Effect of chemical structure on the sonochemical degradation of perfluoroalkyl and polyfluoroalkyl substances (PFASs)

Perfluoroalkyl surfactants include chemicals characterized by a fully fluorinated carbon chain (hydrophobic and oleophobic tail) bound to a hydrophilic head (a carboxyl or sulfonic group). These compounds are toxic and highly resistant to chemical/biological attack, and some are known to be bio-accumulative. This study investigates the sonochemical degradation at 500 kHz of different carboxylic and sulfonic perfluoroalkyl and polyfluoroalkyl substances (PFASs, 1.7 mM total organic fluorine) to assess the effect of chain length, functional head group, and substituents (–CH2–CH2– moiety and ether group) on the degradation rate. Under these conditions, the rates of defluorination determined for two widely used perfluoroalkyl substances, perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), were 3.5 to 3.7 μM F− min−1, respectively. The degradation rate of perfluoroalkyl sulfonates decreased with the perfluorocarbon chain length as indicated by the 1.3 and 1.9-fold lower defluorination rates for perfluorohexane- and perfluorobutane sulfonate than that of PFOS. A similar trend was observed during the sonolysis of perfluoroalkyl carboxylate analogs with 6, 5 or 3 carbon atoms which had 1.1-, 1.8-, and 2.3-fold lower defluorination rates, respectively, than that of PFOA. Furthermore, perfluoroalkyl compounds appeared more amenable to sonolysis than the polyfluoroalkyl analogues with the same number of C atoms (defluorination rate of PFOS/6 : 2 fluorotelomer sulfonate ≈ 2.3). The results demonstrate that sonolysis is a promising approach to treat PFASs in aqueous streams. Furthermore, they underscore that the chemical structure of PFASs has a marked effect on the rate at which they undergo sonochemical degradation

Structural Properties of Thermoresponsive Poly(N-isopropylacrylamide)-poly(ethyleneglycol) Microgels

The application of RNA interference to treat disease is an important yet challenging concept in modern medicine. In particular, small interfering RNA (siRNA) have shown tremendous promise in the treatment of cancer. However, siRNA show poor pharmacological properties, which presents a major hurdle for effective disease treatment especially through intravenous delivery routes. In response to these shortcomings, a variety of nanoparticle carriers have emerged, which are designed to encapsulate, protect, and transport siRNA into diseased cells. To be effective as carrier vehicles, nanoparticles must overcome a series of biological hurdles throughout the course of delivery. As a result, one promising approach to siRNA carriers is dynamic versatile nanoparticles that can perform several in vivo functions. Over the last several years, our research group has investigated hydrogel nanoparticles (nanogels) as candidate delivery vehicles for therapeutics, including siRNA. Throughout the course of our research, we have developed higher order architectures composed entirely of hydrogel components, where several different hydrogel chemistries may be isolated in unique compartments of a single construct. In this Account, we summarize a subset of our experiences in the design and application of nanogels in the context of drug delivery, summarizing the relevant characteristics for these materials as delivery vehicles for siRNA. Through the layering of multiple, orthogonal chemistries in a nanogel structure, we can impart multiple functions to the materials. We consider nanogels as a platform technology, where each functional element of the particle may be independently tuned to optimize the particle for the desired application. For instance, we can modify the shell compartment of a vehicle for cell-specific targeting or evasion of the innate immune system, whereas other compartments may incorporate fluorescent probes or regulate the encapsulation and release of macromolecular therapeutics. Proof-of-principle experiments have demonstrated the utility of multifunctional nanogels. For example, using a simple core/shell nanogel architecture, we have recently reported the delivery of siRNA to chemosensitize drug resistant ovarian cancer cells. Ongoing efforts have resulted in several advanced hydrogel structures, including biodegradable nanogels and multicompartment spheres. In parallel, our research group has studied other properties of the nanogels, including their behavior in confined environments and their ability to translocate through small pores

Methodology and Neuromarkers for Cetaceans’ Brains

Cetacean brain sampling may be an arduous task due to the difficulty of collecting and histologically preparing such rare and large specimens. Thus, one of the main challenges of working with cetaceans’ brains is to establish a valid methodology for an optimal manipulation and fixation of the brain tissue, which allows the samples to be viable for neuroanatomical and neuropathological studies. With this in view, we validated a methodology in order to preserve the quality of such large brains (neuroanatomy/neuropathology) and at the same time to obtain fresh brain samples for toxicological, virological, and microbiological analysis (neuropathology). A fixation protocol adapted to brains, of equal or even three times the size of human brains, was studied and tested. Finally, we investigated the usefulness of a panel of 20 antibodies (neuromarkers) associated with the normal structure and function of the brain, pathogens, age-related, and/or functional variations. The sampling protocol and some of the 20 neuromarkers have been thought to explore neurodegenerative diseases in these long-lived animals. To conclude, many of the typical measures used to evaluate neuropathological changes do not tell us if meaningful cellular changes have occurred. Having a wide panel of antibodies and histochemical techniques available allows for delving into the specific behavior of the neuronal population of the brain nuclei and to get a “fingerprint” of their real status

