Touching reality: Bridging the user-researcher divide in upper-limb prosthetics.

Realistically improving upper-limb prostheses is only possible if we listen to users' actual technological needs.

The presence, morphology and clinical significance of vertebral body malformations in an Australian population of French Bulldogs and Pugs.

OBJECTIVE: To describe the incidence, morphology and clinical significance of congenital vertebral malformations (CVM) in two breeds of brachycephalic dogs presenting to a referral veterinary hospital. DESIGN: Prospective cohort study series. MATERIALS AND METHODS: Forty-nine French Bulldogs and Pugs were prospectively evaluated and placed in one of two groups based on whether or not they presented for neurological signs referable to spinal cord disease. A computed tomography (CT) of their entire spine was obtained and the presence and classification of CVM along with the degree of spinal kyphosis recorded for all dogs. Statistical analysis was performed to identify clinical associations between these factors (P < 0.05). RESULTS: CVM were prevalent across both breeds with the French Bulldog having more malformations than the Pug (Kruskal-Wallis nonparametric analysis of variance, P < 0.0001). Breed associated vertebral malformation subtypes included butterfly subtype in French Bulldogs (Chi-square, P = 0.0002), and transitional subtype in Pugs (odds ratio, 22.7; P = 0.000). A new subtype, dorsal wedge, was observed in 12 cases. The presence, number and subtype of vertebral malformation were not reliable for predicting the development of neurological signs across both breeds (Chi-square, P > 0.05). However, spinal kyphosis >35° calculated via Cobb angle was associated with Pugs that had neurological deficits (Chi-square, P = 0.028). CONCLUSIONS: Congenital vertebral malformations largely appear to be incidental findings in this population of French Bulldogs but are of more significance in the Pug breed when spinal kyphosis is >35°. French Bulldogs that have spinal cord disease and CVM are more likely to have pathology distant to CVM with intervertebral disc herniation most common.

High Seroprevalence but Low Rate of Isolation of Toxoplasma gondii from Wild Elk (Cervus Canadensis) in Pennsylvania.

Toxoplasma gondii infections are prevalent in most warm-blooded animals worldwide. During the 2018 November hunting season in Pennsylvania, fresh (unfixed, not frozen) samples obtained from 99 harvested elk (Cervus canadensis) were tested for T. gondii infection. Antibodies to T. gondii were detected in 69 of 99 (69.7%) elk tested by the modified agglutination test (MAT, 1:25 cut-off). Tongues and hearts from 16 elk with high MAT titers (>1:200) were bioassayed for T. gondii by inoculation in outbred Swiss Webster (SW) and interferon-gamma gene knockout (KO) mice. Viable T. gondii was isolated from tongues of 2 elk with MAT titers of 1:200 and 1:3,200. Toxoplasma gondii from both isolates were successfully propagated in cell culture. Genetic typing on DNA extracted from culture-derived tachyzoites using the PCR restriction fragment length polymorphism with 10 genetic markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) revealed that both isolates belonged to ToxoDB PCR-RFLP genotype #5 that is widely prevalent in wildlife in the United States. Our results suggest that elk may clear T. gondii organisms from their tissues.

Environmental Stability of Swine and Human Pandemic Influenza Viruses in Water under Variable Conditions of Temperature, Salinity, and pH.

UNLABELLED: The movement of influenza A viruses (IAVs) from wild bird reservoirs to domestic animals and humans is well established, but the transmission mechanisms that facilitate efficient movement across and within these host populations are not fully defined. Although predominant routes of transmission vary between host populations, the extent of environmental stability needed for efficient IAV transmission also may vary. Because of this, we hypothesized that virus stability would differ in response to varied host-related transmission mechanisms; if correct, such phenotypic variation might represent a potential marker for the emergence of novel animal or human influenza viruses. Here, the objective was to evaluate the ability of eight swine and six human IAV isolates to remain infective under various pH, temperature, and salinity conditions using a preestablished distilled water system. Swine and human viruses persisted longest at near-neutral pH, at cold temperatures, or under "freshwater" conditions. Additionally, no significant differences in persistence were observed between pandemic and nonpandemic IAVs. Our results indicate that there have been no apparent changes in the environmental stability of the viruses related to host adaptation. IMPORTANCE: This study assessed the environmental stability of eight swine and six human influenza A viruses (IAVs), including viruses associated with the 2009 H1N1 pandemic, in a distilled water system. The important findings of this work are that IAV persistence can be affected by environmental variables and that no marked changes were noted between human and swine IAVs or between pandemic and nonpandemic IAVs.

