Pediatric Electrical Stimulation for Limb Lengthening: A Non-Invasive Approach

Leg Length Discrepancy (LLD) is a problematic ailment for children as the differences in limb lengths can lead to scoliosis, hip, knee, and ankle problems, and back pain. If LLD is untreated, the symptoms will worsen as the child matures. Today LLD is corrected by using the Ilizarov Method, which uses pins that are externally attached to the broken bone for extension over time using a fixator or by using internal plates that do not require externalization. In our project we aim to use external electrical stimulation to correct the limb discrepancies. Several companies, such as Zimmer Biomet, have created an external bone growth stimulator that uses capacitive coupled electrical stimulation to promote bone growth. However, these devices are not designed for use in children. We have designed a device that will also use capacitive coupling to electrically stimulate bone growth in children. We began by using a computational model to measure the optimal current to achieve our goal. Our device was designed to be simple, easy, and comfortable for pediatric patients. Our device consists of an integrated circuit with two portions, a power supply and an oscillator section to generate the square wave intended to deliver the voltage to the patient to stimulate growth at the epiphyseal plate. The device, meant to deliver therapy during the patient’s sleep, allows the patient to wear the device comfortably while not disrupting their everyday life, while simultaneously fixing the discrepancy

An Investigation of Chlorine Ligands in Transition-Metal Complexes via 35Cl Solid-State NMR and Density Functional Theory Calculations

35Cl solid state NMR (SSNMR), in tandem with 35Cl NQR and density functional theory calculations, was used to characterize chlorine ligands in a series of transition-metal complexes exhibiting structural motifs common to organometallic catalysts. The differentiation of the various chlorine environments was possible, and insight into the origins of the 35Cl electric field gradient tensor parameters was provided. The applicability of 35Cl SSNMR to the study of surface supported transition-metal complexes was demonstrated, validating the use of this technique in the characterization of heterogeneous catalysts

NMR-Enhanced Crystallography Aids Open Metal–Organic Framework Discovery Using Solvent-Free Accelerated Aging

We demonstrate the combined use of NMR-enhanced crystallography and solvent-free synthesis by accelerated aging (AA), for the discovery and structural characterization of a novel cadmium-based open metal–organic framework (MOF) belonging to the class of zeolitic imidazolate frameworks (ZIFs). Although solid-state NMR spectroscopy has been used to assist in structural characterization of crystalline solids by powder X-ray diffraction (PXRD), typically through quantification of the contents of the asymmetric unit, this work highlights how it can take a more active role in guiding structure determination, by elucidating the coordination environment of the metal node in a novel MOFs. Exploration of AA reactions of cadmium oxide (CdO) and 2-methylimidazole (HMeIm) enabled the synthesis of not only the previously reported yqt1-topology framework but also a new material (1) exhibiting a Cd/MeIm ratio of 1:3, contrasting the 1:2 ratio expected for a ZIF. Structural characterization of 1 was enabled by using 111Cd solid-state nuclear magnetic resonance (SSNMR) to provide information on the coordination environment of the cadmium node. Specifically, 111Cd SSNMR experiments were conducted on a series of model compounds to correlate the cadmium coordination environment to the observed isotropic chemical shift, δiso(111Cd), followed by multinuclear SSNMR experiments on 1 to determine the nature of the metal coordination environment and the number of distinct chemical sites. This information was used in refinement of the molecular level structure from the available PXRD data, a technique termed NMR-enhanced crystallography, revealing that 1 is an open diamondoid (dia) topology Cd(MeIm)2 framework based on Cd2+ ions tetrahedrally coordinated with MeIm– ligands and additional HMeIm guest molecules within the framework pores. Although AA was initially devised as a clean, mild route for making MOFs, these results provide a proof-of-principle of how, by combining it with SSNMR spectroscopy as a means to overcome limitations of PXRD structure determination, it can be used to screen for new solid phases in the absence of solvents, high temperatures, or mechanical impact that are inherent to other thermally-, solution-, or mechanochemically-based techniques

Characterisation of different polymorphs of tris(8-hydroxyquinolinato)aluminium(III) using solid-state NMR and DFT calculations

