Random, blocky and alternating ordering in supramolecular polymers of chemically bidisperse monomers

As a first step to understanding the role of molecular or chemical polydispersity in self-assembly, we put forward a coarse-grained model that describes the spontaneous formation of quasi-linear polymers in solutions containing two self-assembling species. Our theoretical framework is based on a two-component self-assembled Ising model in which the bidispersity is parameterized in terms of the strengths of the binding free energies that depend on the monomer species involved in the pairing interaction. Depending upon the relative values of the binding free energies involved, different morphologies of assemblies that include both components are formed, exhibiting paramagnetic-, ferromagnetic- or anti ferromagnetic-like order,i.e., random, blocky or alternating ordering of the two components in the assemblies. Analyzing the model for the case of ferromagnetic ordering, which is of most practical interest, we find that the transition from conditions of minimal assembly to those characterized by strong polymerization can be described by a critical concentration that depends on the concentration ratio of the two species. Interestingly, the distribution of monomers in the assemblies is different from that in the original distribution, i.e., the ratio of the concentrations of the two components put into the system. The monomers with a smaller binding free energy are more abundant in short assemblies and monomers with a larger binding affinity are more abundant in longer assemblies. Under certain conditions the two components congregate into separate supramolecular polymeric species and in that sense phase separate. We find strong deviations from the expected growth law for supramolecular polymers even for modest amounts of a second component, provided it is chemically sufficiently distinct from the main one.Comment: Submitted to Macromolecules, 6 figures. arXiv admin note: substantial text overlap with arXiv:1111.176

Determination of Membrane Protein Transporter Oligomerization in Native Tissue Using Spatial Fluorescence Intensity Fluctuation Analysis

Membrane transporter proteins exist in a complex dynamic equilibrium between various oligomeric states that include monomers, dimers, dimer of dimers and higher order oligomers. Given their sub-optical microscopic resolution size, the oligomerization state of membrane transporters is difficult to quantify without requiring tissue disruption and indirect biochemical methods. Here we present the application of a fluorescence measurement technique which combines fluorescence image moment analysis and spatial intensity distribution analysis (SpIDA) to determine the oligomerization state of membrane proteins in situ. As a model system we analyzed the oligomeric state(s) of the electrogenic sodium bicarbonate cotransporter NBCe1-A in cultured cells and in rat kidney. The approaches that we describe offer for the first time the ability to investigate the oligomeric state of membrane transporter proteins in their native state

A Calorimetric Characterization of Cr(VI)-Reducing Arthrobacter oxydans

This is the first of a series of calorimetric studies designed to characterize and understand survival mechanisms of metal-reducing bacteria isolated from metal-polluted environments. In this paper we introduce a new concept of thermal spectrum of the endothermic melting of complex biological systems (e.g., proteins, nucleic acids, ribosomes, membrane structures) in intact cells. All thermal spectra measured are thermograms that describe the temperature dependence of heat capacity change of the complex systems of biologically active substances in bacterial cells. This new concept of thermal spectrum was applied to investigate spectral features from intact cells of Cr(VI)-reducer Arthrobacter oxydans at different points of their growth conditions and stages. Over the temperature range of 40–105°C, we observed that spectral changes are particularly significant in the 40–90°C interval. This may correspond to the orderly changes in subcellular structural elements: proteins, ribosomes and RNA, membranes, and various structural elements of the cell wall during different points of the growth cycle and growth conditions. Spectral changes in the 90–105°C region are less pronounced, implicating that the structural composition of DNA-Protein (DNP) complexes may change little

Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000-2020.

OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], 90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level

Genomic, Proteomic and Physiological Characterization of a T5-like Bacteriophage for Control of Shiga Toxin-Producing Escherichia coli O157:H7

