Insights into molecular and cellular functions of the Golgi calcium/manganese-proton antiporter TMEM165.

The Golgi compartment performs a number of crucial roles in the cell. However, the exact molecular mechanisms underlying these actions are not fully defined. Pathogenic mutations in genes encoding Golgi proteins may serve as an important source for expanding our knowledge. For instance, mutations in the gene encoding Transmembrane protein 165 (TMEM165) were discovered as a cause of a new type of congenital disorder of glycosylation (CDG). Comprehensive studies of TMEM165 in different model systems, including mammals, yeast, and fish uncovered the new realm of Mn2+ homeostasis regulation. TMEM165 was shown to act as a Ca2+/Mn2+:H+ antiporter in the medial- and trans-Golgi network, pumping the metal ions into the Golgi lumen and protons outside. Disruption of TMEM165 antiporter activity results in defects in N- and O-glycosylation of proteins and glycosylation of lipids. Impaired glycosylation of TMEM165-CDG arises from a lack of Mn2+ within the Golgi. Nevertheless, Mn2+ insufficiency in the Golgi is compensated by the activity of the ATPase SERCA2. TMEM165 turnover has also been found to be regulated by Mn2+ cytosolic concentration. Besides causing CDG, recent investigations have demonstrated the functional involvement of TMEM165 in several other pathologies including cancer and mental health disorders. This systematic review summarizes the available information on TMEM165 molecular structure, cellular function, and its roles in health and disease.

The small protein MntS evolved from a signal peptide and acquired a novel function regulating manganese homeostasis in Escherichia coli.

Small proteins (<50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small proteins, such as their molecular mechanism of action, downregulation after they are no longer needed, and their evolutionary provenance, are poorly understood. Here, we show that the MntS small protein involved in manganese (Mn) homeostasis binds and inhibits the MntP Mn transporter. Mn is crucial for bacterial survival in stressful environments but is toxic in excess. Thus, Mn transport is tightly controlled at multiple levels to maintain optimal Mn levels. The small protein MntS adds a new level of regulation for Mn transporters, beyond the known transcriptional and post-transcriptional control. We also found that MntS binds to itself in the presence of Mn, providing a possible mechanism of downregulating MntS activity to terminate its inhibition of MntP Mn export. MntS is homologous to the signal peptide of SitA, the periplasmic metal-binding subunit of a Mn importer. Remarkably, the homologous signal peptide regions can substitute for MntS, demonstrating a functional relationship between MntS and these signal peptides. Conserved gene neighborhoods support that MntS evolved from the signal peptide of an ancestral SitA protein, acquiring a life of its own with a distinct function in Mn homeostasis.

Tailoring Auger Recombination Dynamics in CsPbI3 Perovskite Nanocrystals via Transition Metal Doping.

Auger recombination is a pivotal process for semiconductor nanocrystals (NCs), significantly affecting charge carrier generation and collection in optoelectronic devices. This process depends mainly on the NCs' electronic structures. In our study, we investigated Auger recombination dynamics in manganese (Mn2+)-doped CsPbI3 NCs using transient absorption (TA) spectroscopy combined with theoretical and experimental structural characterization. Our results show that Mn2+ doping accelerates Auger recombination, reducing the biexciton lifetime from 146 to 74 ps with increasing Mn doping concentration up to 10%. This accelerated Auger recombination in Mn-doped NCs is attributed to increased band edge wave function overlap of excitons and a larger density of final states of Auger recombination due to Mn orbital involvement. Moreover, Mn doping reduces the dielectric screening of the excitons, which also contributes to the accelerated Auger recombination. Our study demonstrates the potential of element doping to regulate Auger recombination rates by modifying the materials' electronic structure.

Redox Couple Strategy for Improving the Oxygen Redox Activity and Reversibility of Li- and Mn-Rich Cathode Materials.

