Miracle-dz/UniFAR-FTUs huggingface dataset:
Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke

Fate mapping study via a new transgenic mouse line reveals monocyte-to-microglia conversion in development and after brain injury. Whether monocytes contribute to the brain microglial pool in development or after brain injury remains contentious. To address this issue, we generated CCR2-CreER mice to track monocyte derivatives in a tamoxifen-inducible manner. This method labeled Ly6Chi and Ly6Clo monocytes after tamoxifen dosing and detected a surge of perivascular macrophages before blood-brain barrier breakdown in adult stroke. When dosed by tamoxifen at embryonic day 17 (E17), this method captured fetal hematopoietic cells at E18, subdural Ki67+ ameboid cells at postnatal day 2 (P2), and perivascular microglia, leptomeningeal macrophages, and Iba1+Tmem119+P2RY12+ parenchymal microglia in selective brain regions at P24. Furthermore, this fate mapping strategy revealed an acute influx of monocytes after neonatal stroke, which gradually transformed into a ramified morphology and expressed microglial marker genes (Sall1, Tmem119, and P2RY12) for at least 62 days after injury. These results suggest an underappreciated level of monocyte-to-microglia transition in development and after neonatal stroke.
Neogene precipitation, vegetation, and elevation history of the Central Andean Plateau

Fossil plants from the Central Andes reveal Neogene wetter conditions than previously estimated and the birth of the Puna. Andean uplift played a fundamental role in shaping South American climate and species distribution, but the relationship between the rise of the Andes, plant composition, and local climatic evolution is poorly known. We investigated the fossil record (pollen, leaves, and wood) from the Neogene of the Central Andean Plateau and documented the earliest evidence of a puna-like ecosystem in the Pliocene and a montane ecosystem without modern analogs in the Miocene. In contrast to regional climate model simulations, our climate inferences based on fossil data suggest wetter than modern precipitation conditions during the Pliocene, when the area was near modern elevations, and even wetter conditions during the Miocene, when the cordillera was around ~1700 meters above sea level. Our empirical data highlight the importance of the plant fossil record in studying past, present, and future climates and underscore the dynamic nature of high elevation ecosystems.
Cardiolipin, conformation, and respiratory complex-dependent oligomerization of the major mitochondrial ADP/ATP carrier in yeast

The structural assembly and conformation of yeast’s major ADP/ATP carrier is dependent on the signature lipid of mitochondria. The phospholipid cardiolipin has pleiotropic structural and functional roles that are collectively essential for mitochondrial biology. Yet, the molecular details of how this lipid supports the structure and function of proteins and protein complexes are poorly understood. To address this property of cardiolipin, we use the mitochondrial adenosine 5′-diphosphate/adenosine 5′-triphosphate carrier (Aac) as a model. Here, we have determined that cardiolipin is critical for both the tertiary and quaternary assembly of the major yeast Aac isoform Aac2 as well as its conformation. Notably, these cardiolipin-provided structural roles are separable. In addition, we show that multiple copies of Aac2 engage in shared complexes that are largely dependent on the presence of assembled respiratory complexes III and IV or respiratory supercomplexes. Intriguingly, the assembly state of Aac2 is sensitive to its transport-related conformation. Together, these results expand our understanding of the numerous structural roles provided by cardiolipin for mitochondrial membrane proteins.
Multisite Tumor Sampling Reveals Extensive Heterogeneity of Tumor and Host Immune Response in Ovarian Cancer

Background/Aim: Ovarian cancer (OVCA) is characterized by genomic/molecular intra-patient heterogeneity (IPH). Tissue histology and morphological features are surrogates of the underlying genomic/molecular contexture. We assessed the morphological IPH of OVCA tumor compartments and of lymphocytic infiltrates in multiple matched samples per patient. Materials and Methods: We examined 294 hematoxylin & eosin (H&E) OVCA tumor whole sections from 70 treatment-naïve patients who had undergone cytoreductive surgery. We assessed morphological subtypes as immunoreactive (IR), solid – proliferative (SD), papilloglandular (PG), and mesenchymal transition (MT); subtype load per patient; stromal tumor-infiltrating lymphocyte (sTIL) density as average per sample; and, as maximal sTIL values (max-TILs) among all samples per patient, ovaries and implants. Results: Among all 294 tumor sections, the most frequent primary morphological subtype was PG (n=150, 51.0%), followed by MT (71, 24.1%), SD (48, 16.3%) and IR (15, 5.1%). Subtype combinations were observed in 67/294 sections (22.8%) and IPH in 48/70 patients (68.6%). PG prevailed in ovaries (p<0.001), SD and MT in implants (p=0.023 and p<0.001, respectively). sTILs were higher in SD compared to non-SD (p=0.019) and lower in PG, respectively (p<0.001). sTIL density was higher in implants than in ovaries (p<0.001). Higher max-TILs were associated with stage IV disease (p=0.043), upper abdominal dissemination (p=0.024), endometrioid histology (p=0.013), and grade 3 tumors (p=0.021). Favorable prognosticators were higher max-TILs per patient (PFS, OS) and higher SD-load (PFS). Conclusion: Clinically relevant morphological and host immune-response IPH appear to be the norm in OVCA. This may complicate efforts to decipher sensitivity of the tumor to certain treatment modalities from a single pre-operative biopsy.
A simple and rapid method for separation and isolation of marine algal species from naturally evolved populations

