Miracle-dz/UniFAR-FTUs huggingface dataset:
Blocking Formation of the Stable HIV Reservoir: A New Perspective for HIV-1 Cure

Recent studies demonstrate that the stable HIV-1 reservoir in resting CD4+ T cells is mostly formed from viruses circulating when combination antiretroviral therapy (ART) is initiated. Here we explore the immunological basis for these observations. Untreated HIV-1 infection is characterized by a progressive depletion of memory CD4+ T cells which mostly express CD127, the α chain of the IL-7 receptor (IL-7R). Depletion results from both direct infection and bystander loss of memory CD4+ T cells in part attributed to dysregulated IL-7/IL-7R signaling. While IL-7/IL7R signaling is not essential for the generation of effector CD4+ T cells from naïve cells, it is essential for the further transition of effectors to memory CD4+ T cells and their subsequent homeostatic maintenance. HIV-1 infection therefore limits the transition of CD4+ T cells from an effector to long-lived memory state. With the onset of ART, virus load (VL) levels rapidly decrease and the frequency of CD127+ CD4+ memory T cells increases, indicating restoration of effector to memory transition in CD4+ T cells. Collectively these data suggest that following ART initiation, HIV-1 infected effector CD4+ T cells transition to long-lived, CD127+ CD4+ T cells forming the majority of the stable HIV-1 reservoir. We propose that combining ART initiation with inhibition of IL-7/IL-7R signaling to block CD4+ T cell memory formation will limit the generation of long-lived HIV-infected CD4+ T cells and reduce the overall size of the stable HIV-1 reservoir.
Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids

Cystatin B (CSTB) is a ubiquitous protein belonging to a superfamily of protease inhibitors. CSTB may play a critical role in brain physiology because its mutations cause progressive myoclonic epilepsy-1A (EPM1A), the most common form of progressive myoclonic epilepsy. However, the molecular mechanisms underlying the role of CSTB in the central nervous system (CNS) are largely unknown. To investigate the possible involvement of CSTB in the synaptic plasticity, we analyzed its expression in synaptosomes as a model system in studying the physiology of the synaptic regions of the CNS. We found that CSTB is not only present in the synaptosomes isolated from rat and mouse brain cortex, but also secreted into the medium in a depolarization-controlled manner. In addition, using biorthogonal noncanonical amino acid tagging (BONCAT) procedure, we demonstrated, for the first time, that CSTB is locally synthesized in the synaptosomes. The synaptic localization of CSTB was confirmed in a human 3D model of cortical development, namely cerebral organoids. Altogether, these results suggest that CSTB may play a role in the brain plasticity and open a new perspective in studying the involvement of CSTB deregulation in neurodegenerative and neuropsychiatric diseases.
Perspectives on Endosymbiosis in Coralloid Roots: Association of Cycads and Cyanobacteria

Past endosymbiotic events allowed photosynthetic organisms to flourish and evolve in terrestrial areas. The precursor of chloroplasts was an ancient photosynthetic cyanobacterium. Presently, cyanobacteria are still capable of establishing successful symbioses in a wide range of hosts. One particular host plant among the gymnosperms is cycads (Order Cycadales) in which a special type of root system, referred to as coralloid roots, develops to house symbiotic cyanobacteria. A number of studies have explained coralloid root formation and cyanobiont invasion but the questions on mechanisms of this host-microbe association remains vague. Most researches focus on diversity of symbionts in coralloid roots but equally important is to explore the underlying mechanisms of cycads-Nostoc symbiosis as well. Besides providing an overview of relevant areas presently known about this association and citing putative genes involved in cycad-cyanobacteria symbioses, this paper aims to identify the limitations that hamper attempts to get to the root of the matter and suggests future research directions that may prove useful.
Seismic Retrofit of Hospitals by Means of Hysteretic Braces: Influence on Acceleration-Sensitive Non-structural Components

