Discerning Localized Thermal Heating from Mechanical Strain Using an Embedded Distributed Optical Fiber Sensor Network.

Prior research has demonstrated that distributed optical fiber sensors (DOFS) based on Rayleigh scattering can be embedded in carbon fiber/epoxy composite structures to rapidly detect temperature changes approaching 1000 °C, such as would be experienced during a high energy laser strike. However, composite structures often experience mechanical strains that are also detected during DOFS interrogation. Hence, the combined temperature and strain response in the composite can interfere with rapid detection and measurement of a localized thermal impulse. In this research, initial testing has demonstrated the simultaneous response of the DOFS to both temperature and strain. An embedded DOFS network was designed and used to isolate and measure a localized thermal response of a carbon fiber/epoxy composite to a low energy laser strike under cyclic bending strain. The sensor interrogation scheme uses a simple signal processing technique to enhance the thermal response, while mitigating the strain response due to bending. While our ultimate goal is rapid detection of directed energy on the surface of the composite, the technique could be generalized to structural health monitoring of temperature sensitive components or smart structures.

High Temperature Effects during High Energy Laser Strikes on Embedded Fiber Bragg Grating Sensors.

As the applications of fiber Bragg gratings (FBGs) continue to grow and become more advanced, it becomes necessary to understand their behavior when exposed to high temperatures in unique situations. In these experiments, uniform 1530-nm fiber Bragg gratings and Type K Cr-Al thermocouples were embedded in three-ply carbon fiber composites. A 100 W high energy laser (HEL) heated the composites to high temperatures over timespans less than one second, and FBG spectral data and thermocouple temperature data were collected during each HEL heating test. The data from three high energy laser tests that represent different levels of damage to the FBG are analyzed to explore the spectral response and thermal decay of embedded FBG sensors when exposed to high temperatures over short timespans. Results are compared to a previously proposed power-law model describing the decay of FBGs in bare fiber when held at constant temperatures over much longer timespans.

Identification and characterization of Nanobodies targeting the EphA4 receptor.

The ephrin receptor A4 (EphA4) is one of the receptors in the ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease. Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders. Therefore, the aim of our study was to generate potent and selective Nanobodies against the ligand-binding domain of the human EphA4 receptor. We identified two Nanobodies, Nb 39 and Nb 53, that bind EphA4 with affinities in the nanomolar range. These Nanobodies were most selective for EphA4, with residual binding to EphA7 only. Using Alphascreen technology, we found that both Nanobodies displaced all known EphA4-binding ephrins from the receptor. Furthermore, Nb 39 and Nb 53 inhibited ephrin-induced phosphorylation of the EphA4 protein in a cell-based assay. Finally, in a cortical neuron primary culture, both Nanobodies were able to inhibit endogenous EphA4-mediated growth-cone collapse induced by ephrin-B3. Our results demonstrate the potential of Nanobodies to target the ligand-binding domain of EphA4. These Nanobodies may deserve further evaluation as potential therapeutics in disorders in which EphA4-mediated signaling plays a role.

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration.

Zinc finger motifs are distributed amongst many eukaryotic protein families, directing nucleic acid-protein and protein-protein interactions. Zinc finger protein 106 (ZFP106) has previously been associated with roles in immune response, muscle differentiation, testes development and DNA damage, although little is known about its specific function. To further investigate the function of ZFP106, we performed an in-depth characterization of Zfp106 deficient mice (Zfp106(-/-)), and we report a novel role for ZFP106 in motor and sensory neuronal maintenance and survival. Zfp106(-/-) mice develop severe motor abnormalities, major deficits in muscle strength and histopathological changes in muscle. Intriguingly, despite being highly expressed throughout the central nervous system, Zfp106(-/-) mice undergo selective motor and sensory neuronal and axonal degeneration specific to the spinal cord and peripheral nervous system. Neurodegeneration does not occur during development of Zfp106(-/-) mice, suggesting that ZFP106 is likely required for the maintenance of mature peripheral motor and sensory neurons. Analysis of embryonic Zfp106(-/-) motor neurons revealed deficits in mitochondrial function, with an inhibition of Complex I within the mitochondrial electron transport chain. Our results highlight a vital role for ZFP106 in sensory and motor neuron maintenance and reveal a novel player in mitochondrial dysfunction and neurodegeneration.

