bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia
Authors: Galetta Kristin M. , Chapman Kimberly R. , Essis Maritza D. , Alosco Michael L. , Gillard Danielle , Steinberg Eric , Dixon Diane , Martin Brett , Chaisson Christine E. , Kowall Neil W. , Tripodis Yorghos , Balcer Laura J. , Stern Robert A.
Published: June 2016

The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer’s Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.
The physics of stratum corneum lipid membranes
Authors: Das Chinmay , Olmsted Peter D.
Published: June 2016

The stratum corneum (SC), the outermost layer of skin, comprises rigid corneocytes (keratin-filled dead cells) in a specialized lipid matrix. The continuous lipid matrix provides the main barrier against uncontrolled water loss and invasion of external pathogens. Unlike all other biological lipid membranes (such as intracellular organelles and plasma membranes), molecules in the SC lipid matrix show small hydrophilic groups and large variability in the length of the alkyl tails and in the numbers and positions of groups that are capable of forming hydrogen bonds. Molecular simulations provide a route for systematically probing the effects of each of these differences separately. In this article, we present the results from atomistic molecular dynamics of selected lipid bilayers and multi-layers to probe the effect of these polydispersities. We address the nature of the tail packing in the gel-like phase, the hydrogen bond network among head groups, the bending moduli expected for leaflets comprising SC lipids and the conformation of very long ceramide lipids in multi-bilayer lipid assemblies.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Soft electrostatic repulsion in particle monolayers at liquid interfaces: surface pressure and effect of aggregation
Authors: Kralchevsky Peter A. , Danov Krassimir D. , Petkov Plamen V.
Published: June 2016

Non-densely packed interfacial monolayers from charged micrometre-sized colloid particles find applications for producing micropatterned surfaces. The soft electrostatic repulsion between the particles in a monolayer on an air/water (or oil/water) interface is mediated by the non-polar fluid, where Debye screening is absent and the distances between the particles are considerably greater than their diameters. Surface pressure versus area isotherms were measured at the air/water interface. The experiments show that asymptotically the surface pressure is inversely proportional to the third power of the interparticle distance. A theoretical model is developed that predicts not only the aforementioned asymptotic law but also the whole surface pressure versus area dependence. An increase in the surface pressure upon aggregation of charged particles in the interfacial monolayers is experimentally established. This effect is explained by the developed theoretical model, which predicts that the surface pressure should linearly increase with the square root of the particle mean aggregation number. The effect of added electrolyte on the aggregation is also investigated. The data lead to the conclusion that ‘limited aggregation’ exists in the monolayers of charged particles. In brief, the stronger electrostatic repulsion between the bigger aggregates leads to a higher barrier to their coalescence that, in turn, prevents any further aggregation, i.e. negative feedback is present.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
A phenomenological description of BslA assemblies across multiple length scales
Authors: Morris Ryan J. , Bromley Keith M. , Stanley-Wall Nicola , MacPhee Cait E.
Published: June 2016

Intrinsically interfacially active proteins have garnered considerable interest recently owing to their potential use in a range of materials applications. Notably, the fungal hydrophobins are known to form robust and well-organized surface layers with high mechanical strength. Recently, it was shown that the bacterial biofilm protein BslA also forms highly elastic surface layers at interfaces. Here we describe several self-assembled structures formed by BslA, both at interfaces and in bulk solution, over a range of length scales spanning from nanometres to millimetres. First, we observe transiently stable and highly elongated air bubbles formed in agitated BslA samples. We study their behaviour in a range of solution conditions and hypothesize that their dissipation is a consequence of the slow adsorption kinetics of BslA to an air–water interface. Second, we describe elongated tubules formed by BslA interfacial films when shear stresses are applied in both a Langmuir trough and a rheometer. These structures bear a striking resemblance, although much larger in scale, to the elongated air bubbles formed during agitation. Taken together, this knowledge will better inform the conditions and applications of how BslA can be used in the stabilization of multi-phase materials.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Curvature-driven assembly in soft matter
Authors: Liu Iris B. , Sharifi-Mood Nima , Stebe Kathleen J.
Published: June 2016

Control over the spatial arrangement of colloids in soft matter hosts implies control over a wide variety of properties, ranging from the system’s rheology, optics, and catalytic activity. In directed assembly, colloids are typically manipulated using external fields to form well-defined structures at given locations. We have been developing alternative strategies based on fields that arise when a colloid is placed within soft matter to form an inclusion that generates a potential field. Such potential fields allow particles to interact with each other. If the soft matter host is deformed in some way, the potential allows the particles to interact with the global system distortion. One important example is capillary assembly of colloids on curved fluid interfaces. Upon attaching, the particle distorts that interface, with an associated energy field, given by the product of its interfacial area and the surface tension. The particle’s capillary energy depends on the local interface curvature. We explore this coupling in experiment and theory. There are important analogies in liquid crystals. Colloids in liquid crystals elicit an elastic energy response. When director fields are moulded by confinement, the imposed elastic energy field can couple to that of the colloid to define particle paths and sites for assembly. By improving our understanding of these and related systems, we seek to develop new, parallelizable routes for particle assembly to form reconfigurable systems in soft matter that go far beyond the usual close-packed colloidal structures.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Manufacture of poly(methyl methacrylate) microspheres using membrane emulsification
Authors: Bux Jaiyana , Manga Mohamed S. , Hunter Timothy N. , Biggs Simon
Published: June 2016

