bluuebunny/crossref_metadata_2025 huggingface dataset:
Tradition as ‘Formative Environment’: Congar and Christian Formation
Authors: Queirós Anthony
Published: January 2024

Although the theology of Tradition of the Dominican Yves Congar was highly influential in drafting the Dogmatic Constitution Dei Verbum at the Second Vatican Council, postconciliar debates neglected some of the most original aspects of this theology. This article proposes a retrieval of the notion of Tradition as ‘milieu éducatif’, advanced by the theologian in Tradition and Traditions, as a valuable resource for contemporary discussions on Christian formation. It intends to highlight how Congar connected the theological realities of revelation and its transmission by the Church with the concrete practice of Christian life. This notion is, then, put in conversation with contemporary Christian thinkers who have reflected on the practical aspects of Christian formation, chiefly James K.A. Smith. This dialogue aims to show the relevance of Congar’s notion to current discussions. While the theology of Tradition exposed by the French Dominican can be completed and specified by current proposals, it can also offer a new theological depth to those proposals.
Pride and Probability
Authors: Zaffora Blando Francesca
Published: January 2024

Bayesian agents, argues Belot, are orgulous: they believe in inductive success even when guaranteed to fail on a topologically typical collection of data streams. Here we shed light on how pervasive this phenomenon is. We identify several classes of inductive problems for which Bayesian convergence to the truth is topologically typical. However, we also show that, for all sufficiently complex classes, there are inductive problems for which convergence is topologically atypical. Last, we identify specific topologically typical collections of data streams, observing which guarantees convergence to the truth across all problems from certain natural classes of effective inductive problems.
NEAR OPTIMAL THRESHOLDS FOR EXISTENCE OF DILATED CONFIGURATIONS IN
Authors: BHOWMIK PABLO , RAKHMONOV FIRDAVS
Published: January 2024

Let
$\mathbb {F}_q^d$
denote the d-dimensional vector space over the finite field
$\mathbb {F}_q$
with q elements. Define for
$\alpha = (\alpha _1, \dots , \alpha _d) \in \mathbb {F}_q^d$
. Let
$k\in \mathbb {N}$
, A be a nonempty subset of
$\{(i, j): 1 \leq i < j \leq k + 1\}$
and
$r\in (\mathbb {F}_q)^2\setminus {0}$
, where
$(\mathbb {F}_q)^2=\{a^2:a\in \mathbb {F}_q\}$
. If
$E\subset \mathbb {F}_q^d$
, our main result demonstrates that when the size of the set E satisfies
$|E| \geq C_k q^{d/2}$
, where
$C_k$
is a constant depending solely on k, it is possible to find two
$(k+1)$
-tuples in E such that one of them is dilated by r with respect to the other, but only along
$|A|$
edges. To be more precise, we establish the existence of
$(x_1, \dots , x_{k+1}) \in E^{k+1}$
and
$(y_1, \dots , y_{k+1}) \in E^{k+1}$
such that, for
$(i, j) \in A$
, we have
$\lVert y_i - y_j \rVert = r \lVert x_i - x_j \rVert $
, with the conditions that
$x_i \neq x_j$
and
$y_i \neq y_j$
for
$1 \leq i < j \leq k + 1$
, provided that
$|E| \geq C_k q^{d/2}$
and
$r\in (\mathbb {F}_q)^2\setminus \{0\}$
. We provide two distinct proofs of this result. The first uses the technique of group actions, a powerful method for addressing such problems, while the second is based on elementary combinatorial reasoning. Additionally, we establish that in dimension 2, the threshold
$d/2$
is sharp when
$q \equiv 3 \pmod 4$
. As a corollary of the main result, by varying the underlying set A, we determine thresholds for the existence of dilated k-cycles, k-paths and k-stars (where
$k \geq 3$
) with a dilation ratio of
$r\in (\mathbb {F}_q)^2\setminus \{0\}$
. These results improve and generalise the findings of Xie and Ge [‘Some results on similar configurations in subsets of
$\mathbb {F}_q^d$
’, Finite Fields Appl.91 (2023), Article no. 102252, 20 pages].
ON THE CHARACTERISATION OF ALTERNATING GROUPS BY CODEGREES
Authors: DOLORFINO MALLORY , MARTIN LUKE , SLONIM ZACHARY , SUN YUXUAN , YANG YONG
Published: January 2024

Let G be a finite group and
$\mathrm {Irr}(G)$
the set of all irreducible complex characters of G. Define the codegree of
$\chi \in \mathrm {Irr}(G)$
as
$\mathrm {cod}(\chi ):={|G:\mathrm {ker}(\chi ) |}/{\chi (1)}$
and let
$\mathrm {cod}(G):=\{\mathrm {cod}(\chi ) \mid \chi \in \mathrm {Irr}(G)\}$
be the codegree set of G. Let
$\mathrm {A}_n$
be an alternating group of degree
$n \ge 5$
. We show that
$\mathrm {A}_n$
is determined up to isomorphism by
$\operatorname {cod}(\mathrm {A}_n)$
.
COMPLETE EMBEDDINGS OF GROUPS
Authors: BRIDSON MARTIN R. , SHORT HAMISH
Published: January 2024

