Field-Induced Breakup of Emulsion Droplets Stabilized by Colloidal Particles

We simulate the response of a particle-stabilized emulsion droplet in an external force field, such as gravity, acting equally on all $N$ particles. We show that the field strength required for breakup (at fixed initial area fraction) decreases markedly with droplet size, because the forces act cumulatively, not individually, to detach the interfacial particles. The breakup mode involves the collective destabilization of a solidified particle raft occupying the lower part of the droplet, leading to a critical force per particle that scales approximately as $N^{-1/2}$.Comment: 4 pages, plus 3 pages of supplementary materia

Prediction of progression in idiopathic pulmonary fibrosis using CT scans atbaseline: A quantum particle swarm optimization - Random forest approach

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by an unpredictable progressive declinein lung function. Natural history of IPF is unknown and the prediction of disease progression at the time ofdiagnosis is notoriously difficult. High resolution computed tomography (HRCT) has been used for the diagnosisof IPF, but not generally for monitoring purpose. The objective of this work is to develop a novel predictivemodel for the radiological progression pattern at voxel-wise level using only baseline HRCT scans. Mainly, thereare two challenges: (a) obtaining a data set of features for region of interest (ROI) on baseline HRCT scans andtheir follow-up status; and (b) simultaneously selecting important features from high-dimensional space, andoptimizing the prediction performance. We resolved the first challenge by implementing a study design andhaving an expert radiologist contour ROIs at baseline scans, depending on its progression status in follow-upvisits. For the second challenge, we integrated the feature selection with prediction by developing an algorithmusing a wrapper method that combines quantum particle swarm optimization to select a small number of featureswith random forest to classify early patterns of progression. We applied our proposed algorithm to analyzeanonymized HRCT images from 50 IPF subjects from a multi-center clinical trial. We showed that it yields aparsimonious model with 81.8% sensitivity, 82.2% specificity and an overall accuracy rate of 82.1% at the ROIlevel. These results are superior to other popular feature selections and classification methods, in that ourmethod produces higher accuracy in prediction of progression and more balanced sensitivity and specificity witha smaller number of selected features. Our work is the first approach to show that it is possible to use onlybaseline HRCT scans to predict progressive ROIs at 6 months to 1year follow-ups using artificial intelligence

Expression and Action of Transforming Growth Factor Beta (TGFβ1, TGFβ2, and TGFβ3) during Embryonic Rat Testis Development1

The objective of the current study was to determine the role of transforming growth factor beta (TGF) during seminiferous cord formation and embryonic testis development. The expression pattern of mRNA for TGF isoforms was evaluated during testis development through a quantitative reverse transcription-polymerase chain reaction (QRT-PCR) procedure. Expression of mRNA for TGF1 was highest at postnatal day 0 (P0) and P10. In contrast, TGF2 was high at embryonic day 15 (E15), declined at E16, and showed a transient increase at P0 through P3 of testis development. Interestingly, expression of mRNA for TGF3 was high during embryonic development and then declined after P3. Immunohistochemical localization of TGF1 and TGF2 demonstrated expression in Sertoli cells at E14 and in the seminiferous cords at P0. Selective interstitial cells expressed high concentrations of TGF1 and TGF2 in P0 testis. TGF3 was expressed in selective cells at the junction of the E14 testis and mesonephros. The cells expressing TGF3 in the testis appeared to be preperitubular cells that resided around the seminiferous cords. TGF3 was localized to gonocytes in P0 testis. TGF1 was found to have no influence on seminiferous cord formation in embryonic organ cultures of E13 testis. In contrast, growth of both E13 and E14 embryonic organ cultures was inhibited by TGF1 and resulted in reduced testis size (40% of controls) with fewer cords present. A P0 testis cell culture and thymidine incorporation assay were used to directly examine the effects of recombinant TGF1. TGF1 alone had no influence on thymidine incorporation in P0 testis cell cultures when compared to controls. Interestingly, TGF1 inhibited epi-dermal growth factor (EGF), and 10% calf serum stimulated P0 testis cell growth but not FSH-stimulated growth. Therefore, TGF1 appears to inhibit testis growth in both the embryonic and early postnatal periods. The hormonal regulation of TGF expression was measured using P0 testis cell cultures and a QRT-PCR procedure for each TGF isoform. High concentrations of EGF stimulated expression of mRNA for TGF1 after 24 h but suppressed expression of TGF3. In contrast, there was no effect of FSH on TGF isoform expression. In summary, TGF regulates embryonic and P0 testis growth through inhibiting the actions of positive growth factors such as EGF. In addition, EGF but not FSH appears to regulate TGF isoform expression. Combined observations from the present study demonstrate that TGF iso-forms are differentially expressed and appear to be regulators of testis growth during the embryonic and early postnatal periods

