Diaphanous-related formin 1 (DIAPH1) is a formin homology F-actin elongating protein encoded by DIAPH1. Homozygous recessive variants resulting in the loss of DIAPH1 function cause seizures, cortical blindness, and microcephaly syndrome (SCBMS), but hearing loss has not been reported. In contrast, dominant variants of human DIAPH1 are associated with DFNA1 non-syndromic sensorineural hearing loss. The deafness phenotype is due partly to abnormal F-actin elongation activity caused by disruption of the DIAPH1 autoinhibitory mechanism. We report an elderly female heterozygous for the c.3145C>T: p.R1049X variant who showed late-onset sensorineural hearing loss in her fifth decade. p.R1049X lacks F-actin elongation activity because this variant truncates one-third of the FH2 domain, which is vital for DIAPH1 dimerization and processive F-actin elongation activity. Concordantly, no increase of F-actin or processive F-actin elongation activity was observed after overexpression of p.R1049X DIAPH1 in HeLa cells or by single-molecule microscopy using Xenopus XTC cells. However, overexpression of the p.R1049X variant impairs formation of cell-cell junctions and mitosis. We speculate that late-onset hearing loss is a long-term consequence of heterozygosity for the recessive p.R1049X variant, a phenotype that may have been overlooked among carriers of other recessive alleles of DIAPH1.

Recent understandings ofArabidopsiszygote. Body axis formation is essential for the proper development of multicellular organisms. The apical-basal axis in Arabidopsis thaliana is determined by the asymmetric division of the zygote, following its cellular polarization. However, the regulatory mechanism of zygote polarization is unclear due to technical issues. The zygote is located deep in the seed (ovule) in flowers, which prevents the living dynamics of zygotes from being observed. In addition, elucidation of molecular pathways by conventional forward genetic screens was not enough because of high gene redundancy in early development. Here, we present a review introducing two new methods, which have been developed to overcome these problems. Method 1: the two-photon live-cell imaging method provides a new system to visualize the dynamics of intracellular structures in Arabidopsis zygotes, such as cytoskeletons and vacuoles. Microtubules form transverse rings and control zygote elongation, while vacuoles dynamically change their shapes along longitudinal actin filaments and support polar nuclear migration. Method 2: the transcriptome method uses isolated Arabidopsis zygotes and egg cells to reveal the gene expression profiles before and after fertilization. This approach revealed that de novo transcription occurs extensively and immediately after fertilization. Moreover, inhibition of the de novo transcription was shown to sufficiently block the zygotic division, thus indicating a strong possibility that yet unidentified zygote regulators can be found using this transcriptome approach. These new strategies in Arabidopsis will help to further our understanding of the fundamental principles regarding the proper formation of plant bodies from unicellular zygotes.

It is clearly established that there is not a unique response to soil water deficit but that there are as many responses as soil water deficit characteristics: Drought intensity, drought duration, and drought position during plant cycle. For a same soil water deficit, responses can also differ on plant genotype within a same species. In spite of this variability, at least for leaf production and expansion processes, robust tendencies can be extracted from the literature when similar watering regimes are compared. Here, we present response curves and multi-scale dynamics analyses established on tomato plants exposed to different soil water deficit treatments. Results reinforce the trends already observed for other species: Reduction in plant leaf biomass under water stress was due to reduction in individual leaf biomass and areas whereas leaf production and specific leaf area were not affected. The dynamics of leaf expansion was modified both at the leaf and cell scales. Cell division and expansion were reduced by drought treatments as well as the endoreduplication process. Combining response curves analyses together with dynamic analyses of tomato compound leaf growth at different scales not only corroborate results on simple leaf responses to drought but also increases our knowledge on the cellular mechanisms behind leaf growth plasticity.

Supernumerary elements of the genome are often called B chromosomes. They usually consist of various autosomal sequences and, because of low selective pressure, are mostly pseudogenized and contain many repeats. There are numerous reports on B chromosomes in mammals, fish, invertebrates, plants, and fungi, but only a few of them have been studied using sequencing techniques. However, reptilian supernumerary chromosomes have been detected only cytogenetically and never sequenced or analyzed at the molecular level. One model squamate species with available genome sequence is Anolis carolinensis. The scope of the present article is to describe the genetic content of A. carolinensis supernumerary chromosomes. In this article, we confirm the presence of B chromosomes in this species by reverse painting and synaptonemal complex analysis. We applied low-pass high-throughput sequencing to analyze flow-sorted B chromosomes. Anole B chromosomes exhibit similar traits to other supernumerary chromosomes from different taxons: they contain two genes related to cell division control (INCENP and SPIRE2), are enriched in specific repeats, and show a high degree of pseudogenization. Therefore, the present study confirms that reptilian B chromosomes resemble supernumerary chromosomes of other taxons.

