Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene Therapy Applications for Fracture Repair

Cassandra A. Strohbach1, Donna D. Strong2 and Charles H. Rundle3 1Military Performance Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA, 2VA Loma Linda HealthCare system, Research 151, Loma Linda, CA Department of Medicine, Biochemistry & Microbiology, Loma Linda University, Loma Linda, CA 3Musculoskeletal Disease Center, VA Loma Linda HealthCare system, Research 151, Loma Linda, CA, Department of Medicine, Loma Linda University, Loma Linda, CA, USA
Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis

We examined the relation between adalimumab and infliximab plasma trough levels, anti‐adalimumab and anti‐infliximab antibody formation. We analyzed plasma from 32 adalimumab‐treated and 20 infliximab‐treated psoriasis patients for evaluating trough levels of each drug. The presence of anti‐adalimumab and anti‐infliximab antibodies was analyzed and the severity of psoriasis was evaluated. At week 28, 25 out of 32 and at week 48, 21 out of 30 adalimumab‐treated patients maintained as more than PASI 75. At week 28, 12 out of 20 and at week 48, nine out of 18 infliximab‐treated patients were evaluated as more than PASI 75. In patients treated with 40 mg adalimumab every other week, the mean trough level was 7.62 μg/mL (range, 0.05–10.6) at week 48. In patients treated with 80 mg adalimumab every other week, the mean trough level was 8.61 μg/mL (range, 0.08–13.5) at week 48. Mean trough level of infliximab‐treated cases (4.1–5.2 mg/kg; mean, 4.6) was 4.64 μg/mL (range, 0.03–16.9) at week 48. Anti‐adalimumab antibody was detected in five out of 32 cases and anti‐infliximab antibody was detected in six out of 20 cases, respectively, at weeks 24 and 48. The optimal cut‐off values of adalimumab and infliximab concentration for more than PASI 75 were more than 7.84 μg/mL and more than 0.92 μg/mL, respectively. The trough levels of adalimumab and infliximab in psoriasis patients were positively associated with clinical response and were significantly lower in cases having anti‐adalimumab or anti‐infliximab antibodies.
Analysis of splenic Gr‐1int immature myeloid cells in tumor‐bearing mice

It is known that the number of ImC, expressing myeloid markers, CD11b and Gr‐1, increase with tumor growth and ImC play a role in the escape of tumor cells from immunosurveillance in tumor‐bearing mice and cancer patients. However, the mechanisms by which ImC suppress immune responses in tumor‐bearing mice have not been completely elucidated. In the present study, we investigated the function of splenic ImC freshly isolated from tumor‐bearing mice and splenic ImC differentiated in vitro by GM‐CSF. Freshly isolated splenic ImC were divided into two groups depending on Gr‐1 expression, Gr‐1 high (Gr‐1hi) and intermediate (Gr‐1int). Freshly isolated splenic Gr‐1int ImC, but not Gr‐1hi ImC, from tumor‐bearing mice reduced production of IFN‐γ in CD8+ T cells, but neither splenic Gr‐1int ImC nor Gr‐1hi ImC isolated from naive mice did. Both Gr‐1int and Gr‐1hi ImC differentiated in vitro by GM‐CSF inhibited production of IFN‐γ in both CD8+ and CD4+ T cells. In addition, the differentiated Gr‐1int ImC, one‐third of which were CD11c+F4/80+ cells, and their culture supernatants suppressed proliferative responses of T cells stimulated by CD3 ligation, but the differentiated Gr‐1hi ImC and their culture supernatants did not. These results suggest that Gr‐1int ImC are altered to immune‐suppressive cells in tumor circumstances and that they are differentiated by GM‐CSF progressively into CD11c+F4/80+ cells with further suppressive activity against T cells.
The influence of selected factors on dentists’ delivery of a set of 5A-like intervention strategies for eating disorders in Oregon

