Miracle-dz/UniFAR-FTUs huggingface dataset:
Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model

Significance Elevated expression of the presynaptic protein α-synuclein underlies familial and sporadic Parkinson disease (PD). However, our understanding of how increases in α-synuclein levels drive the sequence of events leading to PD is incomplete. Here, we apply a multidisciplinary longitudinal analysis to a new α-synuclein transgenic mouse model. We show that early-stage decreases in dopamine release and vesicle reclustering precede late-stage changes in neuronal firing properties, measured by in vivo recordings from vulnerable neurons. Accumulated deficits in dopamine neurotransmission and altered neuronal firing are associated with cell death and motor abnormalities, in the absence of protein aggregation in the substantia nigra. These findings have important implications for developing therapies. The pathological end-state of Parkinson disease is well described from postmortem tissue, but there remains a pressing need to define early functional changes to susceptible neurons and circuits. In particular, mechanisms underlying the vulnerability of the dopamine neurons of the substantia nigra pars compacta (SNc) and the importance of protein aggregation in driving the disease process remain to be determined. To better understand the sequence of events occurring in familial and sporadic Parkinson disease, we generated bacterial artificial chromosome transgenic mice (SNCA-OVX) that express wild-type α-synuclein from the complete human SNCA locus at disease-relevant levels and display a transgene expression profile that recapitulates that of endogenous α-synuclein. SNCA-OVX mice display age-dependent loss of nigrostriatal dopamine neurons and motor impairments characteristic of Parkinson disease. This phenotype is preceded by early deficits in dopamine release from terminals in the dorsal, but not ventral, striatum. Such neurotransmission deficits are not seen at either noradrenergic or serotoninergic terminals. Dopamine release deficits are associated with an altered distribution of vesicles in dopaminergic axons in the dorsal striatum. Aged SNCA-OVX mice exhibit reduced firing of SNc dopamine neurons in vivo measured by juxtacellular recording of neurochemically identified neurons. These progressive changes in vulnerable SNc neurons were observed independently of overt protein aggregation, suggesting neurophysiological changes precede, and are not driven by, aggregate formation. This longitudinal phenotyping strategy in SNCA-OVX mice thus provides insights into the region-specific neuronal disturbances preceding and accompanying Parkinson disease.
Relationship between sensitivity to dietary fat and dietary cholesterol.

A group of 56 hypercholesterolemic and normocholesterolemic men and women were given approximately 700 mg a day of egg yolk cholesterol in a double-blind, crossover study while they were on a background diet containing approximately 30% of energy as fat. Overall there was a 0.23 mmol/l rise in plasma cholesterol (3.7%, p less than 0.001) after 4 weeks, a 0.19 mmol/l rise in low density lipoprotein (LDL) cholesterol (4.9%, p = 0.002), and a 0.07 mmol/l rise in high density lipoprotein (HDL) cholesterol (5.4%, p less than 0.001). Plasma triglycerides fell by 0.07 mmol/l (5.1%). Normocholesterolemic individuals (plasma cholesterol less than 5.2 mmol/l) experienced small, nonsignificant rises of 0.06, 0.02, and 0.05 mmol/l in total, LDL, and HDL cholesterol, respectively. Hypercholesterolemic subjects were classified on the basis of their response to a low fat diet. Diet-sensitive subjects were defined by a greater than 10% fall in plasma cholesterol on a 25% fat, low cholesterol (less than 200 mg/day) diet. These individuals were found to be more responsive to the effect of dietary cholesterol than were diet-insensitive subjects; the respective changes in the two groups were rises of 0.36 mmol/l versus 0.19 mmol/l in plasma cholesterol (p = 0.06) and rises of 0.30 versus 0.15 mmol/l in LDL cholesterol (p = 0.06). In addition to elevating HDL cholesterol by 0.09 mmol/l and 0.07 mmol/l, respectively, dietary cholesterol also produced an increase in the proportion of HDL2, from 40% to 44% of HDL protein (p less than 0.001). (ABSTRACT TRUNCATED AT 250 WORDS)
The Consequences of Including Seductive Details during Lecture