Accurate control of particle size at relatively narrow polydispersity remains a key challenge in the production of synthetic polymer particles at scale. A cross-flow membrane emulsification (XME) technique was used here in the preparation of poly(methyl methacrylate) microspheres at a 1–10 l h
−1
scale, to demonstrate its application for such a manufacturing challenge. XME technology has previously been shown to provide good control over emulsion droplet sizes with careful choice of the operating conditions. We demonstrate here that, for an appropriate formulation, equivalent control can be gained for a precursor emulsion in a batch suspension polymerization process. We report here the influence of key parameters on the emulsification process; we also demonstrate the close correlation in size between the precursor emulsion and the final polymer particles. Two types of polymer particle were produced in this work: a solid microsphere and an oil-filled matrix microcapsule.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Non-ionic surfactant phase diagram prediction by recursive partitioning
Authors: Bell Gordon
Published: June 2016

A model has been designed to predict the phase which forms in water for a non-ionic surfactant, at a given concentration and temperature. The full phase diagram is generated by selecting enough data points to cover the region of interest. The model estimates the probability for each one of 10 possible phases and selects the one with the highest likelihood. The probabilities are based on the recursive partitioning of a dataset of 10 000 known observations. The model covers alkyl chain length and branching, ethoxylate head length and number, and end capping of one or more of the ethoxylate chains. The relationship between chemical structure, shape and phase behaviour is discussed.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Self-assembly of small peptide amphiphiles, the structures formed and their applications. (A foods and home and personal care perspective)
Authors: Frith W. J.
Published: June 2016

In this opinion piece, some specific challenges in the field of peptide self-assembly and gel formation are discussed. One major hurdle to finding functional small peptides is that there are a huge number of compounds to explore, which increases exponentially with the peptide size. This in itself creates a barrier to the discovery and application of materials, both through the difficulty of finding the peptides, and because protecting inventions also becomes more difficult. Recent work has shown that computer simulations may provide us a route to explore such a huge compound space; this is discussed along with the prospect for future developments. At the microscopic scale, many fibril-forming peptides form gels, apparently through a process of lateral association of primary self-assembled filaments, which leads to a relatively coarse-grained structure of rigid interconnects. However, recent data obtained on Fmoc-tyrosine gels appear to indicate that the gel microstructure is both more flexible and finer grained than previously believed. As such, it is clear that there is a considerable amount that is still not understood regarding this class of gel.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Some modification of cellulose nanocrystals for functional Pickering emulsions
Authors: Saidane Dorra , Perrin Emilie , Cherhal Fanch , Guellec Florian , Capron Isabelle
Published: June 2016

Cellulose nanocrystals (CNCs) are negatively charged colloidal particles well known to form highly stable surfactant-free Pickering emulsions. These particles can vary in surface charge density depending on their preparation by acid hydrolysis or applying post-treatments. CNCs with three different surface charge densities were prepared corresponding to 0.08, 0.16 and 0.64 e nm
−2
, respectively. Post-treatment might also increase the surface charge density. The well-known TEMPO-mediated oxidation substitutes C
6
-hydroxyl groups by C
6
-carboxyl groups on the surface. We report that these different modified CNCs lead to stable oil-in-water emulsions. TEMPO-oxidized CNC might be the basis of further modifications. It is shown that they can, for example, lead to hydrophobic CNCs with a simple method using quaternary ammonium salts that allow producing inverse water-in-oil emulsions. Different from CNC modification before emulsification, modification can be carried out on the droplets after emulsification. This way allows preparing functional capsules according to the layer-by-layer process. As a result, it is demonstrated here the large range of use of these biobased rod-like nanoparticles, extending therefore their potential use to highly sophisticated formulations.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Middle Pliocene hominin diversity:
Australopithecus deyiremeda
and
Kenyanthropus platyops
Authors: Spoor Fred , Leakey Meave G. , O'Higgins Paul
Published: June 2016