Every countable group G can be embedded in a finitely generated group
$G^*$
that is hopfian and complete, that is,
$G^*$
has trivial centre and every epimorphism
$G^*\to G^*$
is an inner automorphism. Every finite subgroup of
$G^*$
is conjugate to a finite subgroup of G. If G has a finite presentation (respectively, a finite classifying space), then so does
$G^*$
. Our construction of
$G^*$
relies on the existence of closed hyperbolic 3-manifolds that are asymmetric and non-Haken.
Association between n-3 PUFA and lung function: results from the NHANES 2007–2012 and Mendelian randomisation study
Authors: Li Jingli , Sun Jian , Liu Lingjing , Zhang Chunyi , Liu Zixiang
Published: January 2024

This study aimed to investigate the association between n-3 PUFA and lung function. First, a cross-sectional study was conducted based on the National Health and Nutrition Examination Survey (NHANES) 2007–2012 data. n-3 PUFA intake was obtained from 24-h dietary recalls. A multivariable linear regression model was used to assess the observational associations of n-3 PUFA intake with lung function. Subsequently, a two-sample Mendelian randomisation (MR) was performed to estimate the potential causal effect of n-3 PUFA on lung function. Genetic instrumental variables were extracted from published genome-wide association studies. Summary statistics about n-3 PUFA was from UK Biobank. Inverse variance weighted was the primary analysis approach. The observational study did not demonstrate a significant association between n-3 PUFA intake and most lung function measures; however, a notable exception was observed with significant findings in the highest quartile for forced vital capacity (FVC) and % predicted FVC. The MR results also showed no causal effect of circulating n-3 PUFA concentration on lung function (forced expiratory volume in one second (FEV1), β = 0·01301, se = 0·01932, P = 0·5006; FVC, β = −0·001894, se = 0·01704, P = 0·9115; FEV1:FVC, β = 0·03118, se = 0·01743, P = 0·07359). These findings indicate the need for further investigation into the impact of higher n-3 PUFA consumption on lung health.
Kato’s main conjecture for potentially ordinary primes
Authors: Müller Katharina
Published: January 2024

In this paper, we prove Kato’s main conjecture for
$CM$
modular forms for primes of potentially ordinary reduction under certain hypotheses on the modular form.
The acquisition of the semantics of Japanese numeral classifiers: The methodological value of nonsense
Authors: KUBOTA Maki , MATSUOKA Yuko , ROTHMAN Jason
Published: January 2024

This study examined the acquisition of numeral classifiers in 120 monolingual Japanese children. Previous research has argued that the complex semantic system underlying classifiers is late acquired. Thus, we set out to determine the age at which Japanese children are able to extend the semantic properties of classifiers to novel items/situations. Participants completed a comprehension task with a mouse-tracking extension and a production task with nonce and familiar items. While the comprehension results showed ceiling effects on familiar and nonce items, age significantly modulated a difference in accuracy between familiar and nonce items in the production task. The findings suggest that the acquisition of the underlying semantic system is acquired much earlier than previously argued. Previously attested issues with Japanese classifier production in young(er) children are more likely to reflect accessing difficulties than indexing the underlying grammatical competence of the classifier system.
Public health nurse-delivered cognitive behavioral therapy for postpartum depression: Assessing the effects of maternal treatment on infant emotion regulation
Authors: Amani Bahar , Krzeczkowski John E. , Schmidt Louis A. , Van Lieshout Ryan J.
Published: January 2024

The effects of maternal postpartum depression (PPD) on offspring emotion regulation (ER) are particularly deleterious as difficulties with ER predict an increased risk of psychopathology. This study examined the impact of maternal participation in a public health nurse (PHN)-delivered group cognitive behavioral therapy (CBT) intervention on infant ER. Mothers/birthing parents were ≥ 18 years old with an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10, and infants were < 12 months. Between 2017 and 2020, 141 mother–infant dyads were randomized to experimental or control groups. Infant ER was measured at baseline (T1) and nine weeks later (T2) using two neurophysiological measures (frontal alpha asymmetry (FAA) and high-frequency heart rate variability (HF-HRV)), and informant-report of infant temperament. Mothers were a mean of 30.8 years old (SD = 4.7), 92.3% were married/ common-law, and infants were a mean of 5.4 months old (SD = 2.9) and 52.1% were male. A statistically significant group-by-time interaction was found to predict change in HF-HRV between T1 and T2 (F(1,68.3) = 4.04, p = .04), but no significant interaction predicted change in FAA or temperament. Results suggest that PHN-delivered group CBT for PPD may lead to adaptive changes in a neurophysiological marker of infant ER, highlighting the importance of early maternal intervention.
How adolescents’ lives were disrupted over the course of the COVID-19 pandemic: A longitudinal investigation in 12 cultural groups in 9 nations from March 2020 to July 2022
Authors: Rothenberg W. Andrew , Skinner Ann T. , Lansford Jennifer E. , Bacchini Dario , Bornstein Marc H. , Chang Lei , Deater-Deckard Kirby , Di Giunta Laura , Dodge Kenneth A. , Gurdal Sevtap , Junla Daranee , Liu Qin , Long Qian , Oburu Paul , Pastorelli Concetta , Sorbring Emma , Steinberg Laurence , Tirado Liliana Maria Uribe , Yotanyamaneewong Saengduean , Alampay Liane Peña , Al-Hassan Suha M.
Published: January 2024

