Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphoproteome Dynamics Upon Changes in Plant Water Status Reveal Early Events Associated With Rapid Growth Adjustment in Maize Leaves*

Plant growth adjustment during water deficit is a crucial adaptive response. The rapid fine-tuned control achieved at the post-translational level is believed to be of considerable importance for regulating early changes in plant growth reprogramming. Aiming at a better understanding of early responses to contrasting plant water statuses, we carried out a survey of the protein phosphorylation events in the growing zone of maize leaves upon a range of water regimes. In this study, the impact of mild and severe water deficits were evaluated in comparison with constant optimal watering and with recovery periods lasting 5, 10, 20, 30, 45, and 60 min. Using four biological replicates per treatment and a robust quantitative phosphoproteomic methodology based on stable-isotope labeling, we identified 3664 unique phosphorylation sites on 2496 proteins. The abundance of nearly 1250 phosphorylated peptides was reproducibly quantified and profiled with high confidence among treatments. A total of 138 phosphopeptides displayed highly significant changes according to water regimes and enabled to identify specific patterns of response to changing plant water statuses. Further quantification of protein amounts emphasized that most phosphorylation changes did not reflect protein abundance variation. During water deficit and recovery, extensive changes in phosphorylation status occurred in critical regulators directly or indirectly involved in plant growth and development. These included proteins influencing epigenetic control, gene expression, cell cycle-dependent processes and phytohormone-mediated responses. Some of the changes depended on stress intensity whereas others depended on rehydration duration, including rapid recoveries that occurred as early as 5 or 10 mins after rewatering. By combining a physiological approach and a quantitative phosphoproteomic analysis, this work provides new insights into the in vivo early phosphorylation events triggered by rapid changes in plant water status, and their possible involvement in plant growth-related processes.
Molecular Identification of a Papilloma Virus from Cutaneous Lesions of Captive and Free-ranging Florida Manatees

Cutaneous papillomatous lesions were biopsied from three captive Florida manatees (Trichechus manatus latirostris) at Homosassa Springs State Wildlife Park (HSSWP), Homosassa, Florida, USA, and from six free-ranging Florida manatees from Crystal and Homosassa rivers, Florida. Total DNA extracted from these lesions was assayed for the presence of papilloma virus genomes using the polymerase chain reaction (PCR) with primers that target the L1 capsid protein gene. The amplification generated DNA fragments 458 base pairs in length that encompassed a highly conserved domain within the L1 capsid protein and translated into identical polypeptides of 152 amino acids, suggesting the involvement of a single papilloma virus genotype. Multiple amino acid sequence and phylogenetic analyses of the L1 fragment indicated that the Florida manatee papilloma virus is a unique and quite distinct papillomavirus from other known papilloma viruses. The emergence of this new pathogen raises concerns about its potential impact on the already endangered Florida manatee.
The BZLF1 Homolog of an Epstein-Barr-Related γ-Herpesvirus Is a Frequent Target of the CTL Response in Persistently Infected Rhesus Macaques1

Although CD8+ T lymphocytes targeting lytic infection proteins dominate the immune response to acute and persistent EBV infection, their role in immune control of EBV replication is not known. Rhesus lymphocryptovirus (rhLCV) is a γ-herpesvirus closely related to EBV, which establishes persistent infection in rhesus macaques. In this study, we investigated cellular immune responses to the rhLCV BZLF1 (rhBZLF1) homolog in a cohort of rhLCV-seropositive rhesus macaques. rhBZLF1-specific IFN-γ ELISPOT responses ranging between 56 and 3070 spot-forming cells/106 PBMC were detected in 36 of 57 (63%) rhesus macaques and were largely mediated by CD8+ T lymphocytes. The prevalence and magnitude of ELISPOT responses were greater in adult (5–15 years of age) rather than juvenile macaques (<5 years of age), suggesting that rhBZLF1-specific CTL increase over time following early primary infection. A highly immunogenic region in the carboxyl terminus of the rhBZLF1 protein containing overlapping CTL epitopes restricted by Mamu-A*01 and other as yet unidentified MHC class I alleles was identified. The presence of a robust CD8+ T lymphocyte response targeting this lytic infection protein in both rhesus macaques and humans suggests that these CTL may be important for immune control of EBV-related γ-herpesvirus infection. These data underscore the utility of the rhLCV-macaque model for studies of EBV pathogenesis.
Embryonic stem cell.

