RAGE polymorphisms and oxidative stress levels in Hashimoto's thyroiditis.

BACKGROUND: Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been studied in various autoimmune disorders, but not in Hashimoto's thyroiditis. Also, increased oxidative stress has been described in patients with Hashimoto's thyroiditis. The aim of this study was to investigate the possible role of two common RAGE polymorphisms (-429T>C, -374T>A) in Hashimoto's thyroiditis; in parallel, we studied oxidative stress levels. MATERIALS AND METHODS: A total of 300 consecutive euthyroid women were examined and classified into three groups: Hashimoto's thyroiditis with treatment (n = 96), Hashimoto's thyroiditis without treatment (n = 109) and controls (n = 95). For a rough evaluation of oxidative stress, total lipid peroxide levels in serum were measured. The -429T>C AluI and -374T>A MfeI polymorphisms of RAGE were studied in genomic DNA. RESULTS: Significant association of the RAGE system with Hashimoto's thyroiditis was found only with regard to the prevalence of the -429T>C, but not with -374T>A polymorphism. The levels of oxidative stress were significantly elevated in Hashimoto's thyroiditis patients under treatment. Further analysis demonstrated that an oxidative stress cut-off value of 590 µmol/L is associated with an increased risk of progression of Hashimoto's thyroiditis from euthyroidism to hypothyroidism; this risk is further increased in carriers of the RAGE -429T>C polymorphism. CONCLUSIONS: Our findings indicate that both examined risk factors may be implicated in the occurrence of Hashimoto's thyroiditis, but this covers only a fraction of the pathophysiology of the disease.

Interplay of dFOXO and two ETS-family transcription factors determines lifespan in Drosophila melanogaster.

Forkhead box O (FoxO) transcription factors (TFs) are key drivers of complex transcriptional programmes that determine animal lifespan. FoxOs regulate a number of other TFs, but how these TFs in turn might mediate the anti-ageing programmes orchestrated by FoxOs in vivo is unclear. Here, we identify an E-twenty six (ETS)-family transcriptional repressor, Anterior open (Aop), as regulated by the single Drosophila melanogaster FoxO (dFOXO) in the adult gut. AOP, the functional orthologue of the human Etv6/Tel protein, binds numerous genomic sites also occupied by dFOXO and counteracts the activity of an ETS activator, Pointed (Pnt), to prevent the lifespan-shortening effects of co-activation of dFOXO and PNT. This detrimental synergistic effect of dFOXO and PNT appears to stem from a mis-regulation of lipid metabolism. At the same time, AOP activity in another fly organ, the fat body, has further beneficial roles, regulating genes in common with dfoxo, such as the secreted, non-sensory, odorant binding protein (Obp99b), and robustly extending lifespan. Our study reveals a complex interplay between evolutionarily conserved ETS factors and dFOXO, the functional significance of which may extend well beyond animal lifespan.

Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with severe socio-economic impact. A hallmark of ALS pathology is the presence of aberrant cytoplasmic inclusions composed of misfolded and aggregated proteins, including both wild-type and mutant forms. This review highlights the critical role of misfolded protein species in ALS pathogenesis, particularly focusing on Cu/Zn superoxide dismutase (SOD1) and TAR DNA-binding protein 43 (TDP-43), and emphasizes the urgent need for innovative therapeutic strategies targeting these misfolded proteins directly. Despite significant advancements in understanding ALS mechanisms, the disease remains incurable, with current treatments offering limited clinical benefits. Through a comprehensive analysis, the review focuses on the direct modulation of the misfolded proteins and presents recent discoveries in small molecules and peptides that inhibit SOD1 and TDP-43 aggregation, underscoring their potential as effective treatments to modify disease progression and improve clinical outcomes.

Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling.

FoxO transcription factors, inhibited by insulin/insulin-like growth factor signalling (IIS), are crucial players in numerous organismal processes including lifespan. Using genomic tools, we uncover over 700 direct dFOXO targets in adult female Drosophila. dFOXO is directly required for transcription of several IIS components and interacting pathways, such as TOR, in the wild-type fly. The genomic locations occupied by dFOXO in adults are different from those observed in larvae or cultured cells. These locations remain unchanged upon activation by stresses or reduced IIS, but the binding is increased and additional targets activated upon genetic reduction in IIS. We identify the part of the IIS transcriptional response directly controlled by dFOXO and the indirect effects and show that parts of the transcriptional response to IIS reduction do not require dfoxo. Promoter analyses revealed GATA and other forkhead factors as candidate mediators of the indirect and dfoxo-independent effects. We demonstrate genome-wide evolutionary conservation of dFOXO targets between the fly and the worm Caenorhabditis elegans, enriched for a second tier of regulators including the dHR96/daf-12 nuclear hormone receptor.

