Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic, transcriptomic, and metabolic characterization of 2-Phenylethanol-resistant Saccharomyces cerevisiae obtained by evolutionary engineering

2-Phenylethanol is an aromatic compound commonly used in the food, cosmetic, and pharmaceutical industries. Due to increasing demand for natural products by consumers, the production of this flavor by microbial fermentation is gaining interest, as a sustainable alternative to chemical synthesis or expensive plant extraction, both processes relying on the use of fossil resources. However, the drawback of the fermentation process is the high toxicity of 2-phenylethanol to the producing microorganism. The aim of this study was to obtain a 2-phenylethanol-resistant Saccharomyces cerevisiae strain by in vivo evolutionary engineering and characterize the adapted yeast at the genomic, transcriptomic and metabolic levels. For this purpose, the tolerance to 2-phenylethanol was developed by gradually increasing the concentration of this flavor compound through successive batch cultivations, leading to an adapted strain that could tolerate 3.4 g/L of 2-phenylethanol, which was about 3-times better than the reference strain. Genome sequencing of the adapted strain identified point mutations in several genes, notably in HOG1 that encodes the Mitogen-Activated Kinase of the high-osmolarity signaling pathway. As this mutation is localized in the phosphorylation lip of this protein, it likely resulted in a hyperactive protein kinase. Transcriptomic analysis of the adapted strain supported this suggestion by revealing a large set of upregulated stress-responsive genes that could be explained in great part by HOG1-dependent activation of the Msn2/Msn4 transcription factor. Another relevant mutation was found in PDE2 encoding the low affinity cAMP phosphodiesterase, the missense mutation of which may lead to hyperactivation of this enzyme and thereby enhance the stressful state of the 2-phenylethanol adapted strain. In addition, the mutation in CRH1 that encodes a chitin transglycosylase implicated in cell wall remodeling could account for the increased resistance of the adapted strain to the cell wall-degrading enzyme lyticase. Finally, the potent upregulation of ALD3 and ALD4 encoding NAD+ -dependent aldehyde dehydrogenase together with the observed phenylacetate resistance of the evolved strain suggest a resistance mechanism involving conversion of 2-phenylethanol into phenylacetaldehyde and phenylacetate implicating these dehydrogenases.
Arthropod co-occurrence networks indicate environmental differences between islands and signal introduced species in Azorean native forest remnants

Island biotas are in imminent threat from anthropogenic impacts. Of these impacts, the negative effects of exotic species on the taxonomic and functional diversity of the local fauna are of major concern. Exotics may also have a detrimental effect on interspecific interactions which, in turn, can destabilize ecological networks. Species co-occurrence networks can detect species-to-species associations and are used to predict ecological interaction networks and utilized as tools to assess environmental impacts on community structure. Here, we aim to investigate whether or not topological differences of the arthropod co-occurrence networks among native forest fragments from seven Azorean islands can reveal the influence of the abiotic environment and exotic species on these networks. Co-occurrence networks were sensitive to environmental and community dissimilarities, showing a clear separation between islands and pinpointed differences between indigenous and exotic networks. Most exotics were little connected and exotic networks had a large proportion of unconnected species. The resulting decreased connectance and the increased modularity with the increase of the proportions of exotics in the networks suggest that most exotics have too low prevalence to show associations with other species, and only a few dominants drive co-occurrences. The proportion of negative links, as indicators of competition, did not increase with the increase of exotics in the habitats, suggesting that exotics provided new functional roles when they colonized native forest remnants. However, when the theoretical networks consisting of only indigenous species were investigated, connectance decreased and closeness increased with the increase of exotics, suggesting processes of network degradation. Since our study provides ample evidence for the usefulness of co-occurrence network analysis in studying island ecosystems, we recommend the use of this tool for ecosystem assessments, early warning systems and decision-making in island biodiversity conservation.
Development of the sickle Pan-African research consortium registry in Tanzania: opportunity to harness data science for sickle cell disease