<p>Abstract</p> <p>Background</p> <p>Organic light emitting devices (OLED) are becoming important and characterisation of them, in terms of structure, charge distribution, and intermolecular interactions, is important. Tris(8-hydroxyquinolinato)-aluminium(III), known as Alq₃, an organomettalic complex has become a reference material of great importance in OLED. It is important to elucidate the structural details of Alq₃in its various isomeric and solvated forms. Solid-state nuclear magnetic resonance (NMR) is a useful tool for this which can also complement the information obtained with X-ray diffraction studies.</p> <p>Results</p> <p>We report here ²⁷Al one-dimensional (1D) and two-dimensional (2D) multiple-quantum magic-angle spinning (MQMAS) NMR studies of the meridional (<it>α</it>-phase) and the facial (<it>δ</it>-phase) isomeric forms of Alq₃. Quadrupolar parameters are estimated from the 1D spectra under MAS and anisotropic slices of the 2D spectra and also calculated using DFT (density functional theory) quantum-chemical calculations. We have also studied solvated phase of Alq₃containing ethanol in its lattice. We show that both the XRD patterns and the quadrupolar parameters of the solvated phase are different from both the <it>α</it>-phase and the <it>δ</it>-phase, although the fluorescence emission shows no substantial difference between the <it>α</it>-phase and the solvated phase. Moreover, we have shown that after the removal of ethanol from the matrix the solvated Alq₃has similar XRD patterns and quadrupolar parameters to that of the <it>α</it>-phase.</p> <p>Conclusion</p> <p>The 2D MQMAS experiments have shown that all the different modifications of Alq₃have ²⁷Al in single unique crystallographic site. The quadrupolar parameters predicted using the DFT calculation under the isodensity polarisable continuum model resemble closely the experimentally obtained values. The solvated phase of Alq₃containing ethanol has structural difference from the <it>α</it>-phase of Alq₃(containing meridional isomer) from the solid-state NMR studies. Solid-state NMR can hence be used as an effective complementary tool to XRD for characterisation and structural elucidation.</p

Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen

Состояние системы гемостаза у беременных с врожденными пороками развития плода в сочетании с плацентарной дисфункцией

