Miracle-dz/UniFAR-FTUs huggingface dataset:
Active site structure and stereospecificity of Escherichia coli pyridoxine-5'-phosphate oxidase.

Pyridoxine-5'-phosphate oxidase catalyzes the oxidation of either the C4' alcohol group or amino group of the two substrates pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate to an aldehyde, forming pyridoxal 5'-phosphate. A hydrogen atom is removed from C4' during the oxidation and a pair of electrons is transferred to tightly bound FMN. A new crystal form of the enzyme in complex with pyridoxal 5'-phosphate shows that the N-terminal segment of the protein folds over the active site to sequester the ligand from solvent during the catalytic cycle. Using (4'R)-[(3)H]PMP as substrate, nearly 100 % of the radiolabel appears in water after oxidation to pyridoxal 5'-phosphate. Thus, the enzyme is specific for removal of the proR hydrogen atom from the prochiral C4' carbon atom of pyridoxamine 5'-phosphate. Site mutants were made of all residues at the active site that interact with the oxygen atom or amine group on C4' of the substrates. Other residues that make interactions with the phosphate moiety of the substrate were mutated. The mutants showed a decrease in affinity, but exhibited considerable catalytic activity, showing that these residues are important for binding, but play a lesser role in catalysis. The exception is Arg197, which is important for both binding and catalysis. The R197 M mutant enzyme catalyzed removal of the proS hydrogen atom from (4'R)-[(3)H]PMP, showing that the guanidinium side-chain plays an important role in determining stereospecificity. The crystal structure and the stereospecificity studies suggests that the pair of electrons on C4' of the substrate are transferred to FMN as a hydride ion.
Increased risk of asthma among Finnish construction workers.

AIM To determine the risk of asthma among 7891 Finnish construction workers in the Pirkanmaa Region of southern Finland. METHOD Retrospective cohort study of hospital records of the Tampere University Hospital. A population of Pirkanmaa paper mill workers (n=2686) and the Pirkanmaa working age population (n=252,500) served as reference populations. RESULTS There were 147 new cases of asthma among the construction workers in 1991-1995. The annual rate was 37 per 10,000 workers and the odds ratio was 2.1 [95% confidence interval (CI)=1.2-3.6] for the women and 1.8 (95% CI=1.5-2.2) for the men when compared with the general working age population. In general, the risk of asthma among the paper mill workers did not differ from the risk of asthma among the general working age population. The construction workers had an increased risk for asthma, although the number of reported cases of occupational asthma was lower for the construction workers than for the paper mill workers or for the working population. CONCLUSION Construction work, especially dusty tasks, was associated with an elevated risk of asthma. Thus the effect of exposure to irritant agents may have a role in the development of asthma among construction workers. For the most part, these cases of asthma do not meet the criteria for occupational asthma because the specified causal agent can not be defined. The aetiologic agents and mechanisms of asthma in construction work should be clarified for preventive measures.
A double-blind randomized trial on the clinical effect of different shunt valve settings in idiopathic normal pressure hydrocephalus.

OBJECTIVE The study aim was to examine the effect of gradually reducing the opening pressure on symptoms and signs in the shunt treatment of idiopathic normal pressure hydrocephalus (iNPH). METHODS In this prospective double-blinded, randomized, controlled, double-center study on patients with iNPH, a ventriculoperitoneal shunt with an adjustable Codman Medos Valve was implanted in 68 patients randomized into 2 groups. In 1 group (the 20-4 group) the valve setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the course of the 6-month study period. In the other group (the 12 group), the valve was kept at a medium level of 12 cm H2O during the whole study period. All patients were clinically evaluated using 4 tests preoperatively as well as postoperatively at 1, 2, 3, 4, and 6 months. The test scores between the 2 groups (20-4 and 12) were compared for each clinical evaluation. RESULTS Fifty-five patients (81%) were able to complete the study. There were no significant differences between the 2 groups (20-4 and 12) preoperatively or at any time postoperatively. Both groups exhibited significant clinical improvement after shunt insertion at all valve settings compared with the preoperative score, with the greatest improvement observed at the first postoperative evaluation. The clinical improvement was significant within the first 3 months, and thereafter no significant improvement was seen in either group. CONCLUSIONS Gradual reduction of the valve setting from 20 to 4 cm H2O did not improve outcome compared with a fixed valve setting of 12 cm H2O. Improvement after shunt surgery in iNPH patients was evident within 3 months, irrespective of valve setting.
Erythrophagocytosis by neoplastic cells in a patient with myelodysplastic syndrome.

