bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Hidden Potential of Traditional Rice Landraces and Mutants for Iron and Zinc Concentration in Brown Rice to Develop Bio-fortified Rice Varieties
Authors: Parte Deepika , Sahu Parmeshwar K. , Patel Ravi Raj S. , Sao Richa , Baghel Samrath , Bhainsa Kuber , Das B.K. , Sharma Deepak
Published: January 2024

In the present study, 58 rice genotypes were evaluated for three consecutive seasons to enucleate the elite lines with high Fe and Zn contents. ANOVA revealed significant differences among the genotypes for Fe and Zn contents during all three seasons. Furthermore, PCV and GCV were moderate to high for Fe and Zn content during all three seasons. Similarly, high level of heritability and genetic advance were also recorded for both the traits. Iron content of Safri mutant 17-2-48 was consistently high for all the seasons whereas zinc content of Loktimachi was high for two seasons. Interestingly, rice genotypes Chhindmauri, Badsahbhog, Rudra, Danighoda and Suapankhi have been identified to have moderate to high Fe and Zn contents which could be used as donors for developing bio-fortified rice varieties. Stability analysis revealed that the genotypes Jhimiprass, Loktimachi, and CG Zinc Rice 2 for iron content and Rela Dhan, Chhindmauri, and CG Zinc Rice-1 for zinc content have had an average response to environment, making them appropriate for all seasons
Screening of Wild and Cultivated Vigna Accessions for Resistance to Bruchid (Callosobruchus maculatus F.)
Authors: Subramaniyan Ragul , Narayana Manivannan
Published: January 2024

The bruchid beetles (Callosobruchus maculatus) is one of the primary causes for the loss in pulses due to the seed damages during storage. The wild relatives of crop species are essential sources of new genes for crop improvement. A set of 40 wild Vigna accessions and cultivated Vigna species were screened for C. maculatus resistance. Based on the results, the accessions viz., V. radiata var. sublobata, V. trilobata and V. umbellata were found resistant as it recorded less adult emergence, lesser seed damage, low index of susceptibility and less seed weight loss among bruchid resistance traits. These traits are more influential principal components and have a high correlation. The identified accessions can be involved in the resistance breeding program as a donor to introgress resistance against bruchid beetles towards developing superior cultivars. One of the identified key traits, viz.,seed weight loss or seed damage or index of susceptibility, should be given more importance while framing the breeding program for reliable and stable bruchid resistance among the cultivar.
Outcome of fracture shaft of humerus fixed with dynamic compression plate in B. P. Koirala Institute of Health Sciences, Dharan, Nepal
Authors: Shah Kalawar Rosan Prasad , Chaudhary Pashupati
Published: January 2024

Introduction: Open reduction and internal fixation with dynamic compression plate (DCP) is necessary for fracture shaft of humerus (SoH) whose closed reduction is not acceptable or cannot be retained in slab or cast.

Objectives: Aim of the study was to evaluate outcome of fracture SoH fixed with DCP.

Methodology: Patients with fracture SoH fixed with DCP in BPKIHS in 2015-16 were prospectively studied for one year for perioperative issues and functional outcome using DASH score.

Results: There were 87 patients of fracture SoH fixed with DCP. Among 87 patients, 65.5% were male and 34.5% were female. The mean age was 36.4 years. The most common mode of injury was road traffic accident followed by fall from height, work place injury. The average operating time was 71 minutes with standard deviation 15.6. The mean blood loss was 205ml ± 45.60. Post-operative hospital mean stay was 4.5 days. There was post-operative radial nerve palsy in 4.6%. Only 69 patients can be followed up for one year for evaluation. Radial nerve palsy recovered fully in those with post-operative palsy. Disability of shoulder arm and hand (DASH) score was 82.50±9.6 after one year of surgery. Fracture was not united in 3(4.3%) patients out of 69 patients who reported for follow up at one year of injury and needed bone grafting and secondary intervention. This shows satisfactory functional outcome in fracture SoH fixed with DCP.

Conclusion: Dynamic compression plating for SoH fracture has satisfactory outcome.
Knowledge Attitude And Practice Regarding Superficial Fungal Infections In Dermatology Patients In Eastern Nepal
Authors: Yamu Sabrina , Choudhary Dilip , Aryal Shweta
Published: January 2024

Introduction: Superficial fungal infection is one of the most common diseases in dermatology evolving like an epidemic. Hence further research is necessary to minimize the occurrence and prevention of the disease.
Objectives: To assess the knowledge, attitude and practice about superficial fungal infection and implicate the result in educating the patients thereby minimizing its further recurrence and re-infections.
Methodology: A hospital based observational descriptive quantitative crosssectional study was conducted in all patients with superficial fungal infections attending dermatology outpatient department at Birat Medical College Teaching Hospital. A selfdesigned questionnaire which was double translated by two individuals in different translations and validated was used to assess knowledge, attitude and practice (KAP) regarding superficial fungal infections. Data were entered in Microsoft excel and analyzed in terms of proportions and percentage.
Results: Out of total 162 patients participating in the study, less than half of the study population was aware that it was a fungal infection; majority did not know how to apply medication in an appropriate technique. They strongly believed that hot weather was the cause. They practiced daily bath, but did not change their clothes often. They preferred taking over the counter medications and visited dermatologists less often and did not complete the total dose of prescribed medication and shared their prescription with their family members for similar problem.
Consclusion: All clinicians treating with superficial fungal infection should emphasize on counseling the patients regarding behavioural changes which will not only aid in treatment but will also focus on its preventive aspect.
Dally is not essential for Dpp spreading or internalization but for Dpp stability by antagonizing Tkv-mediated Dpp internalization
Authors: Simon Niklas , Safyan Abu , Pyrowolakis George , Matsuda Shinya
Published: January 2024

