bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of recombinant and endogenous mouse melatonin receptors by monoclonal antibodies targeting the C‐terminal domain
Authors: Cecon Erika , Ivanova Anna , Luka Marine , Gbahou Florence , Friederich Anne , Guillaume Jean‐Luc , Keller Patrick , Knoch Klaus , Ahmad Raise , Delagrange Philippe , Solimena Michele , Jockers Ralf
Published: November 2018

Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT1 and MT2, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT1 and MT2. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT1 and MT2 by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT1 or MT2. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT2 expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies.
Combined effects of guanidinoacetic acid, coenzyme Q10 and taurine on growth performance, gene expression and ascites mortality in broiler chickens
Authors: Faraji Mehrab , Karimi Dehkordi Saeid , Zamiani Moghadam Abdol Karim , Ahmadipour Behnam , Khajali Fariborz
Published: November 2018

High levels of guanidinoacetate acid (GAA) deteriorate growth response in broiler chickens. We propose using coenzyme Q10, an antioxidant, and taurine (TAU), a methyl donor, to cope with the situation when high level of GAA included in diet. GAA was supplemented at 0 (control), 0.75, 1.5 and 2.25 g/kg in isoenergetic and isonitrogenous diets and fed to broilers (Cobb 500) from 1 to 40 days post‐hatch. Three additional diets were prepared by adding CoQ10 (40 mg/kg), TAU (40 mg/kg) or their combination (both CoQ10 and TAU at 40 mg/kg) to the 2.25 g/kg GAA group. The experimental design used was a completely randomized design. While weight gain (p = 0.038) and feed conversion ratio (p = 0.024) improved when GAA added at 1.5 g/kg, higher supplementation (2.25 g/kg) deteriorated these responses. These responses, however, were significantly restored by using CoQ10, TAU or their combination. Abdominal fat deposition was significantly decreased when TAU added to broiler diets by virtue of upregulating peroxisome proliferator‐activated receptor alpha. Supplementing broiler diets with CoQ10 and TAU or their combination significantly decrease ascites mortality. In conclusion, CoQ10 and TAU have shown beneficial effects when high level of GAA included in broiler diets.
The therapeutic potential of regulatory T lymphocytes in periodontitis: A systematic review
Authors: Cafferata Emilio Alfredo , Jerez Alfredo , Vernal Rolando , Monasterio Gustavo , Pandis Nikolaos , Faggion Clovis M.
Published: November 2018

This systematic review aimed to: (a) generate a descriptive synthesis of preclinical studies assessing the therapeutic potential of regulatory T lymphocytes (Tregs) to arrest periodontitis, (b) evaluate the methodological heterogeneity of the reviewed animal studies and (c) assess the risk of bias (RoB) of the included studies. The electronic search for animal studies included the MEDLINE, EMBASE, Web of Science and LILACS databases. In addition, a manual search assessed the high‐ranked scientific journals in “periodontics/immunology” and the references listed in the included studies. There were no language, year or publication status restrictions. Two independent reviewers selected and extracted the data, and Cohen's Kappa coefficient was calculated to determine the inter‐examiner agreement. The Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE) tool was used to assess the RoB. A total of 21 of the 425 studies obtained from the database search were included. Treg function was mainly described in Porphyromonas gingivalis‐induced periodontitis (57.1%) in mice (76.2%), where Treg suppression was strongly related to disease progression and Treg induction was strongly related to immuno‐inflammatory response reduction. Of those 21 studies, eight included eight animal experiments using three distinct therapeutic approaches, including: P. gingivalis‐driven immunization (n = 3), retinoic acid inoculation (n = 2) and anti‐inflammatory molecules in polymeric carriers (n = 3), which could modulate the Treg activity through cytokine production (interleukin‐10 and transforming growth factor‐β1), CC‐chemokine‐ and CC‐chemokine receptor‐mediated chemoattraction (CCL22 and CCR4) or Th17‐associated receptor activator of nuclear factor κB ligand (RANKL) downregulation. However, the studies with animal experiments did not specify the randomization sequences and housing conditions that were used, and therefore, 42.11% of the entries were rated as unclear RoB. Distinct therapeutic strategies involving Tregs could potentially suppress the immuno‐inflammatory response and restore alveolar bone homeostasis during periodontitis. Nevertheless, important methodological variability, poor reporting of treatment effect estimates and unclear RoB suggest using caution when assessing the results of these studies.
A comprehensive study on donor‐matched comparisons of three types of mesenchymal stem cells‐containing cells from human dental tissue
Authors: Xing Yixiao , Zhang Yunpeng , Wu Xuan , Zhao Bin , Ji Yawen , Xu Xin
Published: November 2018

Background and Objective

Mesenchymal stem cells (MSCs) have been widely used in tissue engineering, such as for regenerating the supporting structures of teeth destroyed by periodontal diseases. In recent decades, dental tissue‐derived MSCs have drawn much attention owing to their accessibility, plasticity and applicability. Dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs) and gingival MSCs (GMSCs) are the most readily available MSCs among all types of dental MSCs. The purpose of this study was to comprehensively compare the characteristics of MSCs from dental pulp (DP), periodontal ligament (PDL) and gingiva (G) in vitro and thus provide insight into optimizing the performance of cells and seed cell selection strategies for tissue regeneration.