The paper illustrates an investigation on the effectiveness of dissipative bracing (DB) systems for seismic retrofit of buildings with sensitive non-structural components (NSCs) and technological content (TC), such as medical centres. The “Giovanni Paolo II” hospital, located in a high seismic prone area in Southern Italy , is chosen as case-study. The retrofit intervention with hysteretic braces is designed according to the Italian Building Code. The seismic response of the hospital building is investigated by means of nonlinear history analyses carried out in OpenSees FE code and, in order to verify the full-operation after the earthquake, the integrity of NSCs and TC is checked. The retrofit design, thanks to the stiffening and damping effects introduced by DB system, proves suitable to protect both the structural frame and “drift-sensitive” non-structural components and content even under severe earthquakes (PGA=0.45g). Nevertheless, some concerns arise about the suitability of hysteretic braces for the protection of the “acceleration-sensitive” elements of the medical complex. Indeed, during weak earthquakes (PGA=0.17g), failures of several of these components are detected which can substantially impair the operation of the hospital in the aftermath of the seismic event.
Halophiles and Their Vast Potential in Biofuel Production

Global warming and the limitations of using fossil fuels are a main concern of all societies, and thus, the development of alternative fuel sources is crucial to improving the current global energy situation. Biofuels are known as the best alternatives of unrenewable fuels and justify increasing extensive research to develop new and less expensive methods for their production. The most frequent biofuels are bioethanol, biobutanol, biodiesel, and biogas. The production of these biofuels is the result of microbial activity on organic substrates like sugars, starch, oil crops, non-food biomasses, and agricultural and animal wastes. Several industrial production processes are carried out in the presence of high concentrations of NaCl and therefore, researchers have focused on halophiles for biofuel production. In this review, we focus on the role of halophilic microorganisms and their current utilization in the production of all types of biofuels. Also, the outstanding potential of them and their hydrolytic enzymes in the hydrolysis of different kind of biomasses and the production of biofuels are discussed.
Rifted Margins: State of the Art and Future Challenges

Improvements in seismic imaging, computing capabilities and analytical methods, as well as a number of industry deep-water wells sampling distal offshore settings, have underpinned new concepts for rifted margin evolution developed in the last two decades; these mark significant progress in our understanding of extensional systems. For example, the tectonic, sedimentary and magmatic processes linked to the formation of rifted margins have been overhauled, giving rise to more quantitative approaches and new concepts. However, these processes cannot be understood in isolation, requiring consideration of the continuum in which inheritance and physical processes are integrated within a plate tectonic framework. The major progress and fundamental developments of past research in rifted margins have been made hand-in-hand with other domains of Earth Sciences and have fundamental implications for the understanding of key geological systems such as active rifts, the ocean lithosphere, subduction zones, and collisional orogens. The 'IMAGinING RIFTING' workshop, organized in Pontresina-Switzerland in September 2017, gathered researchers from all disciplines working on rifts and rifted margins, and included participants from academia and industry. This contribution summarizes the workshop discussions, in addition to outlining our state-of-the-art knowledge of rifted margins. We highlight future challenges in unravelling the processes and conditions under which these extensional systems form and, ultimately, how tectonic plates rupture and new oceans are born. Our aims here are to provide a framework for future research endeavours and to promote collaboration not only within the rift and rifted margins communities, but across other Earth Science disciplines.
Stand Up, Students! Decisional Cues Reduce Sedentary Behavior in University Students

