Miracle-dz/UniFAR-FTUs huggingface dataset:
Colocalization of Tau and Alpha‐Synuclein Epitopes in Lewy Bodies

The major protein constituent of Lewy bodies (LBs), the pathological hallmark of Parkinson disease and dementia with Lewy bodies, is considered to be α-synuclein, but other proteins, in particular the microtubule-associated protein tau, have been implicated in the pathogenesis of LBs. Tau is the major structural component of neurofibrillary tangles (NFTs). Both direct immunochemical studies of partially purified LBs and indirect immunohistochemical studies have suggested that LBs may contain tau, but most of these studies were based upon a single tau antibody, and immunologic cross-reactivity was not completely excluded. To gain insight into the relation between tau and α-synuclein in LBs, double immunostaining was performed in Lewy body cases with a rabbit polyclonal antibody to α-synuclein and a panel of monoclonal antibodies to phospho- and nonphospho-tau epitopes (Alz50, CP9, CP13, PG5, TG3, PHF1) that spanned the length of the tau molecule. Tau-immunoreactive LBs were present in the medulla in 80% of the cases, irrespective of Braak stage. All tau antibodies recognized at least some LBs, arguing against nonspecific antibody cross-reactivity. In most lesions the tau immunostaining was present at the periphery of the LB. The phospho-tau antibody, TG3, detected more LBs than any of the other tau antibodies. The proportion of LBs with tau immunoreactivity was greatest in neurons vulnerable to NFTs, such as those in the locus ceruleus and basal nucleus of Meynert, and least in neurons resistant to NFTs, such as the dorsal motor nucleus of the vagus in the medulla. The present results suggest that tau may coaggregate with α-synuclein in LBs, especially in neuronal populations vulnerable to both NFTs and LBs.
Roles of Antioxidative Enzymes in Wound Healing

Since skin is the first barrier separating the body from the external environment, impaired wound healing can be life threatening to living organisms. Delayed healing processes are observed in animals under certain circumstances, such as advanced age, diabetes, and immunosuppression, but the underlying mechanisms of the abnormality remain elusive. Redox homeostasis is defined as the balance between the levels of reactive oxygen species (ROS) and antioxidants in which antioxidative enzymes play central roles in scavenging ROS. In addition to deleterious effects, ROS also exert beneficial functions on some cellular processes such as transducing phosphorylation signaling, but excessive antioxidants may impede the healing process. Hence, strict control over the amounts of antioxidants is desirable when applied for therapeutic purposes. Here we overview recent findings regarding the relationships between antioxidative enzymes and wound healing. Unveiling the role of antioxidative enzymes is expected to contribute to our understanding of the wound healing processes.
Alzheimer’s disease and immunotherapy: what is wrong with clinical trials?

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and is the most common cause of dementia. Immunotherapy has recently been regarded as a potential treatment for AD. This stems from the fact that the clinical and pathological findings from the active AD vaccine trial suggests that such vaccine therapy may be effective for AD. However, this trial was halted because of the occurrence of meningoencephalitis in some patients. Avoiding excessive immune reaction is necessary for the success of vaccine therapy. For this purpose, adjuvant-free vaccine therapies (eg, passive immunization or DNA vaccines) are currently under investigation. However, the results of clinical trials employing both active and passive anti-amyloid-beta immunotherapy have been unsatisfactory. In this article, we will analyze the reasons for the limited efficacy of currently available immunotherapies and discuss the effectiveness of new vaccine therapies. Finally, we will speculate on the possibility of its clinical application.
Prenatal development of cat retinogeniculate axon arbors in the absence of binocular interactions

