bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of q-Baskakov Operators by Wavelets and Approximation Properties
Authors: Nasiruzzaman Md. , Kilicman Adem , Ayman-Mursaleen Mohammad
Published: October 2022

We use wavelets to define the Kantorovich variant of q-Baskakov type operators, and for $$1\le p< \infty$$

1
≤
p
<
∞

, we study the $$L_{p}$$

L
p

-approximation. Let $$\xi$$
ξ
be any positive constant and $$\Psi _{k}(x)$$

Ψ
k

(
x
)

be any continuous derivative function such that $$\int _{\mathbb {R}}x^{s}\Psi _{k}(x)\mathrm {d}_{q}x=0$$

∫
R

x
s

Ψ
k

(
x
)

d
q

x
=
0

where $$0\le s \le k,\;k\in \mathbb {N}$$

0
≤
s
≤
k
,

k
∈
N

, $$0<q<1$$

0
<
q
<
1

$$.$$
.
For all $$\Psi \in L_{\infty }(\mathbb {R})$$

Ψ
∈

L
∞

(
R
)

suppose the following conditions hold: (i) a finite positive $$\xi$$
ξ
exits with the property $$\sup \Psi \subset [0,\xi ],$$

sup
Ψ
⊂
[
0
,
ξ
]
,

(ii) its first k moments vanish: For $$1\le s \le k,\;k\in \mathbb {N}$$

1
≤
s
≤
k
,

k
∈
N

, we have $$\int _{\mathbb {R}}t^{s}\Psi (t)\mathrm {d}_{q}t=0$$

∫
R

t
s

Ψ

(
t
)

d
q

t
=
0

and $$\int _{\mathbb {R} }\Psi (t)\mathrm {d}_{q}t=1$$

∫
R

Ψ

(
t
)

d
q

t
=
1

. Then in the sense of Haar basis for $$0<q<1,$$

0
<
q
<
1
,

the $$q-$$

q
-

analogue of Baskakov–Kantorovich type wavelets operators are defined by $$\begin{aligned} \left( \mathcal {S}_{r,s,q}\;g\right) (x)=[r]_{q}\sum_{s =0}^{\infty }q^{s -1}B_{r,s,q}(x)\int _{\mathbb {R}}g\left( t\right) \Psi \left( q^{s-1}[r]_{q}t-[s ]_{q}\right) \mathrm {d}_{q}t. \end{aligned}$$

S

r
,
s
,
q

g

(
x
)

=

[
r
]

q

∑

s
=
0

∞

q

s
-
1

B

r
,
s
,
q

(
x
)

∫
R

g

t

Ψ

q

s
-
1

[
r
]

q

t
-

[
s
]

q

d
q

t
.
Culture collections as a source of historic strains for genomic studies in plant pathology
Authors: Ryan Matthew J. , Peck Lily D. , Smith David , Flood Julie , Barraclough Timothy G.
Published: October 2022

The first microbial culture collection was established in 1890, and subsequently, over the course of the twentieth century, the number of culture collections grew substantially. One such collection was the CABI-IMI Genetic Resources Collection, informally initiated at the origins of the Commonwealth Mycological Institute in 1920 and established as a UK National Collection in 1947. Its holdings reflect the activities of CABI in agriculture and the environment. Like many collections, it was originally established as a taxonomic reference resource. Over the years, deposits have included strains isolated from disease outbreaks in major crops from all parts of the world. Recent developments in genome sequencing technology and bioinformatic analysis have opened up the potential to characterise historic strains to shed more insights on their biology and evolution. In this paper we describe how the resources held within the CABI-IMI culture collection have helped track the emergence and divergence of Fusarium xylarioides, the coffee wilt pathogen, with a specific focus on the evolution of pathogenicity. Such studies illustrate the value held within the world’s culture collections—their importance in underpinning science and developing our understanding and evolution of plant diseases as well as how the impact of disease can be mitigated in response to climate change, in order to increase yields and feed the world’s burgeoning population.
Blinded by and Stuck in Negative Emotions: Is Psychological Inflexibility Across Different Domains Related?
Authors: Moeck Ella K. , Mortlock Jessica , Onie Sandersan , Most Steven B. , Koval Peter
Published: October 2022

Psychological inflexibility is theorized to underlie difficulties adjusting mental processes in response to changing circumstances. People show inflexibility across a range of domains, including attention, cognition, and affect. But it remains unclear whether common mechanisms underlie inflexibility in different domains. We investigated this possibility in a pre-registered replication and extension examining associations among attentional, cognitive, and affective inflexibility measures. Participants (N = 196) completed lab tasks assessing (a) emotion-induced blindness, the tendency for task-irrelevant emotional stimuli to impair attention allocation to non-emotional stimuli; (b) emotional inertia, the tendency for feelings to persist across time and contexts; and global self-report measures of (c) repetitive negative thinking, the tendency to repeatedly engage in negative self-focused thoughts (i.e., rumination, worry). Based on prior research linking repetitive negative thinking with negative affect inertia, on one hand, and emotion-induced blindness, on the other, we predicted positive correlations among all three measures of inflexibility. However, none of the three measures were related and Bayes factors indicated strong evidence for independence. Supplementary analyses ruled out alternative explanations for our findings, e.g., analytic decisions. Although our findings question the overlap between attentional, cognitive, and affective inflexibility measures, this study has methodological limitations. For instance, our measures varied across more than their inflexibility domain and our sample, relative to previous studies, included a high proportion of Asian participants who may show different patterns of ruminative thinking to non-Asian participants. Future research should address these limitations to confirm that common mechanisms do not underlie attentional, cognitive, and affective inflexibility.
Survey Result for E-labeling Initiatives in Asia
Authors: Matsui Rie , Yamaguchi Koji , Lee Jadz Jevz Venzon , Ting Ivy , Khairilisani Destita , Chang Jenny , Seo Jeong-Min , Park Ina , Chee Alice Seat Mee , Quizon Paul Marvin , Harnpramukkul Usanee , Sem Ellen , Nguyen Thuy , Padhye Anagha , Mo Runyi
Published: October 2022

