Bidirectional cargo transport by kinesin and dynein is essential for cell viability and defects are linked to neurodegenerative diseases. The competition between motors is described as a tug-of-war, and computational modeling suggests that the load-dependent off-rate is the strongest determinant of which motor 'wins'. Optical tweezer experiments find that the load-dependent detachment sensitivity of transport kinesins is kinesin-3 > kinesin-2 > kinesin-1.
View Article and Find Full Text PDFRecently, the addition of moringa to skincare products has become a popular trend, especially in the natural beauty industry. It is being marketed for its intended moisturizing, antioxidant, and anti-aging properties; however, data are scarce demonstrating its clinical effects as well as standardized concentration, formula, source, and extraction methods. Skin specialists must be aware of this trendy ingredient, including its recent claims in marketing material and current evidence in the literature.
View Article and Find Full Text PDFBicaudal D2 (BICD2) is responsible for recruiting cytoplasmic dynein to diverse forms of subcellular cargo for their intracellular transport. Mutations in the human BICD2 gene have been found to cause an autosomal dominant form of spinal muscular atrophy (SMA-LED2), and brain developmental defects. Whether and how the latter mutations are related to roles we and others have identified for BICD2 in brain development remains little understood.
View Article and Find Full Text PDFThe recent demand for noninvasive fat reduction and muscle toning has generated the need for a variety of noninvasive body contouring devices, including cryolipolysis, radiofrequency, focused ultrasound, laser energy, and high intensity focused electromagnetic energy. Many of the recent technologies are still relatively new, and clinical trials are limited. There is also a lack of comparison between modalities, which makes it difficult for practitioners to select the best treatment option for patients.
View Article and Find Full Text PDFFemale genitourinary treatments in aesthetics utilize energy-based treatments and other noninvasive modalities. These include CO and Erbium YAG lasers, radiofrequency, high-intensity focused electromagnetic energy, hyaluronic acid injection, platelet-rich plasma, and silicone thread treatments with an objective to treat sexual dysfunction and symptoms of genitourinary syndrome associated with menopause, which include atrophic vaginitis, urinary incontinence, and vulvovaginal laxity that is characterized by vaginal dryness, thinning of the epithelium, laxity, prolapse, incontinence, dyspareunia, and increased bacterial infections. The body of evidence is growing for the use of these modalities to improve signs and symptoms of the genitourinary syndrome associated with menopause and sexual function, as well as for rejuvenating the appearance of the external female genitalia.
View Article and Find Full Text PDFBackground: Non-invasive body contouring has experienced recent growth. To meet demand, medical spas and non-physician operators have grown. Insights into their practice can provide information on their impact.
View Article and Find Full Text PDFBackground: Medical spas have experienced a recent rise in popularity by consumers. Their regulations vary from state to state, especially concerning oversight and credentialing. A majority of aesthetic physicians were shown to have a medical spa within 5 minutes of their workplace.
View Article and Find Full Text PDFNup358 is a protein subunit of the nuclear pore complex that recruits the opposing microtubule motors kinesin-1 and dynein [via the dynein adaptor Bicaudal D2 (BicD2)] to the nuclear envelope. This pathway is important for positioning of the nucleus during the early steps of mitotic spindle assembly and also essential for an important process in brain development. It is unknown whether dynein and kinesin-1 interact with Nup358 simultaneously or whether they compete.
View Article and Find Full Text PDFDynein adaptors such as Bicaudal D2 (BicD2) recognize cargo for dynein-dependent transport, and cargo-bound adaptors are required to activate dynein for processive transport, but the mechanism of action is unknown. Here we report the X-ray structure of the cargo-binding domain of human BicD2 and investigate the structural dynamics of the coiled-coil. Our molecular dynamics simulations support the fact that BicD2 can switch from a homotypic coiled-coil registry, in which both helices of the homodimer are aligned, to an asymmetric registry, where a portion of one helix is vertically shifted, as both states are similarly stable and defined by distinct conformations of F743.
View Article and Find Full Text PDFIncremental refinements were made to a generic Nordmøre-grid to minimise bycatches of blue swimmer crabs Portunus armatus and giant cuttlefish Sepia apama, while maintaining catches of western king prawns Melicertus latisulcatus in the Spencer Gulf penaeid-trawl fishery. These refinements involved varying bar spaces, escape-exit areas and guiding-panel lengths, and were compared against a conventional trawl. Catches of teleosts and M.
