Miracle-dz/UniFAR-FTUs huggingface dataset:
The Microphthalmia Transcription Factor (Mitf) Controls Expression of the Ocular Albinism Type 1 Gene: Link between Melanin Synthesis and Melanosome Biogenesis

ABSTRACT Melanogenesis is the process that regulates skin and eye pigmentation. Albinism, a genetic disease causing pigmentation defects and visual disorders, is caused by mutations in genes controlling either melanin synthesis or melanosome biogenesis. Here we show that a common transcriptional control regulates both of these processes. We performed an analysis of the regulatory region of Oa1, the murine homolog of the gene that is mutated in the X-linked form of ocular albinism, as Oa1's function affects melanosome biogenesis. We demonstrated that Oa1 is a target of Mitf and that this regulatory mechanism is conserved in the human gene. Tissue-specific control of Oa1 transcription lies within a region of 617 bp that contains the E-box bound by Mitf. Finally, we took advantage of a virus-based system to assess tissue specificity in vivo. To this end, a small fragment of the Oa1 promoter was cloned in front of a reporter gene in an adeno-associated virus. After we injected this virus into the subretinal space, we observed reporter gene expression specifically in the retinal pigment epithelium, confirming the cell-specific expression of the Oa1 promoter in the eye. The results obtained with this viral system are a preamble to the development of new gene delivery approaches for the treatment of retinal pigment epithelium defects.
Inorganic phosphorus reduces hypercalciuria during total parenteral nutrition by enhancing renal tubular calcium absorption.

BACKGROUND Increasing the inorganic phosphorus content of total parenteral nutrition (TPN) formulas has been shown to decrease TPN-induced hypercalciuria in experimental animals and humans. The mechanism of this effect, however, has been uncertain. METHODS By using a randomized cross-over design, seven patients on cyclic TPN were given otherwise identical formulas providing either 15 or 45 mmol/d of inorganic phosphorus. Urinary calcium excretion, serum ultrafilterable calcium, filtered calcium load, fractional calcium excretion, urinary cyclic adenosine 5'-monophosphate (cAMP), and serum levels of ionized calcium, parathyroid hormone (PTH), and vitamin D metabolites were determined at the end of each study period. RESULTS Urinary calcium excretion was significantly lower when the patients received the higher inorganic phosphorus formula. Increasing the inorganic phosphorus in the TPN formula did not change ultrafilterable calcium or filtered calcium load, but significantly reduced fractional calcium excretion. No differences in serum levels of ionized calcium, PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or urinary cAMP were observed between treatments. CONCLUSIONS These results demonstrate that increasing the inorganic phosphorus content of the TPN formula decreases urinary calcium excretion by increasing renal tubular calcium resorption. This effect is not due to alterations in the PTH-1,25-dihydroxyvitamin D axis, but likely reflects a direct action of inorganic phosphorus on the renal tubules.
Genomic Diversity of Lactobacillus salivarius

ABSTRACT Strains of Lactobacillus salivarius are increasingly employed as probiotic agents for humans or animals. Despite the diversity of environmental sources from which they have been isolated, the genomic diversity of L. salivarius has been poorly characterized, and the implications of this diversity for strain selection have not been examined. To tackle this, we applied comparative genomic hybridization (CGH) and multilocus sequence typing (MLST) to 33 strains derived from humans, animals, or food. The CGH, based on total genome content, including small plasmids, identified 18 major regions of genomic variation, or hot spots for variation. Three major divisions were thus identified, with only a subset of the human isolates constituting an ecologically discernible group. Omission of the small plasmids from the CGH or analysis by MLST provided broadly concordant fine divisions and separated human-derived and animal-derived strains more clearly. The two gene clusters for exopolysaccharide (EPS) biosynthesis corresponded to regions of significant genomic diversity. The CGH-based groupings of these regions did not correlate with levels of production of bound or released EPS. Furthermore, EPS production was significantly modulated by available carbohydrate. In addition to proving difficult to predict from the gene content, EPS production levels correlated inversely with production of biofilms, a trait considered desirable in probiotic commensals. L. salivarius displays a high level of genomic diversity, and while selection of L. salivarius strains for probiotic use can be informed by CGH or MLST, it also requires pragmatic experimental validation of desired phenotypic traits.
Pulpal Regeneration Following Allogenic Tooth Transplantation into Mouse Maxilla