Patient predictors of response to cognitive behaviour therapy and schema therapy for depression.

OBJECTIVE: Few studies have examined differential predictors of response to psychotherapy for depression. Greater understanding about the factors associated with therapeutic response may better enable therapists to optimise response by targeting therapy for the individual. The aim of the current exploratory study was to examine patient characteristics associated with response to cognitive behaviour therapy and schema therapy for depression. METHODS: Participants were 100 outpatients in a clinical trial randomised to either cognitive behaviour therapy or schema therapy. Potential predictors of response examined included demographic, clinical, functioning, cognitive, personality and neuropsychological variables. RESULTS: Individuals with chronic depression and increased levels of pre-treatment negative automatic thoughts had a poorer response to both cognitive behaviour therapy and schema therapy. A treatment type interaction was found for verbal learning and memory. Lower levels of verbal learning and memory impairment markedly impacted on response to schema therapy. This was not the case for cognitive behaviour therapy, which was more impacted if verbal learning and memory was in the moderate range. CONCLUSION: Study findings are consistent with the Capitalisation Model suggesting that therapy that focuses on the person's strengths is more likely to contribute to a better outcome. Limitations were that participants were outpatients in a randomised controlled trial and may not be representative of other depressed samples. Examination of a variety of potential predictors was exploratory and requires replication.

A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity.

Transgenic mouse models expressing mutant superoxide dismutase 1 (SOD1) have been critical in furthering our understanding of amyotrophic lateral sclerosis (ALS). However, such models generally overexpress the mutant protein, which may give rise to phenotypes not directly relevant to the disorder. Here, we have analysed a novel mouse model that has a point mutation in the endogenous mouse Sod1 gene; this mutation is identical to a pathological change in human familial ALS (fALS) which results in a D83G change in SOD1 protein. Homozgous Sod1(D83G/D83G) mice develop progressive degeneration of lower (LMN) and upper motor neurons, likely due to the same unknown toxic gain of function as occurs in human fALS cases, but intriguingly LMN cell death appears to stop in early adulthood and the mice do not become paralyzed. The D83 residue coordinates zinc binding, and the D83G mutation results in loss of dismutase activity and SOD1 protein instability. As a result, Sod1(D83G/D83G) mice also phenocopy the distal axonopathy and hepatocellular carcinoma found in Sod1 null mice (Sod1(-/-)). These unique mice allow us to further our understanding of ALS by separating the central motor neuron body degeneration and the peripheral effects from a fALS mutation expressed at endogenous levels.

Three-year follow-up after psychotherapy for young people with bipolar disorder.

OBJECTIVES: (1) To examine the differences between interpersonal and social rhythm therapy (IPSRT) and specialist supportive care (SSC) in the longer term impacts of IPSRT and SSC on cumulative depression and mania symptoms over a further 78-week follow-up period post treatment. (2) To calculate the survival time before recurrence of a new mood episode over the 3-year period. METHODS: One hundred young people with bipolar disorder aged between 15 and 36 years who had been randomized to treatment with either IPSRT or SSC for 78 weeks were followed up for a subsequent 78 weeks. The Longitudinal Interval Follow-up Evaluation was completed at 26-week intervals. A Mann-Whitney U test was used to determine if there were significant differences between therapy types and a Kaplan-Meier survival analysis was used to determine time to recurrence. Cox regression was used to assess the association between time to relapse and therapy type. RESULTS: There were no significant differences between therapies at each of the data points for either depression or mania scores. The mean change in depression and mania in both groups was significantly different for all three follow-up data points. The actuarial cumulative recurrence rates were 53% for IPSRT and 49% for SSC. There was no significant difference between the groups in time to recurrence. CONCLUSIONS: While there were no significant differences between the two therapies, there was an overall reduction in symptoms in both therapies. There may be sustained benefits in providing intensive psychotherapies in conjunction with pharmacotherapy for young people with bipolar disorder.