In March 2003, a 69-year-old man entered the hospital because of pancytopenia. Based on the cytological features observed on a bone-marrow smear, a diagnosis of myelodysplastic syndrome was proposed. In October 2003, due to the worsening of his haematological conditions, a bone marrow biopsy was performed. The latter showed a clear-cut trilinear dysplasia, with a number of CD34 myeloid precursors that did not exceed 5% of the marrow cellularity. Notably, dysplastic myeloid elements (MPO+, CD68/PG-M1-, LAT-) displayed prominent erythrophagocytosis (Figures 1-4, arrowed). Phenomena of erythrophagocytosis and emperipolesis by macrophages (CD68/PG-M1: Figure 3, encircled) and megakaryocytes (LAT: Figure 4, encircled) were minimal. Based on these findings, a diagnosis of refractory cytopenia with multilineage dysplasia associated with erythrophagocytosis by neoplastic cells was made. Erythrophagocytosis by reactive histiocytes is a quite common feature. Less frequently neoplastic cells are themselves capable of erythrophagocytic activity: this has been observed in a series of tumours, including lymphoma, histiocytic sarcoma, malignant melanoma, carcinoma etc. 1 Erythrophagocytosis has also been exceptionally recorded in precursors cells of the granulopoiesis, especially during the course of acute myeloid leukaemias. To the best of our knowledge, this is the first true example of erythrophagocytosis by abnormal granulopoietic precursors in a patient with myelodysplastic syndrome. A previously reported case characterised by erythrophagocytic activity by dysplastic myeloid elements was in fact a refractory anaemia with excess of blasts in transformation (RAEB-t), a condition which is now included among acute leukaemias.
Neuroleptics and enrichment environment treatment in memory disorders and other central nervous system function observed in prenatally stressed rats

It is believed that the most effective method of treatment in schizophrenia is pharmacotherapy, in particular, the use of atypical neuroleptics like aripiprazole (ARI) and olanzapine (OLA). Moreover, studies of many authors have shown that enriched living conditions and tobacco smoke exposure can also affect the cognitive functions that are disturbed in the course of schizophrenia. The aim of the study was to find whether tobacco smoke and enrichment living conditions have the influence on cognitive functions in the newborn offspring of prenatally stressed rats and whether drugs such as ARI (1.5 mg/kg intraperitoneally (i.p.)) and OLA (0.5 mg/kg ip) in single and chronic treatment modify those functions (Morris water maze). The study (in the same conditions) also analyses immobility time (Porsolt test) and motor activity of animals that received ARI and OLA. It has been shown that ARI and OLA as well as enriched environment reduce cognitive function disorders and modify cognitive functions in rats exposed to tobacco smoke. In turn, current research has shown that nicotine has increased cognitive function disorders compared to the previous study (animals without tobacco smoke exposure).
Wall stress analysis of abdominal aortic aneurysms using 3D ultrasound

Wall stress analysis of abdominal aortic aneurysms is a novel tool that has proven high potential to improve risk stratification of abdominal aortic aneurysms (AAAs). Wall stress analysis is based on computed tomography (CT) and magnetic resonance imaging, however, 3D ultrasound (US) has not been used yet. In this study, the feasibility of 3D US based wall stress analysis is investigated and compared to CT. Three-dimensional US and CT data were acquired in 15 patients (diameter 35 - 90 mm). US data were segmented manually and compared to automatically acquired CT geometries by calculating the similarity index (SI) and Hausdorff distance (HD). Wall stresses were simulated at p = 140 mmHg using a non-linear material model (Raghavan & Vorp). The SI of US vs CT was 0.75 - 0.91, with a median HD of 5 - 15 mm, with the higher values found at the proximal and distal sides of the AAA. Wall stresses were in accordance with literature and a good agreement was found between US and CT-based median stresses and inter-quartile stresses. Stress values of US were typically higher, the result of geometrical irregularities, caused by the manual segmentation of the US data. In future work, an automated segmentation approach is the essential point of improvement.
Mast Cells Have Prognostic Value in Merkel Cell Carcinoma