Materials and Methods

In this study, patient‐matched (n = 5) cells derived from DP, PDL and G which, respectively, contained DPSCs, PDLSCs and GMSCs were evaluated using multiple methods in terms of their proliferation, senescence, apoptosis, multilineage differentiation and stemness maintenance after long‐term passage.

Results

Mesenchymal stem cells‐containing cells from G (MSCs/GCs) showed superior proliferation capability, whereas patient‐matched MSCs‐containing cells from PDL (MSCs/PDLCs) exhibited excellent osteogenic and adipogenic differentiation ability; MSCs‐containing cells from DP (MSCs/DPCs) achieved mediocre results in both aspects. In addition, MSCs/GCs were the least susceptible to senescence, while MSCs/PDLCs were the most prone to ageing. Furthermore, the biological properties of these three types of cells were all affected after long‐term in vitro culture.

Conclusion

These three types of dental MSCs showed different biological characteristics. MSCs/PDLCs are the best candidate cells for bone regeneration, but the application of MSCs/PDLCs might be limited to certain number of passages. Improving the differentiation of MSCs/GCs remains the key issue regarding their application in tissue engineering.
A forced‐choice preferential looking task for the assessment of vision in dogs: pilot study
Authors: Graham K. L. , Byosiere S.‐E. , Feng L. C. , Sanders M. , Bennett P. C. , Caruso K. , McCowan C. I. , White A.
Published: November 2018

Objectives

To describe preliminary use of a forced‐choice preferential looking task for the clinical assessment of vision in dogs.

Materials and Methods

The vision of 18 pet dogs was investigated in two separate studies using a forced‐choice preferential looking task: multiple observers watched eye, head and body movements on video recordings to identify cues suggesting when a dog had seen the feature of interest. Human observer reliability was determined using eight dogs and computer‐generated stimuli. Visual acuity was assessed using computer‐generated grating stimuli: in real‐time, an observer watched each dog's eye movement patterns and behaviour to decide whether each grating was seen. Stimuli were presented in a step‐wise manner and were controlled by the observer. Acuity was estimated as the highest spatial frequency the dog was determined to have seen.

Results

Median estimated visual acuity was better at 1 m compared to that at 3 m. Average test time was longer at a 3‐m distance than at 1 m. Inter‐ and intra‐observer reliability was better from 1 m than from 3 m.

Clinical Significance

Preliminary use of a forced‐choice preferential looking task for measurement of visual acuity in dogs has potential use as a clinical tool for the assessment of vision in dogs.
Explaining Expulsions of U.S. Diplomatic Personnel from Latin America, 1991–2016
Authors: Jordan Anthony , Tuman John P.
Published: November 2018

This article examines expulsions of U.S. diplomats from Latin America and the Caribbean between 1991 and 2016. Employing an original data set of expulsions of U.S. diplomatic personnel, the analysis focuses on the number of first‐mover expulsions—cases where the Latin American government was the first to expel a U.S. diplomat in a year. The models are estimated with pooled negative binomial regression with robust standard errors. The results suggest there were more first‐mover expulsions in countries governed by radical, populist‐left presidents. For the radical, populist Left, expulsions offered a low‐cost mechanism to pursue opposition to U.S. influence in Latin America while also giving executives an opportunity to strengthen ties to their electoral base. Results also show that presidential election years had a positive and significant effect. Prior retaliatory expulsions, alleged U.S. interference, other types of executive‐party control, and economic ties with the United States and China had no effect on expulsions. Oil exports to the United States were associated positively with higher expulsion counts, which we attribute to the unwillingness of radical populists—and of the United States—to escalate diplomatic tensions into wider economic conflicts.
Video Modeling and Explicit Instruction: A Comparison of Strategies for Teaching Mathematics to Students with Learning Disabilities
Authors: Satsangi Rajiv , Hammer Rachel , Hogan Christina D.
Published: November 2018

As classrooms begin to adopt a greater number of digital technologies such as computers and tablets, it is important for educators to understand how effective such tools can be in aiding in the delivery of instruction to students who struggle in mathematics, such as those identified with a learning disability in mathematics. One digital‐based instructional strategy with a limited research base for students with a learning disability is video modeling. Through a single subject alternating treatments design, this study compared the use of video modeling to face‐to‐face explicit instruction for teaching geometry word problems to three secondary students with a learning disability in mathematics. Across 10 sessions of intervention, all three students demonstrated improved performance on all dependent variables with both interventions, while the explicit instruction condition produced slightly greater accuracy scores for two of the three students. The results and their implications for the field of mathematics are discussed.
The status of research on the mammals of Sulawesi, Indonesia
Authors: Broto Bayu , Mortelliti Alessio
Published: November 2018

The Indonesian island of Sulawesi is widely considered a mammal conservation hotspot, mainly due to the high number of threatened endemic species with limited geographical ranges that are found there, and also due to the biogeographical importance of Sulawesi as the largest island in the Wallacea region.

To date, there has been no comprehensive review to evaluate the status of what we know about mammals in Sulawesi. The overarching goal of our review is to contribute towards identifying knowledge gaps in the biology and ecology of mammals in Sulawesi.

