Dimensionality reduction beyond neural subspaces with slice tensor component analysis

Recent work has argued that large-scale neural recordings are often well described by patterns of coactivation across neurons. Yet the view that neural variability is constrained to a fixed, low-dimensional subspace may overlook higher-dimensional structure, including stereotyped neural sequences or slowly evolving latent spaces. Here we argue that task-relevant variability in neural data can also cofluctuate over trials or time, defining distinct ‘covariability classes’ that may co-occur within the same dataset. To demix these covariability classes, we develop sliceTCA (slice tensor component analysis), a new unsupervised dimensionality reduction method for neural data tensors. In three example datasets, including motor cortical activity during a classic reaching task in primates and recent multiregion recordings in mice, we show that sliceTCA can capture more task-relevant structure in neural data using fewer components than traditional methods. Overall, our theoretical framework extends the classic view of low-dimensional population activity by incorporating additional classes of latent variables capturing higher-dimensional structure

Changes in the composition of marine and sea-ice diatoms derived from sedimentary ancient DNA of the eastern Fram Strait over the past 30 000 years

The Fram Strait is an area with a relatively low and irregular distribution of diatom microfossils in surface sediments, and thus microfossil records are scarce, rarely exceed the Holocene, and contain sparse information about past richness and taxonomic composition. These attributes make the Fram Strait an ideal study site to test the utility of sedimentary ancient DNA (sedaDNA) metabarcoding. Amplifying a short, partial rbcL marker from samples of sediment core MSM05/5-712-2 resulted in 95.7 % of our sequences being assigned to diatoms across 18 different families, with 38.6 % of them being resolved to species and 25.8 % to genus level. Independent replicates show a high similarity of PCR products, especially in the oldest samples. Diatom sedaDNA richness is highest in the Late Weichselian and lowest in Mid- and Late Holocene samples. Taxonomic composition is dominated by cold-water and sea-ice-associated diatoms and suggests several reorganisations – after the Last Glacial Maximum, after the Younger Dryas, and after the Early and after the Mid-Holocene. Different sequences assigned to, amongst others, Chaetoceros socialis indicate the detectability of intra-specific diversity using sedaDNA. We detect no clear pattern between our diatom sedaDNA record and the previously published IP25 record of this core, although proportions of pennate diatoms increase with higher IP25 concentrations and proportions of Nitzschia cf. frigida exceeding 2 % of the assemblage point towards past sea-ice presence

Zusammenhänge zwischen der Fähigkeit zur Perspektivenübernahme und dem Textverstehen im Vor- und Grundschulalter

"Im vorliegenden Beitrag wird der Zusammenhang zwischen der Fähigkeit zur Perspektivenübernahme und sinnverstehendem Lesen dargestellt. Auf der Grundlage von Arbeiten zum Textverstehen sowie zu Perspektivenübernahme und Theory of Mind wurde ein positiver Zusammenhang zwischen Perspektivenübernahmefähigkeit und Textverstehensleistung erwartet. Diese Hypothese wurde an zwei Stichproben unterschiedlichen Alters geprüft: In der ersten Studie beantworteten 37 Vorschulkinder Fragen zu vorgelesenen Geschichten sowie Perspektivenübernahme-Aufgaben. Zwischen den Bereichen fand sich eine deutliche positive Korrelation, die bei Kontrolle der Intelligenz erhalten blieb. An der zweiten Studie nahmen 69 Grundschulkinder der dritten Jahrgangsstufe teil, die Texte lasen und Aufgaben dazu wie auch zur Perspektivenübernahme bearbeiteten. In dieser Stichprobe fand sich der erwartete Zusammenhang ausschließlich in der Teilgruppe der guten Leser. Er blieb bei Kontrolle der Intelligenz erhalten. Die Ergebnisse werden auch in Hinblick auf die Förderung der Lesekompetenz diskutiert." (Autorenreferat)"Topic of the article is the relation between perspective taking and reading comprehension. Based on research regarding text, comprehension, perspective taking and theory of mind, the authors assume a positive correlation between perspective taking and text comprehension. This hypothesis is tested in two studies: In the first study, stories were read to 37 preschoolers (5-6 years). Afterwards, they answered questions regarding the text and perspective taking. Text comprehension and perspective taking were positively correlated, even if intelligence was controlled. In the second study, 69 primary school students (8-10 years) read several stories. Afterwards, they answered questions considering the texts and perspective taking. The hypothesized correlation between text comprehension and perspective taking was only found in the sub-sample of good readers. This correlation remained stable if intelligence was controlled. Among other consequences, perspective taking training is discussed as a method to improve reading literacy." (author's abstract

Diversity und Diversity Management in Berliner Unternehmen: im Fokus: Personen mit Migrationshintergrund ; Ergebnisse einer quantitativen und qualitativen empirischen Studie

"Das vorliegende Buch befasst sich mit der betrieblichen Integration von Personen mit Migrationshintergrund. Im Zentrum stehen die Ergebnisse einer telefonischen Befragung von Personalverantwortlichen in 500 Berliner Unternehmen sowie von 40 darauf aufbauenden Tiefen-Interviews mit verschiedenen betrieblichen Akteuren aus sechs Unternehmen, die zu Fallstudien verdichtet wurden. Damit wird aus Diversity-Perspektive beleuchtet, inwieweit sich die Vielfalt auf dem Berliner Arbeitsmarkt in der Personalstruktur der Unternehmen widerspiegelt und welcher personalpolitische Umgang damit verbunden ist. Auf der Basis der empirischen Befunde sowie weiterer Konzepte zur Förderung von Chancengleichheit werden zudem Ansatzpunkte für das Personalmanagement aufgezeigt: Durch eine entsprechende Organisationsanalyse kann der Handlungsbedarf ermittelt werden. Gezielte Maßnahmen können dann darauf hinwirken, dass die Vielfalt im Unternehmen erhöht wird, Personen mit Migrationshintergrund besser integriert und die Potenziale der Vielfalt genutzt werden." (Autorenreferat

