2,566 research outputs found
Dark Matter Deficient Galaxies Produced via High-velocity Galaxy Collisions in High-resolution Numerical Simulations
Abstract
The recent discovery of diffuse dwarf galaxies that are deficient in dark matter appears to challenge the current paradigm of structure formation in our universe. We describe numerical experiments to determine if so-called dark matter deficient galaxies (DMDGs) could be produced when two gas-rich, dwarf-sized galaxies collide with a high relative velocity of ∼300 km s−1. Using idealized high-resolution simulations with both mesh-based and particle-based gravito-hydrodynamics codes, we find that DMDGs can form as high-velocity galaxy collisions and separate dark matter from the warm disk gas, which subsequently is compressed by shock and tidal interaction to form stars. Then using the large simulated universe IllustrisTNG, we discover a number of high-velocity galaxy collision events in which DMDGs are expected to form. However, we did not find evidence that these types of collisions actually produced DMDGs in the TNG100-1 run. We argue that the resolution of the numerical experiment is critical to realizing the “collision-induced” DMDG formation scenario. Our results demonstrate one of many routes in which galaxies could form with unconventional dark matter fractions.</jats:p
The Glyceraldehyde-3-Phosphate Dehydrogenase and the Small GTPase Rab 2 Are Crucial for Brucella Replication
The intracellular pathogen Brucella abortus survives and replicates inside host cells within an endoplasmic reticulum (ER)-derived replicative organelle named the “Brucella-containing vacuole” (BCV). Here, we developed a subcellular fractionation method to isolate BCVs and characterize for the first time the protein composition of its replicative niche. After identification of BCV membrane proteins by 2 dimensional (2D) gel electrophoresis and mass spectrometry, we focused on two eukaryotic proteins: the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the small GTPase Rab 2 recruited to the vacuolar membrane of Brucella. These proteins were previously described to localize on vesicular and tubular clusters (VTC) and to regulate the VTC membrane traffic between the endoplasmic reticulum (ER) and the Golgi. Inhibition of either GAPDH or Rab 2 expression by small interfering RNA strongly inhibited B. abortus replication. Consistent with this result, inhibition of other partners of GAPDH and Rab 2, such as COPI and PKC ι, reduced B. abortus replication. Furthermore, blockage of Rab 2 GTPase in a GDP-locked form also inhibited B. abortus replication. Bacteria did not fuse with the ER and instead remained in lysosomal-associated membrane vacuoles. These results reveal an essential role for GAPDH and the small GTPase Rab 2 in B. abortus virulence within host cells
Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report
<p>Abstract</p> <p>Introduction</p> <p>Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus.</p> <p>Case presentation</p> <p>Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus.</p> <p>Conclusions</p> <p>In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.</p
Exhausted CD8 T Cells Downregulate the IL-18 Receptor and Become Unresponsive to Inflammatory Cytokines and Bacterial Co-infections
During many chronic infections virus-specific CD8 T cells succumb to exhaustion as they lose their ability to respond to antigenic activation. Combinations of IL-12, IL-18, and IL-21 have been shown to induce the antigen-independent production of interferon (IFN)-γ by effector and memory CD8 T cells. In this study we investigated whether exhausted CD8 T cells are sensitive to activation by these cytokines. We show that effector and memory, but not exhausted, CD8 T cells produce IFN-γ and upregulate CD25 following exposure to certain combinations of IL-12, IL-18, and IL-21. The unresponsiveness of exhausted CD8 T cells is associated with downregulation of the IL-18-receptor-α (IL-18Rα). Although IL-18Rα expression is connected with the ability of memory CD8 T cells to self-renew and efflux rhodamine 123, the IL-18Rαlo exhausted cells remained capable of secreting this dye. To further evaluate the consequences of IL-18Rα downregulation, we tracked the fate of IL-18Rα-deficient CD8 T cells in chronically infected mixed bone marrow chimeras and discovered that IL-18Rα affects the initial but not later phases of the response. The antigen-independent responsiveness of exhausted CD8 T cells was also investigated following co-infection with Listeria monocytogenes, which induces the expression of IL-12 and IL-18. Although IL-18Rαhi memory cells upregulated CD25 and produced IFN-γ, the IL-18Rαlo exhausted cells failed to respond. Collectively, these findings indicate that as exhausted T cells adjust to the chronically infected environment, they lose their susceptibility to antigen-independent activation by cytokines, which compromises their ability to detect bacterial co-infections
The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation
Peer reviewedPublisher PD
Proctors exploit three-dimensional ghost tools during clinical-like training scenarios: a preliminary study
Phonon-driven spin-Floquet magneto-valleytronics in MoS2