During prenatal development of the cat's retinogeniculate projection, inputs from the ganglion cell axons of the two eyes are initially intermixed with each other within the lateral geniculate nucleus (LGN). As development proceeds, the inputs sort out to give rise to the eye- specific layers characteristic of the adult. During this sorting out process, individual axons undergo a stereotyped sequence of morphological changes that ultimately produce the characteristic pattern of arborization in which axon arbors are restricted in extent only to those layers of the LGN appropriate for the eye of origin (Sretavan and Shatz, 1984, 1986). Here, we examine whether binocular interactions between retinal ganglion cell axons from the two eyes are required for the formation of this restricted pattern of terminal arborization. To examine this question, one eye was removed at embryonic day 23 (E23), when ganglion cell axons have not yet reached the optic chiasm, and the ganglion cell axons from the remaining eye were allowed to develop in the complete absence of binocular interactions. At E59, when segregation into eye-specific layers is normally almost complete, the retinogeniculate projection from the remaining eye was then examined both by anterograde transport following intraocular injections of 3H-leucine and by the in vitro filling of individual ganglion cell axons with HRP. Results from the intraocular injections showed that in the absence of one eye, the remaining eye is still capable of forming both ipsilateral and contralateral optic tracts; however, the projection was distributed diffusely throughout each LGN, rather than being confined to normal eye-specific territories. When individual HRP-filled axons were reconstructed and examined, it was remarkable to find that the pattern of terminal arborization was virtually indistinguishable from normal axons. As usual, arbors were restricted to the distal portion of each axon trunk, and measurements showed that the total linear length of axon contributing to each arbor was within the normal range (enucleated, 2310 +/- 920 microns; normal, 2520 +/- 810 microns). Furthermore, the terminal arborizations of axons appeared to be organized into a series of tiers within the LGN in a pattern surprisingly similar to the pattern of eye-specific layers normally present by E59. Also unchanged was the normally occurring loss of axons from the remaining optic nerve: Counts at E59 showed that about 2.3 X 10(5) axons were present in enucleated animals as compared to 2.5 X 10(5) axons in controls. (ABSTRACT TRUNCATED AT 400 WORDS)
Women, Politics, and Power: A Global Perspective

List of Figures, Tables, and Maps About the Authors Preface 1. Introduction to Women in Politics Arguments for Women's Representation in Politics A Brief Overview of Women's Participation in Politics Orienting Theories 2. Women's Struggle for the Vote: The History of Women's Suffrage Suffrage in the United States Suffrage Movements Outside the United States The International Women's Movement Women's Suffrage After 1945 3. Women Struggle for Representation: Accessing Positions of Power First Female Members of Parliament Women Access Parliaments: Patterns of Representation Women in Top Leadership Positions Women in Cabinet Positions 4. Explaining the Political Representation of Women - Culture and Social Structure Beliefs Have Consequences: Culture But Who Will Run? Social Structure 5. Explaining the Political Representation of Women - Politics Democracy Electoral Systems Characteristics of Political Parties From Candidate to Legislator Quotas 6. Explaining the Political Representation of Women: Overarching Factors Armed Conflict: Devastation Yet Hope? International Influences 7. Do Women Make a Difference? Thinking Differently: Women's Views on Women and Their Policy Priorities Acting Differently: Women's Voting Patterns and Bill Sponsorship Acting Successfully: Women's Legislative Effectiveness Legislating Differently: Women's Legislative Style Do Numbers Matter? Critical Mass and Women's Impact Women's Movements and Women's Policy Machinery as Alternate Sources of Influence In Summary: What Do We Know? 8. All Regions Are Not Created Equal The Geography of Women in Politics Western Industrialized Countries Eastern Europe and Central Asia Latin America and the Caribbean Sub-Saharan Africa Asia and the Pacific Islands Middle East and North Africa 9. Middle of the Pack: Women and Politics in the United States Women in the U.S. Senate and House of Representatives: Growing Slowly Women in the States Women and the American Presidency Explanations Donkeys and Elephants: The Influence of Political Parties The Rise and Fall of the Equal Rights Amendment Gender Gaps in American Politics International Comparisons 10. Where Do We Go From Here? And How Do We Get There? Where Are We Now? Where Are We Going? How Do We Get There? In Conclusion: What Would a 50/50 World Look Like? References Glossary/Index
The UV spectrum of HS 1700+6416. I. Predicting the metal line content of the far UV spectrum

