Miracle-dz/UniFAR-FTUs huggingface dataset:
Subcellular proteomics for determining iron‐limited remodeling of plastids in the model diatom Thalassiosira pseudonana (Bacillariophyta)

Diatoms are important primary producers in the world's oceans, yet their growth is constrained in large regions by low bioavailable iron (Fe). Low‐Fe stress‐induced limitation of primary production is due to requirements for Fe in components of essential metabolic pathways including photosynthesis and other chloroplast plastid functions. Studies have shown that under low‐Fe stress, diatoms alter plastid‐specific processes, including components of electron transport. These physiological changes suggest changes of protein content and in protein abundances within the diatom plastid. While in silico predictions provide putative information on plastid‐localized proteins, knowledge of diatom plastid proteins remains limited in comparison to well‐studied model photosynthetic organisms. To address this, we employed shotgun proteomics to investigate the proteome of subcellular plastid‐enriched fractions from Thalassiosira pseudonana to gain a better understanding of how the plastid proteome is remodeled in response to Fe limitation. Using mass spectrometry‐based peptide identification and quantification, we analyzed T. pseudonana grown under Fe‐replete and ‐limiting conditions. Through these analyses, we inferred the relative quantities of each protein, revealing that Fe limitation regulates major metabolic pathways in the plastid, including the Calvin cycle. Additionally, we observed changes in the expression of light‐harvesting proteins. In silico localization predictions of proteins identified in this plastid‐enriched proteome allowed for an in‐depth comparison of theoretical versus observed plastid‐localization, providing evidence for the potential of additional protein import pathways into the diatom plastid.
Impairment of platelet function in both mild and severe COVID‐19 patients

Abnormalities of platelet function were reported in patients with severe COVID‐19 (severe‐C), but few data are available in patients with mild COVID‐19 (mild‐C) and after COVID‐19 recovery. The aim of this study was to investigate platelet parameters in mild‐C patients (n = 51), with no evidence of pneumonia, and severe‐C patients (n = 49), during the acute phase and after recovery, compared to 43 healthy controls. Both mild‐C and severe‐C patients displayed increased circulating activated platelets, low δ‐granule content (ADP, serotonin), impaired platelet activation by collagen (light transmission aggregometry) and impaired platelet thrombus formation on collagen‐coated surfaces under controlled flow conditions (300/s shear rate). The observed abnormalities were more marked in severe‐C patients than in mild‐C patients. Overall, 61% (30/49) of mild‐C and 73% (33/45) of severe‐C patients displayed at least one abnormal platelet parameter. In a subgroup of just 13 patients who showed no persisting signs/symptoms of COVID‐19 and were re‐evaluated at least 1 month after recovery, 11 of the 13 subjects exhibited normalization of platelet parameters. In conclusion, mild abnormalities of platelet parameters were present not only in severe‐C but also, albeit to a lesser extent, in mild‐C patients during the acute phase of COVID‐19 and normalized in most tested patients after clinical recovery.
Defecation symptoms in primary health care patients with irritable bowel syndrome

Abstract Background The objectives of the present study were to (a) measure the prevalence of defecation symptoms in IBS, (b) investigate the relationship between stool consistency and defecation symptoms in IBS, and (c) investigate the association of defecation symptoms with health-related quality of life (HRQL) and self-reported stress in patients with IBS cared for in a primary health care setting. Methods Ten primary health care centres joined the study. 282 patients with IBS as well as 372 non-IBS controls filled in gastrointestinal symptom diaries prospectively for two weeks as well as the Perceived Stress Scale-14 (PSS14) and the EuroQol barometer to measure perceived stress and HRQL, respectively. Results Incomplete evacuation was present in 51% vs. 21% of the stools among the IBS patients and the non-IBS controls, respectively. The need to strain during defecation was existing in 41% vs. 33% of the stools for the IBS patients and the non-IBS controls, respectively. Urgency was experienced in 37% of the stools in the IBS patients compared with 18% of the stools in the non-IBS controls. Patients with IBS experienced in a significant higher degree of overlapping symptoms per stool (p < 0.001 to p = 0.007). The occurrence of all defecation symptoms in the same patient was related to decreased HRQL, and increased stress (p = 0.001 to p < 0.001). Conclusions An overlap between IBS and symptoms from the anorectal region related to defecation was found in a primary health care population. Defecation symptoms are very common in primary care IBS-patients, it co-occurs with increased self-perceived stress, and decreased HRQL.
Nutraceutical Activity of Anthocyanins from the Edible Berries of Rhamnus pompana