The role of aqp3 in amnion cells exposed to an osmotic stress

INTRODUCTION: AQPs in fetal membranes have been proposed to regulate the amniotic fluid volume. Altered expression of these proteins might be associated with oligo and polyhydramnios syndromes. However, we recently observed that the blocking of AQP3 did not prevent cell swelling in amnion cells. In addition, under osmotic stress the pattern expression of amnion AQP3 was different from other AQPs, suggesting a different role for this protein. OBJETIVE: To study the regulation of AQP3 and its role in the amnion.METHODS: Amnion-derived WISH cells were cultured in hypo (150 mOsm) and hyperosmolar (400 mOsm) conditions. Levels of phosphorylated ERK (pERK), JUNK (pJNK) and p38 (p-p38) were studied. Nf-ĸB and tonEBP expressions were assessed in nuclear and cytosolic fractions. AQP3 expression was analyzed after the inhibition of Nf-ĸB and tonEBP pathways with Sodium Salicylate and Cyclosporine-A, respectively. Cell viability was studied by MTT assay. Apoptosis was studied by TUNEL assay and Bax/Bcl-2 ratio after the inhibition of AQP3 using CuSO4 or the specific siRNA. RESULTS: pERK levels increased in hyperosmolarity and did not change in hypoosmolarity (p<0.001; n=6). No significant differences were observed in p-p38 and pJNK (ns; n=6). Nf-ĸB and tonEBP expressions increased in nuclear fraction only in hyperosmolarity (p<0.05; n=5; p<0.01; n=5). In this condition, the blocking of Nf-ĸB pathway increased AQP3 expression (p<0.001; n=5) compared to controls, while the inhibition of tonEBP pathway did not modify its expression. Regarding cell viability in hiperosmolarity, the blocking of AQP3 decreased MTT incorporation (p<0.01; n=8). Moreover, Bax/Bcl-2 ratio and the number of apoptotic nuclei increased after CuSO4 treatment (p<0.001; n=5; p<0.001; n=9) and AQP3 silencing (p<0.05; n=5; p<0.01; n=10).CONCLUSION: Our findings suggest that AQP3 may have an important role in the survival of the amniotic cells and its expression may be regulated by ERK, Nf-ĸB and tonEBP pathways.Fil: Di Paola, Mauricio Adriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Sierra, M. N.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaFil: Fernandez, N.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Erlejman, A.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Castro Parodi, M.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Damiano, Alicia Ermelinda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaLXV Reunión anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de FisiologíaBuenos AiresArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Fisiologí

Detecting the footprint of selection on the genomes of Murciano-Granadina goats

Artificial selection is one of the major forces modifying the genetic composition of livestock populations. Identifying genes under selection could be useful to elucidate their impact on phenotypic variation. We aimed to identify genomic regions targeted by selection for dairy and pigmentation traits in Murciano-Granadina goats. Performance of a selection scan based on the integrated haplotype score test in a population of 1183 Murciano-Granadina goats resulted in the identification of 77 candidate genomic regions/SNPs. The most significant selective sweeps mapped to chromosomes 1 (69.86&nbsp;Mb), 4 (41.80–49.95&nbsp;Mb), 11 (65.74&nbsp;Mb), 12 (31.24 and 52.51&nbsp;Mb), 17 (34.76–37.67&nbsp;Mb), 22 (31.75&nbsp;Mb), and 26 (26.69–31.05&nbsp;Mb). By using previously generated RNA-Seq data, we built a catalogue of 6414 genes that are differentially expressed across goat lactation (i.e. 78&nbsp;days post-partum, early lactation; 216&nbsp;days post-partum, late lactation; 285&nbsp;days post-partum, dry period). Interestingly, 183 of these genes mapped to selective sweeps and several of them display functions related with lipid, protein, and carbohydrate metabolism, insulin signaling, cell proliferation, as well as mammary development and involution. Of particular interest are the CSN3 and CSN1S2 genes, which encode two major milk proteins. Additionally, we found three pigmentation genes (GLI3, MC1R, and MITF) co-localizing with selective sweeps. Performance of a genome-wide association study and Sanger sequencing and TaqMan genotyping experiments revealed that the c.801C&gt;G (p.Cys267Trp) polymorphism in the melanocortin 1 receptor (MC1R) gene is the main determinant of the black (GG or GC genotypes) and brown (CC genotypes) colorations of Murciano-Granadina goats