Geometric morphometric shape analyses are used to compare the maxillae of the
Kenyanthropus platyops
holotype KNM-WT 40000, the
Australopithecus deyiremeda
holotype BRT-VP-3/1 and other australopiths. The main aim is to explore the relationship between these two specimens and contemporary
Australopithecus afarensis
. Five landmarks placed on lateral views of the maxillae quantify key aspects of the morphology. Generalized Procrustes analyses and principal component analyses of the resulting shape coordinates were performed. The magnitudes of differences in shape and their significances were assessed using Procrustes and Mahalanobis' distances, respectively. Both KNM-WT 40000 and BRT-VP-3/1 show statistically significant differences in maxillary shape from
A. afarensis
, but do so in dissimilar ways. Moreover, the former differs more from
A. afarensis
than the latter. KNM-WT 40000 has a more anteriorly positioned zygomatic process with a transversely flat, and more orthognathic subnasal clivus. BRT-VP-3/1 has a more inferiorly positioned zygomatic process, a slightly retracted dental arcade, but without shortening of the anterior maxilla. These findings are consistent with previous conclusions that the two fossils should be attributed to separate species, rather than to
A. afarensis
, and with the presence of three contemporary hominin species in the Middle Pliocene of eastern Africa.

This article is part of the themed issue ‘Major transitions in human evolution’.
The origin and evolution ofHomo sapiens
Authors: Stringer Chris
Published: June 2016

If we restrict the use ofHomo sapiensin the fossil record to specimens which share a significant number of derived features in the skeleton with extantH. sapiens, the origin of our species would be placed in the African late middle Pleistocene, based on fossils such as Omo Kibish 1, Herto 1 and 2, and the Levantine material from Skhul and Qafzeh. However, genetic data suggest that we and our sister speciesHomo neanderthalensisshared a last common ancestor in the middle Pleistocene approximately 400–700 ka, which is at least 200 000 years earlier than the species origin indicated from the fossils already mentioned. Thus, it is likely that the African fossil record will document early members of thesapienslineage showing only some of the derived features of late members of the lineage. On that basis, I argue that human fossils such as those from Jebel Irhoud, Florisbad, Eliye Springs and Omo Kibish 2 do represent early members of the species, but variation across the African later middle Pleistocene/early Middle Stone Age fossils shows that there was not a simple linear progression towards latersapiensmorphology, and there was chronological overlap between different ‘archaic’ and ‘modern’ morphs. Even in the late Pleistocene within and outside Africa, we findH. sapiensspecimens which are clearly outside the range of Holocene members of the species, showing the complexity of recent human evolution. The impact on species recognition of late Pleistocene gene flow between the lineages of modern humans, Neanderthals and Denisovans is also discussed, and finally, I reconsider the nature of the middle Pleistocene ancestor of these lineages, based on recent morphological and genetic data.

This article is part of the themed issue ‘Major transitions in human evolution’.
A demographic perspective on the Middle to Later Stone Age transition from Nasera rockshelter, Tanzania
Authors: Tryon Christian A. , Faith J. Tyler
Published: June 2016

Increased population density is among the proposed drivers of the behavioural changes culminating in the Middle to Later Stone Age (MSA–LSA) transition and human dispersals from East Africa, but reliable archaeological measures of demographic change are lacking. We use Late Pleistocene–Holocene lithic and faunal data from Nasera rockshelter (Tanzania) to show progressive declines in residential mobility—a variable linked to population density—and technological shifts, the latter associated with environmental changes. These data suggest that the MSA–LSA transition is part of a long-term pattern of changes in residential mobility and technology that reflect human responses to increased population density, with dispersals potentially marking a complementary response to larger populations.

This article is part of the themed issue ‘Major transitions in human evolution’.
The transition to foraging for dense and predictable resources and its impact on the evolution of modern humans
Authors: Marean Curtis W.
Published: June 2016

Scientists have identified a series of milestones in the evolution of the human food quest that are anticipated to have had far-reaching impacts on biological, behavioural and cultural evolution: the inclusion of substantial portions of meat, the broad spectrum revolution and the transition to food production. The foraging shift to dense and predictable resources is another key milestone that had consequential impacts on the later part of human evolution. The theory of economic defendability predicts that this shift had an important consequence—elevated levels of intergroup territoriality and conflict. In this paper, this theory is integrated with a well-established general theory of hunter–gatherer adaptations and is used to make predictions for the sequence of appearance of several evolved traits of modern humans. The distribution of dense and predictable resources in Africa is reviewed and found to occur only in aquatic contexts (coasts, rivers and lakes). The palaeoanthropological empirical record contains recurrent evidence for a shift to the exploitation of dense and predictable resources by 110 000 years ago, and the first known occurrence is in a marine coastal context in South Africa. Some theory predicts that this elevated conflict would have provided the conditions for selection for the hyperprosocial behaviours unique to modern humans.

