bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen application at anthesis increases barley grain protein by enhancing phloem amino acid mobilisation
Authors: Boero J. J. , Gutierrez Boem F. H. , Prystupa P. , Veliz C. G. , Criado M. V. , Gomez F. M. , Caputo C.
Published: October 2022

Context In the malting industry, the low protein content of barley grains is a major issue. A useful strategy to overcome this problem is to complement the initial fertilisation with a foliar application of nitrogen (N) near anthesis. Aims This study aimed to advance knowledge of the metabolic adjustments displayed by plants grown under common management practices in response to foliar N fertilisation at anthesis. Methods Field experiments with two different rates of foliar N application near anthesis were performed at three commercial sites under the common practice of each farmer. Key results Grain protein content increased upon foliar fertilisation in all sites without affecting leaf senescence or N remobilisation efficiency. Barley plants also showed a rapid assimilation of the N applied at anthesis, increasing the leaf N organic pools and the global phloem amino acid mobilisation during grain filling. These results could be attributed to the increase in the gene expression of glutamine synthetase 1 and two amino acid transporters (HvAAP6 and HvAAP7). Conclusions Foliar N applied was rapidly assimilated and exported with high efficiency to the grain with no negative impact over the contribution of N from vegetative organs. Furthermore, phloem N contribution was shown to be of major importance for grain protein content. Implications Foliar fertilisation near anthesis is an efficient strategy to correct grain protein content to meet maltsters’ requirements because it did not affect pre-assimilated N remobilisation, and was useful under the different nutrient availabilities explored here (N sufficiency, N deficiency and sulfur deficiency).
Bip-Yorkie interaction determines oncogenic and tumor-suppressive roles of Ire1/Xbp1s activation
Authors: Yang Shuai , Jiang Hua , Bian Weixiang , Xu Wenyan , Guo Yifan , Song Sha , Zheng Jiadong , Kuang Xiaoyu , Wu Chenxi , Ding Xiang , Guo Xiaowei , Xue Lei , Yu Zijing , Zhang Yongdeng , Ryoo Hyung Don , Li Xu , Ma Xianjue
Published: October 2022

Unfolded protein response (UPR) is the mechanism by which cells control endoplasmic reticulum (ER) protein homeostasis. ER proteostasis is essential to adapt to cell proliferation and regeneration in development and tumorigenesis, but mechanisms linking UPR, growth control, and cancer progression remain unclear. Here, we report that the Ire1/Xbp1s pathway has surprisingly oncogenic and tumor-suppressive roles in a context-dependent manner. Activation of Ire1/Xbp1s up-regulates their downstream target Bip, which sequesters Yorkie (Yki), a Hippo pathway transducer, in the cytoplasm to restrict Yki transcriptional output. This regulation provides an endogenous defensive mechanism in organ size control, intestinal homeostasis, and regeneration. Unexpectedly,
Xbp1
ablation promotes tumor overgrowth but suppresses invasiveness in a
Drosophila
cancer model. Mechanistically, hyperactivated Ire1/Xbp1s signaling in turn induces JNK-dependent developmental and oncogenic cell migration and epithelial-mesenchymal transition (EMT) via repression of Yki. In humans, a negative correlation between
XBP1
and YAP (Yki ortholog) target gene expression specifically exists in triple-negative breast cancers (TNBCs), and those with high
XBP1
or
HSPA5
(Bip ortholog) expression have better clinical outcomes. In human TNBC cell lines and xenograft models, ectopic XBP1s or HSPA5 expression alleviates tumor growth but aggravates cell migration and invasion. These findings uncover a conserved crosstalk between the Ire1/Xbp1s and Hippo signaling pathways under physiological settings, as well as a crucial role of Bip-Yki interaction in tumorigenesis that is shared from
Drosophila
to humans.
The full activation mechanism of the adenosine A
1
receptor revealed by GaMD and Su-GaMD simulations
Authors: Li Yang , Sun Jixue , Li Dongmei , Lin Jianping
Published: October 2022

The full activation process of G protein–coupled receptor (GPCR) plays an important role in cellular signal transduction. However, it remains challenging to simulate the whole process in which the GPCR is recognized and activated by a ligand and then couples to the G protein on a reasonable simulation timescale. Here, we developed a molecular dynamics (MD) approach named supervised (Su) Gaussian accelerated MD (GaMD) by incorporating a tabu-like supervision algorithm into a standard GaMD simulation. By using this Su-GaMD method, from the active and inactive structure of adenosine A
1
receptor (A
1
R), we successfully revealed the full activation mechanism of A
1
R, including adenosine (Ado)–A
1
R recognition, preactivation of A
1
R, and A
1
R–G protein recognition, in hundreds of nanoseconds of simulations. The binding of Ado to the extracellular side of A
1
R initiates conformational changes and the preactivation of A
1
R. In turn, the binding of G
i2
to the intracellular side of A
1
R causes a decrease in the volume of the extracellular orthosteric site and stabilizes the binding of Ado to A
1
R. Su-GaMD could be a useful tool to reconstruct or even predict ligand–protein and protein–protein recognition pathways on a short timescale. The intermediate states revealed in this study could provide more detailed complementary structural characterizations to facilitate the drug design of A
1
R in the future.
Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines
Authors: Falahati Hanieh , Wu Yumei , Feuerer Vanessa , Simon Hans-Georg , De Camilli Pietro
Published: October 2022