Under the COVID-19 pandemic, various electronic labeling initiatives have accelerated worldwide in the healthcare and pharmaceutical fields as part of a wider digital transformation [1, 2]. Although there is no universal definition of electronic labeling (e-labeling) globally, it is widely understood that e-labeling refers to the product information that is distributed via electronic means. There are 5 factors to be considered in e-labeling, and these are discussed in this publication. APAC is an industry-driven initiative with 13 R&D-based pharmaceutical associations joining from 11 markets in Asia. e-labeling was discussed as a new topic starting in 2020, and a 22-question survey was conducted in November 2021 to understand the current e-labeling status. The survey results showed that e-labeling initiatives were at different levels of maturity in the Asian region, although most markets have started to discuss e-labeling initiatives. Various challenges exist around e-labeling initiatives due to a variety of different approaches being taken in the region. It would be advisable to develop regional guidance on how to proceed with e-labeling initiatives in the Asian region to have a consistent and efficient approach. The close collaboration between agencies, Health Care Professionals (HCPs), patients, and industry associations is important to move e-labeling initiatives forward in Asia.
Wirnt von Gravenberg's Wigalois
Authors: Thomas Neil
Published: October 2022

Reappraisal of Wirnt von Gravenberg's Wigalois, showing how it confronts and takes issue with - rather than simply imitating - earlier German Arthurian romance.
The Concept of Legitimacy
Authors: Adams N. P.
Published: October 2022

I argue that legitimacy discourses serve a gatekeeping function. They give practitioners telic standards for riding herd on social practices, ensuring that minimally acceptable versions of the practice are implemented. Such a function is a necessary part of implementing formalized social practices, especially including law. This gatekeeping account shows that political philosophers have misunderstood legitimacy. It is not secondary to justice and only necessary because we cannot agree about justice; instead, it is a necessary feature of actual human social practices, which must be implemented via practitioners’ discretion in changing contexts.
Time Motion Studies for Conduct of Population Monitoring During Functional Radiological Exercises at Community Reception Centers
Authors: Finklea Lauren , Salame-Alfie Adela , Ansari Armin
Published: October 2022

Objective:

The objectives of this study were to: validate current capacity estimates for radiological emergency response by collecting time motion observations from stations that would be used for screening and decontaminating populations, and use collected times to evaluate potential impact on current throughput calculations.

Methods:

Time observations were collected at 11 functional radiation exercises across the country and aggregated for analysis for population monitoring activities, including contamination screening, decontamination, and registration. Collected times were compared to published estimates in current planning guidance, and evaluated to determine the suitability of using exercise observations to estimate throughput capacity.

Results:

2532-time observations were collected from 11 functional exercises. Of those, 2380 were validated and used for analysis. Contamination screening times varied greatly from current guidance, ranging from 19% below to 267% above existing estimates. Measurements indicate that capacity to perform contamination screening is significantly overestimated when using current estimates of service times and calculations when compared to observed aggregate service times.i

Conclusion:

Aggregate service time data presented in this study can be used to yield a more realistic estimate of capacity to respond to a radiation event.
From Neolithic Boom-and-Bust to Iron Age Peak and Decline: Population and Settlement Dynamics in Southern Sweden Inferred from Summed Radiocarbon Dates
Authors: Friman Bo , Lagerås Per
Published: October 2022

This article presents 6637 radiocarbon dates from archaeological sites in southernmost Sweden, from 9000 cal bc to the present. Based on summed probability distributions (SPDs) of the calibrated radiocarbon dates, the authors consider long-term trends in settlement and human population. Most dates are from the fertile and densely populated plains of south-western Scania, but coastal lowlands and forested uplands are also represented, allowing for a discussion of the relationship between central and peripheral areas. The authors distinguish between different types of archaeological contexts and features and between different types of dated material, so as to better understand the processes behind population and settlement change. They highlight three periods and phenomena revealed by the SPDs: a strong population increase at the onset of the Neolithic (4000–3700 cal bc), followed by a sharp decline; a steady and long-lasting expansion from the Early Bronze Age to the Roman Iron Age (1500 cal bc–cal ad 200); and a decrease in the Nordic Late Iron Age (seventh century ad), particularly in recently colonized upland areas. The SPDs presented provide a new framework for archaeology in southern Sweden and offer an empirical basis for discussion of long-term trends in settlement and population development.
The politics of pension policy responses to COVID-19: comparative insights from Chile, Bolivia and Peru
Authors: Carrera Leandro N. , Angelaki Marina
Published: October 2022

