bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species
Authors: Nachman Eliana , Wentink Anne , Madiona Karine , Bousset Luc , Katsinelos Taxiarchis , Kampinga Harm , McEwan William A. , Jahn Thomas R. , Melki Ronald , Mogk Axel , Bukau Bernd , Nussbaum-Krammer Carmen 
Published: December 2019

AbstractThe accumulation of amyloid Tau aggregates is implicated in Alzheimer’s disease and other Tauopathies. Molecular chaperones are known for their function in maintaining protein homeostasis by preventing the formation or promoting the disaggregation of amorphous and amyloid protein aggregates. Here we show that an ATP-dependent human chaperone system disassembles Tau fibrilsin vitro. This function is mediated by the core chaperone Hsc70, assisted by specific co-chaperones, in particular class B J-domain proteins and an Hsp110-type NEF. Recombinant fibrils assembled from all six Tau isoforms as well as Sarkosyl-resistant Tau aggregates extracted from cell culture were processed by the Hsp70 disaggregation machinery, demonstrating the ability of this machinery to recognize a broad range of Tau aggregates. Chaperone treatment released monomeric, and small oligomeric Tau species, which induced the aggregation of self-propagating Tau species in a Tau cell culture model. We infer from these results that the activity of the Hsp70 disaggregation machinery is a double-sided sword as it attempts to eliminate Tau amyloids but with the price of generating new seeds. The Hsp70 disaggregase therefore has a crucial function in the Tau propagation cycle, rendering it a potential drug target in Tauopathies.
Amyloid-like aggregates cause lysosomal defects in neurons via gain-of-function toxicity
Authors: Riera-Tur Irene , Schäfer Tillman , Hornburg Daniel , Mishra Archana , Fernández-Mosquera Lorena , Feigenbutz Dennis , Auer Patrick , Mann Matthias , Baumeister Wolfgang , Klein Rüdiger , Meissner Felix , Raimundo Nuno , Fernández-Busnadiego Rubén , Dudanova Irina 
Published: December 2019

AbstractThe autophagy-lysosomal pathway is impaired in many neurodegenerative diseases characterized by protein aggregation, but the link between aggregation and lysosomal dysfunction remains poorly understood. Here, we combine cryo-electron tomography, proteomics and cell biology studies to investigate the effects of protein aggregates in primary neurons. We use artificial amyloid-like β-sheet proteins (β proteins) to focus on the gain-of-function aspect of aggregation. These proteins form fibrillar aggregates and cause neurotoxicity. We show that late stages of autophagy are impaired by the aggregates, resulting in lysosomal alterations reminiscent of lysosomal storage disorders. Mechanistically, β proteins interact with and sequester AP-3μ1, a subunit of the AP-3 adaptor complex involved in protein trafficking to lysosomal organelles. This leads to destabilization of the AP-3 complex, missorting of AP-3 cargo, and lysosomal defects. Restoring AP-3μ1 expression ameliorates neurotoxicity caused by β proteins. Altogether, our results highlight the link between protein aggregation and neurotoxicity, pointing to lysosomes as particularly vulnerable organelles.
PrkA controls peptidoglycan biosynthesis through the essential phosphorylation of ReoM
Authors: Wamp Sabrina , Rutter Zoe J. , Rismondo Jeanine , Jennings Claire E. , Möller Lars , Lewis Richard J. , Halbedel Sven 
Published: December 2019

ABSTRACTPeptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that sense PG fragments. However, only a few PG biosynthetic enzymes are direct kinase substrates. Here, we identify the conserved ReoM protein as a novel PASTA-eSTK substrate in the Gram-positive pathogenListeria monocytogenes. Our data show that the phosphorylation of ReoM is essential as it controls ClpCP-dependent proteolytic degradation of the essential enzyme MurA, which catalyses the first committed step in PG biosynthesis. We also identify ReoY as a second novel factor required for degradation of ClpCP substrates. Collectively, our data imply that the first committed step of PG biosynthesis is activated through control of ClpCP protease activity in response to signals of PG homeostasis imbalance.
Metabolic modelling of the C3-CAM continuum revealed the establishment of a starch/sugar-malate cycle in CAM evolution
Authors: Tay Ignacius Y. Y. , Odang Kristoforus Bryant , Cheung C. Y. Maurice 
Published: December 2019