The spine apparatus is a specialized compartment of the neuronal smooth endoplasmic reticulum (ER) located in a subset of dendritic spines. It consists of stacks of ER cisterns that are interconnected by an unknown dense matrix and are continuous with each other and with the ER of the dendritic shaft. While this organelle was first observed over 60 y ago, its molecular organization remains a mystery. Here, we performed in vivo proximity proteomics to gain some insight into its molecular components. To do so, we used the only known spine apparatus–specific protein, synaptopodin, to target a biotinylating enzyme to this organelle. We validated the specific localization in dendritic spines of a small subset of proteins identified by this approach, and we further showed their colocalization with synaptopodin when expressed in nonneuronal cells. One such protein is Pdlim7, an actin binding protein not previously identified in spines. Pdlim7, which we found to interact with synaptopodin through multiple domains, also colocalizes with synaptopodin on the cisternal organelle, a peculiar stack of ER cisterns resembling the spine apparatus and found at axon initial segments of a subset of neurons. Moreover, Pdlim7 has an expression pattern similar to that of synaptopodin in the brain, highlighting a functional partnership between the two proteins. The components of the spine apparatus identified in this work will help elucidate mechanisms in the biogenesis and maintenance of this enigmatic structure with implications for the function of dendritic spines in physiology and disease.
Polycomb group (PcG) proteins prevent the assembly of abnormal synaptonemal complex structures during meiosis
Authors: Feijão Tália , Marques Bruno , Silva Rui D. , Carvalho Célia , Sobral Daniel , Matos Ricardo , Tan Tian , Pereira António , Morais-de-Sá Eurico , Maiato Hélder , DeLuca Steven Z. , Martinho Rui Gonçalo
Published: October 2022

The synaptonemal complex (SC) is a proteinaceous scaffold that is assembled between paired homologous chromosomes during the onset of meiosis. Timely expression of SC coding genes is essential for SC assembly and successful meiosis. However, SC components have an intrinsic tendency to self-organize into abnormal repetitive structures, which are not assembled between the paired homologs and whose formation is potentially deleterious for meiosis and gametogenesis. This creates an interesting conundrum, where SC genes need to be robustly expressed during meiosis, but their expression must be carefully regulated to prevent the formation of anomalous SC structures. In this manuscript, we show that the Polycomb group protein Sfmbt, the
Drosophila
ortholog of human MBTD1 and L3MBTL2, is required to avoid excessive expression of SC genes during prophase I. Although SC assembly is normal after Sfmbt depletion, SC disassembly is abnormal with the formation of multiple synaptonemal complexes (polycomplexes) within the oocyte. Overexpression of the SC gene
corona
and depletion of other Polycomb group proteins are similarly associated with polycomplex formation during SC disassembly. These polycomplexes are highly dynamic and have a well-defined periodic structure. Further confirming the importance of Sfmbt, germ line depletion of this protein is associated with significant metaphase I defects and a reduction in female fertility. Since transcription of SC genes mostly occurs during early prophase I, our results suggest a role of Sfmbt and other Polycomb group proteins in downregulating the expression of these and other early prophase I genes during later stages of meiosis.
Discrete scale invariance of the quasi-bound states at atomic vacancies in a topological material
Authors: Shao Zhibin , Li Shaojian , Liu Yanzhao , Li Zi , Wang Huichao , Bian Qi , Yan Jiaqiang , Mandrus David , Liu Haiwen , Zhang Ping , Xie X. C. , Wang Jian , Pan Minghu
Published: October 2022

Recently, log-periodic quantum oscillations have been detected in the topological materials zirconium pentatelluride (ZrTe
5
) and hafnium pentatelluride (HfTe
5
), displaying an intriguing discrete scale invariance (DSI) characteristic. In condensed materials, the DSI is considered to be related to the quasi-bound states formed by massless Dirac fermions with strong Coulomb attraction, offering a feasible platform to study the long-pursued atomic-collapse phenomenon. Here, we demonstrate that a variety of atomic vacancies in the topological material HfTe
5
can host the geometric quasi-bound states with a DSI feature, resembling an artificial supercritical atom collapse. The density of states of these quasi-bound states is enhanced, and the quasi-bound states are spatially distributed in the “orbitals” surrounding the vacancy sites, which are detected and visualized by low-temperature scanning tunneling microscope/spectroscopy. By applying the perpendicular magnetic fields, the quasi-bound states at lower energies become wider and eventually invisible; meanwhile, the energies of quasi-bound states move gradually toward the Fermi energy (
E
F
). These features are consistent with the theoretical prediction of a magnetic field–induced transition from supercritical to subcritical states. The direct observation of geometric quasi-bound states sheds light on the deep understanding of the DSI in quantum materials.
Attenuation of relapsing fever neuroborreliosis in mice by IL-17A blockade
Authors: Cheng Meihui , Xu Jingwen , Ding Kaiyun , Zhang Jing , Lu Wei , Liu Jiansheng , Gao Jiahong , Alugupalli Kishore R. , Liu Hongqi
Published: October 2022