Mouse embryonic stem (ES) cells are the cells that possess pluripotential differentiation activity into not only all somatic cells but also germ cells. Genetic alteration of mouse ES cells can be easily achieved and such genetic modification can be introduced into the animal, since ES cells are differentiated into germ cells in vivo. This technology enables us to analyze the function of any particular genes of interest in mice. And in vitro differentiation induction of mouse ES cells into various cell lineages, such as blood cells, neural cells, and cardiac muscle cells, has been studied. In vitro hematopoietic differentiation experiments were carried out most extensively and can be regarded as a model system of induction. Recently, human ES cells have been established. Many scientists, clinicians and even mass media have entertained the idea that human ES cells can be used after changing the cells into lineage-specific stem cells or progenitor cells such as hematopoietic stem cells and neural progenitor cells.
Investigating the Molecular Basis for the Virulence of Escherichia coli K5 by Nuclear Magnetic Resonance Analysis of the Capsule Polysaccharide

The capsular polysaccharide of Escherichia coli K5 has been hypothesised to promote virulence through its molecular mimicry of host heparan sulphate. To test this hypothesis, we have produced pure oligosaccharides from K5 capsular polysaccharide and investigated their conformational properties with ultra-high-field nuclear magnetic resonance (NMR) (900 MHz). Ultra-high-field affords a significant resolution enhancement over previous studies and allowed a full-atomic assignment of the K5 hexasaccharide for the first time. All carbohydrate rings adopt a 4C1 conformation, the amide sidechains have a trans orientation and the hydroxymethyl group is freely exposed to bulk solvent. Initial models of the glycosidic linkage conformation based upon simple interpretation of NOE cross-peaks suggests that the β1→4 linkage adopts a 3D geometry of φ ≈ 60°, ψ ≈ 0° and the α1→4 linkage prefers φ ≈ –30°, ψ ≈ –30° (φ and ψ being defined by dihedral angles involving linkage protons). In this conformation the overall molecular geometries of K5 polysaccharide, heparan sulphate and even fully-sulphated heparin are remarkably similar. These results substantiate the hypothesis that the K5 capsular polysaccharide confers virulence to E. coli K5 by being a 3D molecular mimetic of host heparan sulphate, helping it to evade detection by the mammalian immune system.
Exocellular glycopeptide from a Penicillium charlesii mutant incapable of growth on D-galactose

The compositions of exocellular saccharide-containing polymers from six mutants of Penicillium charlesii incapable of growing on galactose were investigated. The polymers from the mutants contain a much smaller percentage of galactose than that reported for the peptidophosphogalactomannan (PPGM) from the wild-type organism (Gander et al. 1974). A polymer containing only one galactosyl residue per 49 mannosyl residues was investigated in detail. This polymer is a glycopeptide (peptidomannan) with an amino acid composition similar to that of peptidophospogalactomannan and a mass of about 23,000 daltons. Treatment of peptidomannan with 0.4 N NaOH releases mannan, mannopentaose, mannotetraose, mannotriose, mannobiose, and mannose residues, which are attached to the peptide by O-glycosidic linkage to seryl and threonyl groups. The quantity of glycerol and threitol, derived from mannosyl and internal galactofuranosyl residues, respectively, following Smith degradation, showed that peptidomannan contains 2 mol of internal galactofuranosyl residues per mol of polymer. The polymer contains only 3 mol of (1 yields 5)-linked galactofuranosyl residues per mol of polymer, as described by analysis of the methylation products. Methylation analysis also indicates that the polysaccharide contains primarily (1 yields 2)-linked (67.5%) and (1 yields 6)-linked (20.2%) mannopyranosyl residues. However, acetolysis of the polymer suggests that 37% of the residues are (1 yields 6)-linked. Mannopentaose, mannotetraose, mannotriose, mannobiose, and mannose in a molar ratio of 0.30:0.11:0.15:0.39:0.06, respectively, are released by acetolysis. This result is similar to that obtained with peptidophosphogalactomannan. We conclude that the occurrence of large numbers of galactofuranosyl residues in the major extracellular glycopeptide is not an obligatory requirement for glycopeptide formation.
The chemotherapy of rodent malaria. LXII. Drug combinations to impede the selection of drug resistance, part 5: rates of development of resistance to some inhibitors of folate metabolism and to artesunate