Role of insulin-like signalling in Drosophila lifespan.

Regulation of lifespan by the insulin/insulin-like growth factor-like signalling (IIS) pathway has been conserved during evolution from the nematode worm to the mouse. In the insect Drosophila, regulation of lifespan by the IIS pathway was established by data showing that many mutations in single genes encoding IIS components result in an increase in lifespan. Recently, however, the focus has shifted from studying the effects of single gene mutations with ubiquitous effects to finding interventions that alter IIS in specific tissues and at specific stages in the life history of the fruitfly, in order to elucidate the signalling pathways at work and the mechanisms by which alterations in the IIS pathway can extend lifespan.

The impact of impaired "Theory of Mind" on social interactions in schizophrenia.

Given the importance of social dysfunction in schizophrenia, many studies have explored how social cognition, and, particularly, Theory of Mind (ToM) may affect patients' social interactions. In the present study, we investigated the impact of ToM deficits on social interactions, taking into account overall neuropsychological functioning as well as clinical and demographic characteristics. We assessed 28 patients with schizophrenia and 30 healthy participants on a series of tasks including tests of ToM, neuropsychological tests focused on functions potentially relevant to ToM and role plays as an indicator of social interactions. Patients performed more poorly than healthy controls across most ToM and some of the neuropsychological tests. Correlations and hierarchical regression analyses indicated the impact of some, but not all, facets of ToM on patients' social interactions, over and above neuropsychological functioning, positive and negative symptom ratings, duration of illness and demographic characteristics. These findings suggest that remediation of ToM deficits in patients with schizophrenia may help to improve their social interactions.

Humor appreciation of captionless cartoons in obsessive-compulsive disorder.

BACKGROUND: It seems that the core neural regions and cognitive processes implicated in obsessive-compulsive disorder (OCD) pathophysiology may overlap with those involved in humor appreciation. However, to date, there have been no studies that have explored humor appreciation in OCD. The purpose of the present work was to investigate humor appreciation in a group of patients with OCD. METHODS: We examined 25 patients with OCD and 25 healthy controls, matched by age, education, and gender. We administered Penn's Humor Appreciation Test (PHAT), a computerized test comprising captionless cartoons by Mordillo. Each set of stimuli consisted of two almost identical drawings, one of which was funny due to the alteration of a detail in the cartoon, whereas the other was not funny. Severity of psychopathology was evaluated with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS: No significant effect for group, gender or group × gender interaction was found on the PHAT scores. In OCD patients, humor appreciation was not significantly associated with age of onset, duration of illness, and obsessions, but correlated significantly with compulsions. CONCLUSIONS: Humor appreciation, based on captionless cartoons in OCD, does not seem to be deficient compared to healthy subjects but may be related to illness characteristics.

Sex differences in neuropsychological functioning among schizophrenia patients.

OBJECTIVES: Evidence from the literature addressing sex differences in cognition in schizophrenia remains equivocal, with some researchers suggesting that male schizophrenia patients are more impaired than female subjects, while others report no significant sex differences in cognitive functioning. The aim of the present study was to investigate whether the differential pattern of cognitive performance observed in healthy men and women is preserved in male and female schizophrenia patients. METHOD: Ninety-six schizophrenia patients (56 men) were compared with 62 age- and gender-ratio matched healthy controls (31 men), on a battery of neuropsychological tests that assessed basic cognitive abilities: attention, working memory, abstraction, inhibition, fluency, verbal learning and memory, visual memory, visuospatial skills, and psychomotor speed. RESULTS: As a group, schizophrenia patients were significantly impaired in each of the cognitive domains assessed, with the exception of psychomotor speed. The effect of sex was significant for verbal learning and memory, wherein women outperformed men. No significant group x sex interactions were found in any cognitive domains, indicating that the female advantage typically observed in verbal learning and memory remained the same in the schizophrenia patients. CONCLUSION: The degree of cognitive impairment is the same for male and female schizophrenia patients. Those sex differences found among the patients were typical of the healthy population as well. Therefore, differential decrements in basic cognitive domains do not appear to account for the favourable course of schizophrenia in women relative to men.

