PAMAM6 dendrimers and DNA: pH dependent "beads-on-a-string" behavior revealed by small angle X-ray scattering

DNA interactions with polycations are not only important for our understanding of chromatin compaction but also for characterizing DNA-binding proteins involved in transcription, replication and repair. DNA is known to form several types of liquid-crystalline phases depending, among other factors, on polycation structure and charge density. Theoretical studies and simulations have predicted the wrapping of DNA around spherical positively charged polycations. As a potential mimic of the histone octamer or other DNA wrapping proteins, poly(amido amine) generation 6 (PAMAM6) dendrimers have been chosen for our study. The self-assembly of DNA induced by PAMAM6 has been investigated using small angle X-ray scattering (SAXS) in order to reveal the assemblies' structure dependence on the pH of the environment and on dendrimers concentration. We demonstrate that at pH 8.5 dense phases are formed and characterized by a 2D-columnar hexagonal lattice which is transformed into a 3D hexagonal lattice with increasing dendrimer concentration (charge ratio N/P). Moreover, a systematic analysis of the scattering data collected from diluted samples at pH 8.5 and 5.5 have led us to propose a wrapping scenario of DNA around PAMAM6 at pH 5.5.Comment: 12 pages, 7 figure

MORPHO‐FUNCTIONAL RE‐ESTABLISHMENT OF CRANIO‐FACIAL GROWTH DISORDERS IN PITUITARY DWARFISM BY RHGH THERAPY

The present study evaluates the cranio‐facial growth disorders in a series of patients suffering from pituitary dwarfism, as a result of the therapy with recombinant human growth hormone (rhGH). Included in the study were 15 children diagnosed with pituitary dwarfism in the Endocrinology Clinics of the ”Sf. Spiridon” Hospital of Iasi, subjected to a treatment with rhGH for 2 years. After the application of the therapy, the parameters of general physical development were followed and the dental ortho‐ pantomography and profile cephalometry were analyzed. The results obtained confirm a general physical growth of about 1.3 cm/month in the first year of treatment, followed by values around 1.1 cm/month in the second year. Cranio‐facial development was improved by the increase of both mandibular vertical branch and facial height. At the level of the dental arches, one could observe improved sagital and transversal relations at molar level, as well as a regulating tendency of dental eruption. The therapy with rhGH is thus influent at cranio‐facial level, favourizing the development of maxillaries, regulation of dental eruption and the aesthetic aspects

. Ecological role and phylogenetic position of a new habitat-forming species (Canalipalpata, Sabellidae) from the Mediterranean mesophotic soft-bottoms

This study presents a description of Bispira riccardi sp. nov., a new habitat-forming sabellid polychaete from the mesophotic NW Mediterranean Sea. Individuals, up to 20 cm long, show a peculiar morphology of radioles, thoracic uncini, companion chaetae and ventral shield of the collar. The phylogenetic position of this new taxon in the genus Bispira has been validated using nuclear (18S rRNA) and mitochondrial (COI) markers. Aggregations of B. riccardi sp. nov. were found by ROV on horizontal muddy bottoms between 56 and 85 m, in areas subjected to high trophic inputs. Patches are fragmented and dense (up to 943 individuals m 2) probably accounting for various hectares. A 5-days continuous monitoring, carried out using an autonomous lander, revealed that the contraction of the branchial crown was positively affected by temperature and current, rapidly responding to meteorological events. The filtering activity and high density of these fields suggest a considerable impact on the pelagic-benthic coupling and the amount of organic matter in the sediments. Indeed, meiofaunal abundance and diversity within the aggregations resulted significantly higher than in outer stations. These findings highlight the undisclosed potential of the deep Mediterranean Sea for sabellid diversity and their importance as habitat-forming species on mesophotic soft bottoms

A self-filling microfluidic device for noninvasive and time-resolved single red blood cell experiments