ABSTRACT To improve the study of mixed microalgal populations, three naturally evolved marine microalgal cultures were subjected to a light crushing mechanical treatment using a silicon spatula coupled with zymolyase treatment at four concentrations: 5, 10, 20 and 25 U/ml, for 15, 30, 45 and 60 min before being observed under a microscope. The enzyme concentration of 20 U/ml after 45 min reduces the size of macroscopic microalgal aggregates and improves the microscopic observation of the different microalgal species comprising the population. There was no improvement using the higher enzyme concentration. This paper proposes a new approach to the study of naturally evolved microalgal populations which is useful for distinguishing the morphology of the different species present in the population and allowing for the identification by classical keys, and also to obtain a pure culture from an inoculum of mixed species by using a micromanipulator for cell counting.
Comorbidity Networks in Cardiovascular Diseases

Background: Cardiovascular diseases are the leading causes of mortality worldwide. One reason behind this lethality lies in the fact that often cardiovascular illnesses develop into systemic failure due to the multiple connections to organismal metabolism. This in turn is associated with co-morbidities and multimorbidity. The prevalence of coexisting diseases and the relationship between the molecular origins adds to the complexity of the management of cardiovascular diseases and thus requires a profound knowledge of the genetic interaction of diseases. Objective: In order to develop a deeper understanding of this phenomenon, we examined the patterns of comorbidity as well as their genetic interaction of the diseases (or the lack of evidence of it) in a large set of cases diagnosed with cardiovascular conditions at the national reference hospital for cardiovascular diseases in Mexico. Methods: We performed a cross-sectional study of the National Institute of Cardiology. Socioeconomic information, principal diagnosis that led to the hospitalization and other conditions identified by an ICD-10 code were obtained for 34,099 discharged cases. With this information a cardiovascular comorbidity networks were built both for the full database and for ten 10-years age brackets. The associated cardiovascular comorbidities modules were found. Data mining was performed in the comprehensive ClinVar database with the disease names (as extracted from ICD-10 codes) to establish (when possible) connections between the genetic associations of the genetic interaction of diseases. The rationale is that some comorbidities may have a stronger genetic origin, whereas for others, the environment and other factors may be stronger. Results: We found that comorbidity networks are highly centralized in prevalent diseases, such as cardiac arrhythmias, heart failure, chronic kidney disease, hypertension, and ischemic diseases. Said comorbidity networks are actually modular on their connectivity. Modules recapitulate physiopathological commonalities, e.g., ischemic diseases clustering together. This is also the case of chronic systemic diseases, of congenital malformations and others. The genetic and environmental commonalities behind some of the relations in these modules were also found by resorting to clinical genetics databases and functional pathway enrichment studies. Conclusions: This methodology, hence may allow the clinician to look up for non-evident comorbidities whose knowledge will lead to improve therapeutically designs. By continued and consistent analysis of these types of patterns, we envisaged that it may be possible to acquire, strong clinical and basic insights that may further our advance toward a better understanding of cardiovascular diseases as a whole. Hopefully these may in turn lead to further development of better, integrated therapeutic strategies.
Central Venous Pressure and Clinical Outcomes During Left-Sided Mechanical Support for Acute Myocardial Infarction and Cardiogenic Shock

Background: Right ventricular failure (RVF) is associated with increased mortality among patients receiving left ventricular mechanical circulatory support (LV-MCS) for cardiogenic shock and requires prompt recognition and management. Increased central venous pressure (CVP) is an indicator of potential RVF. Objectives: We studied whether elevated CVP during LV-MCS for acute myocardial infarction complicated by cardiogenic shock is associated with higher mortality. Methods: Between January 2014 and June 2019, we analyzed hemodynamic parameters during Impella LV-MCS from 28 centers in the United States participating in the global, prospective catheter-based ventricular assist device (cVAD) study. A total of 132 patients with a documented CVP measurement while on Impella left-sided support for cardiogenic shock were identified. Results: CVP was significantly higher among patients who died in the hospital (14.0 vs. 11.7 mmHg, p = 0.014), and a CVP >12 identified patients at significantly higher risk for in-hospital mortality (65 vs. 45%, p = 0.02). CVP remained significantly associated with in-hospital mortality even after adjustment in a multivariable model (adjusted OR 1.10 [95% CI 1.02–1.19] per 1 mmHg increase). LV-MCS suction events were non-significantly more frequent among patients with high vs. low CVP (62.11 vs. 7.14 events, p = 0.067). Conclusion: CVP is a single, readily accessible hemodynamic parameter which predicts a higher rate of short-term mortality and may identify subclinical RVF in patients receiving LV-MCS for cardiogenic shock.
A Model of Wheat Grain Growth and Its Applications to Different Temperature and Carbon Dioxide Levels

