Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipoprotein Accumulation in Macrophages via Toll-Like Receptor-4-Dependent Fluid Phase Uptake

Toll-like receptor (TLR)4 recognizes microbial pathogens, such as lipopolysaccharide, and mediates lipopolysaccharide-induced proinflammatory cytokine secretion, as well as microbial uptake by macrophages. In addition to exogenous pathogens, TLR4 recognizes modified self, such as minimally oxidized low-density lipoprotein (mmLDL). Here we report that mmLDL and its active components, cholesteryl ester hydroperoxides, induce TLR4-dependent fluid phase uptake typical of macropinocytosis. We show that mmLDL induced recruitment of spleen tyrosine kinase (Syk) to a TLR4 signaling complex, TLR4 phosphorylation, activation of a Vav1-Ras-Raf-MEK-ERK1/2 signaling cascade, phosphorylation of paxillin, and activation of Rac, Cdc42, and Rho. These mmLDL-induced and TLR4- and Syk-dependent signaling events and cytoskeletal rearrangements lead to enhanced uptake of small molecules, dextran, and, most importantly, both native and oxidized LDL, resulting in intracellular lipid accumulation. An intravenous injection of fluorescently labeled mmLDL in wild-type mice resulted in its rapid accumulation in circulating monocytes, which was significantly attenuated in TLR4-deficient mice. These data describe a novel mechanism leading to enhanced lipoprotein uptake in macrophages that would contribute to foam cell formation and atherosclerosis. These data also suggest that cholesteryl ester hydroperoxides are an endogenous ligand for TLR4. Because TLR4 is highly expressed on the surface of circulating monocytes in patients with chronic inflammatory conditions, and cholesteryl ester hydroperoxides are present in plasma, lipid uptake by monocytes in circulation may contribute to the pathological roles of monocytes in chronic inflammatory diseases.
Longitudinal HIV Risk Behavior Among the Drug Abuse Treatment Outcome Studies (DATOS) Adult Sample

Longitudinal trajectories for HIV risk were examined over 5 years following treatment among 1,393 patients who participated in the nationwide Drug Abuse Treatment Outcome Studies. Both injection drug use and sexual risk behavior declined over time, with most of the decline occurring between intake and the first-year follow-up. However, results of the application of growth mixture models for both sets of trajectories indicated that a subgroup of individuals reverted to a high-risk behavior over time, with a higher level of risk at the 5-year follow-up than their original risk level at intake. Of clients who were engaged in regular injection drug use at intake, 76% continued to inject drug at a moderate—stable or increased rate during the 5-year follow-up.
Primary hepatocellular carcinoma (“hepatoid” carcinoma) of the pancreas: a case report and review of the literature

We present a case of hepatocellular carcinoma located within the pancreas. These tumors occur in the body and tail of the pancreas, with a male predominance, and at a younger age. Tumors with pure hepatocellular histopathology have better survival and recurrence rates and should be offered surgical therapy if possible.
Wnt-expressing cells in the intestines: guides for tissue remodeling

The crypt is a minimal functional unit in the intestinal epithelium. This unique structure is maintained by surrounding mesenchymal cells that focally interact with associated epithelial cells. Canonical and non-canonical Wnt ligands enable specific microenvironments localized to each end of the crypt major axis. While canonical Wnt-expressing cells are localized near the crypt bottom where intestinal stem cells reside, non-canonical Wnt-expressing cells are positioned beneath the luminal surface of epithelial cells. During wound healing, propagation and appropriate relocation of each cell population are thought to ensure subsequent crypt regeneration. In this review, I integrate information from recent studies on Wnt-expressing cells and intestinal fibroblast lineages and discuss their roles in homeostasis and wound healing. More information on the lineages of Wnt-expressing cells will help clarify the mechanisms of epithelial tissue formation.
EFECTO DE LA APLICACIÓN DE GONADOTROPINAS RECOMBINANTES HUMANAS SOBRE LA PRODUCCIÓN Y CALIDAD DE OVOCITOS Y EMBRIONES EN CONEJA