We present the inhibitory properties of the R. pompana anthocyanin fraction (RPAF) and its major constituents on alpha‐glucosidase (AG), pancreatic lipase (PL), HMG‐CoA reductase, and ornithine decarboxylase (ODC). The effect of RPAF was also evaluated in ICR male mice subjected to oral glucose tolerance test (OGTT) and hypercaloric/atherogenic diet for 30 days. RP‐HPLC/MS profiling revealed that RPAF contained five major anthocyanins and induced slight inhibition on PL and HMG‐CoA reductase (IC50, 245–338 μg mL−1) whereas strong activity on AG and ODC (IC50, 130–133 μg mL−1) was observed. Kinetic studies and molecular docking with pelargonidin‐3‐O‐rutinoside (P3R) on ODC, revealed changes in Km (0.9514–0.9746 mM) and Vmax (1.96–2.32 μmol mg−1 min−1) suggesting mixed inhibition and molecular interaction with two active sites of ODC. P3R showed antiproliferative activity (IC50, 46.5 μM) and decreased polyamine accumulation in DLD‐1 cells. The results of OGTT confirmed that RPAF regulates postprandial glucose levels in diabetic animals which experienced a significant glucose depletion (30 %; p<0.001) from 30 to 120 min post‐treatment. Prolonged supplementation of RPAF caused significant decrease (p<0.001) in plasma glucose, total cholesterol, LDL‐c and triglycerides as well as significant increase (p<0.001) of HDL‐c compared with normoglycemic untreated animals.
The SNARE-associated protein Sft2 functions in Imh1-mediated SNARE recycling transport upon ER stress

Vesicular trafficking involving SNARE proteins play a crucial role in the delivery of cargo to the target membrane. Arf-like protein 1 (Arl1) is an important regulator of the endosomal trans-Golgi network (TGN) and secretory trafficking. In yeast, ER stress-enhances Arl1 activation and Golgin Imh1 recruitment to the late-Golgi. Although Arl1 and Imh1 are critical for GARP-mediated endosomal SNARE-recycling transport in response to ER stress, their downstream effectors are unknown. Here, we report that the SNARE-associated protein Sft2 acts downstream of the Arl1–Imh1 axis to regulate SNARE recycling upon ER stress. We first demonstrated that Sft2 is required for Tlg1/Snc1 SNARE-recycling transport under tunicamycin-induced ER stress. Interestingly, we found that Imh1 regulates Tlg2 retrograde transport to the late-Golgi under ER stress, which in turn is required for Sft2 targeting to the late-Golgi. We further showed that Sft2 with 40 amino acids deleted from the N-terminus exhibits defective mediation of SNARE recycling and decreased association with Tlg1 under ER stress. Finally, we demonstrated that Sft2 is required for GARP-dependent endosome-to-Golgi transport in the absence of Rab protein Ypt6. This study highlights Sft2 as a critical downstream effector of the Arl1-Imh1 axis, mediating the endosome-to-Golgi transport of SNAREs.
p53-dependent R-loop formation and HPV pathogenesis

Significance High-risk human papillomaviruses (HPV) are the etiological agents of genital and oropharyngeal cancers. Although prophylactic vaccines are effective in blocking initial infection by these viruses, they are not effective against existing lesions. Understanding the mechanisms regulating HPV pathogenesis is therefore important for the identification of biomarkers and for the development of therapeutics. Our work demonstrates that high levels of trimeric RNA: DNA structures called R-loops are present in HPV-positive cells derived from low-grade cervical lesions as well as in squamous cell carcinomas. These elevated R-loop levels are necessary for both viral gene expression and DNA replication. Our studies demonstrate that R-loops are critical cellular regulators of HPV pathogenesis, and they may be useful as biomarkers for viral infection or therapeutic targets.
Recovery policy, the Endangered Species Act and the Yellowstone grizzly bear (Ursus arctos horribilis): A case study analysis of the role and function of environmental organizations