It is unclear how much adolescents’ lives were disrupted throughout the COVID-19 pandemic or what risk factors predicted such disruption. To answer these questions, 1,080 adolescents in 9 nations were surveyed 5 times from March 2020 to July 2022. Rates of adolescent COVID-19 life disruption were stable and high. Adolescents who, compared to their peers, lived in nations with higher national COVID-19 death rates, lived in nations with less stringent COVID-19 mitigation strategies, had less confidence in their government’s response to COVID-19, complied at higher rates with COVID-19 control measures, experienced the death of someone they knew due to COVID-19, or experienced more internalizing, externalizing, and smoking problems reported more life disruption due to COVID-19 during part or all of the pandemic. Additionally, when, compared to their typical levels of functioning, adolescents experienced spikes in national death rates, experienced less stringent COVID-19 mitigation measures, experienced less confidence in government response to the COVID-19 pandemic, complied at higher rates with COVID-19 control measures, experienced more internalizing problems, or smoked more at various periods during the pandemic, they also experienced more COVID-19 life disruption. Collectively, these findings provide new insights that policymakers can use to prevent the disruption of adolescents’ lives in future pandemics.
Attachment expectations moderate links between social support and maternal adjustment from 6 to 18 months postpartum
Authors: Gu Yufei , Waters Theodore E.A. , Zhu Victoria , Jamieson Brittany , Lim Danielle , Schmitt Gabrielle , Atkinson Leslie
Published: January 2024

Significant links exist between one’s perception of available social support and mental health outcomes, including during the transition to motherhood. Yet, attachment theory posits that individuals do not benefit equally from social support. As such, we examined the influence of attachment representations (i.e., secure base script knowledge) as they potentially moderate links between social support and psychological distress in a 1-year longitudinal study of an ethnically diverse (56% White) sample of infant-mother dyads. We hypothesized that higher social support would predict lower maternal psychological distress and this relation would be strongest in those with higher secure base script knowledge. Results indicated that maternal perceptions of social support were significantly negatively correlated with psychological distress. Analyses revealed that secure base script scores significantly moderated these associations. Interestingly, for those high in script knowledge, low social support predicted greater psychological distress. For those low in script knowledge, social support was unrelated to psychological distress. This pattern suggested that those who expect care (i.e., high secure base script knowledge) but receive minimal support (i.e., low perceived social support) find motherhood uniquely dysregulating. Practitioners may do well to examine individuals’ attachment expectations in relation to their current social support.
Pre-COVID respiratory sinus arrhythmia moderates associations between COVID-19 stress and child externalizing behaviors: Testing neurobiological stress theories
Authors: Skov Hilary , Glackin Erin B. , Drury Stacy S. , Lockman Jeffrey , Gray Sarah A. O.
Published: January 2024

Exposure to stress related to the COVID-19 pandemic contributes to psychopathology risk, yet not all children are negatively impacted. The current study examined a parasympathetic biomarker of stress sensitivity, respiratory sinus arrhythmia (RSA), as a moderator of the effects of exposure to pandemic stress on child internalizing and externalizing behaviors in a sample of children experiencing economic marginalization. Three to five years pre-pandemic, when children were preschool-aged, RSA during baseline and a challenging parent-child interaction were collected. Mid-pandemic, between November 2020 and March 2021, children’s exposure to pandemic stress and internalizing and externalizing behaviors were collected. Results demonstrated that children who, pre-pandemic, demonstrated blunted parasympathetic reactivity (i.e., no change in RSA relative to baseline) during the dyadic challenge exhibited elevated risk for externalizing behaviors mid-pandemic. Further, this risk was greatest for children exposed to high and moderate levels of pandemic stress. Consistent with diathesis stress and polyvagal frameworks, these conditional effects suggest that blunted parasympathetic reactivity in response to stress in early childhood may escalate the development of externalizing behaviors following stress exposure at school age.
The association between symptom burden and processing speed and executive functioning at 4 and 12 weeks following pediatric concussion
Authors: Sicard Veronik , Ledoux Andrée-Anne , Tang Ken , Yeates Keith Owen , Brooks Brian L. , Anderson Peter , Keightley Michelle , Desire Naddley , Beauchamp Miriam H. , Zemek Roger ,   for the Pediatric Emergency Research Canada (PERC) 5P Neuropsych team
Published: January 2024

Objectives:

Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association.

Methods:

This prospective, multicenter cohort study included participants aged 5.00–17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates.