El objetivo de la presente tesis ha sido evaluar la utilizacion de las gonadotropinas recombinantes humanas (rhFSH y rhLH)) sobre la respuesta superovulatoria en conejas, estudiando el efecto de la utilizacion de las mismas sobre la calidad de los ovocitos y embriones obtenidos, y sobre la viabilidad embrionaria tras un proceso de crioconservacion. Asi, en el primer experimento se evaluo el efecto de la aplicacion de 25 UI de rhFSH junto con un 0, 5 o 10% de rhLH sobre el desarrollo de embriones frescos y congelados-descongelados. Se obtuvo una tasa de desarrollo hasta el estadio de blastocisto expandido significativamente mayor en embriones no superovulados frente a los superovulados con rhFSH y 10% de rhLH. En cuanto a la tasa de desarrollo de los embriones congelados-descongelados, fue similar en todos los grupos, alcanzando el estadio de blastocisto expandido el 83,5% de los embriones. Por otra parte, se estudio la evolucion de la tasa de ovulacion y la respuesta inmunitaria por hembra hasta el cuarto tratamiento de superovulacion. Se observo que la tasa de ovulacion disminuia a partir del segundo tratamiento mientras que el nivel de anticuerpos anti-FSH circulantes aumentaba a partir de la tercera aplicacion del tratamiento de superovulacion. En el segundo experimento se estudio como afectaba el protocolo de administracion y la hormona utilizada en el tratamiento de superovulacion a la calidad de los ovocitos producidos, analizando la cantidad de ATP presente en los mismos. Para ello, se comparo la administracion cada 24 horas de rhFSH y de FSH porcina diluidas en PVP y la administracion cada 12 horas de FSH porcina diluida en suero fisiologico. La concentracion de ATP en el grupo de FSH porcina diluida en suero fisiologico fue significativamente menor que en los otros dos grupos de superovulacion (5,63±0,14 frente a 6,42±0,13 y 6,19±0,15 para el grupo de rhFSH y pFSH, respectivamente). Esa disminucion de la concentracion de ATP podria estar relacionada c
Family‐based case–control study of MAOA and MAOB polymorphisms in Parkinson disease

Monoamine oxidase (MAO) is an enzyme regulating metabolism of neurotransmitters such as dopamine. Two distinct forms of enzyme, encoded by genes MAOA and MAOB located on the X chromosome, have been considered as possible factors in the pathogenesis of Parkinson disease (PD). Previous association studies of PD and MAO genes reported inconsistent results. In this study, we used a large family‐based data set to test associations between MAO genes and a risk of PD. The data set includes 298 female discordant sibpairs and 348 male discordant sibpairs. For this study, all subjects analyzed were white and families with known parkin mutations were removed. We analyzed 15 single nucleotide polymorphisms (SNPs) and a dinucleotide repeat marker in the MAO genes. Association was found with the intron 13 SNP of MAOB in the female subset (P = 0.02). No significant association was found in the male subset. Our results add to the evidence of involvement of MAOB in PD and suggest that the effect may be stronger in women. © 2006 Movement Disorder Society
The Temporal Profile of Cytokines in the Bronchoalveolar Lavage Fluid in Mice Exposed to the Industrial Gas Phosgene

