Spatio-temporal organization during group formation in rats.

In the present study, the dynamic process of group formation in eight unfamiliar rats was followed in order to reveal how the group becomes oriented together in time and space, in light of the complexity that accompanies grouping. The focus was on who, where, and when joined together. We found that rats preferred to be in companionship over remaining alone, with all the rats gradually shifting to share the same location as a resting place. Group formation can be viewed as a tri-phasic process, with some rats gradually becoming more social than others, and thus playing a key role in group formation. Starting with seemingly independent traveling, the rats gradually converged to share the same location as a terminal (home base) for roundtrips in the arena. Because such a terminal is considered as the organizer of an individual's spatial behavior, the shared home-base location may be viewed as the organizer of spatial behavior of the entire group. Despite huddling together, the rats continued to travel alone or in duos throughout the 3 h of testing. We suggest that resting together and traveling alone or in duos enabled the maintenance of communal relationship while reducing the complexity involved in traveling in relatively large groups. Taken together, the present results demonstrate the dynamic process during which unfamiliar rats shift from independent to group spatial behavior.

Hairline fractures following volar plating of the distal radius: a recently recognized hardware-related complication.

OBJECTIVES: Intraoperative hairline longitudinal fractures were recently reported in association with distal radius volar plating. Our aim was to further analyze this newly described complication. METHODS: A retrospective radiographic and chart review was performed on 225 patients who underwent distal radius plating between June 2013 and June 2015. The Acu-Loc/Acu-Loc2© plating system (Acumed, Hillsboro, OR, USA) was used in 208 cases, and the VariAx© plating system (Stryker, Kalamazoo, MI, USA) was used in 17 cases. Three independent reviewers performed a blind evaluation of all relevant radiographs for the occurrence of longitudinal fractures around the plate, and validity was considered only when there was agreement among all three of them. RESULTS: Hairline longitudinal fractures were identified in 57 cases (25%), 55 with the Acu-Loc/Acu-Loc2© system and 2 with the VariAx© system. All fractures occurred with volar plating. Fracture occurrence was associated with age over 59 years, female gender, extra-articular fractures, and the use of Hexalobe screws (Acu-Loc/Acu-Loc2© system). CONCLUSIONS: We believe that the source of fracture occurrence lies within the screw design and that better screw design and possibly tapping in patients at risk may reduce the occurrence of intraoperative hairline longitudinal fractures. Further clinical and biomechanical research is needed to better understand this newly reported complication.

Social spatial cognition in rat tetrads: how they select their partners and their gathering places.

Spatial organization is an extensively studied field, in which most of the research has been on how the physical environment is perceived and conceived. There is a consensus that physical attributes such as environment geometry and landmarks are key factors in shaping spatial cognition. Nevertheless, the numerous studies of spatial behavior have usually been carried out on individuals, thereby overlooking the possible impact of the social environment. In the present study, rats were exposed to an unfamiliar open-field, first alone and then in tetrads of unfamiliar individuals, in order to monitor and analyze when and how their individual spatial behavior converged to a group spatial behavior. We found that the unfamiliar rats spent most of their time in companionship, first with preferred partners and ultimately as a quartet. Specifically, group formation was dynamic and gradual, with the rats first forming duos, then trios, and ultimately a quartet. Trios and quartets mostly huddled in the same specific corner that became a shared home base, from which they took solo or duo roundtrips to the arena. The present study unveils how, by means of gradual interactions among self, place, and conspecifics, four unfamiliar rats organized together their social spatial behavior.

"Shall two walk together except they be agreed?" Spatial behavior in rat dyads.

When animals explore an unfamiliar environment, they gather information that enables them to form a cognitive representation of that environment and to use it subsequently in traveling there. In the present study, rats were tested in a large arena as singles, then in dyads, and finally, again as singles, in order to examine the effect of the social environment on exploration. Traveling in dyads facilitated exploration compared to the behavior of the same rats when they explored alone. Specifically, each rat in a dyad traveled a greater distance with higher velocity and took wider turns compared to its lone traveling. Moreover, rats in dyads spent a long time together, shared a home base, and when traveling in the same direction, one rat was leading the other. In addition to exploring the same locations, leaders explored more "private" locations, not visited by the other rat. Features of the dyad behavior were carried over to the behavior of the same rats when tested as individuals, after the dyad trial. Compared to singles, dyads represent the first step toward grouping, and it is suggested that the conspicuous change between the behavior of a rat as single compared to its behavior when in a dyad should be greater than any further changes that may occur in spatial cognitive behavior of triads, quartets, or larger groups. In other words, while the present changes in spatial cognition observed in dyads represent a small step toward grouping, they are a giant leap for the individual.

