bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin treatment has vasculo-protective effects in lipodystrophic mice
Authors: Stürzebecher Paulina Elena , Kralisch Susan , Schubert Marie Ruth , Filipova Vanina , Hoffmann Annett , Oliveira Fabiana , Sheikh Bilal N. , Blüher Matthias , Kogel Alexander , Scholz Markus , Kokot Karoline Elizabeth , Erbe Stephan , Kneuer Jasmin Marga , Ebert Thomas , Fasshauer Mathias , Miehle Konstanze , Laufs Ulrich , Tönjes Anke , Boeckel Jes-Niels
Published: September 2022

Lipodystrophy syndromes (LDs) are characterized by loss of adipose tissue, metabolic complications such as dyslipidemia, insulin resistance, and fatty liver disease, as well as accelerated atherosclerosis. As a result of adipose tissue deficiency, the systemic concentration of the adipokine leptin is reduced. A current promising therapeutic option for patients with LD is treatment with recombinant leptin (metreleptin), resulting in reduced risk of mortality. Here, we investigate the effects of leptin on endothelial to mesenchymal transition (EndMT), which impair the functional properties of endothelial cells and promotes atherogenesis in LD. Leptin treatment reduced inflammation and TGF-β2–induced expression of mesenchymal genes and prevented impairment of endothelial barrier function. Treatment of lipodystrophic- and atherosclerosis-prone animals (Ldlr
−/−
; aP2-nSrebp1c-Tg) with leptin reduced macrophage accumulation in atherosclerotic lesions, vascular plaque protrusion, and the number of endothelial cells with mesenchymal gene expression, confirming a reduction in EndMT in LD after leptin treatment. Treatment with leptin inhibited LD-mediated induction of the proatherosclerotic cytokine growth/differentiation factor 15 (
GDF15
). Inhibition of
GDF15
reduced EndMT induction triggered by plasma from patients with LD. Our study reveals that in addition to the effects on adipose tissue function, leptin treatment exerts beneficial effects protecting endothelial function and identity in LD by reducing
GDF15
.
New light on the use of
Theobroma cacao
by Late Classic Maya
Authors: Ford Anabel , Williams Ann , de Vries Mattanjah S.
Published: September 2022

Cacao seeds,
Theobroma cacao
, provide the basis for a ceremonially important Mesoamerican food. Past efforts to identify cacao in ceramics focused on highly decorative vessel forms associated with elite ceremonial contexts, creating assumptions as to how cacao was distributed and who could access it. This study examines 54 archaeological ceramic sherds from El Pilar (Belize/Guatemala) of Late Classic (600 to 900 CE) residential and civic contexts representing a cross-section of ancient Maya inhabitants. Identification of cacao in ancient sherds has depended on the general presence of theobromine; we used the discrete presence of theophylline, a unique key biomarker for cacao in the region. Analysis was done by grinding off all outside surfaces to reduce contamination, pulverizing the inner clay matrix, extracting absorbed molecules, and concentrating the extractions. In order to obtain especially high selectivity and low limits of detection, our study utilized the technique of resonance-enhanced multiphoton ionization coupled with laser-desorption jet-cooling mass spectrometry. This technique isolates molecules in the cold gas phase where they can be selectively ionized through a resonant two-photon process. Of the sherds analyzed, 30 samples (56%) were found to contain significant amounts of theophylline and thus test positive for cacao. Importantly, cacao is present in all contexts, common to all Maya residents near and far from centers.
Single-molecule investigations of single-chain cellulose biosynthesis
Authors: Hilton Mark A. , Manning Harris W. , Górniak Ireneusz , Brady Sonia K. , Johnson Madeline M. , Zimmer Jochen , Lang Matthew J.
Published: September 2022

Cellulose biosynthesis in sessile bacterial colonies originates in the membrane-integrated bacterial cellulose synthase (Bcs) AB complex. We utilize optical tweezers to measure single-strand cellulose biosynthesis by BcsAB from
Rhodobacter sphaeroides
. Synthesis depends on uridine diphosphate glucose, Mg
2+
, and cyclic diguanosine monophosphate, with the last displaying a retention time of ∼80 min. Below a stall force of 12.7 pN, biosynthesis is relatively insensitive to force and proceeds at a rate of one glucose addition every 2.5 s at room temperature, increasing to two additions per second at 37°. At low forces, conformational hopping is observed. Single-strand cellulose stretching unveiled a persistence length of 6.2 nm, an axial stiffness of 40.7 pN, and an ability for complexes to maintain a tight grip, with forces nearing 100 pN. Stretching experiments exhibited hysteresis, suggesting that cellulose microstructure underpinning robust biofilms begins to form during synthesis. Cellohexaose spontaneously binds to nascent single cellulose strands, impacting polymer mechanical properties and increasing BcsAB activity.
Expanding the genetic toolkit helps dissect a global stress response in the early-branching species
Fusobacterium nucleatum
Authors: Ponath Falk , Zhu Yan , Cosi Valentina , Vogel Jörg
Published: September 2022