Sonographic Evaluation of Pediatric Thyroid Nodules.

A thyroid nodule detected clinically or incidentally at medical imaging is a common indication for ultrasonography (US) in the adult population. This scenario is less frequently the case in pediatric patients, and the approach to evaluation of thyroid nodules deserves modification in these patients because of the increased probability of malignancy in children, compared with adults. Evaluating a thyroid nodule with US in a systematic way requires familiarity with a number of features that can be assessed and the terms that the radiologist uses in each category. The probability of malignancy is influenced by certain features, and several models have emerged to integrate these details into an overall risk assessment to guide management and biopsy of thyroid nodules. Clinical features of thyroid cancer differ between pediatric and adult patients, and risk factors and certain genetic syndromes portend earlier manifestation of thyroid malignancy. This article provides a review of (a) US features of thyroid nodules with an emphasis on the predictive capacity for malignancy, focused on the pediatric age group when the data exist, (b) clinical information, including risk factors and genetic syndromes pertinent to the pediatric population, and (c) the state of the current literature and controversies in diagnosing and managing pediatric thyroid cancer. ©RSNA, 2017.

Predictors of premature termination from psychotherapy for anorexia nervosa: Low treatment credibility, early therapy alliance, and self-transcendence.

OBJECTIVE: Failure to complete treatment for anorexia nervosa (AN) is- common, clinically concerning but difficult to predict. This study examines whether therapy-related factors (patient-rated pretreatment credibility and early therapeutic alliance) predict subsequent premature termination of treatment (PTT) alongside self-transcendence (a previously identified clinical predictor) in women with AN. METHODS: 56 women aged 17-40 years participating in a randomized outpatient psychotherapy trial for AN. Treatment completion was defined as attending 15/20 planned sessions. Measures were the Treatment Credibility, Temperament and Character Inventory, Vanderbilt Therapeutic Alliance Scale and the Vanderbilt Psychotherapy Process Scale. Statistics were univariate tests, correlations, and logistic regression. RESULTS: Treatment credibility and certain early patient and therapist alliance/process subscales predicted PTT. Lower self-transcendence and lower early process accounted for 33% of the variance in predicting PTT. DISCUSSION: Routine assessment of treatment credibility and early process (comprehensively assessed from multiple perspectives) may help clinicians reduce PTT thereby enhancing treatment outcomes.

Mean telomere length is not associated with current health status in a 50-year-old population sample.

OBJECTIVES: Telomeres are nucleoprotein complexes that cap the ends of linear chromosomes. Telomeric DNA decreases with age and shows considerable heterogeneity in the wider population. There is interest in the application of telomere length measures as a biomarker of general health or "biological age," and the possibility of using mean telomere length to gauge individual disease risk, and to promote lifestyle changes to improve health. This study examined the effectiveness of telomere length as a biomarker for an individual's current overall health status by assessing several measures of general health including SF-36v2 score, current smoking status and a comprehensive obesity phenotype. METHODS: Participants were from the Canterbury Health, Ageing and Lifecourse (CHALICE) cohort, a New Zealand population based multidisciplinary study of aging. Telomere length measurements were obtained on DNA from peripheral blood samples at age 49-51 (n = 351), using a quantitative polymerase chain reaction assay. RESULTS: No associations were found between telomere length measured at age 49-51 and any measures of current health status. The only significant association observed was between telomere length and gender, with females having longer telomere length than men. CONCLUSIONS: Our results suggest that telomere length measurements are unlikely to provide information of much predictive significance for an individual's health status.

Localized Temperature Variations in Laser-Irradiated Composites with Embedded Fiber Bragg Grating Sensors.