The half-life of a "teachable moment": The case of Nobel laureates.

Some science-related events stimulate public interest, and create a teachable moment in which the underlying science temporarily becomes more interesting. Here, media attention, expressed by Google News reference volume, and changes in information seeking behavior, expressed by Google Trends, were used to estimate the length of a teachable moment for 2004-2011 Nobel Prize announcements. On average, Nobel Prize announcements attracted the attention of online users for no longer than a week. News coverage declined slower and occasionally displayed seasonal trends. There was a 50% drop in searches between the day of the announcement and the following day, and an analogous pattern for news coverage of all laureates varying for different disciplines. The affordances of using publicly available online data to identify the most effective teachable moments relating to science are discussed.

Colon stem cell and crypt dynamics exposed by cell lineage reconstruction.

Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems.

Tactile cues compensate for unbalanced vestibular cues during progression on inclined surfaces.

A previous study demonstrated that rodents on an inclined square platform traveled straight vertically or horizontally and avoided diagonal travel. Through behavior they aligned their head with the horizontal plane, acquiring similar bilateral vestibular cues - a basic requirement for spatial orientation and a salient feature of animals in motion. This behavior had previously been shown to be conspicuous in Tristram's jirds. Here, therefore jirds were challenged by testing their travel behavior on a circular arena inclined at 0°-75°. Our hypothesis was that if, as typical to rodents, the jirds would follow the curved arena wall, they would need to display a compensating mechanism to enable traveling in such a path shape, which involves a tilted frontal head axis and unbalanced bilateral vestibular cues. We found that with the increase in inclination, the jirds remained more in the lower section of the arena (geotaxis). When tested on the steep inclinations, however, their travel away from the arena wall was strictly straight up or down, in contrast to the curved paths that followed the circular arena wall. We suggest that traveling along a circular path while maintaining contact with the wall (thigmotaxis), provided tactile information that compensated for the unbalanced bilateral vestibular cues present when traveling along such curved inclined paths. In the latter case, the frontal plane of the head was in a diagonal posture in relation to gravity, a posture that was avoided when traveling away from the wall.

Metabolically Healthy Obesity Is a Misnomer: Components of the Metabolic Syndrome Linearly Increase with BMI as a Function of Age and Gender.

OBJECTIVES: We aimed to examine the relationships between body mass index (BMI) and metabolic syndrome (MS) components as a function of age and gender across weight categories. METHODS: This cross-sectional study included 19,328 subjects who participated in a health-screening program. We analyzed 14,093 apparently healthy subjects with a BMI ≥ 18.5 kg/m2 (ranging from 18.5 to 46 kg/m2). RESULTS: At a BMI of 18.5 kg/m2, 16% of subjects had one or more MS components (MS ≥ 1). The number of MS components increased linearly with BMI. The most prevalent components for MS1-4 were hypertension (in men) and increased waist circumference (in women). Among 6391 non-obese subjects with MS = 0, there was a linear increase in blood pressure, glucose, and triglycerides, as well as a decline in high-density lipoprotein cholesterol, as BMI increased. In 2087 subjects with a BMI ≥ 30 kg/m2, a true normometabolic state (MS = 0) was observed in only 7.5%, declining to less than 1% at a BMI ≥ 36 kg/m2 (ATP criteria). Women were metabolically protected relative to men between the ages of 30 and 50 years. CONCLUSIONS: (A) MS components increase linearly with BMI from the lowest normal BMI and continue to increase with age and BMI; (B) metabolically healthy obesity is rare in subjects with a high BMI and declines with age; (C) hypertension is the most common component in men; and (D) in women, MS components are seen at older ages than in men for the same BMI. Metabolic health declines with age and BMI in nearly all subjects with obesity.

Seeking science information online: Data mining Google to better understand the roles of the media and the education system.