Kernel growth after anthesis is simulated as a function of the potential kernel growth rate, current photosynthate production and mobilisation of stored reserves. The potential growth rate of the kernel is simulated as two temperature-sensitive processes, cell production and cell growth. The difference between the potential and actual growth rates of the kernel depends on the carbon supply to the free space of the kernel endosperm, while the carbon supply is itself affected by the actual kernel growth rate. Sensitivity analysis showed that the growth rate of the grain per plant is most sensitive to the potential growth rate of the kernel and number of kernels per plant. This model is able to simulate the observed rates of grain growth and leaf senescence from anthesis to physiological maturity for wheat plants grown in two CO2 concentrations. The simulated temperature response of grain growth agrees well with the experimenal observations.
Cdc42 activity is essential for the interplay between cAMP/PKA pathway and CatSper function

Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca2+ transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 distribution in the principal piece is confined to four linear domains and this localization is disrupted in CatSper1-null sperm. Cdc42 inhibition impaired CatSper activity and other Ca2+-dependent downstream events resulting in a severe compromise of the sperm fertilizing potential. We also demonstrate that Cdc42 is essential for CatSper function by modulating cAMP production by sAC, providing a new regulatory mechanism for the stimulation of CatSper by the cAMP/PKA-dependent pathway. These results reveal a broad mechanistic insight into the regulation of Ca2+ in mammalian sperm, a matter of critical importance in male infertility as well as in contraception.
Mutualistic interaction with Trichoderma longibrachiatum UENF-F476 boosted plant growth-promotion of Serratia marcescens UENF-22GI

BACKGROUND A plethora of bacteria-fungal interactions occurs on the extended fungal hyphae network in soil. The mycosphere of saprophytic fungi can serve as a bacterial niche boosting their survival, dispersion, and activity. Such ecological concepts can be converted to bioproducts for sustainable agriculture. Accordingly, we tested the hypothesis that the well-characterized beneficial bacterium Serratia marcescens UENF-22GI can enhance their plant growth-promoting properties by combination with Trichoderma longibrachiatum UENF-F476. RESULTS The colony and cell interactions demonstrated S. marcescens and T. longibrachiatum compatibility. Bacteria cells were able to attach, forming aggregates-biofilms and migrates through fungal hyphae network. Bacterial migration through growing hyphae was confirmed using two-compartment Petri dishes assay. Fungal inoculation increased the bacteria survival rates into the vermicompost substrate over the experimental time. Also, in vitro indolic compound, phosphorus, and zinc solubilization bacteria activities increased in the presence of the fungus. In line with the ecophysiological bacteria fitness, tomato and papaya plantlet growth was boosted by bacteria-fungi combination applied under plant nursery conditions. CONCLUSION Mutualistic interaction between mycosphere-colonizing bacterium S. marcescens UENF-22GI and the saprotrophic fungi T. longibrachiatum UENF-F467 increased the ecological fitness of the bacteria alongside with beneficial potential for plant growth. A proper combination and delivery of compatible beneficial bacteria-fungus represent an open avenue for biological enrichment of plant substrates technologies in agricultural systems.
An essential amino acid synchronises malaria parasite development with daily host rhythms

The replication of blood-stage malaria parasites is synchronised to the host’s daily feeding rhythm. We demonstrate that a metabolite provided to the parasite from the host’s food can set the schedule for Plasmodium chabaudi’s intraerythrocytic development cycle (IDC). First, a large-scale screen reveals multiple rhythmic metabolites in the blood that match the timing of the IDC, but only one - the amino acid isoleucine - that malaria parasites must scavenge from host food. Second, perturbing the timing of isoleucine provision and withdrawal demonstrate that parasites use isoleucine to schedule and synchronise their replication. Thus, periodicity in the concentration of isoleucine in the blood, driven by host-feeding rhythms, explains why timing is beneficial to the parasite and how it coordinates with host rhythms. Blood-stage replication of malaria parasites is responsible for the severity of disease symptoms and fuels transmission; disrupting metabolite-sensing by parasites offers a novel intervention to reduce parasite fitness.
Contextual Prediction Errors Reorganize Episodic Memories in Time