Relapsing fever due to
Borrelia hermsii
is characterized by recurrent bacteremia episodes. However, infection of
B. hermsii
, if not treated early, can spread to various organs including the central nervous system (CNS). CNS disease manifestations are commonly referred to as relapsing fever neuroborreliosis (RFNB). In the mouse model of
B. hermsii
infection, we have previously shown that the development of RFNB requires innate immune cells as well as T cells. Here, we found that prior to the onset of RFNB, an increase in the systemic proinflammatory cytokine response followed by sustained levels of IP-10 concurrent with the CNS disease phase. RNA sequencing analysis of the spinal cord tissue during the disease phase revealed an association of the interleukin (IL)-17 signaling pathway in RFNB. To test a possible role for IL-17 in RFNB, we compared
B. hermsii
infection in wild-type and IL-17A
−/−
mice. Although the onset of bacteremia and protective anti-
B. hermsii
antibody responses occurred similarly, the blood-brain barrier permeability, proinflammatory cytokine levels, immune cell infiltration in the spinal cord, and RFNB manifestations were significantly diminished in IL-17A
−/−
mice compared to wild-type mice. Treatment of
B. hermsii
-infected wild-type mice with anti-IL-17A antibody ameliorated the severity of spinal cord inflammation, microglial cell activation, and RFNB. These data suggest that the IL-17 signaling pathway plays a major role in the pathogenesis of RFNB, and IL-17A blockade may be a therapeutic modality for controlling neuroborreliosis.
Gluing blood into gel by electrostatic interaction using a water-soluble polymer as an embolic agent
Authors: Jin Zhiping , Fan Hailong , Osanai Toshiya , Nonoyama Takayuki , Kurokawa Takayuki , Hyodoh Hideki , Matoba Kotaro , Takeuchi Akiko , Gong Jian Ping , Fujimura Miki
Published: October 2022

Liquid embolic agents are widely used for the endovascular embolization of vascular conditions. However, embolization based on phase transition is limited by the adhesion of the microcatheter to the embolic agent, use of an organic solvent, unintentional catheter retention, and other complications. By mimicking thrombus formation, a water-soluble polymer that rapidly glues blood into a gel without triggering coagulation was developed. The polymer, which consists of cationic and aromatic residues with adjacent sequences, shows electrostatic adhesion with negatively charged blood substances in a physiological environment, while common polycations cannot. Aqueous polymer solutions are injectable through clinical microcatheters and needles. The formed blood gel neither adhered to the catheter nor blocked the port. Postoperative computed tomography imaging showed that the polymer can block the rat femoral artery in vivo and remain at the injection site without nontarget embolization. This study provides an alternative for the development of waterborne embolic agents.
How digital media drive affective polarization through partisan sorting
Authors: Törnberg Petter
Published: October 2022

Politics has in recent decades entered an era of intense polarization. Explanations have implicated digital media, with the so-called echo chamber remaining a dominant causal hypothesis despite growing challenge by empirical evidence. This paper suggests that this mounting evidence provides not only reason to reject the echo chamber hypothesis but also the foundation for an alternative causal mechanism. To propose such a mechanism, the paper draws on the literatures on affective polarization, digital media, and opinion dynamics. From the affective polarization literature, we follow the move from seeing polarization as diverging issue positions to rooted in sorting: an alignment of differences which is effectively dividing the electorate into two increasingly homogeneous megaparties. To explain the rise in sorting, the paper draws on opinion dynamics and digital media research to present a model which essentially turns the echo chamber on its head: it is not isolation from opposing views that drives polarization but precisely the fact that digital media bring us to interact outside our local bubble. When individuals interact locally, the outcome is a stable plural patchwork of cross-cutting conflicts. By encouraging nonlocal interaction, digital media drive an alignment of conflicts along partisan lines, thus effacing the counterbalancing effects of local heterogeneity. The result is polarization, even if individual interaction leads to convergence. The model thus suggests that digital media polarize through partisan sorting, creating a maelstrom in which more and more identities, beliefs, and cultural preferences become drawn into an all-encompassing societal division.
Chemically coupling SnO
2
quantum dots and MXene for efficient CO
2
electroreduction to formate and Zn–CO
2
battery
Authors: Han Lili , Peng Xianyun , Wang Hsiao-Tsu , Ou Pengfei , Mi Yuying , Pao Chih-Wen , Zhou Jigang , Wang Jian , Liu Xijun , Pong Way-Faung , Song Jun , Lin Zhang , Luo Jun , Xin Huolin L.
Published: October 2022

Electrochemical conversion of CO
2
into formate is a promising strategy for mitigating the energy and environmental crisis, but simultaneously achieving high selectivity and activity of electrocatalysts remains challenging. Here, we report low-dimensional SnO
2
quantum dots chemically coupled with ultrathin Ti
3
C
2
T
x
MXene nanosheets (SnO
2
/MXene) that boost the CO
2
conversion. The coupling structure is well visualized and verified by high-resolution electron tomography together with nanoscale scanning transmission X-ray microscopy and ptychography imaging. The catalyst achieves a large partial current density of −57.8 mA cm
−2
and high Faradaic efficiency of 94% for formate formation. Additionally, the SnO
2
/MXene cathode shows excellent Zn–CO
2
battery performance, with a maximum power density of 4.28 mW cm
−2
, an open-circuit voltage of 0.83 V, and superior rechargeability of 60 h. In situ X-ray absorption spectroscopy analysis and first-principles calculations reveal that this remarkable performance is attributed to the unique and stable structure of the SnO
2
/MXene, which can significantly reduce the reaction energy of CO
2
hydrogenation to formate by increasing the surface coverage of adsorbed hydrogen.
SWEET13 transport of sucrose, but not gibberellin, restores male fertility in
Arabidopsis sweet13;14
Authors: Isoda Reika , Palmai Zoltan , Yoshinari Akira , Chen Li-Qing , Tama Florence , Frommer Wolf B. , Nakamura Masayoshi
Published: October 2022