Dpp/BMP acts as a morphogen to provide positional information in the Drosophila wing disc. Key cell-surface molecules to control Dpp morphogen gradient formation and signaling are heparan sulfate proteoglycans (HSPGs). In the wing disc, two HSPGs, the glypicans Division abnormally delayed (Dally) and Dally-like (Dlp) have been suggested to act redundantly to control these processes through direct interaction of their heparan sulfate (HS) chains with Dpp. Based on this assumption, a number of models on how glypicans control Dpp gradient formation and signaling have been proposed, including facilitating or hindering Dpp spreading, stabilizing Dpp on the cell surface, or recycling Dpp. However, how distinct HSPGs act remains largely unknown. Here, we generate genome-engineering platforms for the two glypicans and find that only Dally is critical for Dpp gradient formation and signaling through interaction of its core protein with Dpp. We also find that this interaction is not sufficient and that the HS chains of Dally are essential for these functions largely without interacting with Dpp. We provide evidence that the HS chains of Dally are not essential for spreading or recycling of Dpp but for stabilizing Dpp on the cell surface by antagonizing receptor-mediated Dpp internalization. These results provide new insights into how distinct HSPGs control morphogen gradient formation and signaling during development.
Passive exposure to task-relevant stimuli enhances categorization learning
Authors: Schmid Christian , Haziq Muhammad , Baese-Berk Melissa M , Murray James M , Jaramillo Santiago
Published: January 2024

Learning to perform a perceptual decision task is generally achieved through sessions of effortful practice with feedback. Here, we investigated how passive exposure to task-relevant stimuli, which is relatively effortless and does not require feedback, influences active learning. First, we trained mice in a sound-categorization task with various schedules combining passive exposure and active training. Mice that received passive exposure exhibited faster learning, regardless of whether this exposure occurred entirely before active training or was interleaved between active sessions. We next trained neural-network models with different architectures and learning rules to perform the task. Networks that use the statistical properties of stimuli to enhance separability of the data via unsupervised learning during passive exposure provided the best account of the behavioral observations. We further found that, during interleaved schedules, there is an increased alignment between weight updates from passive exposure and active training, such that a few interleaved sessions can be as effective as schedules with long periods of passive exposure before active training, consistent with our behavioral observations. These results provide key insights for the design of efficient training schedules that combine active learning and passive exposure in both natural and artificial systems.
TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma
Authors: Tian Maojin , Yang Le , Zhao Ziqian , Li Jigang , Wang Lianqing , Yin Qingqing , Hu Wei , Lou Yunwei , Du Jianxin , Zhao Peiqing
Published: January 2024

TIPE (TNFAIP8) has been identified as an oncogene and participates in tumor biology. However, how its role in the metabolism of tumor cells during melanoma development remains unclear. Here, we demonstrated that TIPE promoted glycolysis by interacting with pyruvate kinase M2 (PKM2) in melanoma. We found that TIPE-induced PKM2 dimerization, thereby facilitating its translocation from the cytoplasm to the nucleus. TIPE-mediated PKM2 dimerization consequently promoted HIF-1α activation and glycolysis, which contributed to melanoma progression and increased its stemness features. Notably, TIPE specifically phosphorylated PKM2 at Ser 37 in an extracellular signal-regulated kinase (ERK)-dependent manner. Consistently, the expression of TIPE was positively correlated with the levels of PKM2 Ser37 phosphorylation and cancer stem cell (CSC) markers in melanoma tissues from clinical samples and tumor bearing mice. In summary, our findings indicate that the TIPE/PKM2/HIF-1α signaling pathway plays a pivotal role in promoting CSC properties by facilitating the glycolysis, which would provide a promising therapeutic target for melanoma intervention.
Simultaneous, vision-based fish instance segmentation, species classification and size regression
Authors: Climent-Perez Pau , Galán-Cuenca Alejandro , Garcia-d’Urso Nahuel E. , Saval-Calvo Marcelo , Azorin-Lopez Jorge , Fuster-Guillo Andres
Published: January 2024

Overexploitation of fisheries is a worldwide problem, which is leading to a large loss of diversity, and affects human communities indirectly through the loss of traditional jobs, cultural heritage, etc. To address this issue, governments have started accumulating data on fishing activities, to determine biomass extraction rates, and fisheries status. However, these data are often estimated from small samplings, which can lead to partially inaccurate assessments. Fishing can also benefit of the digitization process that many industries are undergoing. Wholesale fish markets, where vessels disembark, can be the point of contact to retrieve valuable information on biomass extraction rates, and can do so automatically. Fine-grained knowledge about the fish species, quantities, sizes, etc. that are caught can be therefore very valuable to all stakeholders, and particularly decision-makers regarding fisheries conservation, sustainable, and long-term exploitation. In this regard, this article presents a full workflow for fish instance segmentation, species classification, and size estimation from uncalibrated images of fish trays at the fish market, in order to automate information extraction that can be helpful in such scenarios. Our results on fish instance segmentation and species classification show an overall mean average precision (mAP) at 50% intersection-over-union (IoU) of 70.42%, while fish size estimation shows a mean average error (MAE) of only 1.27 cm.
Neem Leaf Supplement Ameliorates Depressive Like Behaviour in Alzheimer’s Disease Model in Adult Male Wistar Rats
Authors: Memudu Adejoke Elizabeth , Anzaku Fatima Ayinda , Jibaniya Grace Mchibuma , Adanike Rukky Precious
Published: January 2024

