Modeling of B cell Synapse Formation by Monte Carlo Simulation Shows That Directed Transport of Receptor Molecules Is a Potential Formation Mechanism

The formation of the protein segregation structure known as the “immunological synapse” in the contact region between B cells and antigen presenting cells appears to precede antigen (Ag) uptake by B cells. The mature B cell synapse consists of a central cluster of B cell receptor/Antigen (BCR/Ag) complexes surrounded by a ring of LFA-1/ICAM-1 complexes. In this study, we used an in silico model to investigate whether cytoskeletally driven transport of molecules toward the center of the contact zone is a potential mechanism of immunological synapse formation in B cells. We modeled directed transport by the cytoskeleton in an effective manner, by biasing the diffusion of molecules toward the center of the contact zone. Our results clearly show that biased diffusion of BCR/Ag complexes on the B cell surface is sufficient to produce patterns similar to experimentally observed immunological synapses. This is true even in the presence of significant membrane deformation as a result of receptor–ligand binding, which in previous work we showed had a detrimental effect on synapse formation at high antigen affinity values. Comparison of our model’s results to those of experiments shows that our model produces synapses for realistic length, time, and affinity scales. Our results also show that strong biased diffusion of free molecules has a negative effect on synapse formation by excluding BCR/Ag complexes from the center of the contact zone. However, synapses may still form provided the bias in diffusion of free molecules is an order-of-magnitude weaker than that of BCR/Ag complexes. We also show how diffusion trajectories obtained from single-molecule tracking experiments can generate insight into the mechanism of synapse formation

Variations in Helicobacter pylori Cytotoxin-Associated Genes and Their Influence in Progression to Gastric Cancer: Implications for Prevention

Helicobacter pylori (HP) is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag (cytotoxin-associated genes) pathogenicity island (cagPAI), a 40 kb stretch of DNA that encodes components of a type IV secretion system (T4SS). This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI (cagC, cagE, cagL, cagT, cagV and cag Gamma) using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing (454 Roche) methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs (11 non-synonymous and 14 synonymous) showed statistically significant differences (P<0.05), and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer (p-value = 2.07×10−6), and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations

Perspectives on tracking data reuse across biodata resources

c The Author(s) 2024. Published by Oxford University Press.Motivation: Data reuse is a common and vital practice in molecular biology and enables the knowledge gathered over recent decades to drive discovery and innovation in the life sciences. Much of this knowledge has been collated into molecular biology databases, such as UniProtKB, and these resources derive enormous value from sharing data among themselves. However, quantifying and documenting this kind of data reuse remains a challenge. Results: The article reports on a one-day virtual workshop hosted by the UniProt Consortium in March 2023, attended by representatives from biodata resources, experts in data management, and NIH program managers. Workshop discussions focused on strategies for tracking data reuse, best practices for reusing data, and the challenges associated with data reuse and tracking. Surveys and discussions showed that data reuse is widespread, but critical information for reproducibility is sometimes lacking. Challenges include costs of tracking data reuse, tensions between tracking data and open sharing, restrictive licenses, and difficulties in tracking commercial data use. Recommendations that emerged from the discussion include: development of standardized formats for documenting data reuse, education about the obstacles posed by restrictive licenses, and continued recognition by funding agencies that data management is a critical activity that requires dedicated resources

Prevalence of non-communicable diseases in Brazilian children: follow-up at school age of two Brazilian birth cohorts of the 1990's

<p>Abstract</p> <p>Background</p> <p>Few cohort studies have been conducted in low and middle-income countries to investigate non-communicable diseases among school-aged children. This article aims to describe the methodology of two birth cohorts, started in 1994 in Ribeirão Preto (RP), a more developed city, and in 1997/98 in São Luís (SL), a less developed town.</p> <p>Methods</p> <p>Prevalences of some non-communicable diseases during the first follow-up of these cohorts were estimated and compared. Data on singleton live births were obtained at birth (2858 in RP and 2443 in SL). The follow-up at school age was conducted in RP in 2004/05, when the children were 9-11 years old and in SL in 2005/06, when the children were 7-9 years old. Follow-up rates were 68.7% in RP (790 included) and 72.7% in SL (673 participants). The groups of low (<2500 g) and high (≥ 4250 g) birthweight were oversampled and estimates were corrected by weighting.</p> <p>Results</p> <p>In the more developed city there was a higher percentage of non-nutritive sucking habits (69.1% vs 47.9%), lifetime bottle use (89.6% vs 68.3%), higher prevalence of primary headache in the last 15 days (27.9% vs 13.0%), higher positive skin tests for allergens (44.3% vs 25.3%) and higher prevalence of overweight (18.2% vs 3.6%), obesity (9.5% vs 1.8%) and hypertension (10.9% vs 4.6%). In the less developed city there was a larger percentage of children with below average cognitive function (28.9% vs 12.2%), mental health problems (47.4% vs 38.4%), depression (21.6% vs 6.0%) and underweight (5.8% vs 3.6%). There was no difference in the prevalence of bruxism, recurrent abdominal pain, asthma and bronchial hyperresponsiveness between cities.</p> <p>Conclusions</p> <p>Some non-communicable diseases were highly prevalent, especially in the more developed city. Some high rates suggest that the burden of non-communicable diseases will be high in the future, especially mental health problems.</p