Background: University students are prone to sedentary behavior (SB) which is associated with multiple negative health outcomes. Sit-stand desks may allow for a reduction of SB through standing bouts. To promote standing in university students, decisional cues might be a low-cost approach that can easily be implemented. Purpose: To investigate the effects of decisional cues on students' SB, standing, and active behavior. Method: Over 3 weeks, students were observed in a building on a German university campus, which provides sit-stand-desks in study areas, using an adapted version of the SOPLAY protocol. Baseline data was collected in the first week (T1), before posters and table plaques containing decisional cues were set up in the study areas. Effects were measured in the following 2 weeks (T2 and T3). Results: 2,809 (33% female) students were observed. Sitting decreased from 92.9% [SD = 14.9] to 84.5% [SD = 22.1] from T1 to T3 [F(1, 141) = 15.6; p < 0.01; η2 = 0.10]. Standing increased from 5.6% [SD = 13.5] to 10.9% [SD = 14.4] [F(1, 141) = 9.0; p < 0.01; η2 = 0.06] and being active from 1.5% [SD = 6.9] to 4.5% [SD = 14.8] from T1 to T3 [F(1, 141) = 4.2; p < 0.05; η2 = 0.03). Main effect analyses revealed more students standing in the afternoon compared to morning and lunchtime [F(2, 140) = 3.2; p < 0.05; η2 = 0.04). Discussion: Decisional cues could decrease students' SB and promote standing or being active as alternatives. Future research should use a more rigorous study design. The content of the decisional cues should be explored more and expanded to other health promotion areas on campus.
Leukocyte Dynamics Reveal a Persistent Myeloid Dominance in Giant Cell Arteritis and Polymyalgia Rheumatica

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are inflammatory diseases requiring long-term glucocorticoid treatment. Limited data on dynamics in leukocyte counts before, during and after treatment are available. Leukocyte counts were measured, as cellular markers of inflammation, at fixed time points in our prospectively studied cohort of pre-treatment glucocorticoid-naive GCA (N = 42) and PMR (N = 31) patients. Values were compared with age-matched healthy controls (HCs; N = 51) and infection controls (N = 16). We report that before start of treatment monocyte and neutrophil counts were higher in GCA and PMR patients than in HCs, while NK- and B-cell counts were lower. C-reactive protein (CRP) levels correlated positively with monocyte counts in GCA, and negatively with B-cell and NK-cell counts in PMR. During glucocorticoid treatment, myeloid subsets remained elevated whereas lymphoid subsets tended to fluctuate. Interestingly, erythrocyte sedimentation rate (ESR) outperformed CRP as marker for relapses in GCA. We defined stable treatment-free remission groups in both GCA and PMR. GCA patients in treatment-free remission still demonstrated elevated monocytes, neutrophils, ESR, and platelets. PMR patients in treatment-free remission had normalized levels of inflammation markers, but did have elevated monocytes, lowered CD8+ T-cell counts and lowered NK-cell counts. Finally, we showed that low hemoglobin level was predictive for long-term GC treatment in PMR. Overall, leukocyte composition shifts toward the myeloid lineage in GCA and PMR. This myeloid profile, likely induced by effects of inflammation on hematopoietic stem cell differentiation, persisted during glucocorticoid treatment. Surprisingly, the myeloid profile was retained in treatment-free remission, which may reflect ongoing subclinical inflammation.
Trans-generational Immune Priming in Invertebrates: Current Knowledge and Future Prospects

Trans-generational immune priming (TGIP) refers to the transfer of the parental immunological experience to its progeny. This may result in offspring protection from repeated encounters with pathogens that persist across generations. Although extensively studied in vertebrates for over a century, this phenomenon has only been identified 20 years ago in invertebrates. Since then, invertebrate TGIP has been the focus of an increasing interest, with half of studies published during the last few years. TGIP has now been tested in several invertebrate systems using various experimental approaches and measures to study it at both functional and evolutionary levels. However, drawing an overall picture of TGIP from available studies still appears to be a difficult task. Here, we provide a comprehensive review of TGIP in invertebrates with the objective of confronting all the data generated to date to highlight the main features and mechanisms identified in the context of its ecology and evolution. To this purpose, we describe all the articles reporting experimental investigation of TGIP in invertebrates and propose a critical analysis of the experimental procedures performed to study this phenomenon. We then investigate the outcome of TGIP in the offspring and its ecological and evolutionary relevance before reviewing the potential molecular mechanisms identified to date. In the light of this review, we build hypothetical scenarios of the mechanisms through which TGIP might be achieved and propose guidelines for future investigations.
Risk Factors and Neuropsychological Assessments of Subjective Cognitive Decline (plus) in Chinese Memory Clinic

