bluuebunny/crossref_metadata_2025 huggingface dataset:
Macroscopic fossils from the Chuanlinggou Formation of North China: evidence for an earlier origin of multicellular algae in the late Palaeoproterozoic
Authors: Liu Jingqi , Zhang Yang , Shi Xiaoying , Chen Anfeng , Tang Dongjie , Yang Tinglu
Published: December 2023

Multicellular algae are the core topic for understanding the early life evolution on Earth. The timing of origin and cellular differentiation of multicellular algae, however, remains poorly constrained. The Palaeoproterozoic to early Mesoproterozoic is a critical period during which multicellular algae began to occur and evolve in marine environments. This paper reports well‐preserved multicellular fossils from shales of the Chuanlinggou Formation (c. 1.64 Ga) in North China, with emphasis on their holdfast and putative cellular structures. These macroalgal fossils are reasonably diversified and includeChuaria circularis,Tawuia sinensis,Tawuia robusta,Glossophyton ovalis,Glossophytonsp.,Tuanshanziasp. and Changchengiasp.; mainly preserved as carbonaceous compressions, with a few sideritized forms. Field emission scanning electron microscope (FESEM) observation revealed multicellular structures inChuaria, confirming its biological attributes of a multicellular eukaryote and providing direct evidence that multicellular algae had already originated by the terminal Palaeoproterozoic, earlier than previously speculated.Tuanshanziasp. andChangchengiasp. developed with a bare rhizome holdfast, suggesting that they had a benthic sessile lifestyle in their late Palaeoproterozoic oceanic habitat.
Quantitative ichnology: a novel framework to determine the producers of locomotory trace fossils with the ichnogenus Gordia as a case study
Authors: Wang Zekun , Rahman Imran A.
Published: December 2023

Trace fossils record the interactions between organisms and their surroundings, and can therefore provide unique insights into the coevolution of trace makers and the environment. However, identifying the producers of trace fossils is challenging because different animals can create very similar traces and many ichnotaxa can therefore only be attributed to broad morphological grades. For example, simple horizontal traces like Gordia are generally suggested to have been produced by vermiform organisms, potentially encompassing a range of animal phyla. This uncertainty makes it difficult to decipher their palaeobiological significance through major evolutionary events and episodes of environmental change. We have developed new mathematical approaches for identifying previously unrecognized signatures left by the trace makers of simple marine locomotory traces. We calculated the deviation angle series of self‐crossing traces made by extant isopods, polychaetes, gastropods and nematodes, computing the frequency spectrum and autocorrelation function in each case. The results reveal that each of these taxa left unique markers during the trace‐making process, reflecting differences in their anatomy and locomotory behaviour. We were able to identify the possible trace makers of several early Palaeozoic Gordia specimens, demonstrating that ichnospecies within the same ichnogenus can be created by distantly related animals with very different morphologies and/or behaviours. This novel mathematical framework has great potential for identifying the possible producers of diverse trace fossils through deep time, helping to uncover the earliest evidence of certain animals or behaviours. It also has great potential for quantifying ichnotaxonomy, consolidating the link between ichnology and palaeobiology.
New wine in old bottles: Modification of the Na+/K+‐ATPase enzyme activity assay and its application in salmonid aquaculture
Authors: Takvam Marius , Sundell Kristina , Sundh Henrik , Gharbi Naouel , Kryvi Harald , Nilsen Tom Ole
Published: December 2023

The Na+, K+ ATPase (NKA) enzyme is important to generate the transmembrane ion gradient in the gills, intestine, and kidneys, hence, is vital for secondary transport of fluids and different solutes in teleosts. Gill NKA enzyme activity is often used as a proxy for parr–smolt transformation (PST) during which anadromous salmonids prepare for seawater (SW). Increased intensification and production of larger smolts in modern salmonid aquaculture has resulted in reports of gill NKA activity being less reliable as a proxy for smolt quality. Consequently, changes in mRNA nka‐α1b/α1a ratios in gills are increasingly used as indicators of PST. However, nka isoform mRNA abundance may not reflect translation into the functional protein, nor the activity of the mature enzyme. This may limit the predictive power of molecular markers under certain environmental conditions, rearing regimes and biological scenarios. During PST, the osmoregulatory transformations necessary for SW tolerance and survival does not only occur in the gills. Equally important are the changes in ion transporting activities, including NKA activity, in the intestine and kidneys. However, to our knowledge, there are no previous studies addressing the timing and concurrent changes in NKA activity in the three osmoregulatory tissue during PST. Here we present modifications and optimization of the NKA enzyme activity protocols for gill, intestinal and kidney tissue and outline how to best utilize NKA activity measurements as part of a more holistic approach to evaluate overall smolt quality in modern aquaculture.
Fossilized autogenic responses of grain‐size transition to sediment supply and water discharge: Alluvial fan experiments
Authors: Shin Haein , Kim Wonsuck , Lee Hyojae , Johnson Joel P. L. , Paola Chris
Published: December 2023