Association between TAS2R38 gene polymorphisms and colorectal cancer risk

Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99-1.67; P(value) = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06-1.75; P(value) = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12-1.61; P(value) = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin

Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain

<p>Abstract</p> <p>Background</p> <p>Leukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, anti-bacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE) vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS)-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC) on complete Freund's adjuvant-induced inflammatory pain in rats.</p> <p>Results</p> <p>POMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin.</p> <p>Conclusion</p> <p>Although MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.</p

What is it about humanity that we can't give away to intelligent machines? A European perspective

One of the most significant recent technological developments concerns the development and implementation of ‘intelligent machines’ that draw on recent advances in artificial intelligence (AI) and robotics. However, there are growing tensions between human freedoms and machine controls. This article reports the findings of a workshop that investigated the application of the principles of human freedom throughout intelligent machine develop- ment and use. Forty IS researchers from ten different countries discussed four contemporary AI and humanity issues and the most relevant IS domain challenges. This article summarizes their experiences and opinions regarding four AI and humanity themes: Crime & conflict, Jobs, Attention, and Wellbeing. The outcomes of the workshop discussions identify three attributes of humanity that need preservation: a critique of the design and application of AI, and the intelligent machines it can create; human involvement in the loop of intelligent ma- chine decision-making processes; and the ability to interpret and explain intelligent machine decision-making processes. The article provides an agenda for future AI and humanity researchpublishedVersio

Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia

A mechanistic understanding of core cognitive processes, such as working memory, is crucial to addressing psychiatric symptoms in brain disorders. We propose a combined psychophysical and biophysical account of two symptomatologically related diseases, both linked to hypofunctional NMDARs: schizophrenia and autoimmune anti-NMDAR encephalitis. We first quantified shared working memory alterations in a delayed-response task. In both patient groups, we report a markedly reduced influence of previous stimuli on working memory contents, despite preserved memory precision. We then simulated this finding with NMDAR-dependent synaptic alterations in a microcircuit model of prefrontal cortex. Changes in cortical excitation destabilized within-trial memory maintenance and could not account for disrupted serial dependence in working memory. Rather, a quantitative fit between data and simulations supports alterations of an NMDAR-dependent memory mechanism operating on longer timescales, such as short-term potentiation

Regulatory feedback cycle of the insulin-degrading enzyme and the amyloid precursor protein intracellular domain: Implications for Alzheimer's disease

One of the major pathological hallmarks of Alzheimer´s disease (AD) is an accumulation of amyloid-β (Aβ) in brain tissue leading to formation of toxic oligomers and senile plaques. Under physiological conditions, a tightly balanced equilibrium between Aβ-production and -degradation is necessary to prevent pathological Aβ-accumulation. Here, we investigate the molecular mechanism how insulin-degrading enzyme (IDE), one of the major Aβ-degrading enzymes, is regulated and how amyloid precursor protein (APP) processing and Aβ-degradation is linked in a regulatory cycle to achieve this balance. In absence of Aβ-production caused by APP or Presenilin deficiency, IDE-mediated Aβ-degradation was decreased, accompanied by a decreased IDE activity, protein level, and expression. Similar results were obtained in cells only expressing a truncated APP, lacking the APP intracellular domain (AICD) suggesting that AICD promotes IDE expression. In return, APP overexpression mediated an increased IDE expression, comparable results were obtained with cells overexpressing C50, a truncated APP representing AICD. Beside these genetic approaches, also AICD peptide incubation and pharmacological inhibition of the γ-secretase preventing AICD production regulated IDE expression and promoter activity. By utilizing CRISPR/Cas9 APP and Presenilin knockout SH-SY5Y cells results were confirmed in a second cell line in addition to mouse embryonic fibroblasts. In vivo, IDE expression was decreased in mouse brains devoid of APP or AICD, which was in line with a significant correlation of APP expression level and IDE expression in human postmortem AD brains. Our results show a tight link between Aβ-production and Aβ-degradation forming a regulatory cycle in which AICD promotes Aβ-degradation via IDE and IDE itself limits its own production by degrading AICD

Development of the EORTC QLQ-CAX24, a questionnaire for cancer patients with cachexia

Context Cachexia is commonly found in cancer patients and has profound consequences; yet there is only one questionnaire that examines the patient's perspective. Objective To report a rigorously developed module for patient self-reported impact of cancer cachexia. Methods Module development followed published guidelines. Patients from across the cancer cachexia trajectory were included. In Phase 1, health-related quality of life (HRQOL) issues were generated from a literature review and interviews with patients in four countries. The issues were revised based on patient and health care professional (HCP) input. In Phase 2, questionnaire items were formulated and translated into the languages required for Phase 3, the pilot phase, in which patients from eight countries scored the relevance and importance of each item, and provided qualitative feedback. Results A total of 39 patients and 12 HCPs took part in Phase 1. The literature review produced 68 HRQOL issues, with 22 new issues arising from the patient interviews. After patient and HCP input, 44 issues were formulated into questionnaire items in Phase 2. One hundred ten patients took part in Phase 3. One item was reworded, and 20 items were deleted as a consequence of patient feedback. Conclusions The QLQ-CAX24 is a cancer cachexia-specific questionnaire, comprising 24 items, for HRQOL assessment in clinical trials and practice. It contains five multi-item scales (food aversion, eating and weight-loss worry, eating difficulties, loss of control, and physical decline) and four single items