When text passages include seductive details (i.e., interesting, tangentially related adjuncts that are irrelevant to the lesson), students perform worse on recall (Garner, Gillingham, & White, 1989) and problem-solving tests (Harp & Mayer, 1997, 1998) than students reading the same material without seductive details. To determine whether including seductive details during lecture had a similar effect, students listened to a recorded lecture that either contained or did not contain seductive details and took a test on the material. As predicted, students who heard a lecture containing seductive details recalled significantly fewer main points and provided significantly fewer acceptable problem-solving solutions than students who heard the lecture without seductive details. These results suggest that lectures should not include seductive details.
TransformationalLeadership Impact on Teachers'Organizational Commitment

Abstrak. Kepemimpinan transformasional merupakan suatu proses di mana seorangpemimpin menginspirasi perubahan, meningkatkan kinerja diri sendiri dan kinerjaperusahaan. Pemimpin transformasional memampukan para pengikutnya untukbertanggung jawab terhadap diri mereka dan terhadap pekerjaan yang telahdipercayakan kepada mereka. Kepemimpinan transformasional meliputi 4 komponen,yakni: charismatic leadership, inspirational motivation,intellectual stimulation dan individual consideration. Organizationalcommitment atau komitmen organisasididefinisikan sebagai keterikatan dan keterlibatan seseorang terhadaporganisasinya. Komitmen organisasi menunjukkan bagaimana seorang karyawanmengidentifikasi dirinya dengan organisasi tempat kerjanya dan sejauh mana parakaryawan, dalam hal ini, para guru memiliki komitmen terhadap organisasi yaitusekolah. Paper ini membahas bagaimana kepemimpinan transformasional berpengaruhsecara positif terhadap komitmen organisasi para guru. Hal ini dikarenakan olehkarakteristik dari kepemimpinan transformasional yang memampukan seorangpemimpin, dalam hal ini, kepala sekolah, untuk menjadi role model danmenginspirasi para guru untuk berpikir dan bertindak kreatif. Kepala sekolahjuga tidak mengkritik di hadepan umum/forum suatu kesalahan yang dilakukan olehguru. Lebih jauh lagi, kepala sekolah yang memiliki model kepemimpinantransformasional bersedia untuk meluangkan waktu untuk memberikan perhatiankepada para guru dan menghargai perbedaan pribadi masing-masing guru. Seluruhkarakteristik seorang pemimpin transformasional mampu menciptakan suasana yangnyaman dan membangun lingkungan kerja yang komunikatif bagi para guru.Kesemuanya itu dapat meningkatkan organizational commitment para guru terhadapsekolah.
Synergistic effects of growth hormone and insulin‐like growth factor‐I on differentiation and replication of cultured human luteinized granulosa cells

BACKGROUND The present study was designed to assess the effects of insulin-like growth factor-I (IGF-I) alone and in combination with growth hormone (GH) on differentiation and replication in cultured human granulosa cells. METHODS Granulosa cells from patients undergoing in vitro fertilization were isolated and cultured for 2 days in culture medium with 10% serum, the medium was removed and the cells were incubated with IGF-I (1, 10 and 100 ng/ml) with or without GH (10 ng/ml) in serum-free medium and in the presence of 3H-methylthymidine (2 microCi/ml). RESULTS IGF-I alone resulted in a significant dose-dependent increase in medium estradiol (E2) (p<0.05) and progesterone (P) (p<0.001) and suppression of IGF-binding protein-1 (IGFBP-1) (p<0.001), without any increase in [3H]-thymidine incorporation (P=0.10). The combination of IGF-I and GH further increased the release of E2 (p<0.001), and the amount of [3H]-thymidine incorporation (p<0.001). CONCLUSION These results indicate a synergistic effect of IGF-I and GH on differentiation and replication of human granulosa cells, and thus support a role of both GH and IGF-I in regulation of ovarian function.
Zileuton, an Oral 5-Lipoxygenase Inhibitor, Directly Reduces Sebum Production