The COVID-19 pandemic has sparked a debate around the world on whether pension systems should be used to support individuals in economic distress. In Latin America, Chile, Bolivia and Peru have passed legislation allowing withdrawals from pension pots, yet with some significant variation. We argue that these measures cannot be simply understood because of the COVID-19 emergency alone but should also take into consideration the combination of legacies from previous pension re-reforms and the political institutional setting. We find that where previous re-reforms have been difficult to implement or have not been implemented at all and the institutional setting makes change difficult, measures that lead to a significant amount of savings being withdrawn may be favoured by political actors as a way to break the stalemate. By contrast, where re-reforms have been largely implemented and the political institutional setting poses few barriers to change, withdrawals may be more limited.
The influence of temporal heating modulation on non-isothermal floating droplet dynamics
Authors: Nepomnyashchy Alexander , Simanovskii Ilya
Published: October 2022

The action of temporal heating modulation on Marangoni flows in a droplet on a liquid substrate is investigated. The problem is studied numerically in the framework of long-wave amplitude equations and precursor model. It is shown that temporal modulation can lead to a change of the droplet shape. Specifically, rhombic droplets have been obtained. A modulated cooling from below can lead to periodic or quasiperiodic oscillations or the droplet's decomposition.
Implications of the loess record for Holocene climate and human settlement in Heye Catchment, Jiuzhaigou, eastern Tibetan Plateau, Sichuan, China
Authors: Schmidt Amanda H. , Collins Brian D. , Keen-Zebert Amanda , d'Alpoim Guedes Jade , Hein Anke , Womack Andrew , McGuire Casey , Feathers James , Persico Lyman , Fiallo Dominic , Tang Ya , Simonson Bruce
Published: October 2022

We examine the Holocene loess record in the Heye Catchment on the margins of the Tibetan Plateau (TP) and China Loess Plateau (CLP) to determine: the region to which the Heye Catchment climate is more similar; temporal change in wind strength; and modification of the loess record by mass wasting and human activity. Luminescence and radiocarbon dating demonstrate loess deposited in two periods: >11–8.6 ka and <5.1 ka. The 8.6–5.1 ka depositional hiatus, which coincides with the Mid-Holocene Climatic Optimum, is more similar to the loess deposition cessation in the TP than to the loess deposition deceleration in the CLP. Grain-size analysis suggests the Heye loess is a mixture of at least three different grain-size distributions and that it may derive from multiple sources. A greater proportion of coarse sediments in the older loess may indicate stronger winds compared with the more recent depositional period. Gravel incorporated into younger loess most likely comes from bedrock exposed in slump scarps. Human occupation of the catchment, for which the earliest evidence is 3.4 ka, postdates the onset of slumping; thus the slumps may have created a livable environment for humans.
Health-related cues on the packages of processed and ultra-processed products: prevalence and policy implications
Authors: Alcaire Florencia , Vidal Leticia , Machín Leandro , Antúnez Lucía , Giménez Ana , Curutchet María Rosa , Ares Gastón
Published: October 2022

The information included on food packages has a crucial role in influencing consumer product associations and purchase decisions. In particular, visual and textual cues on processed and ultra-processed products can convey health-related associations that influence consumer healthiness perception and purchase decisions. In this context, the present work aimed to explore the use of health-related cues on the packages of processed and ultra-processed products sold in Uruguay to provide insights for policy making. A total of 3813 products from thirty-four different food categories found in four of the most important supermarket chains in Uruguay were surveyed. The textual and visual information included on the packages as well as the nutritional composition of the products were analysed. Results showed that 67 % of the products included at least one health-related cue. Pictures of culinary ingredients, natural and minimally processed foods were the most frequent health-related cue, followed by references to naturalness and claims related to critical nutrients. The prevalence of health-related cues largely differed across product categories, ranging from 100 to 17 %. The relationship between the presence of health-related cues on the packages and the excessive content of nutrients associated with non-communicable diseases was assessed using a gradient boosting model, which showed limited predictive ability. This suggests that the inclusion of health-related cues on food packages was not strongly related to the nutritional composition of products and therefore cannot be regarded as a healthiness indicator. These results stress the need to develop stricter labelling regulations to protect consumers from misleading information.
Transnational Exchange in World Christianity: Racial Reconciliation in the Newfrontiers Network of Churches, 1979–2010
Authors: JEFFERY SAM
Published: October 2022

This article demonstrates how transnational encounters and exchanges can shape and re-shape Christian beliefs and practices in a globalising world. It does this using the example of a transnational network of neo-charismatic churches called Newfrontiers that was founded in the small towns of Sussex during the 1970s but, by 2011, encompassed almost 850 churches in over sixty countries. Drawing on extensive primary research, this article shows how the theological and practical commitment of Newfrontiers churches to racial reconciliation and the building of diverse congregations was forged over thirty years through encounters between British, South African and Ghanaian Christians.
Does Public Financing Motivate Electoral Challengers?
Authors: Mancinelli Abigail
Published: October 2022

