This work reports the results of in vivo assays of an implant composed of the hydrogel Chitosan-g-Glycidyl Methacrylate-Xanthan (CTS-g-GMA)-X in Wistar rats. Degradation kinetics of hydrogels was ...assessed by lysozyme assays. Wistar rats were subjected to laminectomy by cutting the spinal cord with a scalpel. After the surgical procedure, hydrogels were implanted in the injured zone (level T8). Somatosensory evoked potentials (SEPs) obtained by electric stimulation onto periphery nerves were registered in the corresponding central nervous system (CNS) areas. Rats implanted with the biomaterials showed a successful recovery compared with the non-implanted rats after 30days. Lysozyme, derived from egg whites, was used for in vitro assays. This study serves as the basis for testing the biodegradability of the hydrogels (CTS-g-GMA)-X that is promoted by enzymatic hydrolysis. Hydrogels' hydrolysis was studied via lysozyme kinetics at two pH values, 5 and 7, under mechanical agitation at 37°C. Results show that our materials' hydrolysis is slower than pure CTS possibly due to the steric hindrance imposed by the GMA grafting of functionalization. This hydrolysis helps degrade the biomaterial and at the same time it provides support for spinal cord recovery. Combination of these results may prove useful in the use of these hydrogels as scaffolds for cells proliferation and their application as implants in living organisms.
•A novel Chitosan-g-Glycidyl Methacrylate-Xanthan (CTS-g-GMA)-X hydrogel for spinal cord regeneration is reported.•Degradation kinetics was assessed by lysozyme assays.•Somatosensory evoked potentials (SEPs) were successfully recorded.•Rats implanted with the biomaterials showed a successful recovery after 30days.
We tested whether phylogeny, flower size and/or altitude were significant predictors of interspecific variation in nectar production of hummingbird‐visited plants in an assembled database (289 ...species, in 22 orders, 56 families and 131 genera). Although the study is focused on hummingbird‐pollinated plants (241 plant species), plants with different pollinator syndromes (48 species) are also included in the analyses. Nectar volume secreted in a given time period (usually 24 h) by a given flower, its sugar concentration and corolla length were compiled mainly from the literature. Altitude was also obtained from the original references. Sugar production was computed basically as the product of nectar secretion and sugar concentration, and expressed on a per 24‐h basis. All nectar traits and corolla length (all log transformed), as well as altitude, showed statistically significant phylogenetic signal. Both nonphylogenetic and phylogenetically informed (independent contrasts) analyses indicated a highly significant positive correlation between corolla length and both nectar volume and sugar production. In addition, altitude (which is partially a surrogate for temperature) was significantly negatively correlated with both sugar concentration and production. Possible reasons for coadaptation of nectar production and sugar production with corolla length are discussed.
The initial colonization of the Americas remains a highly debated topic
, and the exact timing of the first arrivals is unknown. The earliest archaeological record of Mexico-which holds a key ...geographical position in the Americas-is poorly known and understudied. Historically, the region has remained on the periphery of research focused on the first American populations
. However, recent investigations provide reliable evidence of a human presence in the northwest region of Mexico
, the Chiapas Highlands
, Central Mexico
and the Caribbean coast
during the Late Pleistocene and Early Holocene epochs. Here we present results of recent excavations at Chiquihuite Cave-a high-altitude site in central-northern Mexico-that corroborate previous findings in the Americas
of cultural evidence that dates to the Last Glacial Maximum (26,500-19,000 years ago)
, and which push back dates for human dispersal to the region possibly as early as 33,000-31,000 years ago. The site yielded about 1,900 stone artefacts within a 3-m-deep stratified sequence, revealing a previously unknown lithic industry that underwent only minor changes over millennia. More than 50 radiocarbon and luminescence dates provide chronological control, and genetic, palaeoenvironmental and chemical data document the changing environments in which the occupants lived. Our results provide new evidence for the antiquity of humans in the Americas, illustrate the cultural diversity of the earliest dispersal groups (which predate those of the Clovis culture) and open new directions of research.