Abstract In recent years infection with chloroquine-resistant Plasmodium falciparum has been combatted with two long-acting antimalarials, pyrimethamine and sulfadoxine, in the combination known as Fansidar® that exerts a strong, synergistic action on the asexual stages of the parasite. This second-line regimen, however, is failing increasingly because of the selection of resistant clones in endemic areas, and effective, safe, alternative drugs or drug combinations that are also affordable are urgently needed. Antimalarial drugs with shorter half-lives than those of pyrimethamine or sulfadoxine are likely to be slower to select resistant parasites. In the experiments reported here, the baseline in-vivo responses of rodent malarial parasites to chlorproguanil and proguanil and their active metabolites, chlorcycloguanil and cycloguanil, as well as those to dapsone and artesunate, were explored. In general, the most sensitive parasite to all of these compounds was P. chabaudi. When the drugs were used, individually, to select resistance via the '2%-relapse technique', relatively stable resistance to each was obtained in P. chabaudi as well as in P. berghei and P. yoelii ssp. NS, the last of these being also highly resistant to chloroquine. Of most concern was the rapidity and high level of resistance developed by P. chabaudi to artesunate. The experiments also validated the use of chlorcycloguanil or cycloguanil as surrogates for chlorproguanil or proguanil. Further studies to investigate the possible value of administering chlorproguanil–dapsone, with or without artesunate, are under way and will be reported separately.
Maternal interaction patterns and preschool competence in high-risk children.

BACKGROUND The influence of specific maternal interaction patterns as compensatory mechanisms in promoting development of medically high-risk children has been understudied. OBJECTIVES To investigate the association of three maternal interaction patterns, maternal responsivity, involvement, and control style, with preschool competency in a medically heterogeneous sample. METHOD Children (N= 184) and their mothers participating in a prospective longitudinal study were assessed in a laboratory protocol and home visit. The methods of measurement were maternal self-report, global rating scales, interview, and nationally standardized instruments. RESULTS Evidence of a maternal compensatory mechanism was exhibited in mothers' higher involvement with their children who were born at high medical risk (F(1,183) = 6.26, p = . 01). Mothers of the most competent children demonstrated higher maternal responsivity, involvement, and more appropriate control than mothers of children who were not as competent. In hierarchical regression models, the three maternal interaction patterns were significant predictors after perinatal risk and maternal education were controlled explaining 29-37% of the variance in child competence scores. CONCLUSION These findings imply that differential child outcomes are associated with specific maternal interaction patterns. It suggests that a combination of diverse information revealed in specific maternal interaction pattern is needed to predict cognitive, linguistic, and problem-solving competencies. Future research should consider individual differences in mother-child interaction patterns in order to isolate their significance for optimal child development.
Physiologic Status of Regenerated Hair Cells in the Avian Inner Ear following Aminoglycoside Ototoxicity

Regeneration of avian inner ear hair cells has been demonstrated after administration of aminoglycoside and after acoustic trauma. However, no published study to date has documented functional recovery of these regenerated sensory receptor cells. Newborn chicks were treated with gentamicin sulfate (50 mg/kg/day) for a total of either 5 (n = 10) or 10 (n = 76) days. Evoked potential thresholds were obtained one day after the 5-day treatment, or at intervals between one day and 20 weeks after the 10-day treatment course, and compared to thresholds of age-matched control animals. A significant hearing loss, predominantly in the high frequencies, was present after as few as 5 days of drug administration. The magnitude of hearing loss continued to increase, especially at lower frequencies, as survival increased from 1 day to 5 weeks after gentamicin treatment. Sixteen-to-20 weeks after treatment, partial recovery of thresholds was evident. These findings demonstrate that functional recovery does occur in the avian inner ear following aminoglycoside administration. Recovery occurs at all frequencies, but predominantly at low and middle frequencies, leaving significant residual high-frequency threshold elevation. Recovery lags 14 to 18 weeks behind anatomic evidence of hair cell regeneration, which was demonstrated in one study by 2 weeks after comparable administration of gentamicin.
Pathogenic Old World Hantaviruses Infect Renal Glomerular and Tubular Cells and Induce Disassembling of Cell-to-Cell Contacts