Results:

311 children (65.0% males; median age = 11.92 [IQR = 9.14–14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2= 9.85,p= .043) and Verbal Fluency scores (χ2= 10.48,p= .033) across time points; these associations were not moderated by sex,ps≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores,ps≥ .17.

Conclusions:

Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.
The Postulate of Immortality in the Critique of Practical Reason (and Beyond)
Authors: Pasternack Lawrence
Published: January 2024

It is widely claimed that the second Critique’s argument for the postulate of immortality is relevantly different from the first Critique’s argument for the postulate. It is also widely claimed that after the second Critique, Kant distances himself from its particular version of the argument, and even the postulate altogether. It is the purpose of this article to challenge these claims, arguing instead that (a) there is overwhelming textual evidence showing that Kant did not abandon the postulate; (b) the second Critique does not contain a substantially different argument for the postulate than how it is argued for in the first Critique; and (c) the philosophical objections levied against the second Critique’s argument, including its putative substitution of holiness for virtue, become moot once its argument is better understood.
Ian Satunovskii: Identity and Biography, from the War to the Lyric
Authors: Golburt Luba
Published: January 2024

Ian Satunovskii's war lyric is an extensive corpus drawn from the entirety of his poetic career (early 1940s–early 1980s). Focusing on a few closely read selections, this essay attempts to make sense of this body of work, paying particular attention to the compounding of identities and temporalities in Satunovskii's very short texts. How does Satunovskii's poetry resist the hardening and polarization of identities occasioned by war? And how can we interpret Satunovskii's identification of war as a structuring event of his biography as well as the source of his poetics?
“Anecdote in the Vein of Herodotus”: Shuttling between Particulars and the Universal in Boris Slutskii's and Ian Satunovskii's War Poetry
Authors: Grinberg Marat
Published: January 2024

The article provides a comparative analysis of how two key poets, Boris Slutskii and Ian Satunovskii, responded to World War II, in which they both fought, in the poems written at the front or shortly thereafter. Via Lydia Ginzburg's notion of the deductive and inductive modes in lyric poetry, the article reveals how Slutskii and Satunovskii approach the figure of the enemy and shuttle between particulars and the universal in their verse. Dissimilar in their life choices (official for Slutskii and underground for Satunovskii), they share an aesthetic kinship, with Slutskii pressing harder toward generalizations, often radically revisionist, and Satunovskii insisting on the particulars and aphoristic fragmentariness. Both poets resist the grandiose and odic in figuring out how to navigate between the collective, personal, and intimate in confronting the catastrophe.
“Like a Magician Who Tricks the Eyes”: Demonism, Epistemological Uncertainty, and Religious Heterodoxy in Seventeenth-Century Ukraine
Authors: Bartolini Maria Grazia
Published: January 2024

This paper situates early modern Ukrainian demonological discourse within the framework of the major religious, cultural, and political disruption that affected Ukraine between 1596 and 1686. I will argue that the confessional struggles that followed the Union of Brest, the period of civil war known as “The Ruin,” and the eschatological expectations of the year 1666 contributed to a perception of increased diabolic activity but also to the problem of recognizing the possible discrepancies between reality and non-reality. How could one distinguish true visions from illusory phenomena, if the devil could enter the mind through “bad thoughts” and threaten the stability of one's cognitive experience? Furthermore, if there was more than one church, how could one distinguish between true and false doctrine? These questions, in turn, prompted early modern Ukrainian Orthodox intellectuals to question the role and reliability of sensory perception and human cognition, with issues of epistemology and deception becoming increasingly entangled with confessional polemics and religious dispute.
Radiative loss of coherence in free electrons: a long-range quantum phenomenon
Authors: Velasco Cruz I. , Di Giulio Valerio , García de Abajo F. Javier
Published: January 2024

Quantum physics rules the dynamics of small objects as they interact over microscopic length scales. Nevertheless, quantum correlations involving macroscopic distances can be observed between entangled photons as well as in atomic gases and matter waves at low temperatures. The long-range nature of the electromagnetic coupling between charged particles and extended objects could also trigger quantum phenomena over large distances. Here, we reveal a manifestation of quantum mechanics that involves macroscopic distances and results in a nearly complete depletion of coherence associated with which-way free-electron interference produced by electron–radiation coupling in the presence of distant extended objects. This is a ubiquitous effect that we illustrate through a rigorous theoretical analysis of a two-path electron beam interacting with a semi-infinite metallic plate and find the inter-path coherence to vanish proportionally to the path separation at zero temperature and exponentially at finite temperature. The investigated regime of large distances originates in the coupling of the electron to radiative modes assisted by diffraction at material structures but without any involvement of material excitations. Besides the fundamental interest of this macroscopic quantum phenomenon, our results suggest an approach to measuring the vacuum temperature and nondestructively sensing the presence of distant objects.
Brain and blood transcriptome profiles delineate common genetic pathways across suicidal ideation and suicide
Authors: Sun Shengnan , Liu Qingkun , Wang Zhaoyu , Huang Yung-yu , Sublette M. Elizabeth , Dwork Andrew J. , Rosoklija Gorazd , Ge Yongchao , Galfalvy Hanga , Mann J. John , Haghighi Fatemeh
Published: January 2024

Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to the severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with the presence of suicidal ideation were found within 18 co-expressed modules (p < 0.05), as well as in 3 co-expressed modules associated with suicidal ideation severity (p < 0.05, not explained by severity of depression). Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified and investigated using RNA-seq data from postmortem brain that revealed gene expression differences with moderate effect sizes in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity are associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability.
Persistence of amygdala hyperactivity to subliminal negative emotion processing in the long-term course of depression
Authors: Klug Melissa , Enneking Verena , Borgers Tiana , Jacobs Charlotte M. , Dohm Katharina , Kraus Anna , Grotegerd Dominik , Opel Nils , Repple Jonathan , Suslow Thomas , Meinert Susanne , Lemke Hannah , Leehr Elisabeth J. , Bauer Jochen , Dannlowski Udo , Redlich Ronny
Published: January 2024

Biased emotion processing has been suggested to underlie the etiology and maintenance of depression. Neuroimaging studies have shown mood-congruent alterations in amygdala activity in patients with acute depression, even during early, automatic stages of emotion processing. However, due to a lack of prospective studies over periods longer than 8 weeks, it is unclear whether these neurofunctional abnormalities represent a persistent correlate of depression even in remission. In this prospective case-control study, we aimed to examine brain functional correlates of automatic emotion processing in the long-term course of depression. In a naturalistic design, n = 57 patients with acute major depressive disorder (MDD) and n = 37 healthy controls (HC) were assessed with functional magnetic resonance imaging (fMRI) at baseline and after 2 years. Patients were divided into two subgroups according to their course of illness during the study period (n = 37 relapse, n = 20 no-relapse). During fMRI, participants underwent an affective priming task that assessed emotion processing of subliminally presented sad and happy compared to neutral face stimuli. A group × time × condition (3 × 2 × 2) ANOVA was performed for the amygdala as region-of-interest (ROI). At baseline, there was a significant group × condition interaction, resulting from amygdala hyperactivity to sad primes in patients with MDD compared to HC, whereas no difference between groups emerged for happy primes. In both patient subgroups, amygdala hyperactivity to sad primes persisted after 2 years, regardless of relapse or remission at follow-up. The results suggest that amygdala hyperactivity during automatic processing of negative stimuli persists during remission and represents a trait rather than a state marker of depression. Enduring neurofunctional abnormalities may reflect a consequence of or a vulnerability to depression.
The regulations of telomerase reverse transcriptase (TERT) in cancer
Authors: Liu Mingdi , Zhang Yuning , Jian Yongping , Gu Liting , Zhang Dan , Zhou Honglan , Wang Yishu , Xu Zhi-Xiang
Published: January 2024

Abnormal activation of telomerase occurs in most cancer types, which facilitates escaping from cell senescence. As the key component of telomerase, telomerase reverse transcriptase (TERT) is regulated by various regulation pathways. TERT gene changing in its promoter and phosphorylation respectively leads to TERT ectopic expression at the transcription and protein levels. The co-interacting factors play an important role in the regulation of TERT in different cancer types. In this review, we focus on the regulators of TERT and these downstream functions in cancer regulation. Determining the specific regulatory mechanism will help to facilitate the development of a cancer treatment strategy that targets telomerase and cancer cell senescence.
Epigenetic priming targets tumor heterogeneity to shift transcriptomic phenotype of pancreatic ductal adenocarcinoma towards a Vitamin D susceptible state
Authors: He Bo , Stoffel Lauren , He Clifford Jiajun , Cho Kumsun , Li Albert M. , Jiang Haowen , Flowers Brittany M. , Nguyen Kha The , Wang Kelly Wen , Zhao Audrey Yixin , Zhou Meng-Ning , Ferreira Sofia , Attardi Laura D. , Ye Jiangbin
Published: January 2024

As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance stemming from this heterogeneity remains a significant challenge. Here, we report that Vitamin D-resistant PDAC cells hijacked Vitamin D signaling to promote tumor progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2′-deoxycytidine (5-Aza) overcame Vitamin D resistance and shifted the transcriptomic phenotype of PDAC toward a Vitamin D-susceptible state. Increasing overall H3K27 acetylation with GTA and reducing overall DNA methylation with 5-Aza not only elevated the Vitamin D receptor (VDR) expression but also reprogrammed the Vitamin D-responsive genes. Consequently, Vitamin D inhibited cell viability and migration in the epigenetically primed PDAC cells by activating genes involved in apoptosis as well as genes involved in negative regulation of cell proliferation and migration, while the opposite effect of Vitamin D was observed in unprimed cells. Studies in genetically engineered mouse PDAC cells further validated the effects of epigenetic priming for enhancing the anti-tumor activity of Vitamin D. Using gain- and loss-of-function experiments, we further demonstrated that VDR expression was necessary but not sufficient for activating the favorable transcriptomic phenotype in respond to Vitamin D treatment in PDAC, highlighting that both the VDR and Vitamin D-responsive genes were prerequisites for Vitamin D response. These data reveal a previously undefined mechanism in which epigenetic state orchestrates the expression of both VDR and Vitamin D-responsive genes and determines the therapeutic response to Vitamin D in PDAC.
Short-term response to anti-VEGF as indicator of visual prognosis in refractory age-related macular degeneration
Authors: Gigon Anthony , Iskandar Antonio , Kasser Sophie , Naso Sacha , Zola Marta , Mantel Irmela
Published: January 2024