Optimizing Surveillance for South American Origin Influenza A Viruses Along the United States Gulf Coast Through Genomic Characterization of Isolates from Blue-winged Teal (Anas discors).

Relative to research focused on inter-continental viral exchange between Eurasia and North America, less attention has been directed towards understanding the redistribution of influenza A viruses (IAVs) by wild birds between North America and South America. In this study, we genomically characterized 45 viruses isolated from blue-winged teal (Anas discors) along the Texas and Louisiana Gulf Coast during March of 2012 and 2013, coincident with northward migration of this species from Neotropical wintering areas to breeding grounds in the United States and Canada. No evidence of South American lineage genes was detected in IAVs isolated from blue-winged teal supporting restricted viral gene flow between the United States and southern South America. However, it is plausible that blue-winged teal redistribute IAVs between North American breeding grounds and wintering areas throughout the Neotropics, including northern South America, and that viral gene flow is limited by geographical barriers further south (e.g., the Amazon Basin). Surveillance for the introduction of IAVs from Central America and northern South America into the United States may be further optimized through genomic characterization of viruses resulting from coordinated, concurrent sampling efforts targeting blue-winged teal and sympatric species throughout the Neotropics and along the United States Gulf Coast.

Using quantitative disease dynamics as a tool for guiding response to avian influenza in poultry in the United States of America.

Wild birds are the primary source of genetic diversity for influenza A viruses that eventually emerge in poultry and humans. Much progress has been made in the descriptive ecology of avian influenza viruses (AIVs), but contributions are less evident from quantitative studies (e.g., those including disease dynamic models). Transmission between host species, individuals and flocks has not been measured with sufficient accuracy to allow robust quantitative evaluation of alternate control protocols. We focused on the United States of America (USA) as a case study for determining the state of our quantitative knowledge of potential AIV emergence processes from wild hosts to poultry. We identified priorities for quantitative research that would build on existing tools for responding to AIV in poultry and concluded that the following knowledge gaps can be addressed with current empirical data: (1) quantification of the spatio-temporal relationships between AIV prevalence in wild hosts and poultry populations, (2) understanding how the structure of different poultry sectors impacts within-flock transmission, (3) determining mechanisms and rates of between-farm spread, and (4) validating current policy-decision tools with data. The modeling studies we recommend will improve our mechanistic understanding of potential AIV transmission patterns in USA poultry, leading to improved measures of accuracy and reduced uncertainty when evaluating alternative control strategies.

Demodectic mange, dermatophilosis, and other parasitic and bacterial dermatologic diseases in free-ranging white-tailed deer (Odocoileus virginianus) in the United States from 1975 to 2012.

The white-tailed deer (Odocoileus virginianus) is a common and widespread North American game species. To evaluate the incidence, clinical manifestations, demography, and pathology of bacterial and parasitic dermatologic diseases in white-tailed deer in the southeastern United States, we retrospectively evaluated white-tailed deer cases submitted to the Southeastern Cooperative Wildlife Disease Study from 1975 to 2012. Among 2569 deer examined, bacterial or parasitic dermatologic disease was diagnosed in 88 (3.4%) individuals, with Demodex spp (n = 37; 42.0%) and Dermatophilus congolensis (n = 19; 21.6%) as the most common causes. Demodicosis was significantly more common in deer older than 2 years and was most often detected in the fall; no statistically significant sex predilection was identified. Affected animals had patchy to generalized alopecia, often distributed over the head, neck, limbs, and trunk; microscopic lesions included epidermal crusts and cutaneous nodules with mild perifollicular, lymphoplasmacytic inflammation. Dermatophilosis was most common in males younger than 1 year that were often found dead. Crusting, erythema, and alopecia occurred on the face, ears, and distal extremities. Less commonly, infectious dermatologic diseases were associated with other bacteria (n = 13; 14.8%), fungi (n = 5; 5.7%), ectoparasites (chiggers, lice, mites, and ticks; n = 11; 12.5%), and larval nematodes (n = 7; 8.0%). Population-level effects of these diseases in white-tailed deer are likely minimal; however, due to their dramatic presentation, demodicosis, dermatophilosis, and other infectious skin diseases can be of concern to hunters and, in some cases, may have zoonotic potential.