This Thesis explores the question, "what are the politics of de-listing an endangered species? " The Yellowstone grizzly de-listing process offered environmental organizations a platform to provide the general public with a genuine opportunity to engage with the comments and positions, to the federal government. It contends that a symbolic consensus has been constructed about the American West, Yellowstone National Park and the grizzly bear and these constructed were strong enough to generate the majority of edited responses to the Fish and Wildlife Service during the de-listing process. This thesis looks at the manner in which environmental organizations employ this natural heritage and used it to generate public response against the de-listing process. Finally, this thesis fleshes out three emerging themes that environmental organizations use to generate response: the role of trust in transitioning oversight from the federal to state government, the role of scientific knowledge, and the role of values.
Pulmonary lesions with asteroid bodies in a pig experimentally infected with Actinobacillus pleuropneumoniae serovar 15

Five pigs experimentally infected with Actinobacillus pleuropneumoniae serovar 15 isolated in our previous study were pathologically examined. One pig died at 2 days post inoculation (dpi) and four pigs were euthanized at 7 dpi. Autopsy revealed fibrinohemorrhagic pleuropneumonia in all pigs. Histopathologically, the lesions were characterized by extensive hemorrhage and necrosis, fibrin deposition, and multifocal abscesses composed of numerous neutrophils including oat cells and numerous Gram-negative bacilli. In one survived pig, asteroid body formation was confirmed in the lung. The bacteria within the abscesses and asteroid bodies were immunohistochemically positive for antiserum raised against A. pleuropneumoniae serovar 15. This is the first report describing porcine pleuropneumonia with asteroid bodies in a pig experimentally infected with A. pleuropneumoniae serovar 15.
Generation and propagation of bursts of activity in the developing basal ganglia

Abstract The neonatal brain is characterized by intermittent bursts of oscillatory activity interspersed by relative silence. Although well-characterized for many cortical areas, to what extent these propagate and interact with subcortical brain areas is largely unknown. Here, early network activity was recorded from the developing basal ganglia, including motor/somatosensory cortex, dorsal striatum, and intralaminar thalamus, during the first postnatal weeks in mice. An unsupervised detection and classification method revealed two main classes of bursting activity, namely spindle bursts and nested gamma spindle bursts, characterized by oscillatory activity at ~ 10 and ~ 30 Hz frequencies, respectively. These were reliably identified across all three brain regions and exhibited region-specific differences in their structural, spectral, and developmental characteristics. Bursts of the same type often co-occurred in different brain regions and coherence and cross-correlation analyses reveal dynamic developmental changes in their interactions. The strongest interactions were seen for cortex and striatum, from the first postnatal week onwards, and cortex appeared to drive burst events in subcortical regions. Together, these results provide the first detailed description of early network activity within the developing basal ganglia and suggest that cortex is one of the main drivers of activity in downstream nuclei during this postnatal period.
Circulating and Synovial Monocytes in Arthritis and Ex-Vivo Model to Evaluate Therapeutic Modulation of Synovial Monocytes

ABSTRACT Monocytes are innate immune cells that play a dual role in protection of host against pathogens and initiation and perpetuation of inflammatory disorders including joint diseases. During inflammation, monocytes migrate from peripheral blood to tissues via chemokine receptors where they produce inflammatory factors. Monocytes are classified into three subsets, namely: classical, intermediate and non-classical, each subset has particular function. Synovium of patients with inflammatory joint diseases, such as rheumatoid arthritis and psoriatic arthritis as well as osteoarthritis, is enriched by monocytes that differ from circulatory ones by distinct subsets distribution. Several therapeutic agents used systemically or locally through intra-articular injections in arthritis management modulate monocyte subsets. This scoping review summarized the existing literature delineating the effect of common therapeutic agents used in arthritis management on circulating and synovial monocytes/macrophages. As certain agents have an inhibitory effect on monocytes, we propose to test their potential to inhibit synovial monocytes via an ex-vivo platform based on cultured synovial fluid mononuclear cells derived from patients with rheumatic diseases. Information obtained from the ex-vivo platform can be applied to explore the therapeutic potential of medications in clinical practice.
'This suburb is of value to the whole of Melbourne': Save Our Suburbs and the struggle against inappropriate development

