Short communication: Accuracy of corpus luteum color flow Doppler ultrasonography to diagnose nonpregnancy in dairy cows on day 21 after insemination.

The main objective of this study was to determine the accuracy of corpus luteum color flow Doppler ultrasonography (CLCFDU) to diagnose nonpregnant dairy cows 21 d after insemination. A secondary objective was to determine the accuracy of other indirect tests such as corpus luteum size and progesteronemia. Data from 1,632 Holstein cows (10 commercial herds) were used for the analysis in this prospective cohort study. The herds were visited weekly by a veterinarian and an animal health technician. During farm visits, cows were examined on d 21 after insemination using transrectal B-mode ultrasonography to quantify the presence and size of the corpus luteum. After identification of the corpus luteum, CLCFDU was performed and scored as D0, D1, D2, or D3 when 10% or less, between 11 and 30%, between 31 and 60%, or 61% or more of the corpus luteum surface was colored, respectively. A blood sample from coccygeal vessels was also collected to quantify progesteronemia. Farmers were blinded to these findings and no intervention was performed following examination. On d 32 after insemination, the cows were examined by the regular herd veterinarian using transrectal palpation and B-mode ultrasonography to determine whether the cows were pregnant or not (the reference test). Statistical analyses were conducted using 2 × 2 contingency tables. The apparent prevalence, sensitivity, specificity, positive predictive value, and negative predictive value of CLCFDU for predicting nonpregnancy were 22.0, 36.6, 99.0, 98.1, and 52.0%, respectively, when using D0 only as the diagnostic criterion; they were 47.2, 76.4, 94.8, 93.5, and 73.8%, respectively, for D0+D1 criteria. The same measures for cows with a corpus luteum <15 mm were 8.0, 11.7, 97.5, 86.9, and 43.4%, respectively, and they were 51.9, 67.4, 70.4, 76.6, and 60.0%, respectively, for progesteronemia <1 ng/mL. The measures of accuracy of CLCFDU to identify nonpregnant cows on d 21 after insemination were high, and the apparent prevalence varied depending on the diagnostic criteria used. The measures of accuracy of corpus luteum size (<15 mm) for the same purpose were high; however, apparent prevalence was low. The measures of accuracy of progesteronemia (<1 ng/mL) were low. In conclusion, CLCFDU had excellent accuracy to diagnose nonpregnancy in dairy cows on d 21 after insemination.

Assessment of the American Heart Association's "Life's simple 7" score in French-speaking adults from Québec.

BACKGROUND AND AIMS: The "Life's Simple 7" (LS7) metrics were developed by the American Heart Association (AHA) to assess and promote cardiovascular health in the American population. The purpose of this study was to assess the overall cardiovascular health of French-speaking adults from the Province of Quebec using the LS7 score. METHODS AND RESULTS: A total of 777 age and sex-representative participants of five different administrative regions in the Province of Quebec (387 men and 390 women; mean age ± SEM: 41.9 ± 0.1 years) were included in these analyses. Metrics of the LS7 score (smoking, physical activity, diet, body mass index, blood pressure, fasting total cholesterol and blood glucose) were analysed to generate a final score ranging from 0 to 7. Only 0.5% of participants met all criteria for ideal cardiovascular health. The diet metric showed the lowest prevalence of "ideal" scores (4.8%) whereas not smoking was the metric with the highest prevalence (88.1%). Women had a higher LS7 score than men, while age and education level (negative and positive association, respectively; p < 0.0001) were also associated with the LS7 score. CONCLUSION: Consistent with studies conducted among other populations, very few French-speaking adults from the Province of Quebec achieve an ideal cardiovascular health. These data indicate that further public health efforts aimed at promoting the LS7 metrics, focusing primarily on diet, are urgently needed. Specific groups, including older adults and those with lower levels of education, should be targeted when developing cardiovascular health promotion interventions.

Tomato spotted wilt virus Can Infect Resistant Tomato when Western Flower Thrips Inoculate Blossoms.