Fiber Bragg grating (FBG) temperature sensors are embedded in composites to detect localized temperature gradients resulting from high energy infrared laser radiation. The goal is to detect the presence of radiation on a composite structure as rapidly as possible and to identify its location, much the same way human skin senses heat. A secondary goal is to determine how a network of sensors can be optimized to detect thermal damage in laser-irradiated composite materials or structures. Initial tests are conducted on polymer matrix composites reinforced with either carbon or glass fiber with a single optical fiber embedded into each specimen. As many as three sensors in each optical fiber measure the temporal and spatial thermal response of the composite to high energy radiation incident on the surface. Additional tests use a 2 × 2 × 3 array of 12 sensors embedded in a carbon fiber/epoxy composite to simultaneously measure temperature variations at locations on the composite surface and through the thickness. Results indicate that FBGs can be used to rapidly detect temperature gradients in a composite and their location, even for a direct strike of laser radiation on a sensor, when high temperatures can cause a non-uniform thermal response and FBG decay.

Assessing the distinctiveness of psychotherapies and examining change over treatment for anorexia nervosa with cognitive-behavior therapy, interpersonal psychotherapy, and specialist supportive clinical management.

OBJECTIVE: Therapist adherence to cognitive-behavior therapy (CBT), interpersonal psychotherapy (IPT), and specialist supportive clinical management (SSCM) for anorexia nervosa (AN), was examined across three phases of therapy in a randomized clinical trial. METHOD: Adherence in early, middle, and late phase therapy sessions from 53 of 56 participants in the trial was assessed using the CSPRS-AN by independent raters after listening to complete therapy sessions. RESULTS: The three forms of psychotherapy were distinguishable by blind raters. Subscale scores were higher for the corresponding therapy than the other therapy modalities. In CBT and SSCM, a phase-by-therapy effect was found, with the CBT subscale highest for CBT, intermediate for SSCM, lowest for IPT, and elevated in the middle phase of CBT and SSCM. The SSCM subscale was highest for SSCM, intermediate for CBT, lowest for IPT, and elevated in the middle phase of SSCM. Adherence to activities around normalizing eating, weight gain, and education about anorexia nervosa was higher in SSCM than in either CBT or IPT. DISCUSSION: Ensuring the distinctiveness of therapies in existing clinical trials with differential treatment outcome is essential. Research on adherence to therapy modalities has the potential to help understanding of the effective components of new and existing treatments for AN. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:958-962).

Childhood predictors of lifetime suicide attempts and non-suicidal self-injury in depressed adults.

OBJECTIVE: Adverse childhood experiences are well-recognized risk factors for a variety of mental health issues, including depression, suicide attempts and non-suicidal self-injury. However, less is known about whether childhood adversity, in the form of low parental care, overprotection and abuse, is associated with suicide attempt and non-suicidal self-injury within a sample of depressed adults. METHOD: The sample of outpatients (n = 372) was drawn from two randomized depression trials. Childhood adversity variables, depression severity, age of first depressive episode (major depression episode onset), lifetime suicide attempt and non-suicidal self-injury were recorded at baseline. The association between variables and outcome measures was examined using partial correlations, univariate and multivariate logistic regressions. RESULTS: Low maternal care was significantly associated with suicide attempt; low paternal care was associated with non-suicidal self-injury; overprotection was not associated with either outcome. Other risk factors for suicide attempt were major depression episode onset and baseline depression severity. Major depression episode onset was also a risk factor for non-suicidal self-injury. Abuse, regardless of how it was measured, was not significantly associated with either behaviour after adjusting for its correlations with low maternal or paternal care. CONCLUSION: In this sample of depressed adults, the quality of ongoing, intra-familial relationships, as measured by levels of parental care, had a greater impact on suicide attempt and non-suicidal self-injury than abuse. As the findings were not a priori hypotheses, they require replication. Although the cross-sectional study design limits causal determination, the findings suggest different childhood risk factors for suicide attempt and non-suicidal self-injury and underscore the impact of low parental care on these two behaviours. These findings signal to clinicians the importance of asking specifically about suicide attempts, and non-suicidal self-injury, as well as levels of parental care in childhood. When endorsed, low parental care may be considered an important factor in contextualizing a patient's depression and potential risk for suicide and non-suicidal self-injury.