Fusobacterium nucleatum
, long known as a common oral microbe, has recently garnered attention for its ability to colonize tissues and tumors elsewhere in the human body. Clinical and epidemiological research has now firmly established
F. nucleatum
as an oncomicrobe associated with several major cancer types. However, with the current research focus on host associations, little is known about gene regulation in
F. nucleatum
itself, including global stress-response pathways that typically ensure the survival of bacteria outside their primary niche. This is due to the phylogenetic distance of Fusobacteriota to most model bacteria, their limited genetic tractability, and paucity of known gene functions. Here, we characterize a global transcriptional stress-response network governed by the extracytoplasmic function sigma factor, σ
E
. To this aim, we developed several genetic tools for this anaerobic bacterium, including four different fluorescent marker proteins, inducible gene expression, scarless gene deletion, and transcriptional and translational reporter systems. Using these tools, we identified a σ
E
response partly reminiscent of phylogenetically distant Proteobacteria but induced by exposure to oxygen. Although
F. nucleatum
lacks canonical RNA chaperones, such as Hfq, we uncovered conservation of the noncoding arm of the σ
E
response in form of the noncoding RNA FoxI. This regulatory small RNA acts as an mRNA repressor of several membrane proteins, thereby supporting the function of σ
E
. In addition to the characterization of a global stress response in
F. nucleatum
, the genetic tools developed here will enable further discoveries and dissection of regulatory networks in this early-branching bacterium.
Antagonistic control of active surface integrins by myotubularin and phosphatidylinositol 3-kinase C2β in a myotubular myopathy model
Authors: Samsó Paula , Koch Philipp A. , Posor York , Lo Wen-Ting , Belabed Hassane , Nazare Marc , Laporte Jocelyn , Haucke Volker
Published: September 2022

X-linked centronuclear myopathy (XLCNM) is a severe human disease without existing therapies caused by mutations in the phosphoinositide 3-phosphatase MTM1. Loss of MTM1 function is associated with muscle fiber defects characterized by impaired localization of β-integrins and other components of focal adhesions. Here we show that defective focal adhesions and reduced active β-integrin surface levels in a cellular model of XLCNM are rescued by loss of phosphatidylinositiol 3-kinase C2β (PI3KC2β) function. Inactivation of the
Mtm1
gene impaired myoblast differentiation into myotubes and resulted in reduced surface levels of active β1-integrins as well as corresponding defects in focal adhesions. These phenotypes were rescued by concomitant genetic loss of
Pik3c2b
or pharmacological inhibition of PI3KC2β activity. We further demonstrate that a hitherto unknown role of PI3KC2β in the endocytic trafficking of active β1-integrins rather than rescue of phosphatidylinositol 3-phosphate levels underlies the ability of
Pik3c2b
to act as a genetic modifier of cellular XLCNM phenotypes. Our findings reveal a crucial antagonistic function of MTM1 and PI3KC2β in the control of active β-integrin surface levels, thereby providing a molecular mechanism for the adhesion and myofiber defects observed in XLCNM. They further suggest specific pharmacological inhibition of PI3KC2β catalysis as a viable treatment option for XLCNM patients.
Structures of a large prolate virus capsid in unexpanded and expanded states generate insights into the icosahedral virus assembly
Authors: Fang Qianglin , Tang Wei-Chun , Fokine Andrei , Mahalingam Marthandan , Shao Qianqian , Rossmann Michael G. , Rao Venigalla B.
Published: September 2022

Many icosahedral viruses assemble proteinaceous precursors called proheads or procapsids. Proheads are metastable structures that undergo a profound structural transition known as expansion that transforms an immature unexpanded head into a mature genome-packaging head. Bacteriophage T4 is a model virus, well studied genetically and biochemically, but its structure determination has been challenging because of its large size and unusually prolate-shaped, ∼1,200-Å-long and ∼860-Å-wide capsid. Here, we report the cryogenic electron microscopy (cryo-EM) structures of T4 capsid in both of its major conformational states: unexpanded at a resolution of 5.1 Å and expanded at a resolution of 3.4 Å. These are among the largest structures deposited in Protein Data Bank to date and provide insights into virus assembly, head length determination, and shell expansion. First, the structures illustrate major domain movements and ∼70% additional gain in inner capsid volume, an essential transformation to contain the entire viral genome. Second, intricate intracapsomer interactions involving a unique insertion domain dramatically change, allowing the capsid subunits to rotate and twist while the capsomers remain fastened at quasi-threefold axes. Third, high-affinity binding sites emerge for a capsid decoration protein that clamps adjacent capsomers, imparting extraordinary structural stability. Fourth, subtle conformational changes at capsomers’ periphery modulate intercapsomer angles between capsomer planes that control capsid length. Finally, conformational changes were observed at the symmetry-mismatched portal vertex, which might be involved in triggering head expansion. These analyses illustrate how small changes in local capsid subunit interactions lead to profound shifts in viral capsid morphology, stability, and volume.
ASPM promotes ATR-CHK1 activation and stabilizes stalled replication forks in response to replication stress
Authors: Wu Xingxuan , Xu Shibin , Wang Peipei , Wang Zhao-Qi , Chen Hongxiang , Xu Xingzhi , Peng Bin
Published: September 2022

