Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after ...therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10
cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
The modification of star formation (SF) in galaxy interactions is a complex process, with SF observed to be both enhanced in major mergers and suppressed in minor pair interactions. Such changes ...likely to arise on short time-scales and be directly related to the galaxy–galaxy interaction time. Here we investigate the link between dynamical phase and direct measures of SF on different time-scales for pair galaxies, targeting numerous star- formation rate (SFR) indicators and comparing to pair separation, individual galaxy mass and pair mass ratio. We split our sample into the higher (primary) and lower (secondary) mass galaxies in each pair and find that SF is indeed enhanced in all primary galaxies but suppressed in secondaries of minor mergers. We find that changes in SF of primaries are consistent in both major and minor mergers, suggesting that SF in the more massive galaxy is agnostic to pair mass ratio. We also find that SF is enhanced/suppressed more strongly for short-duration SFR indicators (e.g. Hα), highlighting recent changes to SF in these galaxies, which are likely to be induced by the interaction. We propose a scenario where the lower mass galaxy has its SF suppressed by gas heating or stripping, while the higher mass galaxy has its SF enhanced, potentially by tidal gas turbulence and shocks. This is consistent with the seemingly contradictory observations for both SF suppression and enhancement in close pairs.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows a fast and reliable bacterial identification from culture plates. Direct analysis of clinical ...samples may increase its usefulness in samples in which a fast identification of microorganisms can guide empirical treatment, such as blood cultures (BC). Three hundred and thirty BC, reported as positive by the automated BC incubation device, were processed by conventional methods for BC processing, and by a fast method based on direct MALDI-TOF MS. Three hundred and eighteen of them yield growth on culture plates, and 12 were false positive. The MALDI-TOF MS-based method reported that no peaks were found, or the absence of a reliable identification profile, in all these false positive BC. No mixed cultures were found. Among these 318 BC, we isolated 61 Gram-negatives (GN), 239 Gram-positives (GP) and 18 fungi. Microorganism identifications in GN were coincident with conventional identification, at the species level, in 83.3% of BC and, at the genus level, in 96.6%. In GP, identifications were coincident with conventional identification in 31.8% of BC at the species level, and in 64.8% at the genus level. Fungaemia was not reliably detected by MALDI-TOF. In 18 BC positive for Candida species (eight C. albicans, nine C. parapsilosis and one C. tropicalis), no microorganisms were identified at the species level, and only one (5.6%) was detected at the genus level. The results of the present study show that this fast, MALDI-TOF MS-based method allows bacterial identification directly from presumptively positive BC in a short time (<30 min), with a high accuracy, especially when GN bacteria are involved.
Forkhead box class O family member proteins (FoxOs) are highly conserved transcription factors with important roles in cellular homeostasis. The four FoxO members in humans, FoxO1, FoxO3, FoxO4, and ...FoxO6, are all expressed in skeletal muscle, but the first three members are the most studied in muscle. In this review, we detail the multiple modes of FoxO regulation and discuss the central role of these proteins in the control of skeletal muscle plasticity. FoxO1 and FoxO3 are key factors of muscle energy homeostasis through the control of glycolytic and lipolytic flux, and mitochondrial metabolism. They are also key regulators of protein breakdown, as they modulate the activity of several actors in the ubiquitin–proteasome and autophagy–lysosomal proteolytic pathways, including mitochondrial autophagy, also called mitophagy. FoxO proteins have also been implicated in the regulation of the cell cycle, apoptosis, and muscle regeneration. Depending of their activation level, FoxO proteins can exhibit ambivalent functions. For example, a basal level of FoxO factors is necessary for cellular homeostasis and these proteins are required for adaptation to exercise. However, exacerbated activation may occur in the course of several diseases, resulting in metabolic disorders and atrophy. A better understanding of the precise functions of these transcriptions factors should thus lead to the development of new therapeutic approaches to prevent or limit the muscle wasting that prevails in numerous pathological states, such as immobilization, denervated conditions, neuromuscular disease, aging, AIDS, cancer, and diabetes.