AbstractThe evolution of Crassulacean acid metabolism (CAM) is thought to be along a C3-CAM continuum including multiple variations of CAM such as CAM cycling and CAM idling. Here, we applied large-scale constraint-based modelling to investigate the metabolism and energetics of plants operating in C3, CAM, CAM cycling and CAM idling. Our modelling results suggested that CAM cycling and CAM idling could be potential evolutionary intermediates in CAM evolution by establishing a starch/sugar-malate cycle. Our model analysis showed that by varying CO2exchange during the light period, as a proxy of stomatal conductance, there exists a C3-CAM continuum with gradual metabolic changes, supporting the notion that evolution of CAM from C3could occur solely through incremental changes in metabolic fluxes. Along the C3-CAM continuum, our model predicted changes in metabolic fluxes not only through the starch/sugar-malate cycle that is involved in CAM photosynthetic CO2fixation but also other metabolic processes including the mitochondrial electron transport chain and the tricarboxylate acid cycle at night. These predictions could guide engineering efforts in introducing CAM into C3crops for improved water use efficiency.
Physiological predictors of competitive performance in CrossFit®athletes
Authors: Martínez-Gómez Rafael , Valenzuela Pedro L. , Alejo Lidia B. , Gil-Cabrera Jaime , Montalvo-Pérez Almudena , Talavera Eduardo , Lucia Alejandro , Moral-González Susana , Barranco-Gil David 
Published: December 2019

AbstractThe aim of this study was to determine which physiological variables could predict performance during a CrossFit competition. Fifteen male CrossFit athletes (35 ± 9 years) participated and performed a series of tests (incremental load test for full squat and bench press, jump tests, incremental running test, and Wingate test) that were used as potential predictors of CrossFit performance. Thereafter, they performed the five Workouts of the Day (WODs) corresponding to the CrossFit Games Open 2019, and the relationship between each variable and CrossFit performance was analyzed. Overall Crossfit performance (i.e., final ranking considering all WODs) was significantly related to jump ability, mean and peak power output during the Wingate test, relative maximum strength for the full squat and the bench press, and maximum oxygen uptake and maximum speed during an incremental running test (all p<0.05, r=0.58–0.75), although the relationship of most markers varied depending on the analyzed WOD. Multiple linear regression analysis showed that the combination of maximum oxygen uptake, squat jump ability, and reactive strength index accounted for 81% of the variance in overall CrossFit performance (p=0.0003). CrossFit performance seems dependent on a variety of power-, strength-, and aerobic-related markers, which reflects the complexity of this sport. Improvements in aerobic capacity may help people and athletes in CrossFit performance and well-being. Also, focus on lower body power could be the key to obtain better performance markers.
Shell Morphology, Radula and Genital Structures of New Invasive Giant African Land Snail Species, Achatina fulica Bowdich, 1822,Achatina albopicta E.A. Smith (1878) and Achatina reticulata Pfeiffer 1845 (Gastropoda:Achatinidae) in Southwest Nigeria
Authors: Odaibo Alexander B. , Olayinka Suraj O. 
Published: December 2019