Our specific aims were to: 1) identify taxonomic and geographic bias in published research; 2) identify biases within existing ecological knowledge; and 3) identify key research priorities for the future.

Our review covers a total of 280 articles (published between 1921 and 2017) on 144 species of mammal from Sulawesi.

Through our review we found: 1) a strong taxonomic bias, with the majority of studies being conducted on primates (59% of published articles); 2) a geographic bias, where significantly fewer studies took place in the provinces of West Sulawesi and Gorontalo; and 3) a bias in research topics, with most studies (50% of published research) focusing on taxonomy and behaviour.

As an outcome of this review, we provide specific recommendations for future researchers, including: 1) a checklist of understudied species, with particular emphasis on understudied species of conservation concern; 2) a checklist of understudied research topics, with an emphasis on the need to conduct detailed auto‐ecological studies; and 3) suggestions on how to adjust research methods on population and habitat studies.
Infant growth faltering linked to subclinical mastitis, maternal faecal–oral contamination, and breastfeeding
Authors: Wren‐Atilola Hilary M. , Solomons Noel W. , Scott Marilyn E. , Koski Kristine G.
Published: November 2018

Infant growth faltering occurs in breastfed infants <6 months of age. The possibility that maternal health status contributes to this growth faltering is underexplored. We investigated whether (a) subclinical mastitis (SCM), an asymptomatic inflammation of the breast, (b) maternal intestinal nematode and protozoan infections, indicators of faecal–oral contamination, or (c) poor breastfeeding practices increased the odds of stunting (length‐for‐age z‐score < −2SD), underweight (weight‐for‐age z‐score < −2SD), or low head circumference (head circumference‐for‐age z‐score < −2SD) in breastfed infants in rural indigenous communities in Guatemala. Mother–infant dyads (n = 105) were subdivided into those with and without SCM (milk Na:K ratio > 0.6). Maternal and infant anthropometry were measured at the time of breast milk collection. Maternal stool samples were examined for the presence of intestinal nematodes and protozoa. Questionnaires were used to characterize breastfeeding practices (exclusivity and frequency) and support, hygiene (latrine use and household faucet), and infant diarrhoea. SCM occurred in 14% of women and was associated with increased odds of infant stunting (odds ratio [OR] = 4.3; confidence interval [CI] [1.1, 15.8]), underweight (OR = 9.2; CI [1.8, 48.0]), and low head circumference (OR = 15.9; CI [2.6, 96.9]). Maternal pathogenic protozoa and nematodes were uncommon (<4%), but nonpathogenic protozoa were common (e.g., Entamoeba coli [39%]). Entamoeba coli increased the likelihood (OR = 3.3; CI [1.02, 10.6]) of low head circumference, whereas higher breastfeeding frequency lowered its odds (OR = 0.74, CI [0.56, 0.97]). Prevention of SCM may improve early infant growth, but public health measures that increase breastfeeding frequency and reduce faecal–oral contamination may be required to minimize low head circumference.
Chest X‐ray evaluation training: impact of normal and abnormal image ratio and instructional sequence
Authors: Geel Koos van , Kok Ellen M , Aldekhayel Abdullah D , Robben Simon G F , van Merriënboer Jeroen J G
Published: November 2018

Context

Medical image perception training generally focuses on abnormalities, whereas normal images are more prevalent in medical practice. Furthermore, instructional sequences that let students practice prior to expert instruction (inductive) may lead to improved performance compared with methods that give students expert instruction before practice (deductive). This study investigates the effects of the proportion of normal images and practice–instruction order on learning to interpret medical images. It is hypothesised that manipulation of the proportion of normal images will lead to a sensitivity–specificity trade‐off and that students in practice‐first (inductive) conditons need more time per practice case but will correctly identify more test cases.

Methods

Third‐year medical students (n = 103) learned radiograph interpretation by practising cases with, respectively, 30% or 70% normal radiographs prior to expert instruction (practice‐first order) or after expert instruction (instruction‐first order). After training, students performed a test (60% normal) and sensitivity (% of correctly identified abnormal radiographs), specificity (% of correctly identified normal radiographs), diagnostic performance (% of correct diagnoses) and case duration were measured.

Results

The conditions with 30% of normal images scored higher on sensitivity but the conditions with 70% of normal images scored higher on specificity, indicating a sensitivity and specificity trade‐off. Those who participated in inductive conditions took less time per practice case but more per test case. They had similar test sensitivity, but scored lower on test specificity.

Conclusions

The proportion of normal images impacted the sensitivity–specificity trade‐off. This trade‐off should be an important consideration for the alignment of training with future practice. Furthermore, the deductive conditions unexpectedly scored higher on specificity when participants took less time per case. An inductive approach did not lead to higher diagnostic performance, possibly because participants might already have relevant prior knowledge. Deductive approaches are therefore advised for the training of advanced learners.
Excisionase in Pf filamentous prophage controls lysis‐lysogeny decision‐making in Pseudomonas aeruginosa
Authors: Li Yangmei , Liu Xiaoxiao , Tang Kaihao , Wang Pengxia , Zeng Zhenshun , Guo Yunxue , Wang Xiaoxue
Published: November 2018