The specific capacity of Li- and Mn-rich layered oxide (LMROs) cathodes can be enhanced by the oxidation of lattice oxygen at high voltages. Nevertheless, an irreversible oxygen loss emerges with cycling, which triggers interlocking surface/interface issues and results in the fast deterioration of cycling performance. Herein, we prepare a surface modified LMRO electrode by one step doctor-blade casting and introducing a benzoquinone species DBBQ redox couple. The electrochemical test shows that the DBBQ-modified electrode has a high reversible capacity (>320 mAh g-1) and excellent rate performance, while the cyclic stability has been significantly improved as well. The capacity retention reaches as high as 93.3% after 500 cycles at 1 C. Mechanism analysis shows that DBBQ can not only play a redox couple in LMROs which achieves the adsorption and reduction of surface oxygen gas but also significantly enhance anionic redox in the bulk, thus realizing extraordinary capacity.

Achieving Ultra-High-Energy-Density Lithium Batteries: Elimination of Irreversible Anionic Redox through Controlled Cationic Disordering.

Lithium-rich layered oxides (LLOs) capable of supporting both cationic and anionic redox chemistry are promising cathode materials. Yet, their initial charge to high voltages often trigger significant oxygen evolution, resulting in substantial capacity loss and structural instability. In this study, we applied a straightforward low-potential activation (LOWPA) method alongside a relatively stable electrolyte to address this issue. This approach enables precise control over the order-to-disorder transformation of the transition metal layers in LLOs, producing an in-plane cation-disordered Li1.2Mn0.54Co0.13Ni0.13O2 that averts irreversible oxygen evolution at 4.8 V by stabilizing Mn-O2 or Mn-O3 species within the Li/Mn-disordered nanopores. Consequently, an ultrahigh reversible capacity of 322 mAh g-1 (equating to 1141 Wh kg-1), 91.5% initial Coulombic efficiency, and enhanced durability and rate capability are simultaneously achieved. As LOWPA does not alter any chemical composition of LLOs, it also offers a simple model for untangling the complex phenomena associated with oxygen-redox chemistry.

Exceptional Rate Performances of Li-Rich Mn-Based Cathodes Enabled by Boron-Based Additives-Driven Self-Optimized Interface.

Li-rich Mn-based cathode material (LRM), as a promising cathode for high energy density lithium batteries, suffers from severe side reactions in conventional lithium hexafluorophosphate (LiPF6)-based carbonate electrolytes, leading to unstable interfaces and poor rate performances. Herein, a boron-based additives-driven self-optimized interface strategy is presented to dissolve low ionic conductivity LiF nanoparticles at the outer cathode electrolyte interface, leading to the optimized interfacial components, as well as the enhanced Li ion migration rate in electrolytes. Being attributed to these superiorities, the LRM||Li battery delivers a high-capacity retention of 92.19% at 1C after 200 cycles and a low voltage decay of 1.08 mV/cycle. This work provides a new perspective on the rational selection of functional additives with an interfacial self-optimized characteristic to achieve a long lifespan LRM with exceptional rate performances.

ZnMn2(PO4)2·nH2O: An H2O-Imbedding-Activated Cathode for Robust Aqueous Zinc-Ion Batteries.

Component modulation endows Mn-based electrodes with prominent energy storage properties due to their adjustable crystal structure characteristics. Herein, ZnMn2(PO4)2·nH2O (ZMP·nH2O) was obtained by a hydration reaction from ZnMn2(PO4)2 (ZMP) during an electrode-aging evolution. Benefiting from the introduction of lattice H2O molecules into the ZMP structure, the ion transmission path has been expanded along with the extended d-spacing, which will further facilitate the ZMP → ZMP·nH2O phase evolution and electrochemical reaction kinetics. Meanwhile, the hydrogen bond can be generated between H2O and O in PO43-, which strengthens the structure stability of ZMP·nH2O and lowers the conversion barrier from ZMP to ZMP·4H2O during the Zn2+ uptake/removal process. Thereof, ZMP·nH2O delivers enhanced electrochemical reaction kinetics with robust structure tolerance (106.52 mA h g-1 at 100 mA g-1 over 620 cycles). This high-energy aqueous Zn||ZMP·nH2O battery provides a facile strategy for engineering and exploration of high-performance ZIBs to realize the practical application of Mn-based cathodes.