Aims. In preparation of a study of the $\ion{He}{ii}$/$\ion{H}{i}$ ratio towards the bright QSO HS 1700+6416, we predict the metal line content of the far-UV spectral range by modelling 18 metal absorption line systems with redshifts $0.2 Methods. For that purpose, we investigate the spectral energy distribution of the metagalactic ionizing radiation field. Simple photoionization models based on 8 different shapes of the ionizing background are tested for each system. The adopted energy distributions comprise the Haardt & Madau (2001, HM) model of metagalactic UV background as well as typical spectra of AGN and starburst galaxies. The models are evaluated and the favoured one is estimated. Results. We find that the majority of the considered systems is best reproduced with a HM-like ionizing radiation, where the $\ion{He}{ii}$ break, formally located at 4 Ryd, is shifted to lower energies (~3 Ryd), probably due to the opacity of the higher $\ion{He}{ii}$ Lyman series lines. The remaining systems can be reasonably described with models based on the unmodified HM background or the spectra of AGN or starburst galaxies. This finding supports the idea that the UV background is spatially variable due to both IGM opacity variations and to local sources. In comparison to an unmodified HM background, the resulting ionizing spectrum leads to carbon abundances lower by ~0.5 dex. Furthermore, if the ionizing radiation field as determined from metal line systems was typical for the IGM, the expected $\ion{He}{ii}$/$\ion{H}{i}$ ratio would be 150 to 190.
Prevalence of ischaemic heart disease at admission to intensive care and its influence on red cell transfusion thresholds: multicentre Scottish Study.

BACKGROUND Restrictive transfusion triggers are safe for most critically ill patients, but doubts exist for patients with ischaemic heart disease (IHD). We investigated the prevalence of reported IHD at admission to the intensive care unit (ICU) and investigated how this influenced red cell transfusion triggers. We also compared observed practice with the clinicians' responses to clinical scenarios. METHODS We studied 1023 sequential ICU admissions over 100 days to 10 Scottish ICUs. Daily haemoglobin, red cell transfusion, and haemorrhage data were available for 99.4% of 5638 ICU patient days. We recorded if IHD was recorded in clinical records at ICU admission. We grouped admissions as having a non-cardiac primary ICU diagnosis and no documentary evidence of IHD (Group 1, n=697), a non-cardiac primary ICU diagnosis with evidence of IHD (Group 2, n=213), or a cardiac primary ICU admission diagnosis (Group 3, n=113). We examined pre-transfusion haemoglobin concentration (Hb) for transfusion episodes not associated with haemorrhage. Clinical transfusion scenarios were sent to intensivists in the ICUs after data collection, which were designed to explore the clinicians' attitude to transfusion triggers in patients with IHD. RESULTS Previous myocardial infarction was documented in 159 (16%), cardiac failure in 142 (14%), and angina in 167 (16%). Overall, 28.8% of admissions had >/=1 of these documented. The adjusted mean (se) pre-transfusion Hb concentrations varied across the groups. These were 74 (2.2) g litre(-1) in Group 1, 77 (2.3) g litre(-1) in Group 2, and 79 (3.1) g litre(-1) in Group 3 (P=0.003 across the groups). There was concordance between observed practice and responses to the scenario similar to Group 1, but discordance for patients with IHD (Groups 2 and 3). In scenario responses, intensivists stated these patients should have significantly higher transfusion triggers than were actually observed (median [IQR] response for both groups: 90 [80-100] g litre(-1)). CONCLUSIONS About 29% of patients admitted to Scottish ICUs had documented IHD, which was associated with small adjustments to Hb transfusion triggers. In response to scenarios, clinicians believe that patients with IHD require higher transfusion triggers than are observed in practice.
α6β1 and α7β1 Integrins Are Required in Schwann Cells to Sort Axons