Autogenic feedbacks can produce large‐scale, organized stratigraphic patterns in alluvial fans, but autogenic depositional signatures of specific upstream boundary conditions remain challenging to interpret. Here, a combination of theory, experiment and field application is used to explore how autogenic lithofacies changes can be interpreted as stratigraphic indicators of upstream boundary conditions. Six experiments were conducted to test the effects of sediment supply and water discharge rates on autogenic advance and retreat of the lithofacies boundary (grain‐size transition) in an alluvial fan with two dominant grain sizes. Migration of the grain‐size transition caused a short‐term zigzag pattern in the grain‐size transition position in the dip‐directional deposit section. For each experiment, time‐lapse images and laser topographic scans of the fan surface and stratigraphic cross‐sections of the final deposits were used to quantify characteristic timescales of autogenic processes. Timescales for fan‐margin migration, surface wet‐fraction change and grain‐size transition migration generally shorten as sediment supply rate increases and water discharge rate decreases. Increasing the sediment supply rate shortens the duration of the fluvial sediment storage and release cycle, producing higher frequency zigzags in the grain‐size transition trajectory. Increasing the water discharge tends to widen channels and lengthens the duration of the fluvial sediment storage and release cycle, constructing lower frequency zigzags in the grain‐size transition trajectory. Increasing the water discharge also enables more sediment to transport further downstream during release events, leading to higher magnitude zigzags in the grain‐size transition trajectory. These relationships between upstream boundary conditions and the grain‐size transition trajectory demonstrate how autogenic stratigraphic signals could be used as a tool to infer relative changes in boundary conditions.
An evolutionary view of vanillylamine synthase pAMT, a key enzyme of capsaicinoid biosynthesis pathway in chili pepper
Authors: Kusaka Hirokazu , Nakasato Saika , Sano Kaori , Kobata Kenji , Ohno Sho , Doi Motoaki , Tanaka Yoshiyuki
Published: December 2023

Pungent capsaicinoid is synthesized only in chili pepper (Capsicum spp.). The production of vanillylamine from vanillin is a unique reaction in the capsaicinoid biosynthesis pathway. Although putative aminotransferase (pAMT) has been isolated as the vanillylamine synthase gene, it is unclear how Capsicum acquired pAMT. Here, we present a phylogenetic overview of pAMT and its homologs. The Capsicum genome contained 5 homologs, including pAMT, CaGABA‐T1, CaGABA‐T3, and two pseudogenes. Phylogenetic analysis indicated that pAMT is a member of the Solanaceae cytoplasmic GABA‐Ts. Comparative genome analysis found that multiple copies of GABA‐T exist in a specific Solanaceae genomic region, and the cytoplasmic GABA‐Ts other than pAMT are located in the region. The cytoplasmic GABA‐T was phylogenetically close to pseudo‐GABA‐T harboring a plastid transit peptide (pseudo‐GABA‐T3). This suggested that Solanaceae cytoplasmic GABA‐Ts occurred via duplication of a chloroplastic GABA‐T ancestor and subsequent loss of the plastid transit signal. The cytoplasmic GABA‐T may have been translocated from the specific Solanaceae genomic region during Capsicum divergence, resulting in the current pAMT locus. A recombinant protein assay demonstrated that pAMT had higher vanillylamine synthase activity than those of other plant GABA‐Ts. pAMT was expressed exclusively in the placental septum of mature green fruit, whereas tomato orthologs SlGABA‐T2/4 exhibit a ubiquitous expression pattern in plants. These findings suggested that both the increased catalytic efficiency and transcriptional changes in pAMT may have contributed to establish vanillylamine synthesis in the capsaicinoid biosynthesis pathway. This study provides insights into the establishment of pungency in the evolution of chili peppers.
Seismic Assessment Formula for a Buried Pipeline With Local Wall Thinning
Authors: Onuki Shoma , Mitsuya Masaki
Published: December 2023

The structural strength of buried pipeline may be reduced by local wall thinning owing to corrosion in long-term operations. In seismic active area, it is necessary to ensure the integrity of buried pipeline with wall thinning against seismic motion. This study proposed a seismic assessment formula for a pipe with wall thinning subjected to cyclic axial loading assuming seismic motion. Cyclic axial loading experiments using pipes with wall thinning and finite element analysis (FEA) were conducted to study the failure behavior. The pipe with wall thinning deformed starting from the wall-thinning part, and finally plastic collapse due to elephant foot buckling or leakage at the wall thinning due to low-cycle fatigue occurred in several to ten and several cycles. Based on the deformation mechanism at wall thinning, a seismic assessment formula was proposed. The proposed formula can easily evaluate the seismic performance of the pipe with wall thinning against design seismic motion. The formula was validated by the results of experiments and FEA. In addition, based on the proposed formula, the assessment curves for an allowable wall-thinning size against design seismic motion were illustrated. The formula can be used to formulate standards and assess the safety of pipes with wall thinning that are subjected to seismic motion.
Transient Process Analysis of Oscillating Motion in Oscillating Heat Pipes
Authors: Núñez Roberto , Ma Hongbin
Published: December 2023

During the startup phase, oscillating heat pipes (OHPs) exhibit a transient process in which the working fluid moves erratically until a steady-state oscillatory flow is attained. Understanding the transient process is important to predict how long it takes an oscillating heat pipe to reach normal operation and realize its heat transfer potential after it is started. In this paper, we perform a theoretical study of the transient process of oscillating heat pipes. Based on a one-dimensional mathematical model, we obtain an analytic solution that allows us to predict transient process characteristics of oscillating motions in an oscillating heat pipe, as well as the impact that different design and operating parameters have on this transient process.
Simulation of Heat and Mass Transfer in a Moving Bed Part-Fluidized Boiler
Authors: Wan Guang-Zhong , Guo Qiang , Li Yang , Ma Gui-Yang , Xu Chi , Li Ya-Ya
Published: December 2023

