RESUMO
Building functional mimics of cell membranes is an important task toward the development of synthetic cells. So far, lipid and amphiphilic block copolymers are the most widely used amphiphiles with the bilayers by the former lacking stability while membranes by the latter are typically characterized by very slow dynamics. Herein, a new type of Janus dendrimer containing a zwitterionic phosphocholine hydrophilic headgroup (JDPC ) and a 3,5-substituted dihydrobenzoate-based hydrophobic dendron is introduced. JDPC self-assembles in water into zwitterionic dendrimersomes (z-DSs) that faithfully recapitulate the cell membrane in thickness, flexibility, and fluidity, while being resilient to harsh conditions and displaying faster pore closing dynamics in the event of membrane rupture. This enables the fabrication of hybrid DSs with components of natural membranes, including pore-forming peptides, structure-directing lipids, and glycans to create raft-like domains or onion vesicles. Moreover, z-DSs can be used to create active synthetic cells with life-like features that mimic vesicle fusion and motility as well as environmental sensing. Despite their fully synthetic nature, z-DSs are minimal cell mimics that can integrate and interact with living matter with the programmability to imitate life-like features and beyond.
Assuntos
Membrana CelularRESUMO
The integration of active cell machinery with synthetic building blocks is the bridge toward developing synthetic cells with biological functions and beyond. Self-replication is one of the most important tasks of living systems, and various complex machineries exist to execute it. In Escherichia coli, a contractile division ring is positioned to mid-cell by concentration oscillations of self-organizing proteins (MinCDE), where it severs membrane and cell wall. So far, the reconstitution of any cell division machinery has exclusively been tied to liposomes. Here, the reconstitution of a rudimentary bacterial divisome in fully synthetic bicomponent dendrimersomes is shown. By tuning the membrane composition, the interaction of biological machinery with synthetic membranes can be tailored to reproduce its dynamic behavior. This constitutes an important breakthrough in the assembly of synthetic cells with biological elements, as tuning of membrane-divisome interactions is the key to engineering emergent biological behavior from the bottom-up.
Assuntos
Células Artificiais , Proteínas de Escherichia coli , Proteínas de Bactérias/metabolismo , Divisão Celular , Parede Celular/metabolismo , Escherichia coli/metabolismoRESUMO
The construction of biomembranes that faithfully capture the properties and dynamic functions of cell membranes remains a challenge in the development of synthetic cells and their application. Here a new concept for synthetic cell membranes based on the self-assembly of amphiphilic comb polymers into vesicles, termed ionic combisomes (i-combisomes) is introduced. These combs consist of a polyzwitterionic backbone to which hydrophobic tails are linked by electrostatic interactions. Using a range of microscopies and molecular simulations, the self-assembly of a library of combs in water is screened. It is discovered that the hydrophobic tails form the membrane's core and force the backbone into a rod conformation with nematic-like ordering confined to the interface with water. This particular organization resulted in membranes that combine the stability of classic polymersomes with the biomimetic thickness, flexibility, and lateral mobility of liposomes. Such unparalleled matching of biophysical properties and the ability to locally reconfigure the molecular topology of its constituents enable the harboring of functional components of natural membranes and fusion with living bacteria to "hijack" their periphery. This provides an almost inexhaustible palette to design the chemical and biological makeup of the i-combisomes membrane resulting in a powerful platform for fundamental studies and technological applications.
Assuntos
Biomimética , Lipossomos , Interações Hidrofóbicas e Hidrofílicas , Lipossomos/química , Polímeros/química , ÁguaRESUMO
It has been established that a newly developed cyclopentadienyl rhodium(III) [CpA RhIII ] complex, bearing an acidic secondary amide moiety on the Cp ring, is able to catalyze the ortho-bromination of O-phenyl carbamates with N-bromosuccinimide (NBS) at room temperature. The presence of the acidic secondary amide moiety on the CpA ligand accelerates the bromination by the hydrogen bond between the acidic NH group of the CpA ligand and the carbonyl group of NBS.
RESUMO
The choice of the standard population is important when calculating adjusted rates for a military population: results can influence policies and funding allocations for programs and initiatives for suicide prevention. We describe the methodological considerations and decision-making process used in choosing a standard population for adjusting rates to compare suicide among US Army soldiers and the general US population. We examined 5 different standard populations, using the direct method to adjust annual suicide rates for the Army and the US population, 2004 to 2015, for age and for age and sex. The pattern of the Army and US population age- and sex-adjusted rates remained consistent with crude rates when adjusted to any of the Army standard population distributions. Using an Army distribution as the standard population produces suicide rates consistent with routine messaging about suicide trends among Army soldiers.
Assuntos
Militares/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: Positive volume-outcome relationships in esophagectomy have prompted support for regionalization of care; however, outcomes have not recently been analyzed. This study examines national trends in provision of esophagectomy and reassesses the volume-outcome relationship in light of changing practice patterns and training paradigms. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2006. Quantification of patients' comorbidities was made using the Charlson Index. Using logistic regression modeling, institutions' annual case volumes were correlated with risk-adjusted outcomes over time, as well as presence or absence of fellowship and residency training programs. RESULTS: A nationwide total of 57,676 esophagectomies were recorded. In-hospital unadjusted mortality fell from 12% to 7%. Adjusting for comorbidities, greater esophagectomy volume was associated with improvements in the incidence of most measured complications, though mortality increased once greater than 100 cases were performed. Hospitals supporting fellowship training or a surgical residency program did not have higher rates of mortality or total complications. CONCLUSIONS: The current national mortality rate of 7% following esophagectomy is higher than is reported in most contemporary case series. A greater annual esophagectomy volume improves outcomes, but only up to a point. Current training paradigms are safe.
Assuntos
Adenocarcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Adenocarcinoma/epidemiologia , Adenocarcinoma/mortalidade , Comorbidade , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/mortalidade , Esofagectomia/tendências , Bolsas de Estudo , Gastroenterologia/educação , Mortalidade Hospitalar , Humanos , Internato e Residência , Modelos Logísticos , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
The distinction awards pay scheme for consultants has been the subject of controversy since its introduction in 1948. It has lacked transparency and has been criticised for being inequitable. Many academic consultants receive awards without fulfilling the required service commitment. Chief executives are turning a blind eye to this. Proposals for a revised scheme, due to take effect in April 2003, only address some of the shortcomings.