approved: _____________________________________________ Rebecca J. Donatelle Each year an estimated one million young women in the United States develop an eating disorder. Without early recognition of symptoms and early intervention/treatment, these eating disorders can lead to a host of chronic and debilitating illnesses. Tooth erosion is one of the first signs of an eating disorder, providing dentists with a unique role in detecting potential problems. Little is known about what dentists do with patients suspected of an eating disorder and importantly, no guidelines exist to assist the dentists. The purpose of this study was to: 1) identify potential strategies that experts believe are important for dentists to utilize when intervening with patients suspected of an eating disorder, 2) determine the nature and extent of current intervention strategies for eating disorders by dentists, 3) identify factors that influence dentist delivery of intervention strategies for eating disorders.
Increased susceptibility to tumor necrosis factor‐α in butyric acid‐induced apoptosis is caused by downregulation of cFLIP expression in Jurkat T cells

Butyric acid is one of the major extracellular metabolites of periodontopathic Gram‐negative bacteria. We previously demonstrated that butyric acid induced apoptosis in human T cells. In the present study, we examined the interaction between butyric acid and TNF‐α in Jurkat T‐cell apoptosis. Simultaneous treatment with TNF‐α enhanced butyric acid‐induced apoptosis by promoting caspase activity more than was achieved by either reagent alone. We examined which genes were associated with the increased susceptibility to TNF‐α caused by butyric acid, and revealed that expression of cFLIP decreased with increased concentrations of butyric acid. Furthermore, exogenous expression of cFLIP protein suppressed the enhancing effect by TNF‐α in the apoptosis. These results suggest that butyric acid downregulates cFLIP expression and increases the susceptibility to TNF‐α by activating caspases via the death receptor signal.
Gender and Age Differences in Dietary Behaviors and Food Consumption Pattern of Korean Americans Living in Western Parts of USA

This study was conducted to find the gender and age differences in dietary behaviors and food consumption pattern of Korean American adults living in western parts of USA. The structured survey forms and self-administered food frequency questionnaire were used to assess dietary behavior and nutrient intakes. It was found that younger subjects kept their meal time more irregularly and skipped breakfast more often than older subjects due to lack of time. There were significant age differences in skipping meals, kind of skipping meals, and the reasons for skipping meals. Young subjects consumed more American type food while older subjects consumed more traditional Korean food. Nutrient intakes of males' except for the elderly were significantly higher in energy, protein, Fe and P than those of females'. Vitamin A and vitamin C intake were significantly higher in females. Energy ratio of carbohydrate : protein : fat was 56.2 : 16.8 : 27.0. Females consumed more plant food as their dietary sources of protein, fat, Ca and Fe, compared to males. Ca intakes of participants' were below 75% of RDA except for the youngest male and 30~49 aged male and females. Futhermore, Ca intake was below 70% after age 50 in both genders. Effective nutrition education program targeting Korean Americans in the community should be developed and implemented to increase Ca consumption.
An ethical approach to health promotion in physiotherapy practice.

ISSUE ADDRESSED With increased emphasis on reducing the global burden of non-communicable disease, health professionals who traditionally focused on the individual are being encouraged to address population-level health problems. While physiotherapists are broadening their clinical role to include health promotion strategies in their clinical practice, the ethical foundations of this practice focus have received less attention. METHODS We use a physiotherapy clinical scenario to highlight different physiotherapeutic approaches and to analyse underpinning ethical values and implications for practice. RESULTS We suggest there are potential harms of incorporating health promotion into physiotherapy management of individuals if the population-based research does not resonate with an individual's particular circumstances, capacity to change or view of what counts as important and meaningful. We propose that critical reasoning and ethical judgment by the physiotherapist is required to determine how health promotion messages applied in primary care settings might work to benefit and enhance a client's well being rather than impose burdens or cause harm. CONCLUSION We suggest four ethical reasoning strategies designed to assist physiotherapists to frame and understand fundamental ethical principles of beneficence, harm, autonomy and justice when implementing health promotion and self-management approaches in clinical practice.
The role of age in work team settings

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Activation of mitogen‐activated protein kinases is involved in the induction of interferon β gene in macrophages infected with Orientia tsutsugamushi