An Mn-Enriched Interfacial Layer for Reversible Aqueous Mn Metal Batteries.

Aqueous manganese metal batteries have emerged as promising candidates for stationary storage due to their natural abundance, safety, and high energy density. However, the high chemical reactivity and sluggish migration kinetics of the Mn metal anode induce a severe hydrogen evolution reaction (HER) and dendrite formation, respectively. The situation deteriorates in the low-concentration electrolyte especially. Here, we propose a novel approach to construct an Mn-enriched interfacial layer (Mn@MIL) on the Mn metal anode surface to address these challenges simultaneously. The Mn@MIL acts as a physical barrier to not only suppress HER but also accelerate the Mn2+ diffusion kinetics through the Mn2+ saturated interfacial layer to inhibit dendrite growth. Therefore, in the low-concentration electrolyte (1 M MnCl2), the Mn||Mn symmetric cells and Mn||V2O5 full cells with high mass loading demonstrate promising cycling stability with minimal polarization and parasitic reactions, making them more suitable for practical applications in a smart grid.

Microbe-disease associations prediction by graph regularized non-negative matrix factorization with L 2 , 1 $$ {L}_{2,1} $$ norm regularization terms.

Microbes are involved in a wide range of biological processes and are closely associated with disease. Inferring potential disease-associated microbes as the biomarkers or drug targets may help prevent, diagnose and treat complex human diseases. However, biological experiments are time-consuming and expensive. In this study, we introduced a new method called iPALM-GLMF, which modelled microbe-disease association prediction as a problem of non-negative matrix factorization with graph dual regularization terms and L 2 , 1 $$ {L}_{2,1} $$ norm regularization terms. The graph dual regularization terms were used to capture potential features in the microbe and disease space, and the L 2 , 1 $$ {L}_{2,1} $$ norm regularization terms were used to ensure the sparsity of the feature matrices obtained from the non-negative matrix factorization and to improve the interpretability. To solve the model, iPALM-GLMF used a non-negative double singular value decomposition to initialize the matrix factorization and adopted an inertial Proximal Alternating Linear Minimization iterative process to obtain the final matrix factorization results. As a result, iPALM-GLMF performed better than other existing methods in leave-one-out cross-validation and fivefold cross-validation. In addition, case studies of different diseases demonstrated that iPALM-GLMF could effectively predict potential microbial-disease associations. iPALM-GLMF is publicly available at https://github.com/LiangzheZhang/iPALM-GLMF.

Control of hyperpnoea and pulmonary gas exchange during prolonged exercise: The role of group III/IV muscle afferent feedback.