Aim of the Study: Currently, reports linked neuropathological changes in Alzheimer’s Disease (AD) to be a risk factor in depression. There is a need to develop natural therapeutics, with strong antioxidant property like Neem leaf, to avert AD’s neuropathological and behavioural changes using animal model induced by neurotoxin aluminium chloride. This study is aimed at ascertaining depressive like disorders in AD model while evaluating mechanism through which Neem averts AD neurodegeneration in the fronto-cerebellar cortex and possible depressive like behaviour.
Methodology: Twenty (20) adult male Wistar rats used were grouped (n=5) viz: control group (A), neurodegenerative model given aluminium (B), 200mg/kg Neem leaf supplement (C) and 200mg/kg Neem leaf treated AD model (D). Neurobehavioural changes for reward memory and depressive like behaviour were evaluated using Y-maze (open arm reward test) and the tail suspension test (TST).  The frontal and cerebellar cortices were excised, fixed and processed for  Haematoxylin and Eosin stain (H and E), Cresyl fast violet (CFV) stain for Nissl bodies and astrocytes immunohistochemistry using glial fibrillary acidic protein (GFAP). Behavioural test data were analyzed using ANOVA and test for significance done @ p<0.05.
Results: Aluminum induced neurodegeneration similar to AD pathology characterized by loss of neurons, chromatolysis, proliferation of astrocytes and decline in cognitive function in addition to exhibiting depressive like behaviour seen in a decrease number of reward arm entries, increase in time spent to reach reward arm and immobility time in the TST attributed to loss of cognitive function relative to loss of neurons integrity in the fronto-cerebellar cortex. However, neem leaf supplementation mitigates against AD model neuropathological and neurobehavioural  presentations resulting in an improved neurocognition, neuron survival or repair, decline in astrocytes proliferation and decline in depressive like behavior as compared to Aluminum induced AD model.
Conclusion: Neem leaf alleviates depressive like behaviour associated with neurocognitive impairment through the interaction between neuron-astrocytes to protect neurons against aluminum induced neuroinflamamation and strengthens neural circuit for cognitive function.
Ecological Status of a Tropical Inland Water Using Macroinvertebrate Feeding Groups and Sediment Characteristics
Authors: Oladimeji Adeleke Sikiru , Omokunle Amusan Babatunde , Funmilayo Akin-Aina Olawumi
Published: January 2024

Changing environmental conditions have an important influence on the functional and structural organization of macroinvertebrates in water. The involvements of macroinvertebrates in Bio-monitoring have focused largely on their distribution pattern in water while neglecting the functional and feeding structure. This study aims to use the structure and habitat preferences of macroinvertebrates to provide reliable information on the ecological integrity of Atori Reservoir. Macroinvertebrates were sampled once every two months from selected sample stations in Atori Reservoir for a period covering both wet and dry seasons of an annual cycle. The collected macroinvertebrates were categorized into functional groups using feeding patterns, habitat preferences and mode of locomotion. The reservoir sediment was also analyzed for selected physico-chemical characteristics. Predators (feeding pattern) and Skaters (locomotion and habitat preference) were dominant in the collection. Many of the functional feeding groups were more abundant in the dry season. In fact, Collector-gatherers and shredders were recorded only in the dry season. There was no significant difference in the seasonal variation in the distribution of the macroinvertebrates in the reservoir. The physico-chemical parameters of the sediment did not vary significantly across the sample stations but paired samples T-test showed significant differences in the seasonal variations of physico-chemical parameters of the sediment in the reservoir The dominance of predators and skaters, which are known tolerant species have implications for the ecological integrity of the water. The dominance of tolerant species and the physico-chemical characteristics of the sediment suggested the presence of mild pollution in Atori Reservoir. Proactive conservative measures should be taken in order to prevent further degradation of the water quality as well as prevention of loss of biodiversity in the waterbody.
Ameliorative Activities of Morus and Jamun against Cr Induced Andro-Hepatic Anomalies
Authors: Abbas Tahir , Ahmad Khawaja Raees , Asmatullah  , Akhtar Haider Ali , Fatima Tehreem
Published: January 2024

Chromium (Cr) is a vital micronutrient for sugar metabolism while its unauthorized use may agonize health fatalities. This study was conducted about the novelty about exposure of hexavalent chromium (Cr+6) histopatholgical potentials along with Mulberry Fruit Extract and Jamun Fruit Extract to define the ameliorative aptitude. The histological finding in Cr exposure specify; cessation of testicular seminiferous tubules (ST), annihilation of smooth muscles in basement membrane, Leydig’s cell and spermatids. The ST have halted spermatogenesis, with irregular boundary and dead spermatogonia and Leydig’s cells are disorganized. The sperm head cross sectional area (CSA), tail length and middle piece diameter (p ≤ 0.001) significantly reduced while there is significant elevation of hepatocytes nuclei size, central vein CSA and mean width of Sinusoidal Spaces as compared to control. The protuberant marks of steatosis, fibrosis, dehydration and atrophy were nullified by designated fruit extracts and their possible bio-chelating effects was obvious due to the presence of anthocyanin, β-sitosterol and phytochemicals. The given results specify that hexavalent Cr induce andro-hepatic anomalies when it is freely used without scientific authentication. Cr+6 as food additives in coloring rice and local sweets should be prohibited while bio-products of Morus and Jamun can be recommended and sponsored for traditional medicines.
Immuno-Positivity of HIV among Long Distance Drivers, Short Distance Drivers and Ordinary Drivers in Rivers State
Authors: Williams K. F. , Chioma D. M.
Published: January 2024

