The Notch pathway is an evolutionarily conserved signaling system that is intricately regulated at multiple levels and it influences different aspects of development. In an effort to identify novel components involved in Notch signaling and its regulation, we carried out protein interaction screens which identified non-muscle myosin II Zipper (Zip) as an interacting partner of Notch. Physical interaction between Notch and Zip was further validated by co-immunoprecipitation studies. Immunocytochemical analyses revealed that Notch and Zip co-localize within same cytoplasmic compartment. Different alleles of zip also showed strong genetic interactions with Notch pathway components. Downregulation of Zip resulted in wing phenotypes that were reminiscent of Notch loss-of-function phenotypes and a perturbed expression of Notch downstream targets, Cut and Deadpan. Further, synergistic interaction between Notch and Zip resulted in highly ectopic expression of these Notch targets. Activated Notch-induced tumorous phenotype of larval tissues was enhanced by over-expression of Zip. Notch-Zip synergy resulted in the activation of JNK pathway that consequently lead to MMP activation and proliferation. Taken together, our results suggest that Zip may play an important role in regulation of Notch signaling.

Lymphatic capillaries develop discontinuous cell-cell junctions that permit the absorption of large macromolecules, chylomicrons, and fluid from the interstitium. While excessive vascular endothelial growth factor 2 (VEGFR2) signaling can remodel and seal these junctions, whether and how VEGFR3 can alter lymphatic junctions remains incompletely understood. Here, we use lymphatic-specific Flt4 knockout mice to investigate VEGFR3 signaling in lymphatic junctions. We show that loss of Flt4 prevents specialized button junction formation in multiple tissues and impairs interstitial absorption. Knockdown of FLT4 in human lymphatic endothelial cells results in impaired NOTCH1 expression and activation, and overexpression of the NOTCH1 intracellular domain in Flt4 knockout vessels rescues the formation of button junctions and absorption of interstitial molecules. Together, our data reveal a requirement for VEGFR3 and NOTCH1 signaling in the development of button junctions during postnatal development and may hold clinical relevance to lymphatic diseases with impaired VEGFR3 signaling.

Branching morphogenesis and seamless tube formation in Drosophila melanogaster are essential for the development of vascular and tracheal systems, and instructive in studying complex branched structures such as human organs. Zipper is a myosin II\'s actin-binding heavy chain; hence, it is important for contracting actin, cell proliferation, and cell sheet adhesion for branching of the tracheal system in post-larval development of the D. melanogaster. Nevertheless, the specific role of Zipper in the larva is still in question. This paper intended to investigate the specific role of Zipper in branching morphogenesis and lumenogenesis in early developmental stages. It did so by checking the localization of the protein in the cytoplasm of the terminal cells and also by analyzing the morphology of zipper RNAi loss-of-function mutants in regard to branching and lumen formation in the terminal cells. A rescue experiment of RNAi mutants was also performed to check the sufficiency of Zipper in branching morphogenesis. Confocal imaging showed the localization of Zipper in the cytoplasm of the terminal cells, and respective quantitative analyses demonstrated that zipper RNAi terminal cells develop significantly fewer branches. Such a result hinted that Zipper is required for the regulation of branching in the terminal cells of D. melanogaster. Nevertheless, Zipper is not significantly involved in the formation of seamless tubes. One hypothesis is that Zipper\'s contractility at the lateral epidermis\' leading edge allows cell sheet movement and respective elongation; as a result of such an elongation, further branching may occur in the elongated region of the cell, hence defining branching morphogenesis in the terminal cells of the tracheal system.

UNASSIGNED: Sutures and staples are the mainstay wound closure techniques in total joint arthroplasty. Newer techniques such as zipper devices and novel skin adhesives have emerged because of their potential to decrease operative time and possibly minimize complications. The aim of this study is to compare these newer techniques against conventional sutures with respect to wound complications, closure time, and costs.
UNASSIGNED: A single-center randomized control trial was conducted on 160 patients (52 zipper, 55 suture, 53 mesh) who underwent primary total hip or knee arthroplasty between February 2017 and May 2018. Patients were divided into 3 closure groups: zipper device, monofilament suture plus adhesive, and monofilament plus polyester mesh with adhesive. The primary endpoint was closure time (superficial skin layer). Secondarily we collected perioperative complication rates, including infection, persistent (14-day) wound drainage, 90-day readmission, and emergency room visit rates as well as compared material costs.
UNASSIGNED: There were no differences in baseline characteristics between groups for age, body mass index, and American Society of Anesthesiologists classification. There was a trend toward decreased time to closure for the suture group. There were no significant differences between groups for our secondary endpoint, complications.
UNASSIGNED: Our study shows that the suture group trended toward shorter closure time but suggests that each of the closure methods after total joint arthroplasty has equivalent complication rates. With small differences in closure time and no significant differences in complications, the decision to use one wound closure device or technique over another should be driven by institutional costs and provider familiarity.

We performed an updated meta-analysis to compare the efficacy of the zipper device and sutures for wound closure after surgery. A computerised literature search was performed for published trials in PubMed, Web of Science, the Cochrane Library, and Google Scholar. Two reviewers independently scrutinised the trials, extracted data, and assessed the quality of trials. The primary outcome was surgical site infections (SSI). The secondary outcomes were wound dehiscence, total wound complications, wound closure time, and scar score. Statistical analysis was performed in the Stata 12.0. Of the 130 citations, eight trials (1207 participants) met eligibility criteria and were included. The zipper device achieved a lower SSI rate (RR: 0.63, [95% CI: 0.41-0.96, P = 0.032]), a shorter wound closure time (SMD: -8.53 [95% CI: -11.93 to -5.13, P = 0.000]) and a better scar score (SMD: 0.42 [95% CI: 0.22-0.62, P = 0.000]) than sutures. No significant difference was shown in the incidence of wound dehiscence and total wound complications. Therefore, the zipper device provides the advantages of anti-infection, time-saving, and cosmesis for wound closure.

