Associations of externalizing polygenic scores with externalizing disorders among Mexican youth.

Several studies have examined the association of externalizing polygenic scores (PGS) with externalizing symptoms in samples of European ancestry. However, less is known about the associations of externalizing polygenic vulnerability in relation to phenotypic externalizing disorders among individuals of different ancestries, such as Mexican youth. Here, we leveraged the largest genome-wide association study on externalizing behaviors that included over 1 million individuals of European ancestry to examine associations of externalizing PGS with a range of externalizing disorders in Mexican adolescents, and investigated whether adversity exposure in childhood moderated these associations.

The effects of temperature on elastic energy storage and release in a system with a dynamic mechanical advantage latch.

Changes in temperature alter muscle kinetics and in turn affect whole-organism performance. Some organisms use the elastic recoil of biological springs, structures which are far less temperature sensitive, to power thermally robust movements. For jumping frogs, the use of elastic energy in tendons is facilitated through a geometric latching mechanism that operates through dynamic changes in the mechanical advantage (MA) of the hindlimb.

Pedestrian detection model based on Tiny-Yolov3 architecture for wearable devices to visually impaired assistance.

Wearable assistive devices for the visually impaired whose technology is based on video camera devices represent a challenge in rapid evolution, where one of the main problems is to find computer vision algorithms that can be implemented in low-cost embedded devices. This work presents a Tiny You Only Look Once architecture for pedestrian detection, which can be implemented in low-cost wearable devices as an alternative for the development of assistive technologies for the visually impaired. The recall results of the proposed refined model represent an improvement of 71% working with four anchor boxes and 66% with six anchor boxes compared to the original model.

Unfolding and Aggregation Pathways of Variable Domains from Immunoglobulin Light Chains.

Light chain amyloidosis is the most common form of systemic amyloidosis. This disease is caused by the formation and deposition of amyloid fibers made from immunoglobulin light chains. Environmental conditions such as pH and temperature can affect protein structure and induce the development of these fibers.

Dimers of D76N-β-microglobulin display potent antiamyloid aggregation activity.

Self-association of WT βmicroglobulin (WT-βm) into amyloid fibrils is associated with the disorder dialysis related amyloidosis. In the familial variant D76N-βm, the single amino acid substitution enhances the aggregation propensity of the protein dramatically and gives rise to a disorder that is independent of renal dysfunction. Numerous biophysical and structural studies on WT- and D76N-βm have been performed in order to better understand the structure and dynamics of the native proteins and their different potentials to aggregate into amyloid.

Single residue modulators of amyloid formation in the N-terminal P1-region of α-synuclein.

Alpha-synuclein (αSyn) is a protein involved in neurodegenerative disorders including Parkinson's disease. Amyloid formation of αSyn can be modulated by the 'P1 region' (residues 36-42). Here, mutational studies of P1 reveal that Y39A and S42A extend the lag-phase of αSyn amyloid formation in vitro and rescue amyloid-associated cytotoxicity in C.

Controlling amyloid formation of intrinsically disordered proteins and peptides: slowing down or speeding up?

The pathological assembly of intrinsically disordered proteins/peptides (IDPs) into amyloid fibrils is associated with a range of human pathologies, including neurodegeneration, metabolic diseases and systemic amyloidosis. These debilitating disorders affect hundreds of millions of people worldwide, and the number of people affected is increasing sharply. However, the discovery of therapeutic agents has been immensely challenging largely because of (i) the diverse number of aggregation pathways and the multi-conformational and transient nature of the related proteins or peptides and (ii) the under-development of experimental pipelines for the identification of disease-modifying molecules and their mode-of-action.

Tuning the rate of aggregation of hIAPP into amyloid using small-molecule modulators of assembly.

Human islet amyloid polypeptide (hIAPP) self-assembles into amyloid fibrils which deposit in pancreatic islets of type 2 diabetes (T2D) patients. Here, we applied chemical kinetics to study the mechanism of amyloid assembly of wild-type hIAPP and its more amyloidogenic natural variant S20G. We show that the aggregation of both peptides involves primary nucleation, secondary nucleation and elongation.

Grain splitting is a mechanism for grain coarsening in colloidal polycrystals.

In established theories of grain coarsening, grains disappear either by shrinking or by rotating as a rigid object to coalesce with an adjacent grain. Here we report a third mechanism for grain coarsening, in which a grain splits apart into two regions that rotate in opposite directions to match two adjacent grains' orientations. We experimentally observe both conventional grain rotation and grain splitting in two-dimensional colloidal polycrystals.

The role of the I-state in D76N β-microglobulin amyloid assembly: A crucial intermediate or an innocuous bystander?

The D76N variant of human β-microglobulin (βm) is the causative agent of a hereditary amyloid disease. Interestingly, D76N-associated amyloidosis has a distinctive pathology compared with aggregation of WT-βm, which occurs in dialysis-related amyloidosis. A folding intermediate of WT-βm, known as the I-state, which contains a nonnative Pro-32, has been shown to be a key precursor of WT-βm aggregation However, how a single amino acid substitution enhances the rate of aggregation of D76N-βm and gives rise to a different amyloid disease remained unclear.

A short motif in the N-terminal region of α-synuclein is critical for both aggregation and function.

Aggregation of human α-synuclein (αSyn) is linked to Parkinson's disease (PD) pathology. The central region of the αSyn sequence contains the non-amyloid β-component (NAC) crucial for aggregation. However, how NAC flanking regions modulate αSyn aggregation remains unclear.

Different Dynamics in 6aJL2 Proteins Associated with AL Amyloidosis, a Conformational Disease.