In this study, the immuno-positivity of HIV among long, short distance drivers and ordinary drivers in different motor parks in Choba and Rumuokoro community Rivers State was investigated for their retroviral status. A total of 81 commercial drivers between the ages 30-56 while 15 ordinary drivers between the ages 35-60 years old volunteered for the screening.Questionnaires were administered to the participants before their blood samples were aseptically collected. HIV screening was carried out using Determine HIV ½ strips. The results showed that a 40-year old commercial driver (3%) in the long distance driver category tested positive for HIV 2. However, in the short distance driver category, two commercial drivers aged 38 and 41 respectively (4%) tested positive for HIV 2. The ordinary drivers were all tested negative for HIV 2. The Level of HIV awareness among Long, short distance drivers and ordinary drivers is 84%. Sixteen are aware of all routes of transmission while 16% have very little or no Knowledge of the non-sexual routes. Response from the questionnaire showed a high level (84%) of awareness of HIV infection.  Due to the nature of their occupation, commercial drivers are always exposed to multiple sex partners. Therefore, HIV awareness, prevention and treatment should be vigorously encouraged among commercial drivers.
Studies of some ultratrace elements in antarctic water via crown ether crosslinked chitosan
Authors: Zhang Shu‐Qin , Wang Yu‐Ting , Tang Yu‐Rong
Published: September 2003

A new type of crown ether crosslinked chitosan was prepared by the reaction of chitosan with synthesized 4,4′‐dibromodibenzo‐18‐crown‐6. Its adsorption behaviors for some ultratrace elements at different sites in Antarctica were studied. The results indicated that the adsorption rates were greater than 95% at pH 7.5, the enrichment factor of the ultraelements was greater than 50, and the detection limits of graphite furnace atomic absorption spectroscopy were improved greatly. The proper analysis conditions were examined, and a new method of detecting ultratrace elements in environmental water samples with dibromodibenzo‐18‐crown‐6 crosslinked chitosan was developed. In addition, the elements could easily be eluted off after absorption by dibenzo‐18‐crown‐6 crosslinked chitosan, and so it is possible for this method to be used as a routine and valuable analysis method in environmental inspections. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 806–809, 2003
Preparation of siloxane–silsesquioxane hybrid thin films for large‐scale‐integration interlayer dielectrics with excellent mechanical properties and low dielectric constants
Authors: Yim Jin‐Heong , Lyu Yi‐Yeol , Jeong Hyun‐Dam , Mah Sang Kook , Hyeon‐Lee Jingyu , Hahn Jun‐Hee , Kim Gwang Seok , Chang Seok , Park Jae‐Geun
Published: September 2003

Several kinds of homogeneous organic–inorganic hybrid polymer thin films were designed with improved mechanical properties and low dielectric constants (<3.0). Novel soluble siloxane–silsesquioxane hybrid polymers were synthesized with cyclic and/or cage silane monomers, which had triorganosiloxy (R3Si1/2), diorganosiloxane (R2SiO2/2), and organosilsesquioxane (RSiO3/2) moieties with ethylene bridges at the molecular level, by the hydrolysis and condensation of 2,4,6,8‐tetramethyl‐2,4,6,8‐tetra(trimethoxysilylethyl)cyclotetrasiloxane (a cyclic monomer). The electrical properties of these films, including the dielectric constant (∼2.51), leakage current (6.4 × 10−11 A/cm2 at 0.5 MV/cm), and breakdown voltage (∼5.4 MV/cm) were fairly good. Moreover, the mechanical properties of the hybrid films, including the hardness (∼7 GPa), modulus (∼1.2 GPa), and crack‐free thickness (<2 μm), were excellent in comparison with those of previous spin‐on‐glass materials with low dielectric constants. The excellent mechanical properties were proposed to be due to the high contents of SiOH groups (>30%) and the existence of ethylene bridge and siloxane moieties in the hybrid polymer precursors. In addition, the mechanical properties of the hybrid films were affected by the contents of the cagelike structures. The more cagelike structures a hybrid film contained, the worse its mechanical properties were. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 626–634, 2003
Thermogravimetric analysis of blends of low‐density polyethylene and poly(dimethyl siloxane) rubber: The effects of compatibilizers
Authors: Jana R. N. , Nando G. B.
Published: September 2003