Background Since subjective cognitive decline (SCD) was standardized in 2014, many studies have investigated its features. However, the risk of SCD (plus) progressing to AD is much higher, and yet there have been few studies reporting the risk factors and neuropsychological assessment characteristics of SCD (plus). Objective To characterize SCD (plus) by comparing it with normal control (NC), amnesic mild cognitive impairment (aMCI), and Alzheimer Disease (AD) regarding their demographics, lifestyle, family history of dementia, multimorbidity and the neuropsychological assessments. Methods A total of 135 participants were recruited, including 23 NC, 30 SCD (plus), 45 aMCI and 37 AD. Descriptive statistics were provided. A logistic regression model was used to analyze the affecting factors of SCD (plus), and finally the Receiver Operating Characteristic (ROC) analysis was applied to distinguish between SCD (plus) and NC. Results (1) SCD (plus) group was younger than both the aMCI group and AD group. It consisted of more participants with mental work and higher body mass index (BMI) than the AD group. (2) Scores of Auditory Verbal Learning Test - Immediate recall (AVLT-IR) and AVLT-Long delayed recall (AVLT-LR) decreased in the following order: NC→SCD (plus)→aMCI→AD. (3) The Area Under Curve (AUC) for discriminating SCD (plus) and NC group was from 0.673 to 0.838. Conclusion Aging is an important risk factor of both NC progressing to SCD (plus), and SCD (plus) progressing to aMCI or AD. In addition to aging, lower education level and lower BMI were significantly associated with greater odds of SCD (plus) progressing to aMCI or AD patients, whereas mental work was a protective factor of SCD (plus) progressing to AD. Finally, AVLT is a sensitive indicator of the cognitive decline and impairment in SCD (plus) in relative to normal controls.
In-vivo techniques for determining nephron number.

PURPOSE OF REVIEW Many studies have suggested low nephron endowment at birth contributes to the risk of developing hypertension and chronic kidney disease (CKD) later in life. Loss of nephrons with age and disease is largely a subclinical process. New technologies are needed to count nephrons as glomerular filtration rate (GFR) is a poor surrogate for nephron number. RECENT FINDINGS Cortical volume, glomerular density, and percent globally sclerotic glomeruli are imperfect surrogates for nephron number. The disector-fractionator method is the most accurate method to count nephrons but is limited to autopsy settings. Glomerular density combined with kidney imaging and ultrafiltration coefficient-based methods require a kidney biopsy, and have been applied in living humans (kidney donors). Low nephron number predicts a higher postdonation urine albumin. Contrast-enhanced MRI has detected glomeruli without a biopsy, but so far, not in living humans. SUMMARY Currently, there is no accurate and well tolerated method for determining nephron number in living humans. A clinically useful method may allow GFR to be replaced by its more relevant determinants: nephron number and single nephron GFR. This could revolutionize nephrology by separating the measurement of chronic disease (nephron loss) from more reversible hemodynamic effects (nephron hyperfiltration/hypofiltration).
Source Risks As Constraints to Future Metal Supply

Rising consumer demand is driving concerns around the “availability” and “criticality” of metals. Methodologies have emerged to assess the risks related to global metal supply. None have specifically examined the initial supply source: the mine site where primary ore is extracted. Environmental, social, and governance (“ESG”) risks are critical to the development of new mining projects and the conversion of resources to mine production. In this paper, we offer a methodology that assesses the inherent complexities surrounding extractives projects. It includes eight ESG risk categories that overlay the locations of undeveloped iron, copper, and aluminum orebodies that will be critical to future supply. The percentage of global reserves and resources that are located in complex ESG contexts (i.e., with four or more concurrent medium-to-high risks) is 47% for iron, 63% for copper, and 88% for aluminum. This work contributes to research by providing a more complete understanding of source level constraints and risks to supply.
Risk Factors for the Occurrence of Methicillin-Resistant Staphylococcus aureus in Dairy Herds: An Update