Tomato spotted wilt is a major disease of crops worldwide. Resistant cultivars carrying the Sw-5 allele for resistance to tomato spotted wilt disease (TSW) provide the most effective control method in tomato (Solanum lycopersicum). However, infections of fruit on Sw-5+ tomato plants suggest the virus resistance may not be fully expressed in blossoms or developing fruit. The objective of this study was to determine if the thrips vector, the western flower thrips (Frankliniella occidentalis), can transmit non-resistance breaking Tomato spotted wilt virus (TSWV) isolates when confined to blossoms on plants with and without the Sw-5 resistance allele. Twenty-one percent of 33 Sw-5+ plants inoculated by adult thrips feeding on blossom clusters or small fruit developed infections in the reproductive tissue, whereas 68% of 25 Sw-5- plants developed infections. Systemic infections also occurred following inoculation of blossoms in host genotypes with and without Sw-5. These results were further supported by field experiments that showed high proportions of infected fruit as well as a limited infection of foliage on the same stem as the infected fruit in Sw-5+ plants when F. occidentalis were abundant in blossoms. These findings help to explain observations of abundant late season infections of Sw-5 cultivars in commercial plantings and suggest that management of F. occidentalis infestations during the bloom period may be important for effective management of TSWV in susceptible tomato cultivars as well as cultivars expressing the Sw-5 allele for TSW resistance.

Glycaemic control and self-management behaviours in Type 2 diabetes: results from a 1-year longitudinal cohort study.

AIM: To better understand the associations between changes in self-management behaviours and glycaemic control. METHODS: We conducted a prospective observational study of 295 adult patients with Type 2 diabetes evaluated at baseline, 6 and 12 months. Four self-management behaviours were evaluated using the Summary of Diabetes Self-Care Activities instrument, which assesses healthy diet, physical activity, medication taking and self-monitoring of blood glucose. Using hierarchical linear regression models, we tested whether changes in self-management behaviours were associated with short-term (6-month) or long-term (12-month) changes in glycaemic control, after controlling for demographic and clinical characteristics. RESULTS: Improved diet was associated with a decrease in HbA1c level, both at 6 and 12 months. Improved medication taking was associated with short-term improvement in glycaemic control, while increased self-monitoring of blood glucose frequency was associated with a 12-month improvement in HbA1c . Completely stopping exercise after being physically active at baseline was associated with a rise in HbA1c level at 6-month follow-up. Interaction analysis indicated that a healthy diet benefitted all participant subgroups, but that medication taking was associated with glycaemic control only for participants living in poverty and more strongly for those with lower educational levels. Finally, a higher self-monitoring of blood glucose frequency was associated with better glycaemic control only in insulin-treated participants. CONCLUSIONS: Even after adjusting for potential confounders (including baseline HbA1c ), increased frequency of healthy diet, medication taking and self-monitoring of blood glucose were associated with improved HbA1c levels. These self-management behaviours should be regularly monitored to identify patients at risk of deterioration in glycaemic control. Barriers to optimum self-management should be removed, particularly among socio-economically disadvantaged populations.

Coroners' records on suicide mortality in Montréal: limitations and implications in suicide prevention strategies.

INTRODUCTION: In Montréal, the characteristics of suicide cases may vary between different areas. The information collected by coroners during their investigations of suicides could be used to support local suicide-prevention planning actions. METHODS: This study analyzes all coroners' records on suicide in Montréal from 2007 to 2009 to (1) determine the usefulness of the data available; (2) develop a profile of cases; (3) examine local differences by comparing two areas, one with the highest suicide rate and the other with the lowest. RESULTS: The data collected revealed the lack of a systematic, standardized procedure for recording information about deaths by suicide. The rates of missing data varied, but were very high for antecedents of suicide attempts and recent events that could have precipitated the suicide. We observed differences in the characteristics of suicide cases according to area of residence. CONCLUSION: By adopting a standardized procedure for collecting information on cases of suicide, coroners could provide local decision makers with a more accurate portrait of the people who die by suicide in their area. Local adjustments may improve suicide prevention strategies.