We examined the role of mast cell infiltrates and other clinical and histological factors in the prognosis of Merkel cell carcinoma. Mast cells were stained immunohistochemically in 36 Merkel cell carcinomas with an antibody to tryptase. The number of stainable cells was quantified within the tumors and surrounding stroma. Other clinical and histological parameters were examined, statistically analyzed, and compared to subsequent clinical course and prognosis. Patient prognosis was worse with higher tumor mast cell numbers (P < 0.002). Prognosis was also found to be adversely affected by the presence of lymphovascular invasion (P = 0.03) and increased tumor size (P = 0.05). Increased mast cells counts, tumor size, and lymphovascular invasion are associated with an adverse prognosis in Merkel cell carcinomas. Evaluation of mast cell infiltrates may provide useful prognostic data and ultimately could assist in selecting patients that require adjuvant treatment in this aggressive form of skin cancer.
La expansión internacional de la industria vitivinícola chilena. Estudio empírico de los factores y nivel exportador

[ES] Este trabajo propone una serie de factores como determinantes del nivel de expansion internacional de la industria vitivinicola chilena: i) tamano de la empresa; ii) gestion de la calidad; iii) tecnologias de la informacion y la comunicacion; iv) planificacion de la gestion internacional, y finalmente, v) adaptacion de la estrategia de marketing internacional. El contraste empirico sobre la base de datos de exportacion de la industria vitivinicola chilena entre los anos 2004 y 2007, permitio confirmar seis de las siete hipotesis planteadas. Este estudio concluye con un apartado destinado a resumir las principales contribuciones teoricas y practicas, asi como las limitaciones y futuras lineas de investigacion.
Sexual well-being among partnered women with breast cancer recurrence.

PURPOSE A woman's risk for sexual disruption after breast cancer recurrence has received little clinical or research attention. PATIENTS AND METHODS Breast cancer patients recently diagnosed with recurrence (n = 60) were initially assessed at baseline and completed follow-ups at 4, 8, and 12 months. They were compared by age, stage, and duration and frequency of follow-up with matched patients who remained disease free (n = 120). Using linear mixed modeling, the groups were compared in their trajectories of change on measures of sexuality, relationship satisfaction, cancer-specific stress, and physical functioning. Recurrence subgroups, those with locoregional versus distant disease and those younger versus older than 52 years, were also compared. RESULTS At baseline, the recurrence group had significantly lower intercourse frequency and physical functioning compared with the disease-free group and these differences were maintained. There were no significant differences in the frequencies of kissing or sexual and relationship satisfactions. For the recurrence group patients, the heightened stress of the diagnostic/early recurrence treatment period declined to the lower disease-free levels by 12 months. This effect was largely due to improvement of the patients with distant disease. Finally, sexual changes were most notable for younger patients. CONCLUSION To our knowledge, this is the first longitudinal, controlled study of sexuality-sexuality in the context of other quality of life domains-for women coping with recurrence. Despite disruption, patients maintained their sexual lives. Younger and distant recurrence patients, however, may have greatest risk of sexual disruption. The factors contributing to sexual disruption remain unknown, and studies investigating strategies to help patients maintain this aspect of quality of life are needed.
Induction of lethal experimental allergic encephalomyelitis in nonhuman primates and guinea pigs with human glioblastoma multiforme tissue.