Pf filamentous prophages are prevalent among clinical and environmental Pseudomonas aeruginosa isolates. Pf4 and Pf5 prophages are integrated into the host genomes of PAO1 and PA14, respectively, and play an important role in biofilm development. However, the genetic factors that directly control the lysis‐lysogeny switch in Pf prophages remain unclear. Here, we identified and characterized the excisionase genes in Pf4 and Pf5 (named xisF4 and xisF5, respectively). XisF4 and XisF5 represent two major subfamilies of functional excisionases and are commonly found in Pf prophages. While both of them can significantly promote prophage excision, only XisF5 is essential for Pf5 excision. XisF4 activates Pf4 phage replication by upregulating the phage initiator gene (PA0727). In addition, xisF4 and the neighboring phage repressor c gene pf4r are transcribed divergently and their 5′‐untranslated regions overlap. XisF4 and Pf4r not only auto‐activate their own expression but also repress each other. Furthermore, two H‐NS family proteins, MvaT and MvaU, coordinately repress Pf4 production by directly repressing xisF4. Collectively, we reveal that Pf prophage excisionases cooperate in controlling lysogeny and phage production.
Brain invasion by chronic lymphocytic leukemia
Authors: Otani Ryohei , Uzuka Takeo , Matsuda Hadzki , Higuchi Fumi , Kim Phyo , Ueki Keisuke
Published: November 2018

Brain invasion by chronic lymphocytic leukemia (CLL) is very rare, and only a handful of cases have been reported. We here report a case of 61‐year‐old woman who had been treated for CLL for 14 years presenting with a progressive mental disturbance. Magnetic resonance imaging (MRI) showed discontinuous ring‐enhancing lesions compatible with the “open ring” sign, which was considered a demyelinating disorder, in both the frontal lobes. However, on histological examination of the biopsied specimen, infiltration of small lymphocytes positive for CD5, CD20, and CD23, indicating brain invasion by CLL, was seen. The leukemia cells occupied the Virchow–Robin space and infiltrated into the brain parenchyma. The arterioles in the Virchow–Robin space were compressed and occluded with the tumor cells, while CD163‐positive cells infiltrated the brain parenchyma. Myelin staining demonstrated myelinoclasis in the infiltrated brain tissue. The MRI findings in the present case probably reflected myelinoclasis, suggesting rare brain invasion by CLL. The possibility of lymphoma should not be eliminated based on the MRI findings.
Detecting Co‐Movements in Non‐Causal Time Series
Authors: Cubadda Gianluca , Hecq Alain , Telg Sean
Published: November 2018

This paper introduces the notion of common non‐causal features and proposes tools to detect them in multivariate time series models. We argue that the existence of co‐movements might not be detected using the conventional stationary vector autoregressive (VAR) model as the common dynamics are present in the non‐causal (i.e. forward‐looking) component of the series. We show that the presence of a reduced rank structure allows to identify purely causal and non‐causal VAR processes of order P>1 even in the Gaussian likelihood framework. Hence, usual test statistics and canonical correlation analysis can be applied, where either lags or leads are used as instruments to determine whether the common features are present in either the backward‐ or forward‐looking dynamics of the series. The proposed definitions of co‐movements are also valid for the mixed causal—non‐causal VAR, with the exception that a non‐Gaussian maximum likelihood estimator is necessary. This means however that one loses the benefits of the simple tools proposed. An empirical analysis on Brent and West Texas Intermediate oil prices illustrates the findings. No short run co‐movements are found in a conventional causal VAR, but they are detected when considering a purely non‐causal VAR.
Sarcopenia in patients with non‐alcoholic fatty liver disease: is it a clinically significant entity?
Authors: De Fré C. H. , De Fré M. A. , Kwanten W. J. , Op de Beeck B. J. , Van Gaal L. F. , Francque S. M.
Published: November 2018

Sarcopenia, described as the loss of muscle mass and/or strength, is gaining importance as it can be increasingly related to many chronic diseases. It is also associated with chronic liver disease, and recently it has been more frequently linked to non‐alcoholic fatty liver disease (NAFLD) in particular. Both sarcopenia and NAFLD are subject to complex and intermingled pathophysiological processes, of which some are in common. Furthermore, it is presently unclear if sarcopenia directly contributes to NAFLD or vice versa. The mechanisms that are involved may include obesity, insulin resistance, vitamin D deficiency, aging, physical inactivity and certain cytokines. Current clinical evidence is subject to an important heterogeneity in methods and definitions, with additionally also a relative overrepresentation of evidence in Asian ethnicities. Nonetheless, all studies so far point towards the same association between sarcopenia and NAFLD, including an association with NAFLD‐severity and NAFLD‐related fibrosis. Since the field is in its infancy, clear definitions and further research are needed to aid to improve understanding of the association between NAFLD and sarcopenia. This can eventually lead to additional potential therapeutic interventions. This review attempts to give an overview of the current published literature that links sarcopenia to NAFLD, followed by a discussion of the presumably involved pathophysiological factors, and ends by discussing current unmet needs.
Uprooted by modernity
Authors: Hacke Melanie
Published: November 2018