TITRE: Dossiers des coroners sur la mortalité par suicide à Montréal : limites et incidences sur les stratégies de prévention du suicide. INTRODUCTION: À Montréal, les caractéristiques des cas de suicide sont susceptibles de varier d'un territoire à l'autre. Les données recueillies par les coroners dans le cadre de leurs investigations sur les suicides pourraient servir à appuyer la planification en matière de prévention du suicide à l'échelle locale. MÉTHODOLOGIE: Dans cette étude, nous avons analysé tous les dossiers des coroners relatifs aux décès par suicide survenus à Montréal entre 2007 et 2009 afin de déterminer l'utilité des données disponibles, d'établir un profil des cas de suicide et d'examiner les différences à l'échelle locale en comparant deux territoires, celui ayant le taux de suicide le plus élevé et celui ayant le taux le plus faible. RÉSULTATS: Les données recueillies ont révélé qu'il n'existait pas de procédure uniforme et systématique pour la consignation des données sur les décès par suicide. Quoique les taux de données manquantes aient été variables, ils étaient très élevés en ce qui concerne les antécédents de tentative de suicide et les événements récents qui pourraient avoir provoqué le suicide. Nous avons observé des différences dans les caractéristiques des personnes qui s'enlèvent la vie en fonction du territoire de résidence. CONCLUSION: L'adoption par les coroners d'une procédure uniforme de collecte de données sur les cas de suicide permettrait aux décideurs d'avoir un portrait plus juste des personnes décédées par suicide au sein de leur territoire. S'adapter à la situation locale pourrait améliorer les stratégies de prévention du suicide.

Emerging asymmetric interactions between forage and predator fisheries impose management trade-offs.

A size and trait-based marine community model was used to investigate interactions, with potential implications for yields, when a fishery targeting forage fish species (whose main adult diet is zooplankton) co-occurs with a fishery targeting larger-sized predator species. Predicted effects on the size structure of the fish community, growth and recruitment of fishes, and yield from the fisheries were used to identify management trade-offs among the different fisheries. Results showed that moderate fishing on forage fishes imposed only small effects on predator fisheries, whereas predator fisheries could enhance yield from forage fisheries under some circumstances.

Effects of a tensioned tendon graft in a bone tunnel across the rabbit physis.

Children who sustain anterior cruciate disruption often are denied the standard reconstructive procedures because of the concern that drilling across the physis of the tibia and femur and compression from a tensioned graft will result in growth plate arrest. To test this concept and to assess whether a tendon placed in the tunnel would function in a manner similar to a fat graft after the resection of a physeal bar, tunnels were made across the proximal tibial physis and distal femoral physis in a group of immature rabbits. Four tunnel diameters were used from 1.95 to 3.97 mm, in three rabbits at each diameter, with patellar tendon autografts being used as the reconstruction of the anterior cruciate ligament in two of the animals. The knees were radiographed every 4 weeks, and the animals were euthanized 4 months after surgery. The surgically treated and control knees were salvaged, and each knee was examined grossly, radiographically, and histologically. Eight of the 11 animals had growth arrest of one or both physes. The larger the drill hole diameter the more marked was the deformity. The proximal tibial physis seemed to be the most vulnerable for growth arrest, occurring in eight of the knees. The insertion of a tendon did not seem to offer any protection to physeal arrest. Because of these findings, it is not recommended that tunnels involving 1% or more of the area of the physis be placed across the tibial and femoral physis to reconstruct the anterior cruciate in very skeletally immature children.

Chronically injured supraspinal neurons exhibit only modest axonal dieback in response to a cervical hemisection lesion.

This study examined the extent of axon retraction (dieback) exhibited by injured brain stem neurons in a chronic spinal cord injury (SCI) condition. Adult female rats subjected to a cervical (C3) hemisection lesion were sacrificed 1, 4, 8, or 14 weeks after injury and the spinal cord from C1 to the lesion cavity was removed. One week prior to sacrifice, a microinjection of biotinylated dextran amine (BDA, 0.5 microliter) was made into the red nucleus, lateral vestibular nucleus, or medullary reticular formation of each animal. Horizontal cryostat sections were processed with avidin-HRP to detect supraspinal axons anterogradely labeled with BDA. Terminal end bulbs of axons were identified and their distance from the lesion site was measured by a computerized image analysis program. At all postinjury intervals, numerous rubrospinal, vestibulospinal, and reticulospinal tract axons were found immediately adjacent to the lesion site and over 60% of all terminals were within 500 micrometer at 1 and 4 weeks. The mean axonal distance of 450-500 micrometer from the lesion indicated that many injured axons had retracted farther than 500 micrometer from the lesion site; however, long-term maintenance of the mean axonal distance from the lesion at less than 500 micrometer indicated the absence of progressive dieback after SCI. While some modest changes occur in specific supraspinal pathways following SCI, axonal retraction does not appear to be a contributing factor to the diminished regenerative effort by certain brain stem neurons that has been observed at long postinjury intervals.

