bluuebunny/crossref_metadata_2025 huggingface dataset:
Over the hills and through the farms: Land use and topography influence genetic connectivity of northern leopard frog (Rana pipiens) in the Prairie Pothole Region
Authors: Waraniak Justin M. , Mushet David M. , Stockwell Craig A.
Published: August 2022

Context

Agricultural land-use conversion has fragmented prairie wetland habitats in the Prairie Pothole Region (PPR), an area with one of the most wetland dense regions in the world. This fragmentation can lead to negative consequences for wetland obligate organisms, heightening risk of local extinction and reducing evolutionary potential for populations to adapt to changing environments.

Objectives

This study models biotic connectivity of prairie-pothole wetlands using landscape genetic analyses of the northern leopard frog (Rana pipiens) to (1) identify population structure and (2) determine landscape factors driving genetic differentiation and possibly leading to population fragmentation.

Methods

Frogs from 22 sites in the James River and Lake Oahe river basins in North Dakota were genotyped using Best-RAD sequencing at 2868 bi-allelic single nucleotide polymorphisms (SNPs). Population structure was assessed using STRUCTURE, DAPC, and fineSTRUCTURE. Circuitscape was used to model resistance values for ten landscape variables that could affect habitat connectivity.

Results

STRUCTURE results suggested a panmictic population, but other more sensitive clustering methods identified six spatially organized clusters. Circuit theory-based landscape resistance analysis suggested land use, including cultivated crop agriculture, and topography were the primary influences on genetic differentiation.

Conclusion

While the R. pipiens populations appear to have high gene flow, we found a difference in the patterns of connectivity between the eastern portion of our study area which was dominated by cultivated crop agriculture, versus the western portion where topographic roughness played a greater role. This information can help identify amphibian dispersal corridors and prioritize lands for conservation or restoration.
Derivative of the expected supremum of fractional Brownian motion at $$H=1$$
Authors: Bisewski Krzysztof , Dȩbicki Krzysztof , Rolski Tomasz
Published: August 2022

The H-derivative of the expected supremum of fractional Brownian motion $$\{B_H(t),t\in {\mathbb {R}}_+\}$$

{

B
H

(
t
)

,
t
∈

R
+

}

with drift $$a\in {\mathbb {R}}$$

a
∈
R

over time interval [0, T] $$\begin{aligned} \frac{\partial }{\partial H} {\mathbb {E}}\Big (\sup _{t\in [0,T]} B_H(t) - at\Big ) \end{aligned}$$

∂

∂
H

E

(

sup

t
∈
[
0
,
T
]

B
H

(
t
)

-
a
t

)

at $$H=1$$

H
=
1

is found. This formula depends on the quantity $${\mathscr {I}}$$
I
, which has a probabilistic form. The numerical value of $${\mathscr {I}}$$
I
is unknown; however, Monte Carlo experiments suggest $${\mathscr {I}}\approx 0.95$$

I
≈
0.95

. As a by-product we establish a weak limit theorem in C[0, 1] for the fractional Brownian bridge, as $$H\uparrow 1$$

H
↑
1

.
Graphic novel reading comprehension in Chinese children with developmental language disorder (DLD)
Authors: Wong Simpson W. L. , Li Wang-On , Cheung Anisa
Published: August 2022

Children with developmental language disorder (DLD) have consistently showed poor performances in reading comprehension. Extending from previous studies that presented pure-text, this study aims to test the performances of graphic novel reading. We tested 24 Chinese children who have been diagnosed as DLD and 24 typical readers matched with age and nonverbal IQ. These children were asked to complete a battery of tests assessing graphic novel reading comprehension and related visual-cognitive skills. The results of group comparison indicated that children with DLD performed similarly to the typical readers in graphic novel comprehension. Moreover, significant links between comic convention understanding and both passage and graphic novel reading were found in both groups. Our results imply the benefits of using graphic novel to facilitate reading to learn in children with DLD. (129 words).
Promoting students’ safety and wellbeing: ethical practice in schools
Authors: Graham Anne , Canosa Antonia , Boyle Tess , Moore Tim , Taylor Nicola , Anderson Donnah , Robinson Sally
Published: August 2022

Although ‘child safety’ is now a national policy priority in Australia, there is little research exploring the practices in schools that contribute to children and young people’s felt sense of safety and wellbeing. Drawing on a mixed-method Australian Research Council (ARC) Discovery project, this article presents findings from interviews with school staff (N = 10), leaders (N = 5) and nine focus groups with students (N = 58), in primary and secondary schools in three Australian states (New South Wales, Victoria and South Australia). We employ relational ethics, recognition theory and the theory of practice architectures to explore practices at school that support student wellbeing and safety. The findings contribute significantly to understanding the ‘bundled’ nature of current practices and the conditions that enable and constrain these. Close attention to these findings is critical as schools seek to operationalise the National Child Safe Principles and refine ongoing safeguarding procedures. The findings have informed the development of an online survey that is currently testing, on a much larger scale, which elements of ethical practice are most positively associated with students’ safety, wellbeing and recognition at school.
Examination of Individual Differences in Susceptibility to Food Addiction using Alcohol and Addiction Research Domain Criteria (AARDoC): Recent Findings and Directions for the Future
Authors: Stojek Monika M. , Murphy Cara M.
Published: August 2022

Purpose of Review

Alcohol and Addiction Research Domain Criteria (AARDoC) is a transdiagnostic, circuits-based framework for studying addictive behaviors. We examined parallels in individual differences that might increase susceptibility to FA and other addictive disorders using the following units of analysis in AARDoC domains: craving, relative reinforcing value of food and attention bias in the incentive salience domain; decisional impulsivity (delay discounting) and inhibitory control (Go-No-Go, Conner’s Continuous Performance Test, and the flanker task) in the executive function domain; and emotion dysregulation and negative urgency in the negative emotionality domain.