Struggles around the conservation and development of the built environment can be productively examined through the frameworks provided by Pierre Bourdieu’s conceptions of habitus, field and economic, cultural, social and symbolic capitals. In this paper, I examine, firstly, the strategies and resources mobilised in the defence of specific hierarchies of valuations of urban areas. Secondly, I look at the way in which the Melbourne resident action group, Save Our Suburbs, was able to subsume different sources of conflict under the banner of a particular representation of ‘a home’ in ‘the suburbs’ of ‘Melbourne’ – representations which the state government of Victoria attempted to devalue through emphases on global economic imperatives, free markets in urban land, and images of new ‘global’ workers and residents. Finally, through this examination I suggest the importance of location, place and built form for the Bourdieu-ian concepts of habitus, capitals and distinction.
Alterations of lipid‐mediated mitophagy result in aging‐dependent sensorimotor defects

The metabolic consequences of mitophagy alterations due to age‐related stress in healthy aging brains versus neurodegeneration remain unknown. Here, we demonstrate that ceramide synthase 1 (CerS1) is transported to the outer mitochondrial membrane by the p17/PERMIT transporter that recognizes mislocalized mitochondrial ribosomes (mitoribosomes) via 39‐FLRN‐42 residues, inducing ceramide‐mediated mitophagy. P17/PERMIT‐CerS1‐mediated mitophagy attenuated the argininosuccinate/fumarate/malate axis and induced d‐glucose and fructose accumulation in neurons in culture and brain tissues (primarily in the cerebellum) of wild‐type mice in vivo. These metabolic changes in response to sodium‐selenite were nullified in the cerebellum of CerS1to/to (catalytically inactive for C18‐ceramide production CerS1 mutant), PARKIN−/− or p17/PERMIT−/− mice that have dysfunctional mitophagy. Whereas sodium selenite induced mitophagy in the cerebellum and improved motor‐neuron deficits in aged wild‐type mice, exogenous fumarate or malate prevented mitophagy. Attenuating ceramide‐mediated mitophagy enhanced damaged mitochondria accumulation and age‐dependent sensorimotor abnormalities in p17/PERMIT−/− mice. Reinstituting mitophagy using a ceramide analog drug with selenium conjugate, LCL768, restored mitophagy and reduced malate/fumarate metabolism, improving sensorimotor deficits in old p17/PERMIT−/− mice. Thus, these data describe the metabolic consequences of alterations to p17/PERMIT/ceramide‐mediated mitophagy associated with the loss of mitochondrial quality control in neurons and provide therapeutic options to overcome age‐dependent sensorimotor deficits and related disorders like amyotrophic lateral sclerosis (ALS).
Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies

ABSTRACT Introduction The development of molecularly targeted anticancer therapies and immunotherapy continues to revolutionize the treatment of cancer. FDA accelerated approvals of novel targeted therapies allowed for introduction of these agents into the clinic at a rapid rate. On-and off-target ocular toxicities are prevalent treatment-related adverse events of newer therapies including antibody drug conjugates (ADCs) and immunotherapy. Ocular toxicities associated with ADCs and immunotherapy have heterogeneous presentations and pathogenesis requiring unique and often complex monitoring, and management. Areas covered In this article, we provide an updated review of treatment-emergent ocular toxicity associated with new and novel oncologic therapies and summarize guidelines and best practice strategies for prevention, monitoring and management. A literature search was performed through PubMed, ClinicalTrials.gov, and FDA website (1 January 2017 to 10 May 2023) to identify relevant information. Expert opinion The implementation of a strategy for monitoring, prevention, and management of treatment-related ocular toxicities involves a multi-disciplinary, often cross-center approach. Communication with infusion nursing leadership, clinic staff, and eye care providers is crucial to the successful implementation of eye care plans to prevent and manage ocular toxicity.
A Screening Protocol for Exploring Loop Length Requirements for the Formation of a Three Cytosine-Cytosine+ Base-Paired i-Motif.

