We introduce a microfluidic system for simultaneously measuring single cell mass and cell cycle progression over multiple generations. We use this system to obtain over 1,000 hours of growth data from mouse lymphoblast and pro-B-cell lymphoid cell lines. Cell lineage analysis revealed a decrease in the growth rate variability at the G1/S phase transition, which suggests the presence of a growth rate threshold for maintaining size homeostasis.
Aneuploidy, referring to unbalanced chromosome numbers, represents a class of genetic variation associated with cancer, birth defects and eukaryotic microbes 1 – 4 . Whereas it is known that each aneuploid chromosome stoichiometry can give rise to a distinct pattern of gene expression and phenotypic profile 4 , 5 , it has remained a fundamental question as to whether there are common cellular defects associated with aneuploidy. In this study, we designed a unique strategy that allowed for the observation of common transcriptome changes of aneuploidy by averaging out karyotype-specific dosage effects using aneuploid yeast cell populations with random and diverse chromosome stoichiometry. This analysis uncovered a common aneuploidy gene-expression (CAGE) signature suggestive of hypo-osmotic stress. Consistently, aneuploid yeast exhibited increased plasma membrane (PM) stress leading to impaired endocytosis, and this defect was also observed in aneuploid human cells. Thermodynamic modeling showed that hypo-osmotic-like stress is a general outcome of proteome imbalance caused by aneuploidy and predicted a ploidy-cell size relationship observed in yeast and aneuploid cancer cells. A genome-wide screen further uncovered a general dependency of aneuploid cells on a pathway of ubiquitin-mediated endocytic recycling of nutrient transporters. Loss of this pathway coupled with the aneuploidy-inherent endocytic defect leads to marked alteration of intracellular nutrient homeostasis.
Vestibular neuritis is the most common cause of acute spontaneous vertigo. Vestibular neuritis is ascribed to acute unilateral loss of vestibular function, probably due to reactivation of herpes simplex virus in the vestibular ganglia. The diagnostic hallmarks of vestibular neuritis are spontaneous horizontal-torsional nystagmus beating away from the lesion side, abnormal head impulse test for the involved semicircular canals, ipsilesional caloric paresis, decreased responses of vestibular-evoked myogenic potentials during stimulation of the affected ear, and unsteadiness with a falling tendency toward the lesion side. Vestibular neuritis preferentially involves the superior vestibular labyrinth and its afferents. Accordingly, the function of the posterior semicircular canal and saccule, which constitute the inferior vestibular labyrinth, is mostly spared in vestibular neuritis. However, because the rare subtype of inferior vestibular neuritis lacks the typical features of vestibular neuritis, it may be misdiagnosed as a central vestibular disorder. Even in the patient with the typical pattern of spontaneous nystagmus observed in vestibular neuritis, brain imaging is indicated when the patient has unprecedented headache, negative head impulse test, severe unsteadiness, or no recovery within 1 to 2 days. Symptomatic medication is indicated only during the acute phase to relieve the vertigo and nausea/vomiting. Vestibular rehabilitation hastens the recovery. The efficacy of topical and systemic steroids requires further validation.
Previous studies have demonstrated an association of osteopenia/osteoporosis with idiopathic benign paroxysmal positional vertigo (BPPV). Since vitamin D takes part in the regulation of calcium and phosphorus found in the body and plays an important role in maintaining proper bone structure, decreased bone mineral density in patients with BPPV may be related to decreased serum vitamin D. We measured the serum levels of 25-hydroxyvitamin D in 100 patients (63 women and 37 men, mean age ± SD = 61.8 ± 11.6) with idiopathic BPPV and compared the data with those of 192 controls (101 women and 91 men, mean age ± SD = 60.3 ± 11.3) who had lived in the same community without dizziness or imbalance during the preceding year. The selection of the controls and acquisition of clinical information were done using the data from the Fourth Korean National Health and Nutrition Examination Survey, 2008. The serum level of 25-hydroxyvitamin D was lower in the patients with BPPV than in the controls (mean ± SD = 14.4 ± 8.4 versus 19.1 ± 6.8 ng/ml, p = 0.001). Furthermore, patients with BPPV showed a higher prevalence of decreased serum vitamin D (<20 ng/ml, 80.0 vs. 60.1 %, p < 0.001) than the controls. Multiple logistic regression analyses adjusted for age, sex, body mass index, hypertension, diabetes, proteinuria, regular exercise and the existence of decreased bone mineral density demonstrated that vitamin D insufficiency (10-20 ng/ml) and deficiency (<10 ng/ml) were associated with BPPV with the odds ratios of 3.8 (95 % confidence interval = 1.51-9.38, p = 0.004) and 23.0 (95 % confidence interval = 6.88-77.05, p < 0.001). Our study demonstrated an association between idiopathic BPPV and decreased serum vitamin D. Decreased serum vitamin D may be a risk factor of BPPV.
