Miracle-dz/UniFAR-FTUs huggingface dataset:
Aβ-accelerated neurodegeneration caused by Alzheimer’s-associated ACE variant R1279Q is rescued by angiotensin system inhibition in mice

Ace1 knockin mice have increased neuronal ACE1 and hippocampal neuron loss that is accelerated by Aβ and blocked by approved angiotensin pathway drugs. A rACE to beat Alzheimer’s disease Alzheimer’s disease (AD) has a strong genetic component and several genes have been associated with disease susceptibility, including the angiotensin-converting enzyme (ACE). Here, Cuddy et al. investigated the mechanistic link between ACE and AD using whole-genome sequencing databases and mouse models. The authors identified rare ACE variants associated with AD. They generated mice bearing a disease-associated mutation and showed increased neuronal ACE1 protein, neurodegeneration, and neuroinflammation with female animals developing a more severe phenotype. The variant accelerated disease development in a mouse model of AD and ACE inhibition rescued neuronal loss. The results suggest that ACE inhibitors might be effective in a subgroup of patients with AD. Recent genome-wide association studies identified the angiotensin-converting enzyme gene (ACE) as an Alzheimer’s disease (AD) risk locus. However, the pathogenic mechanism by which ACE causes AD is unknown. Using whole-genome sequencing, we identified rare ACE coding variants in AD families and investigated one, ACE1 R1279Q, in knockin (KI) mice. Similar to AD, ACE1 was increased in neurons, but not microglia or astrocytes, of KI brains, which became elevated further with age. Angiotensin II (angII) and angII receptor AT1R signaling were also increased in KI brains. Autosomal dominant neurodegeneration and neuroinflammation occurred with aging in KI hippocampus, which were absent in the cortex and cerebellum. Female KI mice exhibited greater hippocampal electroencephalograph disruption and memory impairment compared to males. ACE variant effects were more pronounced in female KI mice, suggesting a mechanism for higher AD risk in women. Hippocampal neurodegeneration was completely rescued by treatment with brain-penetrant drugs that inhibit ACE1 and AT1R. Although ACE variant-induced neurodegeneration did not depend on β-amyloid (Aβ) pathology, amyloidosis in 5XFAD mice crossed to KI mice accelerated neurodegeneration and neuroinflammation, whereas Aβ deposition was unchanged. KI mice had normal blood pressure and cerebrovascular functions. Our findings strongly suggest that increased ACE1/angII signaling causes aging-dependent, Aβ-accelerated selective hippocampal neuron vulnerability and female susceptibility, hallmarks of AD that have hitherto been enigmatic. We conclude that repurposed brain-penetrant ACE inhibitors and AT1R blockers may protect against AD.
Blockade of immune checkpoints in lymph nodes through locoregional delivery augments cancer immunotherapy

Anticancer therapeutic effects can be improved by directing immune checkpoint blockade antibodies to tumor-draining lymph nodes. Draining tumors with immunotherapy Immune checkpoint inhibitors have shown great promise against multiple types of cancer, but they are still not sufficiently effective to help many patients. Moreover, systemic administration of immune checkpoint blockade can cause severe immune side effects, which limit its use. To identify safer and more effective ways to administer immune checkpoint blockade, Francis et al. systematically compared different routes of administration, evaluating the accumulation of immune checkpoint antibodies in tumor-draining lymph nodes and in the tumors themselves. Locoregional treatment was both more effective and safer than systemic therapy in multiple mouse models of cancer, and intradermal delivery near the tumor was sufficient, without requiring direct intratumoral injection. Systemic administration of immune checkpoint blockade (ICB) monoclonal antibodies (mAbs) can unleash antitumor functions of T cells but is associated with variable response rates and off-target toxicities. We hypothesized that antitumor efficacy of ICB is limited by the minimal accumulation of mAb within tissues where antitumor immunity is elicited and regulated, which include the tumor microenvironment (TME) and secondary lymphoid tissues. In contrast to systemic administration, intratumoral and intradermal routes of administration resulted in higher mAb accumulation within both the TME and its draining lymph nodes (LNs) or LNs alone, respectively. The use of either locoregional administration route resulted in pronounced T cell responses from the ICB therapy, which developed in the secondary lymphoid tissues and TME of treated mice. Targeted delivery of mAb to tumor-draining lymph nodes (TdLNs) alone was associated with enhanced antitumor immunity and improved therapeutic effects compared to conventional systemic ICB therapy, and these effects were sustained at reduced mAb doses and comparable to those achieved by intratumoral administration. These data suggest that locoregional routes of administration of ICB mAb can augment ICB therapy by improving immunomodulation within TdLNs.
Improved Flavor Stability by Aging Beer in the Presence of Yeast

