bluuebunny/crossref_metadata_2025 huggingface dataset:
Insoluble Aβ overexpression in an App knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, and social and anxiety-related behaviours
Authors: Pervolaraki Eleftheria , Hall Stephen P , Foresteire Denise , Saito Takashi , Saido Takaomi C , Whittington Miles A , Lever Colin , Dachtler James
Published: December 2018

We studied two new App knock-in mice models of Alzheimer’s disease (AppNL-F and AppNL-G-F), which generate elevated levels of Aβ40 and Aβ42 without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related and social behaviours, and neural alterations potentially underlying such changes, driven specifically by Aβ accumulation. AppNL-G-F knock-in mice exhibited subtle deficits in tasks assessing social memory, but not in social motivation tasks. In anxiety-assessing tasks, AppNL-G-F knock-in mice exhibited: 1) increased thigmotaxis in the Open Field (OF), yet; 2) reduced closed-arm, and increased open-arm, time in the Elevated Plus Maze (EPM). Their ostensibly-anxiogenic OF profile, yet ostensibly-anxiolytic EPM profile, could hint at altered cortical mechanisms affecting decision-making (e.g. ‘disinhibition’), rather than simple core deficits in emotional motivation. Consistent with this possibility, alterations in microstructure, glutamatergic-dependent gamma oscillations, and glutamatergic gene expression were all observed in the prefrontal cortex, but not the amygdala, of AppNL-G-F knock-in mice. Thus, insoluble Aβ overexpression drives prefrontal cortical alterations, potentially underlying changes in social and anxiety-related behavioural tasks.

Highlights

AppNL-G-F KI mice displayed differing anxiety behaviours in two tests of anxiety.

Prefrontal gamma was no longer NMDA-receptor dependent in AppNL-G-F KI mice.

Prefrontal expression of Grin2b was reduced in AppNL-G-F KI mice.

DTI found structural alterations in the hippocampus and prefrontal cortex in AppNL-G-F KI mice.
The Case For and Against Double-blind Reviews
Authors: Cox Amelia R , Montgomerie Robert
Published: December 2018

To date, the majority of authors on scientific publications have been men. While much of this gender bias can be explained by historic sexism and discrimination, there is concern that women may still be disadvantaged by the peer review process if reviewers' unconscious biases lead them to reject publications with female authors more often. One potential solution to this perceived gender bias in the reviewing process is for journals to adopt double-blind reviews whereby neither the authors nor the reviewers are aware of each other's identities and genders. To test the efficacy of double-blind reviews, we assigned gender to every authorship of every paper published in 5 different journals with different peer review processes (double-blind vs. single blind) and subject matter (birds vs. behavioral ecology) from 2010-2018 (n = 4865 papers). While female authorships comprised only 35% of the total, the double-blind journal Behavioral Ecology did not have more female authorships than its single-blind counterparts. Interestingly, the incidence of female authorship is higher at behavioral ecology journals (Behavioral Ecology and Behavioral Ecology and Sociobiology) than in the ornithology journals (Auk, Condor, Ibis), for papers on all topics as well as those on birds. These analyses suggest that double-blind review does not currently increase the incidence of female authorship in the journals studied here. We conclude, at least for these journals, that double-blind review does not benefit female authors and may, in the long run, be detrimental.
The bacillithiol pathway is required for biofilm formation in Staphylococcus aureus
Authors: Gulati Megha , Thomas Jason M. , Rawat Mamta , Nobile Clarissa J.
Published: December 2018

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Our data show that the bshC mutant, which is defective in the last step of the bacillithiol pathway and lacks BSH, is impaired in biofilm formation. We also identify a putative S-nitrosobacillithiol reductase (BSNOR), similar to a S-nitrosomycothiol reductase found in M. smegmatis, and show that the BSNOR mutant has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that bacillithiol and nitric oxide are key players in normal biofilm formation in S. aureus.
Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes
Authors: Lamichhane Santosh , Kemppainen Esko , Trost Kajetan , Siljander Heli , Hyoty Heikki , Ilonen Jorma , Toppari Jorma , Veijola Riitta , Hyotylainen Tuulia , Knip Mikael , Oresic Matej
Published: December 2018

Previous studies suggest that metabolic dysregulation precedes the onset of type 1 diabetes (T1D). However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. Here we analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to T1D (PT1D), who seroconverted to one islet autoantibody (Ab) but not to T1D (P1Ab), and Ab-negative controls (CTR). In early infancy, PT1D associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, as compared to CTR. Methionine remained persistently upregulated in PT1D as compared to CTR and P1Ab. Appearance of islet autoantibodies associated with decreased glutamic and aspartic acids. Our findings suggest that children who progress to T1D have a unique metabolic profile, which is however altered with the onset of islet autoantibodies. Our findings may assist in early prediction of T1D.
opentsv prevents the corruption of scientific data by Excel
Authors: De Rijk Peter , D’Hert Svenn , Strazisar Mojca
Published: December 2018