The thermal stability of vulcanizates of low‐density polyethylene (LDPE), poly(dimethyl siloxane) (PDMS) rubber, and their blends was studied by nonisothermal thermogravimetry. Four ethylene copolymers [ethylene methyl acrylate (EMA), ethylene vinyl acetate, ethylene acrylic acid, and a zinc‐salt‐based ionomer (Lotek 4200)] were used as compatibilizers for the blend systems. The thermograms and derivatograms of the blends showed that thermal degradation took place in two stages, whereas those for the base polymers showed single‐stage degradation. Kinetic studies of the blends and pure components showed that the degradation followed first‐order reaction kinetics. The activation energy at 10% degradation was determined with the Freeman–Carroll method and was at a maximum (42.34 kcal/mol) for the 25:75 LDPE/PDMS rubber blend. The half‐life at 200°C was evaluated by the Flynn–Wall method and was at a maximum (812.5 days) for the same blend. Out of four compatibilizers, EMA showed the maximum activation energy (34.25 kcal/mol) for degradation and a maximum half‐life (695.3 days), indicating that EMA was the best compatibilizer for the blend system. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 635–642, 2003
Preparation and characterization of poly(butyl acrylate‐co‐2‐ethylhexyl acrylate) grafting of vinyl chloride resin with good impact resistance
Authors: Pan Mingwang , Zhang Liucheng
Published: September 2003

Crosslinked poly(butyl acrylate‐co‐2‐ethylhexyl acrylate) [P(BA–EHA)] latex was synthesized by seeded emulsion polymerization. P(BA–EHA)/poly(vinyl chloride) (PVC) composite latex was prepared using P(BA–EHA) latex as the seed. The effects of the amount of P(BA–EHA) on the latex particle diameters and mechanical properties of the materials are discussed. The grafting efficiency (GE) of P(BA–EHA)‐grafted vinyl chloride (VC) in the synthesized resin was investigated, and the GE increased with an increasing P(BA–EHA)/VC ratio. The morphology of P(BA–EHA)/PVC was characterized using TEM, SEM, and DMA. TEM indicated that the particles of the P(BA–EHA)/PVC composite latex have a clear core–shell structure. DMA illustrated that the compatibility between P(BA–EHA) and PVC was well improved. With an increasing P(BA–EHA) content, the loss peak in the low‐temperature range became stronger than that of pure PVC, and the maximum values of the loss peaks gradually shifted to higher temperature. SEM showed that the fractured surface of the composite sample exhibited better toughness of the material. The notched impact strength of the material with 4.2 wt % P(BA–EHA) was 11 times that of PVC. TEM showed that P(BA–EHA) was uniformly dispersed in the PVC matrix and that the interface between the two phases was indistinct. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 643–649, 2003
Influence of the short‐chain branch length on the calibration of temperature rising elution fractionation systems
Authors: Savitski Edward P. , Caflisch George B. , Killian Christopher M. , Meadows Michael D. , Merkley Joseph H. , Huff Brenda J.
Published: September 2003

The effects of short‐chain branch (SCB) length on the calibration of temperature rising elution fractionation (TREF) were examined. Samples of ethylene–hexene, ethylene–octene, and a novel polyolefin produced using Eastman Chemical Company's Gavilan catalyst technology were used to prepare TREF calibration curves. Preparative TREF was used to collect fractions of the materials based on their crystallizability, and the branching frequencies of the fractions were determined by NMR. Calibration curves were generated by plotting the branching frequency as a function of the TREF elution temperature. The results indicate that the calibration curves shift to lower TREF elution temperatures as the length of the SCB increases from methyl to butyl to hexyl. Other factors that may contribute to this shift include chain microstructural differences from variations in catalyst structure and process conditions. The shift can be decreased by plotting the data in “number of branches per 1000 backbone carbons” versus TREF elution temperature instead of the more traditional “number of branches per 1000 total carbons.” These data indicate that the branch type must be known a priori to calculate SCB averages and SCB distributions and that unique calibration curves exist for copolymers made using different α‐olefin comonomers. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 722–728, 2003
Synthesis, characterization, and properties of poly(m‐aminophenyl propionic acid) and its copolymers with aniline
Authors: Rivas B. L. , Sánchez C. O. , Bernede J.‐C. , Basaez L.
Published: September 2003

The synthesis of poly(m‐aminophenyl propionic acid) (PAPPA) was carried out by polymerization in different aqueous media, from the respective monomer, using ammonium persulfate as oxidizing agent. The copolymer of aniline and m‐aminophenyl propionic acid was also synthesized. The polymers were characterized by FTIR, UV‐vis, X‐ray electron spectroscopy, nuclear magnetic resonance spectroscopy, elemental analysis, thermal stability analysis (TGA), and electrical conductivity. PAPPA showed a high doping by HCl and H2SO4. If the composition of the comonomer acid decreases, the incorporation of copper ion and the electrical conductivity are increased. Thermal stability is favored by an increase of the content of aniline and copper ions. The polymeric structures have amine and imine groups. The last units are preferentially doped. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 706–715, 2003
Heterogeneity among patients with tumor necrosis factor receptor–associated periodic syndrome phenotypes
Authors: Aganna Ebun , Hammond Linda , Hawkins Philip N. , Aldea Anna , McKee Shane A. , van Amstel Hans Kristian Ploos , Mischung Claudia , Kusuhara Koichi , Saulsbury Frank T. , Lachmann Helen J. , Bybee Alison , McDermott Elizabeth M. , La Regina Micaela , Arostegui Juan I. , Campistol Josep M. , Worthington Sharron , High Kevin P. , Molloy Michael G. , Baker Nicholas , Bidwell Jeff L. , Castañer José L. , Whiteford Margo L. , Janssens‐Korpola P. L. , Manna Raffaele , Powell Richard J. , Woo Patricia , Solis Pilar , Minden Kirsten , Frenkel Joost , Yagüe Jordi , Mirakian Rita M. , Hitman Graham A. , McDermott Michael F.
Published: September 2003

Objective

To investigate the prevalence of tumor necrosis factor receptor–associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS.