AbstractThe aim of this study was to determine the differences in the shell, radula and genital structures of 3 new invasive species, Achatina fulica Bowdich, 1822,Achatina albopicta E.A. Smith (1878) and Achatina reticulata Pfeiffer, 1845 collected from southwestern Nigeria and to determine features that would be of importance in the identification of these invasive species in Nigeria. This is the first report of Achatina albopicta and A. reticulata in Nigeria, but Achatina fulica have since been reported in Nigeria and other African countries outside coastal East Africa. No study has described the external or internal morphology of any of the invasive species in Nigeria. Five to ten live specimens of each species, with complete shell characters, of each species were used for this study. Vernier caliper was used to obtain all shell measurements, with the shell held vertically and the aperture facing the observer. The genital structures were dissected out and fixed in 70% alcohol for 10-15 minutes and examined. The buccal mass was dissected out and digested in 7.5% sodium hydroxide for 24 hrs to free the radula from snail tissues and then examined under the compound microscope.The shells of the 3 new species were dextral, conical with pointed spire and narrow apex. The whorls were separated by deep sutures. The parietal walls and the columella of the three species were white but columella of A. reticulata had a characteristic thick deposit of white porcelain-like material. There were dark brown markings on the whorls of the three species on dirty brown background for A. fulica and A. reticulata and dirty yellowish background for A. albopicta. The shell of A. albopicta was slightly glossy on the body whorl. The whorls of A. albopicta were much more convex than the whorls of A. fulica and A. reticulata. The columella of A. albopicta was truncate above the base of the peristome, moderately concave and slightly curved up at the base, while the columella of A. fulica was truncate sharply at the base of the peristome and straight and the columella of A. reticulata was slantly truncate at the base of the peristome and straight. The genitalia of the three species were very identical but differed slightly in the emergence of the basal vas deferens from the penis. The penes were slender and completely enclosed by the penial sheaths. The length of the penis varied from 10 to 12 mm. The vas deferens, free oviduct and the spermatheca duct were very long. The radula could be differentiated by the structure of central teeth and the first lateral tooth. The study showed that the shell morphology, radula and genital structures can be of importance in the identification of members of the family Achatinidae in Nigeria.
Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice
Authors: Dhital Saphala , Vyavahare Naren R. 
Published: December 2019

ABSTRACTAimAbdominal aortic aneurysms (AAA) is a life-threatening weakening and expansion of the abdominal aorta due to inflammatory cell infiltration and gradual degeneration of extracellular matrix (ECM). There are no pharmacological therapies to treat AAA. We tested the hypothesis that nanoparticle (NP) therapy that targets degraded elastin and delivers anti-inflammatory, anti-oxidative, and ECM stabilizing agent, pentagalloyl glucose (PGG) will reverse advance stage aneurysm in an elastase-induced mouse model of AAA.Method and ResultsPorcine pancreatic elastase (PPE) was applied periadventitially to the infrarenal aorta in mice and AAA was allowed to develop for 14 days. Nanoparticles loaded with PGG (EL-PGG-NPs) were then delivered via IV route at 14-day and 21-day (10 mg/kg of body weight). A control group of mice received no therapy. The targeting of NPs to the AAA site was confirmed with fluorescent dye marked NPs and gold NPs. Animals were sacrificed at 28-d. We found that targeted PGG therapy reversed the AAA by decreasing matrix metalloproteinases MMP-9 and MMP-2, and the infiltration of macrophages in the medial layer. The increase in diameter of the aorta was reversed to healthy controls. Moreover, PGG treatment restored degraded elastic lamina and increased the circumferential strain of aneurysmal aorta to the healthy levels.ConclusionOur results support that site-specific delivery of PGG with targeted nanoparticles can be used to treat already developed AAA. Such therapy can reverse inflammatory markers and restore arterial homeostasis.
The boundary of sustainability reporting: evidence from the FTSE100
Authors: Miles Samantha , Ringham Kate 
Published: December 2019

Purpose
The purpose of this paper is to use a multi-disciplinary theoretical understanding of boundary setting to develop a quadripartite model in which sustainability reporting boundaries are classified as “Reputation Management”, “Ownership and Control”, “Accountability”; and, “Stakeholder Engagement”. Content analysis is then used to empirically test the model.

Design/methodology/approach
Using impression management theory, rationalism, systems and contingency theory, and network theory, a model is created which classifies sustainability reporting boundaries. Content analysis is used to empirically test boundaries across the disclosure of 49 GRI topics by the FTSE100.