Microsoft Excel is widely used by researchers to edit tab- or comma-separated data files. However, Excel often corrupts the data when opening these files, most notably by changing some gene names to a date. Although this problem was cautioned against earlier, we show that every year hundreds of published papers still come with supplementary data files containing these errors. Opentsv was developed to effectively circumvent this problem at the root by providing an easy and transparent way to open delimited data files in Excel without these conversions. Opentsv is freely available at https://github.com/derijkp/opentsv.
Conformational changes in Apolipoprotein N-acyltransferase (Lnt)
Authors: Wiseman Benjamin , Högbom Martin
Published: December 2018

In bacteria, lipoproteins are important components of the cell envelope and are responsible for many essential cellular functions. They are produced by the post-translational covalent attachment of lipids that occurs via a sequential 3-step process controlled by three essential integral membrane enzymes. The last step of this process, unique to Gram negative bacteria, is the N-acylation of the terminal cysteine by Apolipoprotein N-acyltransferase (Lnt) to form the final mature lipoprotein. Here we report 2 crystal forms of this enzyme. In one form the enzyme crystallized with two molecules in the asymmetric unit. In one of those molecules the thioester acyl-intermediate is observed. In the other molecule, the crystal packing suggests one potential mode of apolipoprotein docking to Lnt. In the second crystal form the enzyme crystallized with one molecule in the asymmetric unit in an apparent apo-state remarkably devoid of any bound molecules in the large open substrate entry portal. Taken together, these structures suggest that the movement of the essential W237 is triggered by substrate binding and could help direct and stabilize the interaction between Lnt and the incoming substrate apolipoprotein.

Graphical Abstract
Using Flow Cytometry and Multistage Machine Learning to Discover Label-Free Signatures of Algal Lipid Accumulation
Authors: Tanhaemami Mohammad , Alizadeh Elaheh , Sanders Claire , Marrone Babetta L. , Munsky’ Brian
Published: December 2018

—Most applications of flow cytometry or cell sorting rely on the conjugation of fluorescent dyes to specific biomarkers. However, labeled biomarkers are not always available, they can be costly, and they may disrupt natural cell behavior. Label-free quantification based upon machine learning approaches could help correct these issues, but label replacement strategies can be very difficult to discover when applied labels or other modifications in measurements inadvertently modify intrinsic cell properties. Here we demonstrate a new, but simple approach based upon feature selection and linear regression analyses to integrate statistical information collected from both labeled and unlabeled cell populations and to identify models for accurate label-free single-cell quantification. We verify the method’s accuracy to predict lipid content in algal cells(Picochlorum soloecismus)during a nitrogen starvation and lipid accumulation time course. Our general approach is expected to improve label-free single-cell analysis for other organisms or pathways, where biomarkers are inconvenient, expensive, or disruptive to downstream cellular processes.
OCT4 expression regulated apoptosis and cell cycle in myeloma cells
Authors: Niknamian Sorush
Published: December 2018

Purpose

OCT4 gene is specifically expressed in embryonic stem cells and plays a very important role in the proliferation, differentiation, and self-renewal of these cells. The abnormal expression of the OCT4 gene has been observed in most malignancies. Expression of this gene can affect the proliferation and apoptosis of malignant cells by activating various signaling pathways. The proliferation and excessive accumulation of myeloma cells in the bone marrow causes the essential complications of multiple myeloma. Genetic changes and mutations play a role in unscheduled proliferation and diminishing of the apoptosis of the myeloma cells.

Material and methods

In this study, the expression of the OCT4 gene by quantitative PCR and its effects on proliferation, apoptosis, and cell cycle of the myeloma cells by flow cytometry was investigated.

Results

The results of our study indicated that the myeloma cells express the OCT4 gene; and inhibition of the OCT4 gene by siRNA reduced its expression. The siRNA treated myeloma cells indicated decreased proliferation and increased apoptosis.

Conclusion

As with studies in other malignancies, our study also revealed that the OCT4 gene was expressed in the myeloma cells, with evidences of increased proliferation and reduced apoptosis in these cells.
Gibbs Free Energy of Protein-Protein Interactions Correlates with ATP Production in Cancer Cells
Authors: Golas Stefan M. , Nguyen Amber N. , Rietman Edward A. , Tuszynski Jack A.
Published: December 2018

In this paper we analyze several cancer cell types from two seemingly independent angles: (a) the over-expression of various proteins participating in protein-protein interaction networks and (b) a metabolic shift from oxidative phosphorylation to glycolysis. We use large data sets to obtain a thermodynamic measure of the protein-protein interaction network, namely the associated Gibbs free energy. We find a reasonably strong inverse correlation between the percentage of energy production via oxidative phosphorylation and the Gibbs free energy of the protein networks. The latter is a measure of functional dysregulation within the cell. Our findings corroborate earlier indications that signaling pathway upregulation in cancer cells are linked to the metabolic shift known as the Warburg effect, hence these two seemingly independent characteristics of cancer phenotype may be interconnected.
Martini bead form factors for nucleic-acids and their application in the refinement of protein/nucleic-acid complexes against SAXS data
Authors: Paissoni Cristina , Jussupow Alexander , Camilloni Carlo
Published: December 2018