ABSTRACT Viral hemorrhagic fevers are characterized by enhanced permeability. One of the most affected target organs of hantavirus-induced hemorrhagic fever with renal syndrome is the kidney, and an infection often results in acute renal failure. To study the underlying cellular effects leading to kidney dysfunction, we infected human renal cell types in vitro that are critical for the barrier functions of the kidney, and we examined kidney biopsy specimens obtained from hantavirus-infected patients. We analyzed the infection and pathogenic effects in tubular epithelial and glomerular endothelial renal cells and in podocytes. Both epithelial and endothelial cells and podocytes were susceptible to hantavirus infection in vitro. The infection disturbed the structure and integrity of cell-to-cell contacts, as demonstrated by redistribution and reduction of the tight junction protein ZO-1 and the decrease in the transepithelial resistance in infected epithelial monolayers. An analysis of renal biopsy specimens from hantavirus-infected patients revealed that the expression and the localization of the tight junction protein ZO-1 were altered compared to renal biopsy specimens from noninfected individuals. Both tubular and glomerular cells were affected by the infection. Furthermore, the decrease in glomerular ZO-1 correlates with disease severity induced by glomerular dysfunction. The finding that different renal cell types are susceptible to hantaviral infection and the fact that infection results in the breakdown of cell-to-cell contacts provide useful insights in hantaviral pathogenesis.
Are the Elderly Underrepresented in Clinical Drug Trials?

In many industrialized nations, the elderly comprise the fastest growing subpopulation and constitute an increasing proportion of the total population compared to other age groups. The elderly use a disproportionately larger amount of health care resources since they experience a higher incidence of disease‐related morbidities, consume more drugs, are subject to more extensive multiple medication regimens, and account for more adverse drug events. In response to the great demand for geriatric pharmacotherapy, the pharmaceutical industry has targeted more drugs to the elderly. However, the elderly are too often excluded from clinical trials on drugs primarily destined for their consumption. Comprehensive analyses to assess participation of elderly subjects in clinical drug trials are needed to design and implement trials that will enhance the safety and efficacy of drugs intended for this pharmacologically sensitive subpopulation
Case-control study of a multistate equine herpesvirus myeloencephalopathy outbreak.

BACKGROUND A large multistate outbreak of equine herpesvirus myeloencephalopathy (EHM) occurred in May 2011 among horses that participated in a competitive event. OBJECTIVE To identify EHM risk factors among horses with a common exposure venue. ANIMALS A total of 123 horses: 19 horses with EHM, 14 equine herpesvirus-1 cases with no reported neurologic signs, and 90 control horses. METHODS EHM case survey data were compared with data from EHV-1 cases with no neurologic signs and healthy controls using univariable and multivariable methods. RESULTS Significant factors associated with higher risk for EHM compared with EHV-1 cases with no neurologic signs were (1) greater number of biosecurity risks at the event, (2) female sex, (3) increasing number of classes competed in at the event, and (4) an interaction between sex and number of classes competed in. In the EHM versus controls comparison, in addition to sex and biosecurity risks, factors associated with higher EHM risk included EHV-1 vaccination in the 5 weeks before the event and increasing number of events attended in April 2011; zinc dietary supplementation was associated with decreased risk. An interaction between sex and the number of events attended in April 2011 also was significant. CONCLUSIONS AND CLINICAL IMPORTANCE Findings from this study suggest that dietary zinc supplementation may be associated with decreased risk of EHM. Several factors were associated with increased risk of EHM. Additional investigations of factors associated with risk of EHM are warranted to evaluate the importance of these factors in this complex disease of horses.
Cleavage of the myristoylated alanine-rich C kinase substrate (MARCKS) by cysteine cathepsins in cells and tissues of stefin B-deficient mice