Background Sickle cell disease (SCD) is a severe hereditary form of anemia that contributes between 50% and 80% of under-five mortality in Africa. Eleven thousand babies are born with SCD annually in Tanzania, ranking 4th after Nigeria, the Democratic Republic of Congo and India. The absence of well-described SCD cohorts is a major barrier to health research in SCD in Africa. Objective This paper describes the Sickle Pan African Consortium (SPARCO) database in Tanzania, from the development, design of the study instruments, data collection, analysis of data and management of data quality issues. Methods The SPARCO registry used existing Muhimbili Sickle Cell Cohort (MSC) study case report forms (CRF) and later harmonized data elements from the SickleInAfrica consortium to develop Research Electronic Data Capture (REDCap) instruments. Patients were enrolled through various strategies, including mass screening following media sensitization and health education events during World Sickle Cell Day each June and the SCD awareness month in September. Additional patients were identified through active surveillance of previously participating patients in the MSC. Results Three thousand eight hundred patients were enrolled between October 2017 and May 2021. Of these, 1,946 (51.21%) were males and 1,864 (48.79%) were females. The hemoglobin phenotype distribution was 3,762 (99%) HbSS, 3 (0.08%) HbSC and 35 (0.92%) HbSβ +thalassemia. Hemoglobin levels, admission history, blood transfusion and painful events were recorded from December 2017 to May 2021. Conclusion The Tanzania SPARCO registry will improve healthcare for SCD in Africa through the facilitation of collaborative data-driven research for SCD.
Trends in elevated waist-to-height ratio and waist circumference in U.S. adults and their associations with cardiometabolic diseases and cancer, 1999–2018

Introduction Although waist-to-height ratio (WHtR) has established association with cardiometabolic disease, the trend of changes in elevated WHtR among general population have not been examined adequately. Methods This study examined the prevalence of elevated WHtR and waist circumference (WC) and their trends over time using Joinpoint regression models among adults who participated in the United States National Health and Nutrition Examination Survey (U.S. NHANES) 1999–2018. We performed weighted logistic regression to identify the association between central obesity subtypes and the prevalence of comorbidities, including diabetes, chronic kidney disease, hypertension, cardiovascular disease, and cancer. Results The prevalence of elevated WHtR has increased from 74.8% in 1999–2000 to 82.7% in 2017–2018 while elevated WC also increased from 46.9% in 1999–2000 to 60.3% in 2017–2018. Men, older adults, former smokers, and people with lower education levels were more likely to have elevated WHtR. A total of 25.5% of American adults had normal WC but elevated WHtR, and they had a significantly higher chance of suffering from diabetes (odds ratio [OR] = 2.06 [1.66, 2.55]), hypertension (OR = 1.75 [1.58, 1.93]) and CVD (OR = 1.32 [1.11, 1.57]). Discussion In conclusion, the burden of elevated WHtR and WC have been increasing among U.S. adults throughout the years, and the changes have been more significant across most subgroups. It is also notable that approximately a quarter of the population had normal WC but elevated WHtR, which had increased likelihood of having cardiometabolic diseases, especially diabetes. Future clinical practices should pay more attention to this subgroup of the population with overlooked health risks.
Psychotic disorders of space and time – A contribution of Erwin W. Straus

This paper presents and discusses a manuscript by one of the core founders of phenomenological psychopathology, Erwin W. Straus, concerning psychotic disorders of space and time (see attached Supplementary material). Written in June 1946, the manuscript is published for the first time as supplementary material to this paper. It is a clinical case-study of a patient with psychotic depression from Henry Phipps Clinic. It contains themes known from both Straus’ earlier and later work on lived time and mental illness, in particular a critique of physicalism in psychology, a vindication of primary sensing, a description of the spatiotemporal unity of lived experience, and the notion of temporal becoming. However, it is the only work by Straus that explores in such detail a patient’s case and shows how the lived experience is spatiotemporally structured and intrinsically related to affectivity, embodiment, and action. The manuscript is yet another piece of evidence of Straus’ significance in developing the field of phenomenological psychiatry in both Germany and the United States.
A review of technological innovations leading to modern endovascular brain aneurysm treatment