Unwanted flavor changes occur during beer storage. Because yeast has a large reducing activity on aging compounds, the aim of this study was to examine the effect of refermentation on flavor stability. It was shown that the addition of yeast to aged beer removed aged flavor almost completely. Furthermore, the addition of yeast to fresh beer decelerated beer aging considerably. Both a top-fermenting and a bottom-fermenting yeast strain were able to exert this effect, and it was clear that initiation of a real refermentation process by adding sugar was not required. Finally, several yeast concentrations were tested, and it appeared that even adding an amount as low as 10,000 yeast cells/mL was sufficient to slow beer aging. Nonetheless, the effect was more pronounced when higher concentrations were used.
Pollen Morphology and Plant Taxonomy. Angiosperms. (An Introduction to Palynology. I.)

The intensive study of pollen morphology has added a new dimension to angiosperm taxonomy, of particular value at the generic level. Dr. Erdtman is one of the foremost workers in this field and the publication under review, essentially a reprint of a monograph published in 1954, should be available to any taxonomist concerned with the Other CABI sites 
GEE4FLOOD: rapid mapping of flood areas using temporal Sentinel-1 SAR images with Google Earth Engine cloud platform

Abstract. The present state of the art technologies for flood mapping are typically tested on small geographical regions due to limitation of resources, which hinders the implementation of real-time flood management activities. We proposed a unified framework (GEE4FLOOD) for rapid flood mapping in Google Earth Engine (GEE) cloud platform. With the unexpected spells of extreme rainfall in August 2018, many parts of Kerala state in India experienced a major disastrous flood. Therefore, we tested the GEE4FLOOD processing chain on August 2018 Kerala flood event. GEE4FLOOD utilizes multitemporal Sentinel-1 synthetic aperture radar images available in GEE catalog and an automatic Otsu’s thresholding algorithm for flood mapping. It also utilizes other remote sensing datasets available in GEE catalog for permanent water body mask creation and result validation. The ground truth data collected during the Kerala flood indicates promising accuracy with 82% overall accuracy and 78.5% accuracy for flood class alone. In addition, the entire process from data fetching to flood map generation at a varying geographical extent (district to state level) took ∼2 to 4 min.
Response to Selfing in Seed Set, Seedling Establishment and Nursery Growth Based on Controlled Crosses of Abies nordmanniana Clones

Abstract Nordmann fir (Abies nordmanniana) is used for production of high value Christmas trees in short rotation. Potentially all trees are intended to be sold - no thinnings are normally applied. A high proportion of saleable trees per ha is the main key to secure economic return to the growers. Consumers demand a symmetric and rather uniform tree and, dependent on local traditions, it should be more or less dense and narrow. In Denmark, breeding of Nordmann fir and establishment of seed orchards focus on seed supply and improved Christmas tree quality - aiming at adaption and a rather uniform ideotype Christmas tree. Benefits from employing rather few clones, to maximise gain and uniformity, may potentially be counteracted by increased selfing. The objective of this study was to quantify the effect of selfing on percentage of filled seed and nursery establishment of seedlings. Inbreeding depression was seen for filled seeds (40%), growth traits (5-17%), plus mortality and axial damage (5-12 percent units). Many selfed seedlings survive and develop into marketable seedlings, although with a depression in numbers of 23-37%, or 9-12 percent units. Nursery sorting procedures can only partially reduce the number of inbred seedlings in Nordmann fir. The large variation among clones in the response to selfing indicates that knowledge of the behaviour of selfed progeny from specific clones in ‘small number seed orchards’ is of practical interest. Trade-offs between increased gain by selection of few clones and a penalty paid for increased inbreeding need further studies during a full Christmas tree rotation.
The impact of second language immersion: Evidence from a bi-directional longitudinal cross-linguistic study

