Decoding the diagnostic and therapeutic potential of microbiota using pan-body pan-disease microbiomics.

The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.

Fracture strength of ceramic overlays with immediate dentin sealing and same-day delivery.

Limited research is available evaluating whether the reported in vitro benefit of immediate dentin sealing (IDS)-namely, increased bond strength to tooth structure-can be acquired in the era of same-day (SD) dentistry. The purpose of this study was to compare the fracture strengths of ceramic overlays fabricated with a delayed dentin sealing (DDS) technique or an IDS technique under 1-hour SD or 2-week multiple-day (MD) delivery conditions. Forty extracted, healthy maxillary third molars were prepared for a lithium disilicate overlay restoration and divided into 4 groups of 10 teeth each.

The Rewarding Experience of Serving as a US Air Force Dentist.

Providing care to service members and veterans as an active duty United States Air Force (USAF) dentist is a unique and rewarding experience that can be quite different from the private sector. As a USAF officer, I balance military and dental responsibilities, which has taught me to be flexible and adaptive. Virtually every dentist in the dental corps (DC), unless they are a resident, holds some form of a leadership position, whether that be overseeing clinic operations, the laboratory, an infection control program, or so on.

The MYC-Regulated RNA-Binding Proteins hnRNPC and LARP1 Are Drivers of Multiple Myeloma Cell Growth and Disease Progression and Negatively Predict Patient Survival.

Multiple myeloma (MM) is a malignant plasma cell disorder in which the MYC oncogene is frequently dysregulated. Due to its central role, MYC has been proposed as a drug target; however, the development of a clinically applicable molecule modulating MYC activity remains an unmet challenge. Consequently, an alternative is the development of therapeutic options targeting proteins located downstream of MYC.

Synaptotagmin 9 Modulates Spontaneous Neurotransmitter Release in Striatal Neurons by Regulating Substance P Secretion.

Synaptotagmin 9 (SYT9) is a tandem C2 domain Ca sensor for exocytosis in neuroendocrine cells; its function in neurons remains unclear. Here, we show that, in mixed-sex cultures, SYT9 does not trigger rapid synaptic vesicle exocytosis in mouse cortical, hippocampal, or striatal neurons, unless it is massively overexpressed. In striatal neurons, loss of SYT9 reduced the frequency of spontaneous neurotransmitter release events (minis).

Synaptic vesicle proteins are selectively delivered to axons in mammalian neurons.

Neurotransmitter-filled synaptic vesicles (SVs) mediate synaptic transmission and are a hallmark specialization in neuronal axons. Yet, how SV proteins are sorted to presynaptic nerve terminals remains the subject of debate. The leading model posits that these proteins are randomly trafficked throughout neurons and are selectively retained in presynaptic boutons.

Selection-free endogenous tagging of cell lines by bicistronic co-expression of the surface antigen NGFR.

Endogenous protein tagging, in contrast to exogenous overexpression of tagged proteins, allows to characterize specific protein functions under defined physiological or pathophysiological conditions without the influence of non-physiological protein levels. The development of generic and homology-independent tagging strategies, exploiting the CRISPR/spCas9 gene editing system in combination with generic tag donor plasmids, allows targeted and precise gene modification in mammalian cells for almost any desirable gene. So far, fluorescent tags or antibiotic resistance cassettes coupled to the endogenous fusion protein expression have been applied to isolate correctly modified clones.

EphA1 receptor tyrosine kinase is localized to the nucleus in rhabdomyosarcoma from multiple species.

While the typical role of receptor tyrosine kinases is to receive and transmit signals at the cell surface, in some cellular contexts (particularly transformed cells) they may also act as nuclear proteins. Aberrant nuclear localization of receptor tyrosine kinases associated with transformation often enhances the transformed phenotype (i.e.

Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene.

Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1-6% O), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance.

Intrinsic reactivity of [OUCH] : Apparent synthesis of [OUS] by reaction with CS.

Rationale: Building on our report that collision-induced dissociation (CID) can be used to create the highly reactive U-alkylidyne species [O=U≡CH] , our goal was to determine whether the species could be as an intermediate for synthesis of [OUS] by reaction with carbon disulfide (CS ).

Methods: Cationic uranyl-propiolate precursor ions were generated by electrospray ionization, and multiple-stage CID in a linear trap instrument was used to prepare [O=U≡CH] . Neutral CS was admitted into the trap through a modified He inlet and precision leak valves.

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19.

Background: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed.

Do trained nurses feel more psychologically safe?-Results from a multi-level modelling approach.

Aim: To analyse the associations between a nurse's psychological safety and her/his additional training.

Design: A cross-sectional survey conducted between September 2015 and August 2016.