Background

Some patients with neovascular age-related macular degeneration (nAMD) respond insufficiently to anti-VEGF treatment despite maximal monthly intravitreal injections. Their short-term response between injections was investigated for extent and visual prognosis.

Subjects/Methods

Monocentric retrospective observational study. 45 eyes from 41 patients with refractory nAMD (who previously received at least 12 months of anti-VEGF treatment), evaluated by optical coherence tomography (OCT) in between monthly anti-VEGF injections. The fluid profile on OCT was evaluated before, 1 week after, and 1 month after an intravitreal injection, using central retinal thickness (CRT), manual measurements, and fluid specific volumetric measurements performed by an automated algorithm based on artificial intelligence.

Results

A significant improvement was found at week 1 in terms of CRT (p < 0.0001), intraretinal (IRF) (p = 0.007), subretinal fluid (SRF) (p < 0.0001), and pigment epithelium detachment (PED) volume (p < 0.0001). Volumetric fluid measures revealed a >50% reduction at week 1 for both IRF and SRF for approximately two-thirds of eyes. Poorer short-term response was associated with larger exudative fluid amounts (IRF + SRF) (p = 0.003), larger PED (p = 0.007), lower visual acuity (p = 0.004) and less anatomic changes at treatment initiation (p < 0.0001). Univariate and multivariate analysis revealed that visual outcomes 4 and 5 years later was significantly worse with weaker short-term responsiveness (p = 0.005), with the presence of atrophy (p = 0.01) and larger PED volumes (p = 0.002).

Conclusions

Incomplete responders to anti-VEGF showed a significant short-term response, identifiable at 1 week after injection, with rapid recurrence at 1 month. Weaker short-term responsiveness at 1 week was associated with poorer long term visual prognosis. These patients may need adjuvant treatment to improve their prognosis.
Preclinical dose response study shows NR2E3 can attenuate retinal degeneration in the retinitis pigmentosa mouse model RhoP23H+/−
Authors: McNamee Shannon M. , Chan Natalie P. , Akula Monica , Avola Marielle O. , Whalen Maiya , Nystuen Kaden , Singh Pushpendra , Upadhyay Arun K. , DeAngelis Margaret M. , Haider Neena B.
Published: January 2024

Retinitis pigmentosa (RP) is a heterogeneous disease and the main cause of vision loss within the group of inherited retinal diseases (IRDs). IRDs are a group of rare disorders caused by mutations in one or more of over 280 genes which ultimately result in blindness. Modifier genes play a key role in modulating disease phenotypes, and mutations in them can affect disease outcomes, rate of progression, and severity. Our previous studies have demonstrated that the nuclear hormone receptor 2 family e, member 3 (Nr2e3) gene reduced disease progression and loss of photoreceptor cell layers in RhoP23H−/− mice. This follow up, pharmacology study evaluates a longitudinal NR2E3 dose response in the clinically relevant heterozygous RhoP23H mouse. Reduced retinal degeneration and improved retinal morphology was observed 6 months following treatment evaluating three different NR2E3 doses. Histological and immunohistochemical analysis revealed regions of photoreceptor rescue in the treated retinas of RhoP23H+/− mice. Functional assessment by electroretinogram (ERG) showed attenuated photoreceptor degeneration with all doses. This study demonstrates the effectiveness of different doses of NR2E3 at reducing retinal degeneration and informs dose selection for clinical trials of RhoP23H-associated RP.
Using deep learning to quantify neuronal activation from single-cell and spatial transcriptomic data
Authors: Bahl Ethan , Chatterjee Snehajyoti , Mukherjee Utsav , Elsadany Muhammad , Vanrobaeys Yann , Lin Li-Chun , McDonough Miriam , Resch Jon , Giese K. Peter , Abel Ted , Michaelson Jacob J.
Published: January 2024