Methods

Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) “TRAPS‐like” symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence‐activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes.

Results

Eight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (ΔD42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS‐like conditions was found: 3 members of the “prototype familial Hibernian fever” family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation‐negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants.

Conclusion

The presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with “TRAPS‐like” features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.
Expression of the markers BDCA‐2 and BDCA‐4 and production of interferon‐α by plasmacytoid dendritic cells in systemic lupus erythematosus
Authors: Blomberg Stina , Eloranta Maija‐Leena , Magnusson Mattias , Alm Gunnar V. , Rönnblom Lars
Published: September 2003

Objective

To study the expression of blood dendritic cell antigen 2 (BDCA‐2) and BDCA‐4 molecules by plasmacytoid dendritic cells (PDCs) in the blood of patients with systemic lupus erythematosus (SLE), and to study PDC production of interferon‐α (IFNα) and its inhibition by anti–BDCA‐2 and anti–BDCA‐4 antibodies.

Methods

Peripheral blood mononuclear cells (PBMCs) from SLE patients (SLE PBMCs) and from healthy controls were induced to produce IFNα in vitro by SLE serum containing an endogenous IFNα‐inducing factor (SLE‐IIF) or by herpes simplex virus type 1 (HSV‐1). The frequencies and numbers of BDCA‐2–, BDCA‐3–, and BDCA‐4–expressing cells were analyzed by flow cytometry, and the effects of anti–BDCA‐2 and anti–BDCA‐4 monoclonal antibodies (mAb) on IFNα production were investigated.

Results

IFNα production by SLE PBMCs induced by SLE‐IIF or HSV‐1 was decreased compared with that of healthy control PBMCs (P = 0.002 and P = 0.0007, respectively). The proportions of BDCA‐2– and BDCA‐3–expressing cells in SLE PBMCs were reduced compared with those in PBMCs from healthy controls (P = 0.01 and P = 0.004, respectively). IFNα producers in culture, especially among SLE PBMCs, displayed reduced BDCA‐2 expression and constituted only a minority of the BDCA‐2–positive cells, at least in healthy control PBMCs (median 18%). IFNα production by both SLE and healthy control PBMCs stimulated by SLE‐IIF or HSV‐1 was markedly reduced by anti–BDCA‐2 mAb (median 81–98% inhibition). Anti–BDCA‐4 mAb only partially inhibited SLE‐IIF–induced IFNα production.

Conclusion

SLE patients had a reduced number of BDCA‐2–expressing PDCs, also termed natural IFNα‐producing cells, and their IFNα production could be inhibited by anti–BDCA‐2/4 mAb. Such mAb may be a therapeutic option for inhibiting the ongoing IFNα production in SLE patients.
Prevention of the onset and progression of collagen‐induced arthritis in rats by the potent p38 mitogen‐activated protein kinase inhibitor FR167653
Authors: Nishikawa Masataka , Myoui Akira , Tomita Tetsuya , Takahi Koichiro , Nampei Akihide , Yoshikawa Hideki
Published: September 2003

Objective

FR167653 is a potent inhibitor of p38 mitogen‐activated protein kinase (MAPK) and inhibits tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) production in inflammatory cells. In this study we investigated the effect of FR167653 on collagen‐induced arthritis (CIA).

Methods

Rats with CIA were subcutaneously injected with FR167653 (32 mg/kg/day) starting on the day of the booster injection (day 7) in the prophylactic treatment group and after the onset of arthritis (day 21) in the therapeutic treatment group. Hind‐paw swelling, body weight, radiographic and histologic scores, and osteoclast number were evaluated. Cytokine levels in the serum and tissue were assessed by enzyme‐linked immunosorbent assays. Flow cytometric analysis of T lymphocytes from bone marrow was performed. The effect of FR167653 on in vitro osteoclast formation induced by soluble receptor activator of nuclear factor κB ligand (sRANKL) and TNFα was examined.

Results

Swelling of hind paws and loss of weight occurred in the CIA rats, but this was not evident in the prophylactic treatment group. Therapeutic treatment also significantly reduced paw swelling. The mean radiographic and histologic scores as well as the osteoclast numbers were significantly lower in the treatment group than in the CIA rats without treatment. FR167653 treatment reduced the serum levels of TNFα and IL‐1β, lowered the IL‐1β concentration in the ankle joints, and decreased the CD4−,CD8a+ T cell population in bone marrow. Furthermore, FR167653 inhibited the osteoclast‐like cell differentiation induced by both sRANKL and TNFα in vitro.

Conclusion

FR167653 prevents the onset of arthritis in a prophylactic treatment model and suppresses the progression of joint destruction in a therapeutic treatment model, suggesting that p38 MAPK is a potential therapeutic target for rheumatoid arthritis.
Expression of the MAPK kinases MKK‐4 and MKK‐7 in rheumatoid arthritis and their role as key regulators of JNK
Authors: Sundarrajan Monisha , Boyle David L. , Chabaud‐Riou Martine , Hammaker Deepa , Firestein Gary S.
Published: September 2003

Objective

The mitogen‐activated protein (MAP) kinase JNK is a key regulator of interleukin‐1 (IL‐1)–induced collagenase gene expression and joint destruction in arthritis. Two upstream kinases, MKK‐4 and MKK‐7, have been identified as potential activators of JNK. However, the role of MAP kinase kinases (MAPKKs) and their functional organization within fibroblast‐like synoviocytes (FLS) have not been defined. We therefore evaluated the interactions between the various MAP kinase components and determined their subcellular localization.