It remains unclear whether feedback from group III/IV muscle afferents is of continuous significance for regulating the pulmonary response during prolonged (>5 min), steady-state exercise. To elucidate the influence of these sensory neurons on hyperpnoea, gas exchange efficiency, arterial oxygenation and acid-base balance during prolonged locomotor exercise, 13 healthy participants (4 females; 21 (3) years, V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ : 46 (8) ml/kg/min) performed consecutive constant-load cycling bouts at ∼50% (20 min), ∼75% (20 min) and ∼100% (5 min) of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ with intact (CTRL) and pharmacologically attenuated (lumbar intrathecal fentanyl; FENT) group III/IV muscle afferent feedback from the legs. Pulmonary responses were continuously recorded and arterial blood (radial catheter) periodically collected throughout the exercise. Pulmonary gas exchange efficiency was evaluated using the alveolar-arterial P O 2 ${{P}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ difference ( A - a D O 2 ${\mathrm{A - a}}{{D}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ). There were no differences in any of the variables of interest between conditions before the start of the exercise. Pulmonary ventilation was up to 20% lower across all intensities during FENT compared to CTRL exercise (P < 0.001) and this hypoventilation was accompanied by an up to 10% lower arterial P O 2 ${{P}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and a 2-4 mmHg higher P C O 2 ${{P}_{{\mathrm{C}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ (both P < 0.001). The exercise-induced widening of A - a D O 2 ${\mathrm{A - a}}{{D}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ was up to 25% larger during FENT compared to CTRL (P < 0.001). Importantly, the differences developed within the first minute of each stage and persisted, or further increased, throughout the remainder of each bout. These findings reflect a critical and time-independent significance of feedback from group III/IV leg muscle afferents for continuously regulating the ventilatory response, gas exchange efficiency, arterial oxygenation and acid-base balance during human locomotion. KEY POINTS: Feedback from group III/IV leg muscle afferents reflexly contributes to hyperpnoea during short duration (i.e. <5 min) locomotor exercise. Whether continuous feedback from these sensory neurons is obligatory to ensure adequate pulmonary responses during steady-state exercise of longer duration remains unknown. Lumbar intrathecal fentanyl was used to attenuate the central projection of group III/IV leg muscle afferents during prolonged locomotor exercise (i.e. 45 min) at intensities ranging from 50% to 100% of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ . Without affecting the metabolic rate, afferent blockade compromised pulmonary ventilation and gas exchange efficiency, consistently impairing arterial oxygenation and facilitating respiratory acidosis throughout exercise. These findings reflect the time-independent significance of feedback from group III/IV muscle afferents for regulating exercise hyperpnoea and gas exchange efficiency, and thus for optimizing arterial oxygenation and acid-base balance, during prolonged human locomotion.

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb-/- mice.

Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO• bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and exercise performance in myoglobin knockout mice (Mb-/- ) when compared to control mice (Mb+/+ ). Furthermore, we also studied NO• bioavailability, assessed as nitrite (NO2 - ) and nitrate (NO3 - ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb-/- and in Mb+/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole-body gas exchange measurements. The Mb-/- mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb-/- mice had significantly reduced maximal running performance (P < 0.001). V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ expressed in ml min-1 in Mb-/ - mice was 37% lower than in Mb+/+ mice (P < 0.001) and 13% lower when expressed in ml min-1  kg body mass-1 (P = 0.001). Additionally, Mb-/- mice had significantly lower plasma, heart and locomotory muscle NO2 - levels at rest. During exercise NO2 - increased significantly in the heart and locomotory muscles of Mb-/- and Mb+/+ mice, whereas no significant changes in NO2 - were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance in mice. KEY POINTS: Myoglobin knockout mice (Mb-/- ) possess lower maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and poorer maximal running performance than control mice (Mb+/+ ). Respiratory exchange ratio values at high running velocities in Mb-/- mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb-/- mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO• bioavailability, but does not affect exercise-induced NO2 - changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb-/- mouse model.

A citrate efflux transporter important for manganese distribution and phosphorus uptake in rice.

The plant citrate transporters, functional in mineral nutrient uptake and homeostasis, usually belong to the multidrug and toxic compound extrusion transporter family. We identified and functionally characterized a rice (Oryza sativa) citrate transporter, OsCT1, which differs from known plant citrate transporters and is structurally close to rice silicon transporters. Domain analysis depicted that OsCT1 carries a bacterial citrate-metal transporter domain, CitMHS. OsCT1 showed citrate efflux activity when expressed in Xenopus laevis oocytes and is localized to the cell plasma membrane. It is highly expressed in the shoot and reproductive tissues of rice, and its promoter activity was visible in cells surrounding the vasculature. The OsCT1 knockout (KO) lines showed a reduced citrate content in the shoots and the root exudates, whereas overexpression (OE) line showed higher citrate exudation from their roots. Further, the KO and OE lines showed variations in the manganese (Mn) distribution leading to changes in their agronomical traits. Under deficient conditions (Mn-sufficient conditions followed by 8 days of 0 µm MnCl2 · 4H2 O treatment), the supply of manganese towards the newer leaf was found to be obstructed in the KO line. There were no significant differences in phosphorus (P) distribution; however, P uptake was reduced in the KO and increased in OE lines at the vegetative stage. Further, experiments in Xenopus oocytes revealed that OsCT1 could efflux citrate with Mn. In this way, we provide insights into a mechanism of citrate-metal transport in plants and its role in mineral homeostasis, which remains conserved with their bacterial counterparts.

