Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Peptidomic Approach for Identification of Low and High Molecular Weight Tauopathy Peptides Following Calpain Digestion, and Primary Culture Neurotoxic Challenges

Tauopathy is a class of a neurodegenerative disorder linked with tau hyperphosphorylation, proteolysis, and aggregation. Tau can be subjected to proteolysis upon calpain activation in Alzheimer disease (AD), and traumatic brain injury (TBI). We and others have extensively researched calpain-mediated tau breakdown products (Tau-BDP; 45K, 35K, and 17K). Tau proteolysis might also generate low molecular weight (LMW ≤10K) proteolytic peptides after neurodegenerative damage. In this study, we have subjected purified tau protein (phospho and non-phospho) and mouse brain lysate to calpain-1 digestion to characterize the LMW generated by nano-liquid chromatography coupled to electrospray ionization to tandem mass spectrometry (nano-LC-ESI-MS/MS). We have also challenged differentiated primary cerebrocortical neuronal cultures (CTX) with neurotoxic agents (calcium ionophore calcimycin (A23187), staurosporine (STS), N-methyl-D-aspartate (NMDA), and Maitotoxin (MTX)) that mimic neurodegeneration to investigate the peptidome released into the conditioned cell media. We used a simple workflow in which we fractionate LMW calpain-mediated tau peptides by ultrafiltration (molecular weight cut-off value (MWCO) of 10K) and subject filtrate fractions to nano-LC-MS/MS analysis. The high molecular weight (HMW) peptides and intact proteins retained on the filter were analyzed separately by western blotting using total and phospho-specific tau antibodies. We have identified several novel proteolytic tau peptides (phosphorylated and non-phosphorylated) that are only present in samples treated with calpain or cell-based calpain activation model (particularly N- and C-terminal peptides). Our findings can help in developing future research strategies emphasizing on the suppression of tau proteolysis as a target.
Prucalopride inhibits lung cancer cell proliferation, invasion, and migration through blocking of the PI3K/AKT/mTor signaling pathway

Lung cancer is the main cause of cancer incidence and mortality around the world. Prucalopride is an agonist for the 5-hydroxytryptamine 4 receptor, but it was unknown whether prucalopride could be used to treat lung cancer. To investigate the biological effects of prucalopride on proliferation, apoptosis, invasion, and migration of lung cancer cells, and its underlying molecular mechanism in the progression of lung cancer, we performed this study. The Cell Counting Kit 8 assay was used to measure the proliferation of A549/A427 lung cancer cells treated with prucalopride. Transwell assay was applied to evaluate cell invasion and migration. Cell apoptosis was detected by flow cytometry and Western blot analyses. The expression levels of related proteins in the PI3K/AKT/mTor signaling pathway were analyzed by Western blotting. Prucalopride inhibited the proliferation, invasion, and migration of A549/A427 human lung cancer cells. It also induced autophagy and apoptosis and decreased the expression of the phosphorylated protein kinase B (AKT) and mammalian target of rapamycin (mTor) in these cells. This study implied an inhibitory role for prucalopride in the progression of human lung cancer.
A Bibliometric Analysis of the Health Field Regarding Social Networks and Young People

Social networks have historically been used to share information and support regarding health-related topics, and this usage has increased with the rise of online social media. Young people are high users of social media, both as passive listeners and as active contributors. This study aimed to map the trends in publications focused on social networks, health, and young people over the last 40 years. Scopus and the program VOSviewer were used to map the frequency of the publications, keywords, and clusters of researchers active in the field internationally. A structured keyword search using the Scopus database yielded 11,966 publications. The results reveal a long history of research on social networks, health, and young people. Research articles were the most common type of publication (68%), most of which described quantitative studies (82%). The main discipline represented in this literature was medicine, with 6062 documents. North American researchers dominate the field, both as authors and partners in international research collaborations. The present article adds to the literature by elucidating the growing importance of social networks in health research as a topic of study. This may help to inform future investments in public health research and surveillance using these novel data sources.
Development of Dog Immune System: From in Uterus to Elderly