Moving bed part-fluidized boiler is a new type of furnace. The new combustion method in the furnace has attracted a lot of attention and shown attractive prospects. Two-dimensional computational fluid dynamic (CFD) simulations were performed for a 116 MW moving bed part-fluidized boiler to investigate the different combustion patterns of coal particles of different particle sizes inside the furnace chamber. A low-NOX combustion method based on the combination of laminar combustion and fluidized combustion is proposed. By comparing the effects of different air distributions on the fluidization state of coal particles, the air distribution values required for optimal fluidized combustion were obtained. The temperature field and pollutant distribution in the furnace chamber for the conventional combustion method and the new combustion method were also simulated. The results show that the combustion technology combining laminar combustion and fluidization of a moving bed part-fluidized boiler can significantly improve the combustion rate and reduce the NOX concentration at the furnace exit. When the secondary air speed is up to 15 m/s, the coal particles smaller than 5 mm are fully fluidized and burned in the whole furnace chamber. The coal particles larger than 5 mm are burned on the bed. The pollutant emission of the boiler can reach the best condition. The new type of boiler can reach a super clean emission in which the NOX emission value is below 47 mg/m3, and the SO2 emission value is reduced to 0.15 mg/m3.
Study on Radiofrequency Ablation of Lung and Kidney Tumors With and Without Nanoparticles Using Multi-Tined Electrode
Authors: Ahammed Md. Ezaz , Peravali Mrunal Swaroop , Naik Santosh S. , Yadav Ajay Kumar , Laxminidhi T.
Published: December 2023

Radio frequency ablation (RFA) is an alternative method for the cure of malign tumors in the liver, lung, and kidney. In the present work, finite element method (FEM) analysis is conducted to study the effect of nanoparticles on the temporal and spatial temperature distribution during RFA. Three-dimensional thermoelectrically FEM model consisting of a multitined radio frequency electrode (nine-tine, deployed up to 2 cm) and a cubical tumor of size 50 mm3 is developed. Numerical simulation is carried out under the temperature-controlled mode (95 °C) with 10 min ablation time. A study using multitined electrodes is carried out on different tissues, i.e., lung and kidney, with and without nanoparticles. Results show that the nanoparticles increase the heat conduction rate and decrease the ablation time up to 13% for the inclusion of 6% nanoparticles. It has been found that the spatial temperature distribution becomes uniform with nanoparticle assistance.
Transformation of social relationships in COVID-19 America: Remote communication may amplify political echo chambers
Authors: Lee Byungkyu , Lee Kangsan , Hartmann Benjamin
Published: December 2023

The COVID-19 pandemic, with millions of Americans compelled to stay home and work remotely, presented an opportunity to explore the dynamics of social relationships in a predominantly remote world. Using the 1972–2022 General Social Surveys, we found that the pandemic significantly disrupted the patterns of social gatherings with family, friends, and neighbors but only momentarily. Drawing from the nationwide ego-network surveys of 41,033 Americans from 2020 to 2022, we found that the size and composition of core networks remained stable, although political homophily increased among nonkin relationships compared to previous surveys between 1985 and 2016. Critically, heightened remote communication during the initial phase of the pandemic was associated with increased interaction with the same partisans, although political homophily decreased during the later phase of the pandemic when in-person contacts increased. These results underscore the crucial role of social institutions and social gatherings in promoting spontaneous encounters with diverse political backgrounds.
Global cascade of kinetic energy in the ocean and the atmospheric imprint
Authors: Storer Benjamin A. , Buzzicotti Michele , Khatri Hemant , Griffies Stephen M. , Aluie Hussein
Published: December 2023

Here, we present an estimate for the ocean's global scale transfer of kinetic energy (KE), across scales from 10 to 40,000 km. Oceanic KE transfer between gyre scales and mesoscales is induced by the atmosphere’s Hadley, Ferrel, and polar cells, and the intertropical convergence zone induces an intense downscale KE transfer. Upscale transfer peaks at 300 gigawatts across mesoscales of 120 km in size, roughly one-third the energy input by winds into the oceanic general circulation. Nearly three quarters of this “cascade” occurs south of 15°S and penetrates almost the entire water column. The mesoscale cascade has a self-similar seasonal cycle with characteristic lag time of ≈27 days per octave of length scales; transfer across 50 km peaks in spring, while transfer across 500 km peaks in summer. KE of those mesoscales follows the same cycle but peaks ≈40 days after the peak cascade, suggesting that energy transferred across a scale is primarily deposited at a scale four times larger.
Bringing underserved communities life-saving aid through aerial logistics
Authors: Kremer Pedro , Leyzerovskaya Aleksandra , DuBois Shelley , Lipsitt Jonah , Haruna Florence , Lebed Olga
Published: December 2023

Autonomous drone delivery of medical supplies has improved access to health care for local communities in Africa.
Inhibition of RIP1 improves immune reconstitution and reduces GVHD mortality while preserving graft-versus-leukemia effects
Authors: Prado-Acosta Mariano , Jeong Seihwan , Utrero-Rico Alberto , Goncharov Tatiana , Webster Joshua D. , Holler Ernst , Morales George , Dellepiane Sergio , Levine John E. , Rothenberg Michael E. , Vucic Domagoj , Ferrara James L. M.
Published: December 2023