Non-unitary Leptonic Mixing and Leptogenesis

We investigate the relation between non-unitarity of the leptonic mixing matrix and leptogenesis. We discuss how all parameters of the canonical type-I seesaw mechanism can, in principle, be reconstructed from the neutrino mass matrix and the deviation of the effective low-energy leptonic mixing matrix from unitary. When the mass M' of the lightest right-handed neutrino is much lighter than the masses of the others, we show that its decay asymmetries within flavour-dependent leptogenesis can be expressed in terms of two contributions, one depending on the unique dimension five (d=5) operator generating neutrino masses and one depending on the dimension six (d=6) operator associated with non-unitarity. In low-energy seesaw scenarios where small lepton number violation explains the smallness of neutrino masses, the lepton number conserving d=6 operator contribution generically dominates over the d=5 operator contribution which results in a strong enhancement of the flavour-dependent decay asymmetries without any resonance effects. To calculate the produced final baryon asymmetry, the flavour equilibration effects directly related to non-unitarity have to be taken into account. In a simple realization of this non-unitarity driven leptogenesis, the lower bound on M' is found to be about 10^8 GeV at the onset of the strong washout regime, more than one order of magnitude below the bound in "standard" thermal leptogenesis.Comment: 19 pages, REVTeX4, 2 eps and 2 axodraw figure

Altered sleep and neurovascular dysfunction in alpha-synucleinopathies: the perfect storm for glymphatic failure

Clinical and cognitive progression in alpha-synucleinopathies is highly heterogeneous. While some patients remain stable over long periods of time, other suffer early dementia or fast motor deterioration. Sleep disturbances and nocturnal blood pressure abnormalities have been identified as independent risk factors for clinical progression but a mechanistic explanation linking both aspects is lacking. We hypothesize that impaired glymphatic system might play a key role on clinical progression. Glymphatic system clears brain waste during specific sleep stages, being blood pressure the motive force that propels the interstitial fluid through brain tissue to remove protein waste. Thus, the combination of severe sleep alterations, such as REM sleep behavioral disorder, and lack of the physiological nocturnal decrease of blood pressure due to severe dysautonomia may constitute the perfect storm for glymphatic failure, causing increased abnormal protein aggregation and spreading. In Lewy body disorders (Parkinson’s disease and dementia with Lewy bodies) the increment of intraneuronal alpha-synuclein and extracellular amyloid-β would lead to cognitive deterioration, while in multisystemic atrophy, increased pathology in oligodendroglia would relate to the faster and malignant motor progression. We present a research model that may help in developing studies aiming to elucidate the role of glymphatic function and associated factors mainly in alpha-synucleinopathies, but that could be relevant also for other protein accumulation-related neurodegenerative diseases. If the model is proven to be useful could open new lines for treatments targeting glymphatic function (for example through control of nocturnal blood pressure) with the objective to ameliorate cognitive and motor progression in alpha-synucleinopathies

New nanomaterials for applications in conservation and restoration of stony materials: A review

In recent times, nanomaterials have been applied in the construction and maintenance of the worldÅLs cultural heritage with the aim of improving the consolidation and protection treatments of damaged stone. These nanomaterials include important advantages that could solve many problems found in the traditional interventions. The present paper aims to carry out a review of the state of art on the application of nanotechnology to the conservation and restoration of the stony cultural heritage. We highlight the different types of nanoparticles currently used to produce conservation treatments with enhanced material properties and novel functionalities

Adaptation of antibiotic treatment to clinical practice guidelines in patients aged ⩾65 years hospitalised due to community-acquired pneumonia

[EN] Early, conforming antibiotic treatment in elderly patients hospitalised for community-acquired pneumonia (CAP) is a key factor in the prognosis and mortality. The objective was to examine whether empirical antibiotic treatment was conforming according to the Spanish Society of Pulmonology and Thoracic Surgery guidelines in these patients. Multicentre study in patients aged ⩾65 years hospitalised due to CAP in the 2013–14 and 2014–15 influenza seasons. We collected socio-demographic information, comorbidities, influenza/pneumococcal vaccination history and antibiotics administered using a questionnaire and medical records. Bivariate analyses and multilevel logistic regression were made. In total, 1857 hospitalised patients were included, 82 of whom required intensive care unit (ICU) admission. Treatment was conforming in 51.4% (95% confidence interval (CI) 49.1–53.8%) of patients without ICU admission and was associated with absence of renal failure without haemodialysis (odds ratio (OR) 1.49, 95% CI 1.15–1.95) and no cognitive dysfunction (OR 1.71, 95% CI 1.25–2.35), when the effect of the autonomous community was controlled for. In patients with ICU admission, treatment was conforming in 45.1% (95% CI 34.1–56.1%) of patients and was associated with the hospital visits in the last year (<3 vs. ⩾3, OR 2.70, 95% CI 1.03–7.12) and there was some evidence that this was associated with season. Although the reference guidelines are national, wide variability between autonomous communities was found. In patients hospitalised due to CAP, health services should guarantee the administration of antibiotics in a consensual manner that is conforming according to clinical practice guidelines.S