Mechanisms leading to restoration of muscle size with exercise and transplantation after spinal cord injury.

We have shown that cycling exercise combined with fetal spinal cord transplantation restored muscle mass reduced as a result of complete transection of the spinal cord. In this study, mechanisms whereby this combined intervention increased the size of atrophied soleus and plantaris muscles were investigated. Rats were divided into five groups (n = 4, per group): control, nontransected; spinal cord transected at T10 for 8 wk (Tx); spinal cord transected for 8 wk and exercised for the last 4 wk (TxEx); spinal cord transected for 8 wk with transplantation of fetal spinal cord tissue into the lesion site 4 wk prior to death (TxTp); and spinal cord transected for 8 wk, exercised for the last 4 wk combined with transplantation 4 wk prior to death (TxExTp). Tx soleus and plantaris muscles were decreased in size compared with control. Exercise and transplantation alone did not restore muscle size in soleus, but exercise alone minimized atrophy in plantaris. However, the combination of exercise and transplantation resulted in a significant increase in muscle size in soleus and plantaris compared with transection alone. Furthermore, myofiber nuclear number of soleus was decreased by 40% in Tx and was not affected in TxEx or TxTp but was restored in TxExTp. A strong correlation (r = 0.85) between myofiber cross-sectional area and myofiber nuclear number was observed in soleus, but not in plantaris muscle, in which myonuclear number did not change with any of the experimental manipulations. 5'-Bromo-2'-deoxyuridine-positive nuclei inside the myofiber membrane were observed in TxExTp soleus muscles, indicating that satellite cells had divided and subsequently fused into myofibers, contributing to the increase in myonuclear number. The increase in satellite cell activity did not appear to be controlled by the insulin-like growth factors (IGF), as IGF-I and IGF-II mRNA abundance was decreased in Tx soleus and plantaris, and was not restored with the interventions. These results indicate that, following a relatively long postinjury interval, exercise and transplantation combined restore muscle size. Satellite cell fusion and restoration of myofiber nuclear number contributed to increased muscle size in the soleus, but not in plantaris, suggesting that cellular mechanisms regulating muscle size differ between muscles with different fiber type composition.

Cycling exercise and fetal spinal cord transplantation act synergistically on atrophied muscle following chronic spinal cord injury in rats.

The potential of two interventions, alone or in combination, to restore chronic spinal cord transection-induced changes in skeletal muscles of adult Sprague-Dawley rats was studied. Hind limb skeletal muscles were examined in the following groups of animals: rats with a complete spinal cord transection (Tx) for 8 weeks; Tx with a 4-week delay before initiation of a 4-week motor-assisted cycling exercise (Ex) program; Tx with a 4-week delay before transplantation (Tp) of fetal spinal cord tissue into the lesion cavity; Tx with a 4-week delay before Tp and Ex; and uninjured control animals. Muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas were significantly reduced 8 weeks after transection. Whereas transplantation of fetal spinal cord tissue did not reverse this atrophy and exercise alone had only a modest effect in restoring lost muscle mass, the combination of exercise and transplantation significantly increased muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas in both soleus and plantaris muscles. Spinal cord injury (SCI) also caused changes in myosin heavy chain (MyHC) expression toward faster isoforms in both soleus and plantaris and increased soleus myofiber succinate dehydrogenase (SDH) activity. Combined exercise and transplantation led to a change in the expression of the fastest MyHC isoform in soleus but had no effect in the plantaris. Exercise alone and in combination with transplantation reduced SDH activity to control levels in the soleus. These results suggest a synergistic action of exercise and transplantation of fetal spinal cord tissue on skeletal muscle properties following SCI, even after an extended post-injury period before intervention.

Fibroblasts genetically modified to produce BDNF support regrowth of chronically injured serotonergic axons.