Tools and techniques utilized in endovascular brain aneurysm treatment have undergone rapid evolution in recent decades. These technique and device-level innovations have allowed for treatment of highly complex intracranial aneurysms and improved patient outcomes. We review the major innovations within neurointervention that have led to the current state of brain aneurysm treatment.
Community vertical stratification drives temporal taxonomic and phylogenetic beta diversity in a mixed broadleaf-conifer forest

Temporal change of beta diversity provides a better understanding of the extent and consequences of species composition in forest communities with the ongoing global climate change. However, relatively little is known about temporal beta diversity changes across vertical stratification in the forest. In this study, we divided more than 5,000 tree individuals from a mixed broadleaf-conifer forest into four vertical strata (i.e., shrub, subcanopy, lower canopy, and upper canopy) to quantify how vertical stratification drives the temporal change of taxonomic and phylogenetic beta diversity. We found that taxonomic beta diversity significantly decreased while phylogenetic beta diversity showed an insignificant increase after 5 years. When considering vertical stratification, taxonomic beta diversity in the subcanopy, lower canopy, and upper canopy significantly changed with inconsistent directions, but phylogenetic beta diversity in the shrub significantly increased. Moreover, the significant decrease in taxonomic beta diversity is mainly driven by changes in species composition in shrub and subcanopy stratification (with 85.89% contributions). The changes in phylogenetic beta diversity are driven by shifts in the shrub and upper canopy (with 96.02% contributions). Our study suggests that taking community vertical stratification into consideration contributes to a better understanding of temporal beta diversity in forest communities.
The fNIRS evaluation of frontal and temporal lobe cortical activation in Chinese first-episode medication-naïve and recurrent depression during a verbal fluency task

Background Functional near-infrared spectroscopy (fNIRS) identifies neurophysiological differences between psychiatric disorders by assessing cortical hemodynamic function. Few trials have studied differences in brain functional activity between first-episode medication-naïve depression patients (FMD) and recurrent major depression (RMD). We aimed to determine the differences between FMD and RMD in oxygenated hemoglobin concentration ([oxy-Hb]), and to investigate the correlation between frontotemporal cortex activation and clinical symptoms. Methods We recruited 40 patients with FMD, 53 with RMD, and 38 healthy controls (HCs) from May 2021 to April 2022. Symptom severity was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). A 52-channel fNIRS measured changes in [oxy-Hb] during VFT performance. Results Both patient groups performed poorly during the VFT task compared with HC (FDR p < 0.05), but there was no significant difference between the two patient groups. Analysis of variance showed that mean [oxy-Hb] activation was lower in both the frontal and temporal lobes in the MDD group compared with HCs (FDR p < 0.05). Additionally, patients with RMD had a significantly lower hemodynamic response in the right dorsolateral prefrontal cortex (DLPFC) and dorsal frontal pole cortex (DFPC) than patients with FMD (FDR p < 0.05). No significant correlation was found between changes in mean [oxy-Hb] and either medical history or clinical symptoms (FDR p < 0.05). Conclusion The presence of different neurofunctional activity in some of the same brain regions in FMD and RMD patients implied a link between the level of complexity activation in frontal regions and the stage of MDD. Cognitive impairment may already be present at the beginning of an MDD episode. Clinical trial registration www.chictr. org.cn, identifier ChiCTR2100043432.
The effect of small-amplitude convective disturbances on the size and bursting of a laminar separation bubble

Short laminar separation bubbles can develop on a flat plate due to an externally imposed pressure gradient. Here, these bubbles are computed by means of direct numerical simulations. Laminar–turbulent transition occurs in the bubble, triggered by small disturbance input with fixed frequency, but varying amplitude, to keep the bubbles short. The forcing amplitudes span a range of two orders of magnitude. All resulting bubbles differ with respect to their mean flow, linear-stability characteristics and distance between transition and mean reattachment locations. Mechanisms responsible for these differences are analysed in detail. Switching off the disturbance input or reducing it below a certain, very small threshold causes the short bubble to grow continuously. Eventually, it no longer exhibits typical characteristics of a short laminar separation bubble. Instead, it is argued that bursting has occurred and the bubble displays characteristics of a long-bubble state, even though this state was not a statistically steady state. This hypothesis is backed by a comparison of numerical results with measurements. For long bubbles, the transition to turbulence is not able to reattach the flow immediately. This effect can lead to the bursting of a short bubble, which remains short only when sufficiently large disturbances are convected into the bubble. Large-scale spanwise-oriented vortices at transition are observed for short but not for long bubbles. The failure of the transition process to reattach the flow in the long-bubble case is ascribed to this difference in transitional vortical structures.
Symbiosis preservation: Putative regulation of fatty acyl-CoA reductase by miR-31a within the symbiont harboring bacteriome through tsetse evolution