Findings
Sustainability reporting fails to discharge accountability due to adoption of narrow “Reputation Management” boundaries. Boundaries are significantly (p<0.0001) narrower than previous research suggests. Findings support impression management theory as the strongest theory to predict reporting content. An ownership and control boundary, although widely criticized, represents the boundary of progressive reporters, lending marginal support for economic theories. Accountability boundaries are scarce. No evidence was found for stakeholder engagement boundaries.

Practical implications
The determination of boundary is critical to the discharge of accountability. A critical consideration of boundary setting is required, including authentic stakeholder engagement in determining boundaries and transparency of boundary adopted. The results are ranked to enable benchmarking of the FTSE100. Boundaries can be widened through regulation or “name and shame campaigns”.

Originality/value
This paper provides a theory-informed advancement in thinking on sustainability reporting boundary setting and the importance of this for advancing sustainability reporting quality.
Perceived contributions to national development
Authors: Enkhtur Ariunaa 
Published: December 2019

Purpose
The purpose of this paper is to explore how Mongolian alumni of three different scholarship programs sponsored by governments of Japan and Mongolia view their role in national development after graduation.

Design/methodology/approach
This paper reports findings from a phenomenological study (Creswell, 2007) – the first phase of an exploratory sequential mixed-methods study in a recent PhD study. Based on semi-structured interviews with 24 alumni the study aimed to understand alumni’s perspectives in their voices.

Findings
Alumni were motivated to contribute to their communities, institutions, economic, political, social and legal conditions of Mongolia. However, they faced various structural challenges including getting jobs in the public sector even when they had binding agreements with employers. The findings call for long-term support for alumni projects and hubs as well as policy frameworks that tie the scholarship programs with national development goals.

Originality/value
Despite the high mobility rate of Mongolian scholars and a long history of Japanese Official Development Assistance to develop human resources in developing countries especially in Asia, little is known about the impact of these programs on the Mongolian national development. Through the phenomenological study, this study expands the understanding of ways in which alumni contribute to their national development.
Should we be accepting self-referrals for Autism assessments?
Authors: Whitney Daniel , Stansfield Alison Jane 
Published: December 2019

Purpose
The Leeds Autism Diagnostic Service (LADS) is an all IQ service accepting professional and self-referrals, from age 18, for diagnostic assessment. LADS is unusual compared to other diagnostic services in England, in that it accepts self-referrals. The purpose of this paper is to compare diagnostic outcome between self-referrals and other referral sources.

Design/methodology/approach
This is a service evaluation of all 692 referrals for diagnostic assessment into LADS, over a three year period, from 2016 to 2018. The diagnostic outcomes were compared between self-referrals and other referral sources. Secondary analysis looked at age and gender differences between these groups.

Findings
There were 98 self-referrals over three years with autism diagnosed in 65 per cent. In total, 594 other referrals were received during this time period, with autism diagnosed in 44 per cent. This showed a significant difference of 21 per cent with 95% confidence intervals of 10–31 per cent (p=0.0001) using a n−1 χ2 test. In total, 59 per cent of self-referrals were from patients identifying as female, which compared to 35 per cent identifying as female from other referrals. This was a difference of 24 per cent with 95% confidence interval of 14–34 per cent (p<0.0001) on the n−1 χ2 test.

Research limitations/implications
Factors which may influence the ability to generalise from these results are: that LADS covers a large mainly urban and suburban area with a range of ethnic and socioeconomic diversity; that LADS is an all IQ service unlike some other autism diagnostic services; historical and service-related factors unique to Leeds may be dissimilar to other locations. It was beyond the scope of this evaluation to perform a qualitative analysis to compare the referral sources, but this may be an area for further study.

Practical implications
This evaluation supports the use of a self-referral route for adult autism diagnostic services on a local level and may support its use more widely in other services.

