Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional interaction between PARP‐1 and PARP‐2 in chromosome stability and embryonic development in mouse

The DNA damage‐dependent poly(ADP‐ribose) polymerases, PARP‐1 and PARP‐2, homo‐ and heterodimerize and are both involved in the base excision repair (BER) pathway. Here, we report that mice carrying a targeted disruption of the PARP‐2 gene are sensitive to ionizing radiation. Following alkylating agent treatment, parp‐2−/−‐derived mouse embryonic fibroblasts exhibit increased post‐replicative genomic instability, G2/M accumulation and chromosome mis‐segregation accompanying kinetochore defects. Moreover, parp‐1−/−parp‐2−/− double mutant mice are not viable and die at the onset of gastrulation, demonstrating that the expression of both PARP‐1 and PARP‐2 and/or DNA‐dependent poly(ADP‐ribosyl) ation is essential during early embryogenesis. Interestingly, specific female embryonic lethality is observed in parp‐1+/−parp‐2−/− mutants at E9.5. Meta phase analyses of E8.5 embryonic fibroblasts highlight a specific instability of the X chromosome in those females, but not in males. Together, these results support the notion that PARP‐1 and PARP‐2 possess both overlapping and non‐redundant functions in the maintenance of genomic stability.
Serum cytokine levels in periodontitis patients in relation to the bacterial load.

BACKGROUND Periodontitis is a local inflammatory disease that also has some systemic effects. We investigated the levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2, -4, -5, and -10 in the serum of patients with periodontitis in relation to the bacterial load in the dental plaques. METHODS Serum cytokine levels in patients with generalized periodontitis and healthy control groups were determined using the cytometric bead array kit. Bacterial load in the dental plaque was determined semiquantitatively by real-time polymerase chain reaction. The proportions of different lymphocyte subsets were determined in the peripheral blood of patients with periodontitis by flow cytometry. Finally, relationships between the bacterial load in the subgingival plaques of patients with periodontitis and levels of cytokines and counts of lymphocyte subsets were established. RESULTS Serum levels of IFN-γ, TNF-α, and IL-10 were significantly increased, whereas those of IL-2 were significantly decreased in patients with periodontitis compared to healthy controls. Increased serum levels of IFN-γ and TNF-α in patients with periodontitis were associated with the enhanced dental plaque load with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) and Porphyromonas gingivalis, respectively. Finally, as revealed by analysis of lymphocyte populations, the presence of A. actinomycetemcomitans and Trepomena denticola was associated with an increased population of CD3(-)/CD16(+) and CD3(+)/CD8(+) cells, respectively. CONCLUSION Certain periodontal pathogens could be associated with an increased level of proinflammatory cytokines in the peripheral blood and thus increased risk of systemic diseases.
Decomposing Welfare Inequality in Egypt and Tunisia: an Oaxaca-Blinder Based Approach

In order to understand the main drivers of welfare inequality in Egypt and Tunisia, the present paper presents an Oaxaca-Blinder decomposition approach used to decompose differences across distributions of household expenditures, based on counterfactual distributions in the two countries of analysis. Taking Tunisia as a reference country, we find that changes in the expenditures structure and demographics are inequality decreasing. Changes in the characteristics of the labor market has, however, no, or very limited, impact on inequality as captured by the Gini Index.
Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease.

BACKGROUND In our previous study, higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and the vitamin D receptor (VDR) FokI CC genotype were associated with milder Parkinson disease (PD). OBJECTIVE We evaluated whether vitamin D3 supplementation inhibits the progression of PD on the basis of patient VDR subgroups. DESIGN Patients with PD (n = 114) were randomly assigned to receive vitamin D3 supplements (n = 56; 1200 IU/d) or a placebo (n = 58) for 12 mo in a double-blind setting. Outcomes were clinical changes from baseline and the percentage of patients who showed no worsening of the modified Hoehn and Yahr (HY) stage and Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS Compared with the placebo, vitamin D3 significantly prevented the deterioration of the HY stage in patients [difference between groups: P = 0.005; mean ± SD change within vitamin D3 group: +0.02 ± 0.62 (P = 0.79); change within placebo group: +0.33 ± 0.70 (P = 0.0006)]. Interaction analyses showed that VDR FokI genotypes modified the effect of vitamin D3 on changes in the HY stage (P-interaction = 0.045), UPDRS total (P-interaction = 0.039), and UPDRS part II (P-interaction = 0.021). Compared with the placebo, vitamin D3 significantly prevented deterioration of the HY stage in patients with FokI TT [difference between groups: P = 0.009; change within vitamin D3 group: -0.38 ± 0.48 (P = 0.91); change within placebo group, +0.63 ± 0.77 (P = 0.009)] and FokI CT [difference between groups: P = 0.020; change within vitamin D3 group: ±0.00 ± 0.60 (P = 0.78); change within placebo group: +0.37 ± 0.74 (P = 0.014)] but not FokI CC. Similar trends were observed in UPDRS total and part II. CONCLUSION Vitamin D3 supplementation may stabilize PD for a short period in patients with FokI TT or CT genotypes without triggering hypercalcemia, although this effect may be nonspecific for PD. This trial was registered at UMIN Clinical Trials Registry as UMIN000001841.
ATP‐binding cassette transporters and cholesterol translocation

