A Workflow of Integrated Resources to Catalyze Network Pharmacology Driven COVID-19 Research.

In the event of an outbreak due to an emerging pathogen, time is of the essence to contain or to mitigate the spread of the disease. Drug repositioning is one of the strategies that has the potential to deliver therapeutics relatively quickly. The SARS-CoV-2 pandemic has shown that integrating critical data resources to drive drug-repositioning studies, involving host-host, host-pathogen, and drug-target interactions, remains a time-consuming effort that translates to a delay in the development and delivery of a life-saving therapy.

Morphological Changes in the Myotendinous Junction of mdx Mice.

The myotendinous junction (MTJ) is the interface between muscle and tendon, and it is the main area of force transmission of the locomotor apparatus. Dystrophic processes promote pathological injury which affects the skeletal muscle and can influence the morphology of the MTJ. This study aimed to investigate the adaptations in MTJ morphology of mdx mice in the tibialis anterior muscle.

Myotendinous Junction Components of Different Skeletal Muscles Present Morphological Changes in Obese Rats.

Obesity is characterized by excess adipose tissue and chronic inflammation and promotes extensive changes that can compromise skeletal muscles’ structural and functional integrity. Obesity can seriously impact the force transmission region between the muscle and the tendon, the myotendinous junction (MTJ). The present study aimed to investigate the plasticity of muscle fibers and MTJ regions in high-fat diet-induced obesity in rat tibialis anterior (TA) and soleus (SO) muscles.

A Workflow of Integrated Resources to Catalyze Network Pharmacology Driven COVID-19 Research.

Motivation: In the event of an outbreak due to an emerging pathogen, time is of the essence to contain or to mitigate the spread of the disease. Drug repositioning is one of the strategies that has the potential to deliver therapeutics relatively quickly. The SARS-CoV-2 pandemic has shown that integrating critical data resources to drive drug-repositioning studies, involving host-host, hostpathogen and drug-target interactions, remains a time-consuming effort that translates to a delay in the development and delivery of a life-saving therapy.

SRF and SRFΔ5 Splicing Isoform Recruit Corepressor LSD1/KDM1A Modifying Structural Neuroplasticity and Environmental Stress Response.

Ten to 20% of western countries population suffers from major depression disorder (MDD). Stressful life events represent the main environmental risk factor contributing to the onset of MDD and other stress-related neuropsychiatric disorders. In this regard, investigating brain physiology of stress response underlying the remarkable individual variability in terms of behavioral outcome may uncover stress-vulnerability pathways as a source of candidate targets for conceptually new antidepressant treatments.

Multiple Layers of Regulation in Alzheimer's Disease Implicate Long Non-Coding RNAs.

Cyclin-dependent kinase 5 regulatory subunit 1 () gene encodes for p35, the main activator of Cyclin-dependent kinase 5 (CDK5). The active p35/CDK5 complex is involved in numerous aspects of brain development and function, and its deregulation is closely associated to Alzheimer's disease (AD) onset and progression. We recently showed that miR-15/107 family can negatively regulate expression modifying mRNA stability.

NeuroLSD1: Splicing-Generated Epigenetic Enhancer of Neuroplasticity.

The acquisition and maintenance of the specific neuronal functions underlying learning, memory, and emotion require transduction of environmental stimuli into remodeling of neuronal circuitry. This process occurs via induction of plasticity-related transcriptional programs. The epigenetic enzyme lysine-specific demethylase-1 (LSD1), also known as lysine demethylase 1A (KDM1A), and its neurospecific splicing variant neuroLSD1 have been implicated in this process through an antagonistic mechanism.

LSD1/KDM1A mutations associated to a newly described form of intellectual disability impair demethylase activity and binding to transcription factors.

Genetic diseases often lead to rare and severe syndromes and the identification of the genetic and protein alterations responsible for the pathogenesis is essential to understand both the physiological and pathological role of the gene product. Recently, de novo variants have been mapped on the gene encoding for the lysine-specific histone demethylase 1 (LSD1)/lysine(K)-specific histone demethylase 1A in three patients characterized by a new genetic disorder. We have analyzed the effects of these pathological mutations on the structure, stability and activity of LSD1 using both in vitro and cellular approaches.