Methods

MKKs were identified by immunohistochemistry of rheumatoid arthritis (RA) and osteoarthritis (OA) synovium. Western blotting was used to determine the expression of FLS. Immunoprecipitation experiments using antibodies specific for MKK‐4, MKK‐7, and JNK were performed. Phosphospecific antibodies and immunohistochemistry were used to evaluate the activation state of synovial MKK‐4 and MKK‐7. Confocal microscopy was used to determine the subcellular location of the kinases.

Results

Immunohistochemistry studies demonstrated abundant MKK‐4 and MKK‐7 in RA and OA synovium, but the levels of phosphorylated kinases were significantly higher in RA synovium. MKK‐4 and MKK‐7 were constitutively expressed by cultured RA and OA FLS, and IL‐1 stimulation resulted in rapid phosphorylation of both kinases. JNK was detected in MKK‐4 and MKK‐7 immunoprecipitates. Furthermore, MKK‐4 coprecipitated with MKK‐7 and vice versa, indicating that the 3 kinases form a stable complex in FLS. Confocal microscopy confirmed that JNK, MKK‐4, and MKK‐7 colocalized in the cytoplasm, with JNK migrating to the nucleus after IL‐1 stimulation. The signal complex containing MKK‐4, MKK‐7, and JNK was functionally active and able to phosphorylate c‐Jun after IL‐1 stimulation of FLS.

Conclusion

These studies demonstrate that JNK, MKK‐4, and MKK‐7 form an active signaling complex in FLS. This novel JNK signalsome is activated in response to IL‐1 and migrates to the nucleus. The JNK signalsome represents a new target for therapeutic interventions designed to prevent joint destruction.
Citrullination of synovial proteins in murine models of rheumatoid arthritis
Authors: Vossenaar Erik R. , Nijenhuis Suzanne , Helsen Monique M. A. , van der Heijden Annemarie , Senshu Tatsuo , van den Berg Wim B. , van Venrooij Walther J. , Joosten Leo A. B.
Published: September 2003

Objective

Antibodies directed to citrulline‐containing proteins are highly specific for rheumatoid arthritis (RA) and can be detected in up to 80% of patients with RA. Citrulline is a nonstandard amino acid that can be incorporated into proteins only by posttranslational modification of arginine by peptidylarginine deiminase (PAD) enzymes. The objective of this study was to investigate the presence of anticitrulline antibodies, PAD enzymes, and citrullinated antigens in mouse models of both acute and chronic destructive arthritis: streptococcal cell wall (SCW)–induced arthritis and collagen‐induced arthritis (CIA), respectively.

Methods

Synovial tissue biopsy specimens were obtained from naive mice, mice with CIA, and mice with SCW‐induced arthritis. The expression of messenger RNA (mRNA) for PAD enzymes was analyzed by reverse transcriptase–polymerase chain reaction; the presence of PAD proteins and their products (citrullinated proteins) was analyzed by Western blotting and by immunolocalization. The presence of anticitrullinated protein antibodies was investigated by an anti–cyclic citrullinated peptide (anti‐CCP) enzyme‐linked immunosorbent assay (ELISA) and an ELISA using in vitro citrullinated fibrinogen.

Results

In both mouse models, PAD type 2 (PAD2) mRNA was present in the synovium but was not translated into PAD2 protein. In contrast, PAD4 mRNA, although absent from healthy synovium, was readily transcribed and translated by polymorphonuclear neutrophils infiltrating the synovial tissue during inflammation. As a consequence, several synovial proteins were subjected to citrullination. One of these proteins was identified as fibrin, which has been reported to be citrullinated also in synovium of patients with RA. Although generation of citrullinated antigens during synovial inflammation in the mice was eminent, no anti‐CCP antibodies could be detected.

Conclusion

Citrullination of synovial antigens is an active process during joint inflammation in both mice and humans, but the induction of autoantibodies directed to these proteins is a more specific phenomenon, detectable only in human RA patients.
Osteoarthritis‐like changes and decreased mechanical function of articular cartilage in the joints of mice with the chondrodysplasia gene (cho)
Authors: Xu L. , Flahiff C. M. , Waldman B. A. , Wu D. , Olsen B. R. , Setton L. A. , Li Y.
Published: September 2003

Objective

To investigate whether heterozygosity for a loss‐of‐function mutation in the gene encoding the α1 chain of type XI collagen (Col11a1) in mice (chondrodysplasia, cho) causes osteoarthritis (OA), and to understand the biochemical and biomechanical effects of this mutation on articular cartilage in knee and temporomandibular (TM) joints.

Methods

Articular cartilage from the knee and TM joints of mice heterozygous for cho (cho/+) and their wild‐type littermates (+/+) was examined. The morphologic properties of cartilage were evaluated, and collagen fibrils were examined by transmission electron microscopy. Immunohistochemical staining was performed to examine the protein expression levels of matrix metalloproteinase 3 (MMP‐3) and MMP‐13 in knee joints. In 6‐month‐old animals, fixed‐charge density was determined using a semiquantitative histochemical method, and tensile stiffness was determined using an osmotic loading technique.

