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Separations based on molecular size (molecular sieving) are a solution for environmental remediation. We have synthesized and characterized two new metal-organic frameworks (MOFs) (Zn2M; M = Zn, Cd) with ultramicropores (<0.7 nm) suitable for molecular sieving. We explore the synthesis of these MOFs and the role that the DMSO/H2O/DMF solvent mixture has on the crystallization process. We further explore the crystallographic data for the DMSO and methanol solvated structures at 273 and 100 K; this not only results in high-quality structural data but also allows us to better understand the structural features at temperatures around the gas adsorption experiments. Structurally, the main difference between the two MOFs is that the central metal in the trimetallic node can be changed from Zn to Cd and that results in a sub-Å change in the size of the pore aperture, but a stark change in the gas adsorption properties. The separation selectivity of the MOF when M = Zn is infinite given the pore aperture of the MOF can accommodate CO2 while N2 and/or CH4 is excluded from entering the pore. Furthermore, due to the size exclusion behavior, the MOF has an adsorption selectivity of 4800:1 CO2/N2 and 5 × 1028:1 CO2/CH4. When M = Cd, the pore aperture of the MOF increases slightly, allowing N2 and CH4 to enter the pore, resulting in a 27.5:1 and a 10.5:1 adsorption selectivity, respectively; this is akin to UiO-66, a MOF that is not able to function as a molecular sieve for these gases. The data delineate how subtle sub-Å changes to the pore aperture of a framework can drastically affect both the adsorption selectivity and separation selectivity.
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Glioblastoma (GBM) is a universally fatal disease, complicated by significant cognitive and physical disabilities, inherent to the disease course. The purpose of this study was to retrospectively analyze end-of-life care for GBM patients at an academic center and compare utilization of these services to national quality of care guidelines, with the goal of identifying opportunities to improve end-of-life care. Single center retrospective cohort study of GBM patients at Johns Hopkins Hospital (JHH) between 2009 and 2014, using electronic medical records and hospice records. Comprehensive medical record review of 100 randomly selected patients with GBM, who were actively treated at JHH. Secondary analysis of all JHH GBM patients (n = 45) who received hospice care at Gilchrist Services, our largest provider, during this time period. Of 100 patients, 76 were referred to hospice. Despite the poor survival and changes in mental capacity associated with this disease, only 40% of individuals had documentation of code status and only 17% had any documentation of advance directives (ADs). None had documentation by a health care provider of a formal symptom, psychosocial, or spiritual assessment at greater than 50% of clinic visits. Only 17% used chemotherapy in their last month of life. 37% were hospitalized in the last month of life for an average of 9 days. Of the Gilchrist Services patients, the median length of stay in hospice was 21 days and 64% of these patients died in their residence with hospice services. Documentation of palliative care and end-of-life measures could improve quality of care for GBM patients, especially in the use of ADs, symptom, spiritual, and psychosocial assessments, with earlier use of hospice to prevent end-of-life hospitalizations.
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Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Cuidados Paliativos na Terminalidade da Vida/estatística & dados numéricos , Qualidade da Assistência à Saúde , Assistência Terminal/estatística & dados numéricos , Centros Médicos Acadêmicos/estatística & dados numéricos , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/psicologia , Estudos de Coortes , Feminino , Glioblastoma/mortalidade , Glioblastoma/psicologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The downstream migratory behaviour of wild Atlantic salmon Salmo salar smolts was monitored using passive integrated transponder (PIT) antennae systems over 10 years in the lower reaches of a small chalk stream in southern England, U.K. The timing of smolt movements and the likely occurrence of schooling were investigated and compared to previous studies. In nine of the 10 consecutive years of study, the observed diel downstream patterns of S. salar smolt migration appeared to be synchronized with the onset of darkness. The distribution of time intervals between successive nocturnal detections of PIT-tagged smolts was as expected if generated randomly from observed hourly rates. There were, however, significantly more short intervals than expected for smolts detected migrating during the day. For each year from 2006 to 2011, the observed 10th percentile of the daytime intervals was <4 s, compared to ≥55 s for the simulated random times, indicating greater incidence of groups of smolts. Groups with the shortest time intervals between successive PIT tag detections originated from numerous parr tagging sites (used as a proxy for relatedness). The results suggest that the ecological drivers influencing daily smolt movements in the lower reaches of chalk stream catchments are similar to those previously reported at the onset of migration for smolts leaving their natal tributaries; that smolts detected migrating during the night are moving independently following initiation by a common environmental factor (presumably darkness), whereas those detected migrating during the day often move in groups, and that such schools may not be site (kin)-structured. The importance of understanding smolt migratory behaviour is considered with reference to stock monitoring programmes and enhancing downstream passage past barriers.
