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To Tie or Not to Tie? That Is the Question.

ABSTRACT: In this review, we provide an overview of entangled proteins. Around 6% of protein structures deposited in the PBD are entangled, forming knots, slipknots, lassos and links. We present theoretical methods and tools that enabled discovering and classifying such structures. We discuss the advantages and disadvantages of the non-trivial topology in proteins, based on available data about folding, stability, biological properties and evolutionary conservation. We also formulate intriguing and challenging questions on the border of biophysics, bioinformatics, biology and mathematics, which arise from the discovery of an entanglement in proteins. Finally, we discuss possible applications of entangled proteins in medicine and nanotechnology, such as the chance to design super stable proteins, whose stability could be controlled by chemical potential.

SUBMITTER: Dabrowski-Tumanski P

PROVIDER: S-EPMC6418553 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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To Tie or Not to Tie? That Is the Question.

Dabrowski-Tumanski Pawel P Sulkowska Joanna I JI

Polymers 20170916 9

In this review, we provide an overview of entangled proteins. Around 6% of protein structures deposited in the PBD are entangled, forming knots, slipknots, lassos and links. We present theoretical methods and tools that enabled discovering and classifying such structures. We discuss the advantages and disadvantages of the non-trivial topology in proteins, based on available data about folding, stability, biological properties and evolutionary conservation. We also formulate intriguing and challe ...[more]

PMID: 30965758

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Project description:Objectives/hypothesisNumerous symptoms may arise that prevent mother-infant dyads from maintaining desired breastfeeding intervals. Investigations into treatments that positively influence breastfeeding outcomes allow for improved patient counseling for treatment decisions to optimize breastfeeding quality. This investigation aimed to determine the impact of surgical tongue-tie/lip-tie release on breastfeeding impairment.Study designProspective, cohort study from June 2014 to April 2015 in a private practice setting.MethodsStudy participants consisted of breastfeeding mother-infant (0-12 weeks of age) dyads with untreated ankyloglossia and/or tethered maxillary labial frenula who completed preoperative, 1 week, and 1 month postoperative surveys consisting of the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF), visual analog scale (VAS) for nipple pain severity, and the revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R). Breastmilk intake was measured preoperatively and 1 week postoperatively.ResultsA total of 237 dyads were enrolled after self-electing laser lingual frenotomy and/or maxillary labial frenectomy. Isolated posterior tongue-tie was identified in 78% of infants. Significant postoperative improvements were reported between mean preoperative scores compared to 1 week and 1 month scores of the BSES-SF (F(2) = 212.3; P < .001), the I-GERQ-R (F(2) = 85.3; P < .001), and VAS pain scale (F(2) = 259.8; P < .001). Average breastmilk intake improved 155% from 3.0 (2.9) to 4.9 (4.5) mL/min (P < .001).ConclusionsSurgical release of tongue-tie/lip-tie results in significant improvement in breastfeeding outcomes. Improvements occur early (1 week postoperatively) and continue to improve through 1 month postoperatively. Improvements were demonstrated in both infants with classic anterior tongue-tie and less obvious posterior tongue-tie. This study identifies a previously under-recognized patient population that may benefit from surgical intervention if abnormal breastfeeding symptoms exist.Level of evidence2c Laryngoscope, 127:1217-1223, 2017.

Project description:The endothelial TIE1 and TIE2 receptor tyrosine kinases form a distinct subfamily characterized by their unique extracellular domains. Together with the angiopoietin growth factors (ANGPT1, ANGPT2, ANGPT4, also abbreviated as ANG), the TIE receptors form an endothelial specific signaling pathway with important functions in the regulation of lymphatic and cardiovascular development and vascular homeostasis. Angiopoietins exist in multimeric forms that activate the TIE receptors via unique mechanism. In endothelial cell–cell contacts, angiopoietins induce the formation of homomeric in trans TIE receptor complexes extending across the cell junctions, whereas matrix-bound angiopoietin-1 (ANG1) activates the TIE receptors in a cis configuration. In comparison to the vascular endothelial growth factor receptors, the TIE receptors undergo little ubiquitin-mediated degradation after activation, whereas TIE2 signaling is negatively regulated by the vascular endothelial protein tyrosine phosphatase, VE-PTP. ANG1 activation of TIE2 supports vascular stabilization, whereas angiopoietin-2 (ANG2), a context-dependent weak TIE2 agonist/antagonist, promotes pathological tumor angiogenesis, vascular permeability, and inflammation. Recently, ANG2 has been found to mediate some of its vascular destabilizing and angiogenic functions via integrin signalling. The circulating levels of ANG2 are increased in cancer, and in several human diseases associated with inflammation and vascular leak, for example, in sepsis. Blocking of ANG2 has emerged as a potential novel therapeutic strategy for these diseases. In addition, preclinical results demonstrate that genetic TIE1 deletion in mice inhibits the vascularization and growth of tumor isografts and protects from atherosclerosis, with little effect on normal vascular homeostasis in adult mice. The ability of the ANG-TIE pathway to control vessel stability and angiogenesis makes it an interesting vascular target for the treatment of the various diseases.

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To Tie or Not to Tie? That Is the Question.

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To Tie or Not to Tie? That Is the Question.

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