A series of HIV protease inhibitors possessing a hydroxylaminepentanamide transition state isostere have been developed. Incorporation of a basic amine into the backbone of the L-685,434 (2) series ...provided antiviral potency combined with a highly improved pharmacokinetic profile in animal models. Guided by molecular modeling and an X-ray crystal structure of the inhibited enzyme complex, we were able to design L-735,524. This compound is potent and competitively inhibits HIV-1 PR and HIV-2 PR with Ki values of 0.52 and 3.3 nM, respectively. It also stops the spread of the HIV-1IIIb-infected MT4 lymphoid cells at concentrations of 25-50 nM. To date, numerous HIV-PR inhibitors have been reported, but few have been studied in humans because they lack acceptable oral bioavailability. L-735,524 is orally bioavailable in three animals models, using clinically acceptable formulations, and is currently in phase II human clinical trials.
Most Xanthomonas species translocate Transcription Activator-Like (TAL) effectors into plant cells where they function like plant transcription factors via a programmable DNA-binding domain. ...Characterized strains of rice pathogenic X. oryzae pv. oryzae harbor 9-16 different tal effector genes, but the function of only a few of them has been decoded. Using sequencing of entire genomes, we first performed comparative analyses of the complete repertoires of TAL effectors, herein referred to as TALomes, in three Xoo strains forming an African genetic lineage different from Asian Xoo. A phylogenetic analysis of the three TALomes combined with in silico predictions of TAL effector targets showed that African Xoo TALomes are highly conserved, genetically distant from Asian ones, and closely related to TAL effectors from the bacterial leaf streak pathogen Xanthomonas oryzae pv. oryzicola (Xoc). Nine clusters of TAL effectors could be identified among the three TALomes, including three showing higher levels of variation in their repeat variable diresidues (RVDs). Detailed analyses of these groups revealed recombination events as a possible source of variation among TAL effector genes. Next, to address contribution to virulence, nine TAL effector genes from the Malian Xoo strain MAI1 and four allelic variants from the Burkinabe Xoo strain BAI3, thus representing most of the TAL effector diversity in African Xoo strains, were expressed in the TAL effector-deficient X. oryzae strain X11-5A for gain-of-function assays. Inoculation of the susceptible rice variety Azucena lead to the discovery of three TAL effectors promoting virulence, including two TAL effectors previously reported to target the susceptibility (S) gene OsSWEET14 and a novel major virulence contributor, TalB. RNA profiling experiments in rice and in silico prediction of EBEs were carried out to identify candidate targets of TalB, revealing OsTFX1, a bZIP transcription factor previously identified as a bacterial blight S gene, and OsERF#123, which encodes a subgroup IXc AP2/ERF transcription factor. Use of designer TAL effectors demonstrated that induction of either gene resulted in greater susceptibility to strain X11-5A. The induction of OsERF#123 by BAI3Δ1, a talB knockout derivative of BAI3, carrying these designer TAL effectors increased virulence of BAI3Δ1, validating OsERF#123 as a new, bacterial blight S gene.
The T(z) phase diagram of the Cu sub(2)Zn sub(1-z)Mn sub(z)GeSe sub(4) alloy system is obtained from X-ray diffraction and differential thermal analysis DTA. At room temperature, the X-ray ...diffraction data showed that samples in the ranges 0 < z < 0.375 had the tetragonal stannite alpha structure (I42m), while for 0.725 < z < or =, slant 1 the wurtz-stannite delta structure (Pmn2 sub(1)). The alpha and delta fields are separated by a relative wide three-phase field ( alpha + delta + MnSe sub(2)). The DTA thermograms were used to construct the phase diagram of the Cu sub(2)Zn sub(1-z)Mn sub(z)-GeSe sub(4) alloy system. It was confirmed that the Cu sub(2)ZnGeSe sub(4) and Cu sub(2)MnGeSe sub(4) compounds melt incongruently. It was observed that undercooling effects occur for samples in the range 0.725 < z < 0.925
Injuries in the metatarsophalangeal joint complex of the hallux are seen with greater frequency in athletes, their importance lies in the functional limitation it generates. Early diagnosis and ...treatment can reduce the sequelae, however, the recognition of chronic lesions and with it the implementation of adequate therapeutic management generate improvements in quality of life. This document records a case of inveterate dislocation of the metatarsophalangeal joint of the hallux of more than one year of evolution with involvement of the intersesamoid ligament which was corrected with arthrodesis achieving immediate satisfactory results, in the medium and long term with the subsequent functional recovery and total reduction of pain.