SWEET sucrose transporters play important roles in the allocation of sucrose in plants. Some SWEETs were shown to also mediate transport of the plant growth regulator gibberellin (GA). The close physiological relationship between sucrose and GA raised the questions of whether there is a functional connection and whether one or both of the substrates are physiologically relevant. To dissect these two activities, molecular dynamics were used to map the binding sites of sucrose and GA in the pore of SWEET13 and predicted binding interactions that might be selective for sucrose or GA. Transport assays confirmed these predictions. In transport assays, the N76Q mutant had 7x higher relative GA
3
activity, and the S142N mutant only transported sucrose. The impaired pollen viability and germination in
sweet13;14
double mutants were complemented by the sucrose-selective SWEET13
S142N
, but not by the SWEET13
N76Q
mutant, indicating that sucrose is the physiologically relevant substrate and that GA transport capacity is dispensable in the context of male fertility. Therefore, GA supplementation to counter male sterility may act indirectly via stimulating sucrose supply in male sterile mutants. These findings are also relevant in the context of the role of SWEETs in pathogen susceptibility.
From antenna to reaction center: Pathways of ultrafast energy and charge transfer in photosystem II
Authors: Yang Shiun-Jr , Arsenault Eric A. , Orcutt Kaydren , Iwai Masakazu , Yoneda Yusuke , Fleming Graham R.
Published: October 2022

The photosystem II core complex (PSII-CC) is the smallest subunit of the oxygenic photosynthetic apparatus that contains core antennas and a reaction center, which together allow for rapid energy transfer and charge separation, ultimately leading to efficient solar energy conversion. However, there is a lack of consensus on the interplay between the energy transfer and charge separation dynamics of the core complex. Here, we report the application of two-dimensional electronic-vibrational (2DEV) spectroscopy to the spinach PSII-CC at 77 K. The simultaneous temporal and spectral resolution afforded by 2DEV spectroscopy facilitates the separation and direct assignment of coexisting dynamical processes. Our results show that the dominant dynamics of the PSII-CC are distinct in different excitation energy regions. By separating the excitation regions, we are able to distinguish the intraprotein dynamics and interprotein energy transfer. Additionally, with the improved resolution, we are able to identify the key pigments involved in the pathways, allowing for a direct connection between dynamical and structural information. Specifically, we show that C505 in CP43 and the peripheral chlorophyll Chlz
D1
in the reaction center are most likely responsible for energy transfer from CP43 to the reaction center.
Active entanglement enables stochastic, topological grasping
Authors: Becker Kaitlyn , Teeple Clark , Charles Nicholas , Jung Yeonsu , Baum Daniel , Weaver James C. , Mahadevan L. , Wood Robert
Published: October 2022

Grasping, in both biological and engineered mechanisms, can be highly sensitive to the gripper and object morphology, as well as perception and motion planning. Here, we circumvent the need for feedback or precise planning by using an array of fluidically actuated slender hollow elastomeric filaments to actively entangle with objects that vary in geometric and topological complexity. The resulting stochastic interactions enable a unique soft and conformable grasping strategy across a range of target objects that vary in size, weight, and shape. We experimentally evaluate the grasping performance of our strategy and use a computational framework for the collective mechanics of flexible filaments in contact with complex objects to explain our findings. Overall, our study highlights how active collective entanglement of a filament array via an uncontrolled, spatially distributed scheme provides options for soft, adaptable grasping.
Sustainable pest control inspired by prey–predator ultrasound interactions
Authors: Nakano Ryo , Ito Akio , Tokumaru Susumu
Published: October 2022

Nocturnal moths evolved ultrasound-triggered escape maneuvers for avoiding predatory bats emitting ultrasonic echolocation calls. Using ultrasound for pest control is not a novel concept, but the technique has not been systemized because of the moths’ habituation to sounds and the narrow directionality of conventional ultrasound speakers. Here, we report the use of pulsed ultrasonic white noise, which contributes to achieving ecologically concordant plant protection. An ultrasonic pulse, which is temporal mimicry of the search-phase pulse in the echolocation calls of a sympatric bat, was identified using neuroethological screening of eared moth–repelling ultrasounds; these pulses elicit flight-stopping reactions in moths but have no or little auditory adaptation. Such repellent ultrasounds broadcast from the cylindrical omni-azimuth ultrasound emitters suppressed the intrusion of gravid females of pest moths into cultivation fields. Thus, egg numbers and plant damage by hatched larvae were drastically reduced, enabling farmers to substantially skip applications of chemical insecticides for controlling moth pests.
Connecting sequence features within the disordered C-terminal linker of
Bacillus subtilis
FtsZ to functions and bacterial cell division
Authors: Shinn Min Kyung , Cohan Megan C. , Bullock Jessie L. , Ruff Kiersten M. , Levin Petra A. , Pappu Rohit V.
Published: October 2022