Do attempts to level the financial playing field lead more candidates to run for office? In theory, public financing should increase competition, presumably because additional funding from taxpayers motivates more challengers to run for office. I provide a novel test of this logic with data on all candidates running for state legislature across all US states between 1976 and 2018. The results suggest that public financing exerts a generally positive effect on the total number of candidates running for state legislative office and specifically increases the number of candidates running in elections for every additional year after the passage of public financing. This effect is amplified in states that offer greater amounts of public funds. I conclude that the availability of public financing can be an equalizing force in elections, and that state legislative elections continue to experience increased competition in the years after the introduction of public financing.
Observational Verification of the Cumulative Resilience Screening Index (CRSI) Using Hurricanes, Inland Floods, and Wildfires From 2016 to 2019
Authors: Summers J. Kevin , Lamper Andrea , McMillion Courtney , Harwell Linda
Published: October 2022

Users can apply three processes to develop confidence in decision‐making tools like models and indices—validation, verification, and observation. The utility of the Cumulative Resilience Screening Index (CRSI) was demonstrated by combining the processes of verification and observation using real‐world natural hazard events (i.e., hurricanes, inland flooding, and wildfires). The ability of CRSI to determine the counties most vulnerable to hazards and least likely to recover quickly from natural hazards is demonstrated using these natural hazard events from outside the original index construction data set. Using Hurricane Harvey and Hurricane Michael, the counties in Texas and Florida/Georgia, respectively, experiencing the most damage and the most extended recovery intervals were determined accurately. Similarly, the most vulnerable and least recoverable counties were correctly identified as those associated with the Great Louisiana Flood of 2016. Finally, three different types of wildfires in California were examined to determine the likelihood of recovery and the strength of pre‐event planning. All models and indices developed for use by decision‐makers should consider undertaking this verification or a similar validation operation to enhance user confidence.
Structural Changes Preceding the Rapid Intensification of Typhoon Lekima (2019) Under Moderate Vertical Wind Shear
Authors: Wang Chendi , Fang Juan , Ma Yiming
Published: October 2022

The early development of Super Typhoon Lekima (2019) under moderate vertical wind shear (VWS) is examined on the basis of a convection‐permitting simulation with the Weather Research and Forecast model. The tropical cyclone (TC) evolves from a tilted vortex to an upright vortex with a meso‐γ‐scale high‐vorticity core and finally to a vortex with a well‐defined eyewall preceding rapid intensification. The shift of the upper‐middle‐tropospheric vortex to the upshear‐left quadrant is critical to the establishment of an upright TC vortex with high vorticity concentrated in the center. As the upper‐middle‐tropospheric vortex reaches the upshear‐left quadrant, it drifts toward the TC center under the horizontal advective effect of VWS, leading to a reduction of TC vortex tilt. The low stability and high humidity below the upper‐middle‐tropospheric vortex together with the fast increase of upper‐middle‐tropospheric vorticity promote the convection around the TC center, which is important to the maintenance of the nearly upright TC vortex and the development of the high‐vorticity core in TC vortex. The evolution of the TC from an upright vortex with a high‐vorticity core to a vortex with a well‐defined eyewall is bound with the convection near the radius of maximum azimuthal‐mean tangential velocity. The convection enhances the boundary‐layer inflow and then the supergradient force above the radially inward side of the strong boundary‐layer inflow. In this way, the convergence within and above the boundary layer is strengthened, favoring the formation of a ring of deep convection and high vorticity. Such processes are similar to those leading up to secondary eyewall formation.
Seasons of Ice: Water Ice Migration and Seasonal Transient Shadow at the Lunar Poles
Authors: Luchsinger Kristen M. , Chanover Nancy J.
Published: October 2022

Lunar water ice can be broadly categorized as belonging to one of two populations: deep, ancient, stable deposits, and shallow, transient, recent deposits. However, a third state for lunar ice is also possible. Temporary sequestration occurs when ice is deposited into a transiently shadowed region at the lunar poles. These temporarily sequestered ice deposits are unstable over geologic time scales, but in the short term, are capable of a wide range of migration, sublimation, and retention patterns due to their thermally dependent sublimation and migration rates. We developed a model to characterize the range of possible migration and retention behaviors for temporarily sequestered ice deposits within locations with dynamic illumination conditions. We found that water ice migration, sublimation, and retention varies across the lunar polar environment, with neighboring locations experiencing different illumination and thermal conditions. We found that the residence times of temporarily sequestered ice deposits in some high latitude, non‐shadowed regions can be similar to or greater than the length of time spent above the long term stability temperature of ice during lunar winter months, leading to incomplete removal of surface or near surface ice during the day. We also found that shallowly buried, unstable ice deposits take longer to sublimate than surface deposits, leading to a temporal lag in escaping ice. This work suggests that temporary sequestration can lead to complex ice migration and retention patterns at high latitudes, with ice sublimation efficiency varying across the lunar polar environment due to local, small scale differences in illumination conditions.
Cold Compaction and Macro‐Porosity Removal in Rubble‐Pile Asteroids: 2. Applications
Authors: Zhang Zhongtian , Bercovici David , Elkins‐Tanton Linda
Published: October 2022