Cells genetically modified to release a variety of growth and/or neurotrophic factors have been used for transplantation into the injured spinal cord as a means to deliver therapeutic products. Axon growth into and through such transplants has been demonstrated after intervention after an acute injury. The present study examined their potential to support regeneration in a chronic injury condition. Five weeks after a cervical hemisection in adult rats, the lesion site was debrided of scar tissue and expanded in both rostral and caudal directions. Animals received a transplant of cultured normal fibroblasts (control) or fibroblasts genetically modified to produce brain-derived neurotrophic factor (BDNF). Six weeks later, animals were killed to determine the extent of growth of serotonergic axons into the transplant. Axons immunoreactive for serotonin (5-HT-ir) were found to cross the rostral interface of host spinal cord readily with either type of fibroblast cell transplant, but the number and density of 5-HT-ir axons extending into the BDNF-producing transplants was markedly greater than those in the control fibroblasts. Axons coursed in all directions among normal fibroblast transplants, whereas growth was more oriented along a longitudinal plane when BDNF was being released by the transplanted cells. The length of growth and the percentage of the transplant length occupied by 5-HT-ir axons were significantly greater in BDNF-producing transplants than in the normal fibroblasts. Many serotonergic axons approached the caudal end of the BDNF-producing cell transplants, although most failed to penetrate the host spinal cord distal to the lesion. These results indicate that whereas fibroblast cell transplants alone can support regrowth of axons from chronically injured supraspinal neurons, modification of these cells to produce BDNF results in a significant increase in the extent of growth into the transplant.

Survival of chronically-injured neurons can be prolonged by treatment with neurotrophic factors.

Axonal regeneration by chronically-injured supraspinal neurons can be enhanced by neurotrophic factor treatment at the site of injury, although the number of regenerating neurons decreases as the interval between spinal cord injury and treatment increases. This study investigated whether this decline in regenerative response could be due to continued loss of neurons during the post-injury period. Adult rats received a cervical hemisection lesion and axotomized neurons were labeled by retrograde transport of True Blue from the lesion site. Animals were killed one, four or eight weeks after injury and surviving neurons (True Blue-labeled) were counted in the red nucleus and lateral vestibular nucleus. The neuron number in the lateral vestibular nucleus was stable for eight weeks after spinal cord injury, while survival in the red nucleus decreased by 25% between four and eight weeks. To test how neurons respond to a second injury with or without trophic factor treatment, at four, eight, 14 or 22 weeks after injury the lesion cavity was enlarged by 0.5 mm in a rostral direction. Gel foam saturated with ciliary neurotrophic factor, brain-derived neurotrophic factor or basic fibroblast growth factor was placed into the cavity. Animals were killed four weeks later. Re-injury of the spinal cord caused a significant decrease in neuron survival in both the red nucleus and lateral vestibular nucleus, the effects of which were lessened by treatment with ciliary neurotrophic factor or brain-derived neurotrophic factor for the red nucleus and with ciliary neurotrophic factor for the lateral vestibular nucleus, when re-injured at four or eight weeks. Basic fibroblast growth factor did not affect neuron survival at any time post-injury. Ciliary neurotrophic factor was not effective with longer delays (14 or 22 weeks) between the initial injury and re-injury. These results indicate a delayed pattern of secondary neuronal cell loss after spinal cord injury that is exaggerated by re-injury, but which can be ameliorated by treatment with neurotrophic factors.

Mechanism of serum resistance among Brucella abortus isolates.

It was shown in this study that complement-resistant Brucella abortus used were unable to activate complement in the absence of specific antibody. Complement-resistant isolates possessed O-antigen, but complement-sensitive organisms used are O-antigen deficient. Since B. abortus LPS does not activate the alternative pathway of complement, we concluded that activation of bovine complement must be due to some other mechanism. In this study, it was shown that bovine C1 binds to the outer membrane proteins of B. abortus. Isolated outer membrane proteins of both smooth (O-antigen positive) and rough (O-antigen negative) B. abortus used bind to C1q. However, only rough isolates were killed by complement. All of the O-antigen positive B. abortus isolates were complement-resistant. We propose that O-antigen shields outer membrane proteins and blocks C1q binding.

Activated satellite cells fail to restore myonuclear number in spinal cord transected and exercised rats.