Results

The diameter of collagen fibrils in articular cartilage of knee joints from heterozygous cho/+ mice was increased relative to that in control cartilage, and histologic analysis showed OA‐like degenerative changes in knee and TM joints, starting at age 3 months. The changes became more severe with aging. At 3 months, protein expression for MMP‐3 was increased in knee joints from cho/+ mice. At 6 months, protein expression for MMP‐13 was higher in knee joints from cho/+ mice than in joints from their wild‐type littermates, and negative fixed‐charge density was significantly decreased. Moreover, tensile stiffness in articular cartilage of knee joints from cho/+ mice was moderately reduced and was inversely correlated with the increase in articular cartilage degeneration.

Conclusion

Heterozygosity for a loss‐of‐function mutation in Col11a1 results in the development of OA in the knee and TM joints of cho/+ mice. Morphologic and biochemical evidence of OA appears to precede significant mechanical changes, suggesting that the cho mutation leads to OA through a mechanism that does not initially involve mechanical factors.
A mind to blame: new views on involuntary acts
Authors: Denno Deborah W.
Published: September 2003

This article examines the legal implications linked to recent scientific research on human consciousness. The article contends that groundbreaking revelations about consciousness expose the frailties of the criminal law's traditional dual dichotomies of conscious versus unconscious thought processes and voluntary versus involuntary acts. These binary doctrines have no valid scientific foundation and clash with other key criminal law defenses, primarily insanity. As a result, courts may adjudicate like individuals very differently based upon their (often unclear) understanding of these doctrines and the science that underlies them. This article proposes a compromise approach by recommending that the criminal law's concept of voluntariness consist of three parts: (i) voluntary acts, (ii) involuntary acts, and (iii) semi‐voluntary acts. The semi‐voluntary acts category, which is new, incorporates modern ideas of consciousness and also advances the law. Using some actual criminal cases, this article applies this new three‐part grouping and demonstrates how it enhances a more just outcome for defendants, victims, and society. Copyright © 2003 John Wiley & Sons, Ltd.
Impulsive versus premeditated aggression: implications formens readecisions
Authors: Barratt Ernest S. , Felthous Alan R.
Published: September 2003

Science can provide more information about the nature of aggressive acts, and therefore themens reaof criminal offenses, than is commonly assumed. For example, progress has been made in classifying aggression as impulsive or premeditated within the context of the role of conscious experience in controlling behavior. This review of the status of the scientific ability to distinguish conscious from unconscious acts and more specifically impulsive from premeditated aggressive acts is organized around four themes: (i) How is aggression defined and measured in general? (ii) How does the distinction between impulsive and premeditated aggression relate to the legal concept ofmens rea? (iii) How do various scientific disciplines contribute to the mind/body discourse? (iv) What risk factors are associated with impulsive and premeditated aggression respectively? The authors conclude that the most promising approach to researching the nature of behavioral intention and motivation is to apply a discipline neutral model that integrates the data from multiple disciplines, collectively designated the cognitive neurosciences. Copyright © 2003 John Wiley & Sons, Ltd.
Fine‐needle aspiration biopsy and intraoperative cytologic smear findings in a case of benign mesothelial‐cell inclusions involving a lymph node: Case report and review of the literature
Authors: Paull Gerson , Mosunjac Marina
Published: September 2003

Although first described over a decade ago, the rare entity of mesothelial lymph node inclusions (nonneoplastic mesothelial cells involving lymph node sinuses) is not well‐known among pathologists. Unlike most lymph node inclusions such as Müllerian inclusions or nevus cells, which usually occur in the capsule of the lymph node, mesothelial cells involve the lymph node sinus, mimicking metastatic carcinoma or metastatic mesothelioma. The spectrum of histologic findings ranges from a few mesothelial cells, perhaps only detectable by immunohistochemical stains, to a massive distention of the lymph node sinus with abundant mesothelial cells. Mesothelial‐cell inclusions in lymph nodes are usually found in mediastinal lymph nodes of patients with pleural and/or pericardial effusions. It is hypothesized that the effusion, due to whatever cause, allows for mesothelial‐cell migration into the submesothelial lymphatics and regional lymph nodes. To our knowledge, cytologic findings on aspiration biopsy and intraoperative smear preparations of a lymph node with mesothelial‐cell inclusions have never been described. Familiarity with this entity is important in preventing misdiagnosis of malignancy. Diagn. Cytopathol. 2003;29:163–166. © 2003 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology in lymphadenopathy of HIV‐positive patients
Authors: Nayak Sujata , Mani Reeta , Kavatkar Anita N. , Puranik Shaila C. , Holla Vasudev V.
Published: September 2003

Fine‐needle aspiration cytology (FNAC) of 32 HIV‐positive cases presenting with lymphadenopathy was performed to evaluate its role in this group of patients. For each case air‐dried smears were stained with Leishman, hematoxylin and eosin, and Zeihl‐Neelsen stains for acid fast bacilli (AFB). The results were tuberculous (TB) lymphadenopathy (15), reactive lymphadenopathy (10), acute lymphadenitis/abscess (5), and suspected malignancy (2). In seven cases of TB lymphadenitis findings were suggestive of TB since no AFB was demonstrable on the cytology smears. In TB lymphadenitis, two additional patterns besides necrotising granulomatous (4) and granulomatous (2) were observed. These were necrotising (6) and necrotising suppurative (3) patterns. FNAC is a simple, inexpensive, rapid investigative procedure which can reduce surgical excisions and provide definite guidelines about further management. Diagn. Cytopathol. 2003;29:146–148. © 2003 Wiley‐Liss, Inc.