Episodic memories are contextual experiences ordered in time. Despite knowing its adaptive nature, whether our memories for events can be altered in time is not adequately addressed. The role of prediction errors (PEs) in strengthening declarative memory is well established but has not been investigated in the time dimension of episodic memory. We tested this dual possibility out using a 3-day movie viewing paradigm, wherein memorized events are subjected to expectation violations and later tested for sequence memory. Our results revealed that contextual PEs fundamentally weaken the older memorized sequence of mispredicted events. Interestingly, the newer events having the PEs in them, had comparable memory strength as control events with repeated viewings but without having any PEs. A hierarchical drift diffusion model indicated that a change in decision criterion rather than drift rate accounted for the behavioural measures of memory strength. In summary, these results suggest that the temporal arrangement of naturalistic episodic memories are reorganized by contextual prediction errors.
Cortical activity evoked by voice pitch changes: A combined fNIRS and EEG study

Numerous studies have investigated the cortical representation and time course of responses to auditory signals with and without pitch. However, little is known regarding the responses evoked by pitch changes. To study the spatial as well as temporal characteristics of cortical activity elicited by voice pitch changes, combined functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) data were obtained from normal-hearing listeners presented with continuous vowel sequences in which the prosodic contours either varied between the individual vowels or were the same throughout. The fNIRS topographies and the EEG source reconstructions indicated additional right-hemispheric activity anterior to the primary auditory cortex and in the superior temporal sulcus for sequences with variable prosody. Additionally, the time courses of the fNIRS signals showed that activity was more sustained in response to sequences with changing prosodic contours. The EEG data revealed a similar pattern for the P2 amplitude, which was smaller during the second half for blocks with fixed prosody, whereas the P1 was consistently larger for sequences with variable prosody. Moreover, the sources of the P2, but not the P1, were lateralised to the right, suggesting that the hemispheric asymmetry in the processing of voice pitch changes develops over time.
Single cell BCR and transcriptome analysis after respiratory virus infection reveals spatiotemporal dynamics of antigen-specific B cell responses

B cell responses are a critical component of anti-viral immunity. However, a comprehensive picture of antigen-specific B cell responses, differentiation, clonal proliferation and dynamics in different organs after infection is lacking. Here, we combined single-cell RNA sequencing with single-cell B cell receptor (BCR) characterization of antigen-specific cells in the draining lymph nodes, spleen and lungs after influenza infection. We identify several novel B cell subpopulations forming after infection and find organ-specific differences that persist over the course of the response. We discover important transcriptional differences between memory cells in lungs and lymphoid organs and describe organ-restricted clonal expansion. Strikingly, by combining BCR mutational analysis, monoclonal antibody expression and affinity measurements we find no differences between germinal center (GC)-derived memory and plasmacells, at odds with an affinity-based selection model. By linking antigen-recognition with transcriptional programming, clonal-proliferation and differentiation, these finding provide important advances in our understanding of antiviral B cell immunity.
Studies on elements of the wood in rice plants

Various size and forms of vessel members, parenchyma cells, and fibers were found in roots, leaves and stems of rice plants. The primary walls of protoxylem vessels in leaves and stems were always found destroyed, so it was not made possible to observe their size. The metaxylem vessels of each organ were divided into two types according to length and diameter of their elements; some were longer having smaller diameters (metaxylem I) while others were shorter with larger diameters (metaxylem II). Out of all wood elements, fibers in each organ were the longest with smallest diameters sometimes having wave-like roughness on their surface. In the nodes of stems, various forms of metaxylem vessels with many perforations were found. By the observation on leaves it is assumed that the vessels of connecting tissues are composed of elements of metaxylem. In the protoxylem of each organ, two types of thickening were found, that is annular and spiral. In leaves and stems, especially the wall of annular elements thickens conspicuously. On the contrary, in roots, the thickening of both these two types of elements is less. In the metaxylem I, many types of thickening were observed. In leaves, annular and spiral elements are dominant. In roots and stems besides these, scalariform and pitted ones could also be observed. In the metaxylem II, the type of thickening of vessel elements differs in different organs. In leaves, a kind of scalariform elements is most common. In roots, on the contrary, the most common type of thickening found is pitted. In stems, the thickening shows the intermediate type between those found in roots and leaves. The parenchyma and fiber cells of xylem also show thickening in their cell walls. The walls of fibers are pitted with the pits distributed sparsely. On the walls of parenchyma cells, much variation in the type of thickening was observed. It sometimes resembles that of vessels and sometimes that of fibers. The perforation plate of metaxylem II can be divided into several types, that is, simple transverse, simple oblique, scalariform and tracheid-like. The former two are commonly found in rice plants. But in the shoot, especially in leaves, the latter types are frequenty observed. It is assumed from these observations that the roots are evolutionally the most advanced and the leaves the most primitive organs of the plant.