Immune system recognize and fight back foreign microorganisms and inner modifications that lead to deficient cell and tissue functions. During a dog’s life, the immune system needs to adapt to different physiological conditions, assuring surveillance and protection in a careful and controlled way. Pregnancy alters normal homeostasis, requiring a balance between immunity and tolerance. The embryos and fetus should be protected from infections, while the female dog must tolerate the growing of semi-allografts in her uterus. After birth, newborn puppies are at great risk of developing infectious diseases, because their immune system is in development and immune memory is absent. Passive transfer of immunity through colostrum is fundamental for puppy survival in the first weeks of life, but hampers the development of an active immune response to vaccination. At the end of life, dogs experience a decline in the structure and functional competence of the immune system, compromising the immune responses to novel antigenic challenges, such as infections and vaccines. Therefore, the current article reviews the general processes related to the development of the dog´s immune system, providing an overview of immune activity throughout the dog’s life and its implications in canine health, and highlighting priority research goals.
TRPM7 deficiency suppresses cell proliferation, migration, and invasion in human colorectal cancer via regulation of epithelial-mesenchymal transition.

BACKGROUND It has been documented that transient receptor potential melastatin 7 (TRPM7) plays a pivotal role in the development of multiple cancers. However, the role of TRPM7 in human colorectal cancer (CRC) is poorly understood. Therefore, the aim of this study was to investigate the expression and significance of TRPM7 in CRC. METHODS In this study, TRPM7 expression was first investigated in Gene Expression Omnibus (GEO), and then validated it with the data from our medical center. CCK-8, colony survival, transwell, and flow cytometry assays were employed to evaluate the effects of TRPM7 knockdown on the CRC cell proliferation, migration, and invasion, as well as cell cycle and apoptosis. RESULTS We observed markedly increased TRPM7 expression in CRC tissues. CRC patients with high expression of TRPM7 suggested deeper tumor infiltration, positive lymph node metastasis, distant metastasis, and advanced clinical stage. In addition, TRPM7 was also overexpressed in CRC cell lines. Downregulated TRPM7 in vitro suppressed CRC cell proliferation, migration, and invasion, as well as triggered cell cycle arrest at the G0/G1 phase, reduced the S phase, and promoted apoptosis. Importantly, decreased TRPM7 in CRC cells reversed the epithelial-mesenchymal transition (EMT) status, accompanied by downregulation of N-cadherin and upregulation of E-cadherin. CONCLUSION Our study indicated that the expression of TRPM7 was positively correlated with tumor infiltration, lymph node metastasis, distant metastasis and clinical stage of CRC. Besides, decreased TRPM7 in vitro inhibited CRC cell proliferation, migration and invasion by modulating EMT.
The Ciliary Muscle and Zonules of Zinn Modulate Lens Intracellular Hydrostatic Pressure Through Transient Receptor Potential Vanilloid Channels

Purpose Lenses have an intracellular hydrostatic pressure gradient to drive fluid from central fiber cells to surface epithelial cells. Pressure is regulated by a feedback control system that relies on transient receptor potential vanilloid (TRPV)1 and TRPV4 channels. The ciliary muscle transmits tension to the lens through the zonules of Zinn. Here, we have examined if ciliary muscle tension influenced the lens intracellular hydrostatic pressure gradient. Methods We measured the ciliary body position and intracellular hydrostatic pressures in mouse lenses while pharmacologically causing relaxation or contraction of the ciliary muscle. We also used inhibitors of TRPV1 and TRPV4, in addition to phosphoinositide 3-kinase (PI3K) p110α knockout mice and immunostaining of phosphorylated protein kinase B (Akt), to determine how changes in ciliary muscle tension resulted in altered hydrostatic pressure. Results Ciliary muscle relaxation increased the distance between the ciliary body and the lens and caused a decrease in intracellular hydrostatic pressure that was dependent on intact zonules and could be blocked by inhibition of TRPV4. Ciliary contraction moved the ciliary body toward the lens and caused an increase in intracellular hydrostatic pressure and Akt phosphorylation that required intact zonules and was blocked by either inhibition of TRPV1 or genetic deletion of the p110α catalytic subunit of PI3K. Conclusions These results show that the hydrostatic pressure gradient within the lens was influenced by the tension exerted on the lens by the ciliary muscle through the zonules of Zinn. Modulation of the gradient of intracellular hydrostatic pressure in the lens could alter the water content, and the gradient of refractive index.
Exploration of the Association of Selected Pain Diagnoses with Risky Alcohol Use among Active Duty Soldiers