OsMADS5 interacts with OsSPL14/17 to inhibit rice root elongation by restricting cell proliferation of root meristem under ammonium supply.

Nitrogen (N) is a vital major nutrient for rice (Oryza sativa). Rice responds to different applications of N by altering its root morphology, including root elongation. Although ammonium ( NH 4 + ) is the primary source of N for rice, NH 4 + is toxic to rice roots and inhibits root elongation. However, the precise molecular mechanism that NH 4 + -inhibited root elongation of rice is not well understood. Here, we identified a rice T-DNA insert mutant of OsMADS5 with a longer seminal root (SR) under sufficient N conditions. Reverse-transcription quantitative PCR analysis revealed that the expression level of OsMADS5 was increased under NH 4 + compared with NO 3 - supply. Under NH 4 + conditions, knocking out OsMADS5 (cas9) produced a longer SR, phenocopying osmads5, while there was no significant difference in SR length between wild-type and cas9 under NO 3 - supply. Moreover, OsMADS5-overexpression plants displayed the opposite SR phenotype. Further study demonstrated that enhancement of OsMADS5 by NH 4 + supply inhibited rice SR elongation, likely by reducing root meristem activity of root tip, with the involvement of OsCYCB1;1. We also found that OsMADS5 interacted with OsSPL14 and OsSPL17 (OsSPL14/17) to repress their transcriptional activation by attenuating DNA binding ability. Moreover, loss of OsSPL14/17 function in osmads5 eliminated its stimulative effect on SR elongation under NH 4 + conditions, implying OsSPL14/17 may function downstream of OsMADS5 to mediate rice SR elongation under NH 4 + supply. Overall, our results indicate the existence of a novel modulatory pathway in which enhancement of OsMADS5 by NH 4 + supply represses the transcriptional activities of OsSPL14/17 to restrict SR elongation of rice.

SPLHRNMTF: robust orthogonal non-negative matrix tri-factorization with self-paced learning and dual hypergraph regularization for predicting miRNA-disease associations.

MicroRNAs (miRNAs) have been demonstrated to be closely related to human diseases. Studying the potential associations between miRNAs and diseases contributes to our understanding of disease pathogenic mechanisms. As traditional biological experiments are costly and time-consuming, computational models can be considered as effective complementary tools. In this study, we propose a novel model of robust orthogonal non-negative matrix tri-factorization (NMTF) with self-paced learning and dual hypergraph regularization, named SPLHRNMTF, to predict miRNA-disease associations. More specifically, SPLHRNMTF first uses a non-linear fusion method to obtain miRNA and disease comprehensive similarity. Subsequently, the improved miRNA-disease association matrix is reformulated based on weighted k-nearest neighbor profiles to correct false-negative associations. In addition, we utilize L 2 , 1 norm to replace Frobenius norm to calculate residual error, alleviating the impact of noise and outliers on prediction performance. Then, we integrate self-paced learning into NMTF to alleviate the model from falling into bad local optimal solutions by gradually including samples from easy to complex. Finally, hypergraph regularization is introduced to capture high-order complex relations from hypergraphs related to miRNAs and diseases. In 5-fold cross-validation five times experiments, SPLHRNMTF obtains higher average AUC values than other baseline models. Moreover, the case studies on breast neoplasms and lung neoplasms further demonstrate the accuracy of SPLHRNMTF. Meanwhile, the potential associations discovered are of biological significance.