Вагітність супроводжується складним комплексом ейроендокринних змін, які створюють зміни в системі гемостазу. По мірі збільшення терміну вагітності коагуляційний потенціал змінюється в сторону його підвищення. Дослідження стану регуляції агрегатного стану крові (РАСК) є складним і характеризується високою біологічною варіабельністю. Застосування методів графічної реєстрації процесу згортання цільної крові дозволяє виробити комплексну оцінку стану системи РАСК, дає можливість досить методично та досить точно діагностувати порушення в цій системі. Об’єкти та методи дослідження. Функціональну активність системи PACK проводили методом низькочастотної п’єзоелектричної тромбоеластографії (НПТЕГ). Дослідження проводили в 2 групах. 1-а група (41 вагітна) – вагітні з ВВР плода в поєднанні з ПД (ОГ). 2-а група (10 вагітних) – вагітні, які народили здорових дітей (КГ). Результати дослідження та їх обговорення. Аналіз показників, що характеризують І фазу коагуляції (судино-тромбоцитарну) показав достовірне підвищення початкового показника (66,72±11,28, р < 0,001) та інтенсивності контактної фази коагуляції (137,03±8,07, р < 0,001) і зниження часу контактної фази коагуляції (1,01±0,4, р < 0,001). Показники, які характеризують інтенсивність тромбоутворення та процес полімеризації фібрину (ІІ та ІІІ фази коагуляції) також мали достовірні зміни. Так спостерігалося скорочення часу згортання крові (3,41±0,41, р < 0,01), підвищення коагуляційного драйву (5,93±3,11, р < 0,01), зниження амплітуди полімеризації згустку (501±6,62, р < 0,001), підвищення інтенсивності полімеризації згустку (23,83±0,44, р < 0,001), скорочувався час формування фібринтромбоцитарної структури згустку (20,88±0,81, р < 0,001), максимальної щільності згустку (460,01±6,02, р < 0,001) та підвищувалася інтенсивність загального згортання крові (37,37±2,4, р < 0,05). Збільшення інтенсивності рефракції та лізису згустку (15,48±0,34, р < 0,001) свідчить про активацію фібринолізу. Підтвердженням гіперкоагуляції є патоморфологічні дослідження плаценти у вагітних з ВВР плода та ПД, які характеризувалися міжворсинковим тромбозом та некрозом. Висновки. При ВВР плода в поєднанні з ПД31 спостерігаються порушення у всіх ланках PACK, що свідчить про гіперкоагуляцію в судино-тромбоцитарній та плазмовій ланках. Підвищення показників фібринолізу може бути пов’язане з субкомпенсацією чи декомпенсацією ПД. На фоні порушень гемостазу в судино-тромбоцитарній та плазмовій ланках спостерігається патологічні зміни в плаценті, характерними ознаками яких є тромбоз міжвосинкового простору та некроз.Introduction. Pregnancy is accompanied by a complex set of changes in the hemostatic system. With increasing gestational age, and increased coagulation capability. Study of regulation of blood aggregation (RASK) is characterized by high biological variability. The use of graphic registration process whole blood clotting allows accurately diagnose disorders of RASK. SUBJECTS AND METHODS. The functional activity of the system was carried out by the low-frequency PACK pezoelektricheskoy thromboelastography (NPTEG). The study was conducted in two groups. 1 and Group (41 pregnant) - Women with congenital malformations of the fetus in conjunction with PD (OG). 2 and the group (10 pregnant women) - women rodivshi healthy children (CG). Results and its discussion. An analysis of the indicators characterizing the I phase of coagulation (vessel hundredplatelet) showed a significant increase in the initial index (66,72 ± 11,28, P <0.001), and the intensity of the contact phase of coagulation (137,03 ± 8,07, p <0.001) reduction in its time (1,01 ± 0,4, p <0.001). The indicators characterizing the intensity of thrombosis and fibrin polymerization process (II phase III ua coagulation) also had significant differences. A decline in blood clotting time (3,41 ± 0,41, p <0.01) increase in coagulation drive (5,93 ± 3,11, p <0.01) decrease in the amplitude of the polymerization sgustva (501 ± 6,62, p <0.001), increasing the intensity of clot polymerization (23,83 ± 0,44, p <0.001), reduced the formation of platelet-fibrin clot structure (20,88 ± 0,81, p <0.001), the maximum schplotnosti sgustva (460 01 ± 6,02, p <0.001) and total intensity povyshalosal coagulation (37,37 ± 2,4, p <0.05). Increase the intensity of refraction and clot lysis (15,48 ± 0,34, p <0.001), indicating the activation of fibrinolysis. Podtverdzhdeniem hypercoagulable a pathological study of the placenta in pregnant women with congenital malformations of the fetus, and the fetus of PD, which was characteristic mezhvorsinkovy thrombosis and necrosis. Vivody. When fetal congenital malformations in conjunction with PD have been violations in all parts of PACK, indicating that in the vessels of cash hypercoagulable hundred-platelet and plasma components. Improving indicators of fibrinolysis may Bat subcompensation associated with decompensation or PD. On Phony disorders of hemostasis in vascular trombotsitarom and plasma links of pathological changes take place in the placenta, the characteristics of which have space mezhvosinkovogo thrombosis and necrosis.Беременность сопровождается сложным комплексом изменений в системе гемостаза. По мере увеличения срока беременности, повышается и коагуляционный потенциал. Исследование регуляции агрегатного состояния крови (РАСК) характеризуется высокой биологической вариабельностью. Использование методов графической регистрации процессов свертывания цельной крови позволяет достаточно точно диагностировать нарушения системы РАСК. Объект и методы исследования. Функциональную активность системы PACK проводили методом низкочастотной пьезоелектрической тромбоэластографии (НПТЭГ). Исследование проводили в 2 группах. 1-а група (41 беременная) – женщины с ВПР плода в сочетании с ПД (ОГ). 2-а группа (10 беременных) – женщины, родивши здорових детей (КГ). Результаты и их обсуждение. Анализ показателей, характеризующих І фазу коагуляции (сосуди сто-тромбоцитарную) показал достоверное повышение начального показателя (66,72±11,28, р < 0,001) и интенсивности контактной фазы коагуляции (137,03±8,07, р < 0,001) и снижением ее времени (1,01±0,4, р < 0,001). Показатели,характеризующие интенсивность тромбообразования и процесс полимеризации фибрина (ІІ иа ІІІ фазы коагуляции) также имели достоверные отличия. Наблюдали сокращение времени свертывания крови (3,41±0,41, р < 0,01) повышение коагуляционного драйва (5,93±3,11, р < 0,01), снижение амплитуды полимеризации сгуства (501±6,62, р < 0,001), повышение интенсивности полимеризации сгустка (23,83±0,44, р < 0,001), сокращалось время формирования фибрин-тромбоцитарной структуры сгустка (20,88±0,81, р < 0,001), максимальной щплотности сгуства (460,01±6,02, р < 0,001) и повышалосаль интенсивность общей свертываемости крови (37,37±2,4, р < 0,05). Увеличение интенсивности рефракции и лизиса сгустк (15,48±0,34, р < 0,001) свидетельствует об активации фибринолиза. Подтвердждением гиперкоагуляции является патоморфологические исследования плаценты у беременных с ВПР плода плода и ПД, для которых был характерне межворсинковый тромбозом и некроз. Виводы. При ВПР плода в сочетании с ПД имеют место нарушения во всех звеньях PACK, что свидетельствует о налички гиперкоагуляции в сосуди сто-тромбоцитарном и плазменном звене. Повышение показателей фибринолиза может бать связано с субкомпенсацией или декомпенсацией ПД. На фони нарушений гемостаза в сосудисто-тромбоцитаром и плазменном звеньях имеют место патологические изменения в плаценте, характерними признаками которых есть тромбоз межвосинкового пространства и некроз