Through a close reading of George Eliot's The Mill on the Floss, this paper argues that the genre of the Bildungsroman is particularly suited to an ecocritical interpretation. As a realist Antibildungsroman depicting the tragically problematic Bildung of Maggie Tulliver and her family, The Mill on the Floss counters conventional nineteenth‐century coming‐of‐age novels, which tended to become scripts of industrial capitalism and bourgeois culture. Eliot's portrayal of life at Dorlcote Mill confirms that the human and the natural worlds are inherently intertwined, but also demonstrates that capitalist modernity constructs nature as an entity separate from and inferior to man, thus estranging people from their roots.
Risk of obstructive sleep apnea in patients with bipolar disorder: A nationwide population‐based cohort study in Taiwan
Authors: Chang En‐Ting , Chen Shih‐Fen , Chiang Jen‐Huai , Wang Ling‐Yi , Hsu Chung‐Y , Shen Yu‐Chih
Published: November 2018

Aim

Previous studies have found a high prevalence of risk factors for obstructive sleep apnea (OSA) in patients with bipolar disorder (BD). This study aimed to determine whether BD patients are associated with an increased risk of incident OSA.

Methods

Using the National Health Insurance Research Database of Taiwan, 3650 BD patients and 18 250 non‐BD controls matched by sex and age were enrolled between 2000 and 2010 and followed until the end of 2013. Patients who developed OSA confirmed by a polysomnographic examination during the follow‐up period were identified. Cox regression analysis was performed to examine the risk of OSA between BD patients and comparative controls.

Results

BD patients were prone to developing OSA in the crude analysis (hazard ratio [HR]: 1.63, 95% confidence interval [CI]: 1.07–2.49). After adjusting for demographics and comorbidities, the HR declined and was only marginally significant (HR: 1.54, 95%CI: 0.99–2.37). The stratification analysis by sex revealed that the risk trend with BD and subsequent OSA was mainly contributed by male BD patients (HR: 1.72, 95%CI: 1.02–2.91) and female BD patients weakened the overall association. Additionally, this study found that older age, higher income, living in urbanized areas, and some metabolic comorbidities were potential risk factors for developing OSA.

Conclusion

This study shows that male BD patients are associated with an increased risk of OSA, which has direct implications for the development of targeted prevention interventions or the implementation of a screening algorithm for OSA to reduce its negative health impact.
Treatment of oral manifestations of toxic epidermal necrolysis with low‐level laser therapy in a pediatric patient
Authors: Rocha Amanda Leal , Souza Alessandra Figueiredo De , Nunes Laiz Fernandes Mendes , Cunha Nayara Dias de Souza , Lanza Célia Regina Moreira , Travassos Denise Vieira , Silva Tarcília Aparecida da
Published: November 2018

Drug‐induced reactions are complications associated with high mortality and significant morbidity. Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of these conditions, which are characterized by skin and mucous lesions. Here, we report a case of a 9‐year‐old girl who presented with blisters associated with an extensive vesicular rash and multiple ulcerations on the lips and oral cavity. A drug‐induced hypersensitivity reaction to antibiotics was suspected, and a diagnosis of TEN was made. The patient was managed with withdrawal of the suspected causative agent, and the oral lesions were treated with low‐level laser therapy (LLLT) and oral hygiene. This case highlights that TEN requires interdisciplinary intervention with dental assistance and follow‐up to improve symptoms, nutrition, systemic condition, and quality of life.
Recent empirical work on the relationship between causal judgements and norms
Authors: Willemsen Pascale , Kirfel Lara
Published: November 2018

It has recently been argued that normative considerations play an important role in causal cognition. For instance, when an agent violates a moral rule and thereby produces a negative outcome, she will be judged to be much more of a cause of the outcome, compared to someone who performed the same action but did not violate a norm. While there is a substantial amount of evidence reporting these effects, it is still a matter of debate how this evidence is to be interpreted. In this paper, we engage with the three most influential classes of explanations, namely, (a) the Norm‐Sensitive Cognitive Process View, (b) the Normative Concept View, and (c) the Pragmatics View. We will outline how these theories explain the empirical results and in what ways they differ. We conclude with a reflection on how well these strategies do overall and what questions they still leave unanswered.
How does toxoplasmosis affect the maternal‐foetal immune interface and pregnancy?
Authors: Borges Margarida , Magalhães Silva Tânia , Brito Carina , Teixeira Natércia , Roberts Craig W.
Published: November 2018

Toxoplasma gondii is a zoonotic parasite which, depending on the geographical location, can infect between 10% and 90% of humans. Infection during pregnancy may result in congenital toxoplasmosis. The effects on the foetus vary depending on the stage of gestation in which primary maternal infection arises. A large body of research has focused on understanding immune response to toxoplasmosis, although few studies have addressed how it is affected by pregnancy or the pathological consequences of infection at the maternal‐foetal interface. There is a lack of knowledge about how maternal immune cells, specifically macrophages, are modulated during infection and the resulting consequences for parasite control and pathology. Herein, we discuss the potential of T. gondii infection to affect the maternal‐foetal interface and the potential of pregnancy to disrupt maternal immunity to T. gondii infection.
Absorbing knowledge in the digital age: the key role of integration mechanisms in the context of crowdsourcing for innovation
Authors: Ruiz Émilie , Brion Sébastien , Parmentier Guy
Published: November 2018