Cholesterol, a major component of mammalian cell membranes, plays important structural and functional roles. However, accumulation of excessive cholesterol is toxic to cells. Aberrant cholesterol trafficking and accumulation is the molecular basis for many diseases, such as atherosclerotic cardiovascular disease and Tangier's disease. Accumulation of excessive cholesterol is also believed to contribute to the early onset of Alzheimer's disease. Thus, cellular cholesterol homeostasis is tightly regulated by uptake, de novo synthesis, and efflux. Any surplus of cholesterol must either be stored in the cytosol in the form of esters or released from the cell. Recently, several ATP‐binding cassette (ABC) transporters, such as ABCA1, ABCG1, ABCG5, and ABCG8 have been shown to play important roles in the regulation of cellular cholesterol homeostasis by mediating cholesterol efflux. Mutations in ABC transporters are associated with several human diseases. In this review, we discuss the physiological roles of ABC transporters and the underlying mechanisms by which they mediate cholesterol translocation. © 2013 IUBMB Life, 65(6):505–512, 2013
Solving the Puzzle in the Interest Rate Market

Different anomalies have appeared in the interest rate market after the burst of the credit crunch. A wide wedge has opened between the market quotes of Forward Rate Agreements and their standard spot Libor replication, and large Basis Spreads have appeared for exchanging floating payments with different tenors. Here we tackle these issues under two aspects.In Part 1 we focus on issues of direct interest to market practitioners. We show that the gap between FRA rates and their spot Libor replication can be explained by using the quoted Basis spreads. Then we explain the market patterns of the Basis spreads by modeling them as options on the credit worthiness of the counterparty. We also investigate analytically the FRA market payoff.In Part 2 we study the mathematical representation of the interest rate market in the post-crisis reality. We introduce credit risk at market level, allowing for no-fault standard rule and collateralization. We use subfiltrations to model Libor rates, which now embed relevant credit risk although no default event is possible on Libor itself. We compute change of numeraire and convexity adjustments for collateralized derivatives tied to risky Libor.
Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.
Whose knowledge?: Science education, Indigenous knowledges and teacher praxis

This study investigated how a group of secondary school science teachers considered the implementation of a Cross-Curriculum Priority that mandated the inclusion of Aboriginal and Torres Strait Islander histories and cultures in all learning areas. The inclusion of Indigenous content and perspectives, as a way of promoting intercultural understanding, has been advocated in the Australian context for some time. However, classroom implementation has been lacking with teachers feeling unsure about how to satisfy these curriculum initiatives. With the introduction of the new (national) Australian Curriculum such content and perspectives were mandated. This context enabled an exploration of science teachers’ responses to the Cross-Curriculum Priority as they attempted to translate the intent of the curriculum into classroom practice. The investigation took place through a collaborative and collegial approach using Participatory Action Research. A group of five teachers from different schools proceeded through cycles of inquiry, action and reflection framed by the curriculum requirements. Across the participant group these cycles operated asynchronously as the individual teacher participants had to negotiate their schooling contexts while still being guided by group participation. The teacher participants’ needs and perspectives directed the topics of discussion and progress of the cycles. Advice and guidance around cultural sensitivities inherent in the research were given by three Critical Friends of the project, who all self-identified as Aboriginal people. A bricolage approach was taken to data collection allowing the capture of the experiences of the participants through interviews, group meetings, one-on-one discussions with the researcher, documentary analysis and observation of classroom activities. Data were analysed using a critical theory and pedagogy lens. The study showed that teachers approached the Cross-Curriculum Priority with a hope that it would lead to socially just learning opportunities for both Indigenous and non-Indigenous students. Teacher participants took different approaches to implementing lessons in the science classroom and not all of them implemented classroom activities with Indigenous content or perspectives. The study found that the approach and classroom implementation taken by teachers are related to their epistemological, pedagogical and political positioning. The neo-liberal context of the Australian schooling system was also found to confine and constrain teachers’ efforts in classroom implementation. The study recommends that all of these interconnected factors need to be considered in understanding how teachers engage with such a curriculum innovation. The findings of this study will assist in moving beyond the rhetoric around such curriculum initiatives towards practical implementation of science education inclusive of Indigenous knowledges and perspectives in classrooms.
Healing in peri‐implant gap with BMP‐2 and systemic bisphosphonate is dependent on BMP‐2 dose—A canine study