Recent Findings

There are a number of parallels between FA and other addictions in the incentive salience and negative emotionality domains, but somewhat divergent findings in the executive function domain. Trauma appears to be an important environmental stressor in maintenance of FA.

AARDoC may be a useful organizing framework for studying addictions, including FA. Future studies should incorporate other units of analysis to better characterize FA.
Beaker and Early Bronze Age Tin Exploitation in Cornwall: Cassiterite Processing Identified through Microwear and pXRF Analyses
Authors: Carey Chris , Tsoraki Christina , Jones Andy M. , Harris Oliver J.T. , Crellin Rachel J. , Lyons Peter
Published: August 2022

The appearance of Beaker pottery in Britain and Ireland during the twenty-fifth centurybcmarks a significant archaeological horizon, being synchronous with the first metal artefacts. The adoption of arsenical copper, mostly from Ireland, was followed by that of tin-bronze around 2200bc. However, whilst the copper mine of Ross Island in Ireland is securely dated to the Early Bronze Age, and further such mines in the UK have been dated to the Early and Middle Bronze Age, the evidence for the exploitation of tin ores, the other key ingredient to make bronze, has remained circumstantial. This article contains the detailed analyses of seven stone artefacts from securely dated contexts, using a combination of surface pXRF and microwear analysis. The results provide strong evidence that the tools were used in cassiterite processing. The combined analysis of these artefacts documents in detail the exploitation of Cornish tin during this early phase of metal use in Britain and Ireland.
A sensitivity analysis of a regression model of ocean temperature
Authors: Furner Rachel , Haynes Peter , Munday Dave , Paige Brooks , Jones Daniel C. , Shuckburgh Emily
Published: August 2022

There has been much recent interest in developing data-driven models for weather and climate predictions. However, there are open questions regarding their generalizability and robustness, highlighting a need to better understand how they make their predictions. In particular, it is important to understand whether data-driven models learn the underlying physics of the system against which they are trained, or simply identify statistical patterns without any clear link to the underlying physics. In this paper, we describe a sensitivity analysis of a regression-based model of ocean temperature, trained against simulations from a 3D ocean model setup in a very simple configuration. We show that the regressor heavily bases its forecasts on, and is dependent on, variables known to be key to the physics such as currents and density. By contrast, the regressor does not make heavy use of inputs such as location, which have limited direct physical impacts. The model requires nonlinear interactions between inputs in order to show any meaningful skill—in line with the highly nonlinear dynamics of the ocean. Further analysis interprets the ways certain variables are used by the regression model. We see that information about the vertical profile of the water column reduces errors in regions of convective activity, and information about the currents reduces errors in regions dominated by advective processes. Our results demonstrate that even a simple regression model is capable of learning much of the physics of the system being modeled. We expect that a similar sensitivity analysis could be usefully applied to more complex ocean configurations.
A physical–statistical recipe for representation of small-scale oceanic turbulent mixing in climate models
Authors: Mashayek A. , Cael B.B. , Cimoli L. , Alford M.H. , Caulfield C.P.
Published: August 2022

It is well established that small-scale cross-density (diapycnal) turbulent mixing induced by breaking of overturns in the interior of the ocean plays a significant role in sustaining the deep ocean circulation and in regulating tracer budgets such as those of heat, carbon and nutrients. There has been significant progress in the fluid mechanical understanding of the physics of breaking internal waves. Connection of the microphysics of such turbulence to the larger scale dynamics, however, is significantly underdeveloped. We offer a hybrid theoretical–statistical approach, informed by observations, to make such a link. By doing so, we define a bulk flux coefficient,

$\varGamma _B$

, which represents the partitioning of energy available to an ‘ocean box’ (such as a grid cell of a coarse resolution climate model), from winds, tides, and other sources, into mixing and dissipation. Here,

$\varGamma _B$

depends on both the statistical distribution of turbulent patches and the flux coefficient associated with individual patches,

$\varGamma _i$

. We rely on recent parametrizations of

$\varGamma _i$

and the seeming universal characteristics of statistics of turbulent patches to infer

$\varGamma _B$

, which is the essential quantity for representation of turbulent diffusivity in climate models. By applying our approach to climatology and global tidal estimates, we show that, on a basin scale, energetic mixing zones exhibit moderately efficient mixing that induces significant vertical density fluxes, while quiet zones (with small background turbulence levels), although highly efficient in mixing, exhibit minimal vertical fluxes. The transition between the less energetic to more energetic zones marks regions of intense upwelling and downwelling of deep waters. We suggest that such upwelling and downwelling may be stronger than previously estimated, which in turn has direct implications for the closure of the deep branch of the ocean meridional overturning circulation as well as for the associated tracer budgets.
Novel expansion of a well-established antimicrobial stewardship program: Enhancing program efficiency and reach
Authors: Wirtz Ann L. , Lee Brian R. , Burns Alaina N. , McDonough Ryan J. , Frank Tammy S. , Hall Darrell E. , Vanlandingham Kate , Goldman Jennifer L.
Published: August 2022

Objective:

To evaluate efficiency and impact of a novel antimicrobial stewardship program (ASP) prospective-audit-with-feedback (PAF) review process using the Cerner Multi-Patient Task List (MPTL).