Cold-Driven Hemoglobin Evolution in Antarctic Notothenioid Fishes Prior to Hemoglobin Gene Loss in White-Blooded Icefishes.

Expression of multiple hemoglobin isoforms with differing physiochemical properties likely helps species adapt to different environmental and physiological conditions. Antarctic notothenioid fishes inhabit the icy Southern Ocean and display fewer hemoglobin isoforms, each with less affinity for oxygen than temperate relatives. Reduced hemoglobin multiplicity was proposed to result from relaxed selective pressure in the cold, thermally stable, and highly oxygenated Antarctic waters. These conditions also permitted the survival and diversification of white-blooded icefishes, the only vertebrates living without hemoglobin. To understand hemoglobin evolution during adaptation to freezing water, we analyzed hemoglobin genes from 36 notothenioid genome assemblies. Results showed that adaptation to frigid conditions shaped hemoglobin gene evolution by episodic diversifying selection concomitant with cold adaptation and by pervasive evolution in Antarctic notothenioids compared to temperate relatives, likely a continuing adaptation to Antarctic conditions. Analysis of hemoglobin gene expression in adult hematopoietic organs in various temperate and Antarctic species further revealed a switch in hemoglobin gene expression underlying hemoglobin multiplicity reduction in Antarctic fish, leading to a single hemoglobin isoform in adult plunderfishes and dragonfishes, the sister groups to icefishes. The predicted high hemoglobin multiplicity in Antarctic fish embryos based on transcriptomic data, however, raises questions about the molecular bases and physiological implications of diverse hemoglobin isoforms in embryos compared to adults. This analysis supports the hypothesis that the last common icefish ancestor was vulnerable to detrimental mutations affecting the single ancestral expressed alpha- and beta-globin gene pair, potentially predisposing their subsequent loss.

The Effect of Removal of External Proteins PsbO, PsbP and PsbQ on Flash-Induced Molecular Oxygen Evolution and Its Biphasicity in Tobacco PSII.

The oxygen evolution within photosystem II (PSII) is one of the most enigmatic processes occurring in nature. It is suggested that external proteins surrounding the oxygen-evolving complex (OEC) not only stabilize it and provide an appropriate ionic environment but also create water channels, which could be involved in triggering the ingress of water and the removal of O2 and protons outside the system. To investigate the influence of these proteins on the rate of oxygen release and the efficiency of OEC function, we developed a measurement protocol for the direct measurement of the kinetics of oxygen release from PSII using a Joliot-type electrode. PSII-enriched tobacco thylakoids were used in the experiments. The results revealed the existence of slow and fast modes of oxygen evolution. This observation is model-independent and requires no specific assumptions about the initial distribution of the OEC states. The gradual removal of exogenous proteins resulted in a slowdown of the rapid phase (~ms) of O2 release and its gradual disappearance while the slow phase (~tens of ms) accelerated. The role of external proteins in regulating the biphasicity and efficiency of oxygen release is discussed based on observed phenomena and current knowledge.

Rising Prevalence of Low-Frequency PPM1D Gene Mutations after Second HDCT in Multiple Myeloma.

Multiple myeloma (MM) first-line treatment algorithms include immuno-chemotherapy (ICT) induction, high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) consolidation, followed by lenalidomide maintenance. After these initial therapies, most patients suffer a disease relapse and require subsequent treatment lines including ICT, additional HDCT and ASCT, or novel immunotherapies. The presence of somatic mutations in peripheral blood cells has been associated with adverse outcomes in a variety of hematological malignancies. Nonsense and frameshift mutations in the PPM1D gene, a frequent driver alteration in clonal hematopoiesis (CH), lead to the gain-of-function of Wip1 phosphatase, which may impair the p53-dependent G1 checkpoint and promote cell proliferation. Here, we determined the presence of PPM1D gene mutations in peripheral blood cells of 75 subsequent myeloma patients in remission after first or second HDCT/ASCT. The prevalence of truncating PPM1D gene mutations emerged at 1.3% after first HDCT/ASCT, and 7.3% after second HDCT/ASCT, with variant allele frequencies (VAF) of 0.01 to 0.05. Clinical outcomes were inferior in the PPM1D-mutated (PPM1Dmut) subset with median progression-free survival (PFS) of 15 vs. 37 months (p = 0.0002) and median overall survival (OS) of 36 vs. 156 months (p = 0.001) for the PPM1Dmut and PPM1Dwt population, respectively. Our data suggest that the occurrence of PPM1D gene mutations in peripheral blood cells correlates with inferior outcomes after ASCT in patients with multiple myeloma.