Neuronal activity-dependent transcription directs molecular processes that regulate synaptic plasticity, brain circuit development, behavioral adaptation, and long-term memory. Single cell RNA-sequencing technologies (scRNAseq) are rapidly developing and allow for the interrogation of activity-dependent transcription at cellular resolution. Here, we present NEUROeSTIMator, a deep learning model that integrates transcriptomic signals to estimate neuronal activation in a way that we demonstrate is associated with Patch-seq electrophysiological features and that is robust against differences in species, cell type, and brain region. We demonstrate this method’s ability to accurately detect neuronal activity in previously published studies of single cell activity-induced gene expression. Further, we applied our model in a spatial transcriptomic study to identify unique patterns of learning-induced activity across different brain regions in male mice. Altogether, our findings establish NEUROeSTIMator as a powerful and broadly applicable tool for measuring neuronal activation, whether as a critical covariate or a primary readout of interest.
Structural connectome architecture shapes the maturation of cortical morphology from childhood to adolescence
Authors: Liang Xinyuan , Sun Lianglong , Liao Xuhong , Lei Tianyuan , Xia Mingrui , Duan Dingna , Zeng Zilong , Li Qiongling , Xu Zhilei , Men Weiwei , Wang Yanpei , Tan Shuping , Gao Jia-Hong , Qin Shaozheng , Tao Sha , Dong Qi , Zhao Tengda , He Yong
Published: January 2024

Cortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Here, we show cortical thinning patterns primarily located in the lateral frontal and parietal heteromodal nodes during childhood and adolescence, which are structurally constrained by white matter network architecture and are particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible in another independent dataset. These findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence.
Mechanochemical synthesis of organoselenium compounds
Authors: Chen Shanshan , Fan Chunying , Xu Zijian , Pei Mengyao , Wang Jiemin , Zhang Jiye , Zhang Yilei , Li Jiyu , Lu Junliang , Peng Cheng , Wei Xiaofeng
Published: January 2024

We disclose herein a strategy for the rapid synthesis of versatile organoselenium compounds under mild conditions. In this work, magnesium-based selenium nucleophiles are formed in situ from easily available organic halides, magnesium metal, and elemental selenium via mechanical stimulation. This process occurs under liquid-assisted grinding (LAG) conditions, requires no complicated pre-activation procedures, and operates broadly across a diverse range of aryl, heteroaryl, and alkyl substrates. In this work, symmetrical diselenides are efficiently obtained after work-up in the air, while one-pot nucleophilic addition reactions with various electrophiles allow the comprehensive synthesis of unsymmetrical monoselenides with high functional group tolerance. Notably, the method is applied to regioselective selenylation reactions of diiodoarenes and polyaromatic aryl halides that are difficult to operate via solution approaches. Besides selenium, elemental sulfur and tellurium are also competent in this process, which showcases the potential of the methodology for the facile synthesis of organochalcogen compounds.
MARC-3, a membrane-associated ubiquitin ligase, is required for fast polyspermy block in Caenorhabditis elegans
Authors: Kawasaki Ichiro , Sugiura Kenta , Sasaki Taeko , Matsuda Noriyuki , Sato Miyuki , Sato Ken
Published: January 2024

In many sexually reproducing organisms, oocytes are fundamentally fertilized with one sperm. In Caenorhabditis elegans, chitin layer formation after fertilization by the EGG complex is one of the mechanisms of polyspermy block, but other mechanisms remain unknown. Here, we demonstrate that MARC-3, a membrane-associated RING-CH-type ubiquitin ligase that localizes to the plasma membrane and cortical puncta in oocytes, is involved in fast polyspermy block. During polyspermy, the second sperm entry occurs within approximately 10 s after fertilization in MARC-3-deficient zygotes, whereas it occurs approximately 200 s after fertilization in egg-3 mutant zygotes defective in the chitin layer formation. MARC-3 also functions in the selective degradation of maternal plasma membrane proteins and the transient accumulation of endosomal lysine 63-linked polyubiquitin after fertilization. The RING-finger domain of MARC-3 is required for its in vitro ubiquitination activity and polyspermy block, suggesting that a ubiquitination-mediated mechanism sequentially regulates fast polyspermy block and maternal membrane protein degradation during the oocyte-to-embryo transition.
The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony
Authors: Wang Jin-Lei , Li Ting-Ting , Zhang Nian-Zhang , Wang Meng , Sun Li-Xiu , Zhang Zhi-Wei , Fu Bao-Quan , Elsheikha Hany M. , Zhu Xing-Quan
Published: January 2024

Sexual development inToxoplasma gondiiis a multistep process that culminates in the production of oocysts, constituting approximately 50% of human infections. However, the molecular mechanisms governing sexual commitment in this parasite remain poorly understood. Here, we demonstrate that the transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual commitment during asexual development. Depletion of AP2XI-2 in type II Pru strain induces merogony and production of mature merozoites in an alkaline medium but not in a neutral medium. In contrast, AP2XII-1-depleted Pru strain undergoes several rounds of merogony and produces merozoites in a neutral medium, with more pronounced effects observed under alkaline conditions. Additionally, we identified two additional AP2XI-2-interacting proteins involved in repressing merozoite programming. These findings underscore the intricate regulation of pre-sexual commitment by a network of factors and suggest that AP2XI-2 or AP2XII-1-depleted Pru parasites can serve as a model for studying merogony in vitro.
Chirality manipulation of ultrafast phase switches in a correlated CDW-Weyl semimetal
Authors: Cheng Bing , Cheng Di , Jiang Tao , Xia Wei , Song Boqun , Mootz Martin , Luo Liang , Perakis Ilias E. , Yao Yongxin , Guo Yanfeng , Wang Jigang
Published: January 2024