In this study, possible mechanisms underlying soleus muscle atrophy after spinal cord transection and attenuation of atrophy with cycling exercise were studied. Adult female Sprague-Dawley rats were divided into three groups; in two groups the spinal cord was transected by a lesion at T10. One group was transected and killed 10 days later, and another group was transected and exercised for 5 days starting 5 days after transection. The third group served as an uninjured control. All animals received a continuous-release 5'-bromo-2'-deoxyuridine pellet 10 days before they were killed. Transection alone and transection with exercise lead to activation of satellite cells, but only the exercise group showed a trend toward an increase in the number of proliferating satellite cells. In all cases the number of activated satellite cells was significantly higher than the number that divided. Although the number of cells undergoing proliferation increased with exercise, no increase in fusion of satellite cells into muscle fibers was apparent. Spinal cord transection resulted in a 25% decrease in myonuclear number, and exercise was not associated with a restoration of myonuclear number. The number of apoptotic nuclei was increased after transection, and exercise attenuated this increase. However, the decrease in apoptotic nuclei with exercise did not significantly affect myonuclear number. We conclude that apoptotic nuclear loss likely contributes to loss of nuclei during muscle atrophy associated with spinal cord transection and that exercise can maintain muscle mass, at least in the short term, without restoration of myonuclear number.

Clopidogrel and drug metabolism: absence of effect on hepatic enzymes in healthy volunteers.

The influence of clopidogrel 75 mg, given once daily for 10 days on hepatic P-450 mixed function oxidases, was examined by assessing its effect on the disposition of antipyrine, on urinary 6-betahydroxycortisol (6beta-OHC) and on the plasma activity of gamma-glutamyl transpeptidase. This double-blind, randomized, placebo-controlled study was conducted in two parallel groups of 10 healthy young volunteers. Subjects were required to fast for 12 hours before and for 4 hours after dosing. Antipyrine 10 mg/kg was administered in the morning, two days before treatment (day -2) and 24 hours after the last dose of clopidogrel or placebo. Plasma levels of antipyrine, and urinary excretion of antipyrine, 3-hydroxymethyl-antipyrine and nor-antipyrine were measured over 36 hours post-drug for pharmacokinetic determinations. Bleeding time and platelet aggregation induced by 5 microM of ADP were measured before treatment (baseline) and at regular intervals after dosing during treatment. Clopidogrel treatment had a marked effect on platelet aggregation and bleeding time. No significant change in the disposition of antipyrine was observed after the ingestion of clopidogrel over 10 days: mean AUC ratio (+/-SEM) for plasma antipyrine was 1.021+/-0.023 for the clopidogrel group versus 1.001+/-0.019 for the placebo group; mean day 10/day -2 t 1/2 ratios were 1.019+/-0.018 and 1.027+/-0.023, respectively. Urinary excretions of antipyrine and metabolites were unchanged by clopidogrel compared to placebo. The changes in plasma cortisol concentrations, 6beta-OHC excretion and serum gamma-glutamyl transpeptidase activities observed at the end of treatment were fully comparable between the two treatment groups. Thus, the different tests showed no evidence of hepatic enzyme induction by clopidogrel in a pharmacologically effective dose regimen.

Effects of fetal spinal cord tissue transplants and cycling exercise on the soleus muscle in spinalized rats.

Studies were carried out to determine if an intraspinal transplant (Trpl) of fetal spinal cord tissue or hind limb exercise (Ex) affected the changes in myosin heavy chain (MyHC) composition or myofiber size that occur following a complete transection (Tx) of the lower thoracic spinal cord of the adult rat. In one group of animals, transplants were made acutely, whereas in a second group, daily cycling exercise was initiated 5 days after injury, with animals in both groups being sacrificed 90 days after injury. The soleus muscle is normally composed of myofibers expressing either type I (90%) or type IIa (10%) MyHC. Following a spinal transection, expression of type I MyHC isoform decreased (18% of myofibers), type IIa MyHC expression increased (65% of myofibers), and the majority of myofibers (80%) expressed type IIx MyHC. Most myofibers coexpressed multiple MyHC isoforms. Compared with Tx only, with Ex or with Trpl, there was a decrease in the number of myofibers expressing type I or IIa isoforms but little change in expression of IIx MyHC. Myofibers expressing the IIb isoform appeared in several transplant recipients but not after exercise. Transection resulted in atrophy of type I myofibers to approximately 50% of normal size, whereas myofibers were significantly larger after exercise (74% of control) and in Trpl recipients (77% of control). Type IIa myofibers also were significantly larger in Trpl recipients compared with the Tx only group. Overall, the mean myofiber size was significantly greater after exercise and in Trpl recipients compared with myofibers in Tx only animals. Thus, although neither strategy shifted the MyHC profile towards the control, both interventions influenced the extent of atrophy observed after spinalization. These data suggest that palliative strategies can be developed to modulate some of the changes in hind limb muscles that occur following a spinal cord injury.