This article is part of the themed issue ‘Major transitions in human evolution’.
The empirical case against the ‘demographic turn’ in Palaeolithic archaeology
Authors: Collard Mark , Vaesen Krist , Cosgrove Richard , Roebroeks Wil
Published: June 2016

Recently, it has become commonplace to interpret major transitions and other patterns in the Palaeolithic archaeological record in terms of population size. Increases in cultural complexity are claimed to result from increases in population size; decreases in cultural complexity are suggested to be due to decreases in population size; and periods of no change are attributed to low numbers or frequent extirpation. In this paper, we argue that this approach is not defensible. We show that the available empirical evidence does not support the idea that cultural complexity in hunter–gatherers is governed by population size. Instead, ethnographic and archaeological data suggest that hunter–gatherer cultural complexity is most strongly influenced by environmental factors. Because all hominins were hunter–gatherers until the Holocene, this means using population size to interpret patterns in the Palaeolithic archaeological record is problematic. In future, the population size hypothesis should be viewed as one of several competing hypotheses and its predictions formally tested alongside those of its competitors.

This article is part of the themed issue ‘Major transitions in human evolution’.
Changes in northeast African hydrology and vegetation associated with Pliocene–Pleistocene sapropel cycles
Authors: Rose Cassaundra , Polissar Pratigya J. , Tierney Jessica E. , Filley Timothy , deMenocal Peter B.
Published: June 2016

East African climate change since the Late Miocene consisted of persistent shorter-term, orbital-scale wet–dry cycles superimposed upon a long-term trend towards more open, grassy landscapes. Either or both of these modes of palaeoclimate variability may have influenced East African mammalian evolution, yet the interrelationship between these secular and orbital palaeoclimate signals remains poorly understood. Here, we explore whether the long-term secular climate change was also accompanied by significant changes at the orbital-scale. We develop northeast African hydroclimate and vegetation proxy data for two 100 kyr-duration windows near 3.05 and 1.75 Ma at ODP Site 967 in the eastern Mediterranean basin, where sedimentation is dominated by eastern Sahara dust input and Nile River run-off. These two windows were selected because they have comparable orbital configurations and bracket an important increase in East African C
4
grasslands. We conducted high-resolution (2.5 kyr sampling) multiproxy biomarker, H- and C-isotopic analyses of plant waxes and lignin phenols to document orbital-scale changes in hydrology, vegetation and woody cover for these two intervals. Both intervals are dominated by large-amplitude, precession-scale (approx. 20 kyr) changes in northeast African vegetation and rainfall/run-off. The δ
13
C
wax
values and lignin phenol composition record a variable but consistently C
4
grass-dominated ecosystem for both intervals (50–80% C
4
). Precessional δD
wax
cycles were approximately 20–30‰ in peak-to-peak amplitude, comparable with other δD
wax
records of the Early Holocene African Humid Period. There were no significant differences in the means or variances of the δD
wax
or δ
13
C
wax
data for the 3.05 and 1.75 Ma intervals studied, suggesting that the palaeohydrology and palaeovegetation responses to precessional forcing were similar for these two periods. Data for these two windows suggest that the eastern Sahara did not experience the significant increase in C
4
vegetation that has been observed in East Africa over this time period. This observation would be consistent with a proposed mechanism whereby East African precipitation is reduced, and drier conditions established, in response to the emergence of modern zonal sea surface temperature gradients in the tropical oceans between 3 and 2 Ma.

This article is part of the themed issue ‘Major transitions in human evolution’.
The evolution of body size and shape in the human career
Authors: Jungers William L. , Grabowski Mark , Hatala Kevin G. , Richmond Brian G.
Published: June 2016

Body size is a fundamental biological property of organisms, and documenting body size variation in hominin evolution is an important goal of palaeoanthropology. Estimating body mass appears deceptively simple but is laden with theoretical and pragmatic assumptions about best predictors and the most appropriate reference samples. Modern human training samples with known masses are arguably the ‘best’ for estimating size in early bipedal hominins such as the australopiths and all members of the genus
Homo
, but it is not clear if they are the most appropriate priors for reconstructing the size of the earliest putative hominins such as
Orrorin
and
Ardipithecus
. The trajectory of body size evolution in the early part of the human career is reviewed here and found to be complex and nonlinear. Australopith body size varies enormously across both space and time. The pre-
erectus
early
Homo
fossil record from Africa is poor and dominated by relatively small-bodied individuals, implying that the emergence of the genus
Homo
is probably not linked to an increase in body size or unprecedented increases in size variation. Body size differences alone cannot explain the observed variation in hominin body shape, especially when examined in the context of small fossil hominins and pygmy modern humans.

