bluuebunny/crossref_metadata_2025 huggingface dataset:
The increasing role of muscle MRI to monitor changes over time in untreated and treated muscle diseases
Authors: Nuñez-Peralta Claudia , Alonso-Pérez Jorge , Díaz-Manera Jordi
Published: August 2020

Purpose of review

This review aims to discuss the recent results of studies published applying quantitative MRI sequences to large cohorts of patients with neuromuscular diseases.

Recent findings

Quantitative MRI sequences are now available to identify and quantify changes in muscle water and fat content. These two components have been associated with acute and chronic injuries, respectively. Studies show that the increase in muscle water is not only reversible if therapies are applied successfully but can also predict fat replacement in neurodegenerative diseases. Muscle fat fraction correlates with muscle function tests and increases gradually over time in parallel with the functional decline of patients with neuromuscular diseases. There are new spectrometry-based sequences to quantify other components, such as glycogen, electrolytes or the pH of the muscle fibre, extending the applicability of MRI to the study of several processes in neuromuscular diseases.

The latest results obtained from the study of long cohorts of patients with various neuromuscular diseases open the door to the use of this technology in clinical trials, which would make it possible to obtain a new measure for assessing the effectiveness of new treatments. The challenge is currently the popularization of these studies and their application to the monitoring of patients in the daily clinic.
Climate change mitigation as a co-benefit of regenerative ranching: insights from Australia and the United States
Authors: Gosnell Hannah , Charnley Susan , Stanley Paige
Published: August 2020

‘Managed grazing’ is gaining attention for its potential to contribute to climate change mitigation by reducing bare ground and promoting perennialization, thereby enhancing soil carbon sequestration (SCS). Understanding why ranchers adopt managed grazing is key to developing the right incentives. In this paper, we explore principles and practices associated with the larger enterprise of ‘regenerative ranching’ (RR), which includes managed grazing but infuses the practice with holistic decision-making. We argue that this broader approach is appealing due to a suite of ecological, economic and social benefits, making climate change mitigation an afterthought, or ‘co-benefit’. RR is challenging, however, because it requires a deep understanding of ecological processes along with a set of skills related to monitoring and moving livestock and feeding the soil microbiome. We review the literature regarding links between RR and SCS, then present results of qualitative research focused on motivators, enablers and constraints associated with RR, drawing on interviews with 52 practitioners in New South Wales, Australia and the western United States. Our analysis is guided by a conceptual model of the social–ecological system associated with RR that identifies determinants of regenerative potential. We discuss implications for rancher engagement and conclude with a consideration of leverage points for global scalability.
Flavobacterium ichthyis sp. nov., isolated from a fish pond
Authors: Chen Wen-Ming , Yang Che-Chia , Sheu Ceshing , Kwon Soon-Wo , Sheu Shih-Yi
Published: August 2020

Bacterial strain NST-5T, isolated from a fish pond in Taiwan, was characterized using a polyphasic taxonomy approach. Results of phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that strain NST-5T formed a phylogenetic lineage in the genus

Flavobacterium

. Analysis of 16S rRNA gene sequences showed that strain NST-5T showed the highest similarity to

Flavobacterium enshiense

DK69T (94.9 %),

Flavobacterium ahnfeltiae

10Alg 130T (94.8 %) and

Flavobacterium vireti

THG-SM1T (94.8 %). Strain NST-5T showed 68.9–72.5% average nucleotide identity and 19.1–23.7% digital DNA–DNA hybridization identity with the type strains of other close related

Flavobacterium

species. Cells of the strain were Gram-stain-negative, strictly aerobic, motile by gliding, rod-shaped and formed yellow colonies. Optimal growth occurred at 30 °C, pH 7 and with 0.5% NaCl. Strain NST-5T contained iso-C15:0, C15:0 and iso-C16:0 as the predominant fatty acids. The major hydroxyl fatty acids were iso-C16:0 3-OH and iso-C17:0 3-OH. The polar lipid profile consisted of phosphatidylethanolamine, three uncharacterized aminophospholipids, two uncharacterized phospholipids and one uncharacterized aminolipid. The major polyamine was homospermidine. The major isoprenoid quinone was MK-6. The DNA G+C content of the genomic DNA was 35.5 mol%. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain NST-5T should be classified as a novel species of the genus

Flavobacterium

, for which the name Flavobacterium ichthyis sp. nov. is proposed. The type strain is NST-5T (=BCRC 81198T=LMG 31341T).
Quality and antioxidant properties of wheat cookies supplemented with
pak choi powder
Authors: Lee Jun Ho
Published: August 2020