Experimental infection of bar-headed geese (Anser indicus) and ruddy shelducks (Tadorna ferruginea) with a clade 2.3.2 H5N1 highly pathogenic avian influenza virus.

Since 2005, clade 2.2 H5N1 highly pathogenic avian influenza (HPAI) viruses have caused infections and morbidity among numerous species of wild waterfowl in Eurasia and Africa. However, outbreaks associated with clade 2.3.2 viruses have increased since 2009, and viruses within this clade have become the dominant strain of the H5N1 HPAI virus detected in wild birds, reaching endemic status in domestic birds in select regions of Asia. To address questions regarding the emergence and expansion of clade 2.3.2 viruses, 2 waterfowl species repeatedly involved in outbreaks of H5N1 HPAI viruses, bar-headed geese (Anser indicus) and ruddy shelducks (Tadorna ferruginea), were inoculated with a representative virus. All of 3 infected ruddy shelducks exhibited neurologic signs and died within 4 to 5 days. Two of 3 infected bar-headed geese had transient weakness but all survived. Viral shedding was predominately via the oropharynx and was detected from 1 to 7 days after inoculation. The severity and distribution of microscopic lesions corresponded with clinical disease and influenza-specific immunohistochemical staining of neurons. The predominant lesions were in the brain and were more severe in ruddy shelducks. Increased caspase-3 reactivity in the brains of all infected birds suggests a role for apoptosis in H5N1 HPAI virus pathogenesis in these species. These results demonstrate that similar to clade 2.2 viruses, a clade 2.3.2 H5N1 HPAI virus is neurotropic in some waterfowl species and can lead to neurologic disease with varying clinical outcomes. This has implications for the role that wild waterfowl may play in transmission of this virus in endemic regions.

Dissecting a wildlife disease hotspot: the impact of multiple host species, environmental transmission and seasonality in migration, breeding and mortality.

Avian influenza viruses (AIVs) have been implicated in all human influenza pandemics in recent history. Despite this, surprisingly little is known about the mechanisms underlying the maintenance and spread of these viruses in their natural bird reservoirs. Surveillance has identified an AIV 'hotspot' in shorebirds at Delaware Bay, in which prevalence is estimated to exceed other monitored sites by an order of magnitude. To better understand the factors that create an AIV hotspot, we developed and parametrized a mechanistic transmission model to study the simultaneous epizootiological impacts of multi-species transmission, seasonal breeding, host migration and mixed transmission routes. We scrutinized our model to examine the potential for an AIV hotspot to serve as a 'gateway' for the spread of novel viruses into North America. Our findings identify the conditions under which a novel influenza virus, if introduced into the system, could successfully invade and proliferate.

Making a long story short: noncoding RNAs and chromosome change.

As important as the events that influence selection for specific chromosome types in the derivation of novel karyotypes, are the events that initiate the changes in chromosome number and structure between species, and likewise polymorphisms, variants and disease states within species. Although once thought of as transcriptional 'noise', noncoding RNAs (ncRNAs) are now recognized as important mediators of epigenetic regulation and chromosome stability. Here we highlight recent work that illustrates the influence short and long ncRNAs have as participants in the function and stability of chromosome regions such as centromeres, telomeres, evolutionary breakpoints and fragile sites. We summarize recent evidence that ncRNAs can facilitate chromosome change and present mechanisms by which ncRNAs create DNA breaks. Finally, we present hypotheses on how they may create novel karyotypes and thus affect chromosome evolution.

Centromere conversion and retention in somatic cell hybrids.