Existing approaches to red blood cell (RBC) experiments on the single-cell level usually rely on chemical or physical manipulations that often cause difficulties with preserving the RBC's integrity in a controlled microenvironment. Here, we introduce a straightforward, self-filling microfluidic device that autonomously separates and isolates single RBCs directly from unprocessed human blood samples and confines them in diffusion-controlled microchambers by solely exploiting their unique intrinsic properties. We were able to study the photo-induced oxygenation cycle of single functional RBCs by Raman microscopy without the limitations typically observed in optical tweezers based methods. Using bright-field microscopy, our noninvasive approach further enabled the time-resolved analysis of RBC flickering during the reversible shape evolution from the discocyte to the echinocyte morphology. Due to its specialized geometry, our device is particularly suited for studying the temporal behavior of single RBCs under precise control of their environment that will provide important insights into the RBC's biomedical and biophysical properties

Phytotoxicity assessment of some herbal extracts by Triticum bioassay

Disciplina Botanică farmaceutică şi Biologie celulară, Facultatea de Farmacie, UMF “Carol Davila”, Bucureşti, Romania, Catedra Farmacognozie și Botanică farmaceutică, IP USMF „Nicolae Testemiţanu”, Republica MoldovaObiectiv: Evaluarea fitotoxicităţii a trei extracte hidroalcoolice de origine vegetală, deoarece efectele asupra celulei vegetale, şi în special cele observate la nivelul nucleului, pot oferi indicii despre potenţiala toxicitate asupra celulei animale şi umane. Materiale şi metode: Efectele a două extracte hidroalcoolice obţinute cu etanol 70% din rădăcinile speciilor Glycyrrhiza glabra L., lemn dulce (fam. Fabaceae) şi Withania somnifera (L.) Dunal, ginseng indian (fam. Solanaceae) şi ale unui extract hidrosolubil de origine comercială obţinut din rădăcina speciei Panax notoginseng (Burkill) F. H. Chen ex C. Y. Wu& K. M. Feng, notoginseng (fam. Araliaceae) asupra rădăcinilor embrionare de Triticum aestivum au fost evaluate prin metoda Constantinescu. Din fiecare extract s-au preparat prin diluţii succesive, 6 soluţii de concentraţii diferite: 1%, 0,5%, 0,1%, 0,05%, 0,01% şi 0,001%. Efectele asupra alungirii radiculei principale ale cariopselor germinate de Triticum au fost evaluate cantitativ în comparaţie cu un martor negativ (apă distilată) la 72 de ore de la iniţierea tratamentului; comparaţiile statistice multiple s-au realizat la un nivel alfa=0,5 cu ajutorul testului Kruskal-Wallis, iar comparaţiile post-hoc prin aplicarea testului Wilcoxon cu ajustare pentru multiplicitate prin metoda Holm. Rezultate şi discuţii: Extractul de Liquiritiae radix a inhibat semnificativ (p< 0,01) dezvoltarea radiculelor embrionare de Triticum aestivum la primele 3 niveluri de concentraţie (1%-0,1%), extractul de Withania somnifera radix a inhibat semnificativ diviziunea celulară doar la primele 2 niveluri de concentraţie (1% şi 0,5%), iar cel de Panax notoginseng radix la primele 5 niveluri de concentraţie (1%-0,01%). În cazul Liquiritiae radix, inhibiţia a fost completă (indice de inhibiţie 100%) pentru primele 2 niveluri de concentraţie şi mult diminuată la cel deal 3-lea nivel (indice de inhibiţie, 41,03%). Extractul de Withania somnifera radix a determinat o inhibiţie completă (100%) la primul nivel de concentraţie şi de numai 62,4% la cel de-al doilea nivel, iar cel de Panax notoginseng radix a determinat o inhibiţie moderată, la toate cele 5 niveluri de concentraţie (indicele de inhibiţie variind nelinear între 53,8% şi 75,2%). Concluzii: Toate cele trei extracte vegetale hidroalcoolice (Withania somnifera radix, Liquiritiae radix, Panax notoginseng radix) au efecte mitoinhibitorii moderate la concentraţii ceva mai mari, în special extractul de Panax notoginseng radix. Mulţumiri Acest studiu a fost finanțat din Contractul nr. 8/23.12.2013 (Proiect bilateral Romania-Republica Moldova – Competiția N. Testemițanu)