Intrinsically disordered regions (IDRs) can function as autoregulators of folded enzymes to which they are tethered. One example is the bacterial cell division protein FtsZ. This includes a folded core and a C-terminal tail (CTT) that encompasses a poorly conserved, disordered C-terminal linker (CTL) and a well-conserved 17-residue C-terminal peptide (CT17). Sites for GTPase activity of FtsZs are formed at the interface between GTP binding sites and T7 loops on cores of adjacent subunits within dimers. Here, we explore the basis of autoregulatory functions of the CTT in
Bacillus subtilis
FtsZ (
Bs-
FtsZ). Molecular simulations show that the CT17 of
Bs-
FtsZ makes statistically significant CTL-mediated contacts with the T7 loop. Statistical coupling analysis of more than 1,000 sequences from FtsZ orthologs reveals clear covariation of the T7 loop and the CT17 with most of the core domain, whereas the CTL is under independent selection. Despite this, we discover the conservation of nonrandom sequence patterns within CTLs across orthologs. To test how the nonrandom patterns of CTLs mediate CTT–core interactions and modulate FtsZ functionalities, we designed
Bs-
FtsZ variants by altering the patterning of oppositely charged residues within the CTL. Such alterations disrupt the core–CTT interactions, lead to anomalous assembly and inefficient GTP hydrolysis in vitro and protein degradation, aberrant assembly, and disruption of cell division in vivo. Our findings suggest that viable CTLs in FtsZs are likely to be IDRs that encompass nonrandom, functionally relevant sequence patterns that also preserve three-way covariation of the CT17, the T7 loop, and core domain.
Coevolution of tandemly repeated
hlips
and RpaB-like transcriptional factor confers desiccation tolerance to subaerial
Nostoc
species
Authors: Xu Hai-Feng , Dai Guo-Zheng , Bai Yang , Shang Jin-Long , Zheng Bin , Ye De-Min , Shi Huazhong , Kaplan Aaron , Qiu Bao-Sheng
Published: October 2022

Desert-inhabiting cyanobacteria can tolerate extreme desiccation and quickly revive after rehydration. The regulatory mechanisms that enable their vegetative cells to resurrect upon rehydration are poorly understood. In this study, we identified a single gene family of high light-inducible proteins (Hlips) with dramatic expansion in the
Nostoc flagelliforme
genome and found an intriguingly special convergence formed through four tandem gene duplication. The emerged four independent
hlip
genes form a gene cluster (
hlips-cluster
) and respond to dehydration positively. The gene mutants in
N. flagelliforme
were successfully generated by using gene-editing technology. Phenotypic analysis showed that the desiccation tolerance of
hlips-cluster
–deleted mutant decreased significantly due to impaired photosystem II repair, whereas heterologous expression of
hlips-cluster
from
N. flagelliforme
enhanced desiccation tolerance in
Nostoc
sp. PCC 7120. Furthermore, a transcription factor Hrf1 (
hlips-cluster
repressor factor 1) was identified and shown to coordinately regulate the expression of
hlips-cluster
and desiccation-induced
psbAs
. Hrf1 acts as a negative regulator for the adaptation of
N. flagelliforme
to the harsh desert environment. Phylogenetic analysis revealed that most species in the
Nostoc
genus possess both tandemly repeated Hlips and Hrf1. Our results suggest convergent evolution of desiccation tolerance through the coevolution of tandem Hlips duplication and Hrf1 in subaerial
Nostoc
species, providing insights into the mechanism of desiccation tolerance in photosynthetic organisms.
The unstructured linker of Mlh1 contains a motif required for endonuclease function which is mutated in cancers
Authors: Torres Kendall A. , Calil Felipe A. , Zhou Ann L. , DuPrie Matthew L. , Putnam Christopher D. , Kolodner Richard D.
Published: October 2022

Eukaryotic DNA mismatch repair (MMR) depends on recruitment of the Mlh1-Pms1 endonuclease (human MLH1-PMS2) to mispaired DNA. Both Mlh1 and Pms1 contain a long unstructured linker that connects the N- and carboxyl-terminal domains. Here, we demonstrated the Mlh1 linker contains a conserved motif (
Saccharomyces cerevisiae
residues 391–415) required for MMR. The Mlh1-R401A,D403A-Pms1 linker motif mutant protein was defective for MMR and endonuclease activity in vitro, even though the conserved motif could be >750 Å from the carboxyl-terminal endonuclease active site or the N-terminal adenosine triphosphate (ATP)-binding site. Peptides encoding this motif inhibited wild-type Mlh1-Pms1 endonuclease activity. The motif functioned in vivo at different sites within the Mlh1 linker and within the Pms1 linker. Motif mutations in human cancers caused a loss-of-function phenotype when modeled in
S. cerevisiae
. These results suggest that the Mlh1 motif promotes the PCNA-activated endonuclease activity of Mlh1-Pms1 via interactions with DNA, PCNA, RFC, or other domains of the Mlh1-Pms1 complex.
Microbiome composition modulates secondary metabolism in a multispecies bacterial community
Authors: Chevrette Marc G. , Thomas Chris S. , Hurley Amanda , Rosario-Meléndez Natalia , Sankaran Kris , Tu Yixing , Hall Austin , Magesh Shruthi , Handelsman Jo
Published: October 2022