Graft-versus-host disease (GVHD) remains the major cause of morbidity and nonrelapse mortality (NRM) after hematopoietic cell transplantation (HCT). Inflammatory cytokines mediate damage to key GVHD targets such as intestinal stem cells (ISCs) and also activate receptor interacting protein kinase 1 (RIP1; RIPK1), a critical regulator of apoptosis and necroptosis. We therefore investigated the role of RIP1 in acute GVHD using samples from HCT patients, modeling GVHD damage in vitro with both human and mouse gastrointestinal (GI) organoids, and blocking RIP1 activation in vivo using several well-characterized mouse HCT models. Increased phospho-RIP1 expression in GI biopsies from patients with acute GVHD correlated with tissue damage and predicted NRM. Both the genetic inactivation of RIP1 and the RIP1 inhibitor GNE684 prevented GVHD-induced apoptosis of ISCs in vivo and in vitro. Daily administration of GNE684 for 14 days reduced inflammatory infiltrates in three GVHD target organs (intestine, liver, and spleen) in mice. Unexpectedly, GNE684 administration also reversed the marked loss of regulatory T cells in the intestines and liver during GVHD and reduced splenic T cell exhaustion, thus improving immune reconstitution. Pharmacological and genetic inhibition of RIP1 improved long-term survival without compromising the graft-versus-leukemia (GVL) effect in lymphocytic and myeloid leukemia mouse models. Thus, RIP1inhibition may represent a nonimmunosuppressive treatment for GVHD.
Development of an agar-based screening method for terbinafine, itraconazole, and amorolfine susceptibility testing of
Trichophyton
spp.
Authors: Siopi Maria , Efstathiou Ioanna , Arendrup Maiken C. , Meletiadis Joseph
Published: December 2023

Resistance in dermatophytes is an emerging global public health issue. We, therefore, developed an agar-based method for screening
Trichophyton
spp. susceptibility to terbinafine (TRB), itraconazole (ITC), and amorolfine (AMF) and validated it using molecularly characterized isolates. Α total of 40
Trichophyton
spp. isolates, 28 TRB wild type (WT) (13
T. rubrum
, 10
T. mentagrophytes
, 5
T. interdigitale
) and 12 TRB non-WT (7
T. rubrum
, 5
T. indotineae
) with different alterations in the squalene epoxidase (SQLE) gene, were used. The optimal test conditions (inoculum and drug concentrations, incubation time, and temperature) and stability over time were evaluated. The method was then applied for 86 WT
Trichophyton
spp. clinical isolates (68
T. rubrum
, 7
T. interdigitale
, 6
T. tonsurans
, 5
T. mentagrophytes
) and 4 non-WT
T. indotineae
. Optimal growth of drug-free controls was observed using an inoculum of 20 µL 0.5 McFarland after 5–7 days of incubation at 30°C. The optimal concentrations that prevented the growth of WT isolates were 0.016 mg/L of TRB, 1 mg/L of ITC, and 0.25 mg/L of AMF, whereas 0.125 mg/L of TRB was used for the detection of
Trichophyton
strong SQLE mutants (MIC ≥0.25 mg/L). The agar plates were stable up to 4 months. Inter-observer and inter-experimental agreement were 100%, and the method successfully detected TRB non-WT
Trichophyton
spp. strains showing 100% agreement with the reference EUCAST methodology. An agar-based method was developed for screening
Trichophyton
spp. in order to detect TRB non-WT weak and strong mutant isolates facilitating their detection in non-expert routine diagnostic laboratories.
Precision-cut lung slices as an
ex vivo
model to study
Pneumocystis murina
survival and antimicrobial susceptibility
Authors: Munyonho Ferris T. , Clark Robert D. E. , Lin Dong , Khatun Mst Shamima , Pungan Dora , Dai Guixiang , Kolls Jay K.
Published: December 2023

Pneumocystis
pneumonia (PCP) is a serious fungal lung infection caused by
Pneumocystis jirovecii
in immunosuppressed individuals. The lack of viable
in vitro/ex vivo
PCP models has greatly hindered the progress in studying the biology of these fungi, the host/pathogen interactions, as well as antifungal susceptibility testing. In this study, we show the utility of precision-cut lung slices (PCLS) to support the survival of
Pneumocystis murina in vitro
. We cultured PCLS tissue derived from wild type and immunocompromised mice with a
P. murina
inoculum in submerged or air-liquid interface models for up to 14 days. We isolated total RNA from the cultured lung tissues at days 0, 3, 7, 10, and 14 and analyzed for the expression of host lung genes and
P. murina
genes (
Gsc1
for asci and
Sp
for trophs) by real-time quantitative PCR. When cultured in media alone,
P. murina
died gradually within a few days. However, when cultured on PCLS, both the troph and ascus forms survived throughout the incubation period of 2 weeks. Moreover, immunohistochemistry staining of
P. murina
inoculated PCLS sections using polyclonal anti-
Pneumocystis
sera and showed evidence of fungal aggregation and possible biofilm formation. Additionally,
in vitro
(PCLS) antibiotic susceptibility testing using commonly used antifungal drugs confirmed successful targeting of the troph and ascus forms by trimethoprim sulfamethoxazole and the ascus form by echinocandins.

IMPORTANCE

Our study reveals the potential of precision-cut lung slices as an
ex vivo
platform to study the growth/survival of
Pneumocystis
spp. that can facilitate the development of new anti-fungal drugs.
Complete genome sequence of eight LEE-negative Shiga toxin-producing
Escherichia coli
strains isolated from patients with hemolytic-uremic syndrome
Authors: Kubomura Akiko , Lee Kenichi , Ohnishi Makoto , Iyoda Sunao , Akeda Yukihiro , Working Group EHEC
Published: December 2023

Major serotypes of Shiga toxin-producing
Escherichia coli
(STEC) carry a locus of enterocyte effacement (LEE), which is required for attaching and effacing lesion formation. Genome information of LEE-negative STEC is scarce despite their virulence potential. We present the complete genome sequences of eight LEE-negative STEC isolates from hemolytic-uremic syndrome patients.
Draft genome sequence of
Kluyvera ascorbata
HAK22 isolated from human feces
Authors: Yadav Asha , Shinde Pratik Balwant , Dhar Mahesh S. , Ponnusamy Kalaiarasan , Marwal Robin , V. S. Radhakrishnan , Sharma Krishna Kant
Published: December 2023