Prospective rates of suicide attempts and nonsuicidal self-injury by young people with bipolar disorder participating in a psychotherapy study.

OBJECTIVE: Bipolar disorder is a chronic relapsing disorder associated with high rates of suicide, suicide attempts and nonsuicidal self-injury. The study aimed to prospectively identify the rates of suicide attempts and nonsuicidal self-injury in young people participating in an adjunctive randomised controlled psychotherapy for bipolar disorder and to identify differences in individuals who engaged in nonsuicidal self-injury, made suicide attempts or did both. METHOD: In all, 100 participants aged 15-36 years with bipolar disorder received 78 weeks of psychotherapy and were followed up for a further 78 weeks. Data were collected using the Longitudinal Interval Follow-up Evaluation. RESULTS: Suicide attempts reduced from 11% at baseline to 1% at the end of follow-up (week 156). Similarly, self-harm reduced from 15% at baseline to 7% at the end of follow-up. Individuals who engaged in both nonsuicidal self-injury and made suicide attempts differed from those with who only made suicide attempts, engaged in nonsuicidal self-injury or did neither. They were characterised by a younger age of illness onset and higher comorbidity. CONCLUSION: Adjunctive intensive psychotherapy may be effective in reducing suicide attempts and nonsuicidal self-injury and warrants further attention. Particular attention needs to be paid to individuals with early age of onset of bipolar disorder.

Randomized, controlled trial of Interpersonal and Social Rhythm Therapy for young people with bipolar disorder.

OBJECTIVE: This randomized, controlled clinical trial compared the effect of interpersonal and social rhythm therapy (IPSRT) to that of specialist supportive care (SSC) on depressive outcomes (primary), social functioning, and mania outcomes over 26-78 weeks in young people with bipolar disorder receiving psychopharmacological treatment. METHODS: Subjects were aged 15-36 years, recruited from a range of sources, and the patient groups included bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified. Exclusion criteria were minimal. Outcome measures were the Longitudinal Interval Follow-up Evaluation and the Social Adjustment Scale. Paired-sample t-tests were used to determine the significance of change from baseline to outcome period. Analyses of covariance were used to determine the impact of therapy, impact of lifetime and current comorbidity, interaction between comorbidity and therapy, and impact of age at study entry on depression. RESULTS: A group of 100 participants were randomized to IPSRT (n = 49) or SSC (n = 51). The majority had bipolar I disorder (78%) and were female (76%), with high levels of comorbidity. After treatment, both groups had improved depressive symptoms, social functioning, and manic symptoms. Contrary to our hypothesis, there was no significant difference between therapies. There was no impact of lifetime or current Axis I comorbidity or age at study entry. There was a relative impact of SSC for patients with current substance use disorder. CONCLUSIONS: IPSRT and SSC used as an adjunct to pharmacotherapy appear to be effective in reducing depressive and manic symptoms and improving social functioning in adolescents and young adults with bipolar disorder and high rates of comorbidity. Identifying effective treatments that particularly address depressive symptoms is important in reducing the burden of bipolar disorder.

Changes in neuropsychological function after treatment with metacognitive therapy or cognitive behavior therapy for depression.

