to this study, it was unknown if TMEM154 associations with infection are influenced by SRLV genetic subgroups. Accordingly, our goals were to characterize SRLVs naturally infecting sheep from a diverse U.S. Midwestern flock and test them for associations with TMEM154 E35K genotypes. Two regions of the SRLV genome were targeted for proviral amplification, cloning, sequence analysis, and association testing with TMEM154 E35K genotypes: gag and the transmembrane region of env. Independent analyses of gag and env sequences showed that they clustered in two subgroups (1 and 2), they were distinct from SRLV subtypes originating from Europe, and that subgroup 1 associated with hemizygous and homozygous TMEM154 K35 genotypes and subgroup 2 with hemi- and homozygous E35 genotypes (gag p < 0.001, env p = 0.01). These results indicate that SRLVs in the U.S. have adapted to infect sheep with specific TMEM154 E35K genotypes. Consequently, both host and SRLV genotypes affect the relative risk of SRLV infection in sheep.     

A survey of the prevalence of emerging macrocyclic lactone resistance and of benzimidazole resistance in sheep nematodes in the lower North Island of New Zealand

AIM: To investigate the occurrence of emerging macrocyclic lactone (ML) resistance and of resistance to benzimidazole anthelmintics on a number of sheep farms in the North Island of New Zealand.

METHODS: On commercial sheep farms (n=30) in the Taihape district in the North Island of New Zealand, 30 animals were randomly allocated to one of two equal-sized groups and treated with either half of the recommended dose rate of ivermectin (half of 0.2 mg/kg), or with the full recommended dose rate of oxfendazole (4.5 mg/kg). The ivermectin treatment only was used on a further six properties. Faecal egg counts, accompanied by pooled larval cultures, were conducted on all samples at the time of treatment and 7–10 days later.

RESULTS: Resistance, as indicated by a <95% faecal egg count reduction (FECR) in both instances, was found to oxfendazole on 13/30 (43%) farms and to a half dose of ivermectin on 12/36 (33%) properties. For oxfendazole, such resistance was found to involve all six nematode genera whereas for ivermectin it was almost entirely restricted to Ostertagia and Cooperia infections.

CONCLUSIONS: These results indicate that emerging ML resistance may be more common on sheep farms in New Zealand than is generally realised. They also suggest that the half-dose ivermectin faecal egg count reduction test (FECRT) may offer some very practical benefits for parasite control by providing early warning of developing resistance to ML drenches and by signalling the possible imminent failure of these at their therapeutic dose rates. The sensitivity and reliability of this procedure may be further enhanced by the inclusion of larval cultures.