RESUMEN

Using a newly developed flow test bench, several charge configurations were analyzed to quantify the influence of the charge configuration in the mold in sheet molding compound (SMC) manufacturing. A test bench was developed to satisfy the industrial needs for the incoming goods inspection as well as the need for the flow characterization of rheological models in the simulation. The test setup has a cylindrical opening for the charge placement, from where the material is pressed into a thin flow channel, forcing the material to reorient. A comparison was performed by juxtaposing the resulting compression pressure recorded during the process. The charge for this test series, placed into the cylindrical opening, has two basal configurations, one consisting of a stack of disks, and the second in a rectangular sheet rolled up into a spiral. Six charge variations were tested in total. The amount of material, the batch, the layering and the production direction of the sheet proved to have a significant influence on the necessary compression pressure. Guidelines about the recommended charge configurations could be derived for optimized production settings, such as a reduction in the compression pressure and modifications to the charge.

RESUMEN

The novel multidomain protein, cpSRP43, is a unique subunit of the post-translational chloroplast signal recognition particle (cpSRP) targeting pathway in higher plants. The cpSRP pathway is responsible for targeting and insertion of light-harvesting chlorophyll a/b binding proteins (LHCPs) to the thylakoid membrane. Upon emergence into the stroma, LHCPs form a soluble transit complex with the cpSRP heterodimer, which is composed of cpSRP43 and cpSRP54. cpSRP43 is irreplaceable as a chaperone to LHCPs in their translocation to the thylakoid membrane and remarkable in its ability to dissolve aggregates of LHCPs without the need for external energy input. In previous studies, cpSRP43 has demonstrated significant flexibility and interdomain dynamics. In this study, we explore the structural stability and flexibility of cpSRP43 using a combination of computational and experimental techniques and find that this protein is concurrently highly stable and flexible. In addition to microsecond-level unbiased molecular dynamics (MD), biased MD simulations based on system-specific collective variables are used along with biophysical experimentation to explain the basis of the flexibility and stability of cpSRP43, showing that the free and cpSRP54-bound cpSRP43 has substantially different conformations and conformational dynamics.

Asunto(s)

Proteínas de Cloroplastos , Cloroplastos , Unión Proteica , Proteínas de Cloroplastos/metabolismo , Clorofila A , Cloroplastos/metabolismo , Tilacoides/metabolismo , Complejos de Proteína Captadores de Luz/química , Complejos de Proteína Captadores de Luz/metabolismo

RESUMEN

BACKGROUND: The AARS2 gene encodes a mitochondrial alanyl-transfer RNA synthetase. Defects in this gene have been linked with autosomal recessive inheritance of a variety of different clinical phenotypes. CASE: A 13 year-old boy developed behavioral and psychiatric problems following a mild head injury. At age 21 he developed tremor, parkinsonism, and eye nystagmus. MRI revealed white matter changes consistent with a leukoencephalopathy. Genetic studies revealed two pathogenic mutations in the AARS2 gene (c.647dupG and c.595C > T). LITERATURE REVIEW: Only 47 cases of AARS2-associated disorders have been reported, with equal numbers of males and females, and age at onset ranging from infancy to 44 years. The most common clinical problems include movement disorders (71%), cognitive impairment (67%), corticospinal signs (64%), behavioral or psychiatric features (46%), and eye signs (34%). Imaging evidence suggestive of leukoencephalopathy is common, but not invariant. Premature ovarian failure is frequent in females, but not universal. CONCLUSIONS: Defects in the AARS2 gene are a rare cause for a variety of movement disorders, often associated with brain imaging evidence suggestive of leukoencephalopathy.

Asunto(s)

Alanina-ARNt Ligasa/genética , Traumatismos Craneocerebrales/genética , Leucoencefalopatías/genética , Adolescente , Traumatismos Craneocerebrales/complicaciones , Humanos , Masculino , Ilustración Médica , Mutación , Adulto Joven

Asunto(s)

Ecosistema , Salud Ambiental , Monitoreo del Ambiente/métodos , Investigación Biomédica Traslacional , Australia , Humanos

RESUMEN

Due to progressive erosion of the new Urucurituba Channel, the Amazon River has recently captured almost all discharge from the lower Araguari River (Amapá-AP, Brazil), which previously flowed directly to the Atlantic Ocean. These recent geomorphological changes have caused strong impacts on the landscape and hydrodynamic patterns near the Araguari River mouth, especially the alteration of the riverine drainage system and its water quality. Landsat images were used to assess the estuarine landscape morphodynamic, particularly the expansion of the Urucurituba Channel, 80km from the Araguari River mouth, chronicling its connection to the Amazon River. The results suggest that the Urucurituba developed by headward migration across the Amazon delta; this is perhaps the first observation of estuarine distributary network development by headward channel erosion. The rate of Urucurituba Channel width increase has been ≈5m/month since 2011, increasing drainage capacity of the channel. We also collected in situ hydrodynamic measurements and analyzed 17 water quality parameters. Having 2011 as baseline, the flowrate of Araguari River has been diverted by up to 98% through Urucurituba Channel, with substantial changes in net discharge recorded at 3 monitoring stations. Statistically significant differences in water quality (p<0.05) were observed between 2011 and 2015, associated with the change in the flow pattern. Estuarine salinity and solids concentrations have increased. Overall, we demonstrate changes in landscape, hydrodynamics and water quality of the lower Araguari River.

