The Preparation and Crystal Structures of Octaoxoketocalix[8]arene Derivatives: The Ketocalixarene Counterparts of the Largest "Major" Calixarene.

The purpose of this study was to synthesize and structurally characterize ketocalixarenes (i.e., calixarenes where the bridging methylene bridges are replaced by carbonyl groups) derived from the largest "major" calixarene, namely --butylcalix[8]arene .

Focal adhesions contain three specialized actin nanoscale layers.

Focal adhesions (FAs) connect inner workings of cell to the extracellular matrix to control cell adhesion, migration and mechanosensing. Previous studies demonstrated that FAs contain three vertical layers, which connect extracellular matrix to the cytoskeleton. By using super-resolution iPALM microscopy, we identify two additional nanoscale layers within FAs, specified by actin filaments bound to tropomyosin isoforms Tpm1.

Leishmania profilin interacts with actin through an unusual structural mechanism to control cytoskeletal dynamics in parasites.

Diseases caused by Leishmania and Trypanosoma parasites are a major health problem in tropical countries. Because of their complex life cycle involving both vertebrate and insect hosts, and >1 billion years of evolutionarily distance, the cell biology of trypanosomatid parasites exhibits pronounced differences to animal cells. For example, the actin cytoskeleton of trypanosomatids is divergent when compared with other eukaryotes.

A Quasi-Experimental Assessment of the Effect of the 2009 WIC Food Package Revisions on Breastfeeding Outcomes.

Breastfeeding rates among infants participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) are consistently lower than those of WIC nonparticipants. The 2009 WIC food package revisions were intended to incentivize breastfeeding among the WIC population. To examine the effectiveness of this policy change, we estimated an intent-to-treat regression-adjusted difference-in-difference model with propensity score weighting, an approach that allowed us to control for both secular trends in breastfeeding and selection bias.

Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions.

Filopodia are actin-rich membrane protrusions essential for cell morphogenesis, motility, and cancer invasion. How cells control filopodium initiation on the plasma membrane remains elusive. We performed experiments in cellulo, in vitro, and in silico to unravel the mechanism of filopodium initiation driven by the membrane curvature sensor IRSp53 (insulin receptor substrate protein of 53 kDa).

Caldesmon controls stress fiber force-balance through dynamic cross-linking of myosin II and actin-tropomyosin filaments.

Contractile actomyosin bundles are key force-producing and mechanosensing elements in muscle and non-muscle tissues. Whereas the organization of muscle myofibrils and mechanism regulating their contractility are relatively well-established, the principles by which myosin-II activity and force-balance are regulated in non-muscle cells have remained elusive. We show that Caldesmon, an important component of smooth muscle and non-muscle cell actomyosin bundles, is an elongated protein that functions as a dynamic cross-linker between myosin-II and tropomyosin-actin filaments.

Structural basis of rapid actin dynamics in the evolutionarily divergent Leishmania parasite.

Actin polymerization generates forces for cellular processes throughout the eukaryotic kingdom, but our understanding of the 'ancient' actin turnover machineries is limited. We show that, despite > 1 billion years of evolution, pathogenic Leishmania major parasite and mammalian actins share the same overall fold and co-polymerize with each other. Interestingly, Leishmania harbors a simple actin-regulatory machinery that lacks cofilin 'cofactors', which accelerate filament disassembly in higher eukaryotes.

SHANK3 conformation regulates direct actin binding and crosstalk with Rap1 signaling.

Actin-rich cellular protrusions direct versatile biological processes from cancer cell invasion to dendritic spine development. The stability, morphology, and specific biological functions of these protrusions are regulated by crosstalk between three main signaling axes: integrins, actin regulators, and small guanosine triphosphatases (GTPases). SHANK3 is a multifunctional scaffold protein, interacting with several actin-binding proteins and a well-established autism risk gene.

A functional family of fluorescent nucleotide analogues to investigate actin dynamics and energetics.

Actin polymerization provides force for vital processes of the eukaryotic cell, but our understanding of actin dynamics and energetics remains limited due to the lack of high-quality probes. Most current probes affect dynamics of actin or its interactions with actin-binding proteins (ABPs), and cannot track the bound nucleotide. Here, we identify a family of highly sensitive fluorescent nucleotide analogues structurally compatible with actin.

Tropomodulins Control the Balance between Protrusive and Contractile Structures by Stabilizing Actin-Tropomyosin Filaments.