Bacterial secondary metabolites are a major source of antibiotics and other bioactive compounds. In microbial communities, these molecules can mediate interspecies interactions and responses to environmental change. Despite the importance of secondary metabolites in human health and microbial ecology, little is known about their roles and regulation in the context of multispecies communities. In a simplified model of the rhizosphere composed of
Bacillus cereus
,
Flavobacterium johnsoniae
, and
Pseudomonas koreensis
, we show that the dynamics of secondary metabolism depend on community species composition and interspecies interactions. Comparative metatranscriptomics and metametabolomics reveal that the abundance of transcripts of biosynthetic gene clusters (BGCs) and metabolomic molecular features differ between monocultures or dual cultures and a tripartite community. In both two- and three-member cocultures,
P. koreensis
modified expression of BGCs for zwittermicin, petrobactin, and other secondary metabolites in
B. cereus
and
F. johnsoniae,
whereas the BGC transcriptional response to the community in
P. koreensis
itself was minimal. Pairwise and tripartite cocultures with
P. koreensis
displayed unique molecular features that appear to be derivatives of lokisin, suggesting metabolic handoffs between species. Deleting the BGC for koreenceine, another
P. koreensis
metabolite, altered transcript and metabolite profiles across the community, including substantial up-regulation of the petrobactin and bacillibactin BGCs in
B. cereus
, suggesting that koreenceine represses siderophore production. Results from this model community show that bacterial BGC expression and chemical output depend on the identity and biosynthetic capacity of coculture partners, suggesting community composition and microbiome interactions may shape the regulation of secondary metabolism in nature.
Blockade of the protease ADAM17 ameliorates experimental pancreatitis
Authors: Saad Mohamed I. , Weng Teresa , Lundy Joanne , Gearing Linden J. , West Alison C. , Harpur Christopher M. , Alanazi Mohammad , Hodges Christopher , Croagh Daniel , Kumar Beena , Sagi Irit , Rose-John Stefan , Jenkins Brendan J.
Published: October 2022

Acute and chronic pancreatitis, the latter associated with fibrosis, are multifactorial inflammatory disorders and leading causes of gastrointestinal disease-related hospitalization. Despite the global health burden of pancreatitis, currently, there are no effective therapeutic agents. In this regard, the protease A Disintegrin And Metalloproteinase 17 (ADAM17) mediates inflammatory responses through shedding of bioactive inflammatory cytokines and mediators, including tumor necrosis factor α (TNFα) and the soluble interleukin (IL)-6 receptor (sIL-6R), the latter of which drives proinflammatory IL-6 trans-signaling. However, the role of ADAM17 in pancreatitis is unclear. To address this,Adam17ex/exmice—which are homozygous for the hypomorphicAdam17exallele resulting in marked reduction in ADAM17 expression—and their wild-type (WT) littermates were exposed to the cerulein-induced acute pancreatitis model, and acute (1-wk) and chronic (20-wk) pancreatitis models induced by the cigarette smoke carcinogen nicotine-derived nitrosamine ketone (NNK). Our data reveal that ADAM17 expression was up-regulated in pancreatic tissues of animal models of pancreatitis. Moreover, the genetic (Adam17ex/exmice) and therapeutic (ADAM17 prodomain inhibitor [A17pro]) targeting of ADAM17 ameliorated experimental pancreatitis, which was associated with a reduction in the IL-6 trans-signaling/STAT3 axis. This led to reduced inflammatory cell infiltration, including T cells and neutrophils, as well as necrosis and fibrosis in the pancreas. Furthermore, up-regulation of the ADAM17/IL-6 trans-signaling/STAT3 axis was a feature of pancreatitis patients. Collectively, our findings indicate that the ADAM17 protease plays a pivotal role in the pathogenesis of pancreatitis, which could pave the way for devising novel therapeutic options to be deployed against this disease.
A moral trade-off system produces intuitive judgments that are rational and coherent and strike a balance between conflicting moral values
Authors: Guzmán Ricardo Andrés , Barbato María Teresa , Sznycer Daniel , Cosmides Leda
Published: October 2022

How does the mind make moral judgments when the only way to satisfy one moral value is to neglect another? Moral dilemmas posed a recurrent adaptive problem for ancestral hominins, whose cooperative social life created multiple responsibilities to others. For many dilemmas, striking a balance between two conflicting values (a compromise judgment) would have promoted fitness better than neglecting one value to fully satisfy the other (an extreme judgment). We propose that natural selection favored the evolution of a cognitive system designed for making trade-offs between conflicting moral values. Its nonconscious computations respond to dilemmas by constructing “rightness functions”: temporary representations specific to the situation at hand. A rightness function represents, in compact form, an ordering of all the solutions that the mind can conceive of (whether feasible or not) in terms of moral rightness. An optimizing algorithm selects, among the feasible solutions, one with the highest level of rightness. The moral trade-off system hypothesis makes various novel predictions: People make compromise judgments, judgments respond to incentives, judgments respect the axioms of rational choice, and judgments respond coherently to morally relevant variables (such as willingness, fairness, and reciprocity). We successfully tested these predictions using a new trolley-like dilemma. This dilemma has two original features: It admits both extreme and compromise judgments, and it allows incentives—in this case, the human cost of saving lives—to be varied systematically. No other existing model predicts the experimental results, which contradict an influential dual-process model.
Variety of microstructure and mechanical properties along the laser impact welded interface
Authors: Wang Qihan , Wang Kangnian , Wang Huimin , Zheng Wenyue
Published: October 2022

Laser impact welding (LIW) is an attractive technique for thin film dissimilar materials solid-state welding. To understand the mechanism of laser impact welding, the wave character of wavy interfaces, the morphology of intermetallics, the diffusion phenomenon and the hardness along the welding direction were investigated with Scanning Electron Microscopy (SEM), Energy Dispersive Spectrometer (EDS), and nanoindentation, respectively. There is a microstructure and mechanical property gradient not only along the welding direction, but also perpendicular to it. The variety of both microstructure and mechanical properties is the combined result of impact pressure and impact angle. The gradient of the nanoindentation demonstrated the variety of the strengthening mechanism nearby the weld interface. The study provides valuable knowledge for welding process understanding and control.
Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells
Authors: Weier Ann-Kathrin , Homrich Mirka , Ebbinghaus Stephanie , Juda Pavel , Miková Eliška , Hauschild Robert , Zhang Lili , Quast Thomas , Mass Elvira , Schlitzer Andreas , Kolanus Waldemar , Burgdorf Sven , Gruß Oliver J. , Hons Miroslav , Wieser Stefan , Kiermaier Eva
Published: October 2022