We investigated the role of MAPK in IFN‐β gene expression in macrophages after infection with Orientia tsutsugamushi. ERK1/2 became phosphorylated in Orientia‐stimulated macrophages. Selective inhibition of ERK1/2 and p38 MAPK could all significantly reduce Orientia‐stimulated IFN‐β mRNA expression. Orientia inactivation by heat abolished IFN‐β mRNA induction only, whereas cytochalasin D treatment completely blocked both IFN‐β and chemokine expression, suggesting requirement of cellular internalization by viable bacteria for IFN‐β gene induction. In conclusion, our data indicate that MAPK pathways are required to induce maximal IFN‐β gene expression in macrophages during Orientia infection.
Characterization of the orf1‐tolQRA operon in Pseudomonas aeruginosa

The tol‐pal genes play important roles in maintaining outer membrane integrity, transmembrane transportation, and cell division in Gram‐negative bacteria. In Pseudomonas aeruginosa, an important human opportunistic pathogen, the tol‐oprL genes are organized uniquely in three operons, orf1‐tolQRA, tolB and oprL‐orf2, and are regulated by iron availability. Similarity between TolQRA and the iron transport system ExbBD‐TonB also exists in P. aeruginosa and they can replace each other imperfectly. It is of importance to investigate the regulation and functions of this membrane complex. In the present study, we characterized the promoters and expression profiles of the orf1‐tolQRA operon and investigated the function of Orf1. Primer extension was carried out by using both isotope‐labeled and florescence labeled primers and the expression profiles were determined using both lacZ and luxCDABE‐based transcriptional fusions. Our results revealed two distinct promoters at the upstream region of tolQRA; the one located in front of orf1 was constitutive whereas the other within the orf1 coding region was iron regulated. Expression profiles indicate the tol genes were also downregulated by the quorum‐sensing systems during the late stage of growth. Unlike tolQ and tolA, we were able to construct a viable orf1 knockout strain, and the mutant exhibited altered cell and colony morphology, providing first evidence that Orf1 plays a non‐essential role in the Tol‐OprL complex in P. aeruginosa.
Integrin‐Mediated Interactions Control Macrophage Polarization in 3D Hydrogels

Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin‐mediated interactions between human monocytic THP‐1 cells and collagen‐derived matrix. Surface marker, gene expression, biochemical, and cytokine profiling consistently indicate that THP‐1 cells within a biomaterial lacking cell attachment motifs yield proinflammatory M1 macrophages, whereas biomaterials with attachment sites in the presence of interleukin‐4 (IL‐4) induce an anti‐inflammatory M2‐like phenotype and propagate the effect of IL‐4 in induction of M2‐like macrophages. Importantly, integrin α2β1 plays a pivotal role as its inhibition blocks the induction of M2 macrophages. The influence of the microenvironment of the biomaterial over macrophage polarity is further confirmed by its ability to modulate the effect of IL‐4 and lipopolysaccharide, which are potent inducers of M2 or M1 phenotypes, respectively. Thus, this study represents a novel, versatile, and effective strategy to steer macrophage polarity through integrin‐mediated 3D microenvironment for biomaterial‐based programming.
A bird survey method for Australian tropical savannas

Abstract The tropical savanna of northern Australia is extensive and relatively homogenous compared to the open woodlands of temperate Australia. The avifauna of this biome is unevenly dispersed in the landscape. A standard count method for birds using a timed search along a 100-m transect with eight repeated counts per site over 4 days, has been used extensively over the past decade or more in these savannas, but its effectiveness has never been critically examined. We used data collected from across northern Queensland from 2004 to 2010, comprising 502 single-survey sites (each transect counted eight times) and 60 sites re-sampled four times from 2004 to 2008, to examine species records and accumulation of species over time with respect to time of day, increasing number of repeat counts(from 2 to 32 counts), species turnover, vegetation density effects and distance to first observation. Over 70% of the species in tropical savannas were easily observed and for 93% of the species vegetation structure did not alter detectability. Richness and abundance did not vary significantly across the day. We found that repeated sampling over multiple days, and at different times of the day, provides the best estimate of species richness at a site, and improved detectability.
Increase of regulatory T cells in the peripheral blood of dogs with metastatic tumors