BACKGROUND: Metacognitive therapy (MCT) is an innovative treatment model addressing patterns of negative thinking seen in emotional disorders. Unlike cognitive behavior therapy (CBT), MCT has strategies targeting dysfunctional cognitive and metacognitive processes underlying perseverative thinking patterns and attentional biases. The aim of this pilot study was to compare changes in neuropsychological functioning related to executive function and attention in outpatients with depression following treatment with MCT or CBT. METHODS: Forty-eight participants referred for outpatient treatment of depression were randomized to 12 weeks of MCT (n = 23) or CBT (n = 25). Mood severity and neuropsychological functioning were assessed at pretreatment, 4 weeks, and at end treatment (12 weeks). RESULTS: There were no significant group differences at pretreatment or 4 weeks on any neuropsychological test, although overall both groups showed a small improvement by 4 weeks. At end treatment, the MCT group demonstrated significantly greater improvement in performance on a task requiring spatial working memory and attention than the CBT group. Changes in executive functioning and attention were independent of change in mood symptoms. CONCLUSIONS: MCT may have an advantage over CBT in improving aspects of executive function, including attention. MCT's emphasis on attentional training and flexible control of thinking may have a beneficial effect on neuropsychological functioning, consistent with the purported mechanism of action.

Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis.

Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis. The effects of many of these mutations on channel function have been characterized both in vitro and in vivo. However, little is known about the consequences of SCN4A mutations downstream from their impact on the electrophysiology of the Nav1.4 channel. Here we report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel. Using N-ethyl-N-nitrosourea mutagenesis, we generated and characterized a mouse model (named draggen), carrying the equivalent point mutation (c.1744A>G; p.I582V) to that found in the patient with periodic paralysis and myotonia. Draggen mice have myotonia and suffer from intermittent hind-limb immobility attacks. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms. We discovered metabolic alterations leading to lean mice, as well as abnormal AMP-activated protein kinase activation, which were associated with the immobility attacks and may provide a novel potential therapeutic target.

Weight suppression predicts total weight gain and rate of weight gain in outpatients with anorexia nervosa.

OBJECTIVE: The present study sought to replicate the finding of Wildes and Marcus, Behav Res Ther, 50, 266-274, 2012 that higher levels of weight suppression at pretreatment predict greater total weight gain, faster rate of weight gain, and bulimic symptoms amongst patients admitted with anorexia nervosa. METHOD: Participants were 56 women with anorexia nervosa diagnosed by using strict or lenient weight criteria, who were participating in a randomized controlled psychotherapy trial (McIntosh et al., Am J Psychiatry, 162, 741-747, 2005). Thirty-five women completed outpatient treatment and post-treatment assessment. Weight suppression was the discrepancy between highest lifetime weight at adult height and weight at pretreatment assessment. Outcome variables were total weight gain, rate of weight gain, and bulimic symptoms in the month prior to post-treatment assessment [assessed using the Eating Disorders Examination (Fairburn et al., Binge-Eating: Nature, Assessment and Treatment. New York: Guilford, 1993)]. RESULTS: Weight suppression was positively associated with total weight gain and rate of weight gain over treatment. Regression models showed that this association could not be explained by covariates (age at onset of anorexia nervosa and treatment modality). Weight suppression was not significantly associated with bulimic symptoms in the month prior to post-treatment assessment, regardless of whether bulimic symptoms were examined as continuous or dichotomous variables. DISCUSSION: The present study reinforces the previous finding that weight suppression predicts total weight gain and rate of weight gain amongst patients being treated for anorexia nervosa. Methodological issues may explain the failure of the present study to find that weight suppression predicts bulimic symptoms. Weight suppression at pretreatment for anorexia nervosa should be assessed routinely and may inform treatment planning.

The atypical calpains: evolutionary analyses and roles in Caenorhabditis elegans cellular degeneration.

The calpains are physiologically important Ca(2+)-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca(2+)](i). We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca(2+) dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover.

Rodent models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by the degeneration of upper and lower motor neurons. Recent advances in our understanding of some of the genetic causes of ALS, such as mutations in SOD1, TARDBP, FUS and VCP have led to the generation of rodent models of the disease, as a strategy to help our understanding of the pathophysiology of ALS and to assist in the development of therapeutic strategies. This review provides detailed descriptions of TDP-43, FUS and VCP models of ALS, and summarises potential therapeutics which have been recently trialled in rodent models of the disease. This article is part of a Special Issue entitled: Animal Models of Disease.