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Migração Animal , Fotoperíodo , Salmo salar/fisiologia , Sistemas de Identificação Animal , Animais , Inglaterra , RiosRESUMO
Background: Esophagectomy, an esophageal cancer treatment mainstay, is a highly morbid procedure. Prolonged operative time, only partially predetermined by case complexity, may be uniquely harmful to minimally-invasive esophagectomy (MIE) patients for numerous reasons, including anastomotic leak, tenuous conduit perfusion and protracted single-lung ventilation, but the impact is unknown. This multi-center retrospective cohort study sought to characterize the relationship between MIE operative time and post-operative outcomes. Methods: We abstracted multi-center data on esophageal cancer patients who underwent MIE from 2010 to 2021. Predictor variables included age, sex, comorbidities, body mass index, prior cardiothoracic surgery, stage, and neoadjuvant therapy. Outcomes included complications, readmissions, and mortality. Association analysis evaluated the relationship between predictor variables and operative time. Multivariate logistic regression characterized the influence of potential predictor variables and operative time on post-operative outcomes. Subgroup analysis evaluated the association between MIE >4â h vs. ≤4â h and complications, readmissions and survival. Results: For the 297 esophageal cancer patients who underwent MIE between 2010 and 2021, the median operative duration was 4.8â h [IQR: 3.7-6.3]. For patients with anastomotic leak (5.1%) and 1-year mortality, operative duration was elevated above the median at 6.3â h [IQR: 4.8-8.6], p = 0.008) and 5.3â h [IQR: 4.4-6.8], p = 0.04), respectively. In multivariate logistic regression, each additional hour of operative time increased the odds of anastomotic leak and 1-year mortality by 39% and 19%, respectively. Conclusions: Esophageal cancer is a poor prognosis disease, even with optimal treatment. Operative efficiency, a modifiable surgical variable, may be an important target to improve MIE patient outcomes.
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The storage of red blood cells (RBC) results in increased concentrations of plasma free hemoglobin, potassium, glucose, and lactate, among other undesirable substances. These concentrations continue to increase as RBC products age and can cause deleterious effects to the patient. In the setting of cardiac surgery, the autotransfusion devices are routinely used to wash blood that is shed from the surgical site. These devices could also be used to wash stored RBC units obtained from the blood bank. The objective of this study was to compare the product created by washing a unit of RBCs with the AutoLog autotransfusion device in the operating room to the washed products from a standard cell washer in the blood bank. Eleven outdated RBC units (stored for >42 days at 4 °C) were split in half. One half was washed using the Medtronic AutoLog device; the other half was washed using the blood bank's Cobe 2991 Cell Processor. Analytes were measured on samples from the unwashed parent unit and from the washed daughter units. The parameters measured included hematocrit, free hemoglobin, lactate, lactate dehydrogenase (LDH), potassium, glucose, and pH. When compared to the original untreated RBCs, the glucose, lactate, and potassium levels were decreased when washed in an autotranfusion device. Additionally, the free hemoglobin and LDH levels were significantly lower with the Medtronic Autolog cell saver than in the COBE 2991 Cell Processor. Washing the RBC donor units in an autotransfusion device prior to transfusion can effectively attenuate the increases seen in glucose, potassium, free hemoglobin, and LDH associated with RBC storage lesion.