This article is part of the themed issue ‘Major transitions in human evolution’.
Towards an integration of deep learning and neuroscience
Authors: Marblestone Adam Henry , Wayne Greg , Kording Konrad P
Published: June 2016

Neuroscience has focused on the detailed implementation of computation, studying neural codes, dynamics and circuits. In machine learning, however, artificial neural networks tend to eschew precisely designed codes, dynamics or circuits in favor of brute force optimization of a cost function, often using simple and relatively uniform initial architectures. Two recent developments have emerged within machine learning that create an opportunity to connect these seemingly divergent perspectives. First, structured architectures are used, including dedicated systems for attention, recursion and various forms of short- and long-term memory storage. Second, cost functions and training procedures have become more complex and are varied across layers and over time. Here we think about the brain in terms of these ideas. We hypothesize that (1) the brain optimizes cost functions, (2) these cost functions are diverse and differ across brain locations and over development, and (3) optimization operates within a pre-structured architecture matched to the computational problems posed by behavior. Such a heterogeneously optimized system, enabled by a series of interacting cost functions, serves to make learning data-efficient and precisely targeted to the needs of the organism. We suggest directions by which neuroscience could seek to refine and test these hypotheses.
Sacral agenesis: A pilot whole exome sequencing and copy number study
Authors: Porsch Robert M. , Merello Elisa , De Marco Patrizia , Cheng Guo , Rodriguez Laura , So Manting , Sham Pak C. , Tam Paul K. , Carpa Valeria , Cherny Stacey S. , Garcia-Barcelo Maria-Mercè , Campbell Desmond D.
Published: June 2016

Background

Caudal regression syndrome (CRS) or sacral agenesis is a rare congenital disorder characterized by a constellation of congenital caudal anomalies affecting the caudal spine and spinal cord, the hindgut, the urogenital system, and the lower limbs. CRS is a complex condition, attributed to an abnormal development of the caudal mesoderm, likely caused by the effect of interacting genetic and environmental factors. A well-known risk factor is maternal type 1 diabetes.

Results

In this pilot study, exome sequencing and copy number variation (CNV) analyses of 4 CRS trios implicate a number of candidate genes, includingMORN1,ZNF330,CLTCL1andPDZD2.De novomutations were found inSPTBN5,MORN1andZNF330and inherited predicted damaging mutations inPDZD2(homozygous) andCLTCL1(compound heterozygous) as well as in CRS-related genesPTEN(heterozygous) andVANGL1(heterozygous). In addition, a compound heterozygous mutation inGLTSCR2, a direct regulator ofPTENwas identified.

Two CNV deletions, onede novo(chr3q13.13) and one homozygous (chr8p23.2), were detected in one of our CRS patients. These deletions overlapped with CNVs previously reported in patients with similar phenotype.

Conclusion

Despite the genetic diversity and the complexity of the phenotype, this pilot study identified genetic features common across CRS patients.
Maintaining proton homeostasis is an essential role of glucose metabolism in cell survival
Authors: Cui Yanfen , Wang Yuanyuan , Xing Pan , Qiu Li , Liu Miao , Wang Xin , Ying Guoguang , Li Binghui
Published: June 2016

Aerobic glycolysis, termed “the Warburg Effect”, supports cell proliferation, and glucose deprivation directly elicits necrosis or shifts stimuli-induced apoptosis to necrosis. However, how glucose metabolism regulates cell survival or death choice remains largely unclear. Here we use our recently developed method to monitor in real-time cellular apoptosis and necrosis, and uncover a metabolic homeostasis linked to cell death control. We show that glucose metabolism is the major source to maintain both intracellular and extracellular proton homeostasis. Glucose deficiency leads to lack of proton provision, which provokes a compensatory lysosomal proton efflux and resultant increased lysosomal pH. This lysosomal alkalinization can trigger necrosis. Furthermore, artificial proton supplement enables cells to survive glucose deprivation. Taken together, our results reveal a critical role of glucose metabolism in maintaining cellular microenvironment, and provide a better understanding of the essential requirement of aerobic glycolysis for proliferating cells whose active anabolism consumes a great many protons.
Clustered brachiopod Hox genes are not expressed collinearly and are associated with lophotrochozoan novelties
Authors: Schiemann Sabrina M. , Martín-Durán José M. , Børve Aina , Vellutini Bruno C. , Passamaneck Yale J. , Hejnol Andreas
Published: June 2016

Temporal collinearity is often regarded as the force preserving Hox clusters in vertebrate genomes. Studies that combine genomic and gene expression data in invertebrates would allow generalizing this observation across all animals, but are scarce, particularly within Lophotrochozoa (e.g., snails and segmented worms). Here, we use two brachiopod species –Terebratalia transversa,Novocrania anomala– to characterize the complement, cluster and expression of their Hox genes.T. transversahas an ordered, split cluster with ten genes (lab,pb,Hox3,dfd,scr,lox5,antp,lox4,post2,post1), whileN. anomalahas nine (missingpost1). Ourin situhybridization, qPCR and stage specific transcriptomic analyses show that brachiopod Hox genes are neither strictly temporally nor spatially collinear; onlypb(inT. transversa),Hox3anddfd(in both brachiopods) show staggered mesodermal expression. The spatial expression of the Hox genes in both brachiopod species correlates with their morphology and demonstrates cooption of Hox genes in the chaetae and shell fields, two major lophotrochozoan morphological novelties. The shared and specific expression of a subset of Hox genes,ArxandZicorthologs in chaetae and shell-fields between brachiopods, mollusks, and annelids supports the deep conservation of the molecular basis forming these lophotrochozoan hallmarks. Our findings challenge that collinearity alone preserves lophotrochozoan Hox clusters, indicating that additional genomic traits need to be considered in understanding Hox evolution.
Local and thalamic origins of ongoing and sensory evoked cortical correlations
Authors: Cohen-Kashi Malina Katayun , Mohar Boaz , Rappaport Akiva N. , Liu Miao
Published: June 2016