Which extrinsic cues motivate people to search for science-related information? For many science-related search queries, media attention and time during the academic year are highly correlated with changes in information seeking behavior (expressed by changes in the proportion of Google science-related searches). The data mining analysis presented here shows that changes in the volume of searches for general and well-established science terms are strongly linked to the education system. By contrast, ad-hoc events and current concerns were better aligned with media coverage. The interest and ability to independently seek science knowledge in response to current events or concerns is one of the fundamental goals of the science literacy movement. This method provides a mirror of extrapolated behavior and as such can assist researchers in assessing the role of the media in shaping science interests, and inform the ways in which lifelong interests in science are manifested in real world situations.

Keep a level head to know the way ahead: How rodents travel on inclined surfaces?

Animals traveling on a horizontal surface stabilize their head in relation to the substrate in order to gather spatial information and orient. What, however, do they do when traveling on an incline? We examined how three rodent species differing in motor abilities and habitats explore a platform tilted at 0-90°, hypothesizing that they would attempt to maintain bilateral vestibular cues. We found that traveling up or down was mainly straight vertically rather than diagonally, which results in identical bilateral vestibular cues. This was also achieved when traveling horizontally through rotating the head to parallel the horizontal plane. Traveling diagonally up or down was avoided, perhaps due to different bilateral vestibular cues that could hinder orientation. Accordingly, we suggest that maintaining identical bilateral cues is an orientational necessity that overrides differences in motor abilities and habitats, and that this necessity is a general characteristic of animals in motion.

Identifying protein function and functional links based on large-scale co-occurrence patterns.

OBJECTIVE: The vast majority of known proteins have not been experimentally tested even at the level of measuring their expression, and the function of many proteins remains unknown. In order to decipher protein function and examine functional associations, we developed "Cliquely", a software tool based on the exploration of co-occurrence patterns. COMPUTATIONAL MODEL: Using a set of more than 23 million proteins divided into 404,947 orthologous clusters, we explored the co-occurrence graph of 4,742 fully sequenced genomes from the three domains of life. Edge weights in this graph represent co-occurrence probabilities. We use the Bron-Kerbosch algorithm to detect maximal cliques in this graph, fully-connected subgraphs that represent meaningful biological networks from different functional categories. MAIN RESULTS: We demonstrate that Cliquely can successfully identify known networks from various pathways, including nitrogen fixation, glycolysis, methanogenesis, mevalonate and ribosome proteins. Identifying the virulence-associated type III secretion system (T3SS) network, Cliquely also added 13 previously uncharacterized novel proteins to the T3SS network, demonstrating the strength of this approach. Cliquely is freely available and open source. Users can employ the tool to explore co-occurrence networks using a protein of interest and a customizable level of stringency, either for the entire dataset or for a one of the three domains-Archaea, Bacteria, or Eukarya.

Rethinking Conservative Treatment of Humeral Diaphyseal Fractures in Elderly Patients With Dementia.

OBJECTIVES: To assess outcomes and complications of conservatively managed humeral diaphyseal fractures in elderly patients, with an emphasis on the subgroup diagnosed with dementia. DESIGN: Retrospective. SETTING: Upper extremity surgery unit at an academic Level I trauma center. PATIENTS/PARTICIPANTS: Consecutive patients 65 years of age and older who were managed conservatively for humeral diaphyseal fractures between 2007 and 2015. INTERVENTION: Conservatively managed humeral diaphyseal fractures. MAIN OUTCOME MEASUREMENTS: Complications and radiographic outcomes. RESULTS: One-hundred twenty-four patients who were conservatively managed for humeral diaphyseal fractures were identified. Their mean age was 77 (65-92) years, 36 (30%) of them were male and 88 (70%) were female. Fifty-seven (46%) patients experienced complications associated with their treatment, and 33 (27%) patients were eventually treated surgically. Seventeen (14%) patients were diagnosed with dementia. This subgroup had 64% fracture-related complications, and all of them were operated (P-value <0.01 compared with age-matched patients among the other 107 participants in the study). CONCLUSION: Conservative management of humeral diaphyseal fractures seems to be associated with greater morbidity in elderly patients, especially in those diagnosed with dementia. Therefore, early surgical treatment should be considered. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns.