Making sense of Wnt signaling—linking hair cell regeneration to development

Wnt signaling is a highly conserved pathway crucial for development and homeostasis of multicellular organisms. Secreted Wnt ligands bind Frizzled receptors to regulate diverse processes such as axis patterning, cell division, and cell fate specification. They also serve to govern self-renewal of somatic stem cells in several adult tissues. The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions. In the developing mouse inner ear, Wnt signaling plays diverse roles, including specification of the otic placode and patterning of the otic vesicle. At later stages, its activity governs sensory hair cell specification, cell cycle regulation, and hair cell orientation. In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration. This review describes the current knowledge of the roles of Wnt signaling and Wnt-responsive cells in hair cell development and regeneration. We also discuss possible future directions and the potential application and limitation of Wnt signaling in augmenting hair cell regeneration

Expression and Action of Neurotropin-3 and Nerve Growth Factor in Embryonic and Early Postnatal Rat Testis Development

The current study examines the expression and potential actions of neurotropin-3 (NT3), nerve growth factor (NGF), and their receptors during morphological sex determination (seminiferous cord formation) and perinatal rat testis development. The expression of neurotropins and their receptors was analyzed with immunohistochemistry. Cellular localization of neurotropin ligand and receptor proteins changed during embryonic testis development. Neurotropin-3 was localized to Sertoli cells at Embryonic Day 14 (E14), was present in gonocytes at Postnatal Day 0 (P0), and after birth became localized to the interstitium and Sertoli cells (P3–P5). The expression of trk C (the high affinity receptor for NT3) was localized to mesonephric ducts and cells surrounding the cords (E14–E18). In addition, Sertoli cells and preperitubular cells surrounding the cords at E14 also stained for trk C. Neurotropin-3 was expressed in gonocytes and Sertoli cells at P0–P5. Nerve growth factor was detected in Sertoli cells at E14, was clearly in Sertoli and interstitial cells at E16 and E18, and in Sertoli, germ, and interstitial cells from P0–P5. The expression of trk A (the high affinity receptor for NGF) was located in Sertoli and interstitial cells at E16–P5. To determine the actions of neurotropins during embryonic and perinatal testis development, experiments were conducted on E13 and P0 testis. Antisense oligonucleotide experiments with NT3 were used on E13 testis organ cultures to determine effects on seminiferous cord formation. Cord formation was inhibited in 40% of the organ cultures treated with the antisense NT3 oligonucleotides, while no inhibition was observed with sense oligonucleotides. In P0 testis cultures, both NT3 and NGF alone and in combination stimulated thymidine incorporation into DNA. Therefore, the neurotropins are involved in embryonic morphological events (cord formation; NT3) and in growth of the perinatal testis (P0; NT3 and NGF). To define further the growth effects of neurotropins on testis development, expression of transforming growth factor alpha and beta (TGFα and TGFβ) were examined in response to neurotropins. The P0 testis cultures were treated with neurotropins, and expression of mRNA for TGFα and TGFβ was analyzed utilizing a quantitative reverse transcription-polymerase chain reaction assay. Nerve growth factor and NT3 alone or in combination inhibited expression of mRNA for TGFα while NT3 increased mRNA expression of epidermal growth factor receptor. The combination treatment of neurotropins inhibited expression of TGFβ1 and increased expression of TGFβ3. In summary, observations suggest that NT3, NGF, trk A, and trk C are localized to cells critical to seminiferous cord formation and appear to be important regulators of morphological sex determination. In addition to these morphological effects, both NT3 and NGF stimulate P0 testis growth and may elicit their action through altering the expression of locally produced growth factors such as TGFα and TGFβ. Taken together these results suggest that neurotropins are regulators of paracrine cell-cell interactions that result in morphological sex determination and perinatal testis growth

Action of Retinoids on Embryonic and Early Postnatal Testis Development

The current study investigates the hypothesis that retinoids have a role in embryonic testis development. The action of retinoids on testis development and the expression of retinoic acid receptors (RARα, RARβ, RARγ) were examined. In embryonic day 13 (E13; plug date 5 E0) testis organ cultures an RAR-selective agonist and alltrans retinoic acid completely inhibited seminiferous cord formation. In contrast, an RARα-selective antagonist had no effect. RT-PCR demonstrated that RARα messenger RNA (mRNA) was expressed at all developmental time points evaluated, which included embryonic day 14 (E14) through postnatal day 30 (P30). Expression of RARβ mRNA was present at E15 through P2, whereas RARγ mRNA was expressed at E18 through P2. Cellular localization of receptors by immunohistochemistry indicated that RARα was localized to the interstitium at E18 and to the seminiferous cords by P0. RARβ and RARγ were detected in both interstitium and cords at E16 and by E18 were mainly expressed in the cords. At P0 RARβ and RARγ were localized to the germ cell populations. To examine retinoid actions, the growth of P0 testis cultures were investigated. Interestingly, retinol and retinoic acid did not inhibit growth of P0 testis cultures but did inhibit the action of growth stimulators. Retinoic acid inhibited FSH, EGF, and 10% calf serum stimulated growth in P0 testis cultures. The hypothesis tested was that the inhibitory effects of retinoids on P0 testis growth may be mediated through the growth inhibitor, transforming growth factor-b (TGFβ). The action of retinoids on TGFβ mRNA expression was examined in P0 testis cultures. Retinoic acid stimulated TGFβ3 mRNA expression within 24 h and increased expression of TGFβ1 and TGFβ2 after 72 h. Retinol increased expression of TGFβ1 and TGFβ2 but not TGFβ3 after 72 h of treatment. These observations indicate that retinoic acid can influence seminiferous cord formation and testis growth. The inhibitory actions of retinoids may in part be mediated through increased expression of TGFβ isoforms