Centrosomes play a crucial role during immune cell interactions and initiation of the immune response. In proliferating cells, centrosome numbers are tightly controlled and generally limited to one in G1 and two prior to mitosis. Defects in regulating centrosome numbers have been associated with cell transformation and tumorigenesis. Here, we report the emergence of extra centrosomes in leukocytes during immune activation. Upon antigen encounter, dendritic cells pass through incomplete mitosis and arrest in the subsequent G1 phase leading to tetraploid cells with accumulated centrosomes. In addition, cell stimulation increases expression of polo-like kinase 2, resulting in diploid cells with two centrosomes in G1-arrested cells. During cell migration, centrosomes tightly cluster and act as functional microtubule-organizing centers allowing for increased persistent locomotion along gradients of chemotactic cues. Moreover, dendritic cells with extra centrosomes display enhanced secretion of inflammatory cytokines and optimized T cell responses. Together, these results demonstrate a previously unappreciated role of extra centrosomes for regular cell and tissue homeostasis.
Understanding the effects of temporal waveform modulation of laser emission power in laser powder bed fusion: Part II - Experimental investigation
Authors: Caprio Leonardo , Demir Ali Gökhan , Previtali Barbara
Published: October 2022

The laser powder bed fusion (LPBF) process has historically been operated with high-brilliance fibre laser sources with continuous wave (CW) emission. Nonetheless, temporal waveform modulation of the laser emission power at high-frequency levels can provide a means to enhance the deposition process by modifying the melt dynamics and solidification mechanisms. In order to disclose the effect of different waveform shapes and their parameters, an experimental study using an open LPBF system was conducted. This paper is the second part of an investigation on this topic, which aims to validate the analytical model proposed in the first part of the work. The LPBF system that was developed enabled the power emission profiles to be programmed during single-track depositions. Four different waveform shapes were tested (namely square wave, ramp up, ramp down and triangle wave) at different levels of waveform amplitude (ΔP= 200–400 W) and different frequencies (fw
= 2–4–6–8 kHz) during the single-track deposition of stainless steel AISI316L. High-speed imaging acquisitions allowed the melt dynamics to be disclosed and the melt-oscillation frequency to be identified. Larger waveform amplitudes and waveforms with sudden variations of emission power generated melt ejections and process instabilities. Stable conditions could be identified when employing ramp up and triangle waveforms with ΔP = 200. Melt-surface oscillation frequency corresponded to the values imposed via the modulation of the laser emission power, thus validating the analytical model of Part I, which correlated the melt-surface temperature to the recoil pressure induced over the molten pool. Optical microscopy images and metallographic cross-sections confirmed the high-speed video observations. Three-dimensional reconstructions of the depositions via focus variation microscopy allowed the build rates and roughness of the single tracks to be determined. Build rates obtained in stable deposition conditions with waveform modulation are analogous to values obtainable with CW emission, and beneficial effects over the roughness were reported.
Compact broadband acoustic meta-silencer based on synergy between reactive and resistive units
Authors: Zhang Zhenfang , Yu Dianlong , Xiao Yong , Hu Bing , Bai Yu , Wen Jihong
Published: October 2022

Acoustic silencers are the most effective solution to control noise in ducts. In this paper, we propose a compact acoustic meta-silencer (AMS) based on the synergy between reactive and resistive units that enables the reduction of low-frequency and broadband noise. We first propose a conceptual AMS comprising simple reactive and resistive units to verify its unique sound attenuation performance. To explore its potential for application, we then propose an advanced AMS unit consisting of two independent annular chambers that represent reactive and resistive units, respectively. The synergistic mechanism between reactive and resistive units to achieve superior sound attenuation is revealed. Next, the band structures of the infinite periodic advanced AMS are discussed, and three different types of advanced AMS containing six units are examined. It is demonstrated numerically and experimentally that the optimized AMS with a compact size can achieve a transmission loss higher than 15 dB over a super-wide low-frequency range (290–1344 Hz). The work here provides a new avenue for the design of low-frequency and broadband meta-silencers to control the noise in ducts.
Interface engineering of 9X stacked 3D NAND flash memory using hydrogen post-treatment annealing
Authors: Choi Saeyan , Kim Seungsob , Bang Seain , Kim Jungchun , Park Dong Geun , Jin Seunghee , Kim Min Jung , Kwon Eunmee , Lee Jae Woo
Published: October 2022

This study investigates the effects of hydrogen post-treatment on 3D NAND flash memory. Hydrogen post-treatment annealing (PTA) is suggested to passivate the defects in the tunneling oxide/poly-Si interface and inside the poly-Si channel. However, excess hydrogen PTA can release hydrogen atoms from the passivated defects, which may degrade device performance. Therefore, it is important to determine the appropriate PTA condition for optimization of the device performance. Three different conditions for hydrogen PTA, namely Reference, H, and H++, are applied to observe the effects on device performance. The activation energy (

E

a

) of the device parameters was extracted according to the hydrogen PTA condition to analyze the effects. The extracted

E

a

is about 74 meV for Reference, 53 meV for H, and 58 meV for H++ conditions, with the best performance observed at the H condition. Optimal hydrogen PTA shows the best on-current (51% higher than Reference) and stable short-term retention (66% suppressed