Small-angle X-ray scattering (SAXS) use in combination with molecular dynamics simulation is hampered by its heavy computational cost. The calculation of SAXS from atomic structures can be speed up by using a coarse grain representation of the structure. Here following the work of Niebling, et al. (J. Appl. Cryst., (2014), 47, 1190) we derived the Martini beads form factors for nucleic acids and we implemented them, together with those previously determined for proteins, in the publicly available PLUMED library. We also implemented a hybrid multi-resolution strategy to perform SAXS restrained simulations at atomic resolution by calculating on-the-fly the virtual position of the Martini beads and using them for the calculation of SAXS. The accuracy and efficiency of the method is demonstrated by refining the structure of two protein/nucleic acid complexes. Instrumental for this result is the use of metainference that allows considering and alleviating the approximations at play in our SAXS calculation.
NAD+ treatment can increase directly the antioxidant capacity of rotenone-treated differentiated PC12 cells
Authors: Zhang Jie , Hong Yunyi , Cao Wei , Shi Haibo , Ying Weihai
Published: December 2018

NAD+ administration can produce profound beneficial effects in the animal models of aging and a number of diseases. Since oxidative stress plays key pathological roles in aging and multiple major disorders, it is crucial to elucidate the mechanisms underlying the protective effects of NAD+ administration on oxidative stress-induced cell death. Previous studies have suggested that NAD+ treatment can decrease oxidative cell death indirectly by such mechanisms as preventing mitochondrial permeability transition, while it is unclear if NAD+ administration may decrease oxidative cell death by increasing directly the antioxidant capacity of the cells. Our current study used rotenone-treated differentiated PC12 cells as a cellular model to test our hypothesis that NAD+ treatment may increase directly the antioxidant capacity of the cells exposed to oxidative stress. Our study has indicated that NAD+ treatment can significantly attenuate the rotenone-induced increase in oxidative stress in the cells. Moreover, NAD+ treatment can significantly enhance the GSH/GSSG ratio, a major index of antioxidant capacity, of rotenone-treated cells. Collectively, our study has provided the first evidence indicating that NAD+ treatment can increase directly the antioxidant capacity of cells exposed to oxidative stress. These findings have suggested a novel mechanism underlying the profound protective effects of NAD+ administration in numerous disease models: NAD+ administration can decrease oxidative stress-induced cell death by enhancing directly the antioxidant capacity of the cells. Our finding has also highlighted the nutritional potential of NAD+.
Blood vessels guide Schwann cell migration in the adult demyelinated CNS through Eph/ephrin signaling
Authors: Garcia-Diaz Beatriz , Bachelin Corinne , Coulpier Fanny , Gerschenfeld Gaspard , Deboux Cyrille , Zujovic Violetta , Charnay Patrick , Topilko Piotr , Baron-Van Evercooren Anne
Published: December 2018

Schwann cells (SC) enter the central nervous system (CNS) in pathophysiological conditions. However, how SC invade the CNS to remyelinate central axons remains undetermined. We studied SC migratory behaviorex vivoandin vivoafter exogenous transplantation in the demyelinated spinal cord. Data highlight for the first time that SC migrate preferentially along blood vessel in perivascular ECM, avoiding CNS myelin. We demonstratein vitroandin vivothat this migration route occurs by virtue of a dual mode of action of Eph/ephrin receptor. Indeed, EphrinB3, enriched in myelin, interacts with SC Eph receptors, to drive SC away from CNS myelin, and triggers their preferential adhesion to ECM components, such as fibronectin via integrinβ1 interactions. This complex interplay enhances SC migration along the blood vessel network and together with lesion-induced vascular remodeling facilitates their timely invasion of the lesion site. These novel findings elucidate the mechanism by which SC invade and contribute to spinal cord repair.
Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex
Authors: Gauto Diego , Estrozi Leandro , Schwieters Charles , Effantin Gregory , Macek Pavel , sounier remy , Sivertsen Astrid C. , Schmidt Elena , Kerfah Rime , Mas Guillaume , Colletier Jacques-Philippe , Guntert Peter , Favier Adrien , Schoehn Guy , Boisbouvier Jerome , Schanda Paul
Published: December 2018