Radically Rethinking Agriculture for the 21st Century Fedoroff, N. V.; Battisti, D. S.; Beachy, R. N. ...
Science (American Association for the Advancement of Science),
02/2010, Letnik:
327, Številka:
5967
Journal Article
Recenzirano
Odprti dostop
Population growth, arable land and fresh water limits, and climate change have profound implications for the ability of agriculture to meet this century's demands for food, feed, fiber, and fuel ...while reducing the environmental impact of their production. Success depends on the acceptance and use of contemporary molecular techniques, as well as the increasing development of farming systems that use saline water and integrate nutrient flows.
The spin-orbit interaction couples the electrons' motion to their spin. As a result, a charge current running through a material with strong spin-orbit coupling generates a transverse spin current ...(spin Hall effect, SHE) and vice versa (inverse spin Hall effect, ISHE). The emergence of SHE and ISHE as charge-to-spin interconversion mechanisms offers a variety of novel spintronic functionalities and devices, some of which do not require any ferromagnetic material. However, the interconversion efficiency of SHE and ISHE (spin Hall angle) is a bulk property that rarely exceeds ten percent, and does not take advantage of interfacial and low-dimensional effects otherwise ubiquitous in spintronic hetero- and mesostructures. Here, we make use of an interface-driven spin-orbit coupling mechanism-the Rashba effect-in the oxide two-dimensional electron system (2DES) LaAlO
/SrTiO
to achieve spin-to-charge conversion with unprecedented efficiency. Through spin pumping, we inject a spin current from a NiFe film into the oxide 2DES and detect the resulting charge current, which can be strongly modulated by a gate voltage. We discuss the amplitude of the effect and its gate dependence on the basis of the electronic structure of the 2DES and highlight the importance of a long scattering time to achieve efficient spin-to-charge interconversion.
Essentials
Diagnosis of sitosterolemia, a rare recessive or syndromic disorder, is usually delayed.
Peripheral blood smear is extremely useful for establishing the suspicion of sitosterolemia.
...High‐throughput sequencing technology enables the molecular diagnosis of inherited thrombocytopenias.
Accurate characterization of sitosterolemia helps us determine appropriate management.
Summary
Background
Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PSs) usually result in xanthomas and premature coronary atherosclerosis, although hematologic abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis.
Objectives
To report two novel ABCG5 variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL.
Patient/Methods
A 46‐year‐old female was referred to us with lifelong macrothrombocytopenia. She showed familial hypercholesterolemia‐related xanthomas. Molecular analysis was performed with high‐throughput sequencing. Plasma PS levels were evaluated with gas–liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974.
Results
A blood smear revealed giant platelets and stomatocytes. Novel compound heterozygous variants were detected in exons 7 (c.914C>G) and 13 (c.1890delT) of ABCG5. The patient showed an increased plasma level of sitosterol. These findings support the diagnosis of STSL. In our review, we identified only 25 unrelated STLS patients who presented with hematologic abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematologic abnormalities.
Conclusions
This is the first Spanish STSL patient to be reported and molecularly characterized. The early diagnosis of STLS is strongly supported by the presence of stomatocytes in blood smears. The definitive diagnosis of STSL by measurement of serum PS levels and molecular analyses prompted the use of ezetimibe therapy.
Through combined ferromagnetic resonance, spin pumping, and inverse spin Hall effect experiments in Co|Pt bilayers and Co|Cu|Pt trilayers, we demonstrate consistent values of ℓsfPt=3.4±0.4 nm and ...θSHEPt=0.056±0.010 for the respective spin diffusion length and spin Hall angle for Pt. Our data and model emphasize the partial depolarization of the spin current at each interface due to spin-memory loss. Our model reconciles the previously published spin Hall angle values and explains the different scaling lengths for the ferromagnetic damping and the spin Hall effect induced voltage.
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