Regulation of Slow and Fast Muscle Myofibrillogenesis by Wnt/β-Catenin and Myostatin Signaling

Deviation from proper muscle development or homeostasis results in various myopathic conditions. Employing genetic as well as chemical intervention, we provide evidence that a tight regulation of Wnt/β-catenin signaling is essential for muscle fiber growth and maintenance. In zebrafish embryos, gain-of-Wnt/β-catenin function results in unscheduled muscle progenitor proliferation, leading to slow and fast muscle hypertrophy accompanied by fast muscle degeneration. The effects of Wnt/β-catenin signaling on fast muscle hypertrophy were rescued by misexpression of Myostatin or p21CIP/WAF, establishing an in vivo regulation of myofibrillogenesis by Wnt/β-catenin signaling and Myostatin. Epistatic analyses suggest a possible genetic interaction between Wnt/β-catenin and Myostatin in regulation of slow and fast twitch muscle myofibrillogenesis

Age, gender, and topography influence the clinical and dermoscopic appearance of lentigo maligna

BACKGROUND: Little is known about the frequency of clinical and dermoscopic patterns of lentigo maligna (LM) in relation to specific anatomic subsites and patients characteristics. OBJECTIVE: We sought to assess the frequency of clinical and dermoscopic features of LM and to correlate them to specific anatomic subsites, and patients' age and gender. METHODS: This was a retrospective analysis of clinical and dermoscopic images of a series of consecutive, histopathologically diagnosed, facial and extrafacial LM. RESULTS: A total of 201 cases from 200 patients (mean age 69.51 \ub1 12.26 years) including 120 women were collected. Most cases were located on the face (n = 192, 95.5%). In 102 cases, LM presented as clinically solitary facial macule (s/LM), whereas it was associated with multiple surrounding freckles in the remaining cases. s/LM were significantly smaller (10 mm; P = .020) and associated with younger age compared with LM associated with multiple surrounding freckles (mean age 67.73 \ub1 12.68 years vs 71.34 \ub1 11.59 years, respectively; P = .036). Dermoscopically, gray color irrespective of a specific pattern was the most prevalent finding seen in 178 (88.6%) cases. LIMITATIONS: This was a retrospective study. CONCLUSIONS: The knowledge about patient age, patient gender, and site-related clinical features of LM associated with gray color upon dermoscopy may enhance the clinical recognition of LM

Dermoscopic clues to diagnose acantholytic dyskeratosis

A 61-year-old man presented with multiple small, reddish, eroded papules located on his chest (Figure 1A). Histopathologic examination revealed the typical findings of Grover\u2019s disease

The novel gene asb11:a regulator of the size of the neural progenitor compartment

From a differential display designed to isolate genes that are down-regulated upon differentiation of the central nervous system in Danio rerio embryos, we isolated d-asb11 (ankyrin repeat and suppressor of cytokine signaling box–containing protein 11). Knockdown of the d-Asb11 protein altered the expression of neural precursor genes sox2 and sox3 and resulted in an initial relative increase in proneural cell numbers. This was reflected by neurogenin1 expansion followed by premature neuronal differentiation, as demonstrated by HuC labeling and resulting in reduced size of the definitive neuronal compartment. Forced misexpression of d-asb11 was capable of ectopically inducing sox2 while it diminished or entirely abolished neurogenesis. Overexpression of d-Asb11 in both a pluripotent and a neural-committed progenitor cell line resulted in the stimulus-induced inhibition of terminal neuronal differentiation and enhanced proliferation. We conclude that d-Asb11 is a novel regulator of the neuronal progenitor compartment size by maintaining the neural precursors in the proliferating undifferentiated state possibly through the control of SoxB1 transcription factors

Repression of Smoothened by Patched-Dependent (Pro-)Vitamin D3 Secretion

The developmentally important hedgehog (Hh) pathway is activated by binding of Hh to patched (Ptch1), releasing smoothened (Smo) and the downstream transcription factor glioma associated (Gli) from inhibition. The mechanism behind Ptch1-dependent Smo inhibition remains unresolved. We now show that by mixing Ptch1-transfected and Ptch1 small interfering RNA–transfected cells with Gli reporter cells, Ptch1 is capable of non–cell autonomous repression of Smo. The magnitude of this non–cell autonomous repression of Smo activity was comparable to the fusion of Ptch1-transfected cell lines and Gli reporter cell lines, suggesting that it is the predominant mode of action. CHOD-PAP analysis of medium conditioned by Ptch1-transfected cells showed an elevated 3β-hydroxysteroid content, which we hypothesized to mediate the Smo inhibition. Indeed, the inhibition of 3β-hydroxysteroid synthesis impaired Ptch1 action on Smo, whereas adding the 3β-hydroxysteroid (pro-)vitamin D3 to the medium effectively inhibited Gli activity. Vitamin D3 bound to Smo with high affinity in a cyclopamine-sensitive manner. Treating zebrafish embryos with vitamin D3 mimicked the smo (–/–) phenotype, confirming the inhibitory action in vivo. Hh activates its signalling cascade by inhibiting Ptch1-dependent secretion of the 3β-hydroxysteroid (pro-)vitamin D3. This action not only explains the seemingly contradictory cause of Smith-Lemli-Opitz syndrome (SLOS), but also establishes Hh as a unique morphogen, because binding of Hh on one cell is capable of activating Hh-dependent signalling cascades on other cells

GIANT CONGENITAL NEVUS – CASE REPORT

Congenital nevomelanocitic nevi (CN) are benign melanocitic proliferations present at birth. The incidence of giant CN is 0,002% in the newborns. The paper presents the case of a 20-year old female with giant CN on the skin of the right hand. Dermoscopy is very useful in differential diagnosis of pigmented skin lesions. Dermoscopic characteristics of CN are the presence of uniform globules - the "pebble stone" pattern. Giant CN overtaking more than 5% of the skin has an increased risk of malignant melanoma. Possible therapy modalities for CN are: excision with grafts, dermabrasion, curettage and laser. Periodical check-ups are necessary

Dermoscopy of clear cell acanthoma

A 97-year-old man presented with a 1-year history of a 1.5-cm asymptomatic erythematous nodule on his left leg (Fig 1). Two smaller erythematous lesions appeared more recently in close vicinity to the first lesion. Personal and family history for skin cancer was negative

The importance of gray color as a dermoscopic clue in facial pigmented lesion evaluation: a case report

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