The replacing effect of pak choi powder (PCP) on the quality characteristics and
antioxidant activities of wheat cookies was investigated in order to develop
functionally and nutritionally improved food. The incorporation of PCP to wheat
flour significantly affected the physicochemical properties of the cookie dough
and cookies. Increased levels of incorporation remarkably increased the density
of the cookie dough and the hardness of the cookies but decreased the cookie
spread and loss rate. The L* and b* color values of the cookie
surface significantly decreased while the a* value increased as a result
of increase of PCP substitution (p<0.05). The
2,2-diphenyl-1-picrylhydrazyl (DPPH) and
2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical
scavenging activities significantly increased (p<0.05) with increase of
PCP substitution in a well-correlated manner. Hedonic sensory testing revealed
that cookies supplemented with 2% PCP received satisfactory and
acceptable preference scores. Overall, cookies with acceptable physical
characteristics and superior antioxidant activities can be produced by partially
replacing wheat flour with 2% PCP.
Production of Trimeric SARS-CoV-2 Spike Protein by CHO Cells for Serological COVID-19 Testing
Authors: Johari Yusuf B. , Jaffé Stephen R.P. , Scarrott Joseph M. , Johnson Abayomi O. , Mozzanino Théo , Pohle Thilo H. , Maisuria Sheetal , Bhayat-Cammack Amina , Brown Adam J. , Tee Kang Lan , Jackson Philip J. , Wong Tuck Seng , Dickman Mark J. , Sargur Ravishankar , James David C.
Published: August 2020

We describe scalable and cost-efficient production of full length, His-tagged SARS-CoV-2 spike glycoprotein trimer by CHO cells that can be used to detect SARS-CoV-2 antibodies in patient sera at high specificity and sensitivity. Transient production of spike in both HEK and CHO cells mediated by PEI was increased significantly (up to 10.9-fold) by a reduction in culture temperature to 32°C to permit extended duration cultures. Based on these data GS-CHO pools stably producing spike trimer under the control of a strong synthetic promoter were cultured in hypothermic conditions with combinations of bioactive small molecules to increase yield of purified spike product 4.9-fold to 53 mg/L. Purification of recombinant spike by Nichelate affinity chromatography initially yielded a variety of co-eluting protein impurities identified as host cell derived by mass spectrometry, which were separated from spike trimer using a modified imidazole gradient elution. Purified CHO spike trimer antigen was used in ELISA format to detect IgG antibodies against SARS-CoV-2 in sera from patient cohorts previously tested for viral infection by PCR, including those who had displayed COVID-19 symptoms. The antibody assay, validated to ISO 15189 Medical Laboratories standards, exhibited a specificity of 100% and sensitivity of 92.3%. Our data show that CHO cells are a suitable host for the production of larger quantities of recombinant SARS-CoV-2 trimer which can be used as antigen for mass serological testing.
ApharSeq: An Extraction-free Early-Pooling Protocol for Massively Multiplexed SARS-CoV-2 Detection
Authors: Chappleboim Alon , Joseph-Strauss Daphna , Rahat Ayelet , Sharkia Israa , Adam Miriam , Kitsberg Daniel , Fialkoff Gavriel , Lotem Matan , Gershon Omer , Schmidtner Anna-Kristina , Oiknine-Djian Esther , Klochendler Agnes , Sadeh Ronen , Dor Yuval , Wolf Dana , Habib Naomi , Friedman Nir
Published: August 2020

The global SARS-CoV-2 pandemic created a dire need for viral detection tests worldwide. Most current tests for SARS-CoV-2 are based on RNA extraction followed by quantitative reverse-transcription PCR assays. While automation and improved logistics increased the capacity of these tests, they cannot exceed the lower bound dictated by one extraction and one RT-PCR reaction per sample. Multiplexed next generation sequencing (NGS) assays provide a dramatic increase in throughput, and hold the promise of richer information including viral strains, host immune response, and multiple pathogens.

Here, we establish a significant improvement of existing RNA-seq detection protocols. Our workflow, ApharSeq, includes a fast and cheap RNA capture step, that is coupled to barcoding of individual samples, followed by sample-pooling prior to the reverse transcription, PCR and massively parallel sequencing. Thus, only one non-enzymatic step is performed before pooling hundreds of barcoded samples for subsequent steps and further analysis. We characterize the quantitative aspects of the assay by applying ApharSeq to more than 500 clinical samples in a robotic workflow. The assay results are linear, and the empirical limit of detection is found to be Ct 33 (roughly 1000 copies/ml). A single ApharSeq test currently costs under 1.2$, and we estimate costs can further go down 3-10 fold. Similarly, we estimate a labor reduction of 10-100 fold, automated liquid handling of 5-10 fold, and reagent requirement reduction of 20-1000 fold compared to existing testing methods.
Real-time fMRI neurofeedback training as a neurorehabilitation approach on depressive disorders: A systematic review of randomized control trials
Authors: Méndez Pamela González , Sitaram Ranganatha , Stanley Jeffrey A. , Climent Julio Rodiño
Published: August 2020

BACKGROUND

Depressive disorders are a group of neuropsychiatric disorders that cause significant distress and impairment in social, occupational, and other important areas of functioning. In the last decade, Brain-Computer Interfaces based-neurofeedback training appears as an innovative therapy for this condition and other neuropsychiatric disorders, allowing to volitionally self-regulate brain activity and behavior. Up to date, non-invasive neurofeedback training have been built on different techniques, including EEG, NIRS and fMRI.

OBJECTIVES

This systematic review aims to evaluate the clinical application of fMRI neurofeedback training and its efficacy on treating depressive disorders. As a secondary objective, we intend to extract additional information on the neurofeedback training technique, in order to provide recommendations for future research.