Abstract The myristoylated alanine-rich C kinase substrate (MARCKS) is a substrate of protein kinase C (PKC). Besides regulation at the level of gene transcription, MARCKS concentrations within the cell are also regulated by proteolytic cleavage by cathepsins and calpains, which are cysteine proteinases. Stefin B (cystatin B) is an endogenous inhibitor of lysosomal cysteine cathepsins, but not calpains. We have observed increased cleavage of MARCKS in brain and macrophages, but not in liver and kidney extracts of stefin B-deficient mice compared to wild-type mice. Processing of cathepsin B was unaltered in the brain of stefin B-deficient mice and we conclude that increased cleavage of MARCKS could be attributed to the lack of inhibitor.
Cerebral perfusion pressure between 50 and 60 mm Hg may be beneficial in head-injured patients: a computerized secondary insult monitoring study.

OBJECTIVE To describe the occurrence of secondary insults using a computerized monitoring data collecting system and to investigate their relationship to outcome when the neurointensive care was dedicated to avoiding secondary insults. METHODS Patients 16 to 79 years old admitted to the neurointensive care unit between August 1998 and December 2002 with traumatic brain injury and 54 hours or more of valid monitoring within the first 120 hours after trauma (one value/min) were included. Monitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), systolic blood pressure (BPs), and mean blood pressure (BPm) was required, and insult levels were defined (ICP >25/>35, BPs <100/<90/>160/>180, BPm <80/<70/>110/>120, and CPP <60/<50/>70/>80 mm Hg). Insults were quantified as proportion of valid monitoring time at the insult level. Logistic regression analyses were performed with admission and secondary insult variables as explanatory variables and favorable outcome as dependent variable. RESULTS Eighty-one patients, 63 men and 18 women, with a mean age of 43.0 years, fulfilled the inclusion criteria. Seventy-two patients (89%) had Glasgow Coma Scale scores of 8 or less. Thirty-one patients (38%) had diffuse injury, and 50 (62%) had mass lesions. Mean Injury Severity Score was 26.6. After 6 months, 54% of the patients had achieved a favorable outcome. Most patients spent 5% or less of the monitoring time at the insult level except for CPP greater than 70 mm Hg. Low age, high Glasgow Coma Scale motor score, low Injury Severity Score, and CPP less than 60 mm Hg insults were significant predictors of favorable outcome in the final multiple logistic regression model. CONCLUSION Overall, the secondary insults were rare, except for high CPP. The results suggest that patients with traumatic brain injury might benefit from a CPP slightly less than 60 mm Hg.
Regional risk assessment of the Puyallup River Watershed and the evaluation of low impact development in meeting management goals

The Relative Risk Model (RRM) is a tool used to calculate and assess the likelihood of effects to endpoints when multiple stressors occur in complex ecological systems. In this study, a Bayesian network was used to calculate relative risk and estimate uncertainty (BN‐RRM) in the Puyallup River Watershed. First, we calculated the risk of prespawn mortality of coho salmon. Second, we evaluated the effect of low impact development (LID) as a means to reduce risk. Prespawner mortality in coho salmon within the Puyallup watershed was the endpoint selected for this study. A conceptual model showing causal pathways between stressors and endpoints was created to show where linkages exist. A relative risk gradient was found throughout the watershed. The lowest risk was found in risk regions with the least urban development, and the greatest risk of prespawner mortality was found in the highly urbanized risk regions with the largest amounts of impervious surface. LID did reduce risk but only when implemented at high intensities within the urban watersheds. The structure of the BN‐RRM also provides a framework for water quality‐ and quantity‐related endpoints within this and other watersheds. The framework is also useful for evaluating different strategies for remediation or restoration activities. The adaptability of using BNs for a relative risk assessment provides opportunities for the model to be adapted for other watersheds in the Puget Sound and Salish Sea region. Integr Environ Assess Manag 2014;10:269–278. © 2013 SETAC