ASPM is a protein encoded byprimary microcephaly 5(MCPH5) and is responsible for ensuring spindle position during mitosis and the symmetrical division of neural stem cells. We recently reported that ASPM promotes homologous recombination (HR) repair of DNA double strand breaks. However, its potential role in DNA replication and replication stress response remains elusive. Interestingly, we found that ASPM is dispensable for DNA replication under unperturbed conditions. However, ASPM is enriched at stalled replication forks in a RAD17-dependent manner in response to replication stress and promotes RAD9 and TopBP1 loading onto chromatin, facilitating ATR-CHK1 activation. ASPM depletion results in failed fork restart and nuclease MRE11-mediated nascent DNA degradation at the stalled replication fork. The overall consequence is chromosome instability and the sensitization of cancer cells to replication stressors. These data support a role for ASPM in loading RAD17-RAD9/TopBP1 onto chromatin to activate the ATR-CHK1 checkpoint and ultimately ensure genome stability.
Extracellular carbonic anhydrase activity promotes a carbon concentration mechanism in metazoan calcifying cells
Authors: Matt Ann-Sophie , Chang William W. , Hu Marian Y.
Published: September 2022

Many calcifying organisms utilize metabolic CO
2
to generate CaCO
3
minerals to harden their shells and skeletons. Carbonic anhydrases are evolutionary ancient enzymes that have been proposed to play a key role in the calcification process, with the underlying mechanisms being little understood. Here, we used the calcifying primary mesenchyme cells (PMCs) of sea urchin larva to study the role of cytosolic (iCAs) and extracellular carbonic anhydrases (eCAs) in the cellular carbon concentration mechanism (CCM). Molecular analyses identified iCAs and eCAs in PMCs and highlight the prominent expression of a glycosylphosphatidylinositol-anchored membrane-bound CA (Cara7). Intracellular pH recordings in combination with CO
2
pulse experiments demonstrated iCA activity in PMCs. iCA activity measurements, together with pharmacological approaches, revealed an opposing contribution of iCAs and eCAs on the CCM. H
+
-selective electrodes were used to demonstrate eCA-catalyzed CO
2
hydration rates at the cell surface. Knockdown of Cara7 reduced extracellular CO
2
hydration rates accompanied by impaired formation of specific skeletal segments. Finally, reduced pH
i
regulatory capacities during inhibition and knockdown of Cara7 underscore a role of this eCA in cellular HCO
3
−
uptake. This work reveals the function of CAs in the cellular CCM of a marine calcifying animal. Extracellular hydration of metabolic CO
2
by Cara7 coupled to HCO
3
−
uptake mechanisms mitigates the loss of carbon and reduces the cellular proton load during the mineralization process. The findings of this work provide insights into the cellular mechanisms of an ancient biological process that is capable of utilizing CO
2
to generate a versatile construction material.
Boosting the reaction kinetics in aprotic lithium-carbon dioxide batteries with unconventional phase metal nanomaterials
Authors: Zhou Jingwen , Wang Tianshuai , Chen Lin , Liao Lingwen , Wang Yunhao , Xi Shibo , Chen Bo , Lin Ting , Zhang Qinghua , Ye Chenliang , Zhou Xichen , Guan Zhiqiang , Zhai Li , He Zhen , Wang Gang , Wang Juan , Yu Jinli , Ma Yangbo , Lu Pengyi , Xiong Yuecheng , Lu Shiyao , Chen Ye , Wang Bin , Lee Chun-Sing , Cheng Jianli , Gu Lin , Zhao Tianshou , Fan Zhanxi
Published: September 2022

Given the high energy density and eco-friendly characteristics, lithium-carbon dioxide (Li-CO2) batteries have been considered to be a next-generation energy technology to promote carbon neutral and space exploration. However, Li-CO2batteries suffer from sluggish reaction kinetics, causing large overpotential and poor energy efficiency. Here, we observe enhanced reaction kinetics in aprotic Li-CO2batteries with unconventional phase 4H/face-centered cubic (fcc) iridium (Ir) nanostructures grown on gold template. Significantly, 4H/fcc Ir exhibits superior electrochemical performance over fcc Ir in facilitating the round-trip reaction kinetics of Li+-mediated CO2reduction and evolution, achieving a low charge plateau below 3.61 V and high energy efficiency of 83.8%. Ex situ/in situ studies and theoretical calculations reveal that the boosted reaction kinetics arises from the highly reversible generation of amorphous/low-crystalline discharge products on 4H/fcc Ir via the Ir-O coupling. The demonstration of flexible Li-CO2pouch cells with 4H/fcc Ir suggests the feasibility of using unconventional phase nanomaterials in practical scenarios.
Metabolic novelty originating from horizontal gene transfer is essential for leaf beetle survival
Authors: Kirsch Roy , Okamura Yu , Haeger Wiebke , Vogel Heiko , Kunert Grit , Pauchet Yannick
Published: September 2022

Horizontal gene transfer (HGT) provides an evolutionary shortcut for recipient organisms to gain novel functions. Although reports of HGT in higher eukaryotes are rapidly accumulating, in most cases the evolutionary trajectory, metabolic integration, and ecological relevance of acquired genes remain unclear. Plant cell wall degradation by HGT-derived enzymes is widespread in herbivorous insect lineages. Pectin is an abundant polysaccharide in the walls of growing parts of plants. We investigated the significance of horizontally acquired pectin-digesting polygalacturonases (PGs) of the leaf beetlePhaedon cochleariae. Using a CRISPR/Cas9-guided gene knockout approach, we generated a triple knockout and a quadruple PG-null mutant in order to investigate the enzymatic, biological, and ecological effects. We found that pectin-digestion 1) is exclusively linked to the horizontally acquired PGs from fungi, 2) became fixed in the host genome by gene duplication leading to functional redundancy, 3) compensates for nutrient-poor diet by making the nutritious cell contents more accessible, and 4) facilitates the beetles development and survival. Our analysis highlights the selective advantage PGs provide to herbivorous insects and demonstrate the impact of HGT on the evolutionary success of leaf-feeding beetles, major contributors to species diversity.
Gendered citation patterns among the scientific elite
Authors: Lerman Kristina , Yu Yulin , Morstatter Fred , Pujara Jay
Published: September 2022