Brice et al. (2019) presented data from the first epoch of a longitudinal study of the neurobiological underpinnings of first-language (L1) and second-language (L2) processing. Results showed a similar network of activation for reading across L1 and L2, as well as significant convergence of print and speech processing across a network of left-hemisphere regions in both L1 and L2 with greater activation and convergence for L2 in anterior regions, and greater activation and convergence for L1 in posterior regions of the reading network. Here, we present the first look at longitudinal changes in these effects. L2 showed relatively few changes in activation, with some shifts in the weighting between ventral and dorsal processing. L1, however, showed more widespread differences in processing, suggesting that the neurobiological footprint of reading is dynamic, with both L1 and L2 impacting each other. Print/speech convergence showed very little longitudinal change, suggesting that it is a stable marker of the differences in L1 and L2 processing.
A survey of proximal methods for monitoring leaf phenology in temperate deciduous forests

Tree phenology is a major driver of forest-atmosphere mass and energy exchanges. Yet tree phenology has historically not been recorded at flux measurement sites. Here, we used seasonal time-series of ground-based NDVI (Normalized Difference Vegetation Index), RGB camera GCC (Greenness Chromatic Coordinate), broad-band NDVI, LAI (Leaf Area Index), fAPAR (fraction of Absorbed Photosynthetic Active Radiation), CC (Canopy Closure), fRvis (fraction of Reflected Radiation) and GPP (Gross Primary Productivity) to predict six phenological markers detecting the start, middle and end of budburst and of leaf senescence in a temperate deciduous forest. We compared them to observations of budburst and leaf senescence achieved by field phenologists over a 13-year period. GCC, NDVI and CC captured very well the interannual variability of spring phenology (R2 > 0.80) and provided the best estimates of the observed budburst dates, with a mean absolute deviation (MAD) less than 4 days. For the CC and GCC methods, mid-amplitude (50%) threshold dates during spring phenological transition agreed well with the observed phenological dates. For the NDVI-based method, on average, the mean observed date coincides with the date when NDVI reaches 25% of its amplitude of annual variation. For the other methods, MAD ranges from 6 to 17 days. GPP provides the most biased estimates. During the leaf senescence stage, NDVI- and CC-derived dates correlated significantly with observed dates (R2 =0.63 and 0.80 for NDVI and CC, respectively), with MAD less than 7 days. Our results show that proximal sensing methods can be used to derive robust phenological indexes. They can be used to retrieve long-term phenological series at flux measurement sites and help interpret the interannual variability and decadal trends of mass and energy exchanges. Highlights We used 8 indirect methods to predict the timing of phenological events. GCC, NDVI and CC captured very well the interannual variation of spring phenology. GCC, NDVI and CC provided the best estimates of observed budburst dates. NDVI and CC derived-dates correlated with observed leaf senescence dates.
Assessment of nitrogen uptake and utilization in drought tolerant and Striga resistant tropical maize varieties

Maize (Zea mays L.) is an important food crop in the Guinea savannas of Nigeria. Despite its high production potential, drought, Striga hermonthica parasitsim, and poor soil fertility particularly nitrogen deficiency limit maize production in the savannas. Breeders at IITA have developed drought- and Striga-tolerant cultivars for testing, dissemination, and deployment in the region. Information on the response of these cultivars to N fertilization is, however, not available. This study evaluated grain yield, total N uptake (TNU), N uptake (NUPE), N utilization (NUTE), and N use efficiency (NUE) of selected maize cultivars along with a widely grown improved maize cultivar at two locations in the Guinea savannas of northern Nigeria. Maize grain yield increased with N application. The average grain yield of the maize cultivars was 76% higher at 30, 156% higher at 60, and 203% higher at 120 kg N ha−1 than at 0 kg N ha−1. This suggests that N is a limiting nutrient in the Nigerian savannas. Five drought-tolerant cultivars produced consistently higher yields when N was added at all levels. These cultivars had either high NUPE or NUTE confirming earlier reports that high N uptake or NUTE improves maize grain yield. The study also confirms earlier reports that maize cultivars that are selected for tolerance to drought are also efficient in uptake and use of N fertilizer. This means that these cultivars can be grown with application of less N fertilizer thereby reducing investment on fertilizers and reduction in environmental pollution.
Residue-by-residue analysis of cotranslational membrane protein integration in vivo