During development, Schwann cells extend lamellipodia-like processes to segregate large- and small-caliber axons during the process of radial sorting. Radial sorting is a prerequisite for myelination and is arrested in human neuropathies because of laminin deficiency. Experiments in mice using targeted mutagenesis have confirmed that laminins 211, 411, and receptors containing the β1 integrin subunit are required for radial sorting; however, which of the 11 α integrins that can pair with β1 forms the functional receptor is unknown. Here we conditionally deleted all the α subunits that form predominant laminin-binding β1 integrins in Schwann cells and show that only α6β1 and α7β1 integrins are required and that α7β1 compensates for the absence of α6β1 during development. The absence of either α7β1 or α6β1 integrin impairs the ability of Schwann cells to spread and to bind laminin 211 or 411, potentially explaining the failure to extend cytoplasmic processes around axons to sort them. However, double α6/α7 integrin mutants show only a subset of the abnormalities found in mutants lacking all β1 integrins, and a milder phenotype. Double-mutant Schwann cells can properly activate all the major signaling pathways associated with radial sorting and show normal Schwann cell proliferation and survival. Thus, α6β1 and α7β1 are the laminin-binding integrins required for axonal sorting, but other Schwann cell β1 integrins, possibly those that do not bind laminins, may also contribute to radial sorting during peripheral nerve development.
Competitive market for multiple firms and economic crisis.

The origin of economic crises is a key problem for economics. We present a model of long-run competitive markets to show that the multiplicity of behaviors in an economic system, over a long time scale, emerge as statistical regularities (perfectly competitive markets obey Bose-Einstein statistics and purely monopolistic-competitive markets obey Boltzmann statistics) and that how interaction among firms influences the evolutionary of competitive markets. It has been widely accepted that perfect competition is most efficient. Our study shows that the perfectly competitive system, as an extreme case of competitive markets, is most efficient but not stable, and gives rise to economic crises as society reaches full employment. In the economic crisis revealed by our model, many firms condense (collapse) into the lowest supply level (zero supply, namely, bankruptcy status), in analogy to Bose-Einstein condensation. This curious phenomenon arises because perfect competition (homogeneous competitions) equals symmetric (indistinguishable) investment direction, a fact abhorred by nature. Therefore, we urge the promotion of monopolistic competition (heterogeneous competitions) rather than perfect competition. To provide early warning of economic crises, we introduce a resolving index of investment, which approaches zero in the run-up to an economic crisis. On the other hand, our model discloses, as a profound conclusion, that the technological level for a long-run social or economic system is proportional to the freedom (disorder) of this system; in other words, technology equals the entropy of system. As an application of this concept, we give a possible answer to the Needham question: "Why was it that despite the immense achievements of traditional China it had been in Europe and not in China that the scientific and industrial revolutions occurred? "
Communication and Low Mood (CALM): a randomized controlled trial of behavioural therapy for stroke patients with aphasia

Objective: The aim was to evaluate behavioural therapy as a treatment for low mood in people with aphasia. Design: A randomized controlled trial comparing behavioural therapy plus usual care with a usual care control. Potential participants with aphasia after stroke were screened for the presence of low mood. Those who met the criteria and gave consent were randomly allocated. Setting: Participants were recruited from hospital wards, community rehabilitation, speech and language therapy services and stroke groups. Subjects: Of 511 people with aphasia identified, 105 had low mood and were recruited. Interventions: Behavioural therapy was offered for up to three months. Outcomes were assessed three and six months after random allocation. Main measures: Stroke Aphasic Depression Questionnaire, Visual Analog Mood Scales ‘sad’ item, and Visual Analogue Self-Esteem Scale. Results: Participants were aged 29 to 94 years (mean 67.0, SD 13.5) and 66 (63%) were men. Regression analysis showed that at three months, when baseline values and communication impairment were controlled for, group allocation was a significant predictor of the Stroke Aphasic Depression Questionnaire (P < 0.05), visual analogue ‘sad’ (P = 0.03), and Visual Analogue Self-Esteem Scale (P < 0.01). At six months, group alone was a significant predictor of the Stroke Aphasic Depression Questionnaire (P < 0.05), and remained significant when baseline values were controlled for (P = 0.02). Mean Stroke Aphasic Depression Questionnaire 10-item hospital version scores decreased from baseline to six months by six points in the intervention group as compared with an increase of 1.9 points in the control group. Conclusions: Behavioural therapy seemed to improve the mood of people with aphasia.
First Imported Case of Chikungunya Virus Infection in a Travelling Canadian Returning from the Caribbean

