julilili42/papers huggingface dataset:
Changing Functional Signatures of Microglia along the Axis of Brain Aging
2021-01-22

Microglia, the innate immune cells of the brain, are commonly perceived as resident macrophages of the central nervous system (CNS). This definition, however, requires further specification, as under healthy homeostatic conditions, neither morphological nor functional properties of microglia mirror those of classical macrophages. Indeed, microglia adapt exceptionally well to their microenvironment, becoming a legitimate member of the cellular brain architecture. The ramified or surveillant microglia in the young adult brain are characterized by specific morphology (small cell body and long, thin motile processes) and physiology (a unique pattern of Ca2+ signaling, responsiveness to various neurotransmitters and hormones, in addition to classic “immune” stimuli). Their numerous physiological functions far exceed and complement their immune capabilities. As the brain ages, the respective changes in the microglial microenvironment impact the functional properties of microglia, triggering further rounds of adaptation. In this review, we discuss the recent data showing how functional properties of microglia adapt to age-related changes in brain parenchyma in a sex-specific manner, with a specific focus on early changes occurring at middle age as well as some strategies counteracting the aging of microglia.
Interpreting gaps: A geoarchaeological point of view on the Gravettian record of Ach and Lone valleys (Swabian Jura, SW Germany)
2021-01-22

Unlike other Upper Paleolithic industries, Gravettian assemblages from the Swabian Jura are documented solely in the Ach Valley (35-30 Kcal BP). On the other hand, traces of contemporaneous occupations in the nearby Lone Valley are sparse. It is debated whether this gap is due to a phase of human depopulation, or taphonomic issues related with landscape changes.&#13;\\n&#13;\\nIn this paper we present ERT, EC-logging and GPR data showing that in both Ach and Lone valleys sediments and archaeological materials eroded from caves and deposited above river incisions after 37-32 Kcal BP. We argued that the rate of cave erosion was higher after phases of downcutting, when hillside erosion was more intensive. To investigate on the causes responsible for the dearth of Gravettian materials in the Lone Valley we test two alternative hypotheses: i) Gravettian humans occupied less intensively this part of the Swabian Jura. ii) Erosion of cave deposits did not occur at the same time in the two valleys. We conclude that the second hypothesis is most likely. Ages from the Lone Valley show increasing multimillennial gaps between 36 and 18 Kcal BP, while a similar gap is present in the Ach Valley between 28 and 16 Kcal BP. Based on geoarchaeological data from previous studies and presented in this paper, we interpreted these gaps in radiocarbon data as indicating of cave erosion. Furthermore, we argued that the time difference across the two valleys show that the erosion of cave deposits began and terminated earlier in the Lone Valley, resulting in a more intensive removal of Gravettian-aged deposits. The hypothesis that cave erosion was triggered by regional landscape changes seems to be supported by geochronological data from the Danube Valley, which show that terrace formation at the end of the Pleistocene moved westwards throughout southern Germany with a time lag of few millennia.
Fluorescent detection of PARP activity in unfixed tissue
2021-01-22

Poly-ADP-ribose-polymerase (PARP) relates to a family of enzymes that can detect DNA breaks and initiate DNA repair. While this activity is generally seen as promoting cell survival, PARP enzymes are also known to be involved in cell death in numerous pathologies, including in inherited retinal degeneration. This ambiguous role of PARP makes it attractive to have a simple and fast enzyme activity assay, that allows resolving its enzymatic activity in situ , in individual cells, within complex tissues. A previously published two-step PARP activity assay uses biotinylated NAD + and streptavidin labelling for this purpose. Here, we used the fluorescent NAD + analogues ε-NAD + and 6-Fluo-10-NAD + to assess PARP activity directly on unfixed tissue sections obtained from wild-type and retinal degeneration-1 ( rd1 ) mutant retina. In standard UV microscopy ε-NAD + incubation did not reveal PARP specific signal. In contrast, 6-Fluo-10-NAD + resulted in reliable detection of in situ PARP activity in rd1 retina, especially in the degenerating photoreceptor cells. When the 6-Fluo-10-NAD + based PARP activity assay was performed in the presence of the PARP specific inhibitor olaparib, the activity signal was completely abolished, attesting to the specificity of the assay. The incubation of live organotypic retinal explant cultures with 6-Fluo-10-NAD + , did not produce PARP specific signal, indicating that the fluorescent marker may not be sufficiently membrane-permeable to label living cells. In summary, we present a new, rapid, and simple to use fluorescence assay for the cellular resolution of PARP activity on unfixed tissue, for instance in complex neuronal tissues such as the retina.
Nickel Hydride Catalyzed Cleavage of Allyl Ethers Induced by Isomerization
2021-01-22