It is well known that lymphocytes from patients with advanced‐stage cancer have impaired immune responsiveness and that type1 T lymphocyte subsets in tumor bearing hosts are suppressed. Treg have been reported to comprise a subgroup which inhibits T cell mediated immune responses. In the present study, the percentage of Treg, Th1 and Tc1 in the peripheral blood of tumor bearing dogs with or without metastases was evaluated. The percentages of Th1 and Tc1 in dogs with metastatic tumor were significantly less, and that of Treg was significantly greater, than those of dogs without metastatic tumor. The percentage of Treg showed an inverse correlation with that of Th1 and Tc1 in tumor bearing dogs. It was concluded that an increase in Treg in the peripheral blood of dogs with metastatic tumor may induce suppression of tumor surveillance by the Type1 immune response and lead to metastasis of tumor[0][0]. [0]
Organ‐on‐a‐Chip Technology for Reproducing Multiorgan Physiology

In the drug development process, the accurate prediction of drug efficacy and toxicity is important in order to reduce the cost, labor, and effort involved. For this purpose, conventional 2D cell culture models are used in the early phase of drug development. However, the differences between the in vitro and the in vivo systems have caused the failure of drugs in the later phase of the drug‐development process. Therefore, there is a need for a novel in vitro model system that can provide accurate information for evaluating the drug efficacy and toxicity through a closer recapitulation of the in vivo system. Recently, the idea of using microtechnology for mimicking the microscale tissue environment has become widespread, leading to the development of “organ‐on‐a‐chip. ” Furthermore, the system is further developed for realizing a multiorgan model for mimicking interactions between multiple organs. These advancements are still ongoing and are aimed at ultimately developing “body‐on‐a‐chip” or “human‐on‐a‐chip” devices for predicting the response of the whole body. This review summarizes recently developed organ‐on‐a‐chip technologies, and their applications for reproducing multiorgan functions.
Archetype JC virus efficiently propagates in kidney‐derived cells stably expressing HIV‐1 Tat

Pathogenic JCV with rearranged regulatory regions (PML‐type) causes PML, a demyelinating disease, in the brains of immunocompromised patients. On the other hand, archetype JCV persistently infecting the kidney is thought to be converted to PML‐type virus during JCV replication in the infected host under immunosuppressed conditions. In addition, Tat protein, encoded by HIV‐1, markedly enhances the expression of a reporter gene under control of the JCV late promoter.
RORα switches transcriptional mode of ERRγ that results in transcriptional repression of CYP2E1 under ethanol-exposure

Increased cytochrome P450 2E1 (CYP2E1) expression is the main cause of oxidative stress, which exacerbates alcoholic liver diseases (ALDs). Estrogen-related receptor gamma (ERRγ) induces CYP2E1 expression and contributes to enhancing alcohol-induced liver injury. Retinoic acid-related orphan receptor alpha (RORα) has antioxidative functions; however, potential cross-talk between ERRγ and RORα in the regulation of CYP2E1 has not been studied. We report that RORα suppressed ERRγ-mediated CYP2E1 expression. A physical interaction of RORα with ERRγ at the ERRγ−response element in the CYP2E1 promoter was critical in this suppression. At this site, coregulator recruitment of ERRγ was switched from coactivator p300 to the nuclear receptor corepressor 1 in the presence of RORα. Cross-talk between ERRγ and RORα was demonstrated in vivo, in that administration of JC1–40, a RORα activator, significantly decreased both CYP2E1 expression and the signs of liver injury in ethanol-fed mice, and this was accompanied by coregulator switching. Thus, this non-classical RORα pathway switched the transcriptional mode of ERRγ, leading to repression of alcohol-induced CYP2E1 expression, and this finding may provide a new therapeutic strategy against ALDs.
CAMPR3: a database on sequences, structures and signatures of antimicrobial peptides