The whole genome sequence of rare human pathogen
Kluyvera ascorbata
strain HAK22 is reported. The
K. ascorbata
HAK22 was isolated from healthy human from Gurugram, Haryana, India. The draft genome has a length of 4.7 Mbp, with 54.36% GC content and 4,411 proteins, 4,470 genes, and 18 antimicrobial resistance genes.
Lifetime measurement of the yrast 2$$^+$$ state in $$^{118}$$Te
Authors: Cederlöf E. Ahlgren , Bäck T. , Nyberg J. , Qi C. , Ataç A. , Badran H. , Braunroth T. , Calverley T. , Cox D. M. , Doncel M. , Grahn T. , Greenlees P. , Hilton J. , Julin R. , Juutinen S. , Konki J. , Li H. , Matta S. , Modamio V. , Singh B. S. Nara , Pakarinen J. , Papadakis P. , Partanen J. , Rahkila P. , Ruotsalainen P. , Sandzelius M. , Sarén J. , Scholey C. , Stolze S. , Subramaniam P. , Uusitalo J. , Valiente-Dobón J. J.
Published: December 2023

The electromagnetic transition probabilities of the yrast $$2^+$$

2
+

states in the midshell Te isotopes, two protons above the closed shell at Sn, are of great importance for the understanding of nuclear collectivity in these isotopes and the role played by the neutron-proton interactions and cross-shell excitations. However, the large uncertainty of the experimental data for the midshell nucleus 118Te and the missing data for 116Te make it difficult to pin down the general trend of the evolution of transition probabilities as a function of the neutron number. In this work, the lifetime of the yrast $$2^+$$

2
+

state in 118Te was measured, with the aim of reducing the uncertainty of the previous measurement. The result is $$\tau _{2+}=7.46(19)$$

τ

2
+

=
7.46

(
19
)

 ps. In addition, the lifetime of the $$4^+$$

4
+

state was measured to be $$\tau _{4+} = 4.25(23)$$

τ

4
+

=
4.25

(
23
)

 ps. The experimental transition rates are extracted from the measured lifetimes and compared with systematic large-scale shell-model calculations. The trend of the $$B(\textrm{E2};0^+\rightarrow 2^+)$$

B
(
E2
;

0
+

→

2
+

)

values in the midshell area is in good agreement with the calculations and the calculated $$B_{4/2}$$

B

4
/
2

ratio provide evidence for 118Te as a near perfect harmonic vibrator.
New rate of convergence of series and its application
Authors: Wan Changhua
Published: December 2023

The existing rate of convergence of series requires a known limit of that series. Direct computation of Brun’s constant as the sum of twin prime reciprocals is challenging as the convergence is agonizingly slow. Here, I introduce the relative increase of the partial sum of a series as a new rate of convergence regardless of the limit of the series. With this concept, I extract a slowly convergent part from the original sum for Brun’s constant so that the remaining one converges faster. Computed data demonstrate the usefulness of the concept. As a result, I obtain an improved lower bound for Brun’s constant using less computing resource and establish an approximate mapping that gives a new estimate for the constant at 1.89558413.
Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic lipid and carbohydrate metabolism
Authors: Keshvari Sahar , Masson Jesse J. R. , Ferrari-Cestari Michelle , Bodea Liviu-Gabriel , Nooru-Mohamed Fathima , Tse Brian W. C. , Sokolowski Kamil A. , Batoon Lena , Patkar Omkar L. , Sullivan Mitchell A. , Ebersbach Hilmar , Stutz Cian , Parton Robert G. , Summers Kim M. , Pettit Allison R. , Hume David A. , Irvine Katharine M.
Published: December 2023

CSF1 administration expands tissue macrophages, which transforms systemic metabolism. CSF1 drives fat mobilization and glucose uptake to support liver growth. The effects of CSF1 are independent of normal hormonal metabolic regulation. The effects of CSF1 are rapidly reversible, restoring homeostatic body composition. CSF1-dependent macrophages and liver size are coupled in a dynamic equilibrium.
Monocyte immunometabolic reprogramming in human pregnancy: contribution of trophoblast cells
Authors: Merech Fátima , Gori Soledad , Calo Guillermina , Hauk Vanesa , Paparini Daniel , Rios Daiana , Lara Brenda , Doga Luciana , D’Eramo Luciana , Squassi Aldo , Ramhorst Rosanna , Argüello Rafael J. , Pérez Leirós Claudia , Vota Daiana
Published: December 2023

Immunometabolism stands as a novel perspective to understand the complex regulation of the immune response and to provide small molecule-based therapies. By applying this approach to study monocytes during pregnancy, we found that these cells have a unique activation pattern. They rely more on glycolysis and show increased efferocytosis/IL-10 production, but they do not have the typical proinflammatory responses. We also present evidence that trophoblast cells can shape monocytes into this distinct immunometabolic profile.
Pattern sensitivity of ampakine-hypoxia interactions for evoking phrenic motor facilitation in anesthetized rat
Authors: Thakre Prajwal P. , Fuller David D.
Published: December 2023

Phrenic motor facilitation (pMF) is evoked after repeated episodes of brief hypoxia. pMF can also be induced when an allosteric modulator of AMPA receptors (ampakine) is intravenously delivered immediately before a single brief hypoxic episode. Here we show that ampakine delivery before hypoxia (vs. during or after hypoxia) evokes the largest pMF with minimal impact on arterial blood pressure and heart rate. Ampakine pretreatment may have value in the context of hypoxia-based neurorehabilitation strategies.
ATP-mediated increase in H+ efflux from retinal Müller cells of the axolotl
Authors: Kreitzer Matthew A. , Vredeveld Mason , Tinner Kaleb , Powell Alyssa M. , Schantz Adam W. , Leininger Rachel , Merillat Rajapone , Gongwer Michael W. , Tchernookova Boriana K. , Malchow Robert Paul
Published: December 2023