The generation of somatic cell hybridization-derived cell lines between highly divergent species affords the opportunity to examine the concept of 'genome dominance' in the context of genetic and epigenetic changes. While whole-scale genome dominance has been well documented in natural hybrids among closely related species, an examination of centromere position and sequence retention in 2 marsupial-eutherian hybrids has revealed a mechanism for 'centromere dominance' as a driving force in the generation of stable somatic cell hybrids following an initial period of genomic instability. While one somatic cell hybrid cell line appeared to retain marsupial centromere sequences which remained competent to recruit the centromere-specific histone variant CENP-A in a Chinese hamster background, fusion events between marsupial and mouse-derived chromosomes in another hybrid line led to a centromere sequence conversion from one species to the other. We postulate that the necessity to maintain an epigenetically defined centromere following genome hybridization may be responsible for retention of specific chromosomes and may result in rapid sequence turnover to facilitate the recruitment of CENP-A containing histones.

Effect of LKB1 deficiency on mitochondrial content, fibre type and muscle performance in the mouse diaphragm.

AIM: The liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signalling pathway is a major regulator of skeletal muscle metabolic processes. During exercise, LKB1-mediated phosphorylation of AMPK leads to its activation, promoting mitochondrial biogenesis and glucose transport, among other effects. The roles of LKB1 and AMPK have not been fully characterized in the diaphragm. METHODS: Two methods of AMPK activation were used to characterize LKB1/AMPK signalling in diaphragms from muscle-specific LKB1 knockout (KO) and littermate control mice: (1) acute injection of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and (2) 5-min direct electrical stimulation of the diaphragm. Diaphragms were excised 60 min post-AICAR injection and immediately after electrical stimulation. RESULTS: AMPK phosphorylation increased with AICAR and electrical stimulation in control but not KO mice. Acetyl CoA carboxylase phosphorylation increased with AICAR in control but not KO mice, but increased in both genotypes with electrical stimulation. While the majority of mitochondrial protein levels were lower in KO diaphragms, uncoupling protein 3, complex I and cytochrome oxidase IV protein levels were not different between genotypes. KO diaphragms have a lower percentage of IIx fibres and an elevated percentage of IIb fibres when compared with control diaphragms. While in vitro peak force generation was similar between genotypes, KO diaphragms fatigued more quickly and had an impaired ability to recover. CONCLUSION: LKB1 regulates AMPK phosphorylation, mitochondrial protein expression, fibre type distribution, as well as recovery of the diaphragm from fatigue.

The effect of age on avian influenza viral shedding in mallards (Anas platyrhynchos).

Avian influenza virus (AIV) prevalence in wild aquatic bird populations varies with season, geographic location, host species, and age. It is not clear how age at infection affects the extent of viral shedding. To better understand the influence of age at infection on viral shedding of wild bird-origin low pathogenicity avian influenza (LPAI) viruses, mallards (Anas platyrhynchos) of increasing age (2 wk, 1 mo, 2 mo, 3 mo, and 4 mo) were experimentally inoculated via choanal cleft with a 10(6) median embryo infectious dose (EID50) of either A/Mallard/MN/355779/00 (H5N2) or A/Mallard/MN/199106/99 (H3N8). Exposed birds in all five age groups were infected by both AIV isolates and excreted virus via the oropharynx and cloaca. The 1-month and older groups consistently shed virus from 1 to 4 d post inoculation (dpi), whereas, viral shedding was delayed by 1 d in the 2-wk-old group. Past 4 dpi, viral shedding in all groups varied between individual birds, but virus was isolated from some birds in each group up to 21 dpi when the trial was terminated. The 1-mo-old group had the most productive shedding with a higher number of cloacal swabs that tested positive for virus over the study period and lower cycle threshold values on real-time reverse-transcription PCR. The viral shedding pattern observed in this study suggests that, although mallards from different age groups can become infected and shed LPAI viruses, age at time of infection might have an effect on the extent of viral shedding and thereby impact transmission of LPAI viruses within the wild bird reservoir system. This information may help us better understand the natural history of these viruses, interpret field and experimental data, and plan future experimental trials.

Tenacity of avian influenza viruses.

The goal of this review is to provide an overview of existing research on the environmental tenacity of avian influenza (AI) viruses, to identify gaps in our current understanding, and discuss how this information relates to AI control, eradication, and prevention. We are just beginning to understand the environmental factors that affect infectivity and the extent of variation in environmental tenacity that is present among these viruses. Because the environment can provide a bridge for AI virus transmission between many diverse hosts, including wild and domestic animals and man, understanding the importance of environmental transmission and identifying important points of contact are critical steps in preventing the spread of infection especially related to the introduction of these viruses to new host species.