Models of asteroid collisional evolution suggest that many asteroids are gravitationally‐bound rubble piles. Although rubble piles may be expected to retain large void fractions, compaction may reduce the porosity. We apply models for cold compaction of rubble‐pile bodies developed in a companion paper toward observations of asteroid densities. The model for chondritic boulders is applied to S‐type (stony) and C‐type (carbonaceous) asteroids. The relation between density and size of S‐type asteroids is largely explained by cold compaction of rubble piles through fracturing of boulders, under the assumption that boulder size distributions are narrow before fracturing and fractal‐like afterward. The density variation of C‐type asteroids can only partly be explained by this mechanism, and the removal of micro‐voids inside the boulders would be required to match observations. The model for metal boulders is applied to M‐type asteroids, and the results suggest that, because of cold welding between metal boulders and the high yield strength of metal for either ductile or brittle‐like deformation, metallic rubble piles can preserve large (≳50%) porosities if the boulders are ∼1 m in size. This implies that M‐type asteroids such as Psyche and Kleopatra may be purely metallic, even though their densities are less than half that of iron. We also consider the hypothesis that Psyche is a primitive body of a CB chondrite‐like material. Assuming that the strength of CB chondrite is controlled by a silicate matrix, we predict that the density of a Psyche‐sized rubble pile of CB chondrite is higher than that of Psyche.
Stem cell microencapsulation maintains stemness in inflammatory microenvironment
Authors: Zhao Yajun , Shi Yilin , Yang Huiqi , Liu Mengmeng , Shen Lanbo , Zhang Shengben , Liu Yue , Zhu Jie , Lan Jing , Li Jianhua , Ge Shaohua
Published: October 2022

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with FeIII/tannic acid coordination network to obtain spheroid@[FeIII-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.
The breast milk and childhood gastrointestinal microbiotas and disease outcomes: a longitudinal study
Authors: Lif Holgerson Pernilla , Esberg Anders , West Christina E. , Johansson Ingegerd
Published: October 2022

Background

We aimed to characterize breast milk microbiota and define associations with saliva and fecal microbiota and selected diseases in preschool children.

Methods

In a longitudinal cohort study, the microbiotas from breast milk, mouth, and fecal samples were characterized by 16S rRNA gene sequencing. Questionnaires and medical records provided information on demographics, medical, and dental data.

Results

The phylogeny in breast milk, saliva swabs, and feces differed at all levels (p < 0.0003), though all harbored species in Streptococcus, Veillonella, and Haemophilus. Species richness was highest in breast milk with increasing resemblance with the oral swab microbiota by increasing age. Caries-affected children at age 5 had been fed breast milk with tenfold higher abundance of caries-associated bacteria, e.g., Streptococcus mutans, than caries-free children (p < 0.002). At that age, taxa, e.g., Neisseria sicca were overrepresented in saliva swabs of children with otitis media (LDA score >2, p < 0.05). Gut symbionts, e.g., Bacteroides, were underrepresented in 3-month fecal samples in children later diagnosed with allergic disease (LDA score >2, p < 0.05).

Conclusions

Distinct microbiotas for the three sources were confirmed, though resemblance between milk and oral swab microbiota increased by age. Future studies should evaluate if the observed associations with disease outcomes are causal.

Impact

Few studies have studied the association between breast milk microbiota and gastrointestinal microbiota beyond early infancy.

The present study confirms distinct microbiota profiles in breast milk, saliva swabs, and feces in infancy and indicates increasing resemblance between breast milk and the oral microbiota by increasing age.

The fecal microbiota at 3 months was associated with later allergic disease; the saliva microbiota by age 5 differed between children with and without otitis media at the same age; and children with caries by age 5 had been fed breast milk with a higher abundance of caries-associated bacteria.
Unique H2-utilizing lithotrophy in serpentinite-hosted systems
Authors: Nobu Masaru Konishi , Nakai Ryosuke , Tamazawa Satoshi , Mori Hiroshi , Toyoda Atsushi , Ijiri Akira , Suzuki Shino , Kurokawa Ken , Kamagata Yoichi , Tamaki Hideyuki
Published: October 2022

Serpentinization of ultramafic rocks provides molecular hydrogen (H2) that can support lithotrophic metabolism of microorganisms, but also poses extremely challenging conditions, including hyperalkalinity and limited electron acceptor availability. Investigation of two serpentinization-active systems reveals that conventional H2-/CO2-dependent homoacetogenesis is thermodynamically unfavorable in situ due to picomolar CO2 levels. Through metagenomics and thermodynamics, we discover unique taxa capable of metabolism adapted to the habitat. This included a novel deep-branching phylum, “Ca. Lithacetigenota”, that exclusively inhabits serpentinite-hosted systems and harbors genes encoding alternative modes of H2-utilizing lithotrophy. Rather than CO2, these putative metabolisms utilize reduced carbon compounds detected in situ presumably serpentinization-derived: formate and glycine. The former employs a partial homoacetogenesis pathway and the latter a distinct pathway mediated by a rare selenoprotein—the glycine reductase. A survey of microbiomes shows that glycine reductases are diverse and nearly ubiquitous in serpentinite-hosted environments. “Ca. Lithacetigenota” glycine reductases represent a basal lineage, suggesting that catabolic glycine reduction is an ancient bacterial innovation by Terrabacteria for gaining energy from geogenic H2 even under hyperalkaline, CO2-poor conditions. Unique non-CO2-reducing metabolisms presented here shed light on potential strategies that extremophiles may employ for overcoming a crucial obstacle in serpentinization-associated environments, features potentially relevant to primordial lithotrophy in early Earth.
Integrin-KCNB1 potassium channel complexes regulate neocortical neuronal development and are implicated in epilepsy
Authors: Bortolami Alessandro , Yu Wei , Forzisi Elena , Ercan Koray , Kadakia Ritik , Murugan Madhuvika , Fedele Denise , Estevez Irving , Boison Detlev , Rasin Mladen-Roko , Sesti Federico
Published: October 2022