Tsetse flies are the sole vectors of African trypanosomes. In addition to trypanosomes, tsetse harbor obligate Wigglesworthia glossinidia bacteria that are essential to tsetse biology. The absence of Wigglesworthia results in fly sterility, thus offering promise for population control strategies. Here, microRNA (miRNAs) and mRNA expression are characterized and compared between the exclusive Wigglesworthia-containing bacteriome and adjacent aposymbiotic tissue in females of two evolutionarily distant tsetse species (Glossina brevipalpis and G. morsitans). A total of 193 miRNAs were expressed in either species, with 188 of these expressed in both species, 166 of these were novel to Glossinidae, and 41 miRNAs exhibited comparable expression levels between species. Within bacteriomes, 83 homologous mRNAs demonstrated differential expression between G. morsitans aposymbiotic and bacteriome tissues, with 21 of these having conserved interspecific expression. A large proportion of these differentially expressed genes are involved in amino acid metabolism and transport, symbolizing the essential nutritional role of the symbiosis. Further bioinformatic analyses identified a sole conserved miRNA::mRNA interaction (miR-31a::fatty acyl-CoA reductase) within bacteriomes likely catalyzing the reduction of fatty acids to alcohols which comprise components of esters and lipids involved in structural maintenance. The Glossina fatty acyl-CoA reductase gene family is characterized here through phylogenetic analyses to further understand its evolutionary diversification and the functional roles of members. Further research to characterize the nature of the miR-31a::fatty acyl-CoA reductase interaction may find novel contributions to the symbiosis to be exploited for vector control.
Steady electrocorticogram characteristics predict specific stress-induced behavioral phenotypes

Introduction Depending on the individual, exposure to an intense stressor may, or may not, lead to a stress-induced pathology. Predicting the physiopathological evolution in an individual is therefore an important challenge, at least for prevention. In this context, we developed an ethological model of simulated predator exposure in rats: we call this the multisensorial stress model (MSS). We hypothesized that: (i) MSS exposure can induce stress-induced phenotypes, and (ii) an electrocorticogram (ECoG) recorded before stress exposure can predict phenotypes observed after stress. Methods Forty-five Sprague Dawley rats were equipped with ECoG telemetry and divided into two groups. The Stress group (n = 23) was exposed to an MSS that combined synthetic fox feces odor deposited on filter paper, synthetic blood odor, and 22 kHz rodent distress calls; the Sham group (n = 22) was not exposed to any sensorial stimulus. Fifteen days after initial exposure, the two groups were re-exposed to a context that included a filter paper soaked with water as a traumatic object (TO) reminder. During this re-exposure, freezing behavior and avoidance of the filter paper were measured. Results Three behaviors were observed in the Stress group: 39% developed a fear memory phenotype (freezing, avoidance, and hyperreactivity); 26% developed avoidance and anhedonia; and 35% made a full recovery. We also identified pre-stress ECoG biomarkers that accurately predicted cluster membership. Decreased chronic 24 h frontal Low θ relative power was associated with resilience; increased frontal Low θ relative power was associated with fear memory; and decreased parietal β2 frequency was associated with the avoidant-anhedonic phenotype. Discussion These predictive biomarkers open the way to preventive medicine for stress-induced diseases.
Tryptophan intake, not always the more the better

