Recent advances in spatially resolved transcriptomics (SRT) technologies have enabled comprehensive characterization of gene expression patterns in the context of tissue microenvironment. To ...elucidate spatial gene expression variation, we present SpaGCN, a graph convolutional network approach that integrates gene expression, spatial location and histology in SRT data analysis. Through graph convolution, SpaGCN aggregates gene expression of each spot from its neighboring spots, which enables the identification of spatial domains with coherent expression and histology. The subsequent domain guided differential expression (DE) analysis then detects genes with enriched expression patterns in the identified domains. Analyzing seven SRT datasets using SpaGCN, we show it can detect genes with much more enriched spatial expression patterns than competing methods. Furthermore, genes detected by SpaGCN are transferrable and can be utilized to study spatial variation of gene expression in other datasets. SpaGCN is computationally fast, platform independent, making it a desirable tool for diverse SRT studies.
Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an ...essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating the development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. Although the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size.
Spearman's g is the name for the shared variance across a set of intercorrelating cognitive tasks. For some-but not all-theorists, g is defined as general intelligence. While g is robustly observed ...in Western populations, it is questionable whether g is manifested in cognitive data from other cultural groups. To test whether g is a cross-cultural phenomenon, we searched for correlation matrices or data files containing cognitive variables collected from individuals in non-Western, nonindustrialized nations. We subjected these data to exploratory factor analysis (EFA) using promax rotation and 2 modern methods of selecting the number of factors. Samples that produced more than 1 factor were then subjected to a second-order EFA using the same procedures and a Schmid-Leiman solution. Across 97 samples from 31 countries totaling 52,340 individuals, we found that a single factor emerged unambiguously from 71 samples (73.2%) and that 23 of the remaining 26 samples (88.5%) produced a single second-order factor. The first factor in the initial EFA explained an average of 45.9% of observed variable variance (SD = 12.9%), which is similar to what is seen in Western samples. One sample that produced multiple second-order factors only did so with 1 method of selecting the number of factors in the initial EFA; the alternate method of selecting the number of factors produced a single higher-order factor. Factor extraction in a higher-order EFA was not possible in 2 samples. These results show that g appears in many cultures and is likely a universal phenomenon in humans.
Public Significance Statement
This study shows that one conceptualization of intelligence-called Spearman's g-is present in over 90 samples from 31 non-Western, nonindustrialized nations. This means that intelligence is likely a universal trait in humans. Therefore, it is theoretically possible to conduct cross-cultural research on intelligence, though culturally appropriate tests are necessary for any such research.
Display omitted
Optimization of microalgal growth and high-value metabolite production are key steps in microalgal mass culture for the algae industry. An emerging technology is the use of ...phytohormones, like indole-3-acetic acid (IAA), to promote microalgal growth. This requires an understanding of the biosynthesis of IAA in microalgae-bacteria associations and its function in regulating algal physiology and metabolite production. We review the current advances in understanding of microalgal and bacterial auxin biosynthesis and their implications for algal biotechnology.
Changes in the neuromuscular system affecting the ageing motor unit manifest structurally as a reduction in motor unit number secondary to motor neuron loss; fibre type grouping due to repeating ...cycles of denervation‐reinnervation; and instability of the neuromuscular junction that may be due to either or both of a gradual perturbation in postsynaptic signalling mechanisms necessary for maintenance of the endplate acetylcholine receptor clusters or a sudden process involving motor neuron death or traumatic injury to the muscle fibre. Functionally, these changes manifest as a reduction in strength and coordination that precedes a loss in muscle mass and contributes to impairments in fatigue. Regular muscle activation in postural muscles or through habitual physical activity can attenuate some of these structural and functional changes up to a point along the ageing continuum. On the other hand, regular muscle activation in advanced age (>75 years) loses its efficacy, and at least in rodents may exacerbate age‐related motor neuron death. Transgenic mouse studies aimed at identifying potential mechanisms of motor unit disruptions in ageing muscle are not conclusive due to many different mechanisms converging on similar motor unit alterations, many of which phenocopy ageing muscle. Longitudinal studies of ageing models and humans will help clarify the cause and effect relationships and thus, identify relevant therapeutic targets to better preserve muscle function across the lifespan.
Schematic depiction of the aging motor unit where fibers of the same colour belong to the same motor unit. A degenerating axon is depicted by the dashed orange line.