BACKGROUND: Squamous Cell Carcinoma (SCC) includes several subtypes and these can be classified according to their clinical behaviours from the least invasive to the most aggressive. Moreover, it is appropriate to analyse their clinicalpathological patterns 1. In light of its wide histopathological variability, we encountered a rare malignant cutaneous lesion: a SCC of a proliferating trichilemmal tumour (PTT) nature.
METHODS: We describe the clinical and pathologic findings of an 82-year-old woman, who developed a SCC with areas of trichilemmal differentiation. It has a surprising thickness of 25 mm, which passes through the dermis, infiltrates the hypodermis and evolves quickly.
CONCLUSIONS: Considering its exophytic growth and the negative results of the post operative tests (ultrasounds confirmed absence of metastasis), the tumour was eradicated thanks to the surgical approach (a 1 cm border wide excision, including the periosteum in the central part of the lesion, followed by its reconstruction using a full-thickness skin graft) and the prompt intervention, without need for further complimentary treatments. The overall aesthetic results were pleasing.
UNASSIGNED: Adnexal tumour, PPT, SCC, Surgery.
Il carcinoma sqaumocellulare annovera diversi sottotipi classificabili in base alle loro aggressività. In virtù di questa grande variabilità istopatologica riportiamo il caso clinico di un’ottantaduenne caucasica affetta da una rara forma di carcinoma a cellule squamose, con aree di differenziazione trichilemmale/pilare. Tale paziente giunge alla nosta osservazione con una lesione ulcerata, esofitica, nodulare, di 4 cm x 4 cm, localizzata in regione frontale, già precedentemente sottoposta a biopsia incisionale presso altra struttura e con diagnosi di “adenocarcinoma moderatamente differenziato con immunofenotipo compatibile con istogenesi annessiale cutanea”. Considerate l’età della paziente, le comorbidità nonchè la sua storia clinica, effettuate le dovute indagini preoperatorie, si procede all’intervento chirurgico: ampia escissione en bloc della lesione con un margine radiale di 1 cm e approfondimento fino al periostio, incluso nella porzione centrale della lesione. Chiusura della perdita di sostanza post-chirurgica a mezzo di innesto a tutto spessore prelevato dalla regione anteriore del braccio destro. L’intervento chirurgico è privo di complicanze. Il referto anatomo-patologico diagnostica, con valutazione definitiva, “un carcinoma a cellule squamose, moderatamente differenziato, con aree di differenziazione trichilemmale/ pilare, infiltrante l’ipoderma con uno spessore di 25mm. Margini chirurgici indenni”. Sebbene sia noto un comportamento non invasivo di questo tipo di lesione, la letteratura evidenzia molteplici casi di aggressività locoregionale e presenza di potenziale metastatico, strettamente legati all’infiltrazione dei tessuti adiacenti la neoplasia. Si rendono quindi opportuni follow-up e consulenza oncologica. Alla rivalutazione della paziente, non vi è evidenza di recidiva locale clinicamente nonchè a mezzo di indagine ecografica negativa si per recidia locale che per presenza di metastasi locoregionali. Ecco che nonstante lo spessore, l’invasività della lesione e la rapidità della sua evoluzione, dato anche il suo atteggiamento esofitico, la negatività delle indagini diagnostiche e la prontezza dell’approccio terapeutico, è stato possibile eradicare il tumore grazie al solo approccio chirurgico, scongiurando la necessità di terapie complementari. L’esito estetico è stato soddisfacente.

