Bulbous Tips Research Articles

An Update on the Surgical Management of the Bulbous and Boxy Tip.

The bulbous and box tips are two common morphologies encountered in rhinoplasty. Nasal tip reshaping is a challenging aspect of rhinoplasty. Understanding the classifications of nasal tip morphologies aids when performing a nasal-facial analysis. The management algorithm for both tip morphologies shares various techniques. These techniques include but are not limited to cephalic trim, transdomal sutures, and interdomal sutures. A graduated approach to managing the variations in bulbous and boxy tips will help in achieving consistent results. New concepts applied to the management include supporting alar rims with alar contour grafts, closing dead space through a series of techniques, and managing the soft-tissue envelope, which is often in excess.

Super-resolution imaging reveals cytoskeleton-dependent organelle rearrangement within platelets at intermediate stages of maturation

A steady supply of platelets maintains their levels in the blood, and this is achieved by the generation of progeny from platelet intermediates. Using systematic super-resolution microscopy, we examine the ultrastructural organization of various organelles in different platelet intermediates to understand the mechanism of organelle redistribution and sorting in platelet intermediate maturation as the early step of platelet progeny production. We observe the dynamic interconversion between the intermediates and find that microtubules are responsible for controlling the overall shape of platelet intermediates. Super-resolution images show that most of the organelles are located near the cell periphery in oval preplatelets and confined to the bulbous tips in proplatelets. We also find that the distribution of the dense tubular system and α granules is regulated by actin, whereas that of mitochondria and dense granules is governed by microtubules. Altogether, our results call for a reassessment of organelle redistribution in platelet intermediates.

Nanoscale Surveillance of the Brain by Microglia via cAMP-Regulated Filopodia

Microglia, the brain's immune cells, maintain homeostasis and sense pathological changes by continuously surveying the parenchyma with highly motile large processes. Here, we demonstrate that microglia also use thin actin-dependent filopodia that allow fast nanoscale sensing within discrete regions. Filopodia are distinct from large processes by their size, speed, and regulation mechanism. Increasing cyclic AMP (cAMP) by activating norepinephrine Gs-coupled receptors, applying nitric oxide, or inhibiting phosphodiesterases rapidly increases filopodia but collapses large processes. Alternatively, Gi-coupled P2Y12 receptor activation collapses filopodia but triggers large processes extension with bulbous tips. Similar control of cytoskeletal dynamics and microglial morphology by cAMP is observed in ramified primary microglia, suggesting that filopodia are intrinsically generated sensing structures. Therefore, nanoscale surveillance of brain parenchyma by microglia requires localized cAMP increases that drive filopodia formation. Shifting intracellular cAMP levels controls the polarity of microglial responses to changes in brain homeostasis and alters the scale of immunosurveillance.

Farnesol-induced hyperbranched morphology with short hyphae and bulbous tips of Coriolus versicolor

As the first fungal quorum sensing molecule, farnesol-induced morphological transition is usually studied in dimorphic fungi, but in basidiomycetes the morphological changes regulated by farnesol are rarely investigated. In this study, we found that farnesol made the basidiomycete Coriolus versicolor develop into a hyperbranched morphology with short hyphae and bulbous tips. Farnesol treatment resulted in a significant increase of intracellular oxidative stress level, which influenced the expression of several morphogenesis-related genes, and thereby led to the morphological changes. High oxidative stress level significantly stimulated the expression of laccase genes for improving intracellular laccase biosynthesis. The resulted hyperbranched morphology further accelerated the secretion of intracellular laccase into culture medium. As a result, extracellular laccase production reached a maximum of 2189.2 ± 54.7 U/L in farnesol-induced cultures, which was 6.8-fold greater than that of control cultures. SDS-PAGE and native-PAGE showed that farnesol increased laccase production by promoting the biosynthesis of three laccase isoforms. Together these results provide new opportunities in not only understanding the farnesol-regulated mycelial morphology in basidiomycetes, but also developing novel strategies for enhancing the production of secreted enzymes of biotechnological interest.