Gambling and sexual behaviors in African-American adolescents

Objectives: Late adolescence represents a developmental risk period when many youth become involved in multiple forms of high-risk behaviors with adverse consequences. This study assessed the degree to which two such behaviors, adolescent sexual behaviors and gambling, were associated in a community-based sample with a large African-American presence. Study design: Data are derived from a cohort study. This study focuses on 427 African-American participants with complete information on gambling and sexual behaviors by age 18 (72% of original cohort). Gambling involvement and related problems were based on responses to the South Oaks Gambling Screen — Revised for Adolescents. Several questions assessed sexual behaviors, including age of initiation. Multivariable logistic regression models adjusted for demographics, intervention status, impulsivity, depressive and anxiety symptoms, and alcohol and illegal drug use. Results: Almost half of the sample (49%, n = 211) had gambled at least once before age 18. More gamblers than non-gamblers had initiated sexual intercourse by age 18 (aOR: 2.29 [1.16, 4.52]). Among those who had initiated sexual activity, more gamblers than non-gamblers with high impulsivity levels at age 13 (vs. low impulsivity levels) had become pregnant or had impregnated someone. Among those who had initiated sexual activity by age 18, more male gamblers had impregnated someone by age 18 as compared to female gamblers becoming pregnant. Conclusions: Gambling and sexual behaviors often co-occur among adolescents. Such findings prompt the need for the inclusion of gambling, an often overlooked risky behavior, in behavioral prevention/intervention programs targeting adolescents

Identification of antiviral roles for the exon-junction complex and nonsense-mediated decay in flaviviral infection.

West Nile virus (WNV) is an emerging mosquito-borne flavivirus, related to dengue virus and Zika virus. To gain insight into host pathways involved in WNV infection, we performed a systematic affinity-tag purification mass spectrometry (APMS) study to identify 259 WNV-interacting human proteins. RNA interference screening revealed 26 genes that both interact with WNV proteins and influence WNV infection. We found that WNV, dengue and Zika virus capsids interact with a conserved subset of proteins that impact infection. These include the exon-junction complex (EJC) recycling factor PYM1, which is antiviral against all three viruses. The EJC has roles in nonsense-mediated decay (NMD), and we found that both the EJC and NMD are antiviral and the EJC protein RBM8A directly binds WNV RNA. To counteract this, flavivirus infection inhibits NMD and the capsid-PYM1 interaction interferes with EJC protein function and localization. Depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that WNV sequesters PYM1 to protect viral RNA from decay. Together, these data suggest a complex interplay between the virus and host in regulating NMD and the EJC

Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.

BackgroundThere are no effective treatments or validated clinical response markers in systemic sclerosis (SSc). We assessed imaging biomarkers and performed gene expression profiling in a single-arm open-label clinical trial of tyrosine kinase inhibitor dasatinib in patients with SSc-associated interstitial lung disease (SSc-ILD).MethodsPrimary objectives were safety and pharmacokinetics. Secondary outcomes included clinical assessments, quantitative high-resolution computed tomography (HRCT) of the chest, serum biomarker assays and skin biopsy-based gene expression subset assignments. Clinical response was defined as decrease of >5 or >20% from baseline in the modified Rodnan Skin Score (MRSS). Pulmonary function was assessed at baseline and day 169.ResultsDasatinib was well-tolerated in 31 patients receiving drug for a median of nine months. No significant changes in clinical assessments or serum biomarkers were seen at six months. By quantitative HRCT, 65% of patients showed no progression of lung fibrosis, and 39% showed no progression of total ILD. Among 12 subjects with available baseline and post-treatment skin biopsies, three were improvers and nine were non-improvers. Improvers mapped to the fibroproliferative or normal-like subsets, while seven out of nine non-improvers were in the inflammatory subset (p = 0.0455). Improvers showed stability in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), while both measures showed a decline in non-improvers (p = 0.1289 and p = 0.0195, respectively). Inflammatory gene expression subset was associated with higher baseline HRCT score (p = 0.0556). Non-improvers showed significant increase in lung fibrosis (p = 0.0313).ConclusionsIn patients with SSc-ILD dasatinib treatment was associated with acceptable safety profile but no significant clinical efficacy. Patients in the inflammatory gene expression subset showed increase in skin fibrosis, decreasing pulmonary function and worsening lung fibrosis during the study. These findings suggest that target tissue-specific gene expression analyses can help match patients and therapeutic interventions in heterogeneous diseases such as SSc, and quantitative HRCT is useful for assessing clinical outcomes.Trial registrationClinicaltrials.gov NCT00764309