BACKGROUND: The epigenetic age can now be extrapolated from one of several epigenetic clocks, which are based on age-related changes in DNA methylation levels at specific multiple CpG sites. Accelerated aging, calculated from the discrepancy between the chronological age and the epigenetic age, has shown to predict morbidity and mortality rate. We assumed that deconvolution of epigenetic age to its components could shed light on the diversity of epigenetic, and by inference, on inter-individual variability in the causes of biological aging. RESULTS: Using the Horvath original epigenetic clock, we identified several CpG sites linked to distinct genes that quantitatively explain much of the inter-personal variability in epigenetic aging, with CpG sites related to secretagogin and malin being the most variable. We show that equal epigenetic age in different subjects can result from variable contribution size of the same CpG sites to the total epigenetic age. In a healthy cohort, the most variable CpG sites are responsible for accelerated and decelerated epigenetic aging, relative to chronological age. CONCLUSIONS: Of the 353 CpG sites that form the basis for the Horvath epigenetic age, we have found the CpG sites that are responsible for accelerated and decelerated epigenetic aging in healthy subjects. However, the relative contribution of each site to aging varies between individuals, leading to variable personal aging patterns. Our findings pave the way to form personalized aging cards allowing the identification of specific genes related to CpG sites, as aging markers, and perhaps treatment of these targets in order to hinder undesirable age drifting.

Jargon use in Public Understanding of Science papers over three decades.

Public Understanding of Science is an interdisciplinary journal serving the scholarly community and practitioners. This article reports an analysis of the readability and jargon in articles published in Public Understanding of Science throughout its almost three decades of existence to examine trends in accessibility to diverse audiences. The accessibility of Public Understanding of Science articles published in 1999/2000 (47), 2009 (49) and 2019 (65) was assessed in terms of readability and use of jargon. Readability decreased and use of jargon increased between 1999 and 2000 and the two following decades for empirical and non-empirical papers, and all parts including the abstracts. An analysis of rare words shows that most are not part of the general academic vocabulary or disciplinary jargon, but rather words that appeared only in one article. Public Understanding of Science has moved away from everyday language. This does not mean it is incomprehensible to its scholarly readership, but may have consequences to other audiences such as practitioners.

Conserved interactions required for inhibition of the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The COVID-19 pandemic caused by the SARS-CoV-2 requires a fast development of antiviral drugs. SARS-CoV-2 viral main protease (Mpro, also called 3C-like protease, 3CLpro) is a potential target for drug design. Crystal and co-crystal structures of the SARS-CoV-2 Mpro have been solved, enabling the rational design of inhibitory compounds. In this study we analyzed the available SARS-CoV-2 and the highly similar SARS-CoV-1 crystal structures. We identified within the active site of the Mpro, in addition to the inhibitory ligands' interaction with the catalytic C145, two key H-bond interactions with the conserved H163 and E166 residues. Both H-bond interactions are present in almost all co-crystals and are likely to occur also during the viral polypeptide cleavage process as suggested from docking of the Mpro cleavage recognition sequence. We screened in silico a library of 6900 FDA-approved drugs (ChEMBL) and filtered using these key interactions and selected 29 non-covalent compounds predicted to bind to the protease. Additional screen, using DOCKovalent was carried out on DrugBank library (11,414 experimental and approved drugs) and resulted in 6 covalent compounds. The selected compounds from both screens were tested in vitro by a protease activity inhibition assay. Two compounds showed activity at the 50 µM concentration range. Our analysis and findings can facilitate and focus the development of highly potent inhibitors against SARS-CoV-2 infection.

Conformers of Ubiquitin 6+ for Different Charge Distributions: Atomistic Structures and Ion Mobility Cross Sections.

Despite the fact that protein chemistry occurs in solution, studying the structure of desolvated proteins in mass spectrometry vacuum conditions allows one to study biological molecules in complete isolation. The electrospray ionization process results in charged protein conformers for which the charge locations distribution and the corresponding structure are not known. In this paper, we explore the influence of different charge distributions on the structure of conformers of ubiquitin 6+ in the vacuum conditions of mass spectrometry. Using the Tinker implementation of the AMBER99FF force field, the atomistic lowest-energy structures for those charge distributions were calculated by the DEEPSAM algorithm. Differences among the calculated structures are analyzed and discussed in terms of the relation to experimentally observable ion mobility mass spectrometry cross sections. They also are compared to the neutral ubiquitin's native structure and to the nearly linear structure of the ubiquitin 13+ ion. In general, different charge distributions lead to substantially different structures and ion mobility cross sections. In this study, however, it was found that this is not always the case. Our conclusion is that measurements of ion mobility cross sections cannot be used to help determine a unique charge distribution because different charge distributions lead to structures that approximately agree in terms of experimental cross sections.

Stability of cubic tin sulphide nanocrystals: role of ammonium chloride surfactant headgroups.