Atomic-resolution structure determination is the key requirement for understanding protein function. Cryo-EM and NMR spectroscopy both provide structural information, but currently cryo-EM does not routinely give access to atomic-level structural data, and, generally, NMR structure determination is restricted to small (<30 kDa) proteins. We introduce an integrated structure determination approach that simultaneously uses NMR and EM data to overcome the limits of each of these methods. The approach enabled determination of the high-resolution structure of the 468 kDa large dodecameric aminopeptidase TET2 to a precision and accuracy below 1 Angstrom by combining secondary-structure information obtained from near-complete magic-angle-spinning NMR assignments of the 39 kDa-large subunits, distance restraints from backbone amides and specifically labelled methyl groups, and a 4.1 Angstrom resolution EM map. The resulting structure exceeds current standards of NMR and EM structure determination in terms of molecular weight and precision. Importantly, the approach is successful even in cases where only medium-resolution (up to 8 Angstrom) cryo-EM data are available, thus paving avenues for the structure determination of challenging biological assemblies.
A Heuristic Derived from Analysis of the Ion Channel Structural Proteome Permits the Rapid Identification of Hydrophobic Gates
Authors: Rao Shanlin , Klesse Gianni , Stansfeld Phillip J. , Tucker Stephen J. , Sansom Mark S.P.
Published: December 2018

Ion channel proteins control ionic flux across biological membranes through conformational changes in their transmembrane pores. An exponentially increasing number of channel structures captured in different conformational states are now being determined. However, these newly-resolved structures are commonly classified as either open or closed based solely on the physical dimensions of their pore and it is now known that more accurate annotation of their conductive state requires an additional assessment of the effect of pore hydrophobicity. A narrow hydrophobic gate region may disfavour liquid-phase water, leading to local de-wetting which will form an energetic barrier to water and ion permeation without steric occlusion of the pore. Here we quantify the combined influence of radius and hydrophobicity on pore de-wetting by applying molecular dynamics simulations and machine learning to nearly 200 ion channel structures. This allows us to propose a simple simulation-free heuristic model that rapidly and accurately predicts the presence of hydrophobic gates. This not only enables the functional annotation of new channel structures as soon as they are determined, but may also facilitate the design of novel nanopores controlled by hydrophobic gates.

Significance statement

Ion channels are nanoscale protein pores in cell membranes. An exponentially increasing number of structures for channels means that computational methods for predicting their functional state are needed. Hydrophobic gates in ion channels result in local de-wetting of pores which functionally closes them to water and ion permeation. We use simulations of water behaviour within nearly 200 different ion channel structures to explore how the radius and hydrophobicity of pores determine their hydration vs. de-wetting behaviour. Machine learning-assisted analysis of these simulations enables us to propose a simple model for this relationship. This allows us to present an easy method for the rapid prediction of the functional state of new channel structures as they emerge.
Flexibility, variability and constraint in energy management patterns across vertebrate taxa revealed by long‐term heart rate measurements
Authors: Halsey Lewis G. , Green Jonathan A. , Twiss Sean D. , Arnold Walter , Burthe Sarah J. , Butler Patrick J. , Cooke Steven J. , Grémillet David , Ruf Thomas , Hicks Olivia , Minta Katarzyna J. , Prystay Tanya S. , Wascher Claudia A. F. , Careau Vincent
Published: December 2018

Animals are expected to be judicious in the use of the energy they gain due to the costs and limits associated with its intake. The management of energy expenditure (EE) exhibited by animals has previously been considered in terms of three patterns: the constrained, independent and performance patterns of energy management. These patterns can be interpreted by regressing daily EE against maintenance EE measured over extended periods. From the multiple studies on this topic, there is equivocal evidence about the existence of universal patterns in certain aspects of energy management.

The implicit assumption that animals exhibit specifically one of three discrete energy management patterns, and without variation, seems simplistic. We suggest that animals can exhibit gradations of different energy management patterns and that the exact pattern will fluctuate as their environmental context changes.

To investigate these ideas, and for possible large‐scale patterns in energy management, we analysed long‐term heart rate data—a strong proxy for EE—across and within individuals in 16 species of birds, mammals and fish.

Our analyses of 292 individuals representing 46,539 observation‐days suggest that vertebrates typically exhibit predominantly the independent or performance energy patterns at the across‐individual level, and that the pattern does not associate with taxonomic group. Within individuals, however, animals generally exhibit some degree of energy constraint. Together, these findings indicate that across diverse species, some individuals supply more energy to all aspects of their life than do others, however all individuals must trade‐off deployment of their available energy between competing functions. This demonstrates that within‐individual analyses are essential for the interpretation of energy management patterns.

We also found that species do not necessarily exhibit a fixed energy management pattern but rather temporal variation in their energy management over the year. Animals’ energy management exhibited stronger energy constraint during periods of higher EE, which typically coincided with clear and key life cycle events such as reproduction, suggesting an adaptive plasticity to respond to fluctuating energy demands.

A plain language summary is available for this article.
The meaning of the term ‘function’ in ecology: A coral reef perspective
Authors: Bellwood David R. , Streit Robert P. , Brandl Simon J. , Tebbett Sterling B.
Published: December 2018

The inherent complexity of high‐diversity systems can make them particularly difficult to understand. The relatively recent introduction of functional approaches, which seek to infer ecosystem functioning based on species’ ecological traits, has revolutionized our understanding of these high‐diversity systems. Today, the functional structure of an assemblage is widely regarded as a key indicator of the status or resilience of an ecosystem. Indeed, functional evaluations have become a mainstay of monitoring and management approaches. But is the heavy focus on broad metrics of functional structure grounded in empirical research?