The digital age offers unprecedented opportunities for firms to access new knowledge for innovation. Both academics and managers have identified crowdsourcing (CS) as one relevant way to do so. CS for innovation involves outsourcing problem‐solving or creative tasks to the crowd. To benefit from CS, absorptive capacity (ACAP) is critical; this can be enhanced by prior knowledge and past experience with a partner. However, in the CS context, firms open themselves up to undefined, anonymous partners through the Internet, hence the development of ACAP becomes more difficult. The literature on ACAP describes how internal integration mechanisms encourage the absorption of knowledge but fails to clearly address the way in which uncommon knowledge is integrated. Although literature has acknowledged the beneficial role of a wider spectrum of influential internal and external mechanisms on uncommon knowledge, few empirical studies have addressed the distinctive effect of these mechanisms on the absorption of anonymous partners’ knowledge. To fill this gap, this study identifies relevant integration mechanisms and how they impact upon different ACAP dimensions in the CS context. Five case studies reveal the distinctive influence of integration mechanisms depending on the nature of the CS activity. Our results extend research on ACAP in the little studied digital open context, investigating the absorption of uncommon knowledge from unidentified partners. From a managerial perspective, this study shows that managers need to pay attention to integration mechanisms in order to support the absorption of knowledge from the crowd. More precisely, our study suggests that the main focus should not be on external mechanisms, but also on internal mechanisms. Finally, we open up a new theoretical debate on how these mechanisms should be combined.
Body temperature of bitches in the first week after parturition measured by ingestible loggers
Authors: Schulze Laura S.‐Ch. , Heuwieser Wolfgang , Arlt Sebastian P.
Published: November 2018

Contents

The objective of this study was to identify the physiological ranges of body temperature of bitches in the first 7 days after parturition by measurement with ingestible temperature loggers. Twenty bitches swallowed one ingestible temperature logger daily. Bitches were defined to be healthy by spontaneous parturition and leucocyte concentration. Mean core body temperatures of eight healthy bitches were (Mean ± SD) 38.8°C ± 0.40 on day 0 p.p., 38.9°C ± 0.47 on day 1 p.p., 38.9°C ± 0.35 on day 2 p.p. 38.7°C ± 0.31 on day 3 p.p., respectively. In the following days, the three remaining healthy bitches showed mean core body temperatures (Mean ± SD) of 38.8°C ± 0.30 on day 4 p.p., 38.6°C ± 0.35 on day 5 p.p., 38.5°C ± 0.27 on day 6 p.p. and 38.4°C ± 0.34 on day 7 p.p., respectively. Three out of the eight healthy bitches showed temperatures ≥39.5°C. Bitches with leucocytosis showed significant higher mean core body temperatures (39.0°C ± 0.49) than healthy bitches (38.8°C ± 0.39) during the first 3 days after parturition (p < 0.01). We conclude that the physiological ranges of body temperature of healthy bitches in the first days after parturition do not differ from those of healthy dogs in general, while the appearance of short episodes of febrile temperatures seems to be physiological. Puerperal bitches with leucocytosis show higher body temperatures increased by only 0.2°C.
General and type 2 parvovirus‐specific passive immune transfer in puppies – Evaluation by early growth
Authors: Mila Hanna , Grellet Aurélien , Feugier Alexandre , Desario Costantina , Decaro Nicola , Buonavoglia Canio , Mariani Claire , Chastant‐Maillard Sylvie
Published: November 2018

Contents

Failure of passive immune transfer put puppies at a higher risk of neonatal and weaning mortality due to low immune protection against infectious agents. The aim of this study was to investigate the evolution of the general via serum IgG concentration (IgG) and the specific via serum maternally derived canine parvovirus type 2‐specific antibody titer (CPV2MDA) passive immune transfer within the first 4 weeks of age. Furthermore, the relationship between general and specific immune transfer and the possibility of non‐invasive evaluation was assessed. Puppies (169) were weighed systematically between birth and Day 28. IgG andCPV2MDAwere assayed in serum samples at 2 and at 28 days of age. At Day 2, there was a positive correlation between IgG andCPV2MDA(ρ = 0.71;p < 0.001). At Day 2, 17.9% (27/151) of puppies presented a deficit of passive immune transfer according to IgG result (defined as IgG < 2.3 g/L) and 25.8% (39/151) of puppies were under the minimal protectiveCPV2MDAtiter (defined as <1:160). No correlation between IgG andCPV2MDAwas observed at Day 28 (ρ = 0.14;p = 0.11). Growth rate within the first 48 hours <−2.7% allowed to distinguish puppies at high risk of the general and specific passive immune failure (Youden's index = 0.79 and 0.75, respectively). The threshold value of early growth rate, although applicable only in puppies non‐supplemented with milk replacer, allows identifying via non‐invasive way individuals requiring a special care. Further investigation of the mechanism of passive immune transfer in dogs is necessary to understand the relationship between the general and specific immunoglobulin levels.
Pre‐pubertal treatment with a GnRH agonist in bitches—Effect on the uterus and hormone receptor expression
Authors: Schäfer‐Somi Sabine , Kaya Duygu , Sözmen Mahmut , Kaya Semra , Aslan Selim
Published: November 2018