Light engineering of correlated states in topological materials provides a new avenue of achieving exotic topological phases inaccessible by conventional tuning methods. Here we demonstrate a light control of correlation gaps in a model charge-density-wave (CDW) and polaron insulator (TaSe4)2I recently predicted to be an axion insulator. Our ultrafast terahertz photocurrent spectroscopy reveals a two-step, non-thermal melting of polarons and electronic CDW gap via the fluence dependence of a longitudinal circular photogalvanic current. This helicity-dependent photocurrent reveals continuous ultrafast phase switches from the polaronic state to the CDW (axion) phase, and finally to a hidden Weyl phase as the pump fluence increases. Additional distinctive attributes aligning with the light-induced switches include: the mode-selective coupling of coherent phonons to the polaron and CDW modulation, and the emergence of a non-thermal chiral photocurrent above the pump threshold of CDW-related phonons. The demonstrated ultrafast chirality control of correlated topological states here holds large potentials for realizing axion electrodynamics and advancing quantum-computing applications.
High-spatial resolution functional chemistry of nitrogen compounds in the observed UK meteorite fall Winchcombe
Authors: Vollmer Christian , Kepaptsoglou Demie , Leitner Jan , Mosberg Aleksander B. , El Hajraoui Khalil , King Ashley J. , Bays Charlotte L. , Schofield Paul F. , Araki Tohru , Ramasse Quentin M.
Published: January 2024

Organic matter in extraterrestrial samples is a complex material that might have played an important role in the delivery of prebiotic molecules to the early Earth. We report here on the identification of nitrogen-containing compounds such as amino acids and N-heterocycles within the recent observed meteorite fall Winchcombe by high-spatial resolution spectroscopy techniques. Although nitrogen contents of Winchcombe organic matter are low (N/C ~ 1–3%), we were able to detect the presence of these compounds using a low-noise direct electron detector. These biologically relevant molecules have therefore been tentatively found within a fresh, minimally processed meteorite sample by high spatial resolution techniques conserving the overall petrographic context. Carbon functional chemistry investigations show that sizes of aromatic domains are small and that abundances of carboxylic functional groups are low. Our observations demonstrate that Winchcombe represents an important addition to the collection of carbonaceous chondrites and still preserves pristine extraterrestrial organic matter.
A wearable electrostimulation-augmented ionic-gel photothermal patch doped with MXene for skin tumor treatment
Authors: Ju Xingkai , Kong Jiao , Qi Guohua , Hou Shuping , Diao Xingkang , Dong Shaojun , Jin Yongdong
Published: January 2024

A wearable biological patch capable of producing multiple responses to light and electricity without interfering with daily activities is highly desired for skin cancer treatment, but remains a key challenge. Herein, the skin-mountable electrostimulation-augmented photothermal patch (eT-patch) comprising transparent ionic gel with MXene (Ti3C2Tx) doping is developed and applied for the treatment of melanoma under photostimulation at 0.5 W/cm2. The eT-patch designed has superior photothermal and electrical characteristics owing to ionic gels doped with MXene which provides high photothermal conversion efficiency and electrical conductivity as a medium. Simultaneously, the ionic gel-based eT-patch having excellent optical transparency actualizes real-time observation of skin response and melanoma treatment process under photothermal and electrical stimulation (PES) co-therapy. Systematical cellular study on anti-tumor mechanism of the eT-patch under PES treatment revealed that eT-patch under PES treatment can synergically trigger cancer cell apoptosis and pyroptosis, which together lead to the death of melanoma cells. Due to the obvious advantages of relatively safe and less side effects in healthy organs, the developed eT-patch provides a promising cost-effective therapeutic strategy for skin tumors and will open a new avenue for biomedical applications of ionic gels.
A cytomegalovirus inflammasome inhibitor reduces proinflammatory cytokine release and pyroptosis
Authors: Deng Yingqi , Ostermann Eleonore , Brune Wolfram
Published: January 2024

In response to viral infection, cells can initiate programmed cell death (PCD), leading to a reduction in the release of viral progeny. Viruses have therefore evolved specific mechanisms to curb PCD. Cytomegaloviruses (CMVs) are sophisticated manipulators of cellular defenses and encode potent inhibitors of apoptosis and necroptosis. However, a CMV inhibitor of pyroptosis has not been clearly identified and characterized. Here we identify the mouse cytomegalovirus M84 protein as an inhibitor of pyroptosis and proinflammatory cytokine release. M84 interacts with the pyrin domain of AIM2 and ASC to inhibit inflammasome assembly. It thereby prevents Caspase-1-mediated activation of interleukin 1β (IL-1β), IL-18, and Gasdermin D. Growth attenuation of an M84-deficient MCMV in macrophages is rescued by knockout of either Aim2 or Asc or by treatment with a Caspase-1 inhibitor, and its attenuation in infected mice is partially rescued in Asc knockout mice. Thus, viral inhibition of the inflammasome-pyroptosis pathway is important to promote viral replication in vivo.