On tropical coral reefs, the ocean’s most diverse ecosystems, remarkably few studies directly quantify ecosystem functions and the term ‘function’ is widely used but rarely defined, especially when applied to reef fishes. Our review suggests that most ‘functional’ studies do not study function as it relates to ecological processes. Rather, they look at easy‐to‐measure traits or proxies that are thought to have functional significance. However, these links are rarely tested empirically, severely limiting our capacity to extend results from community structure to the dynamic processes operating within high‐diversity ecosystems such as coral reefs.

With rapid changes in global ecosystems, and in their capacity to deliver ecosystem services, there is an urgent need to understand and empirically measure the role of organisms in various ecosystem functions. We suggest that if we are to understand and manage transitioning coral reefs in the Anthropocene, a broad definition of the word ‘function’ is needed along with a focus on ecological processes and the empirical quantification of functional roles.

In this review, we propose a universal operational definition of the term ‘function’ that works from a cellular to a global level. Specifically, it is the movement or storage of energy or material. Within this broad definitional framework, all functions are part of a continuum that is tied together by the process‐based unifier of material fluxes. With this universal definition at hand, we then present a path forward that will allow us to fully harness the power of functional approaches in understanding and managing high‐diversity systems such as coral reefs.

A plain language summary is available for this article.
Stable isotopes reveal limited Eltonian niche conservatism across carnivore populations
Authors: Manlick Philip J. , Petersen Shelby M. , Moriarty Katie M. , Pauli Jonathan N.
Published: December 2018

Niche conservatism—the retention of ecological traits across space and time—is an emerging topic of interest because it can predict responses to global change. The conservation of Grinnellian niche characteristics, like species‐habitat associations, has received widespread attention, but the conservation of Eltonian traits such as consumer–resource interactions remains poorly understood.

The inability to quantify Eltonian niches through space and time has historically limited the assessment of Eltonian niche conservatism and the dynamics of foraging across populations. Consequently, the relative influence of endogenous factors like phylogeny versus exogenous features like environmental context has rarely been addressed.

We tested Eltonian niche conservatism using a paired design to compare foraging among four populations of American martens Martes americana and Pacific martens Martes caurina, morphologically and ecologically similar sister taxa that are allopatrically distributed throughout western North America. We developed a three‐stage isotopic framework and then quantified dietary niche overlap between the sister species and paired island‐mainland sites to assess the relative influence of endogenous (i.e., species) versus exogenous (i.e., environment) factors on Eltonian niches. First, we calculated pairwise dietary overlap in scaled δ‐space using standard ellipses. We then estimated proportional diets (“p‐space”) for individuals using isotopic mixing models and developed a novel utilization distribution overlap approach to quantify proportional dietary overlap. Lastly, we estimated population‐level proportional diets and quantified the differential use of functional prey groups across sites.

We detected no pairwise overlap of dietary niches in δ‐space, and distributions of individual diets in p‐space revealed little overlap in core diets across populations. All pairwise comparisons of individuals revealed significant differences in diet, and population‐level comparisons detected contrasting use of functional prey groups.

We developed a multi‐faceted isotopic framework to quantify Eltonian niches and found limited evidence of Eltonian niche conservatism across carnivore populations. Our findings are consistent with the growing recognition of dietary plasticity in consumers and suggest that consumer–resource dynamics are largely driven by exogenous environmental factors like land cover and community composition. These results illustrate the context‐dependent nature of foraging and indicate consumer functionality can be dynamic.

A plain language summary is available for this article.
Causes and mechanisms of synchronous succession trajectories in primeval Central European mixed Fagus sylvatica forests
Authors: Rey Fabian , Gobet Erika , Schwörer Christoph , Wey Othmar , Hafner Albert , Tinner Willy
Published: December 2018

Natural succession trajectories of Central European forest ecosystems are poorly understood due to the absence of long‐term observations and the pervasive effects of past human impacts on today's vegetation communities. This knowledge gap is significant given that currently forest ecosystems are expanding in Europe as a consequence of global change.

Annually laminated sediments were extracted from two small lowland lakes (Moossee 521 m a.s.l.; Burgäschisee 465 m a.s.l.) on the Swiss Plateau. We combine high‐resolution palaeoecological and quantitative analyses to assess changes in vegetation during the Neolithic. We test for regionally synchronous land‐use phases and plant successional patterns that may originate from complex interactions between human and climatic impacts.

Mixed Fagus sylvatica forests dominated the Swiss Plateau vegetation over millennia. During the period 6,500–4,200 cal year bp, pronounced forest disruptions accompanied by increased fire and agricultural activities occurred at c. 6,400–6,000 cal year bp, 5,750–5,550 cal year bp, around 5,400 cal year bp and at 5,100–4,600 cal year bp. Biodiversity increased during these land‐use phases, likely in response to the creation of new open habitats. After decades to centuries of land‐use, arboreal vegetation re‐expanded. In a first succession stage, heliophilous Corylus avellana shrubs were replaced by pioneer Betula trees. These open arboreal communities were out‐competed within 150–200 years by late‐successional F. sylvatica and Abies alba forests. Most strikingly, cross‐correlations show that these successions occurred synchronously (±11 years) and repeatedly over large areas (>1,000 km2) and millennia.