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Remoção de Componentes Sanguíneos/métodos , Preservação de Sangue/métodos , Eritrócitos/citologia , Transfusão de Sangue Autóloga/métodos , Transfusão de Eritrócitos/métodos , HumanosRESUMO
Inorganic metal halides offer unprecedented tunability through elemental variation of simple three-element compositions, but can exhibit complicated phase behaviour, degradation, and microscopic phenomena (disorder/dynamics) that play an integral role for the bulk-level chemical and physical properties of these materials. Understanding the halogen chemical environment in such materials is crucial to addressing many of the concerns regarding implementing these materials in commercial applications. In this study, a combined solid-state nuclear magnetic resonance, nuclear quadrupole resonance and quantum chemical computation approach is used to interrogate the Br chemical environment in a series of related inorganic lead bromide materials: CsPbBr3, CsPb2Br5, and Cs4PbBr6. The quadrupole coupling constants (CQ) were determined to range from 61 to 114 MHz for 81Br, with CsPbBr3 exhibiting the largest measured CQ and Cs4PbBr6 the smallest. GIPAW DFT was shown to be an excellent pre-screening tool for estimating the EFG of Br materials and can increase experimental efficiency by providing good starting estimates for acquisition. Finally, the combination of theory and experiment to inform the best methods for expanding further to the other quadrupolar halogens is discussed.
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Brometos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Chumbo , Halogênios/químicaRESUMO
BACKGROUND AND OBJECTIVES: Knowledge, attitude and practice (KAP) surveys have been used in many countries to understand factors that influence blood donation and as the basis for communication and donor mobilization strategies. MATERIALS AND METHODS: A search was conducted of publically available databases, and studies with the following characteristics were selected: (1) the study was a knowledge, attitude and practice or KAP plus behaviour survey; (2) the subject of the survey was blood donation; (3) the survey was performed between 1995 and 2011; and (4) the survey was performed in countries classified as emerging and developing by the International Monetary Fund. RESULTS: Eighteen KAP studies conducted in seventeen developing countries were identified. There was considerable difference in the structure, population surveyed and conduct of the KAP studies. The common following themes emerged: misinformation about blood donation, fear of blood donation, willingness to donate for family and friends, concern about selling blood and a failure to transfer positive attitudes into actual blood donation. CONCLUSION: Despite considerable differences in the culture and demographics of developing countries, several common themes emerged from different KAP surveys.
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Doadores de Sangue/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Coleta de Dados , Países em Desenvolvimento , HumanosRESUMO
Background: The specialty of hospice and palliative medicine struggles to merge the fast-paced technological consultative work of acute hospital palliative care with slower paced and home-based hospice. Each has equal if different merits. Here, we describe creation of a position that allowed half-time hospice employment, alongside academic hospital-based palliative care. Methods: Johns Hopkins Medicine and Gilchrist, Inc., a large nonprofit hospice, partnered to form a joint position with time spent equally between the two locations. Results: Created as a university position with "leasing" to the hospice, specific attention has been paid to mentoring at both sites to allow professional advancement. Both organizations have benefited in terms of recruitment, and more physicians have chosen this dual pathway suggesting that it is working well. Discussion: Hybrid positions are possible and may be desired by those who wish to practice both palliative medicine and hospice. Creation of one successful position helped recruit a second and a third candidate a year later. The original recipient has been promoted within Gilchrist to direct the inpatient unit. Such positions require careful mentoring and coordination to allow success at both sites and this can be done with foresight.