Design:

Retrospective cohort study.

Setting:

A 367-bed free-standing, pediatric academic medical center.

Methods:

The ASP PAF review process expanded to monitor all systemic and inhaled antibiotics through use of the MPTL on July 23, 2020. Average number of daily ASP reviews, absolute number of monthly interventions, and time to conduct ASP reviews were compared between the preimplementation period and the postimplementation period following expansion. Antibiotic days of therapy (DOT) per 1,000 patient days for overall and select antibiotics were compared between periods. ASP intervention characteristics were assessed.

Results:

Average daily ASP reviews significantly increased following program expansion (9 vs 14 reviews; P < .0001), and the absolute number of ASP interventions each month also increased (34 vs 52 interventions; P ≤ .0001). Time to conduct daily ASP reviews increased in the postimplementation period (1.03 vs 1.32 hours). Overall antibiotic DOT per 1,000 patient days significantly decreased in the postimplementation period (457.9 vs 427.9; P < .0001) as well as utilization of select, narrow-spectrum antibiotics such as ampicillin and clindamycin. Intervention type and antibiotics were similar between periods. The ASP documented 128 “nonantibiotic interventions” in the postimplementation period, including culture and/or susceptibility testing (32.8%), immunizations (25.8%), and additional diagnostic testing (22.7%).

Conclusions:

Implementation of an ASP PAF review process using the MPTL allowed for efficient expansion of a pre-existing ASP and a decrease in overall antibiotic utilization. ASP documentation was enhanced to fully track the impact of the program.
ON LINEARISED POLYNOMIALS, SIDON ARRAYS AND FAST CONSTRUCTION OF SIDON SETS
Authors: ANDRADE CESAR , BERMUDEZ YAMIDT , TRUJILLO CARLOS
Published: August 2022

A Sidon set is a subset of an Abelian group with the property that the sums of two distinct elements are distinct. We relate the Sidon sets constructed by Bose to affine subspaces of
$ \mathbb {F} _ {q ^ 2} $
of dimension one. We define Sidon arrays which are combinatorial objects giving a partition of the group
$\mathbb {Z}_{q ^ 2} $
as a union of Sidon sets. We also use linear recurring sequences to quickly obtain Bose-type Sidon sets without the need to use the discrete logarithm.
Associations between early poverty exposure and adolescent well-being: The role of childhood negative emotionality
Authors: De France Kalee , Stack Dale M. , Serbin Lisa A.
Published: August 2022

Using a longitudinal design (Wave 1 n = 164, Mage = 3.57 years, 54% female, predominantly White and French-speaking), the current study sought to answer two questions: 1) does poverty influence children’s negative emotionality through heightened family-level, poverty-related stress? and 2) is negative emotionality, in turn, predictive of adolescent internalizing symptoms, externalizing behaviors, cognitive abilities, and physical health? Results confirmed an indirect pathway from family poverty to child emotionality through poverty-related stress. In addition, negative emotionality was associated with adolescent internalizing symptoms, attention difficulties, and physical health, but not externalizing symptoms, even when controlling for early poverty exposure.
Tau and amyloid biomarkers modify the degree to which cognitive reserve and brain reserve predict cognitive decline
Authors: McKenzie Cathryn , Bucks Romola S. , Weinborn Michael , Bourgeat Pierrick , Salvado Olivier , Gavett Brandon E. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2022

Objective:

Brain reserve, cognitive reserve, and education are thought to protect against late-life cognitive decline, but these variables have not been directly compared to one another in the same model, using future cognitive and functional decline as outcomes. We sought to determine whether the influence of these protective factors on executive function (EF) and daily function decline was dependent upon Alzheimer’s disease (AD) pathology severity, as measured by the total tau to beta-amyloid (T-τ/Aβ1-42) ratio in cerebrospinal fluid (CSF).

Method:

Participants were 1201 older adult volunteers in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Brain reserve was defined using a composite index of structural brain volumes (total brain matter, hippocampus, and white matter hyperintensity). Cognitive reserve was defined as the variance in episodic memory performance not explained by brain integrity and demographics.

Results:

At higher levels of T-τ/Aβ1-42, brain and cognitive reserve predicted slower decline in EF. Only brain reserve attenuated decline at lower levels of T-τ/Aβ1-42. Education had no independent association with cognitive decline.