Methods: A multi-level modelling approach was used considering unit membership.

Last Year of Life Study-Cologne (LYOL-C) (Part II): study protocol of a prospective interventional mixed-methods study in acute hospitals to analyse the implementation of a trigger question and patient question prompt sheets to optimise patient-centred care.

Introduction: The Last Year of Life Study-Cologne Part I (LYOL-C I) has identified general hospital units as the most important checkpoints for transitions in the last year of life of patients. Yet, satisfaction with hospitals, as reported by bereaved relatives, is the lowest of all health service providers. Thus, the LYOL-C Part II (LYOL-C II) focuses on optimising patient-centred care in acute hospitals for patients identified to be in their last year of life.

Efficacy and safety of pharmacotherapy for Alzheimer's disease and for behavioural and psychological symptoms of dementia in older patients with moderate and severe functional impairments: a systematic review of controlled trials.

Background: Many patients with Alzheimer's disease (AD) are physically frail or have substantial functional impairments. There is growing evidence that such patients are at higher risk for medication-induced adverse events. Furthermore, frailty seems to be more predictive of poor clinical outcomes than chronological age alone.

Ca effects on Fe(II) interactions with Mn-binding sites in Mn-depleted oxygen-evolving complexes of photosystem II and on Fe replacement of Mn in Mn-containing, Ca-depleted complexes.

Fe(II) cations bind with high efficiency and specificity at the high-affinity (HA), Mn-binding site (termed the "blocking effect" since Fe blocks further electron donation to the site) of the oxygen-evolving complex (OEC) in Mn-depleted, photosystem II (PSII) membrane fragments (Semin et al. in Biochemistry 41:5854, 2002). Furthermore, Fe(II) cations can substitute for 1 or 2Mn cations (pH dependent) in Ca-depleted PSII membranes (Semin et al.

Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity.

Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold.

Amino acid sensory complex proteins in mTORC1 and macroautophagy regulation.

Autophagy is the highly conserved catabolic process, which enables the survival of a cell under unfavorable environmental conditions. In a constantly changing environment, cells must be capable of dynamically oscillating between anabolism and catabolism in order to maintain cellular homeostasis. In this context, the activity of the mechanistic Target Of Rapamycin Complex 1 (mTORC1) is of major importance.

A blue ring nebula from a stellar merger several thousand years ago.

Stellar mergers are a brief but common phase in the evolution of binary star systems. These events have many astrophysical implications; for example, they may lead to the creation of atypical stars (such as magnetic stars, blue stragglers and rapid rotators), they play an important part in our interpretation of stellar populations and they represent formation channels of compact-object mergers. Although a handful of stellar mergers have been observed directly, the central remnants of these events were shrouded by an opaque shell of dust and molecules, making it impossible to observe their final state (for example, as a single merged star or a tighter, surviving binary).

Priming chromatin for segregation: functional roles of mitotic histone modifications.

Posttranslational modifications (PTMs) of histone proteins are important for various cellular processes including regulation of gene expression and chromatin structure, DNA damage response and chromosome segregation. Here we comprehensively review mitotic histone PTMs, in particular phosphorylations, and discuss their interplay and functions in the control of dynamic protein-protein interactions as well as their contribution to centromere and chromosome structure and function during cell division. Histone phosphorylations can create binding sites for mitotic regulators such as the chromosomal passenger complex, which is required for correction of erroneous spindle attachments and chromosome bi-orientation.

Exploring leading nurses' work values and their association with team safety climate: Results from a questionnaire survey in neonatal intensive care units.

Aim: To explore leading nurses' work values and their effect on the safety climate in neonatal intensive care units (NICUs).

Background: Despite their significance for behaviour, the work values of leading nurses are still insufficiently studied. We explore the impact of work value dimensions (self-transcendence, self-enhancement, conservation, and openness to change) on the safety climate.

Author Correction: Coherent diffractive imaging of microtubules using an X-ray laser.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

ULK1/2 Restricts the Formation of Inducible SINT-Speckles, Membraneless Organelles Controlling the Threshold of TBK1 Activation.

Membraneless organelles (MLOs) are liquid-like subcellular compartments providing spatiotemporal control to biological processes. This study reveals that cellular stress leads to the incorporation of the adaptor protein SINTBAD (TBKBP1) into membraneless, cytosolic speckles. Determination of the interactome identified >100 proteins forming constitutive and stress-inducible members of an MLO that we termed SINT-speckles.

Metabolic Plasticity of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is one of the most common and life-threatening leukemias. A highly diverse and flexible metabolism contributes to the aggressiveness of the disease that is still difficult to treat. By using different sources of nutrients for energy and biomass supply, AML cells gain metabolic plasticity and rapidly outcompete normal hematopoietic cells.