Potassium (K+) channels are robustly expressed during prenatal brain development, including in progenitor cells and migrating neurons, but their function is poorly understood. Here, we investigate the role of voltage-gated K+channel KCNB1 (Kv2.1) in neocortical development. Neuronal migration of glutamatergic neurons was impaired in the neocortices of KCNB1 null mice. Migratory defects persisted into the adult brains, along with disrupted morphology and synaptic connectivity. Mice developed seizure phenotype, anxiety, and compulsive behavior. To determine whether defective KCNB1 can give rise to developmental channelopathy, we constructed Knock In (KI) mice, harboring the gene variantKcnb1R312H(R312H mice) found in children with developmental and epileptic encephalopathies (DEEs). The R312H mice exhibited a similar phenotype to the null mice. Wild type (WT) and R312H KCNB1 channels made complexes with integrins α5β5 (Integrin_K+channel_Complexes, IKCs), whose biochemical signaling was impaired in R312H brains. Treatment with Angiotensin II in vitro, an agonist of Focal Adhesion kinase, a key component of IKC signaling machinery, corrected the neuronal abnormalities. Thus, a genetic mutation in a K+channel induces severe neuromorphological abnormalities through non-conducting mechanisms, that can be rescued by pharmacological intervention. This underscores a previously unknown role of IKCs as key players in neuronal development, and implicate developmental channelopathies in the etiology of DEEs.
Choroidal vascularity index and choroidal thickness: potential biomarkers in retinitis pigmentosa
Authors: Abdolrahimzadeh Solmaz , Di Pippo Mariachiara , Ciancimino Chiara , Di Staso Federico , Lotery Andrew John
Published: October 2022

Retinitis pigmentosa (RP) is the commonest inherited retinal dystrophy. It is characterized by progressive photoreceptor degeneration and cell death and ongoing neuronal and vascular impairment. In recent years, pathophysiological alterations of the choroid have begun to be appreciated in RP. Thus, representing a potential diagnostic and therapeutic biomarker. In particular, choroidal thickness and the choroidal vascularity index can be used to understand the pathogenesis of disease and evaluate new therapeutic possibilities. Photoreceptor changes seen in eyes with RP are directly correlated to a decrease of choroidal flow, leading to a strong association between relative choroidal ischemia and visual impairment. In this review we analyse the literature on choroidal thickness and choroidal vascularity index in patients with RP and assess whether these markers may reflect progression of disease from an anatomical and functional point of view.
The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis
Authors: Zhang Qi , Abdo Rober , Iosef Cristiana , Kaneko Tomonori , Cecchini Matthew , Han Victor K. , Li Shawn Shun-Cheng
Published: October 2022

Brain metastases (BrMs) are a common occurrence in lung cancer with a dismal outcome. To understand the mechanism of metastasis to inform prognosis and treatment, here we analyze primary and metastasized tumor specimens from 44 non-small cell lung cancer patients by spatial RNA sequencing, affording a whole transcriptome map of metastasis resolved with morphological markers for the tumor core, tumor immune microenvironment (TIME), and tumor brain microenvironment (TBME). Our data indicate that the tumor microenvironment (TME) in the brain, including the TIME and TBME, undergoes extensive remodeling to create an immunosuppressive and fibrogenic niche for the BrMs. Specifically, the brain TME is characterized with reduced antigen presentation and B/T cell function, increased neutrophils and M2-type macrophages, immature microglia, and reactive astrocytes. Differential gene expression and network analysis identify fibrosis and immune regulation as the major functional modules disrupted in both the lung and brain TME. Besides providing systems-level insights into the mechanism of lung cancer brain metastasis, our study uncovers potential prognostic biomarkers and suggests that therapeutic strategies should be tailored to the immune and fibrosis status of the BrMs.
A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo
Authors: Kofink Christiane , Trainor Nicole , Mair Barbara , Wöhrle Simon , Wurm Melanie , Mischerikow Nikolai , Roy Michael J. , Bader Gerd , Greb Peter , Garavel Géraldine , Diers Emelyne , McLennan Ross , Whitworth Claire , Vetma Vesna , Rumpel Klaus , Scharnweber Maximilian , Fuchs Julian E. , Gerstberger Thomas , Cui Yunhai , Gremel Gabriela , Chetta Paolo , Hopf Stefan , Budano Nicole , Rinnenthal Joerg , Gmaschitz Gerhard , Mayer Moriz , Koegl Manfred , Ciulli Alessio , Weinstabl Harald , Farnaby William
Published: October 2022