Synthesis. First notable human impact shaped the primeval mixed Fagus sylvatica forests in Central Europe from c. 6,800–6,500 cal year bp on. Agrarian societies were susceptible to climate changes and we hypothesize that climate‐induced, simultaneous agricultural expansion and contraction phases resulted in synchronous regional forest successions. Currently, forests are expanding in Central Europe as a result of land abandonment in marginal areas. Our results imply that mixed Fagus sylvatica forests with Abies alba and Quercus may re‐expand rapidly in these areas, if climate conditions will remain within the range of the mid‐Holocene climatic variability (with summers c. +1–2°C warmer than today).
Maternal anaemia and maternal, fetal, and neonatal outcomes in a prospective cohort study in India and Pakistan
Authors: Parks S , Hoffman MK , Goudar SS , Patel A , Saleem S , Ali SA , Goldenberg RL , Hibberd PL , Moore J , Wallace D , McClure EM , Derman RJ
Published: December 2018

Objective

To describe the association of maternal anaemia with maternal, fetal, and neonatal outcomes.

Design

Prospective cohort study.

Setting

Rural India and Pakistan.

Population

Pregnant women residing in the study catchment area.

Methods

We performed an analysis of a prospective pregnancy registry in which haemoglobin is commonly obtained as well as maternal, fetal, and neonatal outcomes for 42 days post‐delivery. Women 40 years or older who delivered before 20 weeks or had a haemoglobin level of <3.0 g/dl were excluded. Our primary exposure was maternal anaemia, which was categorised in keeping with World Health Organization criteria based on a normal (≥11 g/dl), mild (>10–10.9 g/dl), moderate (7–9.9 g/dl) or severe (<7 g/dl). haemoglobin level. The primary maternal outcome was maternal death, the primary fetal outcome was stillbirth, and the primary neonatal outcome was neonatal mortality <28 days.

Results

A total of 92 247 deliveries and 93 107 infants were included, of which 87.8% were born to mothers who were anaemic (mild 37.9%, moderate 49.1%, and severe 0.7%). Maternal mortality (number per 100 000) was not associated with anaemia: normal 124, mild 106, moderate 135, and severe 325 (P = 0.64). Fetal and neonatal mortality was associated with severe anaemia: stillbirth rate (n/1000)—normal 27.7, mild 25.8, moderate 30.1, and severe 90.9; P < 0.0001; 28‐day neonatal mortality (n/1000)—normal 24.7, mild 22.9, moderate 28.1, and severe 72.6 (P < 0.0001). Severe maternal anaemia was also associated with low birthweight (<2500 and <1500 g), preterm birth, and postpartum haemorrhage.

Conclusion

Severe maternal anaemia is associated with higher risks of poor maternal, fetal, and neonatal outcomes but other degrees of anaemia are not. Interventions directed at preventing severe anaemia in pregnant women should be considered.

Tweetable abstract

Severe maternal anaemia is associated with adverse fetal and neonatal outcomes in low/middle‐income countries.
Genomic sequence capture of haemosporidian parasites: Methods and prospects for enhanced study of host–parasite evolution
Authors: Barrow Lisa N. , Allen Julie M. , Huang Xi , Bensch Staffan , Witt Christopher C.
Published: December 2018

Avian malaria and related haemosporidians (Plasmodium, [Para]Haemoproteus and Leucocytoozoon) represent an exciting multihost, multiparasite system in ecology and evolution. Global research in this field accelerated after the publication in 2000 of PCR protocols to sequence a haemosporidian mitochondrial (mtDNA) barcode and the development in 2009 of an open‐access database to document the geographic and host ranges of parasite mtDNA haplotypes. Isolating haemosporidian nuclear DNA from bird hosts, however, has been technically challenging, slowing the transition to genomic‐scale sequencing techniques. We extend a recently developed sequence capture method to obtain hundreds of haemosporidian nuclear loci from wild bird samples, which typically have low levels of infection, or parasitemia. We tested 51 infected birds from Peru and New Mexico and evaluated locus recovery in light of variation in parasitemia, divergence from reference sequences and pooling strategies. Our method was successful for samples with parasitemia as low as ~0.02% (2 of 10,000 blood cells infected) and mtDNA divergence as high as 15.9% (one Leucocytozoonsample), and using the most cost‐effective pooling strategy tested. Phylogenetic relationships estimated with >300 nuclear loci were well resolved, providing substantial improvement over the mtDNA barcode. We provide protocols for sample preparation and sequence capture including custom probe sequences and describe our bioinformatics pipeline using atram 2.0, phyluce and custom Perl/Python scripts. This approach can be applied to thousands of avian samples that have already been found to have haemosporidian infections of at least moderate intensity, greatly improving our understanding of parasite speciation, biogeography and evolutionary dynamics.
Signal transmission at invaginating cone photoreceptor synaptic contacts following deletion of the presynaptic cytomatrix protein Bassoon in mouse retina
Authors: Babai Norbert , Gierke Kaspar , Müller Tanja , Regus‐Leidig Hanna , Brandstätter Johann H. , Feigenspan Andreas
Published: December 2018