Despite multiple control measures, Escherichia coli O157:H7 (STEC O157:H7) continues to be responsible for many food borne outbreaks in North America and elsewhere. Bacteriophage therapy may prove useful for controlling this pathogen in the host, their environment and food. Bacteriophage vB_EcoS_AKFV33 (AKFV33), a T5-like phage of Siphoviridae lysed common phage types of STEC O157:H7 and not non-O157 E. coli. Moreover, STEC O157:H7 isolated from the same feedlot pen from which the phage was obtained, were highly susceptible to AKFV33. Adsorption rate constant and burst size were estimated to be 9.31×10−9 ml/min and 350 PFU/infected cell, respectively. The genome of AKVF33 was 108,853 bp (38.95% G+C), containing 160 open reading frames (ORFs), 22 tRNA genes and 32 strong promoters recognized by host RNA polymerase. Of 12 ORFs without homologues to T5-like phages, 7 predicted novel proteins while others exhibited low identity (<60%) to proteins in the National Centre for Biotechnology Information database. AKVF33 also lacked the L-shaped tail fiber protein typical of T5, but was predicted to have tail fibers comprised of 2 novel proteins with low identity (37–41%) to tail fibers of E. coli phage phiEco32 of Podoviridae, a putative side tail fiber protein of a prophage from E. coli IAI39 and a conserved domain protein of E. coli MS196-1. The receptor-binding tail protein (pb5) shared an overall identify of 29–72% to that of other T5-like phages, with no region coding for more than 6 amino acids in common. Proteomic analysis identified 4 structural proteins corresponding to the capsid, major tail, tail fiber and pore-forming tail tip (pb2). The genome of AKFV33 lacked regions coding for known virulence factors, integration-related proteins or antibiotic resistance determinants. Phage AKFV33 is a unique, highly lytic STEC O157:H7-specific T5-like phage that may have considerable potential as a pre- and post-harvest biocontrol agent

Regulation of pH During Amelogenesis

During amelogenesis, extracellular matrix proteins interact with growing hydroxyapatite crystals to create one of the most architecturally complex biological tissues. The process of enamel formation is a unique biomineralizing system characterized first by an increase in crystallite length during the secretory phase of amelogenesis, followed by a vast increase in crystallite width and thickness in the later maturation phase when organic complexes are enzymatically removed. Crystal growth is modulated by changes in the pH of the enamel microenvironment that is critical for proper enamel biomineralization. Whereas the genetic bases for most abnormal enamel phenotypes (amelogenesis imperfecta) are generally associated with mutations to enamel matrix specific genes, mutations to genes involved in pH regulation may result in severely affected enamel structure, highlighting the importance of pH regulation for normal enamel development. This review summarizes the intra- and extracellular mechanisms employed by the enamel-forming cells, ameloblasts, to maintain pH homeostasis and, also, discusses the enamel phenotypes associated with disruptions to genes involved in pH regulation

Применение алгоритма искусственного интеллекта для оценки минеральной плотности тел позвонков по данным компьютерной томографии