Genome of the red alga Porphyridium purpureum

The limited knowledge we have about red algal genomes comes from the highly specialized extremophiles, Cyanidiophyceae. Here, we describe the first genome sequence from a mesophilic, unicellular red alga, Porphyridium purpureum. The 8,355 predicted genes in P. purpureum, hundreds of which are likely to be implicated in a history of horizontal gene transfer, reside in a genome of 19.7 Mbp with 235 spliceosomal introns. Analysis of light-harvesting complex proteins reveals a nuclear-encoded phycobiliprotein in the alga. We uncover a complex set of carbohydrate-active enzymes, identify the genes required for the methylerythritol phosphate pathway of isoprenoid biosynthesis, and find evidence of sexual reproduction. Analysis of the compact, function-rich genome of P. purpureum suggests that ancestral lineages of red algae acted as mediators of horizontal gene transfer between prokaryotes and photosynthetic eukaryotes, thereby significantly enriching genomes across the tree of photosynthetic life

Basal Jawed Vertebrate Phylogenomics Using Transcriptomic Data from Solexa Sequencing

The traditionally accepted relationships among basal jawed vertebrates have been challenged by some molecular phylogenetic analyses based on mitochondrial sequences. Those studies split extant gnathostomes into two monophyletic groups: tetrapods and piscine branch, including Chondrichthyes, Actinopterygii and sarcopterygian fishes. Lungfish and bichir are found in a basal position on the piscine branch. Based on transcriptomes of an armored bichir (Polypterus delhezi) and an African lungfish (Protopterus sp.) we generated, expressed sequences and whole genome sequences available from public databases, we obtained 111 genes to reconstruct the phylogenetic tree of basal jawed vertebrates and estimated their times of divergence. Our phylogenomic study supports the traditional relationship. We found that gnathostomes are divided into Chondrichthyes and the Osteichthyes, both with 100% support values (posterior probabilities and bootstrap values). Chimaeras were found to have a basal position among cartilaginous fishes with a 100% support value. Osteichthyes were divided into Actinopterygii and Sarcopterygii with 100% support value. Lungfish and tetrapods form a monophyletic group with 100% posterior probability. Bichir and two teleost species form a monophyletic group with 100% support value. The previous tree, based on mitochondrial data, was significantly rejected by an approximately unbiased test (AU test, p = 0). The time of divergence between lungfish and tetrapods was estimated to be 391.8 Ma and the divergence of bichir from pufferfish and medaka was estimated to be 330.6 Ma. These estimates closely match the fossil record. In conclusion, our phylogenomic study successfully resolved the relationship of basal jawed vertebrates based on transtriptomes, EST and whole genome sequences

Expansion and functional diversification of a leucyl aminopeptidase family that encodes the major protein constituents of Drosophila sperm

<p>Abstract</p> <p>Background</p> <p>The evolutionary diversification of gene families through gene creation (and loss) is a dynamic process believed to be critical to the evolution of functional novelty. Previous identification of a closely related family of eight annotated metalloprotease genes of the M17 Merops family in the <it>Drosophila </it>sperm proteome (termed, Sperm-LeucylAminoPeptidases, S-LAPs 1-8) led us to hypothesize that this gene family may have experienced such a diversification during insect evolution.</p> <p>Results</p> <p>To assess putative functional activities of S-LAPs, we (i) demonstrated that all S-LAPs are specifically expressed in the testis, (ii) confirmed their presence in sperm by two-dimensional gel electrophoresis and mass spectrometry, (iii) determined that they represent a major portion of the total protein in sperm and (iv) identified aminopeptidase enzymatic activity in sperm extracts using LAP-specific substrates. Functionally significant divergence at the canonical M17 active site indicates that the largest phylogenetic group of S-LAPs lost catalytic activity and likely acquired novel, as yet undetermined, functions in sperm prior to the expansion of the gene family.</p> <p>Conclusions</p> <p>Comparative genomic and phylogenetic analyses revealed the dramatic expansion of the S-LAP gene family during <it>Drosophila </it>evolution and copy number heterogeneity in the genomes of related insects. This finding, in conjunction with the loss of catalytic activity and potential neofunctionalization amongst some family members, extends empirical support for pervasive "revolving door" turnover in the evolution of reproductive gene family composition and function.</p