Alar cartilage\u2014an alternative for spreader graft in primary rhinoplasty

BackgroundAlar cartilage can be very useful for tip and dorsum grafts. Depending on its size and thickness, it can be an important alternative for spreader grafts to improve endonasal functional deficiencies, correct deviated noses, and prevent inverted “V” deformities. Caucasian patients with bulbous tips are the most common candidates to achieve such benefits. It is easy to obtain and to frame into a desired graft.MethodsThe authors describe a surgical technique using the alar cartilages as spreader grafts. All Caucasian patients with bulbous tips who underwent primary rhinoplasty were included. All patients have been evaluated after 3 to 4 months and after 1 and 2 years by aesthetical and functional criteria.ResultsThirty-four patients (28 female and 6 male) underwent this procedure between 2001 and 2015: 94% reported a better airflow, 91% reported very good aesthetic results and were very satisfied 2 years postoperatively, and 12% had nasal deviations that were corrected with a one side double-layered spreader grafts. Two patients presented supra-tip deformities and one patient had a columella scar that was revised surgically. No cases of inverted “V” deformity were reported 2 years postoperatively.ConclusionsPatients with functional satisfaction and with a straight and smooth dorsum seem to be the most important benefits that were achieved with this technique using alar cartilage spreader grafts, an alternative that can be offered to improve airflow and to prevent deviated and inverted “V” deformities.Level of Evidence: IV, therapeutic study.

Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria.

Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2‐dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis. Human articular chondrocytes were obtained from healthy and AKU donors. Additionally, healthy chondrocytes were treated with HGA to replicate AKU pathology (+HGA). Diseased cells exhibited shorter cilia with length reductions of 36% and 16% in AKU and +HGA chondrocytes respectively, when compared to healthy controls. Both AKU and +HGA chondrocytes demonstrated disruption of the usual cilia length regulation by actin contractility. Furthermore, the proportion of cilia with axoneme breaks and bulbous tips was increased in AKU chondrocytes consistent with defective regulation of ciliary trafficking. Distribution of the Hedgehog‐related protein Arl13b along the ciliary axoneme was altered such that its localization was increased at the distal tip in AKU and +HGA chondrocytes. These changes in cilia structure/trafficking in AKU and +HGA chondrocytes were associated with a complete inability to activate Hedgehog signaling in response to exogenous ligand. Thus, we suggest that altered responsiveness to Hedgehog, as a consequence of cilia dysfunction, may be a contributing factor in the development of arthropathy highlighting the cilium as a novel target in AKU.

Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome.

ABSTRACTPrimary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139) encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc) was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp) expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

Lymphatic Vessel Memory Stimulated by Recurrent Inflammation

Inflammation stimulates new lymphatic vessel growth (inflammatory lymphangiogenesis). One key question is how recurrent inflammation, a common clinical condition, regulates lymphatic vessel remodeling. We show here that recurrent inflammation accelerated the development a functional lymphatic vessel network. This observation suggests a novel program of lymphangiogenesis and identifies a property of lymphatic vessel memory in response to recurrent inflammation. A brief episode of initial inflammation regressed lymphatic vessels, and a significant increase in CD11b(+) macrophages were associated with the development of lymphatic vessel memory. These vessels had major differences in the structure and the spatial distribution of specialized lymphatic vessel features. Surprisingly, we found that the lymphatic vessel memory response did not depend on the vascular endothelial growth factor C or A pathway, indicating that different molecular pathways regulate inflammatory lymphangiogenesis and lymphatic vessel memory. These findings uncover a priming mechanism to facilitate a rapid lymphatic vessel memory response: a potential important component of peripheral host defense.

Solid pseudopapillary tumor of the pancreas: ‘Experiences’ and ‘Lessons’ at a tertiary‐care oncology center

Solid pseudopapillary tumor of the pancreas (SPT) is a rare and fascinating entity of elusive histogenesis and unpredictable biology. It has a peculiar proclivity to afflict young females and involve the pancreatic body-tail region. Cytology diagnosis of these rare neoplasms remains a challenge. We analyzed the cytology features of all SPT cases diagnosed on fine needle aspiration cytology (FNAC) from 2003 to 2009 along with their histopathology slides. Nineteen consecutive cases were diagnosed as SPT on FNAC. Fifteen out of nineteen cases were confirmed as true SPT on histopathology. Amongst the true SPT, all except one occurred in females. Age ranged from 14 to 50 years. Pseudopapillae bearing stout branches terminating in bulbous tips and enclosing transgressing vessels, separated from a collar of tumor cells by a clear zone of myxohyaline coat were pathognomonic of SPT. Singly dispersed monomorphic tumor cells with bland chromatin formed the second diagnostic component of SPT. Nuclear grooves and hyaline globules were in addition helpful in segregating SPT from its close differentials. In four cases diagnosed as SPT on FNAC, histopathology revealed a different final diagnosis (one case each of paraganglioma, extragastrointestinal stromal tumor, metastatic papillary renal cell carcinoma and inflammatory myofibroblastic tumor). Conversely, one case of SPT had been erroneously diagnosed as neuroendocrine tumor on FNAC. Six cases (40%) developed metastasis; commonest site being liver. In conclusion, cytology in conjunction with clinico-radiologic findings plays a key role in making a correct diagnosis. Awareness of unique cytomorphological features is important in distinguishing this tumor from its diverse mimics.