Psychotic features associated with multiple sclerosis.

Although once considered rare, several more recent investigations have been published describing psychotic features in multiple sclerosis (MS). The association between the two conditions, however, remains unclear. Large-scale hospital-based, epidemiological and case studies have suggested a relationship between psychosis and MS through demonstrating their higher than chance co-occurrence, their temporal relationship, and their association with particular structural abnormalities in the brain (i.e., periventricular white matter and temporal demyelination). The etiology of psychosis in MS has also not been explained adequately. Regional demyelination and the use of corticosteroids have been implicated, yet their mechanisms of action have not been elucidated. The present review addresses what is known at this point in time regarding the occurrence of psychosis in the context of MS, the data regarding possible etiological factors, and the implications of these data and suggestions regarding diagnosis and treatment. Future research should explore the underlying pathophysiology of psychosis and multiple sclerosis to further our understanding of the central nervous system disease process. This research could help determine the features which would guide clinicians in identifying patients at risk of developing psychosis in the context of MS, as well as propose the optimal pharmacological intervention.

Effects of sentence context on lexical ambiguity resolution in patients with schizophrenia.

Previous research has suggested that a failure in processing contextual information may account for the heterogeneous clinical manifestations and cognitive impairments observed in schizophrenia. In the domain of language, context processing in schizophrenia has been investigated mostly with single-word semantic priming paradigms; however, natural language comprehension depends on more than semantic relations between words. The present study aimed to systematically assess sentence context effects in homonym meaning activation in patients with schizophrenia. Fourteen patients with schizophrenia and 14 normal controls matched to the patients on sex, age, education and parental education, were examined using a cross-modal priming paradigm. Primes were sentences biasing the first, second, or neither meaning of a sentence-final equibiased homonym; targets were related to either the first or the second meaning of the homonym and appeared after an interstimulus interval (ISI) of 0ms or 750ms. Patients with schizophrenia exhibited a trend towards facilitation of both target types following unbiased sentences at ISI=0ms, similar to controls. However, in contrast to the pattern of selective target facilitation exhibited by control subjects following first- or second meaning-biased sentences, no significant target facilitation was observed in patients in the same condition. At ISI=750ms, patients did no longer exhibit significant target facilitation in any sentence context condition. This pattern of results is compatible with the assumption of a combined impairment in lexical (automatic spreading of activation within the semantic network) and extralexical (working memory) processes in patients with schizophrenia.

The interaction between FOXO and SIRT1: tipping the balance towards survival.

When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast and the nematode worm Caenorhabditis elegans. In the worm, this extension of lifespan requires the FOXO transcription factor daf-16. Three recent articles focusing on mammalian homologues of Sir2 and FOXO have highlighted the mechanisms that generate this genetic interaction. Mammalian SIRT1 deacetylates FOXO3 and/or FOXO4, thus attenuating FOXO-induced apoptosis and potentiating FOXO-induced cell-cycle arrest. SIRT1 might increase longevity by shifting FOXO dependent responses away from cell death and towards cell survival.

Emotion perception in obsessive-compulsive disorder.

The purpose of the present study was to investigate the ability to perceive facial and vocal affect in a group of patients with obsessive-compulsive disorder (OCD) and to explore the specific emotions that might be troublesome for them. Participants were 25 patients with OCD and 25 healthy controls, matched for age, education, and gender. They were assessed with computerized tests of affect perception using visual faces [Kinney's Affect Matching Test (KAMT)], visual everyday scenarios [Fantie's Cartoon Test (FCT)], and prosody [Affective Prosody Test (APT)], as well as a facial recognition test [Kinney's Identity Matching Test (KIMT)]. Severity of OCD symptoms in the patient group was measured with the Yale-Brown Obsessive Compulsive Scale. Patients with OCD were not impaired in the perception of emotion, in either the visual [still photographs (KAMT) or sketches of everyday scenarios (FCT)] or the vocal (APT) modality, as compared with age-, sex-, and education-matched healthy individuals. Moreover, patients with OCD did not differ from healthy individuals in discriminating facial identity (KIMT). With regard to each emotion type separately, patients performed equally well as healthy individuals in all the emotions examined. Emotion processing of both facial expressions and prosody does not appear to be deficient in patients with OCD (JINS, 2009, 15, 148-153).