Diversity in science is necessary to improve innovation and increase the capacity of the scientific workforce. Despite decades-long efforts to increase gender diversity, however, women remain a small minority in many fields, especially in senior positions. The dearth of elite women scientists, in turn, leaves fewer women to serve as mentors and role models for young women scientists. To shed light on gender disparities in science, we study prominent scholars who were elected to the National Academy of Sciences. We construct author citation networks that capture the structure of recognition among scholars’ peers. We identify gender disparities in the patterns of peer citations and show that these differences are strong enough to accurately predict the scholar’s gender. In contrast, we do not observe disparities due to prestige, with few significant differences in the structure of citations of scholars affiliated with high-ranked and low-ranked institutions. These results provide further evidence that a scholar’s gender plays a role in the mechanisms of success in science.
Omnimodal topological polarization of bilayer networks: Analysis in the Maxwell limit and experiments on a 3D-printed prototype
Authors: Charara Mohammad , McInerney James , Sun Kai , Mao Xiaoming , Gonella Stefano
Published: September 2022

Periodic networks on the verge of mechanical instability, called Maxwell lattices, are known to exhibit zero-frequency modes localized to their boundaries. Topologically polarized Maxwell lattices, in particular, focus these zero modes to one of their boundaries in a manner that is protected against disorder by the reciprocal-space topology of the lattice’s band structure. Here, we introduce a class of mechanical bilayers as a model system for designing topologically protected edge modes that couple in-plane dilational and shearing modes to out-of-plane flexural modes, a paradigm that we refer to as “omnimodal polarization.” While these structures exhibit a high-dimensional design space that makes it difficult to predict the topological polarization of generic geometries, we are able to identify a family of mirror-symmetric bilayers that inherit the in-plane modal localization of their constitutive monolayers, whose topological polarization can be determined analytically. Importantly, the coupling between the layers results in the emergence of omnimodal polarization, whereby in-plane and out-of-plane edge modes localize on the same edge. We demonstrate these theoretical results by fabricating a mirror-symmetric, topologically polarized kagome bilayer consisting of a network of elastic beams via additive manufacturing and confirm this finite-frequency polarization via finite element analysis and laser-vibrometry experiments.
Atomic distribution and local structure in ice VII from in situ neutron diffraction
Authors: Yamashita Keishiro , Komatsu Kazuki , Klotz Stefan , Fabelo Oscar , Fernández-Díaz Maria T. , Abe Jun , Machida Shinichi , Hattori Takanori , Irifune Tetsuo , Shinmei Toru , Sugiyama Kazumasa , Kawamata Toru , Kagi Hiroyuki
Published: September 2022

Ice polymorphs show extraordinary structural diversity depending on pressure and temperature. The behavior of hydrogen-bond disorder not only is a key ingredient for their structural diversity but also controls their physical properties. However, it has been a challenge to determine the details of the disordered structure in ice polymorphs under pressure, because of the limited observable reciprocal space and inaccuracies related to high-pressure techniques. Here, we present an elucidation of the disordered structure of ice VII, the dominant high-pressure form of water, at 2.2 GPa and 298 K, from both single-crystal and powder neutron-diffraction techniques. We reveal the three-dimensional atomic distributions from the maximum entropy method and unexpectedly find a ring-like distribution of hydrogen in contrast to the commonly accepted discrete sites. In addition, total scattering analysis at 274 K clarified the difference in the intermolecular structure from ice VIII, the ordered counterpart of ice VII, despite an identical molecular geometry. Our complementary structure analyses robustly demonstrate the unique disordered structure of ice VII. Furthermore, these findings are related to proton dynamics, which drastically vary with pressure, and will contribute to an understanding of the structural origin of anomalous physical properties of ice VII under pressures.
Sperm-inherited H3K27me3 epialleles are transmitted transgenerationally incis
Authors: Kaneshiro Kiyomi Raye , Egelhofer Thea A. , Rechtsteiner Andreas , Cockrum Chad , Strome Susan
Published: September 2022

The transmission of chromatin states from parent cells to daughter cells preserves cell-specific transcriptional states and thus cell identity through cell division. The mechanism that underpins this process is not fully understood. The role that chromatin states serve in transmitting gene expression information across generations via sperm and oocytes is even less understood. Here, we utilized a model in whichCaenorhabditis eleganssperm and oocyte alleles were inherited in different states of the repressive mark H3K27me3. This resulted in the alleles achieving different transcriptional states within the nuclei of offspring. Using this model, we showed that sperm alleles inherited without H3K27me3 were sensitive to up-regulation in offspring somatic and germline tissues, and tissue context determined which genes were up-regulated. We found that the subset of sperm alleles that were up-regulated in offspring germlines retained the H3K27me3(−) state and were transmitted to grandoffspring as H3K27me3(−) and up-regulated epialleles, demonstrating that H3K27me3 can serve as a transgenerational epigenetic carrier inC. elegans.
A culture-free biphasic approach for sensitive and rapid detection of pathogens in dried whole-blood matrix
Authors: Ganguli Anurup , Lim Jongwon , Mostafa Ariana , Saavedra Carlos , Rayabharam Archith , Aluru Narayana R. , Wester Matthew , White Karen C. , Kumar James , McGuffin Reubin , Frederick Ann , Valera Enrique , Bashir Rashid
Published: September 2022

