Detecting adherence to the recommended childhood vaccination schedule from user-generated content in a US parenting forum

Vaccine hesitancy is considered as one of the leading causes for the resurgence of vaccine preventable diseases. A non-negligible minority of parents does not fully adhere to the recommended vaccination schedule, leading their children to be partially immunized and at higher risk of contracting vaccine preventable diseases. Here, we leverage more than one million comments of 201,986 users posted from March 2008 to April 2019 on the public online forum BabyCenter US to learn more about such parents. For 32% with geographic location, we find the number of mapped users for each US state resembling the census population distribution with good agreement. We employ Natural Language Processing to identify 6884 and 10,131 users expressing their intention of following the recommended and alternative vaccination schedule, respectively RSUs and ASUs. From the analysis of their activity on the forum we find that ASUs have distinctly different interests and previous experiences with vaccination than RSUs. In particular, ASUs are more likely to follow groups focused on alternative medicine, are two times more likely to have experienced adverse events following immunization, and to mention more serious adverse reactions such as seizure or developmental regression. Content analysis of comments shows that the resources most frequently shared by both groups point to governmental domains (.gov). Finally, network analysis shows that RSUs and ASUs communicate between each other (indicating the absence of echo chambers), however with the latter group being more endogamic and favoring interactions with other ASUs. While our findings are limited to the specific platform analyzed, our approach may provide additional insights for the development of campaigns targeting parents on digital platforms.     

Biological function in a non-native partially folded state of a protein

As structural flexibility is known to be required for enzyme catalysis and pattern recognition and a significant fraction of eukaryotic proteins appear to be unfolded or contain unstructured regions, biological activity of conformational states distinct from fully folded structures could be more common than previously thought. By applying a procedure that allows the recovery of enzymatic activity to be monitored in real time, we show that a non-native state populated transiently during folding of the acylphosphatase from Sulfolobus solfataricus is enzymatically active. The structural characterization of this partially folded state reveals that enzymatic activity is possible even if the catalytic site is structurally heterogeneous, whereas the remainder of the structure acts as a scaffold. These results extend the spectrum of biological functions carried out in the absence of a folded state to include enzyme catalysis.     

Macrophyte communities and their impact on benthic fluxes of oxygen, sulphide and nutrients in shallow eutrophic environments

The impact of macrophyte communities on benthic fluxes has been analyzed in three shallow coastal environments: Etang du Prévost (Mediterranean coast of France), characterized by the large floating macro-alga Ulva rigida; Certes fishponds (Bassin d'Arcachon), covered by Ruppia cirrhosa; and the inner intertidal mud-flat in the Arcachon Bay (French Atlantic coast), which has extensive Zostera noltii meadows. In these bodies of water, primary production is dependent primarily on the dominant seagrasses and macroalgae that are also responsible for the large quantity of organic matter deposited on the sediment surface. In 1993 and 1994, fluxes of oxygen, sulphide and nutrients were measured in early and late summer, which were selected in order to represent the production and decomposition phases of the dominant macrophytes. Experimental work was undertaken to measure: (1) standing crop of dominant macroalgae and rooted phanerogams and the elemental and macromolecular composition of plant biomass; (2) benthic fluxes of oxygen, sulphide, nitrogen and phosphorus using incubation of multiple dark and light benthic chambers; (3) water-sediment profiles of free-sulphide in sediment cores with rooted phanerogams (Ruppia) as well as with floating Seaweeds (Ulva).At the selected sampling sites, in addition to external (tides) and/or internal (sediment reactivity) factors, we observed differences in benthic fluxes which were clearly related to growth patterns and structure of the macrophyte communities. The Z. noltii meadows were stable and characterized by slow growth and almost constant biomass. In the more sheltered sampling station in the Certes fishponds, R. cirrhosa beds showed a summer decrease due to extensive epiphyte growth. During the decomposition phase, significant fluxes of free-sulphide occurred inside the dark benthic chambers, probably due to the metabolism of the epiphytic layer. In the Etang du Prévost, U. rigida achieved high biomass levels, even though the macroalgal beds exhibited a patchy distribution due to wind action and the hydrodynamics of the lagoon. In the decomposition phase, which was coincident with the annual dystrophic crisis the rapid decomposition of Ulva led to high fluxes of free sulphide.The shift from the production to decomposition phase resulted in substantial changes in nutrient recycling only in the macro-algal-dominated system. During the growth period dissolved inorganic nitrogen and phosphorus were kept at low levels due to macrophyte uptake. In contrast during the decomposition phase when the macroalgal biomass was mineralised, nitrogen and phosphorus were rapidly recycled. The same processes did not occur in the Certes fishponds probably because of the greater internal buffering capacity linked either to plant morphology/physiology or to the properties of the sediment.     