Abstract This report discloses the deallylation of O- and N-allyl functional groups by using a combination of a Ni-H precatalyst and excess Brønsted acid. Key steps are the isomerization of the O- or N-allyl group through Ni-catalyzed double-bond migration followed by Brønsted acid induced O/N–C bond hydrolysis. A variety of functional groups are tolerated in this protocol, highlighting its synthetic value.
Paid parental leave and fathers’ involvement: capturing fathers’ gender beliefs and fathering perceptions
2021-01-22

This study examines how multidimensional gender and fathering beliefs of fathers may explain their relative involvement in childcare after considering paid leave uptake. We draw on cross-sectional survey data from one German state, which allow us to distinguish three belief dimensions: (1) gender traditionalism and essentialism, (2) fathering attitudes, and (3) fathering self-concepts and self-efficacy. By means of multiple linear regression models we investigate how the different dimensions of gender and fatherhood beliefs relate to fathers’ relative involvement in basic and indirect childcare tasks. Our results show that gender (essentialist) ideologies and fatherhood attitudes were strongly associated with fathers’ relative involvement in both childcare domains. The higher fathers perceived self-efficacy in fathering, the more involved they were in basic but not indirect care. All belief dimensions mediated the positive association of fathers’ uptake of paid leave with their involvement in basic childcare.
Detection and Characterization of Phosphorylation, Glycosylation, and Fatty Acid Bound to Fetuin A in Human Blood
2021-01-22

The hepatokine fetuin A (Fet A) has been associated with diverse pathological states such as insulin resistance, type 2 diabetes, macrovascular disease, and systemic ectopic and vascular calcification. Fet A may also play a role in tumor growth and metastasis. The biological activity of Fet A may be affected by various modifications, including phosphorylation, O- and N-glycosylation and fatty acid binding. We developed an antibody-based assay for the detection of Fet A phosphorylated at serine 312. Fatty acid pattern was determined by gas chromatography. Using the antibody, we found that the phosphorylation was stable in human plasma or serum at room temperature for 8 h. We observed that Fet A is present in several glycosylation forms in human plasma, but the extent of Ser312 phosphorylation was not associated with glycosylation. The phosphorylation pattern did not change during an oral glucose tolerance test (0–120 min). We further found that human Fet A binds preferentially saturated fatty acids (&gt;90%) at the expense of mono- and poly-unsaturated fatty acids. Our results indicate that different molecular species of Fet A are present in human plasma and that these different modifications may determine the different biological effects of Fet A.
Exercise Therapy Teamwork in German Rehabilitation Settings: Results of a National Survey Using Mixed Methods Design
2021-01-22

A key prerequisite for implementing biopsychosocial exercise therapy concepts as parts of multimodal rehabilitation programs is interprofessional teamwork. Based on a nationwide survey of exercise therapy using a mixed methods design, it is of interest to determine to what extent there are links between team-related processes (e.g., interprofessional exchange) and structural features of the exercise therapy departments (e.g., department size) and the individual rating of interprofessional teamwork. The first part of the study involved a questionnaire-based survey, where exercise therapy heads of 1146 rehabilitation facilities were contacted. In the second part of the study, 58 exercise therapy heads held discussions in six focus groups. The results from both parts showed that interprofessional teamwork was rated positively overall. Team meetings were seen as the central platform for exchange. However, particularly in larger facilities, the hierarchical position of medical management and lacking resources were negatively associated with interprofessional exchange. The results affirm empirically that a more binding provision of adequate structural and organizational conditions, such as sufficient time slots for liaising on content, are essential for effective teamwork. This would facilitate and improve the promotion of physical activity in multimodal rehabilitation programs.
New distributional data for the Mediterranean medicinal leech Hirudo verbana Carena, 1820 (Hirudinea, Hirudinidae) in Italy, with a note on its feeding on amphibians
2021-01-22