Two-dimensional materials equipped with strong spin-orbit coupling can display novel electronic, spintronic, and topological properties originating from the breaking of time or inversion symmetry. A lot of interest has focused on the valley degrees of freedom that can be used to encode binary information. By performing ab initio time-dependent density functional simulation on MoS2, here we show that the spin is not only locked to the valley momenta but strongly coupled to the optical E '' phonon that lifts the lattice mirror symmetry. Once the phonon is pumped so as to break time-reversal symmetry, the resulting Floquet spectra of the phonon-dressed spins carry a net out-of-plane magnetization (approximate to 0.024 mu(B) for single-phonon quantum) even though the original system is non-magnetic. This dichroic magnetic response of the valley states is general for all 2H semiconducting transition-metal dichalcogenides and can be probed and controlled by infrared coherent laser excitation
Acute urinary retention in a 23-year-old woman with mild encephalopathy with a reversible splenial lesion: a case report
<p>Abstract</p> <p>Introduction</p> <p>Patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion present with relatively mild central nervous system disturbances. Although the exact etiology of the condition remains poorly understood, it is thought to be associated with infective agents. We present a case of a patient with mild encephalitis/encephalopathy with a reversible splenial lesion, who had the unusual feature of acute urinary retention.</p> <p>Case presentation</p> <p>A 23-year-old Japanese woman developed mild confusion, gait ataxia, and urinary retention seven days after onset of fever and headache. Magnetic resonance imaging demonstrated T2 prolongation in the splenium of the corpus callosum and bilateral cerebral white matter. These magnetic resonance imaging abnormalities disappeared two weeks later, and all of the symptoms resolved completely within four weeks. Except for the presence of acute urinary retention (due to underactive detrusor without hyper-reflexia), the clinical and radiologic features of our patient were consistent with those of previously reported patients with mild encephalitis/encephalopathy with a reversible splenial lesion. To the best of our knowledge, this is the first report of acute urinary retention recognized in a patient with mild encephalitis/encephalopathy with a reversible splenial lesion.</p> <p>Conclusion</p> <p>Our findings suggest that mild encephalitis/encephalopathy with a reversible splenial lesion can be associated with impaired bladder function and indicate that acute urinary retention in this benign disorder should be treated immediately to avoid bladder injury.</p
Zebrafish: A See-Through Host and a Fluorescent Toolbox to Probe Host–Pathogen Interaction
In many ways, the zebrafish represents a hybrid between mouse and invertebrate infection models. Powerful forwardgenetic tools that have made invertebrates justifiably famous are not only relatively accessible in the zebrafish, but have been exploited to yield new insights into human infectious diseases, including leprosy and tuberculosis [1]. Transgenic technologies have enabled detailed, non-invasive in vivo visualization of macrophages and neutrophils in pitched battle with bacteria and fungi [2,3]. Reverse genetics with morpholinos, vivo-morpholinos, and zinc-finger nucleases (but unfortunately not homologous recombination, which for the moment remains out of reach in this organism) enable examination of the roles of specific genes during infection. Flexible genetic systems such as Gal4-UAS and Cre-Lox permit tissue-specific transformation and ablation ([3]; Figure 1)
Persistence of tumor-infiltrating CD8 T cells is tumor-dependent but antigen-independent
How tumor-infiltrating lymphocytes (TILs) that are tumor-specific but functionally tolerant persist in the antigen-expressing tumor tissue is largely unknown. We have previously developed a modified TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model where prostate cancer cells express the T-cell epitope SIYRYYGL (SIY) recognized by CD8 T cells expressing the 2C T-cell receptor (TCR) (referred to as TRP-SIY mice). In TRP-SIY mice, activated 2C T cells rapidly become tolerant following infiltration into the prostate tumor. In this study, we show that tolerant 2C T cells persist in the prostate tumor of TRP-SIY mice by proliferating slowly in a tumor-dependent, but antigen-, interleukin (IL)-7- and IL-15-independent manner. We also show that disappearance of 2C T cells from the lymphoid organs of TRP-SIY mice are due to antigen-induced T-cell contraction rather than altered trafficking or generalized T-cell depletion in the mice. Finally, we show that clonal T cells unreactive to SIY are equally capable of persisting in the prostate tumor. These findings suggest that while functional tolerance of TILs is induced by antigen, persistence of tolerant TILs in the tumor tissue is mediated by a novel mechanism: slow proliferation independent of antigen and homeostatic cytokines. These results also allow CD8 T-cell survival in the tumor environment to be compared with T-cell survival in chronic infection
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