Contents

Aim of the study was to examine the effect of deslorelin on uterine tissues of eleven pre‐pubertal bitches aged 4.2 ± 0.6 m. Implants containing placebo (sodium chloride 0.9%; n = 4, G I), 4.7 mg (n = 3, GII) or 9.4 mg (n = 4, GIII) deslorelin acetate (Suprelorin®; Virbac, France), were administered subcutaneously. Signs of oestrus, vaginal cytology, serum progesterone (P4) and estradiol‐17β (E2) concentrations were monitored until the occurrence of oestrus. Bitches were ovariohysterectomized and sections from the uterine tissue were subjected to immunohistochemistry (IHC) for detection of GnRH receptor (R), Kisspeptin (KP)10, Kisspeptin receptor (GPR54), androgen receptor (AR), oestrogen receptor (ER) α,β, and progesterone receptor (PR). Tissue sections were scored semi‐quantitatively using an immunoreactivity score (IRS) ranging from 0 to 300 (3). Since some animals were ovariohysterectomized before puberty (n = 1 from GII and n = 2 from GIII), and some in metestrus (all controls and 2 from GII and GIII each), results from these animals were separately evaluated and compared to the controls. Results: No abnormalities were seen in uterine tissues. Kisspeptin 10 expression was low in all cell types, highest IRS were seen in the vascular endothelial cells. The GPR54 was mainly detected in the luminal epithelial cells, superficial and deep uterine glands. The expression of GPR54 and ERα,β was especially high in bitches operated prepubertally. No difference was observed between the controls and experimental bitches operated in their first metestrus. The PR and ERα,β were exclusively expressed in superficial and deep uterine glands and luminal surface epithelial cells. The AR and GnRH‐R expression was negative in all cells of all groups. We conclude that application of 4.7 or 9.4 mg deslorelin at the age of 4 months did not cause uterine disturbances. GPR54 expression might be influenced by pre‐pubertal deslorelin treatment or the changings related to approaching puberty; the latter is supposed in case of ERα,β.
Vitrification of cat ovarian tissue: Does fragment size matters?
Authors: Gorricho Camila M. , Tavares Mariana R. , Apparício Maricy , Fonseca‐Alves Carlos E. , Macente Beatrice I. , Mansano Cleber F.M. , Toniollo Gilson H.
Published: November 2018

Contents

The aim of the present study was to investigate whether or not the size of the ovarian fragment influences its resistance to cryostorage. For that purpose, ovaries were collected from 34 queens (various breeds, age 1–5 year) by routine ovariectomy, transported to the laboratory and then sectioned in different sizes (3 mm × 3 mm × 3 mm, 5 mm × 3 mm × 3 mm and 7 mm × 3 mm × 3 mm) and randomly assigned to a control (GC3, GC5 and GC7, respectively) or vitrified (GV3, GV5 and GV7, respectively) groups. Vitrified‐warmed fragments were evaluated by histomorphology and immunohistochemistry (for apoptotic rates by using cleaved caspase‐3). Histological examination reveals that 72.97% of the follicles in GV3 and 72.58% in GV5 were normal while only 42.86% of the follicles in GV7. The main morphological alteration presented in all groups was a detachment of the epithelial cells. Similarly, immunohistochemistry evaluation using caspase 3 revealed a small proportion of apoptotic cells in GV3 (8.43%) while in GV7 30.43% of the cells expressed cleaved caspase‐3. These findings indicate that fragments sectioned in 3 mm × 3 mm × 3 mm (27 mm3) seem more adequate for perfusion of the cryoprotectant, causing less damage to the cell after vitrification‐warming.
Dog cloning—no longer science fiction
Authors: Lee Seok Hee , Oh Hyun Ju , Kim Min Jung , Kim Geon A , Setyawan Erif Maha Nugraha , Ra Kihae , Abdillah Dimas Arya , Lee Byeong Chun
Published: November 2018

Contents

Since the generation of world's first cloned dog, Snuppy, in 2005, somatic cell nuclear transfer (SCNT) in dogs has been widely applied for producing several kinds of dogs with specific objectives. Previous studies have demonstrated that cloned dogs show normal characteristics in growth, blood parameters and behavioural aspect. Also, canine SCNT technique has been applied to propagate working dogs with excellent abilities in fields such as assistance of disabled people, drugs detection and rescue activity. Because dogs have similar habituation properties and share many characteristics including anatomic and physiological aspects with humans, they are also primary candidates for human disease models. Recently, transgenic dogs that express red fluorescent protein gene constitutively and green fluorescent protein gene conditionally have been generated. In addition, transgenic dogs with an overexpression of peroxisome proliferator‐activated receptor‐alpha in specific muscles were generated to enhance physical performance. In 2017, Snuppy was recloned with markedly increased pregnancy and delivery rates compared to the statistics from when Snuppy was first cloned. Such striking improvements in the cloning of dogs using SCNT procedures suggest that dog cloning could be applied in many fields of biomedical science for human diseases research, and the application of cloning is no longer science fiction.
Diversity and characterisation of polymorphic 3' untranslated region haplotypes of MICA and MICB genes
Authors: Cox Steven T. , Hernandez Diana , Danby Robert , Turner Thomas R. , Madrigal J. Alejandro
Published: November 2018

MICA and MICB genes encode ligands that interact with the natural killer (NK) cell activating receptor, NKG2D. These ligands display a highly polymorphic allelic repertoire, although the true functional significance of this polymorphism remains elusive. We previously reported additional polymorphism in the 5' untranslated region (UTR) proximal promoter region of these genes by sequencing international histocompatibility workshop (IHW) cell line DNA promoter and coding regions. The present study extends this analysis by further characterising the 3'UTR region of the same IHW reference panel to achieve a more complete understanding of MICA and MICB haplotype diversity and possible functional relevance.