METHODS AND ANALYSIS

The systematic review complies with the PRISMA guidelines and it was submitted to PROSPERO registration. We will only include randomized control trials assessing participants with a depressive disorder. The intervention of interest is real-time fMRI neurofeedback training, the comparison of interest will be placebo neurofeedback, another active non-neurofeedback control or no treatment. The primary outcome will be effects on behavior (symptomatology/disease severity reduction). The secondary outcomes will assess quality of life, acceptability and adverse effects. Finally, we will evaluate ‘other outcomes’ regarding brain MRI metrics (BOLD activation/connectivity), cognitive tasks performance, and physiology measures. At least two reviewers will independently select studies, extract data and assess the risk of bias. If methodologically possible, for primary and secondary outcomes, a meta-analysis will be performed and the data will be presented in summary tables of results using the GRADE approach.

STRENGTH AND LIMITATIONS

As the number of studies on neurofeedback is increasing every year, and better quality of evidence is available, this systematic review, will include only randomized control trials. To our knowledge, this is the first systematic review assessing randomized control trials on fMRI neurofeedback training as a neurorehabilitation approach on depressive disorders. The main limitation of this systematic review might arise from the low number of extant RCTs.
Why are rare variants hard to impute? Coalescent models reveal theoretical limits in existing algorithms
Authors: Si Yichen , Vanderwerff Brett , Zöllner Sebastian
Published: August 2020

Genotype imputation is an indispensable step in human genetic studies. Large reference panels with deeply sequenced genomes now allow interrogating variants with minor allele frequency < 1% without sequencing. While it is critical to consider limits of this approach, imputation methods for rare variants have only done so empirically; the theoretical basis of their imputation accuracy has not been explored. To provide theoretical consideration of imputation accuracy under the current imputation framework, we develop a coalescent model of imputing rare variants, leveraging the joint genealogy of the sample to be imputed and reference individuals. We show that broadly used imputation algorithms includes model misspecifications about this joint genealogy that limit the ability to correctly impute rare variants. We develop closed-form solutions for the probability distribution of this joint genealogy and quantify the inevitable error rate resulting from the model misspecification across a range of allele frequencies and reference sample sizes. We show that the probability of a falsely imputed minor allele decreases with reference sample size, but the proportion of falsely imputed minor alleles mostly depends on the allele count in the reference sample. We summarize the impact of this error on genotype imputation on association tests by calculating ther2between imputed and true genotype and show that even when modeling other sources of error, the impact of the model misspecification have a significant impact on ther2of rare variants. To evaluate these predictions in practice, we compare the imputation of the same dataset across imputation panels of different sizes. While this empirical imputation accuracy is substantially lower than our theoretical prediction, modeling misspecification seems to further decrease imputation accuracy for variants with low allele counts in the reference. These results provide a framework for developing new imputation algorithms and for interpreting rare variant association analyses.
Single amino acid-promoted reactions link a non-enzymatic chemical network to the early evolution of enzymatic pentose phosphate pathway
Authors: Piedrafita Gabriel , Varma Sreejith , Castro Cecilia , Messner Christoph , Szyrwiel Lukasz , Griffin Julian , Ralser Markus
Published: August 2020

How metabolic pathways emerged in early evolution remains largely unknown. Recently discovered chemical networks driven by iron and sulfur resemble reaction sequences found within glycolysis, gluconeogenesis, the oxidative and reductive Krebs cycle, the Wood Ljungdahl as well as the S-adenosylmethionine pathways, components of the core cellular metabolic network. These findings suggest that the evolution of central metabolism was primed by environmental chemical reactions, implying that non-enzymatic reaction networks served as a “template” in the evolution of enzymatic activities. We speculated that the turning point for this transition would depend on the catalytic properties of the simplest structural components of proteins, single amino acids. Here, we systematically combine constituents of Fe(II)-driven non-enzymatic reactions resembling glycolysis and pentose phosphate pathway (PPP), with single proteinogenic amino acids. Multiple reaction rates are enhanced by amino acids. In particular, cysteine is able to replace (and/or complement) the metal ion Fe(II) in driving the non-enzymatic formation of the RNA-backbone metabolite ribose 5-phosphate from 6-phosphogluconate, a rate-limiting reaction of the oxidative PPP. In the presence of both Fe(II) and cysteine, a complex is formed, enabling the non-enzymatic reaction to proceed at a wide range of temperatures. At mundane temperatures, this ‘minimal enzyme-like complex’ achieves a much higher specificity in the formation of ribose 5-phosphate than the Fe(II)-driven reaction at high temperatures. Hence, simple amino acids can accelerate key steps within metal-promoted metabolism-like chemical networks. Our results imply a stepwise scenario, in which environmental chemical networks served as primers in the early evolution of the metabolic network structure.