Background: Zileuton, a 5-lipoxygenase inhibitor, reduces the number of inflammatory lesions in moderate acne and inhibits the synthesis of sebaceous lipids. Objective: To detect whether zileuton directly reduces sebum synthesis. Methods: A 40-year-old female with mild disseminated sebaceous gland hyperplasia and seborrhea was treated with zileuton 4 × 600 mg/day over 2 weeks, was followed-up for 6 weeks after discontinuation of zileuton and was re-treated with low-dose isotretinoin 10 mg/2nd day over 5 weeks. Casual skin surface lipids and sebum synthesis were determined. Results: Under treatment with zileuton increased casual skin surface lipids were normalized and synthesis of facial sebum was decreased. Six weeks after discontinuation of treatment casual skin surface lipids were increased again and synthesis of sebum returned to baseline. Subsequent low-dose isotretinoin treatment led to similar changes of casual skin surface lipids and sebum synthesis with zileuton already after 2 weeks. Conclusion: Zileuton directly inhibits sebum synthesis in a transient manner with a potency similar to low-dose isotretinoin at least in our patient.
Subacute ruminal acidosis in Dutch dairy herds

The prevalence of subacute ruminal acidosis (SARA) was determined in 197 dairy cows in 18 herds in the Dutch province of Friesland. Samples of rumen fluid were taken by rumenocentesis from between five and 19 animals on each farm and the pH of each sample was determined. The body condition of 139 of the cows was scored approximately three weeks before they calved and three weeks after they calved. The overall prevalence of SARA was 13·8 per cent, and the prevalence on individual farms ranged between 0 per cent (on seven of the farms) and 38 per cent (on one farm). The stage of lactation did not influence the prevalence of SARA but the cows with the condition lost more body condition over the calving period.
University of Groningen Mutational analysis of receptor interaction and membrane fusion activity of Sindbis virus

The spike glycoprotein E2 of Sindbis virus (SIN) is synthesized in the infected cell as a PE2 precursor protein, which matures through cleavage by a cellular furinlike protease. Previous work has shown that SIN mutants, impaired in PE2 cleavage, are non-infectious on BHK-21 cells, the block in infection being localized at a step after virus-receptor interaction but prior to RNA replication. Here, we studied the membrane fusion properties of SIN PE2 cleavage mutants and observed that these viruses are impaired in their ability to form an E1 homotrimer and to fuse with liposomes at a mildly acidic pH. The block in spike rearrangement and fusion could be overridden by exposure of the mutant viruses to very low pH values (pH < 4.5). Cleavage mutants with second-site resuscitating mutations in PE2 were highly infectious for BHK-21 cells. The ability of these viruses to form E1 homotrimers and to fuse at a mildly acidic pH was completely restored, despite a sustained lack of PE2 cleavage. Membrane fusion of Sindbis virus PE2 cleavage mutants 137
Current state and future trends: a citation network analysis of the learning analytics field

This paper provides an evaluation of the current state of the field of learning analytics through analysis of articles and citations occurring in the LAK conferences and identified special issue journals. The emerging field of learning analytics is at the intersection of numerous academic disciplines, and therefore draws on a diversity of methodologies, theories and underpinning scientific assumptions. Through citation analysis and structured mapping we aimed to identify the emergence of trends and disciplinary hierarchies that are influencing the development of the field to date. The results suggest that there is some fragmentation in the major disciplines (computer science and education) regarding conference and journal representation. The analyses also indicate that the commonly cited papers are of a more conceptual nature than empirical research reflecting the need for authors to define the learning analytics space. An evaluation of the current state of learning analytics provides numerous benefits for the development of the field, such as a guide for under-represented areas of research and to identify the disciplines that may require more strategic and targeted support and funding opportunities.
Expanding the Catalytic Triad in Epoxide Hydrolases and Related Enzymes