Dynamics of the action of dFOXO on adult mortality in Drosophila.

The insulin/insulin growth factor (IGF)-like signaling (IIS) pathway has a conserved role in regulating lifespan in Caenorhabditis elegans, Drosophila and mice. Extension of lifespan by reduced IIS has been shown in C. elegans to require the key IIS target, forkhead box class O (FOXO) transcription factor, DAF-16. dFOXO, the Drosophila DAF-16 orthologue, is also an IIS target, and its overexpression in adult fat body increases lifespan. In C. elegans, IIS acts exclusively during adulthood to determine adult survival. We show here, using an inducible overexpression system, that in Drosophila continuous dFOXO overexpression in adult fat body reduces mortality rate throughout adulthood. We switched the IIS status of the flies at different adult ages and examined the effects of these switches on dFOXO expression and mortality rates. dFOXO protein levels were switched up or down by the inducible expression system at all ages examined. If IIS status is reversed early in adulthood, similar to the effects of another intervention that reduces adult mortality in Drosophila, dietary restriction (DR), there is a complete switch of subsequent mortality rate to that of flies chronically exposed to the new IIS regime. At this age, IIS thus acts acutely to determine risk of death. Mortality rates continued to respond to a switch in IIS status up to 4 weeks of adult age, but not thereafter. However, unlike DR, as IIS status was altered at progressively later ages, mortality rates showed incomplete switching and responded with progressively smaller changes. These findings indicate that alteration of expression levels of dFOXO may have declining effects on IIS status with age, that there could be some process that prevents or lessens the physiological response to a switch in IIS status or that, unlike DR, this pathway regulates aging-related damage. The decreased mortality and increased lifespan of dFOXO overexpressing flies was uncoupled from any effect on female fecundity and from expression levels of Drosophila insulin-like peptides in the brain.

Studying social cognition in patients with schizophrenia and patients with frontotemporal dementia: theory of mind and the perception of sarcasm.

We investigated social cognition and theory of mind in patients with schizophrenia and in patients with frontotemporal dementia in order to elucidate the cognitive mechanisms involved in the breakdown of these skills in psychiatric and neurological patients. Our tasks included videotaped scenarios of social interactions depicting sincere, sarcastic and paradoxical remarks, as well as lies. We found impaired performance of the schizophrenia group on all theory of mind conditions despite their intact understanding of sincere statements. In contrast, the FTD group performed poorly only when they had to rely on paralinguistic cues indicating sarcasm or lies, and not on paradoxical remarks or sarcasm when given additional verbal cues. Our findings suggest that, while current deficits in social and interpersonal functioning in patients with FTD may reflect a decrement in previously acquired skills, similar deficits in patients with schizophrenia may reflect an altogether inadequately learned process.

What Is Going On? The Process of Generating Questions about Emotion and Social Cognition in Bipolar Disorder and Schizophrenia with Cartoon Situations and Faces.

Regarding the notion of putative “best” practices in social neuroscience and science in general, we contend that following established procedures has advantages, but prescriptive uniformity in methodology can obscure flaws, bias thinking, stifle creativity, and restrict exploration. Generating hypotheses is at least as important as testing hypotheses. To illustrate this process, we describe the following exploratory study. Psychiatric patients have difficulties with social functioning that affect their quality of life adversely. To investigate these impediments, we compared the performances of patients with schizophrenia and those with bipolar disorder to healthy controls on a task that involved matching photographs of facial expressions to a faceless protagonist in each of a series of drawn cartoon emotion-related situations. These scenarios involved either a single character (Nonsocial) or multiple characters (Social). The Social scenarios were also Congruent, with everyone in the cartoon displaying the same emotion, or Noncongruent (with everyone displaying a different emotion than the protagonist should). In this preliminary study, both patient groups produced lower scores than controls (p < 0.001), but did not perform differently from each other. All groups performed best on the social-congruent items and worst on the social-noncongruent items (p < 0.001). Performance varied inversely with illness duration, but not symptom severity. Complete emotional, social, cognitive, or perceptual inability is unlikely because these patient groups could still do this task. Nevertheless, the differences we saw could be meaningful functionally and clinically significant and deserve further exploration. Therefore, we stress the need to continue developing novel, alternative ways to explore social cognition in patients with psychiatric disorders and to clarify which elements of the multidimensional process contribute to difficulties in daily functioning.