Conclusions:

These results point to a hierarchy of protection against aging- and disease-associated cognitive decline. When pathology is low, only structural brain integrity predicts rate of future EF decline. The ability of cognitive reserve to predict future EF decline becomes stronger as CSF biomarker evidence of AD increases. Although education is typically thought of as a proxy for cognitive reserve, it did not show any protective effects on cognition after accounting for brain integrity and the residual cognitive reserve index.
A dominance analysis of subjective cognitive complaint comorbidities in former professional football players with and without mild cognitive impairment
Authors: Brett Benjamin L. , Kerr Zachary Yukio , Chandran Avinash , Walton Samuel , Aggarwal Neelum T. , Gifford Katherine , Mannix Rebekah , DeFreese J. D. , Echemendia Ruben J. , Guskiewicz Kevin M. , Meehan William P. , McCrea Michael A.
Published: August 2022

Objectives:

Subjective cognitive difficulties (SCDs) are associated with factors commonly reported in older adults and former contact sport athletes, regardless of objective cognitive decline. We investigated the relative contribution of these factors to SCD in former National Football League (NFL)-players with and without a diagnosis of mild cognitive impairment (MCI).

Methods:

Former NFL players (n = 907) aged ≥ 50 years (mean = 64.7 ± 8.9), with (n = 165) and without (n = 742) a diagnosis of MCI completed health questionnaires. Multivariable regression and dominance analyses determined the relative importance of SCD factors on SCD: 1) depression, 2) anxiety, 3) sleep disturbance, 4) pain interference, 5) ability to participate in social roles and activities, 6) stress-related events, 7) fatigue, 8) concussion history, and 9) education. SCD outcomes included Neuro-QoL Emotional-Behavioral Dyscontrol and the PROMIS Cognitive Function. Fisher’s z-transformation compared comorbid contributing factors to SCD across MCI and non-MCI groups.

Results:

Complete dominance of anxiety was established over most comorbid factors across the MCI and non-MCI groups. Fatigue also exhibited complete dominance over most comorbid factors, though its influence in the MCI group was less robust (general dominance). Average contributions to variance accounted for by comorbid factors to ratings of SCD across MCI and non-MCI groups did not statistically differ (Z-statistics <1.96, ps>.05).

Conclusions:

Anxiety and fatigue are the most robust factors associated with SCD in former professional football players across various combinations of clinical presentations (different combinations of comorbid factors), regardless of documented cognitive impairment. Self-reported deficits may be less reliable in detecting objective impairment in the presence of these factors, with multidimensional assessment being ideal.
“Women, Consider Crypto”: Gender in the Virtual Economy of Decentralized Finance
Authors: Henshaw Alexis
Published: August 2022

Decentralized finance, including cryptocurrency and other blockchain-based applications, promises participants benefits such as financial freedom, security, privacy, and wealth accumulation. More recently, it has also offered the promise of participation, lowering financial barriers, and empowerment—especially to women, the poor, and those residing in the Global South. I argue that the rise of decentralized finance as an alternative development platform is explicitly gendered and calls for feminist analysis. I discuss how cryptocurrency-based approaches to development rest on foundations that are gendered, interacting with hierarchies of race/ethnicity and class. I also explore how they are part of a lineage of neoliberalism, leveraging neoliberal beliefs about entrepreneurialism, financial inclusion, and gender roles. The discussion further introduces the concept of neolibertarianism as an extension of neoliberal logics that advocates for bypassing states entirely in favor of private actors. The current analysis compares this new model of decentralized finance to similarly problematic development trends and assesses how it has—as of yet—failed to deliver on the promises of participation, lowering financial barriers, and empowerment. This analysis concludes with a call to action for feminist and critical scholars, encouraging further work on the topic.
Role of vitamin K2 in bone-vascular crosstalk
Authors: Merra Giuseppe , Dominici Francesca , Gualtieri Paola , Capacci Annunziata , Cenname Giuseppe , Esposito Ernesto , Dri Maria , Di Renzo Laura , Marchetti Marco
Published: August 2022

Abstract: Vitamin K (VK) is a fat-soluble vitamin that is indispensable for the activation of vitamin K-dependent proteins (VKDPs). It has been shown to play an important role in the proper calcium deposit at the bone level, hindering that on the vascular walls. The deficiency of this vitamin in European populations is frequent and unknown. It is related to several factors, poor dietary intake, altered intestinal absorption or altered production by bacteria, indicating possible dysbiosis. For Vitamin K2 (VK2), there is currently no official reference daily intake (RDI). However, the effects of VK2 on the improvement of health in cardiovascular diseases, on bone metabolism, on chronic kidney diseases have been the subject of research in recent decades. The microbiota in the gastrointestinal tract plays an important role: Bacteroides are primarily capable of synthetizing very long chain forms of menaquinones and, in addition to the bacteria present in the intestinal flora, VK2 is also produced by bacteria used in food fermentation processes. This review provides an update on the current literature regarding the origin of VK2 and its implications in what is called the “calcium paradox”, namely the lack of calcium in the bone and its storage in the wall of the vessel.
Crustal Thickness Variations in the Central Midcontinent, USA, and Their Tectonic Implications: New Constraints Obtained Using the H‐κ‐c Method
Authors: Xiao Hongyu , DeLucia Michael , Song Xiaodong , Li Jiangtao , Marshak Stephen
Published: August 2022

