The role of the Cdk9/Cyclin T1 complex in T cell differentiation

The Cdk9/Cyclin T1 complex is very important in controlling specific differentiative pathways of several cell types, including muscle cells and neurons. We recently demonstrated the involvement of this complex in B cell activation/differentiation. To check whether the Cdk9/Cyclin T1 complex is also involved in the T cell activation/differentiation process, we isolated different T cell populations by magnetic separation, based on their surface antigens. We observed that the expression level of Cdk9/Cyclin T1 increases in effector T cells (CD27(+)), as well as in activated T cells (CD25(+)) and memory T cells (CD45RA(-)), thus suggesting a specific upregulation of the Cdk9/Cyclin T1 complex following antigen encounter. We have previously demonstrated that in B cells, Cdk9 interacts in vivo with the E2A gene products E12/E47 (members of the basic helix-loop-helix family) which are involved in differentiation. In this article, we show that this interaction also occurs in T cells. This suggests an active role for the Cdk9/Cyclin T1 complex during lymphoid differentiation, through physical binding with E12 and E47. These preliminary results suggest that the Cdk9/Cyclin T1 complex may be important in the activation and differentiation program of lymphoid cells and that its upregulation, which is due to still unknown mechanisms, may contribute to malignant transformation.     

Percussive tool use by Ta? Western chimpanzees and Fazenda Boa Vista bearded capuchin monkeys: a comparison

Percussive tool use holds special interest for scientists concerned with human origins. We summarize the findings from two field sites, Taï and Fazenda Boa Vista, where percussive tool use by chimpanzees and bearded capuchins, respectively, has been extensively investigated. We describe the ecological settings in which nut-cracking occurs and focus on four aspects of nut-cracking that have important cognitive implications, namely selection of tools, tool transport, tool modification and modulation of actions to reach the goal of cracking the nut. We comment on similarities and differences in behaviour and consider whether the observed differences reflect ecological, morphological, social and/or cognitive factors. Both species are sensitive to physical properties of tools, adjust their selection of hammers conditionally to the resistance of the nuts and to transport distance, and modulate the energy of their strikes under some conditions. However, chimpanzees transport hammers more frequently and for longer distances, take into account a higher number of combinations of variables and occasionally intentionally modify tools. A parsimonious interpretation of our findings is that morphological, ecological and social factors account for the observed differences. Confirmation of plausible cognitive differences in nut-cracking requires data not yet available.     

Discovery of a Unique Clp Component,ClpF, in Chloroplasts: A Proposed Binary ClpF-ClpS1 Adaptor Complex Functions in Substrate Recognition and Delivery

Clp proteases are found in prokaryotes, mitochondria, and plastids where they play crucial roles in maintaining protein homeostasis (proteostasis). The plant plastid Clp machinery comprises a hetero-oligomeric ClpPRT proteolytic core, ATP-dependent chaperones ClpC and ClpD, and an adaptor protein, ClpS1. ClpS1 selects substrates to the ClpPR protease-ClpC chaperone complex for degradation, but the underlying substrate recognition and delivery mechanisms are currently unclear. Here, we characterize a ClpS1-interacting protein in Arabidopsis thaliana, ClpF, which can interact with the Clp substrate glutamyl-tRNA reductase. ClpF and ClpS1 mutually stimulate their association with ClpC. ClpF, which is only found in photosynthetic eukaryotes, contains bacterial uvrB/C and YccV protein domains and a unique N-terminal domain. We propose a testable model in which ClpS1 and ClpF form a binary adaptor for selective substrate recognition and delivery to ClpC, reflecting an evolutionary adaptation of the Clp system to the plastid proteome.     

Mitochondrial DNA alteration in obstructive sleep apnea

Background

Obstructive Sleep Apnea (OSAS) is a disease associated with the increase of cardiovascular risk and it is characterized by repeated episodes of Intermittent Hypoxia (IH) which inducing oxidative stress and systemic inflammation. Mitochondria are cell organelles involved in the respiratory that have their own DNA (MtDNA). The aim of this study was to investigate if the increase of oxidative stress in OSAS patients can induce also MtDNA alterations.

Methods

46 OSAS patients (age 59.27 ± 11.38; BMI 30.84 ± 3.64; AHI 36.63 ± 24.18) were compared with 36 control subjects (age 54.42 ± 6.63; BMI 29.06 ± 4.7; AHI 3.8 ± 1.10). In blood cells Content of MtDNA and nuclear DNA (nDNA) was measured in OSAS patients by Real Time PCR. The ratio between MtDNA/nDNA was then calculated. Presence of oxidative stress was evaluated by levels of Reactive Oxygen Metabolites (ROMs), measured by diacron reactive oxygen metabolite test (d-ROM test).

