The functional significance of sleep spindles for overnight memory consolidation and general learning aptitude as well as the effect of four 10-minute sessions of spindle frequency (11.6-16 Hz, ...sigma) neurofeedback-training on subsequent sleep spindle activity and overnight performance change was investigated. Before sleep, subjects were trained on a paired-associate word list task after having received either neurofeedback training (NFT) or pseudofeedback training (PFT). Although NFT had no significant impact on subsequent spindle activity and behavioral outcomes, there was a trend for enhanced sigma band-power during NREM (stage 2 to 4) sleep after NFT as compared to PFT. Furthermore, a significant positive correlation between spindle activity during slow wave sleep (in the first night half) and overall memory performance was revealed. The results support the view that the considerable inter-individual variance in sleep spindle activity can at least be partly explained by differences in the ability to acquire new declarative information. We conclude that the short NFT before sleep was not sufficient to efficiently enhance phasic spindle activity and/or to influence memory processing. NFT was, however, successful in increasing sigma power, presumably because sigma NFT effects become more easily evident in actually trained frequency bands than in associated phasic spindle activity.
Differential gene expression gives rise to the many cell types of complex organisms. Enhancers regulate transcription by binding transcription factors (TFs), which in turn recruit cofactors to ...activate RNA Polymerase II at core promoters. Transcriptional regulation is typically mediated by distinct combinations of TFs, enabling a relatively small number of TFs to generate a large diversity of cell types. However, how TFs achieve combinatorial enhancer control and how enhancers, enhancer-bound TFs, and the cofactors they recruit regulate RNA Polymerase II activity is not entirely clear. Here, we review how TF synergy is mediated at the level of DNA binding and after binding, the role of cofactors and the post-translational modifications they catalyze, and discuss different models of enhancer—core-promoter communication.
One of the most important questions in biology is how transcription factors (TFs) and cofactors control enhancer function and thus gene expression. Enhancer activation usually requires combinations ...of several TFs, indicating that TFs function synergistically and combinatorially. However, while TF binding has been extensively studied, little is known about how combinations of TFs and cofactors control enhancer function once they are bound. It is typically unclear which TFs participate in combinatorial enhancer activation, whether different TFs form functionally distinct groups, or if certain TFs might substitute for each other in defined enhancer contexts. Here we assess the potential regulatory contributions of TFs and cofactors to combinatorial enhancer control with enhancer complementation assays. We recruited GAL4-DNA-binding-domain fusions of 812 Drosophila TFs and cofactors to 24 enhancer contexts and measured enhancer activities by 82,752 luciferase assays in S2 cells. Most factors were functional in at least one context, yet their contributions differed between contexts and varied from repression to activation (up to 289-fold) for individual factors. Based on functional similarities across contexts, we define 15 groups of TFs that differ in developmental functions and protein sequence features. Similar TFs can substitute for each other, enabling enhancer re-engineering by exchanging TF motifs, and TF-cofactor pairs cooperate during enhancer control and interact physically. Overall, we show that activators and repressors can have diverse regulatory functions that typically depend on the enhancer context. The systematic functional characterization of TFs and cofactors should further our understanding of combinatorial enhancer control and gene regulation.
Diel vertical migration (DVM) facilitates biogeochemical exchanges between shallow waters and the deep ocean. An effective way of monitoring the migrant biota is by acoustic observations although the ...interpretation of the scattering layers poses challenges. Here we combine results from acoustic observations at 18 and 38kHz with limited net sampling in order to unveil the origin of acoustic phenomena around the Canary Islands, subtropical northeast Atlantic Ocean. Trawling data revealed a high diversity of fishes, decapods and cephalopods (152 species), although few dominant species likely were responsible for most of the sound scattering in the region. We identified four different acoustic scattering layers in the mesopelagic realm: (1) at 400–500m depth, a swimbladder resonance phenomenon at 18kHz produced by gas-bearing migrant fish such as Vinciguerria spp. and Lobianchia dofleini, (2) at 500–600m depth, a dense 38kHz layer resulting primarily from the gas-bearing and non-migrant fish Cyclothone braueri, and to a lesser extent, from fluid-like migrant fauna also inhabiting these depths, (3) between 600 and 800m depth, a weak signal at both 18 and 38kHz ascribed either to migrant fish or decapods, and (4) below 800m depth, a weak non-migrant layer at 18kHz which was not sampled. All the dielly migrating layers reached the epipelagic zone at night, with the shorter-range migrations moving at 4.6±2.6cms−1 and the long-range ones at 11.5±3.8cms−1. This work reduces uncertainties interpreting standard frequencies in mesopelagic studies, while enhances the potential of acoustics for future research and monitoring of the deep pelagic fauna in the Canary Islands.
•Acoustic scattering and associated deep-sea fauna investigated in the Canary Islands.•Four different scattering layers were observed from 400 to 1000m depth.•Migrant and non-migrant layers were ascribed to different fish a decapod species.•Short (400m) and long-range (700m) migrations moved at 5 and 12cms−1.
The stomach of a spotted wolffish (Anarhichas minor) caught in Icelandic waters was found to contain ~727 greater eelpout larvae (Lycodes esmarkii). All the larvae were of similar size and at a ...similar state of digestion, indicating they were all consumed together. The likely explanation for this observation is that greater eelpout lay their eggs in a nest, with the larvae remaining in the nest for a short period after hatching. The larvae were then predated upon by the spotted wolffish while still in the nest. This study sheds new light on greater eelpout in Icelandic waters, with recently hatched larvae being present in March, breeding at a depth of ~200–250 m, and likely exhibiting nesting behavior, which has not previously been documented.