Social implications
This evaluation, in demonstrating proportionately significantly higher autism diagnosis from self-referrals is likely to be reducing the work load of professionals who would normally make referrals. Alternatively, it may be capturing a subgroup of the autism population who would not otherwise have sought diagnosis. In either scenario, it supports and is consistent with a patient centred approach to accessing appropriate diagnostic services.

Originality/value
The authors are not aware that any previous evaluation of this nature has been conducted and feel this evaluation supports the use of a self-referral pathway in adult autism diagnostic services.
Sustainability disclosure and earnings informativeness: evidence from Sri Lanka
Authors: Swarnapali RM Nayana Chandani 
Published: December 2019

PurposeThe purpose of this paper is to investigate whether the communication that takes place through the sustainability disclosure (SD) route has an effect on earnings informativeness (EI) of firms in an emerging market.Design/methodology/approachThe sample consists of companies listed on the Colombo Stock Exchange in Sri Lanka, where SD is a new phenomenon and a voluntary reporting initiative. Regression analysis is executed on the panel data to achieve the study objective.FindingsThe result reveals a positive association between SD and EI. Sustainability reports may provide useful information that supplements merely financial data, aiding the stakeholders to interpret the financial reporting better. The finding premises that SD enhances EI, communicating value relevant information to capital market participants.Practical implicationsSD does much to reduce capital market participants’ uncertainties, thereby aiding them to assess financial information better.Social implicationsThe findings of the study confirm earlier research findings that indicate a positive association between SD and EI, suggesting that capital market participants are gradually becoming aware of the value relevance of sustainability reports.Originality/valueThis is the first study investigating SD and EI association that is specific to the Sri Lankan context. Owing to the sparse studies done on the SD and EI association, this study should contribute significantly to the existing literature by broadening the geographical coverage.
Earnings persistence, earnings power, and equity valuation in consumer goods firms
Authors: Fatma Nurani , Hidayat Widi 
Published: December 2019

Purpose
The purpose of this paper is to examine the influence of earnings persistence and earnings power on equity valuation.

Design/methodology/approach
The purposive sampling method was applied to determine the samples of selected 100 firms. This study employed secondary data obtained from the annual reports and financial statements of consumer goods firms listed on the Indonesian Stock Exchange for the period 2010–2014. The analysis technique used a multiple regression analysis.

Findings
The study result shows that, partially, earnings persistence and earnings power affect equity valuation by investors. Earnings persistence has a negative influence, whereas earnings power has a positive influence on equity valuation.

Originality/value
This study throws additional lights on equity valuation specific to consumer goods industries.
The interplay of social responsibility consciousness and evaluation mode in consumers’ response toward cause-related marketing-enhanced product
Authors: Park Eun Young , Jang Jung Min 
Published: December 2019

Purpose
The purpose of this paper demonstrate that purchase intention toward a cause-related marketing (CRM)-enhanced product can be positively correlated with consumers’ social responsibility consciousness (SRC) and can be increased or decreased merely by changing the evaluation mode.

Design/methodology/approach
The authors conduct three experimental studies with two levels of SRC (high vs low) × two evaluation modes (joint evaluation (JE) vs separate evaluation (SE)) between-subjects design. The dependent variable is purchase intent toward the CRM-enhanced product.

Findings
The results indicate that consumers with high SRC are more likely than those with low SRC to purchase a CRM-enhanced product when two products are presented side by side (JE). However, consumers’ SRC level does not impact purchase intention when they see only one product (SE) independently (Study 1). The authors confirm that the proposed effect is mediated by perceived price fairness toward the product (Studies 2 and 3).

Research limitations/implications
Future research on CRM-enhanced products should carefully consider that the impact of individuals’ SRC level was in very different directions depending on the evaluation mode. In addition, further investigation is needed to address generalizability issues regarding samples and hypothetical stimuli.

Practical implications
These findings offer recommendations to help practitioners design effective marketing communications about CRM practice for target markets.

Originality/value
To the authors best knowledge, the current study is the first attempt to explore the crucial role of SRC, presentation mode and their interaction on purchase intention toward CRM-enhanced products.