Objectives To investigate the effects of excessive tryptophan intake on the body and the effects of tryptophan metabolism-related aryl hydrocarbon receptor (AhR) pathway in healthy rats and chronic kidney disease rats, to study the adverse effects of excess tryptophan. Design In Part I Experiment, the healthy rats were fed with diet containing 0.6, 1.2 and 1.8% tryptophan for 12 weeks. After the intervention, the blood and kidney tissues were collected. Serum creatinine and blood urea nitrogen were detected. Hematoxylin–eosin (H&E) staining was used to observe renal pathological changes. Enzyme-linked immunosorbent assay was used to detect serum kynurenic acid and AhR levels. The kidney levels of AhR, CyP1A1 and CyP1B1 were detected by western-blot. In Part II Experiment, the chronic kidney disease (CKD) model was induced by intra-gastric gavage with adenine for 4 weeks. Then the CKD rats were given tryptophan at a dose of 100 mg/kg or 500 mg/kg for eight weeks. Rat survival curve, renal function, renal tissue pathology and serum AhR were detected. Tryptophan-targeted ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS) was employed to quantitatively access the tryptophan-targeted metabolites in two parts experiments. Results In part I experiment, high tryptophan diet can increase the level of blood urea nitrogen (BUN) in healthy rats and induce focal renal tubulointerstitial injury. Tryptophan-targeted analyzes showed that high tryptophan diet feeding can significantly increase the concentration of kynurenine and indole metabolites. The serum AhR level and kidney AhR, CyP1A1 and CyP1B1 were also significantly increased in high tryptophan diet rats. In part II experiment, high tryptophan intervention induced a significant increase in mortality, serum creatinine, urea nitrogen levels, and renal pathological damage in CKD rats. The levels of tryptophan-targeted metabolites, kynurenine, xanthurenate, picolinic acid, 5-hydroxyindole-3-acetic acid, indole-3-lactic acid, indoleacetate and indoxyl sulfate, showed an upward trend in the high-dose tryptophan group (Ade + Trp-H) compared with the adenine group. The serum AhR of Ade + Trp-H rats was significantly higher than those of adenine rats. Conclusion Moderate tryptophan intake may be beneficial, but excessive tryptophan can lead to accumulation of kynurenine and indole metabolites, activate AhR pathway and induce kidney injury.
Humans have a basic physical and psychological need to move the body: Physical activity as a primary drive

Physical activity, while less necessary for survival in modern times, is still essential for thriving in life, and low levels of movement are related to numerous physical and mental health problems. However, we poorly understand why people move on a day-to-day basis and how to promote greater energy expenditure. Recently, there has been a turn to understand automatic processes with close examination of older theories of behavior. This has co-occurred with new developments in the study of non-exercise activity thermogenesis (NEAT). In this narrative review, it is hypothesized that psycho-physiological drive is important to understand movement in general and NEAT, specifically. Drive, in short, is a motivation state, characterized by arousal and felt tension, energizing the organism to acquire a basic need. Movement is a biological necessity, like food, water, and sleep, but varies across the lifespan and having the greatest impact before adolescence. Movement meets various criteria for a primary drive: (a) deprivation of it produces feelings of tension, such as an urge or craving, known as affectively-charged motivation states, and particularly the feelings of being antsy, restless, hyper or cooped up, (b) provision of the need quickly reduces tension - one can be satiated, and may even over-consume, (c) it can be provoked by qualities of the environment, (d) it is under homeostatic control, (e) there is an appetite (i.e., appetence) for movement but also aversion, and (f) it has a developmental time course. Evidence for drive has mainly come from children and populations with hyperkinetic disorders, such as those with anorexia nervosa, restless legs syndrome, and akathisia. It is also stimulated in conditions of deprivation, such as bed rest, quarantine, long flights, and physical restraint. It seems to be lacking in the hypokinetic disorders, such as depression and Parkinson’s. Thus, drive is associated with displeasure and negative reinforcement, subsuming it within the theory of hedonic drive, but it may fit better within new paradigms, such as the WANT model (Wants and Aversions for Neuromuscular Tasks). Recently developed measurement tools, such as the CRAVE scale, may permit the earnest investigation of movement drive, satiation, and motivation states in humans.