Results

MtDNA/nDNA was higher in patients with OSAS than in the control group (150.94 ± 49.14 vs 128.96 ± 45.8; p = 0.04), the levels of ROMs were also higher in OSAS subjects (329.71 ± 70.17 vs 226 ± 36.76; p = 0.04) and they were positively correlated with MtDNA/nDNA (R = 0.5, p < 0.01).

Conclusions

In OSAS patients there is a Mitochondrial DNA damage induced by the increase of oxidative stress. Intermittent hypoxia seems to be the main mechanism which leads to this process.     

Trehalose inhibits cell proliferation and amplifies long-term temozolomide- and radiation-induced cytotoxicity in melanoma cells: A role for autophagy and premature senescence

Cutaneous melanomas frequently metastasize to the brain, with temozolomide (TMZ) plus radiotherapy (RT) offering little control of these lesions. We tested whether trehalose, a natural glucose disaccharide proved to induce autophagy, could enhance the effect of TMZ and ionizing radiation (IR). In two melanoma cell lines (A375 and SK-Mel-28), which greatly differ in chemosensitivity and radiosensitivity, trehalose significantly inhibited short-term cell proliferation and also enhanced IR-induced cytostasis. Interestingly, in TMZ-resistant SK-Mel-28 cells, trehalose was more effective than TMZ, and combined trehalose + TMZ further reduced cell proliferation. In long-term experiments, colony-forming capacity was dramatically reduced by trehalose, and even more by combined trehalose + TMZ or trehalose + IR. In resistant SK-Mel-28 cells, although growth was inhibited most with trehalose + TMZ + IR-6 Gy combined treatment, it is notable that trehalose + TMZ treatment was also very effective. Along with a direct antiproliferative effect, two further mechanisms may explain how trehalose potentiates TMZ- and IR-induced effects: the remarkable trehalose-stimulated autophagy in A375 cells, which were sensitive to TMZ- and IR-induced apoptosis; and the notable trehalose-stimulated premature senescence in SK-Mel-28 cells, which were resistant to apoptosis and less prone to autophagy. In normal melanocytes, trehalose induced a minor autophagy and cell proliferation inhibition, without affecting cell viability; moreover, when trehalose was used in combination with TMZ, the slight TMZ-induced cytotoxicity was not significantly reinforced. Together, our results suggest that trehalose, a safe nutrient supplement able to cross the blood–brain barrier, is a promising candidate, worthy to be further explored in vivo, to augment the therapeutic efficacy of TMZ and RT in melanoma brain metastases.     

Key role of streambed moisture and flash storms for microbial resistance and resilience to long‐term drought

相似文献   

The Small Non-coding Vault RNA1-1 Acts as a Riboregulator of Autophagy

1. Download high-res image (136KB)
2. Download full-size image

     

A two alternative forced choice method for assessing vibrotactile discrimination thresholds in the lower limb

The development of an easy to implement, quantitative measure to examine vibration perception would be useful for future application in clinical settings. Vibration sense in the lower limb of younger and older adults was examined using the method of constant stimuli (MCS) and the two-alternative forced choice paradigm. The focus of this experiment was to determine an appropriate stimulation site on the lower limb (tendon versus bone) to assess vibration threshold and to determine if the left and right legs have varying thresholds. Discrimination thresholds obtained at two stimulation sites in the left and right lower limbs showed differences in vibration threshold across the two ages groups, but not across sides of the body nor between stimulation sites within each limb. Overall, the MCS can be implemented simply, reliably, and with minimal time. It can also easily be implemented with low-cost technology. Therefore, it could be a good candidate method to assess the presence of specific deep sensitivity deficits in clinical practice, particularly in populations likely to show the onset of sensory deficits.     

Galanin Neurons Unite Sleep Homeostasis and α2-Adrenergic Sedation

1. Download : Download high-res image (263KB)
2. Download : Download full-size image

     

High frequency viscoelastic behaviour of low molecular weight hyaluronic acid water solutions

Hyaluronic acid (HA) is a polysaccharide widely used in biomedical applications, due to its elevated biocompatibility and the peculiar viscoelastic properties of its solutions. Although the viscoelastic behaviour of HA solutions has been extensively studied in the literature it has been often reported in the range of low frequency (1-100 Hz) and high salt concentration, whereas the main rheological peculiarities of this molecule are expected at high frequency (>100 Hz) and low salt concentration. In this work we studied the viscoelastic properties of low molecular weight HA (155 kDa) in wide range of concentrations (0.01-20 mg/ml) at low ionic strength and over an extended frequency range (0.1-1000 Hz) using both optical tweezers and conventional rheometry. Good agreement between the high frequency dynamic behaviour (optical tweezers) and the viscoelastic properties at low frequency (rheometry) was found. We also found that, in apparent contradiction with polyelectrolyte solution theory, HA solution behaves as liquid-like viscoelastic fluid (G'>G') even at concentrations higher than the entanglement concentration where a weak-gel behavior should be expected.