Diagnosis of an exposure to airborne toxicants can be problematic. Phosgene is used widely in industry for the production of many synthetic products, such as polyfoam rubber, plastics, and dyes. Although nearly 100% of the gas is consumed during processing, there is the potential problem of accidental or even intentional exposure to this irritant/choking agent. Exposure to phosgene has been known to cause latent life-threatening pulmonary edema. A major problem is that there is a clinical latency phase from 3 to 24 h in people before irreversible acute lung injury occurs. Assessment of markers of acute lung injury after a suspected exposure would be useful in developing rational treatment strategies. These experiments were designed to assess bronchoalveolar lavage fluid (BALF) for the presence of the early markers of exposure to phosgene in mice from 1 to 72 h after exposure. Separate groups of 40 CD-1 male mice (Crl:CD-1(ICR)BR) weighing 29 ± 1 g were exposed whole-body to either air or a concentration × time (c × t) amount of 32 mg/m 3 (8 ppm) phosgene for 20 min (640 mg·min/m 3) . BALF from air- or phosgene-exposed mice was taken at 1, 4, 8, 12, 24, 48, and 72 h postexposure. After euthanasia, the trachea was excised, and 800 µl saline was instilled into the lungs and washed 5 ×. BALF was assessed for interleukin (IL)-4, IL-6, tumor necrosis factor (TNF)α, IL-1α, macrophage inflammatory protein (MIP)-2, and IL-10. At 4 h postexposure, IL-6 was 15-fold higher for phosgene-exposed mice than for the time-matched air-exposed control group. At 8 and 12 h, IL-6, IL-1β, MIP-2, and IL-10 were significantly higher in phosgene-exposed mice than in time-matched air-exposed controls, p ≤ . 05 to p ≤ . 001, whereas TNFα reached peak significance from 24 to 72 h. IL-4 was significantly lower in the phosgene-exposed mice than in the air-exposed mice from 4 to 8 h after exposure. These data show that BALF is an important tool in assessing pro- and anti-inflammatory markers of phosgene-induced acute lung injury and that knowledge of these temporal changes may allow for timely treatment strategies to be applied.
A Heterocomplex Formed by the Calcium-binding Proteins MRP8 (S100A8) and MRP14 (S100A9) Binds Unsaturated Fatty Acids with High Affinity*

We show that unsaturated fatty acids (FAs) bind reversibly and with high affinity to a heterocomplex of 34 kDa (FA-p34) formed by the non-covalent association of two calcium-binding proteins of the S100 family: MRP8 (S100A8) and MRP14 (S100A9). Fatty acid-competition studies on the [3H]oleic acid·FA-p34-complex show that oleic, α-linoleic, γ-linolenic, and arachidonic acids have IC50 values of about 1 μM, whereas palmitic and stearic acids are poor competitors. The binding of arachidonic acid is saturable with a single class of binding site per FA-p34, and a dissociation constant (Kd) of 0.13 μM is calculated. The individual subunits MRP8 and MRP14 show no binding properties for fatty acids, whereas a p34 complex reconstituted in vitro by the recombinant molecules exhibits binding properties, suggesting that the fatty acid-binding site of FA-p34 is created through heterocomplex formation. Furthermore, we demonstrate that lowering free Ca2+ levels to 16 nM results in a loss of the fatty acid-binding capacity of purified FA-p34. In calcium-induced differentiating keratinocytes, the amounts of FA-p34 are increased in the particulate (2.0 ± 0.5 pmol of [3H]oleic acid/mg protein) and in the cytosolic (4.5 ± 0.6 pmol of [3H]oleic acid/mg protein) fractions, whereas no FA-p34 can be detected in non-differentiated cultured keratinocytes. In abnormally differentiated keratinocytes (psoriasis) and in human polymorphonuclear leukocytes, FA-p34 is highly expressed (31.35 ± 1.6 and 349.8 ± 17.9 pmol of [3H]oleic acid/mg protein, respectively), pointing toward a role for this heteromer in mediating effects of unsaturated fatty acids in a calcium-dependent way during cell differentiation and/or inflammation.
Cervical Spine Pedicle Screws: A Biomechanical Comparison of Two Insertion Techniques

Study Design. Biomechanical testing of the pullout strengths of pedicle screws placed by two different techniques in adult human cadaveric cervical spines. Objectives. To determine whether there is a significant difference in screw purchase of two commonly proposed methods of cervical pedicle screw insertion. Summary of Background Data. Wiring techniques remain the gold standard for posterior cervical fixation. However, absent or deficient posterior elements may dictate the use of alternative fixation techniques. Cervical pedicle screws have been shown to have significantly higher pullout strength than lateral mass screws. Methods. Fifty fresh disarticulated human vertebrae (C3–C7) were evaluated with computed tomography for anatomic disease and pedicle morphometry. The right and left pedicles were randomly assigned to either a standard method or the Abumi insertion method. In the latter technique the cortex and cancellous bone of lateral mass are removed with a high-speed burr, which provides a direct view of the pedicle introitus. The pedicle is then probed and tapped and a 3.5-mm cortical screw inserted. Each screw was subjected to a uniaxial load to failure. Results. There was no significant difference in the mean pullout resistance between the Abumi (696 N) and standard (636.5 N) insertion techniques (P = 0.41). There was no difference in pullout resistance between vertebral levels or within vertebral levels. Two (4%) minor pedicle wall violations were observed. Conclusion. In selected circumstances pedicle screw instrumentation of the cervical spine may be used to manage complex deformities and patterns of instability. Surgeons need not be concerned about reduced screw purchase when deciding between the Abumi method and its alternatives.
Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties

Abstract This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G2/M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D7.4, all the synthesized compounds follow Lipinski’s rule of five for good permeability (absorption) potential.
Whither goest the right ventricle in obstructive sleep apnea?

5 and control of hemorrhage technically much easier. Those who are unfamiliar with the instrumentation will find themselves lost; those who are overly enthusiastic will find themselves in trouble; and those who lose sight of their priorities will do harm to their patients. Video thoracoscopy rationally practiced by qualified, responsible physicians offers a great deal to our patients. With continued improvements in instru-mentation and increased familiarity with the technique , we can expect to see expanded utilization of this procedure with direct benefit to patients. Its role in the management of primary lung cancer is very limited at present. S ince the initial definition ofobstructive sleep apnea (OSA), numerous attempts have been made to determine the relationship between cardiovascular function and this syndrome. However, much of the data concerning both right and left ventricular manifestations is inconclusive. The study by Hanly et al in this issue of Chest (see page 100) adds to the dilemma. Hypoxic pulmonary vasoconstriction has been recognized since 1947. ' Chronic intermittent hypoxemia is a frequent nocturnal occurrence in OSA, and it may be present continuously as the syndrome worsens. Elevation ofpulmonary artery pressure demonstrated in OSA may be the result of this hypoxemia, and cor pulmonale is not uncommon in OSA.23 Therefore, right ventricular hypertrophy (RVH) in patients who present to a sleep laboratory should be an expected result ofthis elevation in pulmonary artery pressures. Bradley et all have suggested that daytime hypoxemia, in addition to OSA, is necessary to develop cor pulmonale in OSA patients. Krieger et all confirmed that impaired daytime pulmonary function characterized by diffuse airway obstruction contributed to pulmonary hypertension, hypoxemia, and hypercap-nia in OSA. They showed also that the severity of sleep-related breathing disorders played a significant role. In addition, leftward shift ofthe interventricular septum has recently been noted in OSA.6 This phenomenon is secondary to increased right ventricular volume during obstructive inspiratory efforts, with exceedingly negative values of intrathoracic pressure. Such effects on the right ventricle with increases in both preload and afterload may also lead to RVH. This background of data has led to an attempt to determine the status of the right ventricle in newly diagnosed sleep apnea. In this issue of Chest, Hanly et al report the absence ofechocardiographic evidence of RVH in OSA. In a similar study, we found the incidence ofisolated RVH to be 71 percent in patients with newly diagnosed sleep apnea.7 Since our …
Structure-Function Studies with the Unique Hexameric Form II Ribulose-1,5-bisphosphate Carboxylase/Oxygenase (Rubisco) from Rhodopseudomonas palustris*