Glial cells are a key structural part of the tripartite synapse and have been suggested to regulate synaptic transmission, but the regulatory mechanisms remain unclear. We show that extracellular ATP, a potent glial cell activator, induces H+ efflux from axolotl retinal Müller (glial) cells through a calcium-dependent pathway that is likely to involve calmodulin, PKC, Na+/H+ exchange, and monocarboxylate transport, and suggest that such H+ release may play a key role in modulating neuronal transmission.
Analysis of the correlation between immune cell characteristics and insomnia: a Mendelian randomization study
Authors: Han Yupeng , Song Zhiwei , Li Wangyu , Ke Peng , Wu Xiaodan
Published: December 2023

This study investigated the association between 731 immune cell characteristics and insomnia using Mendelian randomization, revealing that 14 immune cell characteristics across four groups of immune traits (MFI, RC, AC, and MP) have a significant and causal association with insomnia risk. Our results contribute to the understanding of the sleep-immune cross talk doctrine and offer a new theoretical basis for immune modulation in treating insomnia.
Fusion of Deep Features from 2D‐DOST of fNIRS Signals for Subject‐Independent Classification of Motor Execution Tasks
Authors: Khani Pouya , Solouk Vahid , Kalbkhani Hashem , Ahmadi Farid
Published: December 2023

Functional near‐infrared spectroscopy (fNIRS) is a low‐cost and noninvasive method to measure the hemodynamic responses of cortical brain activities and has received great attention in brain‐computer interface (BCI) applications. In this paper, we present a method based on deep learning and the time‐frequency map (TFM) of fNIRS signals to classify the three motor execution tasks including right‐hand tapping, left‐hand tapping, and foot tapping. To simultaneously obtain the TFM and consider the correlation among channels, we propose to utilize the two‐dimensional discrete orthonormal Stockwell transform (2D‐DOST). The TFMs for oxygenated hemoglobin (HbO), reduced hemoglobin (HbR), and two linear combinations of them are obtained and then we propose three fusion schemes for combining their deep information extracted by the convolutional neural network (CNN). Two CNNs, LeNet and MobileNet, are considered and their structures are modified to maximize the accuracy. Due to the lack of enough signals for training CNNs, data augmentation based on the Wasserstein generative adversarial network (WGAN) is performed. Several simulations are performed to assess the performance of the proposed method in three‐class and binary scenarios. The results present the efficiency of the proposed method in different scenarios. Also, the proposed method outperforms the recently introduced methods.
Lethal Neural Tube Defects: Reports of Anencephaly and Craniorachischisis Cases and Literature Review
Authors: Lema Alemayehu Shiferaw , Suleyman Jemila Salih
Published: December 2023

Neural tube defects are serious birth defects of the central nervous system that result from a multifaceted disruption of normal embryogenesis of the nervous system. Although largely preventable, they nonetheless pose a serious threat to global morbidity, disability, mortality, and financial expenses. Despite this, it has been neglected and has only been the subject of limited research until recently. Furthermore, surveillance efforts for neural tube defects remain limited, and no decline in defects has been documented in less developed countries. Here, we report two cases of craniorachischisis and one case of discordant twins for anencephaly. Moreover, the relevant works of literature that are necessary to understand and address this unrelenting phenomenon are provided.
Turning SKD 11 Hardened Steel: An Experimental Study of Surface Roughness and Material Removal Rate Using Taguchi Method
Authors: Nipu Shah Ashiquzzaman , Karim Rezaul , Rahman Aquib , Moon Mahjabin , Choudhury I. A. , Omar Junayed Bin , Khushbu Marsia Sultana
Published: December 2023

Heat-treated steel is widely used in industrial applications due to its high strength and other desirable mechanical qualities. Grinding, which requires a lot of power and is expensive, is typically used to harden machining. In recent times, hard machining has emerged as a viable alternative to grind in select applications. In this investigation, turning operations with a carbide insert (CNMA 120408-KR3215) were carried out on SKD 11 (53 HRC) hardened steel. A total of nine machining tests were completed using the L9 orthogonal array. The response variables considered in this study were surface roughness (Ra) and material removal rate (MRR). The analysis of the signal to noise ratio reveals that the optimal combination of cutting process parameters for achieving a desired surface roughness consists of a cutting speed of 119 m/min, a feed rate of 0.11 mm/rev, and a depth of cut of 0.2 mm. The contribution of each process parameter to the machining performance of the carbide tool-work piece combination is determined through the use of ANOVA. Depth of cut has the greatest impact (57.33%) to MRR, while feed rate has the highest contribution (82.15%) to Ra. Moreover, desirability function analysis (DFA) was conducted to optimize the multiple responses. DFA suggested that, to attain a satisfactory response to the output parameters, higher range of cutting speed, depth of cut, and lower range of feed rate are appreciable; therefore, the analytical findings suggest that a cutting speed of 189 m/min, feed rate of 0.11 mm/rev, and a depth of cut of 0.5 mm can induce a favorable Ra of 0.971 μm and MRR of 10.248 cm3/min. In hard machining, cutting speed has a bigger influence on surface finish than feed rate.
Geotechnical Suitability of Soils in Road Construction for Sustainable Development in Tropical Africa: Case of Lateritic Graveled Soils of Bandjoun (West, Cameroon)
Authors: Foko Tamba Carlos , Kengni Lucas , Tematio Paul
Published: December 2023