The effect of obesity and dietary habits on oxidative stress in Hashimoto's thyroiditis

Objective: Increased oxidative stress has been described in patients with Hashimoto's thyroiditis (HT). The aim of the present study was to investigate whether high oxidative stress is further influenced by obesity and dietary habits in euthyroid women with HT. Methods: Two hundred eighteen consecutive euthyroid women with HT were studied and separated in two groups; 102 with thyroxine replacement and 114 without. For the evaluation of oxidative stress, total lipid peroxide levels in serum (TOS) were measured and recoded as 'high TOS' vs 'medium/low TOS'. The type of food and consumption frequency were recorded. Two binary variables were considered; normal vs low fruit consumption and daily vs sporadic vegetable consumption. Results: 'High TOS' was more frequent in women under thyroxine replacement (31.4% vs 14.7%, OR = 2.7, 95% CI: 1.4­5.2). The prevalence of 'high TOS' was higher among overweight/obese women compared to women with normal BMI (30.4% vs 12.5%, OR = 3.1, 95% CI: 1.5­6.4). Low fruit consumption was associated with increased 'high TOS' prevalence (30.6% vs 12.9%, OR = 3.0, 95% CI: 1.4­6.2). Sporadic vegetable consumption was associated with increased 'high TOS' prevalence compared to daily consumption (29.9% vs 13.5%, OR = 2.7, 95% CI: 1.3­5.7). The examined risk factors were independent and additive in their effect on TOS. At least three risk factors had to be concomitantly present for the likelihood of 'high TOS' to be significantly elevated. Conclusions: Oxidative stress is increased in women with HT under thyroxine replacement. Nevertheless, normal BMI, daily fruit and vegetable consumption, all contribute in maintaining oxidative stress at low levels.

Impaired emotion perception in schizophrenia: a differential deficit.

We investigated previously reported contradictory findings regarding the nature of deficits in emotion perception among patients with schizophrenia. Some studies have concluded that such deficits are due to a generalized impairment in visual processing of faces, while others have found it to be restricted to facial emotional expressions. We examined 37 patients and 32 healthy controls, matched on age and education, using three computerized tests: matching facial identity, matching facial emotional expressions, and discrimination of subtle differences in the valence of facial emotional expressions. Our results showed impaired matching of emotions in patients with schizophrenia. This impairment did not manifest on tasks that depended on perceiving the identity of faces or cues of the relative valence of facial emotional expressions. Our findings support the differential deficit hypothesis of emotion perception in schizophrenia.

The impact of healthcare professionals' personality and religious beliefs on the decisions to forego life sustaining treatments: an observational, multicentre, cross-sectional study in Greek intensive care units.

OBJECTIVES: To assess the opinion of intensive care unit (ICU) personnel and the impact of their personality and religious beliefs on decisions to forego life-sustaining treatments (DFLSTs). SETTING: Cross-sectional, observational, national study in 18 multidisciplinary Greek ICUs, with >6 beds, between June and December 2015. PARTICIPANTS: 149 doctors and 320 nurses who voluntarily and anonymously answered the End-of-Life (EoL) attitudes, Personality (EPQ) and Religion (SpREUK) questionnaires. Multivariate analysis was used to detect the impact of personality and religious beliefs on the DFLSTs. RESULTS: The participation rate was 65.7%. Significant differences in DFLSTs between doctors and nurses were identified. 71.4% of doctors and 59.8% of nurses stated that the family was not properly informed about DFLST and the main reason was the family's inability to understand medical details. 51% of doctors expressed fear of litigation and 47% of them declared that this concern influenced the information given to family and nursing staff. 7.5% of the nurses considered DFLSTs dangerous, criminal or illegal. Multivariate logistic regression identified that to be a nurse and to have a high neuroticism score were independent predictors for preferring the term 'passive euthanasia' over 'futile care' (OR 4.41, 95% CI 2.21 to 8.82, p<0.001, and OR 1.59, 95% CI 1.03 to 2.72, p<0.05, respectively). Furthermore, to be a nurse and to have a high-trust religious profile were related to unwillingness to withdraw mechanical ventilation. Fear of litigation and non-disclosure of the information to the family in case of DFLST were associated with a psychoticism personality trait (OR 2.45, 95% CI 1.25 to 4.80, p<0.05). CONCLUSION: We demonstrate that fear of litigation is a major barrier to properly informing a patient's relatives and nursing staff. Furthermore, aspects of personality and religious beliefs influence the attitudes of ICU personnel when making decisions to forego life-sustaining treatments.