Potato epoxide hydrolase 1 exhibits rich enantio- and regioselectivity in the hydrolysis of a broad range of substrates. The enzyme can be engineered to increase the yield of optically pure products as a result of changes in both enantio- and regioselectivity. It is thus highly attractive in biocatalysis, particularly for the generation of enantiopure fine chemicals and pharmaceuticals. The present work aims to establish the principles underlying the activity and selectivity of the enzyme through a combined computational, structural, and kinetic study using the substrate trans-stilbene oxide as a model system. Extensive empirical valence bond simulations have been performed on the wild-type enzyme together with several experimentally characterized mutants. We are able to computationally reproduce the differences between the activities of different stereoisomers of the substrate and the effects of mutations of several active-site residues. In addition, our results indicate the involvement of a previously neglected residue, H104, which is electrostatically linked to the general base H300. We find that this residue, which is highly conserved in epoxide hydrolases and related hydrolytic enzymes, needs to be in its protonated form in order to provide charge balance in an otherwise negatively charged active site. Our data show that unless the active-site charge balance is correctly treated in simulations, it is not possible to generate a physically meaningful model for the enzyme that can accurately reproduce activity and selectivity trends. We also expand our understanding of other catalytic residues, demonstrating in particular the role of a noncanonical residue, E35, as a “backup base” in the absence of H300. Our results provide a detailed view of the main factors driving catalysis and regioselectivity in this enzyme and identify targets for subsequent enzyme design efforts.
A Positive Autoregulatory BDNF Feedback Loop via C/EBPβ Mediates Hippocampal Memory Consolidation

Little is known about the temporal progression and regulation of the mechanisms underlying memory consolidation. Brain-derived-neurotrophic-factor (BDNF) has been shown to mediate the maintenance of memory consolidation, but the mechanisms of this regulation remain unclear. Using inhibitory avoidance (IA) in rats, here we show that a hippocampal BDNF-positive autoregulatory feedback loop via CCAAT-enhancer binding protein β (C/EBPβ) is necessary to mediate memory consolidation. At training, a very rapid, learning-induced requirement of BDNF accompanied by rapid de novo translation controls the induction of a persistent activation of cAMP-response element binding-protein (CREB) and C/EBPβ expression. The latter, in turn, controls an increase in expression of bdnf exon IV transcripts and BDNF protein, both of which are necessary and, together with the initial BDNF requirement, mediate memory consolidation. The autoregulatory loop terminates by 48 h after training with decreased C/EBPβ and pCREB and increased methyl-CpG binding protein-2, histone-deacetylase-2, and switch-independent-3a binding at the bdnf exon IV promoter.
Thermodynamics and kinetics of silica scaling

Silica scaling is probably the principal factor limiting the extraction of energy from high temperature geothermal systems. Silica exists in a number of polymorphs from quartz through to opal A (or amorphous silica). The thermodynamics of the solubility of quartz and amorphous silica with variations in temperature, salt content, pH and pressure are discussed. However, in silica saturated geothermal brines, silica normally precipitates from oversaturated brines as a colloid. The colloid formation and properties are discussed together with mechanisms for colloid deposition.
Oral Manifestations of Human Immunodeficiency Virus-Infected Patients

Introduction: Oral lesions are among the earliest clinical manifestations of human immunodeficiency (HIV) infection and are important in early diagnosis and for monitoring the progression to acquired immunodeficiency syndrome (AIDS). The purpose of this study was to determine the prevalence of oral lesions and their relationship with a number of factors in HIV/AIDS patients attending an HIV center. Materials and Methods: A total of 110 HIV-positive patients were examined to investigate the prevalence of oral lesions according to the criteria established by the European Community Clearing House on Oral Problems Related to HIV Infection. An independent T-test was used for correlation of oral lesions with CD4+ count and a χ2 test was used for analysis of the relationship of co-infection with hepatitis B virus (HBV), sexual contact, route of transmission, history of drug abuse, and history of incarceration. Results: Most of the cases were male patients (82.7%). The mean age across all participants was 36.2±8.1 years. Rampant carries, severe periodontitis and oral candidiasis were the most notable oral lesions. Oral lesions were more prevalent in patients between 26–35 years of age. There was a significant difference between patients with and without pseudomembranous candidiasis and angular cheilitis according to mean level of CD4+. Conclusion: The most common oral presentations were severe periodontitis, pseudomembranous candidiasis and xerostomia.
Scientists and the public understanding of science