This is the first Canadian case of Chikungunya virus (CHIKV) infection reported in a traveller returning from the Caribbean. Following multiple mosquito bites in Martinique Island in January 2014, the patient presented with high fever, headaches, arthralgia on both hands and feet, and a rash on the trunk upon his return to Canada. Initial serological testing for dengue virus infection was negative. Support therapy with nonsteroidal anti-inflammatory drugs was administered. The symptoms gradually improved 4 weeks after onset with residual arthralgia and morning joint stiffness. This clinical feature prompted the clinician to request CHIKV virus serology which was found to be positive for the presence of IgM and neutralizing antibodies. In 2014, over four hundred confirmed CHIKV infection cases were diagnosed in Canadian travellers returning from the Caribbean and Central America. Clinical suspicion of CHIKV or dengue virus infections should be considered in febrile patients with arthralgia returning from the recently CHIKV endemic countries of the Americas.
Plant diversity and identity effects on predatory nematodes and their prey

There is considerable evidence that both plant diversity and plant identity can influence the level of predation and predator abundance aboveground. However, how the level of predation in the soil and the abundance of predatory soil fauna are related to plant diversity and identity remains largely unknown. In a biodiversity field experiment, we examined the effects of plant diversity and identity on the infectivity of entomopathogenic nematodes (EPNs, Heterorhabditis and Steinernema spp.), which prey on soil arthropods, and abundance of carnivorous non-EPNs, which are predators of other nematode groups. To obtain a comprehensive view of the potential prey/food availability, we also quantified the abundance of soil insects and nonpredatory nematodes and the root biomass in the experimental plots. We used structural equation modeling (SEM) to investigate possible pathways by which plant diversity and identity may affect EPN infectivity and the abundance of carnivorous non-EPNs. Heterorhabditis spp. infectivity and the abundance of carnivorous non-EPNs were not directly related to plant diversity or the proportion of legumes, grasses and forbs in the plant community. However, Steinernema spp. infectivity was higher in monocultures of Festuca rubra and Trifolium pratense than in monocultures of the other six plant species. SEM revealed that legumes positively affected Steinernema infectivity, whereas plant diversity indirectly affected the infectivity of HeterorhabditisEPNs via effects on the abundance of soil insects. The abundance of prey (soil insects and root-feeding, bacterivorous, and fungivorous nematodes) increased with higher plant diversity. The abundance of prey nematodes was also positively affected by legumes. These plant community effects could not be explained by changes in root biomass. Our results show that plant diversity and identity effects on belowground biota (particularly soil nematode community) can differ between organisms that belong to the same feeding guild and that generalizations about plant diversity effects on soil organisms should be made with great caution.
Dipoid-Specific Genome Stability Genes of S. cerevisiae: Genomic Screen Reveals Haploidization as an Escape from Persisting DNA Rearrangement Stress

Maintaining a stable genome is one of the most important tasks of every living cell and the mechanisms ensuring it are similar in all of them. The events leading to changes in DNA sequence (mutations) in diploid cells occur one to two orders of magnitude more frequently than in haploid cells. The majority of those events lead to loss of heterozygosity at the mutagenesis marker, thus diploid-specific genome stability mechanisms can be anticipated. In a new global screen for spontaneous loss of function at heterozygous forward mutagenesis marker locus, employing three different mutagenesis markers, we selected genes whose deletion causes genetic instability in diploid Saccharomyces cerevisiae cells. We have found numerous genes connected with DNA replication and repair, remodeling of chromatin, cell cycle control, stress response, and in particular the structural maintenance of chromosome complexes. We have also identified 59 uncharacterized or dubious ORFs, which show the genome instability phenotype when deleted. For one of the strongest mutators revealed in our screen, ctf18Δ/ctf18Δ the genome instability manifests as a tendency to lose the whole set of chromosomes. We postulate that this phenomenon might diminish the devastating effects of DNA rearrangements, thereby increasing the cell's chances of surviving stressful conditions. We believe that numerous new genes implicated in genome maintenance, together with newly discovered phenomenon of ploidy reduction, will help revealing novel molecular processes involved in the genome stability of diploid cells. They also provide the clues in the quest for new therapeutic targets to cure human genome instability-related diseases.