Aim

A key feature of the mammalian retina is the segregation of visual information in parallel pathways, starting at the photoreceptor terminals. Cone photoreceptors establish synaptic contacts with On bipolar and horizontal cells at invaginating, ribbon‐containing synaptic sites, whereas Off bipolar cells form flat, non‐ribbon‐containing contacts. The cytomatrix protein Bassoon anchors ribbons at the active zone, and its absence induces detachment of ribbons from the active zone. In this study we investigate the impact of a missing Bassoon on synaptic transmission at the first synapse of the visual system.

Methods

Release properties of cone photoreceptors were studied in wild‐type and mutant mouse retinae with a genetic disruption of the presynaptic cytomatrix protein Bassoon using whole‐cell voltage‐clamp recordings. Light and electron microscopy revealed the distribution of Ca2+ channels and synaptic vesicles, respectively, in both mouse lines.

Results

Whole‐cell recordings from postsynaptic horizontal cells of the two mouse lines showed that the presence of Bassoon (and a ribbon) enhanced the rate of exocytosis during tonic and evoked release by increasing synaptic vesicle pool size and replenishment rate, while at the same time slowing synaptic vesicle release. Furthermore, the number of Cav1.4 channels and synaptic vesicles was significantly higher at wild‐type than at Bassoon mutant synaptic sites.

Conclusion

The results of our study demonstrate that glutamate release from cone photoreceptor terminals can occur independent of a synaptic ribbon, but seems restricted to active zones, and they show the importance of a the synaptic ribbon in sustained and spatially and temporally synchronized neurotransmitter release.
The survival of pathogenic bacteria and plant growth promoting bacteria during mesophilic anaerobic digestion in full‐scale biogas plants
Authors: Qi Guangdou , Pan Zhifei , Yamamoto Yuki , Andriamanohiarisoamanana Fetra Jules , Yamashiro Takaki , Iwasaki Masahiro , Ihara Ikko , Tangtaweewipat Suchon , Umetsu Kazutaka
Published: December 2018

The introduction of biogas plants is a promising way to recycle organic wastes with renewable energy production and reducing greenhouse gas. Application of anaerobic digestate as a fertilizer reduces the consumption of chemical fertilizers. In this study, the survival of pathogenic bacteria and plant growth promoting bacteria (PGPB) in two full‐scale biogas plants operated at mesophilic condition were investigated. Feedstock and anaerobic digestate samples were collected from biogas plants and bacteria load in samples were detected using standard dilution plate method. Pathogenic bacteria were reduced to not detected level through mesophilic digestion tank except for Campylobacter. However, it could be reduced by 98.7% through a sterilization tank. Bacillus was detected at 8.00 and 7.81 log10 CFU/g dry matter in anaerobic digestates, and it was also resistant to sterilization tank. Bacillus spp. is considered to be the safe bacteria that hold remarkable abilities for promoting plant growth. The results showed that treatment at biogas plants is effective to reduce pathogenic bacteria in dairy manure, and sterilization could further reduce the sanitary risks of pathogenic bacteria relating to anaerobic digestate application. Anaerobic digestates could also be utilized as bio‐fertilizer as the high load of plant growth promoting bacteria.
Evaluation of standardized ileal digestible lysine requirement for 8–20 kg pigs fed low crude protein diets
Authors: Zhou Hua , Chen Daiwen , Mao Xiangbing , He Jun , Yu Jie , Zheng Ping , Luo Junqiu , Gao Jun , Htoo John Khun , Yu Bing
Published: December 2018

Two experiments were conducted to determine the standardized ileal digestible lysine (SID Lys) requirement for weaned pigs fed with low crude protein (CP) diet. In Experiment 1, 144 pigs were fed a normal CP (20%) diet with 12.3 g/kg SID Lys and five low CP (18.5%) diets providing SID Lys levels of 9.8, 11.1, 12.3, 13.5, and 14.8 g/kg, respectively, for 28 days. Reducing dietary CP from 20% to 18.5% enhanced (p < 0.05) the growth performance. The average daily gain (ADG) and gain to feed ratio (G:F) increased (linear and quadratic; p < 0.05), serum urea nitrogen (SUN) decreased (linear and quadratic; p < 0.05) as SID Lys increased. The SID Lys levels required to maximize ADG and optimize G:F were 12.8 and 13.1 g/kg using a curvilinear plateau model, and to minimize SUN was 13.4 g/kg using a two‐slope broken‐line model, which averaged 13.1 g/kg SID Lys. In Experiment 2, 18 pigs were used in a 12‐day N balance trial and received the same diets of Experiment 1. Total N excretion was decreased when dietary CP reduced and further decreased when SID Lys increased. Collectively, 1.5% dietary CP reduction improved the growth performance and decreased the N excretion; the optimal SID Lys requirement was at 13.1 g/kg of 8–20 kg pigs fed with 18.5% CP diet.
Effects of substituting kraft pulp with corn silage on dry matter intake, ruminal mat formation, rumen fermentation, and rumination activity in non‐lactating cows
Authors: Izumi Kenichi , Tamura Tatuya , Fujii Ryoya , Nakatsuji Hiroki , Morita Shigeru
Published: December 2018