We found 17 extended MICA haplotypes encompassing the coding region and 3'UTR, including four novel haplotypes identified in IHW cell line DNA. This increased to 21 when also considering the 5'UTR proximal promoter region. Analysis of the MICB 3'UTR revealed two novel sequences in cell lines KLO and WIN designated MICB‐UTR8 and UTR9, respectively. A total of 11 MICB haplotypes were identified in this study and five were unique. The present study, characterising MICA/B 3'UTR polymorphism utilising IHW reference cell lines, could be useful for future studies investigating the role of microRNA in post‐transcriptional repression of gene expression and for immunotherapy strategies to combat cancer progression.
Frequent blood donations alter susceptibility of red blood cells to storage‐ and stress‐induced hemolysis
Authors: Kanias Tamir , Stone Mars , Page Grier P. , Guo Yuelong , Endres‐Dighe Stacy M. , Lanteri Marion C. , Spencer Bryan R. , Cable Ritchard G. , Triulzi Darrell J. , Kiss Joseph E. , Murphy Edward L. , Kleinman Steve , Gladwin Mark T. , Busch Michael P. , Mast Alan E. ,   for the NHLBI Recipient Epidemiology Donor Evaluation Study (REDS)‐III Program
Published: November 2018

BACKGROUND

Frequent whole blood donations increase the prevalence of iron depletion in blood donors, which may subsequently interfere with normal erythropoiesis. The purpose of this study was to evaluate the associations between donation frequency and red blood cell (RBC) storage stability in a racially/ethnically diverse population of blood donors.

STUDY DESIGN

Leukoreduced RBC concentrate–derived samples from 13,403 donors were stored for 39 to 42 days (1–6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Iron status was evaluated by plasma ferritin measurement and self‐reported intake of iron supplements. Donation history in the prior 2 years was obtained for each subject.

RESULTS

Frequent blood donors enrolled in this study were likely to be white, male, and of older age (56.1 ± 5.0 years). Prior donation intensity was negatively associated with oxidative hemolysis (p < 0.0001) in multivariate analyses correcting for age, sex, and race/ethnicity. Increased plasma ferritin concentration was associated with increased RBC susceptibility to each of the three measures of hemolysis (p < 0.0001 for all), whereas self‐reported iron intake was associated with reduced susceptibility to osmotic and oxidative hemolysis (p < 0.0001 for both).

CONCLUSIONS

Frequent blood donations may alter the quality of blood components by modulating RBC predisposition to hemolysis. RBCs collected from frequent donors with low ferritin have altered susceptibility to hemolysis. Thus, frequent donation and associated iron loss may alter the quality of stored RBC components collected from iron‐deficient donors. Further investigation is necessary to assess posttransfusion safety and efficacy in patients receiving these RBC products.
Validation of Sysmex XT‐2000iV analyzer‐generated quantitative bone marrow differential counts in cynomolgus monkeys, Beagle dogs, and CD‐1 mice
Authors: Criswell Kay A. , Bock Jeffrey H. , Johnson Kjell , Criswell Ryan A. , Giovanelli Richard P.
Published: November 2018

Background

In a previous study, the validation of rat bone marrow (BM) collection, processing, and analysis using the Sysmex XT‐2000iV (Sysmex Corporation, Kobe, Japan) hematology analyzer showed that the Sysmex hematology analyzer produced BM differential counts that were comparable to those obtained with microscopic differential counts.

Objective

This study was conducted to expand the validation of the Sysmex TNCC (total nucleated cell count) and 5‐part BM differential in cynomolgus monkeys, Beagle dogs, and CD‐1 mice, which are alternate species that are also frequently used in preclinical safety studies.

Methods

The Sysmex 5‐part BM differential counts were generated with a two‐step process, whereby proliferating and maturing erythroid and myeloid cells were determined by preset gating and lymphocytes were determined using species‐specific B‐ and T‐lymphocyte antibodies and a magnetic cell‐sorting method (MACS). Agreement with microscopic myelograms with 500‐cell differential counts was determined from BM suspensions of 62 cynomolgus monkeys, 47 Beagle dogs, and 44 CD‐1 mice.

Results

The correlation coefficients between methods for myeloid to erythroid (M:E) ratios in all three species was > 0.928. The Bland‐Altman differences between methods were approximately ± 0.3 units for the M:E ratio in dogs and mice, and +0.6 and −0.4 in monkeys. The upper limits of agreement for all three species were ≤7% for maturing myeloid cells, ≤6% for maturing erythroid cells, and ≤4% for proliferating myeloid cells, proliferating erythroid cells, and lymphocytes.

Conclusions

The Sysmex XT‐2000iV produces an automated M:E ratio and a 5‐part differential count equivalent to microscopic differential counts in cynomolgus monkeys, Beagle dogs, and CD‐1 mice.