Role of Yrn2 under oxidative stress in Deinococcus radiodurans.

Among the two Y RNAs in Deinococcus radiodurans, the functional properties of Yrn2 are still not known. Yrn2 although consists of a long stem-loop for Rsr binding, differs from Yrn1 in the effector binding site. An initial study on Yrn2 delineated it to be a UV-induced noncoding RNA. Apart from that Yrn2 has scarcely been investigated. In the current study, we identified Yrn2 as an γ-radiation induced Y RNA, which is also induced upon H2O2 and mitomycin treatment. Ectopically expressed Yrn2 appeared to be nontoxic to the cell growth. An overabundance of Yrn2 was found to ameliorate cell survival under oxidative stress through the detoxification of intracellular reactive oxygen species with a subsequent decrease in total protein carbonylation. A significant accumulation of intracellular Mn(II) with unaltered Fe(II) and Zn(II) with detected while Yrn2 is overabundant in the cells. This study identified the role of a novel Yrn2 under oxidative stress in D. radiodurans.

MARVEL analysis of high-resolution rovibrational spectra of 13 C 16 O 2 .

A set of empirical rovibrational energy levels, obtained through the MARVEL (measured active rotational-vibrational energy levels) procedure, is presented for the 13 C 16 O 2 isotopologue of carbon dioxide. This procedure begins with the collection and analysis of experimental rovibrational transitions from the literature, allowing for a comprehensive review of the literature on the high-resolution spectroscopy of 13 C 16 O 2 , which is also presented. A total of 60 sources out of more than 750 checked provided 14,101 uniquely measured and assigned rovibrational transitions in the wavenumber range of 579-13,735 cm - 1 . This is followed by a weighted least-squares refinement yielding the energy levels of the states involved in the measured transitions. Altogether 6318 empirical rovibrational energies have been determined for 13 C 16 O 2 . Finally, estimates have been given for the uncertainties of the empirical energies, based on the experimental uncertainties of the transitions. The detailed analysis of the lines and the spectroscopic network built from them, as well as the uncertainty estimates, all serve to pinpoint possible errors in the experimental data, such as typos, misassignment of quantum numbers, and misidentifications. Errors found in the literature data were corrected before including them in the final MARVEL dataset and analysis.

t 2 g d orbital ordering patterns in KBF 3 (B = Sc, Ti, Fe, Co) perovskites.

The orbital ordering (OO) resulting from the partial occupancy of the t 2 g d subshell of the transition metals in KBF 3 (B = Sc, Ti, Ffe, Co) perovskites, and the many possible patterns arising from the coupling between the B sites, have been investigated at the quantum mechanical level ( all electron Gaussian type basis set, B3LYP hybrid functional) in a 40 atoms supercell. The numerous patterns are distributed into 162 classes of equivalent configurations. For each fluoroperovskite, one representative per class has been calculated. The four compounds behave similarly: an identical dependence of the energy and volume (or cell parameters) on the OO pattern; the spanned energy interval is small (1 to 2 mE h per formula unit), suggesting that most of the configurations are occupied at room and even at low temperature. A linear model, taking into account the relative orbital order in contiguous sites, reproduces the energy order in the full set for each compound, suggesting that it could be used for studying OO in larger supercells.