In dairy cows, Staphylococcus aureus is a major mastitis pathogen and methicillin-resistant S. aureus (MRSA) has been reported from dairy farms around the world. The risk of foodborne zoonotic infections with bovine MRSA strains seems to be low since MRSA prevalence is low in dairy herds and milk is commonly heat treated before consumption. However, bovine mastitis caused by MRSA is an important issue in veterinary medicine since treatment options with non-β-lactam antibiotics are limited. For the development of effective MRSA prevention strategies, it is necessary to know which factors increase the risk for MRSA transmission into and within dairy herds. Therefore, the aim of this review is to summarize the risk factors for the occurrence of MRSA in dairy herds and to identify the respective knowledge gaps. MRSA was more frequently detected in conventional dairy farms than in organic farms and in larger farms than in smaller farms. Dairy farms housing pigs along with cattle are more frequently affected by MRSA. Moreover, humans carrying MRSA can probably infect dairy cows. Consequently, pigs and humans may introduce new MRSA strains into dairy herds. MRSA transmission within dairy herds was associated with improper milking hygiene procedures. Furthermore, methicillin-resistant coagulase-negative staphylococci (MR-CoNS) were repeatedly isolated from dairy farms. This is an important issue since MR-CoNS may transfer resistance genes to S. aureus. The role of antimicrobial exposure as a risk factor for the occurrence of MRSA within dairy herds needs to be further investigated.
Evidence that an episodic mode of thinking facilitates encoding of perceptually rich memories for naturalistic events relative to a gist-based mode of thinking

ABSTRACT Several studies have demonstrated that an episodic specificity induction (ESI) can influence cognitive abilities that involve episodic processes at retrieval. To better understand the downstream implications of an “episodic mode of thinking,” we investigate whether an ESI influences encoding of new events. In a between-subjects design, participants were given an ESI or gist (control) induction. In an ostensibly unrelated task, participants then were shown film clips of naturalistic events. After a filled delay, participants were given a surprise memory test, which required narrative recollection of the film clips. Participants who received the ESI generated narratives that contained more perceptual details specifically. Relative to gist thinking, an episodic mode of thinking appears to facilitate encoding of perceptually rich memories for naturalistic events.
Cross‐decades stability of an avian hybrid zone

Hybrid zones are particularly valuable for understanding the evolution of partial reproductive isolation between differentiated populations. An increasing number of hybrid zones have been inferred to move over time, but in most such cases zone movement has not been tested with long‐term genomic data. The hybrid zone between Townsend's Warblers (Setophaga townsendi) and Hermit Warblers (S. occidentalis) in the Washington Cascades was previously inferred to be moving from northern S. townsendi southwards towards S. occidentalis, based on plumage and behavioural patterns as well as a 2000‐km genetic wake of hermit mitochondrial DNA (mtDNA) in coastal Townsend's Warblers. We directly tested whether hybrid zone position has changed over 2–3 decades by tracking plumage, mtDNA and nuclear genomic variation across the hybrid zone over two sampling periods (1987–94 and 2015–16). Surprisingly, there was no significant movement in genomic or plumage cline centres between the two time periods. Plumage cline widths were narrower than expected by neutral diffusion, consistent with a ‘tension zone’ model, in which selection against hybrids is balanced by movement of parental forms into the zone. Our results indicate that this hybrid zone is either stable in its location or moving at a rate that is not detectable over 2–3 decades. Despite considerable gene flow, the stable clines in multiple phenotypic and genotypic characters over decades suggest evolutionary stability of this young pair of sister species, allowing divergence to continue. We propose a novel biogeographic scenario to explain these patterns: rather than the hybrid zone having moved thousands of kilometres to its current position, inland Townsend's met coastal Hermit Warbler populations along a broad front of the British Columbia and Alaska coast and hybridization led to replacement of the Hermit Warbler plumage with Townsend's Warbler plumage patterns along this coastline. Hence, hybrid zones along British Columbia and Alaska moved only a short distance from the inland to the coast, whereas the Hermit Warbler phenotype appears stable in Washington and further south. This case provides an example of the complex biogeographic processes that have led to the distribution of current phenotypes within and among closely related species.