Significance Statement

The evolutionary roots of metabolic pathways are barely understood. Here we show results consistent with a stepwise scenario during the evolution of (enzymatic) metabolism, starting from non-enzymatic chemical networks. By systematic screening of metabolic-like reactivitiesin vitro, and using high-throughput analytical techniques, we identify an iron/cysteine complex to act as a ‘minimal enzymelike complex’, which consists of a metal ion, an amino acid, and a sugar phosphate ligand. Integrated in a metal-driven, non-enzymatic pentose phosphate pathway, it promotes the formation of the RNA-backbone precursor ribose 5-phosphate at ambient temperature.
Adolescent alcohol binge-drinking induces delayed appearance of behavioral defects in mice
Authors: Van Hees Laura , Didone Vincent , Charlet-Briart Manon , Van Ingelgom Théo , Alexandre Alysson , Quertemont Etienne , Nguyen Laurent , Laguesse Sophie
Published: August 2020

Adolescence is a developmental period characterized by significant changes in brain architecture and behavior. The immaturity of the adolescent brain is associated with heightened vulnerability to exogenous agents, including alcohol. Alcohol is the most consumed drug among teenagers, and binge-drinking during adolescence is a major public health concern. Studies have suggested that adolescent alcohol exposure (AAE) may interfere with the maturation of frontal brain regions and lead to long-lasting behavioral consequences. In this study, we used a mouse model of AAE in which adolescent mice reach high blood alcohol concentration after voluntary binge-drinking. In order to assess short- and long-term consequences of AAE, a battery of behavioral tests was performed during late adolescence and during adulthood. We showed that AAE had no short-term effect on young mice behavior but rather increased anxiety- and depressive-like behaviors, as well as alcohol consumption during adulthood. Moreover, alcohol binge-drinking during adolescence dramatically decreased recognition memory performances and behavioral flexibility in both adult males and females. Furthermore, we showed that voluntary consumption of alcohol during adolescence did not trigger any major activation of the innate immune system in the prefrontal cortex (PFC). Together, our data suggest that voluntary alcohol binge-drinking in adolescent mice induces a delayed appearance of behavioral impairments in adulthood.
Human neonatal B cell immunity differs from the adult version by conserved Ig repertoires and rapid, but transient response dynamics
Authors: Budeus Bettina , Kibler Artur , Brauser Martina , Homp Ekaterina , Bronischewski Kevin , Ross J. Alexander , Görgens Andre , Weniger Marc A. , Dunst Josefine , Kreslavsky Taras , da Conceição Castro Symone Vitoriano , Murke Florian , Oakes Christopher C. , Rusch Peter , Andrikos Dimitrios , Kern Peter , Köninger Angela , Lindemann Monika , Johansson Patricia , Hansen Wiebke , Lundell Anna-Carin , Rudin Anna , Dürig Jan , Giebel Bernd , Hoffmann Daniel , Küppers Ralf , Seifert Marc
Published: August 2020

The human infant B cell system is considered premature or impaired. Here we show that most cord blood B cells are mature and functional as seen in adults, albeit with distinct transcriptional programs providing accelerated responsiveness to T cell-independent and T cell-dependent stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into antibody-secreting cells, thereby presumably limiting memory B cell formation. The neonatal Ig-repertoire is highly variable, but conserved, showing recurrent B cell receptor (BCR) clonotypes frequently shared between neonates. Our study demonstrates that cord blood B cells are not impaired but differ from their adult counterpart in a conserved BCR repertoire and rapid but transient response dynamics. These properties may account for the sensitivity of neonates to infections and limited effectivity of vaccination strategies. Humanized mice suggest that the distinctness of cord blood versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice. Still, our findings reveal overall limited comparability of human cord blood B cells and murine B-1 cells.

Significance Statement

Neonates and infants suffer from enhanced susceptibility to infections. Our study contrasts with the current concept of a premature or impaired B cell system in neonates, by showing that most cord blood B cells are mature and functional. However, their responses are rapid but provide only short-term protection, which may help to improve infant vaccination strategies. We propose an altered perspective on the early human B cell system, which looks similar to but functions differently from the adult counterpart. Finally, our analysis indicates that cord blood- and adult B cell development occur layered as in mice, but certain mouse models still may offer a limited view on human neonatal B cell immunity.
Comparative Neuroanatomy of the Lumbosacral Spinal Cord of the Rat, Cat, Pig, Monkey, and Human
Authors: Toossi Amirali , Bergin Bradley , Marefatallah Maedeh , Parhizi Behdad , Tyreman Neil , Everaert Dirk G. , Rezaei Sabereh , Seres Peter , Gatenby J. Christopher , Perlmutter Steve I. , Mushahwar Vivian K.
Published: August 2020

The overall goal of this work was to create a high-resolution MRI atlas of the lumbosacral enlargement of the spinal cord of the rat (Sprague-Dawley), cat, domestic pig, rhesus monkey, and human. These species were chosen because they are commonly used in basic and translational research in spinal cord injuries and diseases. Six spinal cord specimens from each of the studied species (total of 30 specimens) were fixed, extracted, and imaged. Sizes of the spinal cord segments, cross-sectional dimensions, and locations of the spinal cord gray and white matter were quantified and compared across species. The obtained atlas establishes a reference for the neuroanatomy of the intact lumbosacral spinal cord in these species. It can also be used to guide the planning of surgical procedures of the spinal cord, technology design and development of spinal cord neuroprostheses, and the precise delivery of cells/drugs into target regions within the spinal cord parenchyma.
Joint Representation of Color and Shape in Convolutional Neural Networks: A Stimulus-rich Network Perspective
Authors: Taylor JohnMark , Xu Yaoda
Published: August 2020