Autogenic tooth transplantation is now a common procedure in dentistry for replacing a missing tooth. However, there are many difficulties in clinical application of allogenic tooth transplantation because of immunological rejection. This study aims to clarify pulpal regeneration following allogenic tooth transplantation into the mouse maxilla by immunohistochemistry for 5‐bromo‐2′‐deoxyuridine (BrdU) and nestin, and by the histochemistry for tartrate‐resistant acid phosphatase (TRAP). The upper right first molar (M1) of 2‐week‐old mice was extracted and allografted in the original socket in both the littermate and non‐littermate after the extraction of M1. Tooth transplantation weakened the nestin‐positive reactions in the pulp tissue that had shown immunoreactivity for nestin before operation. On postoperative Days 5–7, tertiary dentin formation commenced next to the preexisting dentin where nestin‐positive odontoblast‐like cells were arranged in all cases of the littermate group until Day 14, except for one case showing immunological rejection in the pulp chamber. In the non‐littermate group, bone‐like tissue formation occurred in the pulp chamber in addition to tertiary dentin formation until Day 14. The rate of tertiary dentin was 38%, and the rate of the mixed form of dentin and bone‐like tissue formation was 23% (the remainder was immunological rejection). Interestingly, the periodontal tissue recovered even in the case of immunological rejection in which the pulp chamber was replaced by sparse connective tissue. These results suggest that the selection of littermate or non‐littermate is decisive for the survival of odontoblast‐lineage cells and that the immunological rejection does not influence the periodontal regeneration. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.
Promotion of Social Inclusion through New Steps in Tourism

Social inclusion is one of the interesting topics of our times, taking attention in both political realm and scientific inquiry. For instance, social inclusion is considered among the main goals of rural development programmes (Shortall, 2008), within the mega-events such as Vancouver Olympics in 2010 (Vanwynsberghe et. al., 2013), related to maintaining mental health (Repper & Perkins, 2003) and even subject to transportation policies (Pagliara & Biggiero, 2017). By definition, social inclusion is about making sure all individuals are able to participate as valued, respected and contributing members of the society on the basis of five principles: valued recognition, human development, involvement and engagement, proximity and material well-being (Donnelly & Coakley, 2002). Social inclusion plays a key role in creating a stable social order premised on social action; however it is dependent on the openness of political structures in a country (Shortall, 2008).
Gene therapy of established medullary thyroid carcinoma with herpes simplex viral thymidine kinase in a rat tumor model: relationship of bystander effect and antitumor efficacy.

Bystander effect (BSE) refers to killing of cells adjacent to a cell engineered to express a killing gene segment. BSE is considered an important aspect of suicide gene therapy with thymidine kinase. We evaluated the BSE of adenovirus expressing herpes simplex thymidine kinase (AdCMVtk) in rat medullary thyroid carcinomas (rMTC) and three rat thyroid epithelial cancer cell lines using an in vitro BSE assay. In the assay, different proportions of infected and uninfected cells are mixed. Only the proportion of directly infected cells was inhibited in the proliferation assay using rMTC cells. This indicates that there is little BSE in this cell line. One rat thyroid epithelial cancer cell line (RTC-R2) has a high BSE, with BSE index (BSEi) of 7. In the proliferation assay a greater proportion of cells was inhibited than those directly infected. BSE was also evaluated during in vivo tumor growth by subcutaneous injection of mixtures of AdCMVtk infected and uninfected cells. Ganciclovir (GCV) treatment of tumors developing from a 1:1 mixture of infected to uninfected rMTC cells failed to inhibit their growth. In contrast, GCV treatment of a 2:8 mixture of infected to uninfected RTC-R2 cells completely inhibit tumor development, indicating a high BSE. BSE is related to in vivo antitumor efficacy when replication-defective adenovirus AdCMVtk is directly injected into rMTC tumors. After treatment with 100 mg/kg per day of GCV, a growth-retardation effect was observed in small tumors (<100 mm3), but there was little antitumor activity in large tumors (>100 mm3). Our results indicate that there is a good correlation between this in vitro BSE assay and in vivo treatment efficacy. Not all kinds of tumors are suitable for thymidine kinase (TK)/GCV gene therapy because some lack BSE. Methods to improve BSE and/or transduction efficiency are needed in order to obtain an effective therapeutic result. It will be appropriate to test the BSE in human tumor cells before performing clinical trials with current adenoviral vectors expressing TK.
Selective retention of secretory proteins in the yeast endoplasmic reticulum by treatment of cells with a reducing agent