Rho signaling is a conserved mechanism for generating forces through activation of contractile actomyosin. How this pathway can produce different cell morphologies is poorly understood. In the Drosophila embryonic epithelium, we investigate how Rho signaling controls force asymmetry to drive morphogenesis. We study a distinct morphogenetic process termed \'alignment\'. This process results in striking columns of rectilinear cells connected by aligned cell-cell contacts. We found that this is driven by contractile actomyosin cables that elevate tension along aligning interfaces. Our data show that polarization of Rho effectors, Rok and Dia, directs formation of these cables. Constitutive activation of these effectors causes aligning cells to instead invaginate. This suggests that moderating Rho signaling is essential to producing the aligned geometry. Therefore, we tested for feedback that could fine-tune Rho signaling. We discovered that F-actin exerts negative feedback on multiple nodes in the pathway. Further, we present evidence that suggests that Rok in part mediates feedback from F-actin to Rho in a manner independent of Myo-II. Collectively, our work suggests that multiple feedback mechanisms regulate Rho signaling, which may account for diverse morphological outcomes.

To establish an infection, Salmonella has to interact with eukaryotic cells. Invasion of non-phagocytic cells (i.e., epithelial, fibroblast and endothelial cells) involves either a trigger or a zipper mechanism mediated by the T3SS-1 or the invasin Rck, respectively. Another outer membrane protein, PagN, was also implicated in the invasion. However, other unknown invasion factors have been previously suggested. Our goal was to evaluate the invasion capability of a Salmonella Typhimurium strain invalidated for the three known invasion factors. Non-phagocytic cell lines of several animal origins were tested in a gentamicin protection assay. In most cells, we observed a drastic decrease in the invasion rate between the wild-type and the triple mutant. However, in five cell lines, the triple mutant invaded cells at a similarly high level to the wild-type, suggesting the existence of unidentified invasion factors. For the wild-type and the triple mutant, scanning-electron microscopy, confocal imaging and use of biochemical inhibitors confirmed their cellular uptake and showed a zipper-like mechanism of internalization involving both clathrin- and non-clathrin-dependent pathways. Despite a functional T3SS-1, the wild-type bacteria seemed to use the same entry route as the mutant in our cell model. All together, these results demonstrate the existence of unknown Salmonella invasion factors, which require further characterization.

Many of the major discoveries in the fields of genetics and developmental biology have been made using the fruit fly, Drosophila melanogaster. With regard to heart development, the conserved network of core cardiac transcription factors that underlies cardiogenesis has been studied in great detail in the fly, and the importance of several signaling pathways that regulate heart morphogenesis, such as Slit/Robo, was first shown in the fly model. Recent technological advances have led to a large increase in the genomic data available from patients with congenital heart disease (CHD). This has highlighted a number of candidate genes and gene networks that are potentially involved in CHD. To validate genes and genetic interactions among candidate CHD-causing alleles and to better understand heart formation in general are major tasks. The specific limitations of the various cardiac model systems currently employed (mammalian and fish models) provide a niche for the fly model, despite its evolutionary distance to vertebrates and humans. Here, we review recent advances made using the Drosophila embryo that identify factors relevant for heart formation. These underline how this model organism still is invaluable for a better understanding of CHD.

BACKGROUND: On a daily basis, dermasurgeons are faced with different kinds of wounds that have to be closed. With a plethora of skin closure materials currently available, choosing a solution that combines excellent and rapid cosmetic results with practicality and cost-effectiveness can be difficult, if not tricky.
OBJECTIVE: We aimed to review the available skin closure materials over the past 20 years and the scientific claims behind their effectiveness in repairing various kinds of wounds.
METHODS: The two authors independently searched and scrutinised the literature. The search was performed electronically using Pub Med, the Cochrane Database, Google Scholar and Ovid as search engines to find articles concerning skin closure materials written since 1990.
CONCLUSIONS: Many factors are involved in the choice of skin closure material, including the type and place of the wound, available materials, physician expertise and preferences, and patient age and health. Evidence-based main uses of different skin closure materials are provided to help surgeons choose the appropriate material for different wounds.

The 17- amino acid N-terminal segment of the Huntingtin protein, htt(NT), grows into stable α-helix rich oligomeric aggregates when incubated under physiological conditions. We examined 15 scrambled sequence versions of an htt(NT) peptide for their stabilities against aggregation in aqueous solution at low micromolar concentration and physiological conditions. Surprisingly, given their derivation from a sequence that readily assembles into highly stable α-helical aggregates that fail to convert into β-structure, we found that three of these scrambled peptides rapidly grow into amyloid-like fibrils, while two others also develop amyloid somewhat more slowly. The other 10 scrambled peptides do not detectibly form any aggregates after 100 h incubation under these conditions. We then analyzed these sequences using four previously described algorithms for predicting the tendencies of peptides to grow into amyloid or other β-aggregates. We found that these algorithms-Zyggregator, Tango, Waltz, and Zipper-varied greatly in the number of sequences predicted to be amyloidogenic and in their abilities to correctly identify the amyloid forming members of this scrambled peptide collection. The results are discussed in the context of a review of the sequence and structural factors currently thought to be important in determining amyloid formation kinetics and thermodynamics.