To interact with real-world objects, any effective visual system must jointly code the unique features defining each object. Despite decades of neuroscience research, we still lack a firm grasp on how the primate brain binds visual features. Here we apply a novel network-based stimulus-rich representational similarity approach to study color and shape binding in five convolutional neural networks (CNNs) with varying architecture, depth, and presence/absence of recurrent processing. All CNNs showed near-orthogonal color and shape processing in early layers, but increasingly interactive feature coding in higher layers, with this effect being much stronger for networks trained for object classification than untrained networks. These results characterize for the first time how multiple visual features are coded together in CNNs. The approach developed here can be easily implemented to characterize whether a similar coding scheme may serve as a viable solution to the binding problem in the primate brain.
A New Paradigm of Developing Therapeutics to Infectious Diseases by Combining Insights from Nature and Engineering
Authors: Kim Suhyun
Published: August 2020

Broad host-spectrum antibiotics not only kill pathogens, but also beneficial commensal bacteria of the host microbiome that play crucial roles for health. In Nature, bacteria kill other bacteria much more selectively than antibiotics do. Because there is metabolic cost involved in producing molecules to inhibit others, evolution endowed bacteria with bacteriocins to kill those who are similar enough to compete for the same niche, while leaving more distantly related bacteria, intact. The presence of such narrow host-spectrum antibacterial molecules suggests that by engineering and reprogramming what is found in nature, it may be possible to develop highly effective yet selective therapeutics to infectious diseases, either as purified drugs, or as live bacterial therapeutics. Here, I propose a new paradigm of developing highly selective therapeutics by combining insights from Nature and engineering and applied this against foodborne pathogens, one of the most common causes of bacterial infections for humans.
Beneficial effects of cerebellar tDCS on motor learning are associated with altered putamen-cerebellar connectivity: a simultaneous tDCS-fMRI study
Authors: Liebrand Matthias , Karabanov Anke , Antonenko Daria , Flöel Agnes , Siebner Hartwig R. , Classen Joseph , Krämer Ulrike M. , Tzvi Elinor
Published: August 2020

Non-invasive transcranial stimulation of cerebellum and primary motor cortex (M1) has been shown to enhance motor learning. However, the mechanisms by which stimulation improves learning remain largely unknown. Here, we sought to shed light on the neural correlates of transcranial direct current stimulation (tDCS) during motor learning by simultaneously recording functional magnetic resonance imaging (fMRI). We found that right cerebellar tDCS, but not left M1 tDCS, led to enhanced sequence learning in the serial reaction time task. Performance was also improved following cerebellar tDCS compared to sham in a sequence production task, reflecting superior training effects persisting into the post-training period. These behavioral effects were accompanied by increased learning-specific activity in right M1, left cerebellum lobule VI, left inferior frontal gyrus and right inferior parietal lobule during cerebellar tDCS compared to sham. Despite the lack of group-level changes comparing left M1 tDCS to sham, activity increase in right M1, supplementary motor area, and bilateral superior frontal cortex, under M1 tDCS, was associated with better sequence performance. This suggests that lack of group effects in M1 tDCS relate to inter-individual variability in learning-related activation patterns. We further investigated how tDCS modulates effective connectivity in the cortico-striato-cerebellar learning network. Using dynamic causal modelling, we found altered connectivity patterns during both M1 and cerebellar tDCS when compared to sham. Specifically, during cerebellar tDCS, negative modulation of a connection from putamen to cerebellum was decreased for sequence learning only, effectively leading to decreased inhibition of the cerebellum. These results show specific effects of cerebellar tDCS on functional activity and connectivity in the motor learning network and may facilitate the optimization of motor rehabilitation involving cerebellar non-invasive stimulation.
Unpredictable hummingbirds: Flight path entropy is constrained by speed and wing loading
Authors: Berberi Ilias , Segre Paolo S. , Altshuler Douglas L. , Dakin Roslyn
Published: August 2020

Unpredictable movement can provide an advantage when animals avoid predators and other threats. Previous studies have examined how varying environments can elicit unpredictable movement, but the intrinsic causes of complex, unpredictable behavior are not yet known. We addressed this question by analyzing >200 hours of flight performed by hummingbirds, a group of aerial specialists noted for their extreme agility and escape performance. We used information theory to calculate unpredictability based on the positional entropy of short flight sequences during 30-min and 2-hour trials. We show that a bird’s entropy is repeatable, with stable differences among individuals that are negatively correlated with wing loading: birds with lower wing loading are less predictable. Unpredictability is also positively correlated with a bird’s overall acceleration and rotational performance, and yet we find that moment-to-moment changes in acceleration and rotational velocities do not directly influence entropy. This indicates that biomechanical performance must share an underlying basis with a bird’s ability to combine maneuvers into unpredictable sequences. Contrary to expectations, hummingbirds achieve their highest entropy at relatively slow speeds, pointing to a fundamental trade-off whereby individuals must choose to be either fast or unpredictable.
The sex-specific VC neurons are mechanically activated motor neurons that facilitate serotonin-induced egg laying inC. elegans
Authors: Kopchock Richard J. , Ravi Bhavya , Bode Addys , Collins Kevin M.
Published: August 2020