Introduction
Sarcopenia is defined as a decline in muscle function as well as muscle mass. Sarcopenia itself and sarcopenic obesity, defined as sarcopenia in obese patients, have been used as ...surrogates for a worse prognosis in colorectal cancer. This review aims to determine if there is evidence for sarcopenia as a prognostic parameter in colorectal liver metastases (CRLM).
Methods
PubMed, Embase, Cochrane Central, Web of Science, SCOPUS, and CINAHL databases were searched for articles that were selected in accordance with the PRISMA guidelines. The primary outcomes were overall survival (OS) and disease-free survival (DFS). A random effects meta-analysis was conducted.
Results
After eliminating duplicates and screening abstracts (
n
= 111), 949 studies were screened, and 33 publications met the inclusion criteria. Of them, 15 were selected after close paper review, and 10 were incorporated into the meta-analysis, which comprised 825 patients. No significant influence of sarcopenia for OS (odds ratio (OR), 2.802 (95% confidence interval (CI), 1.094–1.11);
p
= 0.4) or DFS (OR, 1.203 (95% CI, 1.162–1.208);
p
= 0.5) was found, although a trend was defined toward sarcopenia. Sarcopenia significantly influenced postoperative complication rates (OR, 7.905 (95% CI, 1.876–3.32);
p
= 0.001) in two studies where data were available.
Conclusion
Existing evidence on the influence of sarcopenia on postoperative OS as well as DFS in patients undergoing resection for CRLM exists. We were not able to confirm that sarcopenic patients have a significantly worse OS and DFS in our analysis, although a trend toward this hypothesis was visible. Sarcopenia seems to influence complication rates but prospective studies are needed.
In locally advanced breast cancer, axillary lymph node dissection remains a pivotal component of surgical therapy. Apart from this, it has been mostly replaced by sentinel node biopsy. Complications ...after axillary dissection include wound infection, neuropathy, lymphedema and-most frequently-seroma. In this retrospective multi-centre study, we compared the use of LigaSure
with monopolar electrocautery regarding perioperative outcome.
A retrospective data analysis from female breast cancer patients who underwent axillary dissection at two breast centres in Austria that are using two different surgical techniques was performed for this study. We compared the rate of complications and re-operations, length of hospital stay, time to drain removal, total drain fluid, seroma formation after drain removal, number of seroma aspirations and total seroma fluid.
Seventy one female patients with a median age of 63 (30-83) were included in this study. In 35 patients LigaSure
and in 36 monopolar cautery was used for axillary dissection. There was no significant difference regarding intraoperative complications and rate of re-operations between the two groups (2.9 vs. 5.6%; p = 1 and 2.9 vs. 13.9%; p = 0.199). The time to drain removal and the length of hospital stay was similar in both groups. A significant difference in the occurence of postoperative wound infection could also not be shown. However, we found a significantly smaller total drain fluid in the LigaSure
-group compared to the cautery-group (364.6 ml vs. 643.4 ml; p = 0.004). Seroma formation after drain removal was more frequent in the LigaSure
-group (68.6 vs. 41.7%; p = 0.032) with a higher number of outpatient seroma aspirations (2.0 vs. 0.9; p = 0.005).
LigaSure
and monopolar cautery provide equivalent techniques in axillary lymph node dissection with comparable postoperative outcomes.
Sarcopenia, is predictive of a worse outcome after resection for colorectal liver metastases (CRLM). Obesity leads to a metabolic double burden if sarcopenia is as present, prompting malignancy ...progression, known as sarcopenic obesity (SO). This study aimed to compare sarcopenia and SO in patients undergoing CRLM resection, to prognostic parameters.
The skeletal muscle index (SMI) defined sarcopenia using sex specific cut off values (48.4 cm
/m
for females and 59.1 cm
/m
for males) by calculating the preoperative muscle mass at the vertebral height L3 using OSIRIX DICOM viewer. SO was determined as sarcopenia in patients showing obesity, as shown via fat percentage measurements on the preoperative CT scan. Established prognostic parameters (KRAS status, TNM classification, inflammatory response) were evaluated against SMI and SO to assess their predictability for postoperative outcomes.
A total of 251 patients (62% female, median age 68 years) were included. Sarcopenic patients showed a threefold higher risk for postoperative death as compared to non-sarcopenic patients (p=0.04). Prevalent SO increased this risk to fivefold (p=0.01) compared to non-sarcopenic patients. COX regression analysis revealed SO and KRAS positivity as independent prognostic factors for disease-free survival (SO: p=0.038; KRAS: p=0.041; TNM, tumor size, Charlson Comorbidity Index, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio all not significant). Patients risk of death in case of KRAS positivity and SO was seven times higher (p=0.03).
There seems to be a benefit in merging data on mutational status and muscle wasting in patients with CRLM to facilitate an individual, patient-tailored approach.
The interferon (IFN)-stimulated gene factor 3 (ISGF3) transcription factor with its Stat1, Stat2, and interferon regulatory factor 9 (IRF9) subunits is employed for transcriptional responses ...downstream of receptors for type I interferons (IFN-I) that include IFN-α and IFN-β and type III interferons (IFN-III), also called IFN-λ. Here, we show in a murine model of dextran sodium sulfate (DSS)-induced colitis that IRF9 deficiency protects animals, whereas the combined loss of IFN-I and IFN-III receptors worsens their condition. We explain the different phenotypes by demonstrating a function of IRF9 in a noncanonical transcriptional complex with Stat1, apart from IFN-I and IFN-III signaling. Together, Stat1 and IRF9 produce a proinflammatory activity that overrides the benefits of the IFN-III response on intestinal epithelial cells. Our results further suggest that the CXCL10 chemokine gene is an important mediator of this proinflammatory activity. We thus establish IFN-λ as a potentially anticolitogenic cytokine and propose an important role for IRF9 as a component of noncanonical Stat complexes in the development of colitis.
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