Background and Purpose-Isolated nodular infarction has rarely been described in human. The purpose of this study is to report clinical and laboratory findings of isolated nodular infarction. Methods-Eight patients with isolated nodular infarction were recruited from 6 hospitals in Korea. All patients underwent a complete and standardized neurotological evaluation including ocular torsion, bithermal caloric tests, and rotatory chair test in addition to MRI and MR angiography. Results-All patients presented with isolated vertigo and moderate to severe imbalance. The most common manifestation was unilateral nystagmus and falling in the opposite direction, which mimicked peripheral vestibulopathy. Six patients had unilateral lesion, and 2 showed bilateral lesions. The direction of the spontaneous nystagmus was all ipsilesional in the unilateral lesion. However, head impulse and bithermal caloric tests were normal. Other findings include periodic alternating nystagmus, perverted head shaking nystagmus, paroxysmal positional nystagmus, and impaired tilt suppression of the postrotatory nystagmus. Hypoplasia of the ipsilesional vertebral artery was the only abnormal finding on MR angiography in 3 patients. The prognosis was excellent. Conclusions-Isolated
Nicotine concentration labeling on electronic cigarette refill products was often inaccurate but showed improvement recently in products from 1 company. To ensure the safety of refill fluids and DIY products, it is necessary to establish quality control guidelines for the manufacturing and labeling and to monitor products longitudinally.
Vestibular neuritis (VN) mostly involves the superior portion of the vestibular nerve and labyrinth. This study aimed to describe the clinical features of VN involving the inferior vestibular labyrinth and its afferents only. Of the 703 patients with a diagnosis of VN or labyrinthitis at Seoul National University Bundang Hospital from 2004 to 2010, we retrospectively recruited 9 patients (6 women, age range 15-75) with a diagnosis of isolated inferior VN. Diagnosis of isolated inferior VN was based on torsional downbeating spontaneous nystagmus, abnormal head-impulse test (HIT) for the posterior semicircular canal (PC), and abnormal cervical vestibular-evoked myogenic potentials (VEMP) in the presence of normally functioning horizontal and anterior semicircular canals, as determined by normal HIT and bithermal caloric tests. All patients presented with acute vertigo with nausea, vomiting, and imbalance. Three patients also had tinnitus and hearing loss in the involved side. The rotation axis of torsional downbeating spontaneous nystagmus was best aligned with that of the involved PC. HIT was also positive only for the involved PC. Cervical VEMP was abnormal in seven patients, and ocular VEMP was normal in all four patients tested. Ocular torsion and subjective visual vertical tests were mostly within the normal range. Since isolated inferior VN lacks the typical findings of much more prevalent superior VN, it may be mistaken for a central vestibular disorder. Recognition of this rare disorder may help avoid unnecessary workups in patients with acute vestibulopathy.
Corneal transplantation is a typical surgical procedure for severe corneal diseases. However, the waiting time for a donor cornea has gradually increased due to a decrease in supply caused by an aging population and increased cases of laser-based surgeries. Artificial corneas were developed to meet the increase in demand; however, these approaches have suffered from material deterioration resulted by the limited tissue integration. Here, we introduce a cornea-derived decellularized extracellular matrix (Co-dECM) as a bioink for corneal regeneration. The developed Co-dECM bioink had similar quantitative measurement results for collagen and GAGs compared with that of the native cornea and also had the proper transparency for vision. The differentiation potential of human turbinate-derived mesenchymal stem cells (hTMSCs) to a keratocyte lineage was only observed in the Co-dECM group. Moreover, the developed bioink did not have any cytotoxic effect on encapsulated cells for three-dimensional (3D) culture and has great biocompatibility evident by the xeno-implantation of the Co-dECM gel into mice and rabbits for two and one month, respectively. An in vivo safety similar to clinical-grade collagen was seen with the Co-dECM, which helped to maintain the keratocyte-specific characteristics in vivo, compared with collagen. Taken together, the Co-dECM bioink has the potential to be used in various types of corneal diseases based on its corneal-specific ability and design flexibility through 3D cell printing technology.
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