Blood stream infections (BSIs) cause high mortality, and their rapid detection remains a significant diagnostic challenge. Timely and informed administration of antibiotics can significantly improve patient outcomes. However, blood culture, which takes up to 5 d for a negative result, followed by PCR remains the gold standard in diagnosing BSI. Here, we introduce a new approach to blood-based diagnostics where large blood volumes can be rapidly dried, resulting in inactivation of the inhibitory components in blood. Further thermal treatments then generate a physical microscale and nanoscale fluidic network inside the dried matrix to allow access to target nucleic acid. The amplification enzymes and primers initiate the reaction within the dried blood matrix through these networks, precluding any need for conventional nucleic acid purification. High heme background is confined to the solid phase, while amplicons are enriched in the clear supernatant (liquid phase), giving fluorescence change comparable to purified DNA reactions. We demonstrate single-molecule sensitivity using a loop-mediated isothermal amplification reaction in our platform and detect a broad spectrum of pathogens, including gram-positive methicillin-resistant and methicillin-susceptible
Staphylococcus aureus
bacteria, gram-negative
Escherichia coli
bacteria, and
Candida albicans
(fungus) from whole blood with a limit of detection (LOD) of 1.2 colony-forming units (CFU)/mL from 0.8 to 1 mL of starting blood volume. We validated our assay using 63 clinical samples (100% sensitivity and specificity) and significantly reduced sample-to-result time from over 20 h to <2.5 h. The reduction in instrumentation complexity and costs compared to blood culture and alternate molecular diagnostic platforms can have broad applications in healthcare systems in developed world and resource-limited settings.
Molecular oxidation-reduction junctions for artificial photosynthetic overall reaction
Authors: Zhang Lei , Li Run-Han , Li Xiao-Xin , Liu Jiang , Guan Wei , Dong Long-Zhang , Li Shun-Li , Lan Ya-Qian
Published: September 2022

Constructing redox semiconductor heterojunction photocatalysts is the most effective and important means to complete the artificial photosynthetic overall reaction (i.e., coupling CO
2
photoreduction and water photo-oxidation reactions). However, multiphase hybridization essence and inhomogeneous junction distribution in these catalysts extremely limit the diverse design and regulation of the modes of photogenerated charge separation and transfer pathways, which are crucial factors to improve photocatalytic performance. Here, we develop molecular oxidation–reduction (OR) junctions assembled with oxidative cluster (PMo
12
, for water oxidation) and reductive cluster (Ni
5
, for CO
2
reduction) in a direct (
d
-OR), alternant (
a
-OR), or symmetric (
s
-OR) manner, respectively, for artificial photosynthesis. Significantly, the transfer direction and path of photogenerated charges between traditional junctions are obviously reformed and enriched in these well-defined crystalline catalysts with monophase periodic distribution and thus improve the separation efficiency of the electrons and holes. In particular, the charge migration in
s
-OR shows a periodically and continuously opposite mode. It can inhibit the photogenerated charge recombination more effectively and enhance the photocatalytic performance largely when compared with the traditional heterojunction models. Structural analysis and density functional theory calculations disclose that, through adjusting the spatial arrangement of oxidation and reduction clusters, the energy level and population of the orbitals of these OR junctions can be regulated synchronously to further optimize photocatalytic performance. The establishment of molecular OR junctions is a pioneering important discovery for extremely improving the utilization efficiency of photogenerated charges in the artificial photosynthesis overall reaction.
Monosomy X in isogenic human iPSC-derived trophoblast model impacts expression modules preserved in human placenta
Authors: Ahern Darcy T. , Bansal Prakhar , Armillei Maria K. , Faustino Isaac V. , Kondaveeti Yuvabharath , Glatt-Deeley Heather R. , Banda Erin C. , Pinter Stefan F.
Published: September 2022

Mammalian sex chromosomes encode homologous X/Y gene pairs that were retained on the Y chromosome in males and escape X chromosome inactivation (XCI) in females. Inferred to reflect X/Y pair dosage sensitivity, monosomy X is a leading cause of miscarriage in humans with near full penetrance. This phenotype is shared with many other mammals but not the mouse, which offers sophisticated genetic tools to generate sex chromosomal aneuploidy but also tolerates its developmental impact. To address this critical gap, we generated X-monosomic human induced pluripotent stem cells (hiPSCs) alongside otherwise isogenic euploid controls from male and female mosaic samples. Phased genomic variants in these hiPSC panels enable systematic investigation of X/Y dosage-sensitive features using in vitro models of human development. Here, we demonstrate the utility of these validated hiPSC lines to test how X/Y-linked gene dosage impacts a widely used model for human syncytiotrophoblast development. While these isogenic panels trigger a
GATA2/3-
and
TFAP2A/C
-driven trophoblast gene circuit irrespective of karyotype, differential expression implicates monosomy X in altered levels of placental genes and in secretion of placental growth factor (PlGF) and human chorionic gonadotropin (hCG). Remarkably, weighted gene coexpression network modules that significantly reflect these changes are also preserved in first-trimester chorionic villi and term placenta. Our results suggest monosomy X may skew trophoblast cell type composition and function, and that the combined haploinsufficiency of the pseudoautosomal region likely plays a key role in these changes.
The subjunctive in Renaissance French
Authors: Eisenbruch Miriam A.
Published: September 2022