Produse vegetale și fitopreparate cu acțiune hipoglicemiantă

Diabetul zaharat continuă să fie o problemă globală prin frecvența sa și este foarte costisitor pentru societate prin evoluția cronică pe tot parcursul vieții. Tratamentul diabetului este complex, include pe lângă tratamentul medicamentos cel fitoterapic și igieno-dietetic, iar identificarea de noi medicamente, cu un profil de siguranţă mai bun şi efcacitate comparabilă produselor actuale, rămâne o preocupare constantă a cercetărilor ştiinţifi ce, inclusiv prin evaluarea plantelor medicinale hipoglicemiante din flora României și a Republicii Moldova, cât și a principiilor active responsabile de acțiune. Importanţa actuală a fi toterapiei rezidă în ponderea tot mai mare a medicamentelor de origine vegetală, atunci când cota fitopreparatelor cu acțiune hipoglicemiantă în Republica Moldova constituie doar 1,25%, raportate la numărul total de produse înregistrate, cu o tendință de înregistrare a lor ca suplimente alimentare în România (peste 90 suplimente alimentare). Totodată, studiul pune în evidență necesitatea extinderii fitopreparatelor hipoglicemiante, prin testările plantelor medicinale mai puțin studiate până în prezent

Thermoresponsive Hydrogel Containing Viscum album Extract for Topic and Transdermal Use: Development, Stability and Cytotoxicity Activity

Viscum album L. (Santalaceae), also known as European mistletoe, is a semi-parasitic plant that grows on different host trees. Our group recently demonstrated the antitumoral activity of ethanolic V. album extracts in vitro, depending on the dose and the host tree, V. album ssp abietis from Abies alba being the most active extract. The goal of this work focused on the development of a new topical formulation containing V. album extracts, evaluation of in vitro toxicity and ex vivo skin permeation assays. The Poloxamer 407 hydrogel containing 5% of dry (VA_DEH) or aqueous (VA_AEH) extract presented dermal compatible pH and microbiological stability for 180 days. The hydrogels flow curve presented a non-linear relation, characteristic of non-Newtonian fluids, and the mean viscosity for the VA_DEH and VA_AEH was 372.5 ± 7.78 and 331.0 ± 2.83 Pa.s, respectively, being statistically different (Welch’s t test; p < 0.01). Additionally, WST-1 in vitro assays revealed a dose-dependent toxicity for both formulations and VA_DEH presented a higher activity than the VA_AEH. The promising cytotoxic potential of VA_DEH lead to the ex vivo skin permeation assay with 2.73 ± 0.19 µg/cm(2) of chlorogenic acid, which permeated at 8 h, showing a transdermal potential. These in vitro results support the idea that VA_DEH is a novel promising candidate for mistletoe therapy. Therefore, further in vivo and pre-clinical experiments should be performed to evaluate the safety and efficacy of this new dermic delivery system

Emotional, hyperactivity and inattention problems in adolescents with immunocompromising chronic diseases during the COVID-19 pandemic

Objective: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. Methods: A cross-sectional study included&nbsp;343&nbsp;adolescents with immunocompromising diseases and 108&nbsp;healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). Results: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343&nbsp;[32%] vs.&nbsp;38/108 [35%], p&nbsp;=&nbsp;0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs.&nbsp;29/108 [27%], p&nbsp;=&nbsp;0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR&nbsp;=&nbsp;3.76]; 95%&nbsp;Confidence Interval (95%&nbsp;CI) 2.00‒7.05; p &lt; 0.001), poor sleep quality (OR&nbsp;=&nbsp;2.05; 95%&nbsp;CI&nbsp;1.08‒3.88; p&nbsp;=&nbsp;0.028) and intrafamilial violence during pandemic (OR&nbsp;=&nbsp;2.17; 95%&nbsp;CI&nbsp;1.12‒4.19; p&nbsp;=&nbsp;0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR&nbsp;=&nbsp;0.95; 95%&nbsp;CI&nbsp;0.93‒0.96; p &lt; 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR&nbsp;=&nbsp;0.97; 95%&nbsp;CI&nbsp;0.95‒0.99; p&nbsp;=&nbsp;0.010], changes in medical appointments during the pandemic (OR&nbsp;=&nbsp;0.39; 95%&nbsp;CI&nbsp;0.19-0.79; p&nbsp;=&nbsp;0.021), and reliable COVID-19 information (OR&nbsp;=&nbsp;0.35; 95%&nbsp;CI&nbsp;0.16‒0.77; p&nbsp;=&nbsp;0.026) remained inversely associated with abnormal HI scores. Conclusion: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics

The Tyrosine Kinase Inhibitor Dasatinib Induces a Marked Adipogenic Differentiation of Human Multipotent Mesenchymal Stromal Cells

BACKGROUND: The introduction of specific BCR-ABL inhibitors in chronic myelogenous leukemia therapy has entirely mutated the prognosis of this hematologic cancer from being a fatal disorder to becoming a chronic disease. Due to the probable long lasting treatment with tyrosine-kinase inhibitors (TKIs), the knowledge of their effects on normal cells is of pivotal importance. DESIGN AND METHODS: We investigated the effects of dasatinib treatment on human bone marrow-derived mesenchymal stromal cells (MSCs). RESULTS: Our findings demonstrate, for the first time, that dasatinib induces MSCs adipocytic differentiation. Particularly, when the TKI is added to the medium inducing osteogenic differentiation, a high MSCs percentage acquires adipocytic morphology and overexpresses adipocytic specific genes, including PPARγ, CEBPα, LPL and SREBP1c. Dasatinib also inhibits the activity of alkaline phosphatase, an osteogenic marker, and remarkably reduces matrix mineralization. The increase of PPARγ is also confirmed at protein level. The component of osteogenic medium required for dasatinib-induced adipogenesis is dexamethasone. Intriguingly, the increase of adipocytic markers is also observed in MSCs treated with dasatinib alone. The TKI effect is phenotype-specific, since fibroblasts do not undergo adipocytic differentiation or PPARγ increase. CONCLUSIONS: Our data demonstrate that dasatinib treatment affects bone marrow MSCs commitment and suggest that TKIs therapy might modify normal phenotypes with potential significant negative consequences

In-Datacenter Performance Analysis of a Tensor Processing Unit

Many architects believe that major improvements in cost-energy-performance must now come from domain-specific hardware. This paper evaluates a custom ASIC---called a Tensor Processing Unit (TPU)---deployed in datacenters since 2015 that accelerates the inference phase of neural networks (NN). The heart of the TPU is a 65,536 8-bit MAC matrix multiply unit that offers a peak throughput of 92 TeraOps/second (TOPS) and a large (28 MiB) software-managed on-chip memory. The TPU's deterministic execution model is a better match to the 99th-percentile response-time requirement of our NN applications than are the time-varying optimizations of CPUs and GPUs (caches, out-of-order execution, multithreading, multiprocessing, prefetching, ...) that help average throughput more than guaranteed latency. The lack of such features helps explain why, despite having myriad MACs and a big memory, the TPU is relatively small and low power. We compare the TPU to a server-class Intel Haswell CPU and an Nvidia K80 GPU, which are contemporaries deployed in the same datacenters. Our workload, written in the high-level TensorFlow framework, uses production NN applications (MLPs, CNNs, and LSTMs) that represent 95% of our datacenters' NN inference demand. Despite low utilization for some applications, the TPU is on average about 15X - 30X faster than its contemporary GPU or CPU, with TOPS/Watt about 30X - 80X higher. Moreover, using the GPU's GDDR5 memory in the TPU would triple achieved TOPS and raise TOPS/Watt to nearly 70X the GPU and 200X the CPU.Comment: 17 pages, 11 figures, 8 tables. To appear at the 44th International Symposium on Computer Architecture (ISCA), Toronto, Canada, June 24-28, 201