Axl2 Integrates Polarity Establishment, Maintenance, and Environmental Stress Response in the Filamentous Fungus Ashbya gossypii

In budding yeast, new sites of polarity are chosen with each cell cycle and polarization is transient. In filamentous fungi, sites of polarity persist for extended periods of growth and new polarity sites can be established while existing sites are maintained. How the polarity establishment machinery functions in these distinct growth forms found in fungi is still not well understood. We have examined the function of Axl2, a transmembrane bud site selection protein discovered in Saccharomyces cerevisiae, in the filamentous fungus Ashbya gossypii. A. gossypii does not divide by budding and instead exhibits persistent highly polarized growth, and multiple axes of polarity coexist in one cell. A. gossypii axl2Δ (Agaxl2Δ) cells have wavy hyphae, bulbous tips, and a high frequency of branch initiations that fail to elongate, indicative of a polarity maintenance defect. Mutant colonies also have significantly lower radial growth and hyphal tip elongation speeds than wild-type colonies, and Agaxl2Δ hyphae have depolarized actin patches. Consistent with a function in polarity, AgAxl2 localizes to hyphal tips, branches, and septin rings. Unlike S. cerevisiae Axl2, AgAxl2 contains a Mid2 homology domain and may function to sense or respond to environmental stress. In support of this idea, hyphae lacking AgAxl2 also display hypersensitivity to heat, osmotic, and cell wall stresses. Axl2 serves to integrate polarity establishment, polarity maintenance, and environmental stress response for optimal polarized growth in A. gossypii.

A phenotypic study of intraflagellar transport and FLA10 in the lf4 mutant of Chlamydomonas reinhardtii

Flagellar length is a controlled mechanism in the biflagellate alga Chlamydomonas reinhardtii. Several long flagellar mutants have been isolated and used to demonstrate that this is a dynamic process. We characterized the morphology of the lf4 mutant using immunofluorescence (IMF) and scanning and transmission electron microscopy (TEM). Using IMF, the FLA10p and LF4p localized to flagella in a punctate pattern, likely indicating intraflagellar transport (IFT) particles. No bulbous tips were observed in lf4, unlike the lf2 and lf3 mutants as reported by Tam and coworkers (2003, 2007). Multiple IFT particles were observed in cross‐sectional and longitudinal flagellar ultrastructure of lf4 using TEM. Plus, an as yet unidentified electron‐dense structure in an lf4 cross‐section was observed to connect the outer doublet microtubules to the cell membrane. Quantification of IFT particles per length, area and volume of flagella revealed that there were twice as many IFT particles in cross sections of lf4 vs. wild‐type cells. The regulation of flagellar length appears to involve not only regulation of flagellar assembly and disassembly by IFTs but also other signal pathways operating in flagellar assembly and disassembly.

Rhinoplasty in Chinese: management of lower dorsum and bulbous nasal tip

Background Bulbous nasal tips and lower dorsa are common facial features in Chinese people, and surgery to reshape these is frequently requested. The use of silicone implants in rhinoplasty has been widely used in China for many years, but is not suitable for patients seeking Caucasian tip shapes. The creation of an excessively high tip supported only by a silicone implant inevitably leads to implant extrusion. Although many rhinoplasty techniques have been used in Caucasian patients, there is currently no suitable method for Chinese patients, whose anatomy differs from that of Caucasians. The present study was aimed to investigate the clinical outcome of a novel method of rhinoplasty in Chinese people. Methods Eighty patients underwent rhinoplasty using our method between 2002 and 2006. We classified the patients into three types, according to the distance between tip defining points, and used different techniques accordingly. Furthermore, an innovative cartilage carving method and a tip fibro-fatty tissue flap were designed and combined with traditional techniques, such as insertion of silicone implant, cartilage grafts, suture techniques and cephalic trimming to reshape the nasal contours. The followup period was 10–60 months (average, 21 months). Results Remarkable modifications in nasal contours were achieved. No complications developed in any of the 80 patients. Seventy-eight patients were satisfied with the results. The outcomes remained unchanged over time. Conclusion Our method is effective and suitable for the treatment of Chinese patients with lower dorsa and bulbous nasal tips.