Light-chain amyloidosis (AL) is the most common systemic amyloidosis and is caused by the deposition of mainly insoluble immunoglobulin light chain amyloid fibrils in multiple organs, causing organ failure and eventually death. The germ-line λ6a has been implicated in AL, where a single point mutant at amino acid 24 (6aJL2-R24G) has been observed in around 25% of patient samples. Structural analysis has shown only subtle differences between both proteins; nevertheless, 6aJL2-R24G is more prone to form amyloid fibrils.

Recognition of Peptidoglycan Fragments by the Transpeptidase PBP4 From .

Peptidoglycan (PG) is an essential component of the cell envelope, maintaining bacterial cell shape and protecting it from bursting due to turgor pressure. The monoderm bacterium has a highly cross-linked PG, with ~90% of peptide stems participating in DD-cross-links and up to 15 peptide stems connected with each other. These cross-links are formed in transpeptidation reactions catalyzed by penicillin-binding proteins (PBPs) of classes A and B.

Induced conformational changes activate the peptidoglycan synthase PBP1B.

Bacteria surround their cytoplasmic membrane with an essential, stress-bearing peptidoglycan (PG) layer consisting of glycan chains linked by short peptides into a mesh-like structure. Growing and dividing cells expand their PG layer using inner-membrane anchored PG synthases, including Penicillin-binding proteins (PBPs), which participate in dynamic protein complexes to facilitate cell wall growth. In Escherichia coli, and presumably other Gram-negative bacteria, growth of the mainly single layered PG is regulated by outer membrane-anchored lipoproteins.

Localized conformational changes trigger the pH-induced fibrillogenesis of an amyloidogenic λ light chain protein.

Solvent conditions modulate the expression of the amyloidogenic potential of proteins. In this work the effect of pH on the fibrillogenic behavior and the conformational properties of 6aJL2, a model protein of the highly amyloidogenic variable light chain λ6a gene segment, was examined. Ordered aggregates showing the ultrastructural and spectroscopic properties observed in amyloid fibrils were formed in the 2.

Inhibition of Light Chain 6aJL2-R24G Amyloid Fiber Formation Associated with Light Chain Amyloidosis.

Light chain amyloidosis (AL) is a deadly disease characterized by the deposition of monoclonal immunoglobulin light chains as insoluble amyloid fibrils in different organs and tissues. Germ line λ VI has been closely related to this condition; moreover, the R24G mutation is present in 25% of the proteins of this germ line in AL patients. In this work, five small molecules were tested as inhibitors of the formation of amyloid fibrils from the 6aJL2-R24G protein.

Solution structure of 6aJL2 and 6aJL2-R24G amyloidogenics light chain proteins.

AL amyloidosis is the most common amyloid systemic disease and it is characterized by the deposition of immunoglobulin light chain amyloid fibers in different organs, causing organ failure. The immunoglobulin light chain germinal line 6a has been observed to over-express in AL patients, moreover, it was observed that, out of these amyloidogenic proteins, 25% present a mutation of an Arg to Gly in position 24. In vitro studies have shown that this mutation produces proteins with a higher amyloid fiber propensity.

[Evaluation of the management of inhalers by the nursing personnel in a reference hospital].

Objectives: To evaluate the knowledge and skills of nurses on the management of inhaled therapy in different hospitalization wards.

Material And Methods: We carried out a cross-sectional study, in which nurses were asked to perform a practical demonstration of the management of a pressurized canister with an inhalation chamber, without previous theoretical instruction about the technique. The inhalation technique was evaluated step by step following the recommendations of the Spanish Society of Pneumologists and Chest Surgeons (SEPAR).

[Individually tailored medical counseling for pregnant smokers].

Objectives: To identify the characteristics of smoking addiction in a group of pregnant women, to evaluate the efficacy of medical counseling tailored to the patient's stage in the cessation process and to examine factors that might affect the ability of a woman to quit smoking during pregnancy.

Patients And Methods: One hundred sixteen women (mean age 29.71 5.

[Influence of computed tomography of the abdomen for staging lung cancer].

Objectives: To analyze the influence of routine imaging of the upper abdomen by conventional computed tomography (CT) to stage bronchopulmonary carcinoma and to detect liver or adrenal metastasis. A second objective was to describe the characteristics of a large group of patients in our practice.

Material And Methods: Retrospective study of 387 patients (367 men and 20 women; mean age [+/-SD] 62.

[Inhalation technique in patients with chronic respiratory diseases].

Objective: To determine how inhalers are used by patients with chronic respiratory diseases in the Community of Valencia (Spain) and to identify the factors associated with correct use.

Material And Methods: We carried out a prospective study of 554 patients (331 men, 223 women, mean age 50.5 +/- 21.

[Barometric pressure and respiratory quotient for estimating the alveolar-arterial oxygen gradient].

Objective: To evaluate how they influence in the calculatión of the alveolar-arterial oxygen difference (AaPO2) the measurement of the barometric pressure (Pb) and respiratory quotient (R), in patients with chronic respiratory disease.

Method: Prospective study of 39 patients with chronic respiratory disease in stable situation. We calculate: 1.

[Value of ventilation scintigraphy in the diagnosis of pulmonary thromboembolism].

Objectives: The objective of this work has been to know if to all patients with diagnostic suspected of acute pulmonary embolism and pathologic perfusion scanning, ventilation scintigraphy were performed in the assistance context, analyzing etiopathogenic, clinic and diagnostic factors related with the non prescription of the ventilation scintigraphic study.

Methods: In 1992 we have carried out a retrospective and random study of 50 patients with perfusion scintigraphy for diagnostic suspected of acute pulmonary embolism (APE).

Results: A diagnosis of acute pulmonary embolism and deep vein thrombosis was made respectively in 35 (70%) and 22 (44%) of a total of 50 patients.