The Drosophila ortholog of the human XPG gene.

Xeroderma pigmentosum complementation group G (XPG) protein is a junction-specific endonuclease which is indispensable for nucleotide excision repair (NER) of DNA in eukaryotes. Recent studies have hinted at a second, essential function for the XPG protein in higher eukaryotes. We undertook a comparison of the amino acid sequences of multiple XPG orthologs to determine if a motif or domain could be identified that is conserved uniquely in higher eukaryotes. A search of current databases allowed us to retrieve complete amino acid sequences for the human, mouse and Xenopus XPG proteins, and for two yeast orthologs. We also identified an incomplete Drosophila open reading frame (ORF) that was a good candidate for the XPG protein. We cloned a complete Drosophila cDNA for this ORF and examination of the primary amino acid sequence suggests that this cDNA encodes the Drosophila ortholog of XPG. A comparison of all six orthologous polypeptides reveals the presence of two previously unidentified conserved domains. One of these is unique to all four higher eukaryotic sequences. Conceivably this domain evolved to support the essential function of XPG protein.

Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/- mice.

Mice that are genetically engineered to mimic the human hereditary cancer-prone DNA repair-defective disease xeroderma pigmentosum (XP) are highly predisposed to UV radiation-induced skin cancer. It is not clear, however, whether XP mice or humans are predisposed to cancers in other tissues associated with exposure to environmental carcinogens. To test the importance of nucleotide excision repair in protection against chemical carcinogenesis in internal organs, we treated XPC mutant (XPC-/-) mice with 2-acetylaminofluorene and NOH-2-acetylaminofluorene. We observed a significantly higher incidence of chemically induced liver and lung tumors in XPC-/- mice compared with normal and heterozygous littermates In addition, the progression of liver tumors in XPC-/- Trp53+/- mice is accelerated compared with XPC-/- Trp53+/+ animals. Finally, we demonstrate a higher incidence of spontaneous testicular tumors in XPC-/- TrpS3-/- double mutant mice compared with XPC+/+ Trp53-/- mice.

Early changes in muscle fiber size and gene expression in response to spinal cord transection and exercise.

Muscles of spinal cord-transected rats exhibit severe atrophy and a shift toward a faster phenotype. Exercise can partially prevent these changes. The goal of this study was to investigate early events involved in regulating the muscle response to spinal transection and passive hindlimb exercise. Adult female Sprague-Dawley rats were anesthetized, and a complete spinal cord transection lesion (T10) was created in all rats except controls. Rats were killed 5 or 10 days after transection or they were exercised daily on motor-driven bicycles starting at 5 days after transection and were killed 0.5, 1, or 5 days after the first bout of exercise. Structural and biochemical features of soleus and extensor digitorum longus (EDL) muscles were studied. Atrophy was decreased in all fiber types of soleus and in type 2a and type 2x fibers of EDL after 5 days of exercise. However, exercise did not appear to affect fiber type that was altered within 5 days of spinal cord transection: fibers expressing myosin heavy chain 2x increased in soleus and EDL, and extensive coexpression of myosin heavy chain in soleus was apparent. Activation of satellite cells was observed in both muscles of transected rats regardless of exercise status, evidenced by increased accumulation of MyoD and myogenin. Increased expression was transient, except for MyoD, which remained elevated in soleus. MyoD and myogenin were detected both in myofiber and in satellite cell nuclei in both muscles, but in soleus, MyoD was preferentially expressed in satellite cell nuclei, and in EDL, MyoD was more readily detectable in myofiber nuclei, suggesting that MyoD and myogenin have different functions in different muscles. Exercise did not affect the level or localization of MyoD and myogenin expression. Similarly, Id-1 expression was transiently increased in soleus and EDL upon spinal cord transection, and no effect of exercise was observed. These results indicate that passive exercise can ameliorate muscle atrophy after spinal cord transection and that satellite cell activation may play a role in muscle plasticity in response to spinal cord transection and exercise. Finally, the mechanisms underlying maintenance of muscle mass are likely distinct from those controlling myosin heavy chain expression.