Scarce data are currently available about the distribution of the Mediterranean medicinal leech Hirudo verbana in Italy, and most of the known occurrence localities are based on records collected in the nineteenth and the first half of the twentieth century, which were not confirmed in the last decades, mostly due to a lack of surveys. Accordingly, the available knowledge on the distribution of the species is far from being updated and representative, although a significant negative trend of H. verbana throughout the country is supposed. The lack of sound distribution data is a significant shortfall, which hinders the implementation of the monitoring of the species as required by the Article 17 of the “Habitats Directive” on the species of Union concern. To provide recent, validated distributional data for the Mediterranean medicinal leech in Italy to be used as baseline data for further surveys and monitoring, we present herein a set of unpublished observations collected in the last decades in peninsular Italy, Sicily, and Sardinia. Moreover, we report observation of H. verbana feeding on amphibians, a feeding habit to date poorly documented for the Mediterranean medicinal leech. Based on both published and novel data, H. verbana is characterised by a large but fragmented distribution in Italy. Therefore, dedicated monitoring programs and the collection of validated occasional observations are highly desirable to get a clearer picture of the real distribution of the species.
Identification of the Triticoid-type grains (Poaceae) from archaeobotanical assemblages in southwest Asia as Heteranthelium piliferum (Banks & Sol.) Hochst.
2021-01-22

Abstract The so-called Triticoid-type grains are known from several prehistoric sites in southwest Asia and their identification has long been unclear. They resemble the grains of wheats and researchers suggested they may represent an extinct Triticeae species, possibly closely related to wild crop progenitors. In this study we identify the Triticoid-type grains as Heteranthelium piliferum (Banks &amp; Sol.) Hochst. and describe the key identification criteria. The identification is based on morphological analyses of modern and archaeological material from several grass species and was first achieved with well-preserved specimens from Early Neolithic Chogha Golan, Iran. We further examined the Triticoid-type grains from recently excavated samples from Early Neolithic Ganj Dareh, Iran, and archived samples from Late Chalcolithic and Late Bronze Age Tell Brak in northeast Syria, confirming their identification as H. piliferum . Based on the study of herbarium specimens at Royal Botanic Gardens Kew, London, we provide a detailed distribution map and review the species’ biology and ecological adaptations. Collected and cultivated herbarium specimens were analysed in order to understand the high phenotypic plasticity of the growth habit, its correlation with environmental variables and its relation to grain size. In order to understand the high morphological variability of the charred Triticoid-type grains from archaeological deposits, we assessed the effects of experimental carbonisation at different temperatures on grains of H. piliferum , Triticum dicoccum , T. thaoudar and Secale vavilovii . In light of the present study, we discuss the relevance of H. piliferum for reconstructing prehistoric subsistence strategies.
Understanding and assessing flood risk in Vietnam: Current status, persisting gaps, and future directions
2021-01-23

Abstract Vietnam is exposed to different types of floods that cause severe economic losses, damage to infrastructure, and loss of life. Reliable information on the drivers, patterns and dynamics of flood risk is crucial for the identification, prioritization and planning of risk reduction and adaptation measures. Here, we present a systematic review of existing flood risk assessments in Vietnam. We evaluate the current status, persisting gaps, and challenges regarding the understanding and assessment of flood risk in the country. The literature review revealed that: (i) 65 % of the reviewed papers did not provide a clear definition of flood risk, (ii) assessments had a tendency to prioritize physical and environmental drivers of risk over social, economic or governance‐related drivers, (iii) future‐oriented assessments tended to focus on hazard and exposure trends, while vulnerability scenarios were often lacking, (iv) large and middle‐sized cities were assessed more frequently than others, (v) only few studies engaged with relevant local stakeholders for the assessment of risk and the development of potential solutions, and (vi) ecosystem‐based adaptation and flood risk insurance solutions were rarely considered. Based on these findings, we point out several directions for future research on flood risk in Vietnam.
Annihilating dark matter search with 12 yr of Fermi LAT data in nearby galaxy clusters
2021-01-23