This paper discusses the attitudes and opinions of research scientists and engineers to taking part in public understanding of science activities. A survey was carried out at an event in set95 (the UK's 1995 National Week of Science, Engineering and Technology), which involved 168 scientists from the University of Bristol, UK, taking their research work into a shopping mall in Bristol for two days. All participating scientists and engineers were asked to complete a written questionnaire shortly after the event and then at least one participant from each display was contacted seven months later for telephone interview. The results show that while most of the scientists took part because they were told to by senior colleagues, after the event almost all (94 per cent) wanted to take part again mainly because they had found the experience enjoyable. Despite the demands of time and organization, individuals benefited from taking part; participants felt it improved their presentation skills and enhanced morale. They regarded the exhibition as good for communication skills training and did not want formal training for the event. The exhibition was also valued as a team-building exercise both within individual departments and across the University.
Equilibrium Systems

Previous experimental work has demonstrated the power of the classical theory of economic dynamics. In particular, the models have proved to be accurate in predicting the principle directions of movement and orbit-like behavior in general equilibrium systems. Questions left open and addressed in this study are (i) do the markets necessarily converge to a unique interior equilibrium or can markets exhibit the “explosive property” of instability and (ii) among the several variations of the classical model, which, if any, is most accurate in predicting what is actually observed in experiments? Markets were created and studied in the extreme environments identified by Scarf and Hirota. Such environments allow us to study features of market adjustments that are obscured by the complexity of naturally occurring markets. Two fundamental results are reported. First, the instability phenomenon of “expanding orbits” predicted by theory does actually exist in the markets and exists in much the form that theory suggests. That is, prices spiral outwardly around the equilibrium prices and do so in directions predicted by theory. This type of disequilibrium behavior is observed for the first time in actual market behavior. Thus, the principles governing market adjustment are not among those that guarantee convergence to a unique interior equilibrium. Second, the best dynamic model from among those studied is of the form ⎟⎟ ⎠ ⎞ ⎜⎜ ⎝ ⎛ ⎥ ⎦ ⎤ ⎢ ⎣ ⎡ = ⎟ ⎟ ⎟
Acceptance issues of personality-based recommender systems

To understand users' acceptance of the emerging trend of personality-based recommenders (PBR), we evaluated an existing PBR using the technology acceptance model (TAM). We also compare it with a baseline rating-based recommender in a within-subject user study. Our results show that while the personality-based recommender is perceived to be only slightly more accurate than the rating-based one, it is much easier to use. The side-by-side comparison also reveals that users significantly favor the personality-based recommender and have a significantly higher intention to use such a system again. Therefore, we believe that if users accepted rating-based recommenders, they are most likely to accept personality-based recommenders and personality-based recommenders have a high likelihood to be widely adopted despite the fact that rating-based recommenders are now the industry norm. We further point out some preliminary guidelines on how to design personality-based recommender systems.
Forearm Range of Motion in Australovenator wintonensis (Theropoda, Megaraptoridae)

The hypertrophied manual claws and modified manus of megaraptoran theropods represent an unusual morphological adaptation among carnivorous dinosaurs. The skeleton of Australovenator wintonensis from the Cenomanian of Australia is among the most complete of any megaraptorid. It presents the opportunity to examine the range of motion of its forearm and the function of its highly modified manus. This provides the basis for behavioural inferences, and comparison with other Gondwanan theropod groups. Digital models created from computed tomography scans of the holotype reveal a humerus range of motion that is much greater than Allosaurus, Acrocanthosaurus, Tyrannosaurus but similar to that of the dromaeosaurid Bambiraptor. During flexion, the radius was forced distally by the radial condyle of the humerus. This movement is here suggested as a mechanism that forced a medial movement of the wrist. The antebrachium possessed a range of motion that was close to dromaeosaurids; however, the unguals were capable of hyper-extension, in particular manual phalanx I-2, which is a primitive range of motion characteristic seen in allosaurids and Dilophosaurus. During flexion, digits I and II slightly converge and diverge when extended which is accentuated by hyperextension of the digits in particular the unguals. We envision that prey was dispatched by its hands and feet with manual phalanx I-2 playing a dominant role. The range of motion analysis neither confirms nor refutes current phylogenetic hypotheses with regards to the placement of Megaraptoridae; however, we note Australovenator possessed, not only a similar forearm range of motion to some maniraptorans and basal coelurosaurs, but also similarities with Tetanurans (Allosauroids and Dilophosaurus).