RESUMEN

The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Asunto(s)

Autoantígenos/análisis , Feto/química , Glicoproteínas/análisis , Fosfoproteínas/análisis , Proteínas/análisis , Glándulas Salivales/química , Proteínas y Péptidos Salivales/análisis , Epitelio/química , Proteínas de Unión a Ácidos Grasos , Desarrollo Fetal , Edad Gestacional , Cabeza/embriología , Humanos , Inmunohistoquímica , Cuello/embriología , Hueso Paladar/química , Hueso Paladar/embriología , Estudios Retrospectivos , Glándulas Salivales/embriología , Factores de Tiempo , Lengua/química , Lengua/embriología

RESUMEN

Abstract The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Asunto(s)

Humanos , Fosfoproteínas/análisis , Glándulas Salivales/química , Proteínas y Péptidos Salivales/análisis , Autoantígenos/análisis , Glicoproteínas/análisis , Proteínas/análisis , Feto/química , Hueso Paladar/embriología , Hueso Paladar/química , Glándulas Salivales/embriología , Factores de Tiempo , Lengua/embriología , Lengua/química , Inmunohistoquímica , Estudios Retrospectivos , Edad Gestacional , Desarrollo Fetal , Epitelio/química , Cabeza/embriología , Cuello/embriología

RESUMEN

Binaural pitch diplacusis refers to a perceptual anomaly whereby the same sound is perceived as having a different pitch depending on whether it is presented in the left or the right ear. Results in the literature suggest that this phenomenon is more prevalent, and larger, in individuals with asymmetric hearing loss than in individuals with symmetric hearing. However, because studies devoted to this effect have thus far involved small samples, the prevalence of the effect, and its relationship with interaural asymmetries in hearing thresholds, remain unclear. In this study, psychometric functions for interaural pitch comparisons were measured in 55 subjects, including 12 normal-hearing and 43 hearing-impaired participants. Statistically significant pitch differences between the left and right ears were observed in normal-hearing participants, but the effect was usually small (less than 1.5/16 octave, or about 7%). For the hearing-impaired participants, statistically significant interaural pitch differences were found in about three-quarters of the cases. Moreover, for about half of these participants, the difference exceeded 1.5/16 octaves and, in some participants, was as large as or larger than 1/4 octave. This was the case even for the lowest frequency tested, 500 Hz. The pitch differences were weakly, but significantly, correlated with the difference in hearing thresholds between the two ears, such that larger threshold asymmetries were statistically associated with larger pitch differences. For the vast majority of the hearing-impaired participants, the direction of the pitch differences was such that pitch was perceived as higher on the side with the higher (i.e., 'worse') hearing thresholds than on the opposite side. These findings are difficult to reconcile with purely temporal models of pitch perception, but may be accounted for by place-based or spectrotemporal models.

Asunto(s)

Umbral Auditivo , Lateralidad Funcional , Percepción de la Altura Tonal , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Pérdida Auditiva/fisiopatología , Pruebas Auditivas , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven

RESUMEN

The effects of combined treatment with a glucocorticoid receptor (GR) antagonist, Org 34850, and a selective serotonin reuptake inhibitor (SSRI), fluoxetine, were investigated on pre- and postsynaptic aspects of 5-HT neurotransmission. Rats were treated for 14 days with Org 34850 (15 mg per kg per day subcutaneously), fluoxetine (10 mg per kg per day intraperitoneally), or a combination of both drugs. [(3)H]-citalopram binding (an index of 5-HT transporter (5-HTT) expression) was only slightly affected by Org 34850 alone: decreased in cortex and midbrain and increased in hippocampus. In contrast, chronic fluoxetine markedly decreased 5-HTT levels in all regions. Importantly, this decrease was significantly enhanced by combined Org 34850/fluoxetine treatment. There were no changes in the expression of 5-HTT mRNA, suggesting these effects were not due to changes in gene transcription. Expression of tryptophan hydroxylase mRNA and both 5-HT(1A) autoreceptor mRNA and protein (assessed using [(3)H]-8-OH-DPAT binding) were unchanged by any treatment. The expression of postsynaptic 5-HT(1A) receptor protein in the forebrain was unaltered by fluoxetine, Org 34850 or the combined Org 34850/fluoxetine treatment. This downregulation of 5-HTT by fluoxetine and its enhancement by Org 34850 can explain our recent observation that GR antagonists augment the SSRI-induced increase in extracellular 5-HT. In addition, these data suggest that the augmentation of forebrain 5-HT does not result in downregulation of forebrain 5-HT(1A) receptor expression. Given the importance of 5-HT(1A) receptor-mediated transmission in the forebrain to the antidepressant response, these data indicate that co-administration of GR antagonists may be effective in augmenting the antidepressant response to SSRI treatment.