The aim of this study was to explore why the subjunctive, despite its lack of modal productivity, might persist in French. I argue that the subjunctive is a modally void fossil, persisting due to repeated usage following highly entrenched constructions. The focus here is on the behaviour of the subjunctive in Renaissance French, specifically in the sixteenth and early-seventeenth centuries. Content analysis of personal correspondence identified the real subjunctive usage that lies beneath the French polish applied by standardisation. Through analysis of the structures that trigger the subjunctive in complement clause environments, I explore the grammatical behaviour of the subjunctive. The subjunctive was routinised after regularly occurring verbal and non-verbal constructions, strengthening the subjunctive’s position in certain complement clause environments. This study has diachronic importance in identifying which salient forms might persist in French. There are insights into the behaviour – perhaps the foundations – of the subjunctive paradigm in French as it stands today.
Quantum anomalous Hall effect in M2X3 honeycomb Kagome lattice
Authors: Zhang Bingwen , Deng Fenglin , Chen Xuejiao , Lv Xiaodong , Wang Jun
Published: September 2022

The quantum anomalous Hall (QAH) effect has recently drawn great attention in spintronics with extraordinary property of chiral edge states without dissipation in absence of magnetic field. In M2X3 honeycomb Kagome lattice, numerous two-dimensional materials are predicted to be QAH insulators including metal oxides/sulfides and metal organic lattice. In this work, we proposed a general model to explain the mechanism of Dirac half metal with absence of spin orbital coupling and the nontrivial topological property with spin orbital coupling, which could be induced by combination of electron counting rule, crystal field effect and

d

x
z

,

d

y
z

orbitals hybridization. Based on the mechanism, we further predict that triphenyl-metal lattice M2(C6H4)3 (M = V, Nb, Ta) are all QAH insulators with high Curie temperature and large nontrivial band gap for triphenyl-Nb and triphenyl-Ta lattice.
Crilin: A CRystal calorImeter with Longitudinal InformatioN for a future Muon Collider
Authors: Ceravolo S. , Colao F. , Curatolo C. , Di Meco E. , Diociaiuti E. , Lucchesi D. , Paesani D. , Pastrone N. , Saputi A. , Sarra I. , Sestini L. , Tagnani D.
Published: September 2022

The measurement of physics processes at new energy frontier
experiments requires excellent spatial, time, and energy resolutions
to resolve the structure of collimated high-energy jets. In a future
Muon Collider, the beam-induced backgrounds (BIB) represent the main
challenge in the design of the detectors and of the event
reconstruction algorithms. The technology and the design of the
calorimeters should be chosen to reduce the effect of the BIB, while
keeping good physics performance. Several requirements can be
inferred: i) high granularity to reduce the overlap of BIB particles
in the same calorimeter cell; ii) excellent timing (of the order of
100 ps) to reduce the out-of-time component of the BIB; iii)
longitudinal segmentation to distinguish the signal showers from the
fake showers produced by the BIB; iv) good energy resolution (less
than 10%/√E) to obtain good physics performance, as has
been already demonstrated for conceptual particle flow calorimeters.
Our proposal consists of a semi-homogeneous electromagnetic
calorimeter based on lead fluoride crystals (PbF2) read out by
surface-mount UV-extended Silicon Photomultipliers (SiPMs): the
Crilin calorimeter. In this paper, the performance of the Crilin
calorimeter in the Muon Collider framework for hadron jets
reconstruction has been analyzed. We report the characterisation of
individual components together with the development of a small-scale
prototype, consisting of 2 layers of 3 × 3 crystals each.
Study on the Optimized Energy Resolution of Scintillator Detectors Based on SiPMs and LYSO:Ce
Authors: Hu P. , Hua Z.H. , Ma L.S. , Qian S. , Wu Q. , Wang Z.G.
Published: September 2022

The cerium-doped lutetium yttrium silicate (LYSO:Ce) crystal
has many advantages such as high light output and fast decay time,
showing great potential to improve the performance of scintillation
detectors. Silicon photomultipliers (SiPMs) are high-performance
semiconductor photodetectors, which generally have a higher photon
detection efficiency than photomultiplier tubes (PMTs) and are
beneficial to realize a better energy resolution. The energy
resolution and detected light output of SiPM-coupled LYSO:Ce
crystals were studied by optimizing the photon detection efficiency
(PDE), the operating voltage, the wrapper, the surface finish and
the coupling method between the SiPM and crystal. Considering the
output saturation of SiPMs in high light intensity, a preliminary
correction method was applied to the saturation response of SiPMs
and energy resolution of 662 keV gamma-rays from 137Cs was
obtained after correction. The results show that the optimized
energy resolution at 662 keV measured by the SiPM of 50 μm
microcells can reach 7.6%. The light output of the polished and
rough crystal detected by a SiPM of 10 μm microcells were
also measured, which can reach 27000 ± 3200 photons/MeV and
36000 ± 3700 photons/MeV, respectively.
Impact of tropical convective conditions on solar irradiance forecasting based on cloud motion vectors
Authors: Roy Arindam , Hammer Annette , Heinemann Detlev , Lünsdorf Ontje , Lezaca Jorge
Published: September 2022

