Based on the means of his time, Alois Alzheimer supposed that the disease, later carrying his name, is a disease of older age, and that the pathomorphological structures he described are due to ...disturbances in brain metabolism. In this contribution, it is discussed which cellular metabolic abnormalities may be representative for age-related sporadic Alzheimer disease (SAD) the predominant form of SAD in contrast to the very rare hereditary early-onset form. In focus are disturbances in glucose/energy metabolism which involve the deficits in acetylcholine, cholesterol and UDP-N-acetylglucosamine beside ATP. Another leading abnormality is the defect in cell membrane composition. The interrelation between abnormal glucose/energy metabolism and membrane defect may be assumed to form the basis for the induction of both the perturbed metabolism of the amyloid precursor protein leading to increased formation of beta-amyloid and hyperphosphorylation of tau-protein destroying cell structures. Alois Alzheimer may have been so prescient to assume most of this 100 years ago.
The frontoparietal network is involved in multiple tasks, such as visual mental rotation, working memory, or arithmetic. Whether those different cognitive processes are supported by the same ...supramodal network or distinct, but overlapping, functional systems is unresolved. We investigate whether frontoparietal activity can be selectively entrained by rhythmic sensory stimulations (visual rotation) and whether this entrainment can causally modulate task performance in another modality (auditory working memory). We show that rhythmic visual presentations of rotating shapes, known to activate the dorsal pathway, increase frontoparietal connectivity at stimulation frequency as measured with MEG/EEG. We then show that frontoparietal theta oscillations predict auditory working memory performance. Last, we demonstrate that theta rhythmic visual stimulation applied during auditory memory causally enhances performance, and both the rotating properties of the stimulus and its flickering frequency drive the effect. This study provides causal evidence of the supramodal role of the frontoparietal network in human cognition.
The effect of ageing on the activity of enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism was studied in three different types of mitochondria of cerebral cortex of ...1-year old and 2-year old male Wistar rats. We assessed the maximum rate (V(max)) of the mitochondrial enzyme activities in non-synaptic perikaryal mitochondria, and in two populations of intra-synaptic mitochondria. The results indicated that: (i) in normal, steady-state cerebral cortex the values of the catalytic activities of the enzymes markedly differed in the various populations of mitochondria; (ii) in intra-synaptic mitochondria, ageing affected the catalytic properties of the enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism; (iii) these changes were more evident in intra-synaptic "heavy" than "light" mitochondria. These results indicate a different age-related vulnerability of subpopulations of mitochondria in vivo located into synapses than non-synaptic ones.
•IMID's molecular mechanism explain their efficacy in hematological malignancies.•Lenalidomide-treated patients become resistant through cancer-specific mechanisms.•Future research will identify ...novel strategies to target IMiD-resistant clones.
The discovery that the immunomodulatory imide drugs (IMiDs) possess antitumor properties revolutionized the treatment of specific types of hematological cancers. Since then, much progress has been made in understanding why the IMiDs are so efficient in targeting the malignant clones in difficult-to-treat diseases. Despite their efficacy, IMiD resistance arises eventually. Herein we summarize the mechanisms of sensitivity and resistance to lenalidomide in del(5q) myelodysplastic syndrome and multiple myeloma, two diseases in which these drugs are at the therapeutic frontline. Understanding the molecular and cellular mechanisms underlying IMiD efficacy and resistance may allow development of specific strategies to eliminate the malignant clone in otherwise incurable diseases.
New molecular biomarkers for prostate cancer (PC) prognosis are urgently needed. Ratio-based models are attractive, as they require no additional normalization. Here, we train and independently ...validate a novel 4-miRNA prognostic ratio model for PC.
By genome-wide miRNA expression profiling of PC tissue samples from 123 men who underwent radical prostatectomy (RP) (PCA123, training cohort), we identified six top candidate prognostic miRNAs and systematically tested their ability to predict postoperative biochemical recurrence (BCR). The best miRNA-based prognostic ratio model (MiCaP) was validated in two independent cohorts (PCA352 and PCA476) including >800 RP patients in total. Clinical end points were BCR and prostate cancer-specific survival (CSS). The prognostic potential of MiCaP was assessed by univariate and multivariate Cox-regression analyses and Kaplan–Meier analyses.
We identified a 4-miRNA ratio model, MiCaP (miR-23a-3p×miR-10b-5p)/(miR-133a×miR-374b-5p), that predicted time to BCR independently of routine clinicopathologic variables in the training cohort (PCA123) and was successfully validated in two independent RP cohorts. In addition, MiCaP was a significant predictor of CSS in univariate analysis HR 3.35 (95% CI 1.34−8.35), P=0.0096 and in multivariate analysis HR 2.43 (95% CI 1.45–4.07), P=0.0210. As proof-of-principle, we also analyzed MiCaP in plasma samples from 111 RP patients. A high MiCaP score in plasma was significantly associated with BCR (P=0.0036, Kaplan–Meier analysis). Limitations include low mortality rates (CSS: 5.4%).
We identified a novel 4-miRNA ratio model (MiCaP) with significant independent prognostic value in three RP cohorts, indicating promising potential to improve PC risk stratification.
An infrared study of the double nucleus in NGC 3256 Lira, P.; Gonzalez-Corvalan, V.; Ward, M. ...
Monthly notices of the Royal Astronomical Society,
February 2008, Letnik:
384, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We present new resolved near- and mid-infrared (mid-IR) imaging and N-band spectroscopy of the two nuclei in the merger system NGC 3256, the most IR luminous galaxy in the nearby Universe. The ...results from the spectral energy distribution fit to the data are consistent with previous estimates of the amount of obscuration towards the nuclei and the nuclear star formation rates. However, we also find substantial differences in the infrared emission from the two nuclei which cannot be explained by obscuration alone. We conclude that the northern nucleus requires an additional component of warm dust in order to explain its properties. This suggests that local star-forming conditions can vary significantly within the environment of a single system.
By re-processing the data of the second season of the OGLE survey for planetary transits and adding new mesurements on the same fields gathered in subsequent years with the OGLE telescope, we have ...identified 23 new transit candidates, recorded as OGLE-TR-178 to OGLE-TR-200. We studied the nature of these objects with the FLAMES/UVES multi-fiber spectrograph on the VLT. One of the candidates, OGLE-TR-182, was confirmed as a transiting gas giant planet on a 4-day orbit. We characterised it with further observations using the FORS1 camera and UVES spectrograph on the VLT. OGLE-TR-182b is a typical “hot Jupiter” with an orbital period of 3.98 days, a mass of $1.01 \pm 0.15~M_{\rm Jup}$ and a radius of 1.13$^{+0.24}_{-0.08}~R_{\rm Jup}$. Confirming this transiting planet required a large investment in telescope time with the best instruments available, and we comment on the difficulty of the confirmation process for transiting planets in the OGLE survey. We delineate the zone were confirmation is difficult or impossible, and discuss the implications for the CoRoT space mission in its quest for transiting telluric planets.
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