Background Pain and its consequences remain of concern, particularly in high-risk occupations such as the military. Alcohol is a legal and accessible means of self-medication, and risky alcohol use is associated with potentially serious consequences. This exploratory analysis aimed to better understand the association of selected pain diagnoses with risky alcohol use among soldiers returning from deployment. Methods Analysis of data from active duty soldiers returning from Afghanistan or Iraq deployments in fiscal years 2008–2011 who completed Department of Defense health questionnaires after deployment (n = 267,100). Each questionnaire included self-reported alcohol consumption and items yielding AUDIT-C screening scores. Military Health System data were used to identify diagnoses of pain-related conditions. Results About 70% of soldiers had none of the selected pain diagnoses either pre- or post-deployment. 10% had incident pain diagnoses (only post-deployment), 7% had persistent pain diagnoses (both pre- and post-deployment), and 13% had remitted pain diagnoses (only pre-deployment). On the AUDIT-C, 39% screened positive for at-risk drinking and 6% were likely to have severe alcohol problems. Half of the respondents reported any binge drinking; 20% at least monthly binge drinking. Logistic regression analyses found reduced odds of risky alcohol use post-deployment in association with incident and persistent pain diagnoses, compared to no pain diagnoses pre- or post-deployment. Conclusions Pain diagnoses, binge drinking, and risky alcohol use were prevalent among this sample of Army soldiers. An inverse relationship was found between pain diagnosis (incident, persistent) and risky alcohol use post-deployment. Attention should continue to be paid to risky alcohol use in this population, yet these exploratory findings do not suggest that soldiers with the pain diagnoses used in this study are at greater risk. Combat exposure, traumatic brain injury, and psychological health were more important predictors, and should continue to warrant enhanced alcohol screening.
Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness

Gulf War illness (GWI) is characterized by the persistence of inflammatory bowel disease, chronic fatigue, neuroinflammation, headache, cognitive impairment, and other medically unexplained conditions. Results using a murine model show that enteric viral populations especially bacteriophages were altered in GWI. The increased viral richness and alpha diversity correlated positively with gut bacterial dysbiosis and proinflammatory cytokines. Altered virome signature in GWI mice also had a concomitant weakening of intestinal epithelial tight junctions with a significant increase in Claudin-2 protein expression and decrease in ZO1 and Occludin mRNA expression. The altered virome signature in GWI, decreased tight junction protein level was followed by the presence an activation of innate immune responses such as increased Toll-like receptor (TLR) signaling pathways. The altered virome diversity had a positive correlation with serum IL-6, IL-1β, and IFN-γ, intestinal inflammation (IFN-γ), and decreased Brain-Derived Neurotrophic Factor (BDNF), a neurogenesis marker. The co-exposure of Gulf War chemical and antibiotic (for gut sterility) or Gulf War chemical and Ribavirin, an antiviral compound to suppress virus alteration in the gut showed significant improvement in epithelial tight junction protein, decreased intestinal-, systemic-, and neuroinflammation. These results showed that the observed enteric viral dysbiosis could activate enteric viral particle-induced innate immune response in GWI and could be a novel therapeutic target in GWI.
Unraveling the structure and function of the petal appendages in the tribe Schwenckieae (Solanaceae).

The tribe Schwenckieae (Solanaceae) is characterized by the presence of appendages on the corolla, a diagnostic trait for the group. These appendages constitute a median distal projection of the 3-lobed petal and occur into the genera Melananthus and Schwenckia, but are absent in Heteranthia. We investigated the micromorphology and anatomical structure of the appendages and lateral petal lobes of Schwenckia americana (two varieties), S. angustifolia, S. curviflora and S. novaveneciana, and Melananthus fasciculatus. We also performed histochemical tests to determine if the appendages are involved in the production of volatiles, acting as a fragrance secretory structure (osmophores). The appendages have a uniseriate epidermis, whose cells store phenolics and lipids. The parenchyma is starch-rich just prior to anthesis in all species studied. The sensory test and anatomical analyses identified scent-secreting tissues, not only in the appendages, but also in the lateral petal lobes, whose cells are papillose with a sculptured surface. The α-naphthol p-phenylenediamine (NADI) reaction detected volatile (essential oils) compounds in S. americana var. americana and S. americana var. angustifolia. We demonstrated the secretory tissues and the production of lipids in the corolla appendages of Schwenckia and Melananthus, which indicated their osmogenic function and probable scent emission to attract pollinators.
MINI-SYMPOSIUM: MOLECULAR MARKERS IN PATHOLOGY Cyclin E and p27: their putative role as prognostic markers