DNA sequences containing at least four runs of repetitive cytosines can fold into tetra-helical structures called i-Motifs. The interest in these DNA secondary structures is increasing due to their therapeutical and technological applications. Still, limited knowledge of their folding requirements is currently available. We developed a novel step-by-step pipeline for the systematic screening of putative i-Motif forming model sequences. Focusing on structures comprising only three cytosine-cytosine+ base pairs, we investigated what are the minimal lengths of the loops required for formation of an intra-molecular i-Motif. Our data indicate that two and three nucleotides are required to connect the strands through the major and the minor grooves of the i-Motif, respectively. Additionally, they highlight an asymmetric behavior according to the distribution of the cytosines. Specifically, no sequence containing a single cytosine in the first and third run was able to fold into intra-molecular i-Motifs with the same stability of those formed when the first and the third run comprise two cytosines. This knowledge represents a step forward to the development of prediction tools for the proper identification of biologically functional i-Motif as well as for the rational design of these secondary structures as technological devices.
Temporal variations of the three‐dimensional rainfall infiltration process in heterogeneous soil

Preferential flow is considered to play an important role in the conduction of soil water. However, during a natural rain event, whether this significance changes or not and how it changes are still not understood. In this paper, by analyzing three‐dimensional spatial and temporal variations of soil water content at two field sites, temporal variations of the three‐dimensional rainfall infiltration process in a heterogeneous soil were studied. The three‐dimensional soil water contents were obtained by soil moisture tomography. For eight selected rain events, temporal variations of infiltration area, homogeneity of the infiltration process, and average water content increment were analyzed. Relationships between the infiltration homogeneity and the infiltration area and the average water content increment were investigated. The results show that the three‐dimensional rainfall infiltration in heterogeneous soil varies with rainfall process. For rain events with short duration time and low rain intensity, the infiltration process behaves preferentially and heterogeneously. The preferential flow plays an important role in the conduction of soil water. For rain events with long duration time and high rain intensity, the infiltration process shows more homogeneous and plug‐like characteristics. The preferential flow becomes less important. In a rain event, during the initial period of the rain, the infiltration process usually is heterogeneous and preferential, starting from partial areas in the layers. However, with continuing rainfall, the infiltration area gradually expands to the entire layers and the infiltration process becomes more homogeneous and plug‐like.
Dexterous robotic manipulation via a dynamic sliding mode force/position control with bounded inputs

Grasping and manipulation are common robotic tasks which require to properly control the interaction forces and position of multiple robots end-effectors. In this study, the authors focus on the problem of dexterous manipulation of rigid objects by means of a cooperative robotic system. Unlike several works, they consider the more complex case when the manipulated object is not mechanically attached to the robots' end-effectors. In addition, they address the control problem of designing a control law with continuous and bounded input torques for cooperative robots in constrained motion. To guarantee a stable grasp and a fine manipulation a centralised control algorithm based on the Orthogonalisation principle and a dynamic sliding mode control is proposed. The control algorithm does not require the knowledge of the dynamic model of the robot manipulators and manipulated object for implementation. Experimental results are presented to show the good performance of the proposed controller. In addition, the stability analysis of the closed-loop dynamics is developed.
Clinical and laboratory predictors and prevalence of immune reconstitution inflammatory syndrome in patients with Whipple's disease

Whipple's disease (WD) is a rare and potentially fatal infectious disease caused by Tropheryma whipplei. It is characterized by a long prodromal phase that mimics a rheumatological disease, often leading to immunosuppressant treatment. Immune reconstitution inflammatory syndrome (IRIS) is currently the most important complication of WD, requiring prompt recognition and treatment as it can be fatal. However, epidemiological data on IRIS are scarce. We aimed to identify the clinical and laboratory predictors of IRIS at WD diagnosis and to evaluate whether the prevalence of IRIS has changed over time.