Antimicrobial peptides (AMPs) are known to have family-specific sequence composition, which can be mined for discovery and design of AMPs. Here, we present CAMPR3; an update to the existing CAMP database available online at www.camp3. bicnirrh.res.in. It is a database of sequences, structures and family-specific signatures of prokaryotic and eukaryotic AMPs. Family-specific sequence signatures comprising of patterns and Hidden Markov Models were generated for 45 AMP families by analysing 1386 experimentally studied AMPs. These were further used to retrieve AMPs from online sequence databases. More than 4000 AMPs could be identified using these signatures. AMP family signatures provided in CAMPR3 can thus be used to accelerate and expand the discovery of AMPs. CAMPR3 presently holds 10247 sequences, 757 structures and 114 family-specific signatures of AMPs. Users can avail the sequence optimization algorithm for rational design of AMPs. The database integrated with tools for AMP sequence and structure analysis will be a valuable resource for family-based studies on AMPs.
BioGPS: building your own mash-up of gene annotations and expression profiles

BioGPS (http://biogps.org) is a centralized gene-annotation portal that enables researchers to access distributed gene annotation resources. This article focuses on the updates to BioGPS since our last paper (2013 database issue). The unique features of BioGPS, compared to those of other gene portals, are its community extensibility and user customizability. Users contribute the gene-specific resources accessible from BioGPS (‘plugins’), which helps ensure that the resource collection is always up-to-date and that it will continue expanding over time (since the 2013 paper, 162 resources have been added, for a 34% increase in the number of resources available). BioGPS users can create their own collections of relevant plugins and save them as customized gene-report pages or ‘layouts’ (since the 2013 paper, 488 user-created layouts have been added, for a 22% increase in the number of layouts). In addition, we recently updated the most popular plugin, the ‘Gene expression/activity chart’, to include ∼6000 datasets (from ∼2000 datasets) and we enhanced user interactivity. We also added a new ‘gene list’ feature that allows users to save query results for future reference.
Interleukin‐8 induction due to diffusely adherent Escherichia coli possessing Afa/Dr genes depends on flagella and epithelial Toll‐like receptor 5

DAEC is considered potentially diarrheagenic. For diffuse adhesion, the role of the Afa, which was originally identified as a uropathogenic factor, is now understood. However, the role of DAEC in diarrheal disease remains controversial because DAEC is often isolated not only from patients but also from healthy individuals. Previously, we suggested that Afa/Dr DAEC, which can induce high levels of IL‐8 secretion in cultures of human carcinoma epithelial cells (HEp‐2, Caco‐2), is enterovirulent. In the present study, we examined whether IL‐8 secretion induced by certain Afa/Dr DAEC strains was primarily due to flagella via TLR5. All IL‐8 high‐inducing strains were highly motile in swarming tests. Partially purified flagella induced IL‐8 in a dose‐dependent manner. However, IL‐8 induction was inhibited by small‐interfering RNA against TLR5 or by treating flagella with disialoganglioside‐GD1a, a TLR5 blocker. TLR5 is reportedly located on the basolateral side of intestinal epithelia; flagella should not have reached TLR5 from the apical side beyond tight junctions. Reduction in the number of intracellular organisms by wortmannin, a PI3K inhibitor, did not reduce IL‐8 secretion. Afa/Dr DAEC seemed to loosen the tight junctions because it quickly reduced transepithelial electrical resistance after infection. Decreased resistance led to increased IL‐8 production. In conclusion, diffuse adhesion itself is insufficient to induce high levels of IL‐8, and simultaneous stimulation by flagella via TLR5 is likely required for additional induction. Clinically, high motility may be a candidate criterion for predicting the ability of Afa/Dr DAEC strains to induce higher levels of IL‐8 secretion.
Denaturing gradient gel electrophoresis analysis with different primers of subgingival bacterial communities under mechanical debridement

DGGE of 16S rDNA is one of the most frequently used methods to study microbial communities. In this study, the DGGE profiles of different 16S rDNA regions of the periodontal pathogens Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella nigrescens were investigated. The results suggested that V3‐V5 and V6‐V8 fragments may be suitable for community analysis of subgingival bacteria. Further analysis of subgingival samples with V3‐V5 and V6‐V8 regions as target fragments suggested that, in chronic periodontitis, re‐colonization by periodontal bacteria with a population very similar to the baseline may occur by 6 weeks after mechanical debridement.