Dynein-2 affects the regulation of ciliary length but is not required for ciliogenesis in Tetrahymena thermophila.

Eukaryotic cilia and flagella are assembled and maintained by the bidirectional intraflagellar transport (IFT). Studies in alga, nematode, and mouse have shown that the heavy chain (Dyh2) and the light intermediate chain (D2LIC) of the cytoplasmic dynein-2 complex are essential for retrograde intraflagellar transport. In these organisms, disruption of either dynein-2 component results in short cilia/flagella with bulbous tips in which excess IFT particles have accumulated. In Tetrahymena, the expression of the DYH2 and D2LIC genes increases during reciliation, consistent with their roles in IFT. However, the targeted elimination of either DYH2 or D2LIC gene resulted in only a mild phenotype. Both knockout cell lines assembled motile cilia, but the cilia were of more variable lengths and less numerous than wild-type controls. Electron microscopy revealed normally shaped cilia with no swelling and no obvious accumulations of material in the distal ciliary tip. These results demonstrate that dynein-2 contributes to the regulation of ciliary length but is not required for ciliogenesis in Tetrahymena.

First Report of Pythium Root Dysfunction of Creeping Bentgrass Caused by Pythium volutum in North Carolina.

In July and August of 2002 and 2003, a disease of unknown etiology was observed in Charlotte, NC on 'A-1' creeping bentgrass (CRB; Agrostis stolonifera L.) putting greens that were constructed in 2000. Symptoms appeared in irregular patches ranging from 15 to 30 cm in diameter. Grass in the affected areas was initially wilted and chlorotic, but later exhibited a yellow-to-orange foliar decline. Similar symptoms were observed in Durham, NC in July and August of 2003 on CRB greens established in 2001 with a 1:1 blend of 'A-1' and 'A-4'. The disease was initially diagnosed as take-all patch, but attempts to isolate Gaeumannomyces graminis var. avenae and other ectotrophic root pathogens were unsuccessful. Symptoms of the disease reappeared during periods of warm, dry weather in the fall of 2003 and spring of 2004. At that time, examination of affected root tissue revealed bulbous root tips, loose cortical structure, absence of root hairs, and abundant Pythium oospores and hyphae. These signs and symptoms are typical of Pythium root dysfunction (PRD) as described by Hodges and Coleman (2) in 1985 and Feng and Dernoeden (3) in 1999. Isolation of Pythium spp. was performed by plating directly on V8 agar (4) or baiting with 'A-4' CRB seedlings. Eleven Pythium isolates were obtained from Charlotte (seven via baiting) and 10 were obtained from Durham (all via baiting). All isolates were transferred to grass leaf-blade cultures (4) to induce development of sporangia, oospores, and antheridia for identification using the keys and descriptions of Dick (1). All isolates produced lobate sporangia, large oospores (27 to 33 ± 2.8 μm), and three to nine diclinous antheridia typical of Pythium volutum. Cone-Tainers (3.8 × 20 cm) containing sand meeting USGA specifications were seeded with 'A-1' CRB and grown for 6 weeks in the greenhouse. Each Cone-Tainer was inoculated by cutting the root system at a 5 cm depth, placing five to seven infested grass blades onto the surface of fresh sand, and then replacing the turf. Cone-Tainers inoculated with one of three P. volutum isolates and an uninoculated control (six reps each) were placed in a growth chamber with 12 h of light/dark periods at 24/16°C for 4 weeks to allow pathogen infection and disease development. After 4 weeks, the chamber temperature was raised to 32/26°C to induce symptom development. Two weeks after raising the temperature, all P. volutum isolates caused significant (P = <0.0001) foliar chlorosis and dieback (70 to 100% disease) and reduced root depth and mass by 25 to 65% compared with the uninoculated control. Roots of inoculated plants were colonized with Pythium hyphae, contained numerous oospores, and consistently yielded P. volutum in isolations. To our knowledge, this is the first reported occurrence of PRD in North Carolina and provides further support for the importance of P. volutum as a pathogen of creeping bentgrass. On the basis of our observations, the majority of pathogen activity and disease development occurs in the fall and spring, with foliar symptoms being induced by heat or other stresses.