We follow the cotranslational biosynthesis of three multi-spanning E. coli inner membrane proteins in vivo using high-resolution Force Profile Analysis. The force profiles show that the nascent chain is subjected to rapidly varying pulling forces during translation, and reveal unexpected complexities in the membrane integration process. We find that an N-terminal cytoplasmic domains can fold in the ribosome exit tunnel before membrane integration starts, that charged residues and membrane-interacting segments such as re-entrant loops and surface helices flanking a transmembrane helix (TMH) can advance or delay membrane integration, and that point mutations in an upstream TMH can affect the pulling forces generated by downstream TMHs in a highly position-dependent manner, suggestive of residue-specific interactions between TMHs during the integration process.
The 4R Genome Duplication In Salmonine Fishes: Insights From Conserved Non-Coding Elements

Gene and genome duplications are essential processes in evolution. Salmonids are ideal animal model systems to study these processes, as they originated from a tetraploid ancestor. Conserved non-coding elements (CNEs) are of interest because of their highly conserved DNA consensus motifs spanning lineages as diverse and divergent as humans and fish. The main goal of this study is to test CNEs as a tool to study genome duplications and to revisit the “4R” hypothesis and phylogeny of Salmonine fishes (Salmonidae) Salmo salar, Salvelinus alpinus and Oncorhynchus mykiss through the study of copy number and nucleotide variation in six pairs of CNEs. Allele numbers for most CNE sequence pairs are consistent with the 4R hypothesis, as is the symmetric phylogenetic topology shown by some CNE pairs; the estimated date of CNE duplication is consistent with the only reported range of 25-100Mya. However, the phylogenetic relationships within Salmoninae remain unresolved.
Sequence dependence of biomolecular phase separation

Cells are home to a wide variety of biomolecular condensates - phase-separated droplets that lack a membrane. In addition to nonspecific interactions, phase separation depends on specific binding motifs between constituent molecules. Nevertheless, few rules have been established on how these specific, heterotypic interactions drive phase separation. Using lattice-polymer simulations and mean-field theory, we show that the sequence of binding motifs strongly affects a polymer’s ability to phase separate, influencing both phase boundaries and condensate properties (e.g. viscosity and polymer diffusion). We find that sequences with large blocks of a single motif typically form more inter-polymer bonds which promote phase separation. Notably, the sequence of binding motifs influences phase separation primarily by determining the conformational entropy of self-bonding by single polymers. This contrasts with systems where the molecular architecture primarily affects the energy of the dense phase, providing a new entropy-based mechanism for the biological control of phase separation.
Role of the SUT1 and SUT2 sugar transporters during stolbur phytoplasma infection in tomato

Phytoplasmas inhabit phloem sieve elements and cause abnormal growth and altered sugar partitioning. But how they interact with phloem functions is not clearly known. The phloem responses were investigated in tomato infected by ‘Candidatus Phytoplasma solani’, at the beginning of the symptomatic stage of infection, both in symptomatic and asymptomatic leaves, the first symptoms appearing in the sink top leaf at the stem apex. Antisense lines impaired in the phloem sucrose transporters SUT1 and SUT2 were included. The infection in source leaves was not associated with symptoms. In the symptomatic, sink leaf, yellowing and leaf curling was associated with higher starch accumulation and expression of defense genes. The transcriptional analysis of symptomatic leaf midribs indicated that transcript levels for genes acting in the glycolysis and peroxisome metabolism in infected plants differed from these in non-infected plants. Phytoplasma multiplied actively in at least three additional lower leaves although they were symptomless, with no sign of activation of defense markers, although the rate of exudation of sucrose from these symptomless, source leaves was lower for infected plants. A few metabolites in phloem-enriched exudate were affected by the infection, such as glycolate and aspartate, and some of them were also affected in the control SUT1- and SUT2- antisense lines, in which sucrose retrieval or release in the sieve elements are impaired. A metabolic switch could explain the delivery of more glycolate into the sieve elements of infected plants. The findings suggest a link between sugar transport and redox homeostasis. One sentence summary An impairment of sucrose retrieval and release in the sieve elements occurs during phytoplasma infection, associated with changes in sugar and peroxisome metabolism
Control of helical navigation by three-dimensional flagellar beating