We have used four glycoproteins as markers to study how disulfide bond formation and protein folding effect the intracellular transport of proteins in yeast. Under normal conditions, the vacuolar enzyme carboxypeptidase Y (CPY) and the secretory stress‐protein hsp150 acquired disulfide bonds in the endoplasmic reticulum (ER). Treatment of living cells with the reducing agent dithiothreitol (DTT) prevented disulfide formation of newly synthesized CPY and hsp150, resulting in retention of the proteins in the ER. When DTT was removed, the sulfhydryls were reoxidized, and the transport of the proteins to their correct destinations was resumed. Even mature CPY, located in the vacuole, could be reduced with DTT, and reoxidized after removal of the drug. DTT treatment blocked intracellular transport of hsp150 only when present during the synthesis and translocation of the protein. Reduction of folded hsp150, accumulated in the ER due to a sec block prior to DTT treatment, did not inhibit its secretion. The Kar2p/BiP protein, a component of the ER lumen, was found to be associated with fully translocated reduced hsp150, but not with native hsp150, suggesting that Kar2p/BiP may be involved in the putative retention mechanism. The cysteine‐free pro‐α‐factor, and invertase which was shown to have free sulfhydryls, were secreted and modified similarly in the presence and absence of DTT, showing that the secretory pathway of yeast functioned under reducing conditions.
The Association between Air Pollution and Heart Failure, Arrhythmia, Embolism, Thrombosis, and Other Cardiovascular Causes of Death in a Time Series Study

In a time series study, air pollution was associated with specific cardiovascular causes of death. Deaths due to heart failure (ICD-9 428), arrhythmia (ICD-9 427), cerebrovascular causes (ICD-9 430–436), and thrombocytic causes (ICD-9 415.1, 433–4, 444, 452–3) were more strongly associated with air pollution than cardiovascular deaths (ICD-9 390–448) in general. Excess relative risks were 2.5 to 4 times larger for these categories than for total cardiovascular disease mortality. Heart failure deaths, which made up 10% of all cardiovascular deaths, were found to be responsible for about 30% of the cardiovascular deaths related to particulate matter, SO2, CO, and NO2.
‘We know our Terrain’: indigenous knowledge preferred to scientific systems of weather forecasting in the Delta State of Nigeria

It is acknowledged that subsistence farmers in developing countries rely on indigenous knowledge systems (IKS) to determine the appropriate time, the types and quantity of food to produce in a particular farming season. Due to the unprecedented rate in which climate variability is occurring globally, there are concerns that IKS will become unreliable to predict future weather events accurately, which will compromise the ability for farmers to secure their livelihoods. Nonetheless, some scholars are optimistic that if farmers rely on seasonal climate forecast (SCF), it will facilitate the adoption of planned and more efficient adaptation strategies, thereby ensuring that they continue effectively in food production. While most countries in sub-Saharan Africa have been investing in meteorology, farmers still rely heavily on IKS. Drawing on fieldwork conducted in the Delta State of Nigeria, this paper discusses the factors that contribute towards farmer’s willingness to adhere to IKS. The results suggest that being misled by an inaccurate scientific forecast, and the inability to comprehend how anthropogenic activities contribute to climate change, among others, have contributed to the farmer’s continued reliance on IKS. These issues have been explored within the broader contemporary theoretical arguments and debates revolving around IKS and SCF.
The Usefulness of Waveform Score from the Ocular Response Analyzer

Purpose. To study the usefulness of the Waveform Score from the ocular response analyzer (ORA). Methods. Both eyes of sixty-four normal Chinese adults were measured by the ORA. An experienced practitioner who was masked to the score evaluated the waveforms. Four measurements were obtained from each eye, and the average was considered as the gold standard. Agreement was compared for the mean of different multiple measurements to the gold standard. Results. There was no significant difference between the gold standard and the mean of different multiple measurements for all ORA parameters. The Waveform Score of 512 signals (four measurements from each eye of 64 subjects) ranged from 1.58 to 9.06. When the best signal value of four measured signals from each eye was considered, the lowest score was 3.60 from 128 eyes. The lower 10th percentile from all signals had Waveform Scores <3.48. Conclusions. If the Waveform Score provides information on the reliability of the signals, a score <3.50 may indicate an unreliable signal, and the signal should be discarded. We also recommend taking three measurements with all the signals having a Waveform Score of 3.50 or above to increase the precision.
Urbanization and Carbon Emissions in India and China