Successful execution of behavior requires coordinated activity and communication between multiple cell types. Studies using the relatively simple neural circuits of invertebrates have helped to uncover how conserved molecular and cellular signaling events shape animal behavior. To understand the mechanisms underlying neural circuit activity and behavior, we have been studying a simple circuit that drives egg-laying behavior in the nematode wormC. elegans. Here we show that the sex-specific, Ventral C (VC) motor neurons are important for vulval muscle contractility and egg laying in response to serotonin. Ca2+imaging experiments show the VCs are active during times of vulval muscle contraction and vulval opening, and optogenetic stimulation of the VCs promotes vulval muscle Ca2+activity. Blocking VC neurotransmission inhibits egg laying in response to serotonin and increases the failure rate of egg-laying attempts, indicating that VC signaling facilitates full vulval muscle contraction and opening of the vulva for efficient egg laying. We also find the VCs are mechanically activated in response to vulval opening. Optogenetic stimulation of the vulval muscles is sufficient to drive VC Ca2+activity and requires muscle contractility, showing the presynaptic VCs and the postsynaptic vulval muscles can mutually excite each other. Together, our results demonstrate that the VC neurons facilitate efficient execution of egg-laying behavior by coordinating postsynaptic muscle contractility in response to serotonin and mechanosensory feedback.

Significance Statement

Many animal motor behaviors are modulated by the neurotransmitters serotonin and acetylcholine. Such motor circuits also respond to mechanosensory feedback, but how neurotransmitters and mechanoreceptors work together to coordinate behavior is not well understood. We address these questions using the egg-laying circuit inC. eleganswhere we can manipulate presynaptic neuron and postsynaptic muscle activity in behaving animals while recording circuit responses through Ca2+imaging. We find that the cholinergic VC motoneurons are important for proper vulval muscle contractility and egg laying in response to serotonin. Muscle contraction also activates the VCs, forming a positive feedback loop that promotes full contraction for egg release. In all, mechanosensory feedback provides a parallel form of modulation that shapes circuit responses to neurotransmitters.
Predicting ovulation from brain connectivity: Dynamic causal modelling of the menstrual cycle
Authors: Hidalgo-Lopez Esmeralda , Zeidman Peter , Harris TiAnni , Razi Adeel , Pletzer Belinda
Published: August 2020

Longitudinal menstrual cycle research allows the assessment of sex hormones effects on brain organization in a natural framework. Here, we used spectral dynamic causal modelling (spDCM) in a triple network model consisting of the default mode, salience and executive central networks (DMN, SN, and ECN), in order to address the changes in effective connectivity across the menstrual cycle. Sixty healthy young women were scanned three times (menses, pre-ovulatory and luteal phase) and spDCM was estimated for a total of 174 scans. Group level analysis using Parametric empirical Bayes showed lateralized and anterior-posterior changes in connectivity patterns depending on the cycle phase and related to the endogenous hormonal milieu. Right before ovulation the left insula recruited the frontoparietal network, while the right middle frontal gyrus decreased its connectivity to the precuneus. In exchange, the precuneus engaged bilateral angular gyrus, decoupling the DMN into anterior/posterior parts. During the luteal phase, bilateral insula engaged to each other decreasing the connectivity to parietal ECN, which in turn engaged the posterior DMN. Remarkably, the specific cycle phase in which a woman was in could be predicted by the connections that showed the strongest changes. These findings further corroborate the plasticity of the female brain in response to acute hormone fluctuations and have important implications for understanding the neuroendocrine interactions underlying cognitive changes along the menstrual cycle.
The Biogeography ofDromiciopsin Southern South America: middle Miocene transgressions, speciation and associations withNothofagus
Authors: Quintero-Galvis Julian F. , Saenz-Agudelo Pablo , Celis-Diez Juan L. , Amico Guillermo C. , Vazquez Soledad , Shafer Aaron B.A. , Nespolo Roberto F.
Published: August 2020

Aim

Several geological events affecting Southern South America during the middle Miocene climatic optimum acted as important drivers of diversification to the biota. This is the case of Microbiotheria, for whichDromiciopsis considered the sole surviving lineage, the sister group of Eomarsupialia (Australian marsupials). Three mainDromiciopsgenetic lineages are known, whose divergence was initially attributed to recent Pleistocene glaciations. Using fossil-calibrated dating on nuclear and mitochondrial genes, here we reevaluate this hypothesis and report an older (Miocenic) biogeographic history for the genus.

Location

Southern South America.

Methods

Phylogenetic reconstruction using sequences from two mitochondrial DNA and four nuclear DNA genes in 159 specimens, from 31 sites across Chile and Argentina. Divergence time estimation using fossil calibration.