The present study examined the effects of substituting kraft pulp (KP) with corn silage (CS) on dry matter intake (DMI), ruminal mat and rumen fermentation characteristics, and rumination. Four non‐lactating, rumen‐cannulated Holstein cows were fed a CS diet comprising 36% grass silage (GS) and 64% CS or a KP diet comprising 36% GS, 57% KP, and 7% soybean meal. DMI was significantly lower in cows fed the KP diet than in those fed the CS diet (p < 0.05), whereas rumination time did not significantly differ between the treatments. Dry matter content in the rumen immediately before and 3 h after feeding was significantly higher in cows fed the KP diet than in those fed the CS diet (p < 0.05). The consistency and thickness of the ruminal mat did not significantly differ between the treatments. The ruminal mean retention time of feed particles tended to be longer in cows fed the KP diet than in those fed the CS diet (p < 0.10). The ruminal digestion rate of KP was comparable to that of GS and CS. Because ruminal mat was formed and rumination was stimulated, KP was considered to have the equivalent physical effectiveness as CS.
Examining engagement and achievement in learners with individual needs through robotic‐based teaching sessions
Authors: Hughes‐Roberts Thomas , Brown David , Standen Penny , Desideri Lorenzo , Negrini Marco , Rouame Aziz , Malavasi Massimiliano , Wager George , Hasson Conor
Published: December 2018

Research suggests that robotics can provide an engaging learning experience for learners with special educational needs. However, further work is required to explore the impact of robots within the classroom, particularly for learners with intellectual disabilities (ID). This paper seeks to further explore the potential effects of robots on such learners through examining engagement and goal achievement within teaching sessions. Eleven participants with ID were recruited from two countries to take part in the study using an ABAB design where the participants acted as their own controls. An appropriate learning goal for each participant was selected by the teacher and equivalent control sessions designed seeking to achieve the same learning goal but without the robot. Engagement, using eye‐gaze, learning goal achievement with and without help and goals not achieved provided the outcome measures from the sessions. This study found no significant difference between the robot and the control sessions for any of the outcome measures utilized suggesting robots are as effective as teaching tools as traditional methods. Through an increased sample size and a rigorously applied experimental protocol, this study provides new data and methodological considerations for further work based on the techniques applied in this study.

Practitioner Notes

What we already know about this topic

Robots can encourage engagement in the learning process for students with intellectual disabilities.

There is a lack of work examining the potential use of robots within formal learning.

There is a lack of work utilizing experimental protocols to study the use of robots.

What this paper adds

Knowledge of the impact of robots on learner engagement using eye‐gaze as an outcome measure.

Knowledge of the impact of robots on goal achievement in pursuit of structured learning objectives.

Knowledge of the experimental protocol and suggestions for refinement of the outcome measures in future trials.

Implications for practice and/or policy

Robots can be as effective as traditional teaching methods in promoting engagement in learning for students with intellectual disabilities.

Robots can be as effective as traditional teaching methods in the pursuit of learning goals for students with intellectual disabilities.

The effect of robots on learning appears to be variable depending on individual learner characteristics.
Movement segmentation and visual perturbation increase developmental differences in motor control and learning
Authors: Wu Jiamin , Chan John S. Y. , Yan Jin H.
Published: December 2018

We examined the developmental differences in motor control and learning of a two‐segment movement. One hundred and five participants (53 female) were divided into three age groups (7–8 years, 9–10 years and 19–27 years). They performed a two‐segment movement task in four conditions (full vision, fully disturbed vision, disturbed vision in the first movement segment and disturbed vision in the second movement segment). The results for movement accuracy and overall movement time show that children, especially younger children, are more susceptible to visual perturbations than adults. The adults’ movement time in one of the movement segments could be increased by disturbing the vision of the other movement segment. The children's movement time for the second movement segment increased when their vision of the first movement segment was disturbed. Disturbing the vision of the first movement segment decreased the percentage of central control of the second movement in younger children, but not in the other two age groups. The children's normalized jerk was more easily increased by visual perturbations. The children showed greater improvement after practice in the conditions of partial vision disturbance. As the participants’ age increased, practice tended to improve their feedforward motor control rather than their feedback motor control. These results suggest that children's central movement control improves with age and practice. We discuss the theoretical implications and practical significance of the differential effects of visual perturbation and movement segmentation upon motor control and learning from a developmental viewpoint.