Thalamic inputs of layer 4 (L4) cells in sensory cortices are outnumbered by local connections. Thus, it was suggested that robust sensory response in L4 emerges due to synchronized thalamic activity. In order to investigate the role of both inputs in generation of cortical synchronization, we isolated the thalamic excitatory inputs of cortical cells by optogenetically silencing cortical firing. In anesthetized mice, we measured the correlation between isolated thalamic synaptic inputs of simultaneously patched nearby L4 cells of the barrel cortex. In contrast to correlated activity of excitatory synaptic inputs in the intact cortex, isolated thalamic inputs exhibit lower variability and asynchronous spontaneous and sensory evoked inputs. These results were further supported in awake mice when we recorded the excitatory inputs of individual cortical cells simultaneously with the local field potential (LFP) in a nearby site. Our results therefore indicate that cortical synchronization emerges by intracortical coupling.
The CD4+ T cell regulatory network mediates inflammatory responses during acute hyperinsulinemia: a simulation study
Authors: Martinez-Sanchez M.E. , Hiriart M. , Alvarez-Buylla E. R.
Published: June 2016

Obesity is linked to insulin resistance, high insulin levels, chronic inflammation, and alterations in the behavior of CD4+ T cells. Despite the biomedical importance of this condition, the system-level mechanisms that alter CD4+ T cell differentiation and plasticity are not well understood. We model how hyperinsulinemia alters the dynamics of the CD4+ T regulatory network, and this, in turn, modulates cell differentiation and plasticity. Different polarizing micro-environments are simulated under basal and high levels of insulin to assess impacts on cell-fate attainment and robustness in response to transient perturbations. In the presence of high levels of insulin Th1 and Th17 become more stable to transient perturbations and their basin sizes are augmented, IL10 producing regulatory T cells become less stable or disappear, while TGFB producing cells remain unaltered. Hence, the model provides a dynamic system-level explanation for the documented apparently paradoxical role of TGFB in both inflammation and regulation of immune responses and the emergence of the adipose Treg phenotype. Furthermore, our simulations provide novel predictions on the impact of the micro-environment in the coexistence of the different cell types, proposing that in pro-Th1, pro-Th2 and pro-Th17 environments effector and regulatory cells can coexist, but that high levels of insulin severely affect regulatory cells, specially in a pro-Th17 environment. This work provides a system-level formal and dynamic framework to integrate further experimental data in the study of complex inflammatory diseases.
Linking comparative genomics and environmental distribution patterns of microbial populations through metagenomics
Authors: Delmont Tom O. , Eren A. Murat
Published: June 2016

Combining well-established practices from comparative genomics and the emerging opportunities from assembly-based metagenomics can enhance the utility of increasing number of metagenome-assembled genomes (MAGs). Here we used protein clustering to characterize 48 MAGs and 10 cultivars based on their entire gene content, and linked this information to their environmental distribution patterns to better understand the microbial response to the 2010 Deepwater Horizon oil spill in the Gulf of Mexico coastline. Our results suggest that while most oil-associated bacterial populations originated from the ocean, a few actually emerged from the sand rare biosphere. These new findings suggest that there are considerable benefits to employ approaches from comparative genomics to study the whole content of newly identified genomes, and the investigation of emerging patterns in the environmental context can augment the efficacy of assembly-based metagenomic surveys.
Intrinsic functional architecture of the macaque dorsal and ventral lateral frontal cortex
Authors: Goulas Alexandros , Stiers Peter , Hutchison R. Matthew , Everling Stefan , Petrides Michael , Margulies Daniel S.
Published: June 2016

Investigations of the cellular and connectional organization of the lateral frontal cortex (LFC) of the macaque monkey provide indispensable knowledge for generating hypotheses about the human LFC. However, despite numerous investigations, there are still debates on the organization of this brain region. In vivo neuroimaging techniques such as resting-state fMRI can be used to define the functional circuitry of brain areas producing results largely consistent with gold-standard invasive tract-tracing techniques and offering the opportunity for cross-species comparison within the same modality. Our results using resting-state fMRI from macaque monkeys to uncover the intrinsic functional architecture of the LFC corroborate previous findings and inform current debates. Specifically, we show that i) the region in the midline and anterior to the superior arcuate sulcus is divided in two areas separated by the posterior supraprincipal dimple; ii) the cytoarchitectonically defined area 6DC/F2 contains two connectional divisions; and, iii) a distinct area occupies the cortex around the spur of the arcuate, updating what was previously proposed to be the border between dorsal and ventral motor/premotor areas. Within the ventral LFC specifically, the derived parcellation clearly suggests the presence of distinct areas i) with a somatomotor/orofacial connectional signature (putative area 44), ii) with an occulomotor connectional signature (putative frontal eye fields), and iii) premotor areas possibly hosting laryngeal and arm representations. Our results illustrate in detail the intrinsic functional architecture of the macaque LFC, thus providing valuable evidence for debates on its organization.
Genetic and transcriptional analysis of human host response to healthy gut microbiome
Authors: Richards Allison L. , Burns Michael B. , Alazizi Adnan , Barreiro Luis B. , Pique-Regi Roger , Blekhman Ran , Luca Francesca
Published: June 2016