Burnout and job satisfaction of intensive care personnel and the relationship with personality and religious traits: An observational, multicenter, cross-sectional study.

OBJECTIVES: To investigate if burnout in the Intensive Care Unit (ICU) is influenced by aspects of personality, religiosity and job satisfaction. RESEARCH METHODOLOGY: Cross-sectional study, designed to assess burnout in the ICU and to investigate possible determinants. Three different questionnaires were used: the Malach Burnout Inventory, the Eysenck Personality Questionnaire and the Spiritual/Religious Attitudes Questionnaire. Predicting factors for high burnout were identified by multivariate logistic regression analysis. SETTING/PARTICIPANTS: This national study was addressed to physicians and nurses working full-time in 18 Greek ICU departments from June to December 2015. RESULTS: The participation rate was 67.9% (n=149) and 65% (n=320) for ICU physicians and nurses, respectively). High job satisfaction was recorded in both doctors (80.8%) and nurses (63.4%). Burnout was observed in 32.8% of the study participants, higher in nurses compared to doctors (p<0.001). Multivariate analysis revealed that neuroticism was a positive and extraversion a negative predictor of exhaustion (OR 5.1, 95%CI 2.7-9.7, p<0.001 and OR 0.49, 95%CI 0.28-0.87, p=0.014, respectively). Moreover, three other factors were identified: Job satisfaction (OR 0.26, 95%CI 0.14-0.48, p<0.001), satisfaction with current End-of-Life care (OR 0.41, 95%CI 0.23-0.76, p=0.005) and isolation feelings after decisions to forego life sustaining treatments (OR 3.48, 95%CI 1.25-9.65, p=0.017). CONCLUSIONS: Personality traits, job satisfaction and the way End-of-Life care is practiced influence burnout in the ICU.

Transient receptor potential-like channels are essential for calcium signaling and fluid transport in a Drosophila epithelium.

Calcium signaling is an important mediator of neuropeptide-stimulated fluid transport by Drosophila Malpighian (renal) tubules. We demonstrate the first epithelial role, in vivo, for members of the TRP family of calcium channels. RT-PCR revealed expression of trp, trpl, and trpgamma in tubules. Use of antipeptide polyclonal antibodies for TRP, TRPL, and TRPgamma showed expression of all three channels in type 1 (principal) cells in the tubule main segment. Neuropeptide (CAP(2b))-stimulated fluid transport rates were significantly reduced in tubules from the trpl(302) mutant and the trpl;trp double mutant, trpl(302);trp(343). However, a trp null, trp(343), had no impact on stimulated fluid transport. Measurement of cytosolic calcium concentrations ([Ca(2+)](i)) in tubule principal cells using an aequorin transgene in trp and trpl mutants showed a reduction in calcium responses in trpl(302). Western blotting of tubule preparations from trp and trpl mutants revealed a correlation between TRPL levels and CAP(2b)-stimulated fluid transport and calcium signaling. Rescue of trpl(302) with a trpl transgene under heat-shock control resulted in a stimulated fluid transport phenotype that was indistinguishable from wild-type tubules. Furthermore, restoration of normal stimulated rates of fluid transport by rescue of trpl(302) was not compromised by introduction of the trp null, trp(343). Thus, in an epithelial context, TRPL is sufficient for wild-type responses. Finally, a scaffolding component of the TRPL/TRP-signaling complex, INAD, is not expressed in tubules, suggesting that inaD is not essential for TRPL/TRP function in Drosophila tubules.