Helical swimming is a ubiquitous strategy for motile cells to generate self-gradients for environmental sensing. The model biflagellate Chlamydomonas reinhardtii rotates at a constant 1 – 2 Hz as it swims, but the mechanism is unclear. Here, we show unequivocally that the rolling motion derives from a persistent, non-planar flagellar beat pattern. This is revealed by high-speed imaging and micromanipulation of live cells. We construct a fully-3D model to relate flagellar beating directly to the free-swimming trajectories. For realistic geometries, the model reproduces both the sense and magnitude of the axial rotation of live cells. We show that helical swimming requires further symmetry-breaking between the two flagella. These functional differences underlie all tactic responses, particularly phototaxis. We propose a control strategy by which cells steer towards or away from light by modulating the sign of biflagellar dominance.
Profertility effects of aqueous leaf extract of Telfairia occidentalis in adult male Wistar rats

Telfairia occidentalis is a leafy vegetable consumed commonly for its nutritional and medicinal effects. However, few studies have been carried out on its fertility effects in males with most of such studies offering conflicting results. The present study evaluated the effects of aqueous extract of the leaves of T. occidentalis on male fertility in adult wistar rats. The thirty rats used for this study were randomized into groups A, B and C. Rats in groups B & C were treated with 500 and 1000mg/kg.bwt of the leaf extract respectively by gavage for 56 days while group A served as control. The sperm characteristics, male hypothalamo-pituitary gonadal axis hormones and histological studies were carried out according to existing laboratory methods. Results from all the parameters studied showed that the aqueous extract of leaves of T. occidentalis exhibited profertility properties in adult male wistar rats. Further research to determine the components of the leaf extract implicated in the outcomes observed and the mechanism of action would be necessary. Keywords: Profertility, Telfairia occidentali s, Wistar rats
Genome-wide analyses point to differences in genetic architecture of BMI between tall and short people

To examine differences in the genetic architecture of BMI between tall and short people, we conducted genome-wide and follow-up analyses using UK Biobank data. We identify 57 loci as height-specific, detect differences in SNP-based heritability between tall and short people and show how genetic correlations between the two rises during the lifespan. Using phenome-wide analyses (PHEWAS), a significant association between a short people-specific locus on MC4R and energy portion size was detected. We identify one locus (GPC5-GPC6) with different effect directions on BMI in short and tall people. PHEWAS indicates this locus is associated with bone mineral density. Transcriptome-wide analyses hint that genes differentially associated with BMI in short vs tall people are enriched in brain tissue. Our findings highlight the role of height in the genetic underpinnings of BMI, provide biological insight into mechanisms underlying height-dependent differences in BMI and show that in short and tall people obesity is a risk factor that differentially increases susceptibility for disease.
Both adaptive immunity and IL-1R1 dependent signals improve clearance of cytosolic virulent mycobacteria in vivo

Mycobacterium tuberculosis infections claim more than a million lives each year and better treatments or vaccines are required. A crucial pathogenicity factor is translocation from the phago-lysosomes to the cytosol upon phagocytosis by macrophages. The translocation from the phago-lysosome into the cytosol is an ESX-1 dependent process as previously shown in vitro. Here we show that in vivo, mycobacteria also translocate to the cytosol but mainly when host immunity is compromised. We observed only low numbers of cytosolic bacilli in mice, armadillo, zebrafish and patient material infected with M. tuberculosis, M. marinum or M. leprae. In contrast, when innate or adaptive immunity was compromised, as in SCID or IL-1R1 deficient mice, a significant number of cytosolic M. tuberculosis bacilli were detected in lungs of infected mice. Taken together, the cytosolic localization of mycobacteria in vivo is controlled by adaptive immune responses as well as IL-1R1-mediated host resistance to M. tuberculosis.