Many studies have demonstrated the importance of the gut microbiome in healthy and disease states. However, establishing the causality of host-microbiome interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiome in human cells and to shed light on the molecular mechanisms underlying host-gut microbiome interactions. In primary human colonic epithelial cells, we identified over 6,000 genes that change expression at various time points following co-culturing with the gut microbiome of a healthy individual. The differentially expressed genes are enriched for genes associated with several microbiome-related diseases, such as obesity and colorectal cancer. In addition, our experimental system allowed us to identify 87 host SNPs that show allele-specific expression in 69 genes. Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is conditional on the exposure to the microbiome. Of these 12 genes, eight have been associated with diseases linked to the gut microbiome, specifically colorectal cancer, obesity and type 2 diabetes. Our study demonstrates a scalable approach to study host-gut microbiome interactions and can be used to identify putative mechanisms for the interplay between host genetics and microbiome in health and disease.
X-ray nanotomography and focused-ion-beam sectioning for quantitative three-dimensional analysis of nanocomposites
Authors: Shuck Christopher E. , Frazee Mathew , Gillman Andrew , Beason Matthew T. , Gunduz Ibrahim Emre , Matouš Karel , Winarski Robert , Mukasyan Alexander S.
Published: June 2016

Knowing the relationship between three-dimensional structure and properties is paramount for complete understanding of material behavior. In this work, the internal nanostructure of micrometer-size (∼10 µm) composite Ni/Al particles was analyzed using two different approaches. The first technique, synchrotron-based X-ray nanotomography, is a nondestructive method that can attain resolutions of tens of nanometers. The second is a destructive technique with sub-nanometer resolution utilizing scanning electron microscopy combined with an ion beam and `slice and view' analysis, where the sample is repeatedly milled and imaged. The obtained results suggest that both techniques allow for an accurate characterization of the larger-scale structures, while differences exist in the characterization of the smallest features. Using the Monte Carlo method, the effective resolution of the X-ray nanotomography technique was determined to be ∼48 nm, while focused-ion-beam sectioning with `slice and view' analysis was ∼5 nm.
Atomic structure and phason modes of the Sc–Zn icosahedral quasicrystal
Authors: Yamada Tsunetomo , Takakura Hiroyuki , Euchner Holger , Pay Gómez Cesar , Bosak Alexei , Fertey Pierre , de Boissieu Marc
Published: June 2016

The detailed atomic structure of the binary icosahedral (i) ScZn7.33quasicrystal has been investigated by means of high-resolution synchrotron single-crystal X-ray diffraction and absolute scale measurements of diffuse scattering. The average atomic structure has been solved using the measured Bragg intensity data based on a six-dimensional model that is isostructural to the i-YbCd5.7one. The structure is described with a quasiperiodic packing of large Tsai-type rhombic triacontahedron clusters and double Friauf polyhedra (DFP), both resulting from a close-packing of a large (Sc) and a small (Zn) atom. The difference in chemical composition between i-ScZn7.33and i-YbCd5.7was found to lie in the icosahedron shell and the DFP where in i-ScZn7.33chemical disorder occurs on the large atom sites, which induces a significant distortion to the structure units. The intensity in reciprocal space displays a substantial amount of diffuse scattering with anisotropic distribution, located around the strong Bragg peaks, that can be fully interpreted as resulting from phason fluctuations, with a ratio of the phason elastic constantsK2/K1= −0.53,i.e.close to a threefold instability limit. This induces a relatively large perpendicular (or phason) Debye–Waller factor, which explains the vanishing of `high-Qperp' reflections.
Residue contacts predicted by evolutionary covariance extend the application ofab initiomolecular replacement to larger and more challenging protein folds
Authors: Simkovic Felix , Thomas Jens M. H. , Keegan Ronan M. , Winn Martyn D. , Mayans Olga , Rigden Daniel J.
Published: June 2016