View Article and Find Full Text PDFDynein adaptor proteins such as Bicaudal D2 (BicD2) are integral components of the dynein transport machinery, as they recognize cargoes for cell cycle-specific transport and link them to the motor complex. Human BicD2 switches from selecting secretory and Golgi-derived vesicles for transport in G1 and S phase (by recognizing Rab6), to selecting the nucleus for transport in G2 phase (by recognizing nuclear pore protein Nup358), but the molecular mechanisms governing this switch are elusive. Here, we have developed a quantitative model for BicD2/cargo interactions that integrates affinities, oligomeric states, and cellular concentrations of the reactants.
View Article and Find Full Text PDFCyclin-dependent kinase 1 (Cdk1) is a master controller for the cell cycle in all eukaryotes and phosphorylates an estimated 8 - 13% of the proteome; however, the number of identified targets for Cdk1, particularly in human cells is still low. The identification of Cdk1-specific phosphorylation sites is important, as they provide mechanistic insights into how Cdk1 controls the cell cycle. Cell cycle regulation is critical for faithful chromosome segregation, and defects in this complicated process lead to chromosomal aberrations and cancer.
View Article and Find Full Text PDFDermatol Online J
January 2018
Tofacitinib is a targeted inhibitor of janus kinase (JAK), currently approved for the treatment of rheumatoid arthritis. We present a patient on treatment withtofacitinib who had an episode of classic dermatomal herpes zoster followed months later by atypical chronic cutaneous ulcers also caused by herpes zoster.
View Article and Find Full Text PDFPurpose: The objective of this study was to evaluate the palliative treatment benefit of surface-mold computer-optimized high-dose-rate brachytherapy (SMBT) for in-transit cutaneous metastases of Merkel cell carcinoma (MCC).
Methods: Ten patients with in-transit cutaneous MCC metastases were treated with SMBT at the Dana-Farber/Brigham & Women's Cancer Center between 2006 and 2012.
Results: The median age at diagnosis was 76 years (range, 63-87 years).
Background: The use of many of the standard skin-directed mycosis fungoides (MF) therapies on facial skin may be limited by site-specific increased risks of side effects, excessive inflammation, and ocular toxicity.
Objective: Our study aimed to describe the levels of erythema, scale, and induration of facial lesions in MF before and after low-dose high-dose-rate surface applicator brachytherapy and to examine the overall clinical response to brachytherapy.
Methods: A total of 23 facial MF lesions in 10 patients were treated with high-dose-rate brachytherapy doses of 4 Gy per session for a total of 2 fractions at our multidisciplinary cutaneous oncology clinic between August 17, 2009, and March 12, 2012.
Mar Biotechnol (NY)
November 2001
A multiplex polymerase chain reaction (PCR) assay developed for discrimination between garfish larvae (family Hemiramphidae, order Beloniformes) found in southern Australian waters was based on species-specific amplification of part of the mitochondrial control region. The species were easily discerned by the number and distinct sizes of PCR products (Hyporhamphus melanochir, 443 bp; H. regularis, 462 and 264 bp).
View Article and Find Full Text PDFMore than 37 million Americans experience tinnitus, and adults age 40 to 70 are most often affected. Tinnitus is a symptom, not a disease, and as such has many different causes. Tinnitus is classified as vibratory and nonvibratory and is further subdivided into objective and subjective categories.
View Article and Find Full Text PDFWe report an unusual, life-threatening complication of producing fulminant cervical necrotizing fasciitis in a previously healthy 2-year-old girl. We reviewed the literature for necrotizing fasciitis in children and its morbidity, mortality, and treatment. This case illustrates the necessity of prompt recognition and aggressive management in patients presenting with cervical necrotizing fasciitis.
View Article and Find Full Text PDFOtolaryngol Head Neck Surg
October 2001
Introduction: In an earlier study, we demonstrated the feasibility of using electrocochleography (ECoG) to document changes in inner ear function objectively after intranasal challenge of patients with inhalant allergy (with no prior immunotherapy) and Meniere's disease, using the antigen to which they were most sensitive.
Objective: We expand on this earlier study and continue to investigate the feasibility of this model in a subset of patients with inhalant allergy and Meniere's disease after immunotherapy.
Study Design: Prospective study of 11 patients identified with both Meniere's disease and inhalant allergy in the practices of 2 neurotologists at our institution.
Anthropometric profiles together with a 4 compartment criterion model of body composition analysis (total body water, bone mineral, fat and residual masses via a combination of deuterium dilution, dual-energy x-ray absorptiometry and hydrodensitometry) were conducted on 3 elite male bodybuilders 10 wk and then 5 d before competition. A mean body mass reduction from 99.70 (Quetelet's Index = 31.
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