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Transcription factor (TF)-promoter pairs have been repurposed from native hosts to provide tools to measure intracellular biochemical production titer and dynamically control gene expression. Most often, native TF-promoter systems require rigorous screening to obtain desirable characteristics optimized for biotechnological applications. High-throughput techniques may provide a rational and less labor-intensive strategy to engineer user-defined TF-promoter pairs using fluorescence-activated cell sorting and deep sequencing methods (sort-seq). Based on the designed promoter library's distribution characteristics, we elucidate sequence-function interactions between the TF and DNA. In this work, we use the sort-seq method to study the sequence-function relationship of a σ54-dependent, butanol-responsive TF-promoter pair, BmoR-PBMO derived from Thauera butanivorans, at the nucleotide level to improve biosensor characteristics, specifically an improved dynamic range. Activities of promoters from a mutagenized PBMO library were sorted based on gfp expression and subsequently deep sequenced to correlate site-specific sequences with changes in dynamic range. We identified site-specific mutations that increase the sensor output. Double mutant and a single mutant, CA(129,130)TC and G(205)A, in PBMO promoter increased dynamic ranges of 4-fold and 1.65-fold compared with the native system, respectively. In addition, sort-seq identified essential sites required for the proper function of the σ54-dependent promoter biosensor in the context of the host. This work can enable high-throughput screening methods for strain development.
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Developmental Coordination Disorder (DCD) is one of the least studied and understood developmental disorders. One area that has been minimally investigated in DCD is potential issues with sensory modulation. Further, in other neurodevelopmental disorders (e.g., autism spectrum disorder (ASD)) sensory modulation is related to many other challenges (e.g., social issues, repetitive behaviors, anxiety); however, such potential relationships in children with DCD have been largely unexplored. The purpose of this study is to explore sensory modulation differences in DCD and to understand the relationships between sensory modulation and social emotional measures, behavior, and motor skills in DCD in comparison to ASD and typically developing (TD) peers. Participants (aged 8-17) and their caregivers (DCD, N = 26; ASD, N = 57; and TD, N = 53) completed behavioral and clinical measures. The results indicated that 31% of the DCD group showed sensory modulation difficulties, with the DCD group falling between the ASD and TD groups. In the DCD group, sensory modulation was significantly associated with anxiety, empathic concern, repetitive behaviors, and motor skills. Data are compared to patterns seen in ASD and TD groups and implications for interventions are discussed.
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Metal halide perovskites remain top candidates for higher-performance photovoltaic devices, but concerns about leading lead-based materials remain. Ge perovskites remain understudied for use in solar cells compared to their Sn-based counterparts. In this work, we undertake a combined 73Ge and 133Cs solid-state Nuclear Magnetic Resonance (NMR) spectroscopy and density functional theory (DFT) study of the bulk CsGeX3 (X = Cl, Br, or I) series. We show how seemingly small structural variations within germanium halide perovskites have major effects on their 73Ge and 133Cs NMR signatures and reveal a near-cubic phase at room temperature for CsGeCl3 with severe local Ge polyhedral distortion. Quantum chemical computations are effective at predicting the structural impact on NMR parameters for 73Ge and 133Cs. This study demonstrates the value of a combined solid-state NMR and DFT approach for investigating promising materials for energy applications, providing information that is out of reach with conventional characterization methods, and adds the challenging 73Ge nucleus to the NMR toolkit.
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Gene fusions are known to drive many human cancers. Therefore, the functional characterization of newly discovered fusions is critical to understanding the oncobiology of these tumors and to enable therapeutic development. NPM1-TYK2 is a novel fusion identified in CD30 + lymphoproliferative disorders, and here we present the functional evaluation of this fusion gene as an oncogene. The chimeric protein consists of the amino-terminus of nucleophosmin 1 (NPM1) and the carboxyl-terminus of tyrosine kinase 2 (TYK2), including the kinase domain. Using in vitro lymphoid cell transformation assays and in vivo tumorigenic xenograft models we present direct evidence that the fusion gene is an oncogene. NPM1 fusion partner provides the critical homodimerization needed for the fusion kinase constitutive activation and downstream signaling that are responsible for cell transformation. As a result, our studies identify NPM1-TYK2 as a novel fusion oncogene and suggest that inhibition of fusion homodimerization could be a precision therapeutic approach in cutaneous T-cell lymphoma patients expressing this chimera.