LSD1 modulates stress-evoked transcription of immediate early genes and emotional behavior.

Behavioral changes in response to stressful stimuli can be controlled via adaptive epigenetic changes in neuronal gene expression. Here we indicate a role for the transcriptional corepressor Lysine-Specific Demethylase 1 (LSD1) and its dominant-negative splicing isoform neuroLSD1, in the modulation of emotional behavior. In mouse hippocampus, we show that LSD1 and neuroLSD1 can interact with transcription factor serum response factor (SRF) and set the chromatin state of SRF-targeted genes early growth response 1 (egr1) and c-fos Deletion or reduction of neuro LSD1 in mutant mice translates into decreased levels of activating histone marks at egr1 and c-fos promoters, dampening their psychosocial stress-induced transcription and resulting in low anxiety-like behavior.

Epidemiological report on the treatment of patients with gestational trophoblastic disease in 10 Brazilian referral centers: results after 12 years since International FIGO 2000 Consensus.

Objective: To evaluate treatment of Brazilian patients with gestational trophoblastic disease (GTD).

Study Design: A retrospective cohort study with analysis of medical reports performed in 10 Brazilian referral centers from January 2000 to December 2011.

Results: Of 5,250 patients 3 died (0.

Acceptability of telemedicine and other cancer genetic counseling models of service delivery in geographically remote settings.

This work examined acceptability of cancer genetic counseling models of service delivery among Maine residents at risk for hereditary cancer susceptibility disorders. Pre-counseling, participants ranked characteristics reflecting models of care from most to least important including: mode-of-communication (in-person versus telegenetics), provider level of training (genetic specialty versus some training/experience), delivery format (one-on-one versus group counseling), and location (local versus tertiary service requiring travel). Associations between models of care characteristic rankings and patient characteristics, including rural residence, perceived cancer risk, and perceived risk for a hereditary cancer risk susceptibility disorder were examined.

C-Terminal acidic domain of ubiquitin-conjugating enzymes: a multi-functional conserved intrinsically disordered domain in family 3 of E2 enzymes.

E2 ubiquitin-conjugating enzymes are key elements of the ubiquitin (Ub) pathway, since they influence processivity and topology of the Ub chain assembly and, as a consequence, the fate of the target substrates. E2s are multi-domain proteins, with accessory N-terminal or C-terminal domains that can contribute to the specificity for the cognate Ub-like molecules, or even the E3. In this context, the thorough structural characterization of E2 accessory domains is mandatory, in particular when they are associated to specific functions.

Carcinosarcoma and separate neuroendocrine malignant tumor of a malignancy promoter, the gastric stump.

We report a case of carcinosarcoma and separate neuroendocrine malignant tumor of the gastric stump. The case is interesting because of its unique pathological features and it confirms the role of the gastric stump as a very important "malignancy promoter".

[Embolization with adipose tissue (author's transl)].

The authors present their animal experimental work on adipose tissue as an occlusive agent, using the renal and carotid areas as parenchyma in which to test its effect. Work was planned in four series: the first with a survival rate of 24 to 72 h, the second with a survival rate of 7 to 18 days, the third, 45 to 58 days, and the fourth, 58 to 90 days. Angiographic and anatomopathologic postembolization controls were performed, thus supplying conclusive radiologic and histologic documentation on the embolization material under study.

Two cases of glomus tumour treated by unusual embolization.

Two cases of glomus tumour treated by the catheterization technique are reported. In the first case, after it was found impossible to catheterize the external carotid artery by the femoral route, the external carotid was punctured directly, became spasmodic and the catheter could not be introduced, so the inner wall of the external carotid was eroded by manipulating the tip of the metallic guide. This resulted in complete occlusion of the artery 1 cm above the bifurcation of the common carotid.