✓ The introduction of active specific immunotherapy as an adjunct to conventional therapy of the brain-tumor patient creates the risk of the concomitant induction of experimental allergic encephalomyelitis (EAE). The lack of resolution concerning the total group of central nervous system (CNS) antigens which may be encephalitogenic, and the lack of definition of the necessary conditions for the induction of an anti-CNS myelin response complicate the design of an immunotherapeutic regimen for brain-tumor patients. We report here the ready induction of EAE in four of four guinea pigs and both of two nonhuman primates (Macaca fascicularis) with human glioblastoma multiforme (GBM) tissue injected with either complete or incomplete Freund's adjuvant (CFA, IFA). Immunization protocols utilizing encephalitogenic GBM tissue and adjuvant which did not result in EAE induction were established in both of two macaques, and the production of significant levels of antibodies specifically reactive with immunizing GBM-de.
Experimental verification of magnetic field dose effects for the MRI-accelerator

The MRI-linear accelerator system, currently being developed, is designed such that the patient is irradiated in the presence of a magnetic field. This influences the dose distribution due to the Lorentz force working on the secondary electrons. Simulations have shown that the following dose effects occur: the build-up distance is reduced, the lateral profile becomes asymmetric in the direction orthogonal to the magnetic field and at tissue–air interfaces the dose increases due to returning electrons. In this work, GafChromic film measurements were performed in the presence of a magnetic field to experimentally quantify these dose effects. Depth–dose curves were measured in a PMMA–air–PMMA phantom and the lateral profiles were measured in a homogeneous PMMA phantom with the photon beam protruding over the edges of the phantom. The measurement results confirmed the magnetic field dose effects that were predicted by simulations. This enabled us to verify Geant4 Monte Carlo simulations of these MRI-linac specific dose effects: the relative agreement for the depth–dose curves between measurements and simulations was within 2.2%/1.8 mm. The relative agreement for the lateral profiles was 2.3%/1.7 mm. Overall, the magnetic field dose effects that are expected for irradiation with the MRI-linac can be modelled using Geant4 Monte Carlo simulations within measurement accuracy.
Metalloproteins Containing Cytochrome, Iron–Sulfur, or Copper Redox Centers

Redox reactions play important roles in almost all biological processes, including photosynthesis and respiration, which are two essential energy processes that sustain all life on earth. It is thus not surprising that biology employs redox-active metal ions in these processes. It is largely the redox activity that makes metal ions uniquely qualified as biological cofactors and makes bioinorganic enzymology both fun to explore and challenging to study. Even though most metal ions are redox active, biology employs a surprisingly limited number of them for electron transfer (ET) processes. Prominent members of redox centers involved in ET processes include cytochromes, iron–sulfur clusters, and cupredoxins. Together these centers cover the whole range of reduction potentials in biology (Figure ​(Figure1). 1). Because of their importance, general reviews about redox centers1−77 and specific reviews about cytochromes,8,24,78−90 iron–sulfur proteins,91−93 and cupredoxins94−104 have appeared in the literature. In this review, we provide both classification and description of each member of the above redox centers, including both native and designed proteins, as well as those proteins that contain a combination of these redox centers. Through this review, we examine structural features responsible for their redox properties, including knowledge gained from recent progress in fine-tuning the redox centers. Computational studies such as DFT calculations become more and more important in understanding the structure–function relationship and facilitating the fine-tuning of the ET properties and reduction potentials of metallocofactors in proteins. Since this aspect has been reviewed extensively before,105−110 and by other reviews in this thematic issue,2000,2001,2002 it will not be covered here. Figure 1 Reduction potential range of redox centers in electron transfer processes.
Pedigrees and the Study of the Wild Horse Population of Assateague Island National Seashore