Intra-day forecasts of global horizontal solar irradiance (GHI) are widely produced by displacing existing clouds on a geo-stationary satellite image to their future locations with cloud motion vectors (CMVs) derived from preceding images. The CMV estimation methods assume rigid cloud bodies with advective motion, which performs reasonably well in mid-latitudes but can be strained for tropical and sub-tropical climatic zones during prolonged periods of seasonal convection. We study the impact of the South Asian monsoon time convection on the accuracy of CMV based forecasts by analysing 2 years of forecasts from three commonly used CMV methods—Block-match, Farnebäck (Optical flow) and TV-L1 (Optical flow). Forecasted cloud index (CI) maps of the entire image section are validated against analysis CI maps for the period 2018–2019 for forecast lead times from 0 to 5.5 h. Site-level GHI forecasts are validated against ground measured data from two Baseline Surface Radiation Network stations—Gurgaon (GUR) and Tiruvallur (TIR), located in hot semi-arid and tropical savanna climatic zones respectively. The inter-seasonal variation of forecast accuracy is prominent and a clear link is found between the increase in convection, represented by a decrease in outgoing longwave radiation (OLR), and the decrease in forecast accuracy. The GUR site shows the highest forecast error in the southwest monsoon period and exhibits a steep rise of forecast error with the increase in convection. The highest forecast error occurs in the northeast monsoon period of December in TIR. The impact of convection on the number of erroneous time blocks of predicted photovoltaic production is also studied. Our results provide insights into the contribution of convection to errors in CMV based forecasts and shows that OLR can be used as a feature in future forecasting methods to consider the impact of convection on forecast accuracy.
Strong trade-offs characterise water-energy-food related sustainable development goals in the Ganges–Brahmaputra–Meghna River basin
Authors: Siderius Christian , van Walsum Paul , Biemans Hester
Published: September 2022

The United Nations’ sustainable development goals (SDGs) set ambitious policy targets for 2030 to overcome poverty while preserving the planet. These goals are not perfectly aligned; trade-offs emerge during implementation at regional and local levels, such as in a river basin. Here, we quantify important trade-offs between water, energy, and food-related SDGs in the Ganges–Brahmaputra–Meghna River basin, a climate vulnerability hotspot, using multi-objective optimisation based on detailed water resources and crop production modelling and accounting for uncertainties in the costs of water, labour, and land. The trade-off between food production and agricultural profit is strong; the amount of people fed would be reduced by more than two-thirds, were profitability maximized. However, we do see the potential to achieve higher profitability in agriculture against limited loss of food and hydropower production and limited impact on downstream environmental flows, although continued reliance on groundwater and energy, currently unsustainable, needs to be mitigated.
Localization by particle–hole symmetry breaking: a loop expansion
Authors: Ziegler K
Published: September 2022

Localization by a broken particle–hole (PH) symmetry in a random system of non-interacting quantum particles is studied on a d-dimensional lattice. Our approach is based on a chiral symmetry argument and the corresponding invariant measure, where the latter is described by a Grassmann functional integral. Within a loop expansion we find for small loops diffusion in the case of PH symmetry. Breaking the PH symmetry results in the creation of random dimers, which suppress diffusion and lead to localization on the scale

D
/
|
μ
|

, where D is the effective diffusion coefficient at PH symmetry and μ is the parameter related to PH symmetry breaking.
Engineering highly-aligned three-dimensional (3D) cardiac constructs for enhanced myocardial infarction repair
Authors: Han Kang , He Jiankang , Fu Liyan , Mao Mao , Kang Yuming , Li Dichen
Published: September 2022

Native myocardium exhibits well-organized cellular orientations and highly vascularized architectures, which is important for tissue survival and synchronic contraction activities. Mimicking such structural organizations to engineer functional cardiac constructs is a promising approach to treat myocardial infarction in vivo. Here we propose a novel strategy to engineer highly-aligned three-dimensional (3D) cardiac constructs by co-culturing cardiomyocytes and rat aortic endothelial cells (RAECs) along with native extracellular matrix-derived fibrin within electrohydrodynamic-printed microfibrous architectures. Cell-laden fibrin with a relatively rapid gelation rate enables uniform cellular distribution in 3D and can re-organize to form multidirectionally aligned 3D cardiac bands with similar orientations to the printed microfibers. The resultant 3D cardiac constructs show enhanced cardiomyocyte-specific protein expression, synchronous contraction and low excitation threshold. The addition of RAECs significantly increases the width of cardiac bands and enhances their beating frequency. The engineered 3D cardiac constructs with layer-specific orientations were found to effectively reduce infracted area, enhance neovascularization and eventually realize functional repair of infarcted myocardium in vivo. This exploration provides a promising strategy to engineer 3D cardiac constructs with tissue-specific cellular orientations for the functional repair of infarcted myocardium.
Static hand gesture recognition for American sign language using neuromorphic hardware
Authors: Mohammadi Mohammadreza , Chandarana Peyton , Seekings James , Hendrix Sara , Zand Ramtin
Published: September 2022