Background: Rubisco fixes atmospheric CO2 to organic carbon and sustains life on earth. Results: A form II Rubisco structure has been solved, and functional analysis was conducted with divergent residues. Conclusion: The unique structure combined with functional analysis can help better understand and improve Rubisco catalysis. Significance: This is the first high resolution structure of an activated transition-state analog (CABP)-bound form II Rubisco. The first x-ray crystal structure has been solved for an activated transition-state analog-bound form II ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). This enzyme, from Rhodopseudomonas palustris, assembles as a unique hexamer with three pairs of catalytic large subunit homodimers around a central 3-fold symmetry axis. This oligomer arrangement is unique among all known Rubisco structures, including the form II homolog from Rhodospirillum rubrum. The presence of a transition-state analog in the active site locked the activated enzyme in a “closed” conformation and revealed the positions of critical active site residues during catalysis. Functional roles of two form II-specific residues (Ile165 and Met331) near the active site were examined via site-directed mutagenesis. Substitutions at these residues affect function but not the ability of the enzyme to assemble. Random mutagenesis and suppressor selection in a Rubisco deletion strain of Rhodobacter capsulatus identified a residue in the amino terminus of one subunit (Ala47) that compensated for a negative change near the active site of a neighboring subunit. In addition, substitution of the native carboxyl-terminal sequence with the last few dissimilar residues from the related R. rubrum homolog increased the enzyme's kcat for carboxylation. However, replacement of a longer carboxyl-terminal sequence with termini from either a form III or a form I enzyme, which varied both in length and sequence, resulted in complete loss of function. From these studies, it is evident that a number of subtle interactions near the active site and the carboxyl terminus account for functional differences between the different forms of Rubiscos found in nature.
Oxytocin secretion is associated with severity of disordered eating psychopathology and insular cortex hypoactivation in anorexia nervosa.

CONTEXT Animal data suggest that oxytocin is a satiety hormone. We have demonstrated that anorexia nervosa (anorexia), a disorder characterized by food restriction, low weight, and hypoleptinemia, is associated with decreased nocturnal oxytocin secretion. We have also reported functional magnetic resonance imaging (fMRI) hypoactivation in anorexia in brain regions involved in food motivation. The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans. OBJECTIVE The objective of the study was to determine whether the oxytocin response to feeding in anorexia differs from healthy women and to establish the relationship between oxytocin secretion and disordered eating psychopathology and food-motivation neurocircuitry. DESIGN This was a cross-sectional study. SETTING The study was conducted at a clinical research center. PARTICIPANTS Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia (ANWR), and 13 healthy controls (HC). MEASURES Peripheral oxytocin and leptin levels were measured fasting and 30, 60, and 120 min after a standardized mixed meal. The Eating Disorder Examination-Questionnaire was used to assess disordered eating psychopathology. fMRI was performed during visual processing of food and nonfood stimuli to measure brain activation before and after the meal. RESULTS Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR. Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR. Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN. Oxytocin AUC was associated with the severity of disordered eating psychopathology in AN and ANWR, independent of leptin secretion, and was associated with between-group variance in fMRI activation in food motivation brain regions, including the hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula. CONCLUSIONS Oxytocin may be involved in the pathophysiology of anorexia.
Differential effects of temporal pole resection with amygdalohippocampectomy versus selective amygdalohippocampectomy on material‐specific memory in patients with mesial temporal lobe epilepsy

Purpose: In the surgical treatment of mesial temporal lobe epilepsy, there is converging evidence that individually tailored or selective approaches have a favorable cognitive outcome compared to standard resections. There is, however, also evidence that due to collateral damage, selective surgery can be less selective than suggested. As part of a prospective transregional research project the present study evaluated the outcome in memory and nonmemory functions, following two selective approaches: a combined temporal pole resection with amygdalohippocampectomy (TPR+) and transsylvian selective amygdalohippocampectomy (SAH).
Effects of an Internet Intervention on Mothers’ Psychological, Parenting, and Health Care Utilization Outcomes

Aims and Objectives: The purpose of this pilot study was to test the effects of an Internet-based intervention, the New Mothers Network, on single, low-income, adolescent, African American mothers’ psychological, parenting, and health care utilization outcomes. Background: The study was based on social support theory. Methods: For mothers in the Intervention Group, MSNTV™ was installed in subjects’ homes and connected to the Internet. Data were collected at 1 week, 6 weeks, 3 months, and 6 months following the infant’s birth. Results: For infant health services utilization, 70.6% of those in the Control Group took their infant to the emergency room at least once during the study compared to 35.7% of mothers in the Intervention Group. The New Mothers Network allowed mothers to share their experiences and acquire information from nurses about caring for themselves and their infants. Conclusion: The New Mothers Network Web site is well poised for nursing driven social support intervention via the Internet, even though access devices are evolving over time.