The environmental impact of the exploitation of geomaterials and their relatively high cost, coupled with the increasingly low financial capital in developing countries, are pushing road actors to turn to inexpensive local ecological materials. The present study is conducted on lateritic graveled soils of Bandjoun (LGSB) in the West Cameroon Region. The aim is to determine whether lateritic gravel soils, particularly those in Bandjoun, can be an ecological and economical alternative to rock aggregates in road construction, considering their geotechnical parameters and environmental impact. These soils were described in the field and were also subjected to complete geotechnical identification in the laboratory. The LGSB presents Californian bearing ratio indices ranging from 26% to 83.3%, a plasticity index of 10.11%, a fines content of 12.05%, an average methylene blue value of 4.25, a water content at the Proctor optimum of 27.6% and a dry density of 1.75 g/cm3. They are silty or clayey gravels and sands of subgroup A-2-7 according to the Highway Research Board classification; sandy and gravelly soils with fines of class B according to the classification of the Road Construction Guide; and silty gravels according to the classification of the Central Laboratory of Bridges and Highways. These soils can be used naturally in pavement layers, in particular in subgrade for all traffic classes and in subbase for low traffic. The tonnage of these soils has been estimated at 18,389 t. The global warming index shows that the use of these soils (18,389 t) in road construction can reduce 31,629–62,706 kg of carbon emissions. The use of lateritic soils in road construction is a very interesting alternative to reduce the environmental impacts associated with the manufacture of rock aggregates. So, lateritic soils should be used instead of rock aggregates for cleaner, more environmentally friendly road construction. The present work presented a specific evaluation of the geotechnical properties and ecological impact of lateritic graveled soils for road construction, as well as their potential for ecological and economic utilization.
Insights into Sulfhemoglobin Detection: UV-Vis and Fluorescence Spectroscopy Correlations
Authors: Santos-Velázquez Lysmarie , López-Garriga Juan
Published: December 2023

The mechanisms by which drugs and several sulfur chemicals induce sulfhemoglobin formation have not yet been elucidated. However, enzymes producing hydrogen sulfide in mammalian tissues and organs suggest sulfhemoglobin and sulfmyoglobin formation mechanisms are more complex than previously hypothesized. The process involves the interaction of H2S with hemoglobin or myoglobin in the presence of O2 or H2O2 to generate sulfhemoglobin or sulfmyoglobin, respectively. Structurally, the sulfheme product chromophore is a covalent heme modification. This modification involves the incorporation of one sulfur atom within carbon atoms to form a sulfur-carbons ring moiety across the β-β double bond of heme pyrrole B, which shows a characteristic optical band around 623 nm and 618 nm for sulfhemoglobin and sulfmyoglobin, respectively. The results show a linear correlation between the sulfHb electronic charge transfer transition at 623 nm and the emission wavelength of 460 nm upon Soret excitation at 420 nm. The data show no such linear relationship for oxy-Hb or met-aquo Hb. This new approach allows us to measure from 0.02% to 13.5% sulfhemoglobin in mixtures of met-aquo hemoglobin and oxy-hemoglobin. Although additional work is needed, the results suggest that simultaneously monitoring sulfHb electronic transition at 623 nm and emission wavelength at 460 nm upon Soret excitation at 420 nm is a powerful technique to determine the percentage of sulfhemoglobin in blood. The data and techniques presented indicate that fluorescence spectroscopy coupled with UV-vis spectroscopy provides a fast and accurate method for detecting sulfhemoglobin in the blood, facilitating the diagnosis of sulfhemoglobinemia in patients.
Phospholipase PLCE1 Promotes Transcription and Phosphorylation of MCM7 to Drive Tumor Progression in Esophageal Cancer
Authors: Shi Qi , Xu Guixuan , Jiang Yuliang , Yang Ju , Han Xueping , Wang Qian , Li Ya , Zhang Zhiyu , Wang Kaige , Peng Hao , Chen Fangfang , Ma Yandi , Zhao Linyue , Chen Yunzhao , Liu Zheng , Yang Lan , Jia Xingyuan , Wen Tao , Tong Zhaohui , Cui Xiaobin , Li Feng
Published: December 2023

Phospholipase C epsilon 1 (PLCE1) is a well-established susceptibility gene for esophageal squamous cell carcinoma (ESCC). Identification of the underlying mechanism(s) regulated by PLCE1 could lead to a better understanding of ESCC tumorigenesis. In this study, we found that PLCE1 enhances tumor progression by regulating the replicative helicase MCM7 via two pathways. PLCE1 activated PKCα-mediated phosphorylation of E2F1, which led to the transcriptional activation of MCM7 and miR-106b-5p. The increased expression of miR-106b-5p, located in intron 13 of MCM7, suppressed autophagy and apoptosis by targeting Beclin-1 and RBL2, respectively. Moreover, MCM7 cooperated with the miR-106b-25 cluster to promote PLCE1-dependent cell-cycle progression both in vivo and in vitro. In addition, PLCE1 potentiated the phosphorylation of MCM7 at six threonine residues by the atypical kinase RIOK2, which promoted MCM complex assembly, chromatin loading, and cell-cycle progression. Inhibition of PLCE1 or RIOK2 hampered MCM7-mediated DNA replication, resulting in G1–S arrest. Furthermore, MCM7 overexpression in ESCC correlated with poor patient survival. Overall, these findings provide insights into the role of PLCE1 as an oncogenic regulator, a promising prognostic biomarker, and a potential therapeutic target in ESCC.