In this paper, we develop four spiking neural network (SNN) models for two static American sign language (ASL) hand gesture classification tasks, i.e., the ASL alphabet and ASL digits. The SNN models are deployed on Intel’s neuromorphic platform, Loihi, and then compared against equivalent deep neural network (DNN) models deployed on an edge computing device, the Intel neural compute stick 2 (NCS2). We perform a comprehensive comparison between the two systems in terms of accuracy, latency, power consumption, and energy. The best DNN model achieves an accuracy of 99.93% on the ASL alphabet dataset, whereas the best performing SNN model has an accuracy of 99.30%. For the ASL-digits dataset, the best DNN model achieves an accuracy of 99.76% accuracy while the SNN achieves 99.03%. Moreover, our obtained experimental results show that the Loihi neuromorphic hardware implementations achieve up to 20.64× and 4.10× reduction in power consumption and energy, respectively, when compared to NCS2.
Variational principles for nonlinear PDE systems via duality
Authors: Acharya Amit
Published: September 2022

A formal methodology for developing variational principles corresponding to a given nonlinear PDE system is discussed. The scheme is demonstrated in the context of the incompressible Navier-Stokes equations, systems of first-order conservation laws, and systems of Hamilton-Jacobi equations.
Evaluation of the Efficacy and Feasibility of a Telerehabilitation Program Using Language and Cognitive Exercises in Multi-Domain Amnestic Mild Cognitive Impairment
Authors: Nousia Anastasia , Pappa Evangelia , Siokas Vasileios , Liampas Ioannis , Tsouris Zisis , Messinis Lambros , Patrikelis Panayiotis , Manouilidou Christina , Dardiotis Efthimios , Nasios Grigorios
Published: September 2022

Objective

The aim of the present study was to investigate the efficacy and feasibility of a telerehabilitation program in multi-domain amnestic Mild Cognitive Impairment (md-aMCI). The study sample consisted of 30 patients with md-aMCI and aged 60–80 years.

Methods

The participants were randomly divided into two groups. The Training Group (TG), which received cognitive training by using the RehaCom software as well as paper-pencil language training and the Control Group (CG) which received standard clinical care (e.g., psychotherapy or/and physiotherapy). Duration of the telerehabilitation intervention was 15 weeks (twice a week for 60 min/session).

Results

Our results revealed that the neuropsychological performance of the TG group after the telerehabilitation intervention improved on a statistically significant level on the domains of delayed and working memory, confrontation naming, verbal fluency, and global cognition. Comparison between the TG and CG revealed a significant impact of the telerehabilitation program on the domains of memory (delay and working) and language (naming and verbal fluency) as well as global cognition performance.

Conclusion

The findings of the study are promising in that the telerehabilitation intervention appears to be a useful method in improving or stabilizing cognitive decline in md-aMCI individuals and was a particularly effective alternative approach during the period of the pandemic lockdown. Specifically, the beneficial impact of the telerehabilitation intervention on episodic memory (which is one of the first domains to show impairment in md-aMCI patients) provides us with hope and evidence that these types of interventions may be applied with similar success using face-to-face interventions.
Decoding brain memory formation by single-cell RNA sequencing
Authors: Sardoo Atlas M , Zhang Shaoqiang , Ferraro Thomas N , Keck Thomas M , Chen Yong
Published: September 2022

To understand how distinct memories are formed and stored in the brain is an important and fundamental question in neuroscience and computational biology. A population of neurons, termed engram cells, represents the physiological manifestation of a specific memory trace and is characterized by dynamic changes in gene expression, which in turn alters the synaptic connectivity and excitability of these cells. Recent applications of single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) are promising approaches for delineating the dynamic expression profiles in these subsets of neurons, and thus understanding memory-specific genes, their combinatorial patterns and regulatory networks. The aim of this article is to review and discuss the experimental and computational procedures of sc/snRNA-seq, new studies of molecular mechanisms of memory aided by sc/snRNA-seq in human brain diseases and related mouse models, and computational challenges in understanding the regulatory mechanisms underlying long-term memory formation.
PlantBind: an attention-based multi-label neural network for predicting plant transcription factor binding sites
Authors: Yan Wenkai , Li Zutan , Pian Cong , Wu Yufeng
Published: September 2022

Identification of transcription factor binding sites (TFBSs) is essential to understanding of gene regulation. Designing computational models for accurate prediction of TFBSs is crucial because it is not feasible to experimentally assay all transcription factors (TFs) in all sequenced eukaryotic genomes. Although many methods have been proposed for the identification of TFBSs in humans, methods designed for plants are comparatively underdeveloped. Here, we present PlantBind, a method for integrated prediction and interpretation of TFBSs based on DNA sequences and DNA shape profiles. Built on an attention-based multi-label deep learning framework, PlantBind not only simultaneously predicts the potential binding sites of 315 TFs, but also identifies the motifs bound by transcription factors. During the training process, this model revealed a strong similarity among TF family members with respect to target binding sequences. Trans-species prediction performance using four Zea mays TFs demonstrated the suitability of this model for transfer learning. Overall, this study provides an effective solution for identifying plant TFBSs, which will promote greater understanding of transcriptional regulatory mechanisms in plants.