ABSTRACT Galaxy clusters are the largest virialized objects in the Universe and, as such, have high dark matter (DM) concentrations. This abundance of dark matter makes them promising targets for indirect DM searches. Here we report the details of a search, utilizing almost 12 yr of Fermi/LAT data, for gamma-ray signatures from the pair annihilation of WIMP dark matter in the GeV energy band. From this, we present the constraints on the annihilation cross-section for the , W+W−, and γγ channels, derived from the non-detection of a characteristic signal from five nearby, high Galactic latitude, galaxy clusters (Centaurus, Coma, Virgo, Perseus, and Fornax). We discuss the potential of a boost to the signal due to the presence of substructures in the DM haloes of selected objects, as well as the impact of uncertainties in DM profiles on the presented results. We assert that the obtained limits are, within a small factor, comparable to the best available limits of those based on Fermi/LAT observations of dwarf spheroidal galaxies.
Acid sphingomyelinase promotes SGK1-dependent vascular calcification
2021-01-23

Abstract In chronic kidney disease (CKD), hyperphosphatemia is a key factor promoting medial vascular calcification, a common complication associated with cardiovascular events and high mortality. Vascular calcification involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs), but the complex signaling events inducing pro-calcific pathways are incompletely understood. The present study investigated the role of acid sphingomyelinase (ASM)/ceramide as regulator of VSMC calcification. In vitro, both, bacterial sphingomyelinase and phosphate increased ceramide levels in VSMCs. Bacterial sphingomyelinase as well as ceramide supplementation stimulated osteo-/chondrogenic transdifferentiation during control and high phosphate conditions and augmented phosphate-induced calcification of VSMCs. Silencing of serum- and glucocorticoid-inducible kinase 1 (SGK1) blunted the pro-calcific effects of bacterial sphingomyelinase or ceramide. Asm deficiency blunted vascular calcification in a cholecalciferol-overload mouse model and ex vivo isolated-perfused arteries. In addition, Asm deficiency suppressed phosphate-induced osteo-/chondrogenic signaling and calcification of cultured VSMCs. Treatment with the functional ASM inhibitors amitriptyline or fendiline strongly blunted pro-calcific signaling pathways in vitro and in vivo. In conclusion, ASM/ceramide is a critical upstream regulator of vascular calcification, at least partly, through SGK1-dependent signaling. Thus, ASM inhibition by repurposing functional ASM inhibitors to reduce the progression of vascular calcification during CKD warrants further study.
Formal Semisynthesis of Demethylgorgosterol Utilizing a Stereoselective Intermolecular Cyclopropanation Reaction
2021-01-23

Abstract In this study, we report a convenient and high yielding formal semisynthesis of demethylgorgosterol, a marine steroid with an intriguing sidechain containing a cyclopropane unit. This was achieved through the synthesis of an advanced ketone intermediate. The synthetic route features a total of ten steps, starting from commercially available stigmasterol, with an overall yield of 27 %. The key step was a stereoselective intermolecular cyclopropanation reaction. This reaction proceeded in 82 % yield, the resulting cyclopropane carboxylic ester shows a trans/cis ratio of 89 : 11, with a diastereomeric ratio for the trans‐diastereomers of &gt;99 : 1. A reduction/oxidation sequence afforded the corresponding aldehyde, which was used in a Grignard reaction. A final oxidation step then yielded the desired ketone. This novel route presents a platform to further investigate the medicinal applications of gorgosterol‐type steroids and to fully understand their role in coral symbiosis.
The longevity gene mIndy (I’m Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms
2021-01-24

Reduced expression of the plasma membrane citrate transporter INDY (acronym I'm Not Dead, Yet) extends life span in lower organisms. Deletion of the mammalian Indy (mIndy) gene in rodents improves metabolism via mechanisms akin to caloric restriction, known to lower blood pressure (BP) by sympathoadrenal inhibition. We hypothesized that mIndy deletion attenuates sympathoadrenal support of BP. Continuous arterial BP and heart rate (HR) were reduced in mINDY-KO mice. Concomitantly, urinary catecholamine content was lower, and the decreases in BP and HR by mIndy deletion were attenuated after autonomic ganglionic blockade. Catecholamine biosynthesis pathways were reduced in mINDY-KO adrenals using unbiased microarray analysis. Citrate, the main mINDY substrate, increased catecholamine content in pheochromocytoma cells, while pharmacological inhibition of citrate uptake blunted the effect. Our data suggest that deletion of mIndy reduces sympathoadrenal support of BP and HR by attenuating catecholamine biosynthesis. Deletion of mIndy recapitulates beneficial cardiovascular and metabolic responses to caloric restriction, making it an attractive therapeutic target.
Targeting OCT3 attenuates doxorubicin-induced cardiac injury
2021-01-25