Significance:

PLCE1 promotes tumor progression in ESCC by activating PKCα-mediated phosphorylation of E2F1 to upregulate MCM7 and miR-106b-5p expression and by potentiating MCM7 phosphorylation by RIOK2.
Progression in Myeloid Neoplasms: Beyond the Myeloblast
Authors: Faria Carlos , Tzankov Alexandar
Published: December 2023

Disease progression in myelodysplastic syndromes (MDS), myelodysplastic-myeloproliferative neoplasms (MDS/MPN), and myeloproliferative neoplasms (MPN), altogether referred to as myeloid neoplasms (MN), is a major source of mortality. Apart from transformation to acute myeloid leukemia, the clinical progression of MN is mostly due to the overgrowth of pre-existing hematopoiesis by the MN without an additional transforming event. Still, MN may evolve along other recurrent yet less well-known scenarios: (1) acquisition of MPN features in MDS or (2) MDS features in MPN, (3) progressive myelofibrosis (MF), (4) acquisition of chronic myelomonocytic leukemia (CMML)-like characteristics in MPN or MDS, (5) development of myeloid sarcoma (MS), (6) lymphoblastic (LB) transformation, (7) histiocytic/dendritic outgrowths. These MN-transformation types exhibit a propensity for extramedullary sites (e.g., skin, lymph nodes, liver), highlighting the importance of lesional biopsies in diagnosis. Gain of distinct mutations/mutational patterns seems to be causative or at least accompanying several of the above-mentioned scenarios. MDS developing MPN features often acquire MPN driver mutations (usually JAK2), and MF. Conversely, MPN gaining MDS features develop, e.g., ASXL1, IDH1/2, SF3B1, and/or SRSF2 mutations. Mutations of RAS-genes are often detected in CMML-like MPN progression. MS ex MN is characterized by complex karyotypes, FLT3 and/or NPM1 mutations, and often monoblastic phenotype. MN with LB transformation is associated with secondary genetic events linked to lineage reprogramming leading to the deregulation of ETV6, IKZF1, PAX5, PU.1, and RUNX1. Finally, the acquisition of MAPK-pathway gene mutations may shape MN toward histiocytic differentiation. Awareness of all these less well-known MN-progression types is important to guide optimal individual patient management.
PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma
Authors: Abou-Alfa Ghassan K. , Galle Peter R. , Chao Yee , Erinjeri Joseph , Heo Jeong , Borad Mitesh J. , Luca Angelo , Burke James , Pelusio Adina , Agathon Delphine , Lusky Monika , Breitbach Caroline , Qin Shukui , Gane Edward
Published: December 2023

Introduction: Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy. Methods: This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment. The primary endpoint is overall survival (OS). Key secondary endpoints included time to progression (TTP), progression-free survival, overall response rate (ORR), and disease control rate (DCR). Safety was assessed in all patients who received ≥1 dose of study treatment. Results: The study was conducted at 142 sites in 16 countries. From December 30, 2015, to the interim analysis on August 2, 2019, 459 patients were randomly assigned (pexa-vec plus sorafenib: 234, sorafenib: 225). At the interim analysis, the median OS was 12.7 months (95% CI: 9.89, 14.95) in the pexa-vec plus sorafenib arm and 14.0 months (95% CI: 11.01, 18.00) in the sorafenib arm. This led to the early termination of the study. The median TTP was 2.0 months (95% CI: 1.77, 2.96) and 4.2 months (95% CI: 2.92, 4.63); ORR was 19.2% (45 patients) and 20.9% (47 patients); and DCR was 50.0% (117 patients) and 57.3% (129 patients) in the pexa-vec plus sorafenib and sorafenib arms, respectively. Serious adverse events were reported in 117 (53.7%) patients in the pexa-vec plus sorafenib and 77 (35.5%) patients in the sorafenib arm. Liver failure was the most frequently reported in both groups. Conclusion: Sequential pexa-vec plus sorafenib treatment did not demonstrate increased clinical benefit in advanced HCC and fared worse compared to sorafenib alone. The advent of the added value of checkpoint inhibitors should direct any further development of oncolytic virus therapy strategies.
Severe Early-Onset Obesity and Diabetic Ketoacidosis due to a Novel Homozygous c.169C>T p.Arg57* Variant in CEP19 Gene
Authors: Cayir Atilla , Turkyilmaz Ayberk , Rabenstein Hannah , Guven Fadime , Karagoz Yuksel Sumeyra , Vuralli Dogus , Wabitsch Martin , Demirbilek Huseyin
Published: December 2023

Introduction: Early-onset severe obesity is usually the result of an underlying genetic disorder, and several genes have recently been shown to cause syndromic and nonsyndromic forms of obesity. The “centrosomal protein 19 (CEP19)” gene encodes for a centrosomal and ciliary protein. Homozygous variants in the CEP19 gene are extremely rare causes of early-onset severe monogenic obesity. Herein, we present a Turkish family with early-onset severe obesity with variable features. Methods: Sanger sequencing and whole-exome sequencing were performed to identify the genetic etiology in the family. Results: The index case was a 12-year-old female who presented with severe obesity (BMI of 62.7 kg/m2), metabolic syndrome, and diabetic ketoacidosis. Her nonidentical twin female siblings also had early-onset severe obesity, metabolic syndrome, and diabetes. In addition, one of the affected siblings had situs inversus abdominalis, polysplenia, lumbar vertebral fusion, and abnormal lateralization. A novel homozygous nonsense (c.169C>T, p. Arg57*) pathogenic variant was detected in exon 3 of the CEP19 gene in all affected members of the family. One unaffected sister and unaffected parents were heterozygous for the variant. This variant is predicted to cause a stop codon at amino acid sequence 57, leading to a truncated CEP19 protein. Discussion/Conclusion: Our study expands the phenotypical manifestations and variation database of CEP19 variants. The findings in one of our patients reaffirm its role in the assembly and function of both motile and immotile cilia.