Asunto(s)

Encéfalo/metabolismo , Fluoxetina/farmacología , Receptores de Glucocorticoides/antagonistas & inhibidores , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Esteroides/farmacología , Sulfonas/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Análisis de Varianza , Animales , Autorradiografía , Encéfalo/efectos de los fármacos , Citalopram/farmacología , Densitometría , Regulación hacia Abajo/efectos de los fármacos , Hibridación in Situ , Masculino , ARN Mensajero/metabolismo , Ratas , Receptor de Serotonina 5-HT1A/metabolismo , Agonistas del Receptor de Serotonina 5-HT1 , Tritio/farmacología , Triptófano Hidroxilasa/metabolismo

RESUMEN

BACKGROUND AND METHODS: Perturbations in energetic metabolism and impaired atrial contractility may play an important role in the pathogenesis of atrial fibrillation (AF). Besides, atrial stretch is commonly associated with AF. However, the atrial energetics of stretch-related AF are poorly understood. Here, we measured indicators of energy metabolism during acute stretch-related AF. PCr, adenine nucleotides, and derivatives concentrations as well as the activity of the F(0)F(1)-ATPase and Na,K-ATPase were obtained after 1 h of stretch and/or AF in isolated rabbit hearts and compared to control hearts without stretch and AF. RESULTS: After 1 h of stretch-related AF, the total adenine nucleotides' pool was significantly lower (42.2 +/- 2.6 vs. 63.7 +/- 8.3 micromol/g protein in control group, P < 0.05) and the PCr/ATP ratio significantly higher (2.3 +/- 0.3 vs. 1.1 +/- 0.1 in control group P < 0.05), because of ATP, ADP, and AMP decrease and PCr increase. The sum of high-energy phosphate compounds did not change. There were no significant differences in F(0)F(1)-ATPase nor Na,K-ATPase activity between the groups. CONCLUSIONS: Results show that in this experimental model, acute stretch-related AF induces specific modifications of atrial myocytes energetics that may play a pivotal role in the perpetuation of the arrhythmia.

Asunto(s)

Fibrilación Atrial/metabolismo , Metabolismo Energético , Animales , Fibrilación Atrial/enzimología , Fibrilación Atrial/fisiopatología , Técnicas In Vitro , Mitocondrias/enzimología , Fosfatos/metabolismo , Fosfocreatina/metabolismo , ATPasas de Translocación de Protón/metabolismo , Conejos , Periodo Refractario Electrofisiológico , Sarcolema/enzimología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Estrés Mecánico

RESUMEN

Pancreatic stellate cells mediate fibrosis in chronic pancreatitis. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)-1 and -2 are crucial modulators of fibrosis. Transforming growth factor-beta (TGF-beta) is a key regulator of extracellular matrix production and myofibroblast proliferation. We have examined MMP and TIMP synthesis by transformed cultured pancreatic stellate cells and their regulation by TGF-beta 1. By Northern analysis they expressed mRNAs for procollagen 1, TIMP-1, TIMP-2, and MMP-2. Expression of membrane type-1 MMP was confirmed by Western blotting. By immunohistochemistry these enzymes localized to fibrotic areas in human chronic pancreatitis. Active TGF-beta 1 constitutes 2 to 5% of total TGF-beta 1 secreted by pancreatic stellate cells; they express TGF-beta receptors I and II. Exogenous TGF-beta 1 (10 ng/ml) significantly increased procollagen-1 mRNA by 69% and collagen protein synthesis by 34%. Similarly TGF-beta 1 at 0.1, 1, and 10 ng/ml significantly reduced cellular proliferation rate by 37%, 44%, and 44%, respectively, whereas pan-TGF-beta-neutralizing antibody increased proliferation by 40%. TGF-beta1 (10 ng/ml) down-regulated MMP-9 by 54% and MMP-3 by 34% whereas TGF-beta 1-neutralizing antibody increased MMP-9 expression by 39%. Pancreatic stellate cells express both mediators of matrix remodeling and the regulatory cytokine TGF-beta 1 that, by autocrine inhibition of MMP-3 and MMP-9, may enhance fibrogenesis by reducing collagen degradation.

Asunto(s)

Matriz Extracelular/metabolismo , Páncreas/metabolismo , Pancreatitis/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Actinas/genética , Actinas/metabolismo , Animales , Northern Blotting , Western Blotting , División Celular/genética , División Celular/fisiología , Células Cultivadas , Enfermedad Crónica , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Regulación hacia Abajo , Expresión Génica , Humanos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasas de la Matriz Asociadas a la Membrana , Metaloendopeptidasas/genética , Metaloendopeptidasas/metabolismo , Músculo Liso/química , Páncreas/citología , Pancreatitis/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta1