Miracle-dz/UniFAR-FTUs huggingface dataset:
LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior

Lamins form stable filaments at the nuclear periphery in metazoans. Unlike B-type lamins, lamins A and C localize also in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2α). We show that lamin A in the nuclear interior is formed from newly expressed pre-lamin A during processing and from soluble mitotic mature lamins in a LAP2α-independent manner. Binding of LAP2α to lamins A/C in the nuclear interior during interphase inhibits formation of higher order structures of lamin A/C in vitro and in vivo, keeping lamin A/C in a mobile low assembly state independent of lamin A/C S22 phosphorylation. Loss of LAP2α causes formation of larger, less mobile and biochemically stable lamin A/C structures in the nuclear interior, which reduce the mobility of chromatin. We propose that LAP2α is essential to maintain a mobile lamin A/C pool in the nuclear interior, which is required for proper nuclear functions.
The role of pregnancy-specific glycoproteins on trophoblast motility in three-dimensional gelatin hydrogels

Trophoblast invasion is a complex biological process necessary for establishment of pregnancy; however, much remains unknown regarding what signaling factors coordinate the extent of invasion. Pregnancy-specific glycoproteins (PSGs) are some of the most abundant circulating trophoblastic proteins in maternal blood during human pregnancy, with maternal serum concentrations rising to as high as 200-400 μg/mL at term. Here, we employ three-dimensional (3D) trophoblast motility assays consisting of trophoblast spheroids encapsulated in 3D gelatin hydrogels to quantify trophoblast outgrowth area, viability, and cytotoxicity in the presence of PSG1 and PSG9 as well as epidermal growth factor and Nodal. We show PSG9 reduces trophoblast motility whereas PSG1 increases motility. Further, we assess bulk nascent protein production by encapsulated spheroids to highlight the potential of this approach to assess trophoblast response (motility, remodeling) to soluble factors and extracellular matrix cues. Such models provide an important platform to develop a deeper understanding of early pregnancy. Graphical Abstract
Elongation Patterns of Basal Internodes in Sweet Sorghum (Sorghum bicolor Moench)

Based on the plant age (AL) indicated by leaf number, we analyzed the elongation patterns of basal internodes from the third internode (IN3) through IN10. Using two cultivars, Syrup sorgo 2 (S2, late-maturing) and High-sugar sorgo (HI, early-maturing) grown under field conditions in 1993, 20 plants were sampled when the leaf blade of the 4th through the 14th just fully expanded, and every internode length in the main stem was recorded. All internodes in IN9 and IN10 were classified as 'elongated internodes' (EIN: defined as that with final length more than 1.0cm), while those from IN3 through IN6 were classified as non 'elongated internodes'(non-EIN: defined as that with final length less than 1.0cm). In IN7 and IN8, both EIN and non-EIN existed. The EIN rapidly elongated from AL (n+1) when the (n+1) th leaf had just fully expanded to AL (n+3) and reached its maximum length by AL (n+4). This elongation pattern was similar to that of IN10 through IN19 as was reported previously. The non-EIN elongated from AL (n+1) to AL (n+2) and reached its maximum length by AL (n+3). At log phase of internode growth, the elongation rate of non-EIN was remarkably lower than that of EIN. It was suggested that the formation of intercalary meristem did not occur in the non-EIN. It is not likely that the elongation pattern of EIN and that of non-EIN were influenced by the cultivars.
Novelty is not Surprise: Exploration and learning in human sequential decision-making

Drivers of reinforcement learning (RL), beyond reward, are controversially debated. Novelty and surprise are often used equivocally in this debate. Here, using a deep sequential decision-making paradigm, we show that reward, novelty, and surprise play different roles in human RL. Surprise controls the rate of learning, whereas novelty and the novelty prediction error (NPE) drive exploration. Exploitation is dominated by model-free (habitual) action choices. A theory that takes these separate effects into account predicts on average 73 percent of the action choices of human participants after the first encounter of a reward and allows us to dissociate surprise and novelty in the EEG signal. While the event-related potential (ERP) at around 300ms is positively correlated with surprise, novelty, NPE, reward, and the reward prediction error, the ERP response to novelty and NPE starts earlier than that to surprise.
Black-Bellied Sandgrouse (Pterocles orientalis) and Pin-Tailed Sandgrouse (Pterocles alchata): Closely Related Species with Differing Bioenergetic Adaptations to Arid Zones

Sandgrouse of the genus Pterocles are good models for studying adaptations to deserts, with 14 species living in different parts of a habitat spectrum ranging from semiarid to extreme desert. To evaluate possible differences in bioenergetic and thermoregulatory ability within the group, we studied two species, black-bellied sandgrouse (Pterocles orientalis) and pin-tailed sandgrouse (Pterocles alchata). These two species are partly sympatric, but the latter also occurs in hotter and more arid regions than the former. Black-bellied sandgrouse had a mean resting metabolic rate (RMR) similar to the allometric prediction (5.53 m W g⁻¹ by day, 5.04 mWg⁻¹ at night; 97% and 110% of allometric prediction, respectively), whereas mean RMR in pin-tailed sandgrouse was lower than predicted (4.04 mW g⁻¹ by day; 62% of allometric prediction). Similarly, the pin-tailed sandgrouse was the better thermoregulator of the two species, especially at high temperatures, with a well-developed evaporative cooling ability. At 40°C, evaporative heat loss (Ḣe) dissipated 89% of metabolic heat production (Ḣm), and at 25°C, Ḣe was 152% of the allometric prediction. This compares to 53% at 40°C and 101% at 25°C for black-bellied sandgrouse. However, both species had high lower and upper critical temperatures, and metabolism at high ambient temperatures (Ta's) was relatively insensitive to increasing temperature. Black-bellied sandgrouse showed greatly increased thermal conductance (Cd) at high temperatures facilitating nonevaporative heat loss. This species also demonstrated labile body temperature (Tb), especially at low Ta), allowing energy savings under cooler conditions. It was not possible to measure Tb for pin-tailed sandgrouse because of the birds' behavior.
Evidence that an HDAC2-targeted ASO persistently upregulates cortical acetylcholine and dopamine signaling via a CREB | Gs positive feedback loop

Epigenetic modulation of neural circuits facilitates learning and memory. Here, we examined specific inhibition of histone deacetylase 2 (HDAC2) expression in rats receiving a single intracerebroventricular injection of HDAC2-targeted anti-sense oligonucleotides (ASOs) one month prior to cognitive testing. The HDAC2 ASO-injected rats displayed increased novelty preference, decreased cortical and hippocampal HDAC2 mRNA and protein, and upregulated gene expression that persisted 1-month post-injection. Cortical RNA-seq revealed strongly increased transcription of a subset of cyclic adenosine monophosphate (cAMP)-response element binding (CREB) genes known to influence synaptic plasticity, along with dopamine (DRD1, DRD2) and adenosine (ADORA2A) G-protein-coupled receptors (GPCRs). Our analysis identified evidence of a positive-feedback loop that amplified expression of CREB-regulated Gs GPCRs and genes in cAMP/Gs/Gi signaling pathways. Additionally, we found differential expression of enzymes that shift neurotransmitter biosynthesis away from norepinephrine and toward dopamine and acetylcholine (DBH, CHAT). We also observed increased expression of genes important for neurotransmitter packaging (SV2C, VMAT) and release (SYT9). The data indicate that persistent inhibition of HDAC2 expression enables long-lived enhancement of aspects of cognition through increased cortical transcription of a subset of CREB-regulated genes amplified by a positive-feedback mechanism that increases synaptic plasticity and shifts neurotransmitter balance toward increased dopaminergic and cholinergic signaling.
Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Core and Medial Shell

Although the cerebellum is now recognized as part of a long-range brain network that serves limbic functions and motivated behavior, knowledge of cerebello-limbic connectivity is limited, and nothing is known about how the cerebellum connects functionally to the nucleus accumbens (NAc). Here, we report that stimulation of cerebellar nuclei in mice of both sexes modulates spiking activity in both NAc core and medial shell with fast excitation and slower, less synchronized inhibition. Fast responses would be well poised to support rapid communication of information critical to the control of motivated behavior, whereas slower responses may be suggestive of a regulatory function, such as gain control. Tracing experiments to chart cerebellar nuclei-NAc pathways identified disynaptic pathways that recruit the ventral tegmental area (VTA) and intralaminar thalamus (Centromedial and Parafascicular nuclei) as intermediary nodes. Optogenetic activation of cerebellar axons in each of these nodes was sufficient to evoke responses in both NAc core and medial shell, albeit with distinct, node-dependent properties. These pathways and the functional connectivity they support could underlie the role of the cerebellum in motivated behavior.
Organization of Peptidoglycan Synthesis in Nodes and Separate Rings at Different Stages of Cell Division of Streptococcus pneumoniae

Bacterial peptidoglycan (PG) synthesis requires strict spatial and temporal organization to reproduce specific cell shapes. In the ovoid-shaped, pathogenic bacterium Streptococcus pneumoniae (Spn), septal and peripheral (sidewall-like) PG synthesis occur simultaneously at midcell. To uncover the organization of proteins and activities that carry out these two modes of PG synthesis, we examined Spn cells vertically oriented onto their poles to image the division plane at the high lateral resolution of 3D-SIM (structured-illumination microscopy). Using fluorescent D-amino acid (FDAA) probes, we show that areas of new transpeptidase (TP) activity catalyzed by penicillin-binding proteins (PBPs) separate into a pair of concentric rings early in division, representing peripheral PG (pPG) synthesis (outer ring) and the leading-edge (inner ring) of septal PG (sPG) synthesis. Fluorescently tagged PBP2x or FtsZ locate primarily to the inner FDAA-marked ring, whereas PBP2b and FtsX remain in the outer ring, suggesting roles in sPG or pPG synthesis, respectively. Short pulses of FDAA labeling revealed an arrangement of separate regularly spaced “nodes” of TP activity around the division site of predivisional cells. Control experiments in wild-type and mutant strains support the interpretation of nodal spacing of TP activity, and statistical analysis confirmed that the number of nodes correlates with different ring diameters. This nodal pattern of FDAA labeling is conserved in other ovoid-shaped species. Tagged PBP2x, PBP2b, and FtsX proteins also exhibited nodal patterns with spacing comparable to that of FDAA labeling. Together, these results reveal a highly ordered PG synthesis apparatus in ovococcal bacteria at different stages of division. SIGNIFICANCE The spatial organization of PBPs and their TP activity at division septa is not well understood. In some bacteria, TP activity and PBP localization seem to be nodal (also called punctate), whereas in other bacteria, discrete foci of PBP activity are infrequently or not observed. Here we report two basic properties of the organization of PBPs and TP activity in the ovoid-shaped bacterium Spn. First, there is distinct spatial separation of the sPG machine, including FtsZ, from the pPG synthesis machine at the midcell of dividing Spn cells. Second, in predivisional cells, PBPs and TP activity are organized heterogeneously into regularly spaced nodes, whose number and dynamic distribution are likely driven by the PG synthesis of PBP:SEDS complexes.
Distribución de materia seca en el frijol, Vigna unguiculata (L.) Walp variedad ojo negro y tres de sus mutantes en los alrededores de Maracaibo

Con el objeto de evaluar el patron de distribucion de materia . seca en frijol variedad ojo negro y tres de sus mutantes (ON-30(1), ON-30(5) y ON-30(6)), ,;e condujo un ensayo bajo condiciones de bosque seco tropical, utilizandose un diseno completamente aleatorizado, con arreglo de parcelas divididas. A plantas muestreadas cada 7 dias se les separo cada uno de sus organos a los cuales se les determino el peso seco. El analisis de varianza para peso de foliolos senescentes (PFS) y peso de vainas secas (PVS) detecto diferencia significativa (P ˂ .01) para la interaccion genotipo x edad, mientras que para el peso de tallos (PT), peciolos (PP), foliolos verdes (PFV), ramas (PR), ramas florales (PRF), vainas verdes (PVV), vainas secas (PVS) y peso seco total (PST), detecto diferencias significativas (P
Learning rule validation in neural network

The brain is using a learning algorithm which is yet to be discovered. Here we demonstrate that the ability of a neuron to predict its expected future activity may be an important missing component to understand learning in the brain. We show that comparing predicted activity with the actual activity can provide an error signal for modifying synaptic weights. Importantly, this learning rule can be derived from minimizing neuron metabolic cost. This reveals an unexpected connection, that learning in neural networks could result from simply maximizing energy balance by each neuron. We validated this predictive learning rule in neural network simulations and in data recorded from awake animals. We found that neurons in the sensory cortex can indeed predict their activity ~10-20ms in the future. Moreover, in response to stimuli, cortical neurons changed their firing rate to minimize surprise: i.e. the difference between actual and expected activity, as predicted by our model. Our results also suggest that spontaneous brain activity provides “training data” for neurons to learn to predict cortical dynamics. Thus, this work demonstrates that the ability of a neuron to predict its future inputs could be an important missing element to understand computation in the brain.
MogR is a ubiquitous transcriptional repressor affecting motility, biofilm formation and virulence in the Bacillus cereus group

Flagellar motility is considered an important virulence factor in a range of different pathogenic bacteria. In Listeria monocytogenes the transcriptional repressor MogR regulates motility in a temperature-dependent manner by directly repressing flagellar- and chemotaxis genes. The only other bacteria known to carry a mogR homolog are members of the Bacillus cereus group, which includes both motile and non-motile species. Furthermore, the motility locus in B. cereus group bacteria appears to be more closely related to L. monocytogenes than to Bacillus subtilis. In this study we show that in Bacillus thuringiensis, overexpression of MogR results in non-motile host cells devoid of flagella. Global gene expression profiling showed that 110 genes were differentially regulated by MogR overexpression, including flagellar motility genes, but also genes associated with virulence, stress response and a biofilm lifestyle. Accordingly, phenotypic assays showed that MogR also affects cytotoxicity and biofilm formation in B. thuringiensis. Overexpression of a MogR variant mutated in two key amino acids within the putative DNA binding domain restored phenotypes to those of a wild type empty vector control strain. In line with this, the introduction of these mutations resulted in complete loss in the ability of MogR to bind to its putative target site within the flagellar motility locus in vitro. In contrast to L. monocytogenes, MogR appears to be regulated in a growth-phase dependent and temperature-independent manner in B. thuringiensis 407. Interestingly, mogR was found to be conserved also in non-motile B. cereus group species with highly reduced motility loci, such as Bacillus mycoides and Bacillus pseudomycoides, and is expressed in non-motile Bacillus anthracis, providing further indications of an expanded and unexpected set of functions for MogR in B. cereus group species, in addition to motility regulation. In conclusion, MogR constitutes a novel B. cereus group pleiotropic transcriptional regulator, acting as a repressor of motility genes, and affecting the expression of a variety of additional genes involved in biofilm formation and virulence.
An optimal set of inhibitors for Reverse Engineering via Kinase Regularization

We present a comprehensive resource of 257 kinase inhibitor profiles against 365 human protein kinases using gold-standard kinase activity assays. We show the utility of this dataset with an improved version of Kinome Regularization (KiR) to deconvolve protein kinases involved in a cellular phenotype. We assayed protein kinase inhibitors against more than 70% of the human protein kinome and chose an optimal subset of 58 inhibitors to assay at ten doses across four orders of magnitude. We demonstrate the effectiveness of KiR to identify key kinases by using a quantitative cell migration assay and updated machine learning methods. This approach can be widely applied to biological problems for which a quantitative phenotype can be measured and which can be perturbed with our set of kinase inhibitors.
A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2

A key step to the SARS-CoV-2 infection is the attachment of its Spike receptor-binding domain (S RBD) to the host receptor ACE2. Considerable research have been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. Simple and effective strategies to increase potency are desirable for such studies when antibodies are only modestly effective. Here, we identify and characterize a high-affinity synthetic nanobody (sybody, SR31) as a fusion partner to improve the potency of RBM-antibodies. Crystallographic studies reveal that SR31 binds to RBD at a conserved and ‘greasy’ site distal to RBM. Although SR31 distorts RBD at the interface, it does not perturb the RBM conformation, hence displaying no neutralizing activities itself. However, fusing SR31 to two modestly neutralizing sybodies dramatically increases their affinity for RBD and neutralization activity against SARS-CoV-2 pseudovirus. Our work presents a tool protein and an efficient strategy to improve nanobody potency.
Assessment of gamma induced genetic divergence in M2 generation of soybean