Summary Abnormalities or derangements ofthe orderly proliferation and cycling of cells is the quintessential de¢nition of a cancer or malignant cell.The complex nature of the interaction of several interdependent cell cycle proteins has and continues to be unravelled.Key functions have been ascribed to many of the proteins and the delicate balance that maintains cell normal cell cycling is now understood.Within the cell cycle, the G1proteins have come under intense scrutiny, especially the interaction between cyclin E and p27. Essentially, cyclin E drives the cell cycle forward towards mitosis, while p27 acts as a brake preventing cell cycle progression.The levels of these two proteins, independently and together, have been analysed in many studies in several tumour types. A pattern or trend has emerged: high cyclin E with low p27 is an adverse prognostic indicator in the majority of commonly encountered malignant tumours. Furthermore, in several instances, there is a stepwise increase of cyclin E and decrease of p27 that matches the progression from dysplastic, pre-invasive lesions to full-blown invasive malignanttumours. As a cautionary note, there are exceptions to this tenet as exempli¢ed by bladder and oesophagealcancers, where the relationship between cyclin E and p27 is not straightforward. The body of evidence in the literature points to both cyclin E and p27 as being useful adjuncts to prognostication indices, but not unreservedly as independent portenders of outcome. c 2002 Elsevier Science Ltd.
Treatment of displaced proximal humeral fractures in elderly patients

The optimal treatment for patients with displaced fractures of the proximal humerus, especially elderly patients with osteoporosis, is still controversial. For the 2and 3-part fractures according to the Neer classification, there is a trend towards more frequent surgical interventions with modern locking plates. For the more comminuted 4-part fracture with a higher risk for avascular necrosis, a primary hemiarthroplasty (HA) has been the accepted treatment. The alternative treatment for these fractures is non-operative with a short immobilization period and early physiotherapy. The latest Cochrane review regarding this topic concludes that there is insufficient evidence from randomized controlled trials (RCTs) to determine which interventions are the most appropriate for the management of different types of fractures. It is also stated that future trials should use validated outcome measures, including patient-assessed functional outcomes such as health-related quality of life (HRQoL). However, due to their design, quality-of-life instruments may be less sensitive for detecting small but yet important changes, i.e. they may have a limited responsiveness. In a prospective cohort study with a 2-year follow-up, 50 elderly patients with a displaced 2-part fracture of the proximal humerus were treated with open reduction and internal fixation with a locking plate. The result showed that locking plates appear to be a good treatment alternative with an acceptable complication rate and an acceptable functional outcome. In an RCT with a 2-year follow-up, 60 elderly patients with a displaced 3-part fracture of the proximal humerus were allocated to treatment with open reduction and internal fixation with a locking plate or non-operative treatment. The results of the study indicated an advantage in functional outcome and HRQoL in favor of the locking plate as compared to non-operative treatment, but at a cost of additional surgery in 30% of the patients. The main advantage of the locking plate appeared to be an improved range of motion (ROM). In an RCT with a 2-year follow-up, 55 patients with a displaced 4-part fracture of the proximal humerus were allocated to treatment with a primary HA or non-operative treatment. The results of the study demonstrated a significant advantage in quality of life in favor of HA as compared to non-operative treatment. The main advantage of HA appeared to be less pain, while there were no differences in ROM. 145 patients with a displaced proximal humeral fracture were included in a study with the aim to evaluate the responsiveness of the EQ-5D instrument. The EQ-5D displayed good internal and external responsiveness and can be recommended for use as a quality-of-life measure in patients with this particular injury. An additional conclusion of the studies was that, regardless of primary treatment, a displaced fracture of the proximal humerus results in a substantial negative effect upon the patients’ HRQoL.
Forward osmosis with an algal draw solution to concentrate municipal wastewater and recover resources