Several different models of myogenesis describing early stages of amphibian paraxial myotomal myogenesis are known. Myoblasts of Xenopus laevis and Hymenochirus boettgeri change their position from perpendicular to parallel, in relation to axial organs, and differentiate into mononucleate myotubes. In Bombina variegate the myotomal myoblasts change their shape from round to elongate and then differentiate into mononuclear, morphologically mature myotubes. In Pelobates fuscus and Triturus vulgaris, myoblasts fuse into multinuclear myotubes. Mono- and multinucleate myotubes achieve morphological maturity during the differentiation process. During myogenesis of B. variegata, the nuclei of mononucleate, differentiating myotubes contain a tetraploid quantity of DNA (4C DNA). The stable quantity of DNA is confirmed by lack of 3H-thimidine incorporation into myotube nuclei. This outcome is a proof that myoblasts withdraw from the cell cycle in the G2 phase. The further development of myotomal myotubes involves myoblasts of mesenchymal origin. These myoblasts fuse with myotubes in X. laevis and B. variegate in the G1 phase. Secondary muscle fibres in amphibian myotomes have only mesenchymal origin. Mesenchymal myoblasts fuse into multinucleated myotubes. Myofibril development in the differentiating myotube and lack of DNA replication confirm the classical paradigm of myogenesis. Mesenchymal myoblasts are taking part in the myogenesis of musculus rectus abdominis and limb muscles. The mesenchymal cells in the myogenesis process show one model of myogenesis, which is a classical model of myogenesis. The mesenchymal cells probably come from dermatome.

The number of studies in cell biology in which quantitative models accompany experiments has been growing steadily. Roughly, mathematical and computational techniques of these models can be classified as \"differential equation based\" (DE) or \"agent based\" (AB). Recently AB models have started to outnumber DE models, but understanding of AB philosophy and methodology is much less widespread than familiarity with DE techniques. Here we use the history of modeling a fundamental biological problem-positioning of the cleavage furrow in dividing cells-to explain how and why DE and AB models are used. We discuss differences, advantages, and shortcomings of these two approaches.

Columnar epithelia (e.g., kidney, intestine) and hepatocytes embody the two major organizational phenotypes of non-stratified epithelial cells. Columnar epithelia establish their apical and basal domains at opposing poles and organize in monolayered cysts and tubules, in which their apical surfaces form a single continuous lumen whereas hepatocytes establish their apical domains in the midst of their basolateral domains and organize a highly branched capillary luminal network, the bile canaliculi, in which a single hepatocyte can engage in lumen formation with multiple neighbors. To maintain their distinct tissue architectures, columnar epithelial cells bisect their luminal domains during symmetric cell divisions, while the cleavage furrow in dividing hepatocytes avoids bisecting the bile canalicular domains. We discuss recently discovered molecular mechanisms that underlie the different cell division phenotypes in columnar and hepatocytic model cell lines. The serine/threonine kinase Par1b determines both the epithelial lumen polarity and cell division phenotype via cell adhesion signaling that converges on the small GTPase RhoA.

Metformin is a widely prescribed anti-diabetic drug and its use is associated with lower cancer incidence. The mechanisms by which metformin attenuates tumorigenesis are not clearly understood. In a paper published in Proceedings of the National Academy of Sciences of the United States of America, Hirsch and colleagues show that metformin interferes with a signaling pathway, mediated by the transcription factor NF-κB, which drives cell transformation and is required for the maintenance of cancer stem cells.

A 7-day-exposure time experiment was designed to investigate the phytotoxicity of chlorobenzenes (CBs) on Zea mays seedlings, focusing on the growth and generation of oxidative stress. Significant growth inhibition (based on biomass gain) was observed for exposure to monochlorobenzene (MCB), dichlorobenzene (DCB) and trichlorobenzene (TCB) concentrations higher than 10 mg l(-1). It would seem that CBs inhibit cell division, since the mitotic index decreased for roots exposed to DCB at 80 mg l(-1) dose (8%) and to all the TCB concentrations tested (20% inhibition). CBs exposure resulting in an increase in the oxidative stress response in maize seedlings [reactive oxygen species like H(2)O(2), antioxidant enzymes (POD, GR), lipid peroxidation] correlated to the compound\'s degree of chlorination, where damage increasing with the number of chlorine atoms (MCB < DCB < TCB). This biological response was also dependent on the dose-exposure. Z. mays exposed to CBs at concentrations <10 mg l(-1) did not induce sufficient oxidative damage to cause root cell death. Therefore, CBs at current environmental concentrations are unlikely to produce evident phytotoxic effects on Z. mays seedlings.