The central midcontinent of the USA's cratonic platform is a region of low elevation and relief underlain by tectonic basins, domes, faults, and monoclines. To investigate potential correlations among shallow crustal structure and crustal thickness, we produced a high‐resolution Moho‐depth map of the region by applying the recently developed H‐κ‐c receiver‐function method to data from EarthScope Transportable‐Array and Flexible‐Array stations. Results indicate that Moho depth varies from 38 to 57 km. Changes of Moho depth and of Vp/Vs ratios do not correlate with Precambrian tectonic boundaries, suggesting that they reflect post‐accretion tectonics. Deeper Moho underlies sedimentary basins, implying a relationship between crustal thickness and lithospheric subsidence. Thicker crust may be due to rift‐related underplating, and thinner crust may have undergone delamination. Some depth changes underlie known faults and fold zones. Since short‐wavelength undulations were detected only under high‐density seismic arrays, they may occur more widely but have yet to be resolved.
Sinking Sargassum
Authors: Putman Nathan F. , Hu Chuanmin
Published: August 2022

Blooms and coastal inundations of pelagic Sargassum have caused major problems to coastal communities and ecosystems throughout the tropical Atlantic over the past decade. Understanding Sargassum growth, movement, and mortality is essential to being able to predict and mitigate these events. In principle, tropical cyclones that occur in this area could have an impact on all three processes. In a recent article, Sosa‐Gutierrez et al. (2022, https://doi.org/10.1029/2021GL097484) investigated the potential impacts of tropical cyclones (TCs) on pelagic Sargassum using satellite‐based Sargassum maps and 86 hurricane tracks during 2011–2020. Their statistical analysis showed an average drop of 40% in Sargassum coverage under TC trajectories, which was attributed to possible sinking of Sargassum. Here, we discuss implications of these findings, and advocate continued research on how storms and other physical factors influence the dynamics of growth, movement, and mortality in this ecologically and economically important macroalgae.
Going Beyond Low Flows: Streamflow Drought Deficit and Duration Illuminate Distinct Spatiotemporal Drought Patterns and Trends in the U.S. During the Last Century
Authors: Hammond John C. , Simeone Caelan , Hecht Jory S. , Hodgkins Glenn A. , Lombard Melissa , McCabe Greg , Wolock Dave , Wieczorek Michael , Olson Carolyn , Caldwell Todd , Dudley Rob , Price Adam N.
Published: August 2022

Streamflow drought is a recurring challenge, and understanding spatiotemporal patterns of past droughts is needed to manage future water resources. We examined regional patterns in streamflow drought metrics and compared these metrics to low flow timing and magnitude using long‐term daily records for 555 minimally disturbed watersheds. For each streamgage, we calculated streamflow drought duration (number of days) and deficit (flow volume below a specified threshold) for each climate year (April 1–March 31). We identified drought using five thresholds (2%–30%) and two approaches: variable thresholds with unique values for each day of the year, and a fixed threshold based on all period‐of‐record flows. We then analyzed drought trends using the Mann‐Kendall test with persistence adjustment for 1921–2020, 1951–2020, and 1981–2020, and computed correlations between annual streamflow drought metrics and climate metrics using values from a monthly water balance model. Spatial patterns in drought metrics were consistent between variable and fixed approaches, though fixed threshold durations were typically longer and variable threshold deficits larger. High interannual variability in drought duration emerged in the central, interior west, and southwestern U.S., with high deficit variability in the interior west. Drought metrics were weakly correlated with low flow magnitude and timing, providing unique information. Drought duration and deficit increased in the southern and western U.S. for both 1951–2020 and 1981–2020, particularly using fixed thresholds, and paralleled trends in aridity. Projections of continued aridification for the southern and western U.S. may increase drought durations and deficits and intensify water availability impacts.
Loss of AID exacerbates the malignant progression of CLL
Authors: Lee Avery C. , Pingali Sai Ravi , Pinilla-Ibarz Javier A. , Atchison Michael L. , Koumenis Constantinos , Argon Yair , Thomas-Tikhonenko Andrei , De Trez Carl , Hu Chih-Chi Andrew , Tang Chih-Hang Anthony
Published: August 2022

Activation-induced cytidine deaminase (AID) has been implicated as both a positive and a negative factor in the progression of B cell chronic lymphocytic leukemia (CLL), but the role that it plays in the development and progression of this disease is still unclear. We generated an AID knockout CLL mouse model, AID−/−/Eμ-TCL1, and found that these mice die significantly earlier than their AID-proficient counterparts. AID-deficient CLL cells exhibit a higher ER stress response compared to Eμ-TCL1 controls, particularly through activation of the IRE1/XBP1s pathway. The increased production of secretory IgM in AID-deficient CLL cells contributes to their elevated expression levels of XBP1s, while secretory IgM-deficient CLL cells express less XBP1s. This increase in XBP1s in turn leads AID-deficient CLL cells to exhibit higher levels of B cell receptor signaling, supporting leukemic growth and survival. Further, AID−/−/Eμ-TCL1 CLL cells downregulate the tumor suppressive SMAD1/S1PR2 pathway and have altered homing to non-lymphoid organs. Notably, CLL cells from patients with IgHV-unmutated disease express higher levels of XBP1s mRNA compared to those from patients with IgHV-mutated CLL. Our studies thus reveal novel mechanisms by which the loss of AID leads to worsened CLL and may explain why unmutated CLL is more aggressive than mutated CLL.
Creating and moving nanoantenna cold spots anywhere
Authors: Vernon Alex J. , Rodríguez-Fortuño Francisco J.
Published: August 2022