Significance Understanding the initiating mechanisms of cardiac injury associated with doxorubicin is fundamental to the development of novel preventative strategies. Evidence suggests that expression of membrane transporters contributes to the initial accumulation of doxorubicin in cardiomyocytes and, subsequently, cellular injury. Using patient-derived cardiomyocytes, we identified a candidate membrane transporter contributing to this debilitating phenotype and performed validation studies using engineered cell-based and animal models to demonstrate that targeting this transport mechanism can afford cardio-protection without compromising the anticancer properties of doxorubicin. Our findings provide insights that addresses an unmet therapeutic need in cancer patients receiving doxorubicin-based treatment.
Outcome of pregnancies with recent primary cytomegalovirus infection in first trimester treated with hyperimmunoglobulin: observational study
2021-01-25

ABSTRACT Objective To examine the efficacy of hyperimmunoglobulin (HIG) treatment in women with a recent primary cytomegalovirus (CMV) infection up to 14 weeks' gestation. Methods This is an ongoing observational study conducted at the prenatal medicine departments of the University Hospitals of Tübingen, Bonn, Cologne and Erlangen, Germany, as well as at the Laboratory Prof. Gisela Enders and Colleagues in Stuttgart, Germany and the Institute for Medical Virology at the University of Tübingen, Tübingen, Germany. Enrolment criteria were the presence of confirmed recent primary CMV infection in the first trimester and a gestational age at first HIG administration of ≤ 14 weeks. The following inclusion criteria indicated a recent primary infection: low anti‐immunoglobulin (Ig)‐G levels, low anti‐CMV‐IgG avidity in the presence of a positive CMV‐IgM test and no positive reactivity or just seroconversion anti‐gB2‐IgG‐reactivity. HIG administration was started as soon as possible within a few days after the first visit. HIG was administered intravenously at a dose of 200 IU/kg maternal body weight and repeated every 2 weeks until about 18 weeks' gestation. The primary outcome was maternal–fetal transmission at the time of amniocentesis. Multivariate logistic regression analysis was used to determine significant covariates that could predict maternal–fetal transmission. Results We included 149 pregnancies (153 fetuses) that completed the treatment. Median maternal age and weight were 32.0 years and 65.0 kg, respectively. Median gestational age at the time of first referral to one of the four centers was 9.4 weeks. Median anti‐CMV‐IgG level, anti‐CMV‐IgM index and CMV‐IgG avidity were 5.7 U/mL, 2.5 and 22.3%, respectively. HIG treatment was started at a median gestational age of 10.6 weeks and ended at a median of 17.9 weeks. Within this time frame, HIG was administered on average four times in each patient. Amniocentesis was carried out at a median gestational age of 20.4 weeks. In 143 (93.5%) of the 153 cases, the fetus was not infected. Maternal–fetal transmission occurred in 10 cases (6.5% (95% CI, 3.2–11.7%)). On uni‐ and multivariate logistic regression analysis, the level of anti‐IgM index was the only factor associated significantly with maternal–fetal transmission at amniocentesis. However, only four (40.0%) of the 10 cases with maternal–fetal transmission had an anti‐IgM index above 11.4, which corresponds to the 95 th centile of pregnancies without transmission. Conclusions HIG is a treatment option to prevent maternal–fetal transmission in pregnancy with a primary CMV infection. However, HIG treatment seems to be beneficial primarily in women with a recent primary infection in the first trimester or during the periconceptional period, and when it is administered at a biweekly dose of 200 IU/kg. © 2021 The Authors. Ultrasound in Obstetrics &amp; Gynecology published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.