Goal: To develop a method for automated assessment of the volumetric bone mineral density (BMD) of the vertebral bodies using an artificial intelligence (AI) algorithm and a phantom modeling method.Materials and Methods: Evaluation of the effectiveness of the AI algorithm designed to assess BMD of the vertebral bodies based on chest CT data. The test data set contains 100 patients aged over 50 y.o.; the ratio between the subjects with/without compression fractures (Сfr) is 48/52. The X-ray density (XRD) of vertebral bodies at T11-L3 was measured by experts and the AI algorithm for 83 patients (205 vertebrae). We used a recently developed QCT PK (Quantitative Computed Tomography Phantom Kalium) method to convert XRD into BMD followed by building calibration lines for seven 64-slice CT scanners. Images were taken from 1853 patients and then processed by the AI algorithm after the calibration. The male to female ratio was 718/1135.Results: The experts and the AI algorithm reached a strong agreement when comparing the measurements of the XRD. The coefficient of determination was R2=0.945 for individual vertebrae (T11-L3) and 0.943 for patients (p=0.000). Once the subjects from the test sample had been separated into groups with/without Сfr, the XRD data yielded similar ROC AUC values for both the experts – 0.880, and the AI algorithm – 0.875. When calibrating CT scanners using a phantom containing BMD samples made of potassium hydrogen phosphate, the following averaged dependence formula BMD =0.77*HU-1.343 was obtained. Taking into account the American College Radiology criteria for osteoporosis, the cut-off value of BMD&lt;80 mg/ml was 105.6HU; for osteopenia BMD&lt;120 mg/ml was 157.6HU. During the opportunistic assessment of BMD in patients aged above 50 years using the AI algorithm, osteoporosis was detected in 31.72% of female and 18.66% of male subjects.Conclusions: This paper demonstrates good comparability for the measurements of the vertebral bodies’ XRD performed by the AI morphometric algorithm and the experts. We presented a method and demonstrated great effectiveness of opportunistic assessment of vertebral bodies’ BMD based on computed tomography data using the AI algorithm and the phantom modeling.Цель работы: разработать методику автоматизированной оценки объемной минеральной плотности кости (МПК) тел позвонков с помощью алгоритма искусственного интеллекта (ИИ) и метода фантомного моделирования.Материалы и методы: Для оценки эффективности алгоритма ИИ, проводящего измерение МПК тел позвонков по данным КТ органов грудной клетки (ОГК), подготовлен набор данных: 100 пациентов старше 50 лет и отношением с/без компрессионных переломов (КП) 48/52. Из них у 83 алгоритмом ИИ и экспертами была измерена рентгеновская плотность (РП) тел позвонков на уровне Th11-L3 (205 позвонков). Для перевода РП (HU) в МПК применялась разработанная ранее методика ККТ ФК (Количественная компьютерная томография фантом калиевый) с построением калибровочных прямых для семи 64-срезовых КТ сканеров. После проведения калибровки были выполнены и обработаны алгоритмом ИИ КТ ОГК 1853 пациентов в соотношении мужчин и женщин составило 718/1135.Результаты: В ходе оценки эффективности алгоритма ИИ получено хорошее соответствие при сравнении измерений МПК по данным экспертов и алгоритма ИИ. Коэффициент детерминации составил R2= 0,945 для отдельных позвонков (Th11-L3) и 0,943 для пациентов (р=0,000). При разделении пациентов из тестовой выборки на группы с/без КП по данным РП были получены сходные показатели ROC AUC для экспертной разметки 0,880 и по данным алгоритма ИИ 0,875. При калибровке КТ сканеров с помощью фантома, содержащего образцы МПК на основе гидрофосфата калия, получена усредненная формула зависимости МПК=0,77*HU-1,343. С учетом критериев American College Radiology для остеопороза граничное значение МПК&lt;80 мг/мл составило 105,6HU для остеопении МПК&lt;120 мг/мл – 157,6HU. При оппортунистическом определении МПК у пациентов старше 50 лет по данным алгоритма ИИ было установлено, что остеопороз выявлен у 31,72% женщин и 18,66% мужчин.Вывод: Продемонстрирована хорошая сопоставимость результатов определения РП тел позвонков по данным морфометрического алгоритма ИИ и при экспертной разметке. Предложена методика и продемонстрирована эффективность оппортунистического определения МПК тел позвонков по данным КТ с помощью алгоритма ИИ и использования фантомного моделирования

Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women

Progression From Paroxysmal to Persistent Atrial Fibrillation. Clinical Correlates and Prognosis

Objectives: We investigated clinical correlates of atrial fibrillation (AF) progression and evaluated the prognosis of patients demonstrating AF progression in a large population. Background: Progression of paroxysmal AF to more sustained forms is frequently seen. However, not all patients will progress to persistent AF. Methods: We included 1,219 patients with paroxysmal AF who participated in the Euro Heart Survey on AF and had a known rhythm status at follow-up. Patients who experienced AF progression after 1 year of follow-up were identified. Results: Progression of AF occurred in 178 (15%) patients. Multivariate analysis showed that heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension were the only independent predictors of AF progression. Using the regression coefficient as a benchmark, we calculated the HATCH score. Nearly 50% of the patients with a HATCH score &gt;5 progressed to persistent AF compared with only 6% of the patients with a HATCH score of 0. During follow-up, patients with AF progression were more often admitted to the hospital and had more major adverse cardiovascular events. Conclusions: A substantial number of patients progress to sustained AF within 1 year. The clinical outcome of these patients regarding hospital admissions and major adverse cardiovascular events was worse compared with patients demonstrating no AF progression. Factors known to cause atrial structural remodeling (age and underlying heart disease) were independent predictors of AF progression. The HATCH score may help to identify patients who are likely to progress to sustained forms of AF in the near future. \ua9 2010 American College of Cardiology Foundation