Targeted protein degradation offers an alternative modality to classical inhibition and holds the promise of addressing previously undruggable targets to provide novel therapeutic options for patients. Heterobifunctional molecules co-recruit a target protein and an E3 ligase, resulting in ubiquitylation and proteosome-dependent degradation of the target. In the clinic, the oral route of administration is the option of choice but has only been achieved so far by CRBN- recruiting bifunctional degrader molecules. We aimed to achieve orally bioavailable molecules that selectively degrade the BAF Chromatin Remodelling complex ATPase SMARCA2 over its closely related paralogue SMARCA4, to allow in vivo evaluation of the synthetic lethality concept of SMARCA2 dependency in SMARCA4-deficient cancers. Here we outline structure- and property-guided approaches that led to orally bioavailable VHL-recruiting degraders. Our tool compound, ACBI2, shows selective degradation of SMARCA2 over SMARCA4 in ex vivo human whole blood assays and in vivo efficacy in SMARCA4-deficient cancer models. This study demonstrates the feasibility for broadening the E3 ligase and physicochemical space that can be utilised for achieving oral efficacy with bifunctional molecules.
A neural theory for counting memories
Authors: Dasgupta Sanjoy , Hattori Daisuke , Navlakha Saket
Published: October 2022

Keeping track of the number of times different stimuli have been experienced is a critical computation for behavior. Here, we propose a theoretical two-layer neural circuit that stores counts of stimulus occurrence frequencies. This circuit implements a data structure, called acount sketch, that is commonly used in computer science to maintain item frequencies in streaming data. Our first model implements a count sketch using Hebbian synapses and outputs stimulus-specific frequencies. Our second model uses anti-Hebbian plasticity and only tracks frequencies within four count categories (“1-2-3-many”), which trades-off the number of categories that need to be distinguished with the potential ethological value of those categories. We show how both models can robustly track stimulus occurrence frequencies, thus expanding the traditional novelty-familiarity memory axis from binary to discrete with more than two possible values. Finally, we show that an implementation of the “1-2-3-many” count sketch exists in the insect mushroom body.
Scleral PERK and ATF6 as targets of myopic axial elongation of mouse eyes
Authors: Ikeda Shin-ichi , Kurihara Toshihide , Jiang Xiaoyan , Miwa Yukihiro , Lee Deokho , Serizawa Naho , Jeong Heonuk , Mori Kiwako , Katada Yusaku , Kunimi Hiromitsu , Ozawa Nobuhiro , Shoda Chiho , Ibuki Mari , Negishi Kazuno , Torii Hidemasa , Tsubota Kazuo
Published: October 2022

Axial length is the primary determinant of eye size, and it is elongated in myopia. However, the underlying mechanism of the onset and progression of axial elongation remain unclear. Here, we show that endoplasmic reticulum (ER) stress in sclera is an essential regulator of axial elongation in myopia development through activation of both PERK and ATF6 axis followed by scleral collagen remodeling. Mice with lens-induced myopia (LIM) showed ER stress in sclera. Pharmacological interventions for ER stress could induce or inhibit myopia progression. LIM activated all IRE1, PERK and ATF6 axis, and pharmacological inhibition of both PERK and ATF6 suppressed myopia progression, which was confirmed by knocking down above two genes via CRISPR/Cas9 system. LIM dramatically changed the expression of scleral collagen genes responsible for ER stress. Furthermore, collagen fiber thinning and expression of dysregulated collagens in LIM were ameliorated by 4-PBA administration. We demonstrate that scleral ER stress and PERK/ATF6 pathway controls axial elongation during the myopia development in vivo model and 4-PBA eye drop is promising drug for myopia suppression/treatment.
Charge self-regulation in 1T'''-MoS2 structure with rich S vacancies for enhanced hydrogen evolution activity
Authors: Guo Xiaowei , Song Erhong , Zhao Wei , Xu Shumao , Zhao Wenli , Lei Yongjiu , Fang Yuqiang , Liu Jianjun , Huang Fuqiang
Published: October 2022

Active electronic states in transition metal dichalcogenides are able to prompt hydrogen evolution by improving hydrogen absorption. However, the development of thermodynamically stable hexagonal 2H-MoS2 as hydrogen evolution catalyst is likely to be shadowed by its limited active electronic state. Herein, the charge self-regulation effect mediated by tuning Mo−Mo bonds and S vacancies is revealed in metastable trigonal MoS2 (1T'''-MoS2) structure, which is favarable for the generation of active electronic states to boost the hydrogen evolution reaction activity. The optimal 1T'''-MoS2 sample exhibits a low overpotential of 158 mV at 10 mA cm−2 and a Tafel slope of 74.5 mV dec−1 in acidic conditions, which are far exceeding the 2H-MoS2 counterpart (369 mV and 137 mV dec−1). Theoretical modeling indicates that the boosted performance is attributed to the formation of massive active electronic states induced by the charge self-regulation effect of Mo−Mo bonds in defective 1T'''-MoS2 with rich S vacancies.
Atomic model of vesicular stomatitis virus and mechanism of assembly
Authors: Zhou Kang , Si Zhu , Ge Peng , Tsao Jun , Luo Ming , Zhou Z. Hong
Published: October 2022