This article understands, from an empirical perspective, the determinants of carbon emissions, using internationally comparable data, and cross-national regressions for India and China. Next, it explores the relationship between urban land use regulations and carbon emissions in India’s cities. Urbanization has no impact on carbon emissions per capita or per unit of geographical area. Electricity consumption in China and electricity produced from coal in India have a positive effect on carbon emissions. GDP per capita has a positive effect in India and not so in China, but per capita GDP squared has a negative impact on emissions in both the countries. Does this imply that urbanization should be ignored in the two countries? The answer is no, because a city’s urban form, to which policy contributes, is correlated with carbon emissions. More suburbanized cities which sprawl more also emit more carbon. India’s land use regulations relating to building height restrictions are conservative, hence Indian cities sprawl, which lead to carbon emissions. Hence, the focus of urban policy has to be on the development of compact cities. The article concludes with caveats of the data.
Association between hypertensive disorders of pregnancy and risk of autism in offspring: a systematic review and meta-analysis of observational studies

Background Autism spectrum disorder (ASD) is a common severe pervasive neurodevelopmental disorder of undetermined etiology. Environmental exposures, especially pregnancy complications, have been increasingly recognized as a potential risk factor for ASD. Our aim was to (1) systematically evaluate the association between hypertensive disorders of pregnancy (HDP) and the risk of ASD in offspring, (2) specifically draw a subgroup analysis of disease severity in patients with HDP to achieve more sufficient evidence on this issue. Results A total of 21 studies were identified with more than 6.5 million participants, including 31,027 ASD probands. A comparative meta-analysis established that offspring born premature to HDP were significantly associated with ASD than matched controls (OR = 1.42, 95% CI: 1.34–1.50). Subgroup analysis of clinical classification include: (1) gestational hypertension, (2) pre-eclampsia, (3) chronic hypertension complicating pregnancy (CHP). The offspring of mothers with pre-eclampsia and CHP have slightly higher risk (OR = 1.43; OR = 1.48, respectively) of ASD than those of mothers with gestational hypertension (OR = 1.37). In consistence with most previous researches, higher ASD prevalence was observed in male than female (OR = 1.38), indicating a potential role for gender in the pathophysiology of ASD. Materials and Methods We conducted a systematic literature search on PubMed, EMBASE, Web of Science, PsycINFO database and China National Knowledge Infrastructure up to Jun. 2017. Statistical analysis was performed using Stata 10.0. Conclusions This meta-analysis implies a possible link between HDP and the risk of ASD in offspring. However, further investigation should be conducted to confirm this conclusion, and intensive prenatal surveillance and early prediction for ASD is needed.
以語言模型判斷學習者文句流暢度(Analyzing Learners ‘Writing Fluency Based on Language Model)[In Chinese]

由於現代科技以及 3C 產品的普及,使得孩子頻繁的接觸電視、網路、手機. 等,因此 容易缺乏與人之間互動、溝通以及情感的表達,相對的,學生寫的作文常常是以流水帳 交代經過,有的學校甚至不考作文,但隨著教育政策的變動,國中教育會考加入了作文 評量的項目,使的作文再度受到學生及家長的重視。 可是受限於學校教學時數,作文較 弱的學生容易缺少補救的機會。 我們認為未來自學作文以及在家練習,可以藉由自動化 的作文教學系統輔助。 而本系統開發作文教學系統之句子流暢度偵測,經由系統回饋的 診斷結果可以讓學生對詞句組合的理解力有所提升,幫助學生寫出較流暢的句子,藉此 提高他們的作文分數。 系統所依賴的 N-gram 語言模型,它的特性是計算字詞間組合的 機率,機率越高的話字詞組合的正確性越高也就是越流暢,而語言模型效果相當依賴大 型的訓練語料,這是語言模型然能待克服的缺點,例如資料稀疏(Data sparseness)的問題, 可以使用平滑(smoothing)的方法解決;以及跨領域的問題,只要訓練語料的性質越不同 於測試的文章,我們所建立語言模型的效果就越差,因此語料庫也要跟著改變。
Rumination and Cortisol Responses to Laboratory Stressors