Eukaryotic cells have diverse protrusive and contractile actin filament structures, which compete with one another for a limited pool of actin monomers. Numerous actin-binding proteins regulate the dynamics of actin structures, including tropomodulins (Tmods), which cap the pointed end of actin filaments. In striated muscles, Tmods prevent actin filaments from overgrowing, whereas in non-muscle cells, their function has remained elusive.

Mechanism of synergistic actin filament pointed end depolymerization by cyclase-associated protein and cofilin.

The ability of cells to generate forces through actin filament turnover was an early adaptation in evolution. While much is known about how actin filaments grow, mechanisms of their disassembly are incompletely understood. The best-characterized actin disassembly factors are the cofilin family proteins, which increase cytoskeletal dynamics by severing actin filaments.

Feasibility of a Multidisciplinary and Culturally Adapted Pediatric Weight Management Program for Latino Families: Results From the Vidas Activas y Familias Saludables Pilot Study.

Objective: To determine the feasibility of a pediatric weight management program for low-income Latino families.

Methods: A pretest-posttest pilot study was conducted among 60 Latino children, aged 4-9, who were overweight/obese (body mass index-for-age ≥85th percentile). The 10-week group-based community program addressed diet, exercise, and behavior modification.

Racial and Ethnic Differences in Reasons for Breastfeeding Cessation Among Women Participating in the Special Supplemental Nutrition Program for Women, Infants, and Children.

Introduction: Breastfeeding rates among women participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) are lower compared with those of nonparticipants. The objective of this study was to assess racial and ethnic differences in self-reported reasons for breastfeeding cessation during the first year postpartum.

Methods: This was a secondary analysis of data from women participating in the WIC Infant and Toddler Feeding Practices Study-2.

UTAP: User-friendly Transcriptome Analysis Pipeline.

Background: RNA-Seq technology is routinely used to characterize the transcriptome, and to detect gene expression differences among cell types, genotypes and conditions. Advances in short-read sequencing instruments such as Illumina Next-Seq have yielded easy-to-operate machines, with high throughput, at a lower price per base. However, processing this data requires bioinformatics expertise to tailor and execute specific solutions for each type of library preparation.

Calponin-3 is critical for coordinated contractility of actin stress fibers.

Contractile actomyosin bundles, stress fibers, contribute to morphogenesis, migration, and mechanosensing of non-muscle cells. In addition to actin and non-muscle myosin II (NMII), stress fibers contain a large array of proteins that control their assembly, turnover, and contractility. Calponin-3 (Cnn3) is an actin-binding protein that associates with stress fibers.

Part-time practice in healthcare: Impact on operational versus medical performance.

We explore how reliance on part-time medical staff affects operational and medical outcome performance in two general surgery departments Whereas prior research has indicated that operational performance is positively associated with medical performance, we find that heavier reliance on part-time practice may deteriorate operational performance but not necessarily medical-outcome performance. For so-called "complex" patients, reliance on part-time practice may even override the effect of patients' characteristics on medical-outcome performance. This result calls into question common perceptions in behavior marketing literature regarding part-time employees' working patterns and efficiency, and thereby provides a new perspective regarding current labor-market trends.

Zebrafish GDNF and its co-receptor GFRα1 activate the human RET receptor and promote the survival of dopaminergic neurons in vitro.

Glial cell line-derived neurotrophic factor (GDNF) is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFRα1) and receptor tyrosine kinase "RET", several signaling pathways crucial in the development and sustainment of multiple neuronal populations. We decided to study whether non-mammalian orthologs of these three proteins have conserved their function: can they activate the human counterparts? Using the baculovirus expression system, we expressed and purified Danio rerio RET, and its binding partners GFRα1 and GDNF, and Drosophila melanogaster RET and two isoforms of co-receptor GDNF receptor-like. Our results report high-level insect cell expression of post-translationally modified and dimerized zebrafish RET and its binding partners.

Tropomyosin Isoforms Specify Functionally Distinct Actin Filament Populations In Vitro.

Actin filaments assemble into a variety of networks to provide force for diverse cellular processes [1]. Tropomyosins are coiled-coil dimers that form head-to-tail polymers along actin filaments and regulate interactions of other proteins, including actin-depolymerizing factor (ADF)/cofilins and myosins, with actin [2-5]. In mammals, >40 tropomyosin isoforms can be generated through alternative splicing from four tropomyosin genes.

The structure and catalytic cycle of a sodium-pumping pyrophosphatase.

Membrane-integral pyrophosphatases (M-PPases) are crucial for the survival of plants, bacteria, and protozoan parasites. They couple pyrophosphate hydrolysis or synthesis to Na(+) or H(+) pumping. The 2.