For many protein families, the deluge of new sequence information together with new statistical protocols now allow the accurate prediction of contacting residues from sequence information alone. This offers the possibility of more accurateab initio(non-homology-based) structure prediction. Such models can be used in structure solution by molecular replacement (MR) where the target fold is novel or is only distantly related to known structures. Here,AMPLE, an MR pipeline that assembles search-model ensembles fromab initiostructure predictions (`decoys'), is employed to assess the value of contact-assistedab initiomodels to the crystallographer. It is demonstrated that evolutionary covariance-derived residue–residue contact predictions improve the quality ofab initiomodels and, consequently, the success rate of MR using search models derived from them. For targets containing β-structure, decoy quality and MR performance were further improved by the use of a β-strand contact-filtering protocol. Such contact-guided decoys achieved 14 structure solutions from 21 attempted protein targets, compared with nine for simpleRosettadecoys. Previously encountered limitations were superseded in two key respects. Firstly, much larger targets of up to 221 residues in length were solved, which is far larger than the previously benchmarked threshold of 120 residues. Secondly, contact-guided decoys significantly improved success with β-sheet-rich proteins. Overall, the improved performance of contact-guided decoys suggests that MR is now applicable to a significantly wider range of protein targets than were previously tractable, and points to a direct benefit to structural biology from the recent remarkable advances in sequencing.
Disodium hydrogen citrate sesquihydrate, Na2HC6H5O7(H2O)1.5
Authors: Rammohan Alagappa , Sarjeant Amy A. , Kaduk James A.
Published: June 2016

The crystal structure of disodium hydrogen citrate sesquihydrate, 2Na2+·C6H6O72−·1.5H2O, has been solved and refined using laboratory X-ray single-crystal diffraction data, and optimized using density functional techniques. The asymmetric unit contains two independent hydrogen citrate anions, four sodium cations and three water molecules. The coordination polyhedra of the cations (three with a coordination number of six, one with seven) share edges to form isolated 8-rings. The un-ionized terminal carboxylic acid groups form very strong hydrogen bonds to non-coordinating O atoms, with O...O distances of 2.46 Å.
Crystal structure of (E)-2-[(2-bromopyridin-3-yl)methylidene]-6-methoxy-3,4-dihydronaphthalen-1(2H)-one and 3-[(E)-(6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-ylidene)methyl]pyridin-2(1H)-one
Authors: Zingales Sarah K. , Moore Morgan E. , Goetz Andrew D. , Padgett Clifford W.
Published: June 2016

The title compounds C17H14BrNO2, (I), and C17H15NO3, (II), were obtained from the reaction of 6-methoxy-3,4-dihydro-2H-naphthalen-1-one and 2-bromonicotinaldehyde in ethanol. Compound (I) was the expected product and compound (II) was the oxidation product from air exposure. In the crystal structure of compound (I), there are no short contacts or hydrogen bonds. The structure does display π–π interactions between adjacent benzene rings and adjacent pyridyl rings. Compound (II) contains two independent molecules,AandB, in the asymmetric unit; both are non-planar, the dihedral angles between the methoxybenzene and 1H-pyridin-2-one mean planes being 35.07 (9)° inAand 35.28 (9)°inB. In each molecule, the 1H-pyridin-2-one unit participates in intermolecular N—H...O hydrogen bonding to another molecule of the same type (AtoAorBtoB). The structure also displays π–π interactions between the pyridyl and the benzene rings of non-equivalent molecules (viz.,AtoBandBtoA).
Crystal structure of dimethyl 3,4,5,6-tetraphenylcyclohexa-3,5-diene-1,2-dicarboxylate
Authors: Greenberg Fred H. , Nazarenko Alexander Y.
Published: June 2016

In the title compound, C34H28O4, the cyclohexadiene ring has a screw-boat conformation with a torsion angle between the double bonds being on averageca15° [15.2 (3) and −15.3 (3) in the two independent molecules]. All four phenyl rings in both molecules are arranged in a propeller-like conformation. The two molecules exhibit S,R- andR,S- chirality, respectively, and are connectedviaC—H...O intermolecular interactions. In turn, these weakly bound dimers form the molecular crystal.
2-Chloro-N-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]acetamide
Authors: Saravanan K. , Priya K. , Anand S. Athavan Alias , Kabilan S. , Selvanayagam S.
Published: June 2016

In the title acetamide, C11H8Cl2N2OS, the chlorophenyl ring is oriented at an angle of 7.1 (1)° with respect to the thiazole ring. In the crystal, molecules are linkedviaC—H...O intermolecular interactions, formingC(10) chains propagating in a zigzag manner along thebaxis.
Methyl 8-oxo-2-phenyl-1-oxaspiro[4.5]deca-2,6,9-triene-3-carboxylate
Authors: Gomes Ralph C. , Simoni Deborah de Alencar , Coelho Fernando
Published: June 2016

The title compound, C17H14O4, is a 5/6 spiro-ring fused system, where the five- and six-membered rings are inclined to one another by 89.79 (5)° at the spiro-carbon. In the crystal, non-classical C—H ... O hydrogen bonds form inversion dimers and connect the molecules into chains along [001].