The bone–implant interface of cementless orthopedic implants can be described as a series of uneven sized gaps with discontinuous areas of direct bone–implant contact. Bridging these voids and crevices by addition of an anabolic stimulus to increase new bone formation can potentially improve osseointegration of implants. Bone morphogenetic protein 2 (BMP‐2) stimulates osteoblast formation to increase new bone formation but also indirectly stimulates osteoclast activity. In this experiment, we investigate the hypothesis that osseointegration, defined as mechanical push‐out and histomorphometry, depends on the dose of BMP‐2 when delivered as an anabolic agent with systemic administration of the anti‐resorptive agent zoledronate to curb an increase in osteoclast activity. Four porous coated titanium implants (one with each of three doses of surface‐applied BMP‐2 (15 µg; 60 µg; 240 µg) and untreated) surrounded by a 0.75 mm empty gap, were inserted into the distal femurs of each of twelve canines. Zoledronate IV (0.1 mg/kg) was administered 10 days into the observation period of 4 weeks. Bone–implant specimens were evaluated by mechanical push‐out test and histomorphometry. The 15 µg implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to the untreated, 60 and 240 µg implants, as well as the highest volume of new bone in the implant gap compared to 60 and 240 µg implants. The results in a canine implant model demonstrated that a narrow range of BMP‐2 doses have opposite effects in bridging an empty peri‐implant gap with bone, when combined with systemic zoledronate. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1406–1414, 2018.
Circular Slot Antenna Systems for OAM Waves Generation

In this letter, two simple and novel circular slot antenna systems to generate OAM waves are proposed. Special feeding networks, which can be used to generate two OAM modes, are designed at 2.4 GHz to feed the circular slot antenna. Furthermore, two antenna systems are fabricated and tested. Both the simulation and measurement results demonstrate the effectiveness of the antenna systems for generating OAM waves.
Auxin Stimulates Its Own Transport by Shaping Actin Filaments1

The directional transport of the plant hormone auxin has been identified as central element of axis formation and patterning in plants. This directionality of transport depends on gradients, across the cell, of auxin-efflux carriers that continuously cycle between plasma membrane and intracellular compartments. This cycling has been proposed to depend on actin filaments. However, the role of actin for the polarity of auxin transport has been disputed. The organization of actin, in turn, has been shown to be under control of auxin. By overexpression of the actin-binding protein talin, we have generated transgenic rice (Oryza sativa) lines, where actin filaments are bundled to variable extent and, in consequence, display a reduced dynamics. We show that this bundling of actin filaments correlates with impaired gravitropism and reduced longitudinal transport of auxin. We can restore a normal actin configuration by addition of exogenous auxins and restore gravitropism as well as polar auxin transport. This rescue is mediated by indole-3-acetic acid and 1-naphthyl acetic acid but not by 2,4-dichlorophenoxyacetic acid. We interpret these findings in the context of a self-referring regulatory circuit between polar auxin transport and actin organization. This circuit might contribute to the self-amplification of auxin transport that is a central element in current models of auxin-dependent patterning.
Capsaicin treatment induces histamine release and perfusion changes in psoriatic skin