Abstract Recently, a number of papers have addressed the use of pedigrees in the study of wild populations, highlighting the value of pedigrees in conservation management. We used pedigrees to study the horses (Equus caballus) of Assateague Island National Seashore, Maryland, USA, one of a small number of free-ranging animal populations that have been the subject of long-term studies. This population grew from 28 in 1968 to 175 in 2001, causing negative impacts on the island ecosystem. To minimize these effects, an immunocontraception program was instituted, and horse numbers are slowly decreasing. However, there is concern that this program may negatively affect the genetic health of the herd. We found that although mitochondrial DNA diversity is low, nuclear diversity is comparable to that of established breeds. Using genetic data, we verified and amended maternal pedigrees that had been primarily based on behavioral data and inferred paternity using genetic data along with National Park Service records of the historic ranges of males. The resulting pedigrees enabled us to examine demography, founder contributions, rates of inbreeding and loss of diversity over recent generations, as well as the level of kinship among horses. We then evaluated the strategy of removing individuals (using nonlethal means) with the highest mean kinship values. Although the removal strategy increased the retained diversity of founders and decreased average kinship between individuals, it disproportionately impacted sizes of the youngest age classes. Our results suggest that a combined strategy of controlled breeding and immunocontraception would be more effective than removing individuals with high mean kinships in preserving the long-term health and viability of the herd.
Multiple Myeloma in Horses, Dogs and Cats: A Comparative Review Focused on Clinical Signs and Pathogenesis

Multiple myeloma (MM) or plasma cell myeloma is a neoplastic proliferation of plasma cells that primarily involves the bone marrow but may originate from extramedullary sites [1-4]. Although it is uncommon in veterinary medicine, it has been reported in several species, in‐ cluding cats, dogs and, horses [1,3,5-10]. The frequency of MM in cats is slightly <1% of all malignant neoplasms. Canine MMs account for only 0.3% of all malignancies in dogs. MMs account approximately 2% of all hematopoietic neoplasms in both dogs and cats [4]. Most of the reports in the literature are limited to 1 to 16 case studies [4,11-16]. However, in a recent report regarding the incidence of bone disorders diagnosed in dogs, MM was the second most frequently diagnosed neoplastic condition in canine bone marrow [17].
Timing for Administration of an Antihypertensive Drug in the Treatment of Essential Hypertension

To find the best timing for administration of long-acting antihypertensive drugs, we gave nitrendipine, a calcium antagonist of the dihydropyridine group, once a day to six hospitalized and drug-free patients with essential hypertension, changing the time of administration and studying the effects on the circadian rhythm of blood pressure. After control values of 24-hour blood pressure variations were taken with patients on placebo, a 10-mg tablet of nitrendipine was given for 3 days on three occasions –at 6 AM on awakening, at 8:30 AM after breakfast, and at 6 PM after supper; 24-hour blood pressure values for each period were recorded on the third day. The 24-hour blood pressure values during the control period showed a biphasic circadian rhythm, with higher values during wakefulness and lower values during sleep. The control period was also characterized by a rapid rise in blood pressure on awakening, the so-called morning surge of blood pressure, and a gradual decline during sleep at night. Although the morning surge was not completely suppressed by nitrendipine given after breakfast, it was diminished by the drug given on awakening or after supper, the latter brought a deeper decline in blood pressure during sleep compared with other times. The average of 24-hour blood pressure values obtained by nitrendipine given on awakening was the lowest among the three occasions. Thus, administration of long-acting calcium antagonists with a rapid onset of action on awakening in the early morning seems to be a more rational and beneficial alternative than the conventional administration after breakfast. The earlier administration may prevent dangerous cardiovascular catastrophes, including stroke, myocardial infarction, and sudden death, known to occur often during the morning surge of blood pressure.
Molecular cloning and expression of rat contraception associated protein 1 (CAP1), a protein putatively involved in fertilization.

Epididymal fluid from rats rendered infertile by oral administration of ornidazole contains a protein CAP1 (contraception-associated protein 1) that is absent from epididymal fluid, but present on epididymal sperm, from fertile vehicle-treated rats. The gene for CAP1 has been isolated from a rat testis cDNA library and its expression investigated in different tissues. The deduced protein sequence of CAP1 contains 189 amino-acid residues and database searches revealed a high degree of homology (83-95%) with human and mouse DJ-1 at the nucleotide and amino acid levels. Northern blot hybridisation from different rat tissues indicated that CAP1 is encoded by a 1.6-kilobase RNA transcript and seems to be ubiquitiously expressed in the rat with a high level of expression in the testis.