Objective: For some, a stressor’s psychological and physiological influence ceases on removal; for others, the effects may persist through rumination. These repetitive, intrusive thoughts might prolong physiological stress responses. Previous studies produced mixed results, indicating a need to clarify the relationship between rumination and cortisol responses. The current study investigated whether a laboratory speech task is sufficient to elicit rumination and whether those who ruminated in response to the speech task have elevated cortis of responses. Additionally, whether trait depressive rumination follows a similar pattern was examined. It was hypothesized that those delivering speeches in a social-evaluative context would experience more posttask rumination and that greater posttask rumination would predict elevated cortisol responses. Methods: Eighty-nine participants performed a speech in front of an evaluative panel (SET) or in one of two nonexplicitly evaluative conditions. Participants indicated the frequency of the thoughts they experienced during a 10-minute rest period after the speech as a measure of posttask rumination. Salivary cortisol was collected at five time points throughout the session. Results: The SET condition elicited more posttask rumination than the nonexplicitly evaluative conditions. Posttask rumination was associated with amplified and prolonged elevations in cortisol across all conditions. Trait depressive rumination was associated with blunted cortisol responses in the SET condition. There was no association between trait depressive rumination and cortisol responses in the nonexplicitly evaluative conditions. Conclusion: Results suggest that the nature of the relationship between cortisol activation and rumination may be contingent on how rumination is conceptualized and measured. HPA = hypothalamic-pituitary-adrenocortical; SET = social-evaluative threat; neSET = nonexplicitly evaluative; RSQ-22 = 22-item Rumination Subscale of the Responses Style Questionnaire; TQ = Thoughts Questionnaire; ELISA = enzyme-linked immunosorbent assay.
Control of the Unfolded Protein Response in Health and Disease

The unfolded protein response (UPR) is an integrated, adaptive biochemical process that is inextricably linked with cell homeostasis and paramount to maintenance of normal physiological function. Prolonged accumulation of improperly folded proteins in the endoplasmic reticulum (ER) leads to stress. This is the driving stimulus behind the UPR. As such, prolonged ER stress can push the UPR past beneficial functions such as reduced protein production and increased folding and clearance to apoptotic signaling. The UPR is thus contributory to the commencement, maintenance, and exacerbation of a multitude of disease states, making it an attractive global target to tackle conditions sorely in need of novel therapeutic intervention. The accumulation of information of screening tools, readily available therapies, and potential pathways to drug development is the cornerstone of informed clinical research and clinical trial design. Here, we review the UPR’s involvement in health and disease and, beyond providing an in-depth description of the molecules found to target the three UPR arms, we compile all the tools available to screen for and develop novel therapeutic agents that modulate the UPR with the scope of future disease intervention.
Experimental Ascaris suum infection in the pig: protective memory response after three immunizations and effect of intestinal adult worm population

The protective immune response to larval migration in pigs, with or without adult intestinal worm populations, 10 weeks after 3 weekly Ascaris suum inoculations, was studied in 45 pigs. Controlled adult worm populations were achieved by oral transfer of 10 adult worms to previously immunized pigs after anthelmintic drenching. A significant reduction in larval recovery from lungs on day 7, and small intestine on day 14, was observed in immunized pigs compared with previously uninfected control pigs after challenge inoculation. The strong anamnestic response to larval migration was characterized by blood eosinophilia and specific immune responses measured by peripheral blood enzyme‐linked immunospot and immunosorbent assays using larval excretory‐secretory products and adult body fluid as well as Western blotting with a panel of stage‐specific A. suum antigens. Immune detection of a previously unreported 10 kDa band, specific to the L2 larval stage and egg hatch fluid, emerged in all pigs after challenge, while the major adult body fluid constituent, ABA‐1, remained unrecognized. No significant effect of an intestinal adult worm burden on the larval recovery after a challenge inoculation or on the immune response before or after challenge inoculation could be detected. These results indicate that a significant protective memory immune response to A. suum challenge inoculation can be induced in pigs, and that this protective immunity is not significantly modulated by the presence of adult parasites in the gut.