Cold spots are sub-wavelength regions which might emerge near a nanoantenna, should one or more components of some far-field illumination cancel out with scattered light. We show that by changing only the polarisation, amplitude, and phase of two plane waves, a unique, zero-magnitude and highly sub-wavelength cold spot can be created and moved anywhere in the space around a nanoantenna of any arbitrary shape. This can be achieved using ultra-fast modulated pulses, or a time-harmonic approximation. Easily disturbed by a change in the nanoantenna’s material or position, a manufactured cold spot is fragile and could be used in nanoscale sensing. Our technique exploits the linearity of Maxwell’s equations and could be adapted to manipulate any phenomena governed by the linear wave equation, including acoustic scattering. This is a means for potentially ultra-fast sub-wavelength electric field manipulation.
The RING finger protein family in health and disease
Authors: Cai Chunmei , Tang Yan-Dong , Zhai Jingbo , Zheng Chunfu
Published: August 2022

Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the RING domain, exerts E3 ubiquitin ligase that mediates the covalent attachment of ubiquitin (Ub) to target proteins. Multiple reviews have summarized the critical roles of the tripartite-motif (TRIM) protein family, a subgroup of RNF proteins, in various diseases, including cancer, inflammatory, infectious, and neuropsychiatric disorders. Except for TRIMs, since numerous studies over the past decades have delineated that other RNF proteins also exert widespread involvement in several diseases, their importance should not be underestimated. This review summarizes the potential contribution of dysregulated RNF proteins, except for TRIMs, to the pathogenesis of some diseases, including cancer, autoimmune diseases, and neurodegenerative disorder. Since viral infection is broadly involved in the induction and development of those diseases, this manuscript also highlights the regulatory roles of RNF proteins, excluding TRIMs, in the antiviral immune responses. In addition, we further discuss the potential intervention strategies targeting other RNF proteins for the prevention and therapeutics of those human diseases.
High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes
Authors: Xu Ting , Ma Ding , Chen Sheng , Tang Rui , Yang Jianling , Meng Chunhui , Feng Yang , Liu Li , Wang Jiangfen , Luo Haojun , Yu Keda
Published: August 2022

Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous disease with few effective targeted therapies and precision therapeutic options over a long period. It is generally considered that TNBC is an estrogen-independent breast cancer, while a new estrogen receptor, namely G protein-coupled estrogen receptor (GPER), is demonstrated to mediate estrogenic actions in TNBC. Based on our transcriptomic analysis, expression of GPER was correlated with clinicopathological variables and survival of 360 TNBC patients. GPER expression at mRNA level was significantly correlated with immunohistochemistry scoring in 12 randomly chosen samples. According to the cutoff value, 26.4% (95/360) of patients showed high GPER expression and significant correlation with the mRNA subtype of TNBC (P = 0.001), total metastatic events (P = 0.019) and liver metastasis (P = 0.011). In quantitative comparison, GPER abundance is correlated with the high-risk subtype of TNBC. At a median follow-up interval of 67.1 months, a significant trend towards reduced distant metastasis-free survival (DMFS) (P = 0.014) was found by Kaplan–Meier analysis in patients with high GPER expression. Furthermore, univariate analysis confirmed that GPER was a significant prognostic factor for DMFS in TNBC patients. Besides, high GPER expression was significantly linked to the worse survival in patients with lymph node metastasis, TNM stage III as well as nuclear grade G3 tumors. Transcriptome-based bioinformatics analysis revealed that GPER was linked to pro-metastatic pathways in our cohort. These results may supply new insights into GPER-mediated estrogen carcinogenesis in TNBC, thus providing a potential strategy for endocrine therapy of TNBC.
Realistic magnetic thermodynamics by local quantization of a semiclassical Heisenberg model
Authors: Walsh Flynn , Asta Mark , Wang Lin-Wang
Published: August 2022

Classical Monte Carlo simulation of the Heisenberg model poorly describes many thermodynamic phenomena due to its neglect of the quantum nature of spins. Alternatively, we discuss how to semiclassically approach the quantum problem and demonstrate a simple method for introducing a locally approximate form of spin quantization. While the procedure underestimates magnetic short-range order, our results suggest a simple correction for recovering realistic spin–spin correlations above the critical temperature. Moreover, ensemble fluctuations are found to provide reasonably accurate thermodynamics, largely reproducing quantum mechanically calculated heat capacities and experimental magnetometry for ferromagnetic Fe and antiferromagnetic RbMnF3. Extensions of the method are proposed to address remaining inaccuracies.
Enhancing first-principles simulations of complex solid-state ion conductors using topological analysis of procrystal electron density
Authors: Golov Andrey , Carrasco Javier
Published: August 2022

Atomistic-level understanding of ion migration mechanisms holds the key to design high-performance solid-state ion conductors for a breadth of electrochemical devices. First-principles simulations play an important role in this quest. Yet, these methods are generally computationally-intensive, with limited access to complex, low-symmetry structures, such as interfaces. Here we show how topological analysis of the procrystal electron density can be applied to efficiently mitigate this issue. We discuss how this methodology goes beyond current state of the art capabilities and demonstrate this with two examples. In the first, we examine Li-ion transport across grain boundaries in Li3ClO electrolyte. Then, we compute diffusion coefficients as a function of charge carrier concentration in spinel LiTiS2 electrode material. These two case studies do not exhaust the opportunities and might constitute motivations for still more complex applied materials.
Exploration of two surfaces observed in Weyl semimetal BaMnSb2
Authors: Zou Qiang , Huang Silu , Ko Wonhee , Fu Mingming , Yang Yifan , Zhao Kun , Crittenden Scott R. , Plummer E. W. , Jin Rongying , Gai Zheng
Published: August 2022