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Fully oxidized ß-carotene (OxBC) containing ß-carotene-oxygen copolymers is proposed as an alternative to antimicrobial growth promoters. Two trials were conducted to determine the efficacy of OxBC in enhancing growth and feed intake (FI) in male and female Ross × Ross 308 broilers in Ontario, Canada, and in Ross 308 male broilers in the United Kingdom. In the first trial, 0, 1, 2, or 5 ppm OxBC were added to diets in a 20% cornstarch premix, whereas in the second trial, 0, 2, or 5 ppm OxBC were added in a 1% cornstarch or 1% corncob grits premix. In trial 1, 2, and 5 ppm OxBC improved bird final body weights (BW) compared with the unsupplemented, nonmedicated (no bacitracin methylene disalicylate included), negative control birds after 39 d of feeding under commercial conditions (P < 0.05). All levels of OxBC improved feed conversion (FCR) during the finisher period (P < 0.05), whereas 2 and 5 ppm OxBC enhanced FCR relative to the negative control group during the full production cycle (P < 0.05). Average daily FI was not affected by OxBC, whereas 2 and 5 ppm OxBC increased broiler average daily gain (ADG) (P < 0.05). Oxidized ß-carotene did not affect bird mortality. The optimal OxBC dose was 2 ppm under the conditions used. In trial 2, 2 or 5 ppm OxBC on cornstarch and 5 ppm OxBC on corncob grits improved ADG, BW, and FI when fed for 35 d, as compared with the negative, nonmedicated control (P < 0.05). Feed conversion was not improved in the OxBC groups compared with the control group (P > 0.05). There were no differences among the 3 OxBC groups (P > 0.05). When birds were fed 2 ppm OxBC on corncob grits, the overall ADG, BW, and FI were lower than the respective control values (P < 0.001). Overall bird mortality was higher than expected for all groups, including the control group, but no dose effect was evident. Cornstarch was the preferred carrier for OxBC, and 2 ppm OxBC was the optimal dose under the conditions used.
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Fenômenos Fisiológicos da Nutrição Animal , Galinhas , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Masculino , Ontário , beta CarotenoRESUMO
Silicon nanoparticles (SiNPs) can be challenging to prepare with defined size, crystallinity, composition, and surface chemistry. As is the case for any nanomaterial, controlling these parameters is essential if SiNPs are to realize their full potential in areas such as alternative energy generation and storage, sensors, and medical imaging. Numerous teams have explored and established innovative synthesis methods, as well as surface functionalization protocols to control these factors. Furthermore, substantial effort has been expended to understand how the abovementioned parameters influence material properties. In the present review we provide a commentary highlighting the benefits and limitations of available methods for preparing silicon nanoparticles as well as demonstrations of tailoring optical and electronic properties through definition of structure (i.e., crystalline vs. amorphous), composition and surface chemistry. Finally, we highlight potential opportunities for future SiNP studies.
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Coumadin (R/S-warfarin) anticoagulant therapy is highly efficacious in preventing the formation of blood clots; however, significant inter-individual variations in response risks over or under dosing resulting in adverse bleeding events or ineffective therapy, respectively. Levels of pharmacologically active forms of the drug and metabolites depend on a diversity of metabolic pathways. Cytochromes P450 play a major role in oxidizing R- and S-warfarin to 6-, 7-, 8-, 10-, and 4'-hydroxywarfarin, and warfarin alcohols form through a minor metabolic pathway involving reduction at the C11 position. We hypothesized that due to structural similarities with warfarin, hydroxywarfarins undergo reduction, possibly impacting their pharmacological activity and elimination. We modeled reduction reactions and carried out experimental steady-state reactions with human liver cytosol for conversion of rac-6-, 7-, 8-, 4'-hydroxywarfarin and 10-hydroxywarfarin isomers to the corresponding alcohols. The modeling correctly predicted the more efficient reduction of 10-hydroxywarfarin over warfarin but not the order of the remaining hydroxywarfarins. Experimental studies did not indicate any clear trends in the reduction for rac-hydroxywarfarins or 10-hydroxywarfarin into alcohol 1 and 2. The collective findings indicated the location of the hydroxyl group significantly impacted reduction selectivity among the hydroxywarfarins, as well as the specificity for the resulting metabolites. Based on studies with R- and S-7-hydroxywarfarin, we predicted that all hydroxywarfarin reductions are enantioselective toward R substrates and enantiospecific for S alcohol metabolites. CBR1 and to a lesser extent AKR1C3 reductases are responsible for those reactions. Due to the inefficiency of reactions, only reduction of 10-hydroxywarfarin is likely to be important in clearance of the metabolite. This pathway for 10-hydroxywarfarin may have clinical relevance as well given its anticoagulant activity and capacity to inhibit S-warfarin metabolism.