This study aimed to concentrate and recover resources from municipal wastewater with a novel forward osmosis (FO) system. The FO system used synthetic seawater as the draw solution (DS) to extract water from the feed solution (FS) (synthetic raw municipal wastewater). Because ammonium passed through the FO membrane from the FS to the DS, we cultivated an algal strain (Chlorella vulgaris) in the DS to remove and recover ammonium. For three consecutive FO cycles, the algal FO system removed 35.4% of the ammonium from the DS, increased the concentrations of COD and PO43--P in the FS by 43.0%, and achieved a water flux of 11.59 ± 0.49 L m−2 hr−1. Throughout the FO cycles, the algal biomass concentration of the DS stayed at 606 ± 29 mg COD/L due to simultaneous algal growth and DS dilution. This FO process may be feasible to implement for full‐scale applications to concentrate wastewater and recover resources.
Subarachnoid hemorrhage and cerebral perfusion are associated with brain volume decrease in a cohort of predominantly mild traumatic brain injury patients.

Biomarkers are needed to identify traumatic brain injury patients at risk for accelerated brain volume loss and its associated functional impairment. Subarachnoid hemorrhage (SAH) has been shown to affect cerebral volume and perfusion, possibly by induction of inflammation and vasospasm. The purpose of this study was to assess the impact of SAH due to trauma on cerebral perfusion and brain volume. For this, MRI was performed <48 hours and at 90 days after TBI. The <48h scan was used to assess SAH presence and perfusion. Brain volume changes were assessed quantitatively over time. Differences in brain volume change and perfusion were compared between SAH and non-SAH patients. A linear regression analysis with clinical and imaging variables was used to identify predictors of brain volume change. All patients had a relatively good status on admission, and 83% presented with the maximum Glasgow coma scale score. Brain volume decrease was greater in the 11 SAH patients (-3.2%, IQR -4.8 - -1.3%) compared to the 46 non-SAH patients (-0.4%, IQR -1.8 - 0.9%; P<0.001). Brain perfusion was not affected by SAH, but it was correlated with brain volume change (ρ=0.39; P<0.01). Forty-three percent of brain volume change was explained by SAH (β -0.40, P=0.001), loss of consciousness (β -0.24, P=0.035) and peak perfusion curve signal intensity height (0.27, P=0.012). Subarachnoid hemorrhage and lower perfusion in the acute phase may identity traumatic brain injury patients at increased risk for accelerated brain volume loss, in addition to loss of consciousness occurrence. Future studies should determine whether the findings apply to TBI patients with worse clinical status on admission. SAH predicts brain volume decrease independent of brain perfusion. This indicates the adverse effects of SAH extend beyond vasoconstriction, and that hypoperfusion also occurs separately from SAH.
The Endocrine Function of the Heart: Physiology and Involvements of Natriuretic Peptides and Cyclic Nucleotide Phosphodiesterases in Heart Failure

Besides pumping, the heart participates in hydro-sodium homeostasis and systemic blood pressure regulation through its endocrine function mainly represented by the large family of natriuretic peptides (NPs), including essentially atrial natriuretic (ANP) and brain natriuretic peptides (BNP). Under normal conditions, these peptides are synthesized in response to atrial cardiomyocyte stretch, increase natriuresis, diuresis, and vascular permeability through binding of the second intracellular messenger’s guanosine 3′,5′-cyclic monophosphate (cGMP) to specific receptors. During heart failure (HF), the beneficial effects of the enhanced cardiac hormones secretion are reduced, in connection with renal resistance to NP. In addition, there is a BNP paradox characterized by a physiological inefficiency of the BNP forms assayed by current methods. In this context, it appears interesting to improve the efficiency of the cardiac natriuretic system by inhibiting cyclic nucleotide phosphodiesterases, responsible for the degradation of cGMP. Recent data support such a therapeutic approach which can improve the quality of life and the prognosis of patients with HF.