To determine whether neurogenic factors may be of importance in the regulation of histamine release and blood flow in psoriatic plaque, the effect of capsaicin was studied in 22 psoriatic patients with active, untreated psoriatic lesions. In each of 12 patients, one microdialysis fibre was placed in non‐lesional skin and one was placed in lesional skin at depths of 0.7 and 0.9 mm, respectively. Dialysates were collected for the analysis of histamine in the resting state and after 60 min of repetitive epicutaneous application of 1% capsaicin above the microdialysis catheter. In 10 patients, topical capsaicin and placebo were applied for 24 h to lesional/lesion‐free skin. Skin blood flow and perfusion (evaluated using the 133xenon clearance technique and scanning laser Doppler, respectively) were measured before the application of capsaicin and after removal. After 60 min of capsaicin treatment, both the perfusion and interstitial concentration of histamine, as well as the net release of histamine, were significantly increased in affected (from 38 ± 6 to 45 ± 6 nmol/L, mean ± SEM) and unaffected (from 15 ± 2 to 19 ± 2 nmol/L) skin. Compared with placebo, 24 h of treatment with capsaicin caused a 15% decrease in perfusion in lesional skin. The results are compatible with the hypothesis that capsaicin‐sensitive nerves may induce histamine release in non‐lesional and lesional skin and that afferent unmyelinated nerve fibres may contribute to the high blood flow in psoriatic plaques.
Somatoform disorders in the workplace in Japan

The literature related to somatoform disorders in the workplace is very limited, and these disorders need more attention from mental health professionals in the workplace as well as from employers. Over the last decade, major changes have taken place in the work environment in Japan. More stress and less support from supervisors or colleagues in the workplace have made employees stressed out. The number of employees with mental disorders, including somatoform disorders, taking sick leave has significantly increased. In our multi-centre collaborative study, somatoform disorders were the third most prevalent psychiatric disorder in employees, after mood and schizophrenic disorders. Employees with neurotic disorders manifested physical symptoms more frequently than those without. Young employees frequently reported somatic symptoms such as general malaise, nausea, constipation, diarrhoea, headache, stiff shoulder, and dizziness. A rational new approach is needed to tackle this important psychopathology increasingly seen among employees.
Memory impairment in schizophrenia: its extent, affiliations and neuropsychological character

SYNOPSIS In a sample of 60 schizophrenic patients encompassing all grades of severity and chronicity memory impairment was found to be prevalent, often substantial, and disproportionate to the overall level of intellectual impairment. The deficits were not easily attributable to poor cooperation, attention or motivation; nor were they related to neuroleptic or anticholinergic medication. Memory impairment was significantly associated with severity and chronicity of illness and also with negative symptoms and formal thought disorder. There was evidence from the sample as a whole, and from a more detailed examination of five patients with relatively isolated deficits, that schizophrenic memory impairment conformed to the pattern seen in the classical amnesic syndrome. Additionally, there was preliminary evidence for a marked deficit in semantic memory.
Induction of lung emphysema is prevented by L‐arginine‐threonine‐arginine

In patients with chronic obstructive pulmonary disease (COPD), an inflammatory process is ongoing in the lungs, with concomitant damage of the alveolar structures and loss of airway function. In this inflammatory process, extracellular matrix degradation is observed. During this lung matrix degradation, small peptide fragments consisting of proline and glycine repeats generated from collagen fibers are liberated from the matrix by matrix metalloproteinases. Chemotactic activities of these collagen‐derived peptides such as N‐acetyl‐proline‐glycine‐proline (PGP) via CXCR1 and CXCR2 have been reported. We show here that PGP induces neutrophil migration in vivo, which is dose dependent. Moreover, PGP is involved in the development of emphysema‐like changes in the airways. The complementary peptide, l‐arginine‐threonine‐arginine (RTR), has been shown to bind to PGP sequences and inhibit neutrophil infiltration. We show that RTR impedes both PGP‐ and interleukin‐8‐induced chemotaxis in vitro. In vivo, RTR prevents both migration and activation of neutrophils induced by PGP. Furthermore, RTR completely inhibits PGP‐induced lung emphysema, assessed by changes in alveolar enlargement and right ventricular hypertrophy. In conclusion, these data indicate that collagen breakdown products, especially PGP, are important in the pathogenesis of COPD and that PGP antagonism via RTR ameliorates lung emphysema. —van Houwelingen, A. H. , Weathington, N. M. , Verweij, V. , Blalock, J. E. , Nijkamp, F. P., Folkerts, G. Induction of lung emphysema is prevented by L‐arginine‐threonine‐arginine. FASEB J. 22, 3403–3408 (2008)
Characterization of symptoms in irritable bowel syndrome with mixed bowel habit pattern

Irritable bowel syndrome (IBS) with mixed bowel habits (IBS‐M) is a heterogeneous subtype with varying symptoms of constipation and diarrhea, and has not been well characterized. We aimed to characterize gastrointestinal (GI) and non‐GI symptoms in IBS‐M patients from a US patient population, and to compare them with IBS with constipation (IBS‐C) and diarrhea (IBS‐D).