Genetic diversity in twenty four M2 treatments resulted from 10, 20, 30, 40 and 50 kR gamma irradiated soybean varieties was studied. These treatments were grouped into six different clusters. Genetic diversity was independent of varieties and doses of gamma rays. Sufficient amount of variability due to induced mutations for different polygenic characters over the parent variety was observed in M2 families. It formed basis for restricted desirable selections.
Comparative study of ectoparasites on Nile tilapia (Oreochromis niloticus) cultured under integrated and unintegrated pond systems

A survey of occurrence of ectoparasites on Oreochromis niloticus (Linneaus) in a fish-cum-piggery pond and a pond stocked with fish only was carried out at the African Regional Aquaculture Centre, Aluu near Port-Harcourt. There was occurrence of ectoparasites from fish samples collected in both systems. Monogenean trematodes (83.8 and 79.8%), Protozoa (15.9 and 19.7%) and Copepods (0.3 and 0.5%) were found in integrated and unintegrated ponds respectively. There was no significant difference (P>0.05) in the incidence of these ectoparasites on O. niloticus obtained from the two pond systems. However, rank correlation analysis revealed a higher level of fish parasitic infestation in the integrated pond compared to the unintegrated pond. The regular piggery waste supply to the integrated pond probably facilitated the propagation of the parasites.
Ultrafast Sample Placement on Existing Trees (UShER) Empowers Real-Time Phylogenetics for the SARS-CoV-2 Pandemic

As the SARS-CoV-2 virus spreads through human populations, the unprecedented accumulation of viral genome sequences is ushering a new era of “genomic contact tracing” – that is, using viral genome sequences to trace local transmission dynamics. However, because the viral phylogeny is already so large – and will undoubtedly grow many fold – placing new sequences onto the tree has emerged as a barrier to real-time genomic contact tracing. Here, we resolve this challenge by building an efficient, tree-based data structure encoding the inferred evolutionary history of the virus. We demonstrate that our approach improves the speed of phylogenetic placement of new samples and data visualization by orders of magnitude, making it possible to complete the placements under real-time constraints. Our method also provides the key ingredient for maintaining a fully-updated reference phylogeny. We make these tools available to the research community through the UCSC SARS-CoV-2 Genome Browser to enable rapid cross-referencing of information in new virus sequences with an ever-expanding array of molecular and structural biology data. The methods described here will empower research and genomic contact tracing for laboratories worldwide. Software Availability USHER is available to users through the UCSC Genome Browser at https://genome.ucsc. edu/cgi-bin/hgPhyloPlace. The source code and detailed instructions on how to compile and run UShER are available from https://github.com/yatisht/usher.
Phage-shock-protein ( Psp ) Envelope Stress Response : Evolutionary History & Discovery of Novel Players

The phage shock protein (Psp) stress-response system protects bacteria from envelope stress and stabilizes the cell membrane. Recent work from our group suggests that the psp systems have evolved independently in distinct Gram-positive and Gram-negative bacterial clades to effect similar stress response functions. Despite the prevalence of the key effector, PspA, and the functional Psp system, the various genomic contexts of Psp proteins, as well as their evolution across the kingdoms of life, have not yet been characterized. We have developed a computational pipeline for comparative genomics and protein sequence-structure-function analyses to identify sequence homologs, phyletic patterns, domain architectures, gene neighborhoods, and evolution of the candidates across the tree of life. This integrative pipeline enabled us to make several new discoveries, including the truly universal nature of PspA and the ancestry of the PspA/Snf7 dating all the way back to the Last Universal Common Ancestor. Using contextual information from conserved gene neighborhoods and their domain architectures, we delineated the phyletic patterns of all the Psp members. Next, we systematically identified all possible ‘flavors’ and genomic neighborhoods of the Psp systems. Finally, we traced their evolution, leading us to several interesting findings of their occurrence and co-migration that together point to the functions and roles of Psp in stress-response systems that are often lineage-specific. Conservation of the Psp systems across bacterial phyla emphasizes the established importance of this stress response system in prokaryotes, while the modularity in various lineages is indicative of adaptation to bacteria-specific cell-envelope structures, lifestyles, and adaptation strategies. We also developed an interactive web application that hosts all the data and results in this study that researchers can explore ( https://jravilab.shinyapps.io/psp-evolution ).