Δ

V
T than Reference) in 9X stacked 3D NAND flash memory.
Renewable and eco-friendly ZnO immobilized onto dead sea sponge floating materials with dual practical aspects for enhanced photocatalysis and disinfection applications
Authors: Bhatti Muhammad Ali , Almani Khalida Faryal , Shah Aqeel Ahmed , Tahira Aneela , Chana Iftikhar Ahmed , Aftab Umair , Ibupoto Mazhar Hussain , Mirjat Abdul Nabi , Aboelmaaref Amal , Nafady Ayman , Vigolo Brigitte , Ibupoto Zafar Hussain
Published: October 2022

In this study, we have investigated the role of natural dead sea sponge (DSS, Porifera) as a three-dimensional (3D) porous host substrate for the immobilization of nanostructured ZnO material towards the development of ZnO based floating photocatalysts for efficient removal of methylene blue (MB) dye under the illumination of sunlight. After photodegradation, the treated water after dye degradation contains several pathogens, different disinfectants or chemical reagents that are essentially used. This is not the case for DSS as it can naturally kill any pathogens during the wastewater treatment process. To explore these functions, ZnO nanosheets were incorporated onto DSS via hydrothermal protocol and the as prepared ZnO/DSS hybrid material exhibited approximately ∼100% degradation efficiency for the removal of MB. Importantly, the degradation kinetics associated with the fabricated ZnO/DSS was remarkably accelerated as evidenced by the high values of degradation reaction rate constants (3.35 × 10–2 min−1). The outperformance of ZnO/DSS could be attributed to the adsorption caused by its 3D porous structure together with the high rapid oxidation of MB. Furthermore, the high charge separation of electron–hole pairs, natural porosity, and abundant catalytic sites offered by the hybrid ZnO/DSS floating photocatalyst have enabled quantitative (∼100%) degradation efficiency for MB. Finally, the excellent reusability results confirm the feasibility of using natural ZnO/DSS-based photocatalyst for practical solution of wastewater treatment and other environmental problems.
Deep learning-based remote-photoplethysmography measurement from short-time facial video
Authors: Li Bin , Jiang Wei , Peng Jinye , Li Xiaobai
Published: October 2022

Objective. Efficient non-contact heart rate (HR) measurement from facial video has received much attention in health monitoring. Past methods relied on prior knowledge and an unproven hypothesis to extract remote photoplethysmography (rPPG) signals, e.g. manually designed regions of interest (ROIs) and the skin reflection model. Approach. This paper presents a short-time end to end HR estimation framework based on facial features and temporal relationships of video frames. In the proposed method, a deep 3D multi-scale network with cross-layer residual structure is designed to construct an autoencoder and extract robust rPPG features. Then, a spatial-temporal fusion mechanism is proposed to help the network focus on features related to rPPG signals. Both shallow and fused 3D spatial-temporal features are distilled to suppress redundant information in the complex environment. Finally, a data augmentation strategy is presented to solve the problem of uneven distribution of HR in existing datasets. Main results. The experimental results on four face-rPPG datasets show that our method overperforms the state-of-the-art methods and requires fewer video frames. Compared with the previous best results, the proposed method improves the root mean square error (RMSE) by 5.9%, 3.4% and 21.4% on the OBF dataset (intra-test), COHFACE dataset (intra-test) and UBFC dataset (cross-test), respectively. Significance. Our method achieves good results on diverse datasets (i.e. highly compressed video, low-resolution and illumination variation), demonstrating that our method can extract stable rPPG signals in short time.
On weak lensing response functions
Authors: Munshi D. , Takahashi R. , McEwen J.D.
Published: October 2022

We introduce the response function approach
to model the weak lensing statistics in the context of
separate universe formalism.
Numerical results for the RFs are presented for various
semi-analytical models
that includes perturbative modelling and variants of halo models.
These results extend the recent
studies of the Integrated Bispectrum and Trispectrum to
arbitrary order. We find that
due to the line-of-sight projection effects, the expressions for RFs are
not identical to the squeezed correlation functions of the same order.
We compute the RFs in three-dimensions using the spherical
Fourier-Bessel formalism
which provides a natural framework for
incorporating photometric redshifts, and relate these expressions to tomographic and projected statistics.
We generalise the concept of k-cut power spectrum to k-cut response functions.
In addition to response functions, we also
define their counterparts in real space, since they are easier to
estimate from surveys with low sky-coverage and non-trivial survey boundaries.
Waterfall stiff period can generate observable primordial gravitational waves
Authors: Dimopoulos Konstantinos
Published: October 2022

A toy-model is studied, which considers two flat directions meeting at an
enhanced symmetry point such that they realise the usual hybrid inflation
mechanism. The kinetic term of the waterfall field features a pole at its
Planckian vacuum expectation value (VEV), as with α-attractors.
Consequently, after the phase transition which terminates hybrid inflation,
the waterfall field never rolls to its VEV. Instead, it drives a stiff period,
where the barotropic parameter of the Universe w ≈ 1/2 results in a
peak in the spectrum of primordial gravitational waves, which will be
observable by the forthcoming LISA mission as well as by Advanced LIGO.
Consequences of neutron decay inside neutron stars
Authors: Husain Wasif , Motta Theo F. , Thomas Anthony W.
Published: October 2022

The hypothesis that neutrons might decay into dark matter is explored using neutron stars as a testing ground. It is found that in order to obtain stars with masses at the upper end of those observed, the dark matter must experience a relatively strong self-interaction. Conservation of baryon number and energy then require that the star must undergo some heating, with a decrease in radius, leading to an increase in speed of rotation over a period of days.