Single crystalline BaMnSb2 is considered as a 3D Weyl semimetal with the 2D electronic structure containing Dirac cones from the Sb sheet. We report experimental investigation of low-temperature cleaved BaMnSb2 surfaces using scanning tunneling microscopy/spectroscopy and low energy electron diffraction. By natural cleavage, we find two terminations: one is Ba (above the orthorhombically distorted Sb sheet) and another Sb2 (at the surface of the Sb/Mn/Sb sandwich layer). Both terminations show the 2 × 1 surface reconstructions, with drastically different morphologies and electronic properties, however. The reconstructed structures, defect types and nature of the electronic structures of the two terminations are extensively studied. The quasiparticle interference (QPI) analysis is conducted at the energy range between −2 V and 2 V, although no interesting states are observed near the Fermi level, the surface-projected electronic band structures strongly depend on the surface termination above 1.6 V. The existence of defects can greatly modify the local density of states to create electronic phase separations on the surface in the order of tens of nm scale. Our observation on the atomic structures of the terminations and the corresponding electronic structures provides critical information towards an understanding of topological properties of BaMnSb2.
Precuneus brain response changes differently during human–robot and human–human dyadic social interaction
Authors: Spatola Nicolas , Chaminade Thierry
Published: August 2022

Human–human interactions (HHI) and human–robot interactions (HRI) are compared to identify differences between cognitive processes reflecting bonding in social interactions with natural and artificial agents. We capitalize on a unique corpus of neuroimaging data (fMRI) recorded while participants freely discussed with another human or a conversational robotic head, in order to study a crucial parameter of human social cognition, namely that social interactions are adaptive bidirectional processes that evolve over time. We used linear statistics to identify regions of the brain where activity changes differently when participants carry out twelve one-minute conversations, alternating between a human and a robotic interlocutor. Results show that activity in the posterior cingulate cortex, a key region associated with social cognition, increases over time in HHI but not in HRI. These results are interpreted as reflecting a process of strengthening social bonding during repeated exchanges when the interacting agent is a human, but not a robot.
Overt and implicit prosody contribute to neurophysiological responses previously attributed to grammatical processing
Authors: Glushko Anastasia , Poeppel David , Steinhauer Karsten
Published: August 2022

Recent neurophysiological research suggests that slow cortical activity tracks hierarchical syntactic structure during online sentence processing. Here we tested an alternative hypothesis: electrophysiological activity peaks at constituent phrase as well as sentence frequencies reflect cortical tracking of overt or covert (implicit) prosodic grouping. Participants listened to series of sentences presented in three conditions while electroencephalography (EEG) was recorded. First, prosodic cues in the sentence materials were neutralized. We found an EEG spectral power peak elicited at a frequency that only ‘tagged’ covert, implicit prosodic change, but not any major syntactic constituents. In the second condition, participants listened to a series of sentences with overt prosodic grouping cues that either aligned or misaligned with the syntactic phrasing in the sentences (initial overt prosody trials). Following each overt prosody trial, participants were presented with a second series of sentences lacking overt prosodic cues (instructed prosody trial) and were instructed to imagine the prosodic contour present in the previous, overt prosody trial. The EEG responses reflected an interactive relationship between syntactic processing and prosodic tracking at the frequencies of syntactic constituents (sentences and phrases): alignment of syntax and prosody boosted EEG responses, whereas their misalignment had an opposite effect. This was true for both overt and imagined prosody conditions. We conclude that processing of both overt and covert prosody is reflected in the frequency-tagged neural responses at sentence constituent frequencies. These findings need to be incorporated in any account that aims to identify neural markers reflecting syntactic processing.
Guiding and monitoring focused ultrasound mediated blood–brain barrier opening in rats using power Doppler imaging and passive acoustic mapping
Authors: Singh Aparna , Kusunose Jiro , Phipps M. Anthony , Wang Feng , Chen Li Min , Caskey Charles F.
Published: August 2022

The blood–brain barrier (BBB) prevents harmful toxins from entering brain but can also inhibit therapeutic molecules designed to treat neurodegenerative diseases. Focused ultrasound (FUS) combined with microbubbles can enhance permeability of BBB and is often performed under MRI guidance. We present an all-ultrasound system capable of targeting desired regions to open BBB with millimeter-scale accuracy in two dimensions based on Doppler images. We registered imaging coordinates to FUS coordinates with target registration error of 0.6 ± 0.3 mm and used the system to target microbubbles flowing in cellulose tube in two in vitro scenarios (agarose-embedded and through a rat skull), while receiving echoes on imaging transducer. We created passive acoustic maps from received echoes and found error between intended location in imaging plane and location of pixel with maximum intensity after passive acoustic maps reconstruction to be within 2 mm in 5/6 cases. We validated ultrasound-guided procedure in three in vivo rat brains by delivering MRI contrast agent to cortical regions of rat brains after BBB opening. Landmark-based registration of vascular maps created with MRI and Doppler ultrasound revealed BBB opening inside the intended focus with targeting accuracy within 1.5 mm. Combined use of power Doppler imaging with passive acoustic mapping demonstrates an ultrasound-based solution to guide focused ultrasound with high precision in rodents.
Nanoplastic incorporation into an organismal skeleton
Authors: Joppien Marlena , Westphal Hildegard , Chandra Viswasanthi , Stuhr Marleen , Doo Steve S.
Published: August 2022