Like other negative-strand RNA viruses (NSVs) such as influenza and rabies, vesicular stomatitis virus (VSV) has a three-layered organization: a layer of matrix protein (M) resides between the glycoprotein (G)-studded membrane envelope and the nucleocapsid, which is composed of the nucleocapsid protein (N) and the encapsidated genomic RNA. Lack of in situ atomic structures of these viral components has limited mechanistic understanding of assembling the bullet-shaped virion. Here, by cryoEM and sub-particle reconstruction, we have determined the in situ structures of M and N inside VSV at 3.47 Å resolution. In the virion, N and M sites have a stoichiometry of 1:2. The in situ structures of both N and M differ from their crystal structures in their N-terminal segments and oligomerization loops. N-RNA, N-N, and N-M-M interactions govern the formation of the capsid. A double layer of M contributes to packaging of the helical nucleocapsid: the inner M (IM) joins neighboring turns of the N helix, while the outer M (OM) contacts G and the membrane envelope. The pseudo-crystalline organization of G is further mapped by cryoET. The mechanism of VSV assembly is delineated by the network interactions of these viral components.
Rapid and efficient hydrogen clathrate hydrate formation in confined nanospace
Authors: Farrando-Perez Judit , Balderas-Xicohtencatl Rafael , Cheng Yongqiang , Daemen Luke , Cuadrado-Collados Carlos , Martinez-Escandell Manuel , Ramirez-Cuesta Anibal J. , Silvestre-Albero Joaquin
Published: October 2022

Clathrate hydrates are crystalline solids characterized by their ability to accommodate large quantities of guest molecules. Although CH4 and CO2 are the traditional guests found in natural systems, incorporating smaller molecules (e.g., H2) is challenging due to the need to apply higher pressures to stabilize the hydrogen-bonded network. Another critical limitation of hydrates is the slow nucleation and growth kinetics. Here, we show that specially designed activated carbon materials can surpass these obstacles by acting as nanoreactors promoting the nucleation and growth of H2 hydrates. The confinement effects in the inner cavities promote the massive growth of hydrogen hydrates at moderate temperatures, using pure water, with extremely fast kinetics and much lower pressures than the bulk system.
Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA
Authors: Yang Xiaoyun , Li Zongqiang , Zhao Liang , She Zhun , Gao Zengqiang , Sui Sen-Fang , Dong Yuhui , Li Yanhua
Published: October 2022

PldA, a phospholipase D (PLD) effector, catalyzes hydrolysis of the phosphodiester bonds of glycerophospholipids—the main component of cell membranes—and assists the invasion of the opportunistic pathogen Pseudomonas aeruginosa. As a cognate immunity protein, PA3488 can inhibit the activity of PldA to avoid self-toxicity. However, the precise inhibitory mechanism remains elusive. We determine the crystal structures of full-length and truncated PldA and the cryogenic electron microscopy structure of the PldA–PA3488 complex. Structural analysis reveals that there are different intermediates of PldA between the “open” and “closed” states of the catalytic pocket, accompanied by significant conformational changes in the “lid” region and the peripheral helical domain. Through structure-based mutational analysis, we identify the key residues responsible for the enzymatic activity of PldA. Together, these data provide an insight into the molecular mechanisms of PldA invasion and its neutralization by PA3488, aiding future design of PLD-targeted inhibitors and drugs.
Giant enhancement of superconducting critical temperature in substitutional alloy (La,Ce)H9
Authors: Bi Jingkai , Nakamoto Yuki , Zhang Peiyu , Shimizu Katsuya , Zou Bo , Liu Hanyu , Zhou Mi , Liu Guangtao , Wang Hongbo , Ma Yanming
Published: October 2022

A sharp focus of current research on superconducting superhydrides is to raise their critical temperature Tc at moderate pressures. Here, we report a discovery of giant enhancement of Tc in CeH9 obtained via random substitution of half Ce by La, leading to equal-atomic (La,Ce)H9 alloy stabilized by maximum configurational entropy, containing the LaH9 unit that is unstable in pure compound form. The synthesized (La,Ce)H9 alloy exhibits Tc of 148–178 K in the pressure range of 97–172 GPa, representing up to 80% enhancement of Tc compared to pure CeH9 and showcasing the highest Tc at sub-megabar pressure among the known superhydrides. This work demonstrates substitutional alloying as a highly effective enabling tool for substantially enhancing Tc via atypical compositional modulation inside suitably selected host crystal. This optimal substitutional alloying approach opens a promising avenue for synthesis of high-entropy multinary superhydrides that may exhibit further increased Tc at even lower pressures.
Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing
Authors: Gonzalez Trevor J. , Simon Katherine E. , Blondel Leo O. , Fanous Marco M. , Roger Angela L. , Maysonet Maribel Santiago , Devlin Garth W. , Smith Timothy J. , Oh Daniel K. , Havlik L. Patrick , Castellanos Rivera Ruth M. , Piedrahita Jorge A. , ElMallah Mai K. , Gersbach Charles A. , Asokan Aravind
Published: October 2022

Recombinant adeno-associated viral (AAV) vectors are a promising gene delivery platform, but ongoing clinical trials continue to highlight a relatively narrow therapeutic window. Effective clinical translation is confounded, at least in part, by differences in AAV biology across animal species. Here, we tackle this challenge by sequentially evolving AAV capsid libraries in mice, pigs and macaques. We discover a highly potent, cross-species compatible variant (AAV.cc47) that shows improved attributes benchmarked against AAV serotype 9 as evidenced by robust reporter and therapeutic gene expression, Cre recombination and CRISPR genome editing in normal and diseased mouse models. Enhanced transduction efficiency of AAV.cc47 vectors is further corroborated in macaques and pigs, providing a strong rationale for potential clinical translation into human gene therapies. We envision that ccAAV vectors may not only improve predictive modeling in preclinical studies, but also clinical translatability by broadening the therapeutic window of AAV based gene therapies.