A novel patient with Cooks syndrome supports splitting from “classic” brachydactyly type B

We report on a 2-year-old girl affected by an isolated form of brachydactyly type B (BDB)-like malformation of the limbs consistent with Cooks syndrome (CS). A literature review was carried out in an attempt to delineate the CS clinical spectrum and separate it from BDB. The two conditions can be differentiated on clinical, radiological, and genetic grounds. In particular, CS shows a characteristic pattern of ungueal and phalangeal anomalies. In the hands, all rays are involved to a similar extent with bulbous tips. The feet are generally more severely affected than the hands. Involvement of the nails appears to be a primary feature and not secondary to phalangeal hypo/aplasia. Also, radial and ulnar rays are similarly affected. The CS clinical spectrum is expanded to include ungueal tumor-like lesions, observed in the present patient.

Cytoplasmic contractions in growing fungal hyphae and their morphogenetic consequences

Video-enhanced light microscopy of the apical and subapical regions of growing hyphae of several fungal species revealed the existence of momentary synchronized motions of subcellular organelles. First discovered in a temperature-sensitive morphological mutant (ramosa-1) of Aspergillus niger, these seemingly spontaneous cytoplasmic contractions were also detected in wild-type hyphae of A. niger, Neurospora crassa, and Trichoderma atroviride. Cytoplasmic contractions in all fungi lasted about 1 s. Although the cytoplasm recovered its motility and appearance, the contraction usually led to drastic changes in Spitzenkörper (apical body) behavior and hyphal morphology, often both. Within 10 s after the contraction, the Spitzenkörper commonly became dislodged from its polar position; sometimes it disassembled into phase-dark and phase-light components; more commonly, it disappeared completely. Whether partial or complete, the dislocation of the Spitzenkörper was always accompanied by a sharp reduction or cessation of growth, and was usually followed by marked morphological changes that included bulbous hyphal tips, bulges in the hyphal profile, and formation of subapical and apical branches. The cytoplasmic contractions are vivid evidence that the most conspicuous cell organelles (membrane-bound) in living hyphae are interconnected via a contractile cytoskeletal network.

Photodynamic Therapy

Photodynamic Therapy

CVD synthesis of boron nitride nanotubes without metal catalysts

An efficient CVD synthetic route for bulk quantities of boron nitride nanotubes (BN-NTs) was developed, where a B–N–O precursor generated from melamine diborate (C 3N 6H 6·2H 3BO 3) was employed as the precursor and no metal catalyst was used. The resultant tubes all show remarkable ordering of the concentric atomic layers and exhibit stoichiometric BN composition. It is commonly found that the nanotubes have bulbous tips showing B–N–O amorphous clusters encapsulated in BN cages. The amorphous clusters might play the catalytic role in the nanotube `tip-growth' process as the metal catalysts do in the metal-catalyzed CVD method.

Self-assembly of Si nanostructures

Flower-like Si nanostructures are formed in high yield, by heating an SiO 2 plate at ca. 1600 °C (Ta heater) under Ar (100 Torr). The product consists of metal-free cubic phase Si nanowires surmounted by bulbous Si tips. HRTEM observations show that the nanowires contain kink and twinning defects, whereas the tips are generally well-crystallized and covered with a thin layer of amorphous SiO x ( x = 1–2). A growth model is proposed to account for these observations.

Morphological changes (including filamentation) in Escherichia coli grown under starvation conditions on silicon wafers and other surfaces.

Using a scanning electron microscope, pleomorphism (notably filamentation) was seen when Escherichia coli was grown under starvation conditions for 14 d on microporous silicon wafers, titanium, glass and plastic discs. Under these conditions, the 'standard', rod shaped cell (1-3 microns) failed to separate after division and filaments developed, some as long as 50 microns, with many showing bulbous tips. Filamentation began to occur 5 d after the imposition of starvation conditions. Dumbbell shaped cells were also observed, although apparent 'Y' and 'V'-shaped cells proved to be artefacts, caused by overlapping rods. The implications of the appearance of pleomorphism in E. coli, when grown under starvation conditions, is discussed in relation to its pathogenicity and growth in the environment.