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer. In the United States it is second leading cause of cancer related deaths in men. PCa is often treated via radical ...prostatectomy (RP). However, 15-30% of the patients develop biochemical recurrence (i.e. increased serum prostate specific antigen (PSA) levels). Interleukin-15 (IL-15) is a secreted cytokine found over expressed in patients with recurrence-free survival after RP. In our study, we aim to determine the role of IL-15 in PCa using in vitro and in vivo models, and gene expression analysis. PC3 (androgen-independent) and 22RV1 (androgen-dependent) cell lines were treated with IL-15 at 0.0013 ng/mL and 0.1 ng/mL. Tumor growth was evaluated using an orthotopic xenograft model. The anterior prostate lobes of SCID mice were injected with 250,000 22RV1 cells and IL-15 was administered bi-weekly with intraperitoneal (IP) injections during 4 weeks. Tumor tissue was collected for immunohistochemical and gene expression analysis. To study changes in gene expression, we looked at "Tumor Metastasis" and "PI3K pathway" using commercially available PCR arrays. In addition, we employed a microarray approach using the Affymetrix Hugene 2.0 ST array chip followed by analysis with Ingenuity Pathways Analysis (IPA) software. In vitro studies showed that IL-15 decreased PCa cell motility at both concentrations. In vivo studies showed that IL-15 increased neutrophil infiltration, and the expression of adiponectin, desmin and alpha smooth muscle actin (α-sma) in the tumor tissue. Angiogenesis analysis, using CD31 immunohistochemistry, showed that IL-15 decreased the number of blood vessels. Gene expression analysis identified Cancer, Cell Death, Immune Response and Lipid Metabolism as the major diseases and functions altered in tumors treated with IL-15. This suggests that IL-15 causes inflammation and changes in stroma that can promote decreased tumor cell proliferation.
"Distress disorders," which include generalized anxiety disorder and major depression are often highly comorbid with each other and appear to be characterized by common temperamental features that ...reflect heightened sensitivity to underlying motivational systems related to threat/safety and reward/loss. Further, individuals with distress disorders tend to utilize self-referential processes (e.g., worry, rumination, self-criticism) in a maladaptive attempt to respond to motivationally relevant distress, often resulting in suboptimal contextual learning. Despite the success of cognitive behavioral therapies for emotional disorders, a sizable subgroup of patients with distress disorders fail to evidence adequate treatment response. Emotion Regulation Therapy (ERT) is a theoretically derived, evidence based, treatment that integrates principles (e.g., skills training, exposure) from traditional and contemporary therapies with findings from basic and translational affective science to offer a framework for improving intervention by focusing on the motivational responses and corresponding regulatory characteristics of individuals with high levels of chronic distress. Open and randomized controlled trials have demonstrated preliminary support for the utility of ERT as reflected by strong effect sizes comparable to and exceeding established intervention approaches. In addition, pilot findings support the role of underlying proposed mechanisms in this efficacious response. This article presents the functional model associated with ERT and describes the proposed mechanisms of the treatment. Additionally, a clinical case is presented, allowing the reader to gain a greater applied understanding of the different components of the ERT model and treatment.
Extreme El Niño events stand out not only because they have powerful impacts but also because they are significantly different from other El Niños. In Ecuador, such events are accountable for
...negatively impacting the economy, infrastructure, and population. Spatial–temporal
dynamics of precipitation anomalies from various types of extreme El
Niño events are analyzed and compared. Results show that for eastern Pacific (EP) and coastal Pacific (COA) El Niño types, most precipitation extremes occur in the first half of the second year of the event. Any significant difference
between events becomes more evident at this stage. Spatially, for any event, 50 % of all extreme anomalies occurred at elevations < 150 m. The difference between events was significant when considering the altitude when reaching 80 % of all extreme anomalies: the eastern Pacific (EP) El Niño from 1997/98 (EP98) at 500 m, the El Niño from January to April 2017 (COA17) at 800 m, and the EP El
Niño from 1982/83 (EP83) at 1000 m. Nevertheless, in some sectors of the Andean Cordillera, the El Niño–Southern
Oscillation (ENSO) signal could be detected at 3200–3900 m. The distance to the coastline and the
steepness of relief may play a determining role. At lowlands, anomalies are
most severe in regions where the seasonality index is the highest. These results
are useful at different decision-making levels for identifying the most
appropriate practices reducing vulnerability from a potential increase in
extreme El Niño frequency and intensity.
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