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We present a potential solution to the problem of extraction of photogenerated holes from CdS nanocrystals and nanowires. The nanosheet form of C3N5 is a low-band-gap (Eg = 2.03 eV), azo-linked graphenic carbon nitride framework formed by the polymerization of melem hydrazine (MHP). C3N5 nanosheets were either wrapped around CdS nanorods (NRs) following the synthesis of pristine chalcogenide or intercalated among them by an in situ synthesis protocol to form two kinds of heterostructures, CdS-MHP and CdS-MHPINS, respectively. CdS-MHP improved the photocatalytic degradation rate of 4-nitrophenol by nearly an order of magnitude in comparison to bare CdS NRs. CdS-MHP also enhanced the sunlight-driven photocatalytic activity of bare CdS NWs for the decolorization of rhodamine B (RhB) by a remarkable 300% through the improved extraction and utilization of photogenerated holes due to surface passivation. More interestingly, CdS-MHP provided reaction pathway control over RhB degradation. In the absence of scavengers, CdS-MHP degraded RhB through the N-deethylation pathway. When either hole scavenger or electron scavenger was added to the RhB solution, the photocatalytic activity of CdS-MHP remained mostly unchanged, while the degradation mechanism shifted to the chromophore cleavage (cycloreversion) pathway. We investigated the optoelectronic properties of CdS-C3N5 heterojunctions using density functional theory (DFT) simulations, finite difference time domain (FDTD) simulations, time-resolved terahertz spectroscopy (TRTS), and photoconductivity measurements. TRTS indicated high carrier mobilities >450 cm2 V-1 s-1 and carrier relaxation times >60 ps for CdS-MHP, while CdS-MHPINS exhibited much lower mobilities <150 cm2 V-1 s-1 and short carrier relaxation times <20 ps. Hysteresis in the photoconductive J-V characteristics of CdS NWs disappeared in CdS-MHP, confirming surface passivation. Dispersion-corrected DFT simulations indicated a delocalized HOMO and a LUMO localized on C3N5 in CdS-MHP. C3N5, with its extended π-conjugation and low band gap, can function as a shuttle to extract carriers and excitons in nanostructured heterojunctions, and enhance performance in optoelectronic devices. Our results demonstrate how carrier dynamics in core-shell heterostructures can be manipulated to achieve control over the reaction mechanism in photocatalysis.
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Genetic diversity within the geobiosphere encompasses enormous sensing capabilities and many non-model bacteria are of biotechnological interest. Biosensing, or more generally inducible, systems are a vital component of metabolic engineering, as they allow tight control of gene expression as well as the basis for high-throughput screens on non-growth-related phenotypes. While these inducible systems, primarily transcription factor/promoter pairs, have been utilized extensively in Escherichia coli, progress in other bacteria is limited because of differences in transcription machinery, physiological compatibility of parts and proteins, and other nuances. Here, we provide an overview of the available genetic biosensing elements in non-model organisms and state-of-the-art efforts to engineer them, and then discuss challenges preventing these methods from common use in non-model bacteria.
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Técnicas Biossensoriais , Fatores de Transcrição , Bactérias/genética , Escherichia coli/genética , Engenharia Metabólica , Fatores de Transcrição/genéticaRESUMO
* We used an inadvertent whole-ecosystem 14C label at a temperate forest in Oak Ridge, Tennessee, USA to develop a model (Radix1.0) of fine-root dynamics. Radix simulates two live-root pools, two dead-root pools, non-normally distributed root mortality turnover times, a stored carbon (C) pool, and seasonal growth and respiration patterns. * We applied Radix to analyze measurements from two root size classes (< 0.5 and 0.5-2.0 mm diameter) and three soil-depth increments (O horizon, 0-15 cm and 30-60 cm). * Predicted live-root turnover times were < 1 yr and approximately 10 yr for short- and long-lived pools, respectively. Dead-root pools had decomposition turnover times of approximately 2 yr and approximately 10 yr. Realistic characterization of C flows through fine roots requires a model with two live fine-root populations, two dead fine-root pools, and root respiration. These are the first fine-root turnover time estimates that take into account respiration, storage, seasonal growth patterns, and non-normal turnover time distributions. * The presence of a root population with decadal turnover times implies a lower amount of belowground net primary production used to grow fine-root tissue than is currently predicted by models with a single annual turnover pool.
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Carbono/metabolismo , Respiração Celular , Raízes de Plantas/crescimento & desenvolvimento , Árvores/crescimento & desenvolvimento , Isótopos de Carbono , Ecossistema , Marcação por Isótopo/métodos , Modelos Biológicos , Raízes de Plantas/metabolismo , Estações do Ano , Tennessee , Fatores de Tempo , Árvores/metabolismoRESUMO
The effect of nerve growth factor (NGF), a substance that promotes the differentiation and maintenance of certain neurons, was studied via scanning electron microscopy utilizing the PC12 clonal NGF-responsive pheochromocytoma cell line. After 2-4 d of exposure to NGF, these cells acquire many of the properties of normal sympathic neurons. However, by phase microscopy, no changes are discernible within the first 12-18 h. Since the primary NGF receptor appears to be a membrane receptor, it seemed likely that some of the initial responses to the factor may be surface related. PC12 cells maintained without NGF are round to ovoid and have numerous microvilli and small blebs. After the addition of NGF, there is a rapidly initiated sequential change in the cell surface. Ruffles appear over the dorsal surface of the cells with 1 min, become prominent by 3 min, and almost disappear by 7 min. Microvilli, conversely, disappear as the dorsal ruffles become prominent. Ruffles are seen at the the periphery of cell at 3 min, are prominent on most of the cells by 7 min and are gone by 15 min. The surface remains smooth from 15 min until 45 min when large blebs appear. The large blebs are present on most cells at 2 h and are gone by 4 h. The surface remains relatively smooth until 6-7 h of NGF treatment, when microvilli reappear as small knobs. These microvilli increase in both number and length to cover the cell surface by 10 h. These changes were not observed with other basic proteins, with alpha-bungarotoxin (which binds specifically to PC12 membranes), and were not affected by an RNA synthesis inhibitor that blocks initiation of neurite outgrowth. Changes in the cell surface architecture appear to be among the earlist NGF responses yet detected and may represent or reflect primary events in the mechanism of the factor's action.
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Fatores de Crescimento Neural/farmacologia , Neurônios/efeitos dos fármacos , Animais , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Microscopia Eletrônica de Varredura , Microvilosidades/ultraestrutura , Neurônios/ultraestrutura , Feocromocitoma/ultraestrutura , RatosRESUMO
Magnetization measurements of the European eel Anguilla anguilla demonstrated the presence of magnetic material concentrated in the region of the mandibular canals of the lateral line system. The data suggest that the material is magnetite, has a size suitable for magnetoreception and is of biogenic origin. The presence of magnetic particles in the lateral line system is discussed in relation to their possible role in allowing the fish to orientate with respect to the geomagnetic field during their extensive oceanic spawning migrations.