Atrophy is a defining feature of aging skeletal muscle that contributes to progressive weakness and an increased risk of mobility impairment, falls, and physical frailty in very advanced age. Amongst ...the most frequently implicated mechanisms of aging muscle atrophy is mitochondrial dysfunction. Recent studies employing methods that are well-suited to interrogating intrinsic mitochondrial function find that mitochondrial respiration and reactive oxygen species emission changes are inconsistent between aging rat muscles undergoing atrophy and appear normal in human skeletal muscle from septuagenarian physically active subjects. On the other hand, a sensitization to permeability transition seems to be a general property of atrophying muscle with aging and this effect is even seen in atrophying muscle from physically active septuagenarian subjects. In addition to this intrinsic alteration in mitochondrial function, factors extrinsic to the mitochondria may also modulate mitochondrial function in aging muscle. In particular, recent evidence implicates oxidative stress in the aging milieu as a factor that depresses respiratory function in vivo (an effect that is not present ex vivo). Furthermore, in very advanced age, not only does muscle atrophy become more severe and clinically relevant in terms of its impact, but also there is evidence that this is driven by an accumulation of severely atrophied denervated myofibers. As denervation can itself modulate mitochondrial function and recruit mitochondrial-mediated atrophy pathways, future investigations need to address the degree to which skeletal muscle mitochondrial alterations in very advanced age are a consequence of denervation, rather than a primary organelle defect, to refine our understanding of the relevance of mitochondria as a therapeutic target at this more advanced age.
Tournament Theory Connelly, Brian L.; Tihanyi, Laszlo; Crook, T. Russell ...
Journal of management,
01/2014, Letnik:
40, Številka:
1
Journal Article
Recenzirano
Tournament theory is useful for describing behavior when reward structures are based on relative rank rather than absolute levels of output. Accordingly, management scholars have used tournament ...theory to describe a wide range of inter- and intraorganizational competitions, such as promotion contests, innovation contests, and competition among franchisees. While the use of tournament theory has gained considerable momentum in recent years, the ideas that underlie the theory have become blurred and potentially useful insights remain trapped within disciplines. We, therefore, provide a synthesis of the theory’s foundational concepts, review its use in the management literature, identify advancements from related disciplines that may be imported to management research, and delineate the steps likely to be critical to moving the theory forward. Our hope is this review will make tournament theory more accessible and salient to management researchers with a view toward developing more nuanced versions of the theory and applying it in a wider range of contexts.
Upper echelon theory highlights the importance of top management teams in large and established firms; however, effects are not always clear outside of this context. Due to the unique nature of new ...ventures, the composition of entrepreneurial teams and its effects on performance is worthy of investigation. Accordingly, we meta–analyze the effect of three characteristics of entrepreneurial team composition (i.e., aggregated, heterogeneity, team size) on new venture performance. Our meta–analysis, which includes 55 empirical samples and 8,892 observations, finds significant and unique effects of entrepreneurial team characteristics on new ventures. Based on our findings, we derive avenues for future research.
Manipulation of DNA by CRISPR-Cas enzymes requires the recognition of a protospacer-adjacent motif (PAM), limiting target site recognition to a subset of sequences. To remove this constraint, we ...engineered variants of
Cas9 (SpCas9) to eliminate the NGG PAM requirement. We developed a variant named SpG that is capable of targeting an expanded set of NGN PAMs, and we further optimized this enzyme to develop a near-PAMless SpCas9 variant named SpRY (NRN and to a lesser extent NYN PAMs). SpRY nuclease and base-editor variants can target almost all PAMs, exhibiting robust activities on a wide range of sites with NRN PAMs in human cells and lower but substantial activity on those with NYN PAMs. Using SpG and SpRY, we generated previously inaccessible disease-relevant genetic variants, supporting the utility of high-resolution targeting across genome editing applications.
With the proliferation of multi-site neuroimaging studies, there is a greater need for handling non-biological variance introduced by differences in MRI scanners and acquisition protocols. Such ...unwanted sources of variation, which we refer to as “scanner effects”, can hinder the detection of imaging features associated with clinical covariates of interest and cause spurious findings. In this paper, we investigate scanner effects in two large multi-site studies on cortical thickness measurements across a total of 11 scanners. We propose a set of tools for visualizing and identifying scanner effects that are generalizable to other modalities. We then propose to use ComBat, a technique adopted from the genomics literature and recently applied to diffusion tensor imaging data, to combine and harmonize cortical thickness values across scanners. We show that ComBat removes unwanted sources of scan variability while simultaneously increasing the power and reproducibility of subsequent statistical analyses. We also show that ComBat is useful for combining imaging data with the goal of studying life-span trajectories in the brain.
•Cortical thickness (CT) measurements are highly scanner specific.•Identifying scanner effects is crucial for inference and biomarker development.•We propose to use ComBat to harmonize cortical thickness values across scanners.
PDF