Studies on the effects of global marine plastic pollution have largely focused on physiological responses of few organism groups (e.g., corals, fishes). Here, we report the first observation of polymer nanoparticles being incorporated into the calcite skeleton of a large benthic foraminifera (LBF), a significant contributor to global carbonate production. While previous work on LBF has documented selectivity in feeding behaviour and a high degree of specialization regarding skeletal formation, in this study, abundant cases of nanoplastic encrustation into the calcite tests were observed. Nanoplastic incorporation was associated with formation of new chambers, in conjunction with rapid nanoplastic ingestion and subsequent incomplete egestion. Microalgae presence in nanoplastic treatments significantly increased the initial feeding response after 1 day, but regardless of microalgae presence, nanoplastic ingestion was similar after 6 weeks of chronic exposure. While ~ 40% of ingesting LBF expelled all nanoplastics from their cytoplasm, nanoplastics were still attached to the test surface and subsequently encrusted by calcite. These findings highlight the need for further investigation regarding plastic pollution impacts on calcifying organisms, e.g., the function of LBF as potential plastic sinks and alterations in structural integrity of LBF tests that will likely have larger ecosystem-level impacts on sediment production.
Prediction of the structural interface between fibroblast growth factor23 and Burosumab using alanine scanning and molecular docking
Authors: Kanhasut Karnpob , Tharakaraman Kannan , Ruchirawat Mathuros , Satayavivad Jutamaad , Fuangthong Mayuree , Sasisekharan Ram
Published: August 2022

Burosumab, an FGF23 targeting monoclonal antibody, was approved by the FDA in 2018 for use in children and adults with X-linked hypophosphatemia (or XLH). While several clinical studies have demonstrated the long-term safety and efficacy of Burosumab, the molecular basis of FGF23-Burosumab interaction which underpins its mechanism of action remains unknown. In this study, we employed molecular docking combined with alanine scanning of epitope and paratope to predict a model of FGF23-Burosumab interaction. Then, we used the model to understand the species-species cross-reactivity of Burosumab and to reverse engineer mouse FGF23 with 'back to human' mutations to bind Burosumab. Finally, we redesigned the CDRs with two mutations to engineer an affinity enhanced variant of the antibody. Our study provides insights into the FGF23-Burosumab interaction and demonstrates that alanine-scanning coupled with molecular docking can be used to optimize antibody candidates (e.g., structure-guided affinity maturation) for therapeutic use.
NMR analysis suggests the terminal domains of Robo1 remain extended but are rigidified in the presence of heparan sulfate
Authors: Williams Robert V. , Huang Chin , Moremen Kelley W. , Amster I. Jonathan , Prestegard James H.
Published: August 2022

Human roundabout 1 (hRobo1) is an extracellular receptor glycoprotein that plays important roles in angiogenesis, organ development, and tumor progression. Interaction between hRobo1 and heparan sulfate (HS) has been shown to be essential for its biological activity. To better understand the effect of HS binding we engineered a lanthanide-binding peptide sequence (Loop) into the Ig2 domain of hRobo1. Native mass spectrometry was used to verify that loop introduction did not inhibit HS binding or conformational changes previously suggested by gas phase ion mobility measurements. NMR experiments measuring long-range pseudocontact shifts were then performed on 13C-methyl labeled hRobo1-Ig1-2-Loop in HS-bound and unbound forms. The magnitude of most PCSs for methyl groups in the Ig1 domain increase in the bound state confirming a change in the distribution of interdomain geometries. A grid search over Ig1 orientations to optimize the fit of data to a single conformer for both forms produced two similar structures, both of which differ from existing X-ray crystal structures and structures inferred from gas-phase ion mobility measurements. The structures and degree of fit suggest that the hRobo1-Ig1-2 structure changes slightly and becomes more rigid on HS binding. This may have implications for Robo-Slit signaling.
Densification in transparent SiO2 glasses prepared by spark plasma sintering
Authors: Masai Hirokazu , Kimura Hiromi , Kitamura Naoyuki , Ikemoto Yuka , Kohara Shinji , Masuno Atsunobu , Fujii Yasuhiro , Miyazaki Takamichi , Yanagida Takayuki
Published: August 2022

Recently, spark plasma sintering (SPS) has become an attractive method for the preparation of solid-state ceramics. As SPS is a pressure-assisted low-temperature process, it is important to examine the effects of temperature and pressure on the structural properties of the prepared samples. In the present study, we examined the correlation between the preparation conditions and the physical and structural properties of SiO2 glasses prepared by SPS. Compared with the conventional SiO2 glass, the SPS-SiO2 glasses exhibit a higher density and elastic modulus, but a lower-height first sharp diffraction peak of the X-ray total structure factor. Micro-Raman and micro-IR spectra suggest the formation of heterogeneous regions at the interface between the SiO2 powders and graphite die. Considering the defect formation observed in optical absorption spectra, reduction reaction mainly affects the densification of SPS-SiO2 glass. Hence, the reaction at the interface is important for tailoring the structure and physical properties of solid-state materials prepared by the SPS technique.