Results

Our phylogenetic analysis resolved four well supported clades with discrete geographic distributions. The oldest and most differentiated clade corresponds to that of the northern distribution (35.2°S to 39.3°S), which would be a different species (D. bozinovici, sensu D’elia et al. 2016). According to our estimations, this species shared a common ancestor withD. gliroides(southern clades) about 13 million years ago (95% CI: 6.4-25.3). The southern clades (39.6°S to 42.0°S), showed a divergence time ranging from 9.57 to 6.5 Mya. Strong genetic structure was detected from north to south but not across the Andes, or between Chiloé island/ mainland. Demographic equilibrium is inferred to the northern clade, and recent demographic expansions was detected in the central and southern clades.

Main conclusions

The whole diversification ofDromiciopsoccurred within the Miocene, being the Middle Miocene transgression (MMT), the massive marine flooding that covered several lowlands of the western face of los Andes between 38-48° S, the most likely diversifying force. This was the result of an increase in global sea levels due to the Miocene climatic optimum, which shaped the biogeographic origin of several species, includingNothofagusforests, the habitat main ofDromiciops.
Bio-informatic Analysis of Missense Single Nucleotide Polymorphisms (SNPs) in Human CD38 Gene Associated with B-Chronic Lymphocytic Leukemia
Authors: Fadl Hiba Awadelkareem Osman , Abdelmoneim Abdelrahman Hamza , Elbager Sahar Gamal
Published: August 2020

Background

CLL: Chronic lymphocytic leukemia is a chronic type of haematological malignancies that evoked from lymph proliferative origin of bone marrow and secondary lymphoid tissue, resultant in proliferation and progressive accumulation of distinct monoclonal CD5 /CD19 /CD23 B lymphocytes in the bone marrow, peripheral blood, and lymphatic organs.CD38is a multifunctional ecto-enzyme, known to be a direct contributor in pathogenesis of CLL by poorly understood mechanism. Even though, it highly expressed in CLL. At specific position of CD38 gene sequence, substitution of single nucleotide may result in change in amino acid that ends by consequent alteration of protein structure.

Aim

To study CD38 polymorphism and to predict its effect on structure and subsequently function of CD38 molecule.

Methodology and Result

The bioinformatic analysis of CD38 gene had been carried out by using several soft wares. Functional analysis by SIFT, Polyphen2, and PROVEAN reveled 12 deleterious SNPs. These SNPs were further analyzed by SNAP2, SNP@GO. PMut, STRING and other soft wars. Furthermore, Stability analysis was done using I-Mutant and MUpro software where seven SNPs were found to decrease the stability of the protein by I-Mutant, while two SNPs increase it. At the same time, eight SNPs were found to decrease the stability by Mupro software while only one SNP is predicted to increase it. Finally, Physiochemical analysis was done using Project Hope.

Conclusion

In summary, CD38 genotype seems to have twelve SNP that possibly will result in deleterious effect on Protein Structure. This genetic variation eventually will lead to alteration in potential molecule functions. Which effect the progression of CLL By the end.
A Sub-Minute Resolution Prediction of Brain Temperature Based on Sleep-Wake State in the Mouse
Authors: Sela Yaniv , Hoekstra Marieke M.B. , Franken Paul
Published: August 2020

While brain temperature is of neurobiological and clinical importance, it is still unclear which factors contribute to its daily dynamics and to what degree. We recorded cortical temperature in mice alongside sleep-wake state during 4 days including a 6h sleep deprivation, and developed a mathematical tool to simulate temperature based on the sleep-wake sequence. The model estimated temperature with remarkable precision accounting for 91% of its variance based on three main factors with the sleep-wake sequence accounting for most of the variance (74%) and time-of-day (‘circadian’) the least (9%). As third factor, prior wake prevalence, was discovered to up-regulate temperature, explaining 43% of the variance. With similar accuracy the model predicted cortical temperature in a second, independent cohort using the parameters optimized for the first. Our model corroborates the profound influence of sleep-wake state on brain temperature, and can help differentiate thermoregulatory from sleep-wake driven effects in experiments affecting both.
Endothelial Cell Cycle State Determines Propensity for Arterial-Venous Fate
Authors: Chavkin Nicholas W. , Genet Gael , Poulet Mathilde , Genet Nafiisha , Marziano Corina , Vasavada Hema , Nelson Elizabeth A. , Kour Anupreet , McDonnell Stephanie P. , Huba Mahalia , Walsh Kenneth , Hirschi Karen K.
Published: August 2020

Formation and maturation of a functional blood vascular system is required for the development and maintenance of all tissues in the body. During the process of blood vessel development, primordial endothelial cells are formed and become specified toward arterial or venous fates to generate a circulatory network that provides nutrients and oxygen to, and removes metabolic waste from, all tissues1-3. Specification of arterial and venous endothelial cells occurs in conjunction with suppression of endothelial cell cycle progression4,5, and endothelial cell hyperproliferation is associated with potentially lethal arterial-venous malformations6. However, the mechanistic role that cell cycle state plays in arterial-venous specification is unknown. Herein, studying retinal vascular development in Fucci2aR reporter mice7, we found that venous and arterial endothelial cells are in distinct cell cycle states during development and in adulthood. That is, venous endothelial cells reside in early G1 state, while arterial endothelial cells reside in late G1 state. Endothelial cells in early vs. late G1 exhibited significant differences in gene expression and activity, especially among BMP/TGF-β signaling components. The early G1 state was found to be essential for BMP4-induced venous specification, whereas late G1 state is essential for TGF-β1-induced arterial specification. In a mouse model of endothelial cell hyperproliferation and disrupted vascular remodeling, pharmacological inhibition of endothelial cell cycle rescues the arterial-venous specification defects. Collectively, our results show that endothelial cell cycle control plays a key role in arterial-venous network formation, and distinct cell cycle states provide distinct windows of opportunity for the molecular induction of arterial vs. venous specification.
MACMIC Reveals Dual Role of CTCF in Epigenetic Regulation of Cell Identity Genes
Authors: Wang Guangyu , Xia Bo , Zhou Man , Lv Jie , Zhao Dongyu , Li Yanqiang , Bu Yiwen , Wang Xin , Cooke John P. , Cao Qi , Lee Min Gyu , Zhang Lili , Chen Kaifu
Published: August 2020

Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome, likely because such relationship can be easily identified by many established methods for correlation analysis. However, two features with little correlation may still colocalize at many genomic sites to implement important functions. There is no bioinformatic tool for researchers to specifically identify such feature pair. Here, we develop a method to identify feature pair in which two features have maximal colocalization but minimal correlation (MACMIC) across the genome. By MACMIC analysis of 3,385 feature pairs in 15 cell types, we reveal a dual role of CTCF in epigenetic regulation of cell identity genes. Although super-enhancers are associated with activation of target genes, only a subset of super-enhancers colocalized with CTCF regulate cell identity genes. At super-enhancers colocalized with CTCF, the CTCF is required for the active marker H3K27ac in cell type requiring the activation, and also required for the repressive marker H3K27me3 in other cell types requiring the repression. Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity.
Correlative single-molecule fluorescence barcoding of gene regulation inSaccharomyces cerevisiae
Authors: Shashkova Sviatlana , Nyström Thomas , Leake Mark C , Wollman Adam JM
Published: August 2020

Most cells adapt to their environment by switching combinations of genes on and off through a complex interplay of transcription factor proteins (TFs). The mechanisms by which TFs respond to signals, move into the nucleus and find specific binding sites in target genes is still largely unknown. Single-molecule fluorescence microscopes, which can image single TFs in live cells, have begun to elucidate the problem. Here, we show that different environmental signals, in this case carbon sources, yield a unique single-molecule fluorescence pattern of foci of a key metabolic regulating transcription factor, Mig1, in the nucleus of the budding yeast,Saccharomyces cerevisiae. This pattern serves as a ‘barcode’ of the gene regulatory state of the cells which can be correlated with cell growth characteristics and other biological function.

Highlights

Single-molecule microscopy of transcription factors in live yeast

Barcoding single-molecule nuclear fluorescence

Correlation with cell growth characteristics

Growth in different carbon sources
Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2
Authors: Yang Ziwei , Zhang Xiaolin , Wang Fan , Wang Peihui , Kuang Ersheng , Li Xiaojuan
Published: August 2020

Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKK, subsequently leading to IRF3 and NF-κB phosphorylation. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral agents indicates that SARS-CoV-2 escapes from antiviral immune responses via an unknown mechanism. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses. It downregulates the expression of type I IFNs, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and impairing its K63-linked polyubiquitination. Our findings reveal that NSP8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.

Importance

The large-scale spread of COVID-19 is causing mass casualties worldwide, and the failure of antiviral immune treatment suggests immune evasion. It has been reported that several nonstructural proteins of severe coronaviruses suppress antiviral immune responses; however, the immune suppression mechanism of SARS-CoV-2 remains unknown. Here, we revealed that NSP8 protein of SARS-CoV-2 directly blocks the activation of the cytosolic viral dsRNA sensor MDA5 and significantly downregulates antiviral immune responses. Our study contributes to our understanding of the direct immune evasion mechanism of SARS-CoV-2 by showing that NSP8 suppresses the most upstream sensor of innate immune responses involved in the recognition of viral dsRNA.
KIAA1841, a novel SANT and BTB domain-containing protein, inhibits class switch recombination
Authors: Zheng Simin , Matthews Allysia J. , Rahman Numa , Herrick-Reynolds Kayleigh , Choi Jee Eun , Sible Emily , Ng Yan Kee , Rhodes Daniela , Elledge Stephen J. , Vuong Bao Q.
Published: August 2020

Class switch recombination (CSR) enables B cells to produce different immunoglobulin isotypes and mount an effective immune response against pathogens. Timely resolution of CSR prevents damage due to an uncontrolled and prolonged immune response. While many positive regulators of CSR have been described, negative regulators of CSR are relatively unknown. Using a shRNA library screen in a mouse B cell line, we have identified the novel protein KIAA1841 (NM_027860) as a negative regulator of CSR. KIAA1841 is an uncharacterized protein of 82kD containing SANT and BTB domains. The BTB domain of KIAA1841 exhibited characteristic properties such as self-dimerization and interaction with co-repressor proteins. Overexpression of KIAA1841 inhibited CSR in primary mouse splenic B cells, and inhibition of CSR is dependent on the BTB domain while the SANT domain is largely dispensable. Thus, we have identified a new member of the BTB family that serves as a negative regulator of CSR.