Inhibition of colonic motility and defecation by RS-127445 suggests an involvement of the 5-HT2B receptor in rodent large bowel physiology.

BACKGROUND: 5-HT(2B) receptors are localized within the myenteric nervous system, but their functions on motor/sensory neurons are unclear. To explore the role of these receptors, we further characterized the 5-HT(2B) receptor antagonist RS-127445 and studied its effects on peristalsis and defecation. EXPERIMENTAL APPROACH: Although reported as a selective 5-HT(2B) receptor antagonist, any interactions of RS-127445 with 5-HT(4) receptors are unknown; this was examined using the recombinant receptor and Biomolecular Interaction Detection technology. Mouse isolated colon was mounted in tissue baths for isometric recording of neuronal contractions evoked by electrical field stimulation (EFS), or under an intraluminal pressure gradient to induce peristalsis; the effects of RS-127445 on EFS-induced and on peristaltic contractions were measured. Faecal output of rats in grid-bottom cages was measured over 3 h following i.p. RS-127445 and separately, validation of the effective doses was achieved by determining the free, unbound fraction of RS-127445 in blood and brain. KEY RESULTS: RS-127445 (up to 1 micromol x L(-1)) did not interact with the 5-HT(4) receptor. RS-127445 (0.001-1 micromol x L(-1)) did not affect EFS-induced contractions of the colon, although at 10 micromol x L(-1) the contractions were reduced (to 36 +/- 8% of control, n= 4). RS-127445 (0.1-10 micromol x L(-1)) concentration-dependently reduced peristaltic frequency (n= 4). RS-127445 (1-30 mg x kg(-1)), dose-dependently reduced faecal output, reaching significance at 10 and 30 mg x kg(-1) (n= 6-11). In blood and brain, >98% of RS-127445 was protein-bound. CONCLUSIONS AND IMPLICATIONS: High-protein binding of RS-127445 indicates that relatively high doses are required for efficacy. The results suggest that 5-HT(2B) receptors tonically regulate colonic motility.

5-hydroxyindalpine, an agonist at the putative 5-HT receptor, has no activity on human recombinant monoamine receptors but accelerates distension-induced peristalsis in mouse isolated colon.

Although the putative 5-HT(1P) receptor has been implicated to have a role in peristalsis, experiments which suggest this function are preliminary or have measured only components of the reflex. We have, therefore, further characterized a reported agonist at this receptor (5-hydroxyindalpine; 5-OHIP) and investigated the effects of 5-OHIP and 5-hydroxytrytophan-dipeptide (5-HTP-DP), a reported 5-HT(1P) receptor antagonist, on distension-induced peristalsis in mouse colon. The effects of 5-OHIP on intracellular calcium, cyclic adenosine monophosphate concentrations or GTPgammaS binding were measured in cell lines expressing human recombinant 5-HT(1A, 1B, 1D, 2A, 2B, 2C, 3, 4, 6, 7) and alpha(1A), alpha(1B), D(1), D(2), D(3), H(1), H(3) receptors. The effects of 5-OHIP and 5-HTP-DP on peristalsis were assessed by measuring changes in frequency and times to reach threshold of peristaltic contractions, as well as the threshold and maximum pressures of each peristaltic stroke. 5-hydroxyindalpine (1 nmol L(-1)-10 micromol L(-1)) had no significant activity at any of the receptors studied. However, 5-OHIP (0.1 nmol L(-1)-1 micromol L(-1)) concentration-dependently increased the frequency of peristalsis (EC(50) = 4.4 nmol L(-1)) and reduced the time taken to reach threshold and threshold pressure, without altering maximum pressures. The maximum effect of 5-OHIP was at 1 micromol L(-1) (68.0 +/- 14.5% increase in frequency); 10 micromol L(-1) decreased peristalsis. 5-hydroxytrytophan-dipeptide (1-300 nmol L(-1)) also increased the frequency of peristalsis and prevented the actions of 5-OHIP. The higher concentration (1 micromol L(-1)) transiently inhibited peristalsis and after recovery, prevented the actions of 5-OHIP but not the excitatory activity of the cholinesterase inhibitor neostigmine. In summary, the present data demonstrate an interaction of '5-HT(1P)-ligands' with the peristaltic reflex. However, the absence of an effect of 5-OHIP on a range of different monoamine receptors continues to highlight the need to investigate the identity of the putative 5-HT(1P) receptor.

AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle.

One characteristic of ageing skeletal muscle is a decline in mitochondrial function. Activation of AMP-activated protein kinase (AMPK) occurs in response to an increased AMP/ATP ratio, which is one potential result of mitochondrial dysfunction. We have previously observed higher AMPK activity in old (O; 30 months) vs young adult (YA; 8 months) fast-twitch muscle in response to chronic overload. Here we tested the hypothesis that AMPK would also be hyperactivated in O vs YA fast-twitch extensor digitorum longus muscles from Fischer(344) x Brown Norway (FBN) rats (n = 8 per group) in response to high-frequency electrical stimulation of the sciatic nerve (HFES) or injection of AICAR, an activator of AMPK. Muscles were harvested immediately after HFES (10 sets of six 3-s contractions, 10 s rest between contractions, 1 min rest between sets) or 1 h after AICAR injection (1 mg (g body weight)(-1) subcutaneously). The phosphorylations of AMPKalpha and acetyl-CoA carboxylase (ACC2; a downstream AMPK target) were both greatly increased (P

Oral administration of a centrally acting ghrelin receptor agonist to conscious rats triggers defecation.

Agonists of ghrelin receptors that cross the blood-brain barrier, but not ghrelin itself, administered peripherally (intravenous or subcutaneous), cause defecation by acting on centres in the lumbo-sacral spinal cord. It is not established whether orally administered ghrelin receptor agonists can have this action. We tested GSK894281 for its effectiveness at the ghrelin receptor and its ability to cross the blood-brain barrier. GSK894281 was effective at the human and rat ghrelin receptors at 1-10 nmol L(-1), but was >1000-fold less potent at the motilin receptor. It achieved a similar blood concentration by oral or intravenous administration. Oral bioavailability was 74% and brain : blood ratio at steady state was 0.7 : 1. GSK894281 administered orally (1-100 mg kg(-1)) caused a prompt, dose-related production of faecal pellets; at 10 mg kg(-1) faecal output was four times greater than after carrier. The output was the greatest in the first half hour and subsided over the next 90 min. At an oral dose of 10 mg kg(-1), the compound was effective on eight successive days. Faecal output was, on average, increased threefold over control in the 2 h after administration on each of the 8 days. This dose also significantly increased food consumption. Rats showed no adverse behavioural effects to the drug on a single application, but at the end of a week of administration they avoided the gavaging pipette. Oral administration of ghrelin receptor agonists that enter the central nervous system could possibly be used to relieve acute cases of constipation or to clear the bowel for colonoscopy.

Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1alpha in rat muscle.

Expression of all of the isoforms of the subunits of AMP-activated protein kinase (AMPK) and AMPK activity is increased in skeletal muscle of hyperthyroid rats. Activity of AMPK in skeletal muscle is regulated principally by the upstream kinase, LKB1. This experiment was designed to determine whether the increase in AMPK activity is accompanied by increased expression of the LKB1, along with binding partner proteins. LKB1, MO25, and downstream targets were determined in muscle extracts in control rats, in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 4 wk, and in rats given 0.01% propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) in drinking water for 4 wk (hypothyroid group). LKB1 and MO25 increased in the soleus of thyroid hormone-treated rats vs. the controls. In other muscle types, LKB1 responses were variable, but MO25 increased in all. In soleus, MO25 mRNA increased with thyroid hormone treatment, and STRAD mRNA increased with PTU treatment. Phospho-AMPK and phospho-ACC were elevated in soleus and gastrocnemius of hyperthyroid rats. Thyroid hormone treatment also increased the amount of phospho-cAMP response element binding protein (CREB) in the soleus, heart, and red quadriceps. Four proteins having CREB response elements (CRE) in promoter regions of their genes (peroxisome proliferator-activated receptor-gamma coactivator-1alpha, uncoupling protein 3, cytochrome c, and hexokinase II) were all increased in soleus in response to thyroid hormones. These data provide evidence that thyroid hormones increase soleus muscle LKB1 and MO25 content with subsequent activation of AMPK, phosphorylation of CREB, and expression of mitochondrial protein genes having CRE in their promoters.