New semiconducting metastable cubic phases have been recently discovered in the tin monosulfide and monoselenide systems. Surface energy calculations and experimental studies indicate that this cubic π-phase is stabilized by specific ligand adsorption on the surface. In this work, it is shown experimentally that the synthesis carried out using mixtures of oleylamine and oleylammonium chloride (OACl) surfactants results in the cubic phase, transforming the growth from orthorhombic to cubic nanoparticles with increasing OACl concentration up to a limiting point. Complementary ab initio calculations find that adsorbed ligands lower the surface energies for both the cubic phase and the orthorhombic phase, relative to the pristine surfaces. The decrease in the surface energy increases with ligand coverage. Stronger binding energies to the cubic phase suggest a higher coverage, and therefore preferential stabilization of this phase. Upon further increasing the coverage, the surface energy becomes negative, effectively destabilizing the particles in agreement with experimental observations. Bonding analysis shows that Cl bonds to Sn and replaces missing Sn-S bonds at the surface of the cubic structure. In the competing orthorhombic layered phase, Cl also bonds to a Sn atom but at the expense of one of the Sn-S bonds of this Sn atom. This observation can explain the trends of the surface energies. This combined experimental and computational analysis sheds light on the stabilization processes of these nano-materials and indicates the path to improve synthetic routes.

Global and local "teachable moments": The role of Nobel Prize and national pride.

This study examined to what extent Nobel Prize announcements and awards trigger global and local searches or "teachable moments" related to the laureates and their discoveries. We examined the longitudinal trends in Google searches for the names and discoveries of Nobel laureates from 2012 to 2017. The findings show that Nobel Prize events clearly trigger more searches for laureates, but also for their respective discoveries. We suggest that fascination with the Nobel prize creates a teachable moment not only for the underlying science, but also about the nature of science. Locality also emerged as playing a significant role in intensifying interest.

Automatic identification of optimal marker genes for phenotypic and taxonomic groups of microorganisms.

Finding optimal markers for microorganisms important in the medical, agricultural, environmental or ecological fields is of great importance. Thousands of complete microbial genomes now available allow us, for the first time, to exhaustively identify marker proteins for groups of microbial organisms. In this work, we model the biological task as the well-known mathematical "hitting set" problem, solving it based on both greedy and randomized approximation algorithms. We identify unique markers for 17 phenotypic and taxonomic microbial groups, including proteins related to the nitrite reductase enzyme as markers for the non-anammox nitrifying bacteria group, and two transcription regulation proteins, nusG and yhiF, as markers for the Archaea and Escherichia/Shigella taxonomic groups, respectively. Additionally, we identify marker proteins for three subtypes of pathogenic E. coli, which previously had no known optimal markers. Practically, depending on the completeness of the database this algorithm can be used for identification of marker genes for any microbial group, these marker genes may be prime candidates for the understanding of the genetic basis of the group's phenotype or to help discover novel functions which are uniquely shared among a group of microbes. We show that our method is both theoretically and practically efficient, while establishing an upper bound on its time complexity and approximation ratio; thus, it promises to remain efficient and permit the identification of marker proteins that are specific to phenotypic or taxonomic groups, even as more and more bacterial genomes are being sequenced.

π-Phase Tin and Germanium Monochalcogenide Semiconductors: An Emerging Materials System.

Cubic π-phase monochalcogenides (MX, M = Sn, Ge; X = S, Se) are an emerging new class of materials that has recently been discovered. Here, their thermodynamic stability, progress in synthetic routes, properties, and prospective applications are reviewed. The thermodynamic stability is demonstrated through density functional theory total energy and phonon spectra calculations, which show that the π-phase polytype is stable across the monochalcogenide family. To date, only π-phase tin monochalcogenides have been observed experimentally while π-phase Ge-monochalcogenides are predicted to be stable but are yet to be experimentally realized. Various synthetic preparation protocols of π-SnS and π-SnSe are described, focusing on surfactant-assisted nanoparticle synthesis and chemical deposition of thin films from aqueous-bath compositions. These techniques provide materials with different surface energies, which are likely to play a major role in stabilizing the π-phase in nanoscale materials. The properties of this newly discovered family of semiconducting materials are discussed in comparison with their conventional orthorhombic polymorphs. These could benefit a number of photovoltaic and optoelectronic applications since, apart from being cubic, they also possess characteristic advantages, such as moderately low toxicity and natural abundance.