Benthic oxygen respiration, ammonium and phosphorus regeneration in surficial sediments of the Sacca di Goro (Northern Italy) and two French coastal lagoons: a comparative study

During 1994 net sediment-water fluxes of oxygen, ammonium and inorganic phosphorus as well as sediment profiles of organic matter, nitrogen, phosphorus and iron were determined in three shallow eutrophic environments. Investigations were conducted monthly from March to December at five stations in the Sacca di Goro (Po River Delta, Italy). In the late summer, samples were collected from a single site in the Prévost lagoon (French Mediterranean coast) and three stations in the Bassin d'Arcachon (French Atlantic coast). In the Sacca di Goro, water-sediment exchanges of O₂, NH ₄ ⁺ and PO ₄ ^3– were estimated by means of core incubation in the dark. Benthic fluxes for the French lagoons were in part determined experimentally using benthic chambers and in part from the literature.In general in the Sacca di Goro the highest oxygen uptake and nutrient release rates were found at the central sites, affected by macroalgal growth. At the sampling site adjacent to the freshwater inlet, sediment-water exchanges were principally influenced by tidal activity. In terms of organic matter and nutrient levels, sediments from the Sacca di Goro and from the Prévost lagoon, both colonised by the floating macroalga Ulva rigida C. Agardh, were similar. Sediments from the inner sheltered site in the Bassin d'Arcachon, invaded by the rooted macrophyte Ruppia cirrhosa (Pet.) Grande, showed the highest total N and P content (363 ± 157 µmol N cm^–3 and 15 ± 2 µmol P cm^–3 as average values in the top 10 cm of sediment), but were low in pore water ammonium and orthophosphate probably due to the high sequestering capacity of the system and/or efficient coupling between bacterial nutrient regeneration and assimilation by the plant roots. In addition the outer tidal stations in the Bassin d'Arcachon, invaded by rooted macrophytes, were low in pore water nutrients. A different trend was evident in the Prévost lagoon where the concentrations of exchangeable inorganic phosphorus and ammonium were appreciable (0.28 ± 0.07 µmol P cm^–3 and 2.4 ± 1.4 µmol N cm^–3 as average values in the top 10 cm of sediment). High amounts of dissolved organic nitrogen were found in the pore water at all the sites investigated showing the key role of the organic nitrogen in the recycling of nitrogen in these systems.The hypothesis that iron is a key factor in controlling phosphorus release is discussed since the Sacca di Goro, which is subject to dystrophic crises, is richer in iron than the Bassin d'Arcachon, which is a more buffered system.     

Glutamatergic Postsynaptic Density Protein Dysfunctions in Synaptic Plasticity and Dendritic Spines Morphology: Relevance to Schizophrenia and Other Behavioral Disorders Pathophysiology,and Implications for Novel Therapeutic Approaches

Emerging researches point to a relevant role of postsynaptic density (PSD) proteins, such as PSD-95, Homer, Shank, and DISC-1, in the pathophysiology of schizophrenia and autism spectrum disorders. The PSD is a thickness, detectable at electronic microscopy, localized at the postsynaptic membrane of glutamatergic synapses, and made by scaffolding proteins, receptors, and effector proteins; it is considered a structural and functional crossroad where multiple neurotransmitter systems converge, including the dopaminergic, serotonergic, and glutamatergic ones, which are all implicated in the pathophysiology of psychosis. Decreased PSD-95 protein levels have been reported in postmortem brains of schizophrenia patients. Variants of Homer1, a key PSD protein for glutamate signaling, have been associated with schizophrenia symptoms severity and therapeutic response. Mutations in Shank gene have been recognized in autism spectrum disorder patients, as well as reported to be associated to behaviors reminiscent of schizophrenia symptoms when expressed in genetically engineered mice. Here, we provide a critical appraisal of PSD proteins role in the pathophysiology of schizophrenia and autism spectrum disorders. Then, we discuss how antipsychotics may affect PSD proteins in brain regions relevant to psychosis pathophysiology, possibly by controlling synaptic plasticity and dendritic spine rearrangements through the modulation of glutamate-related targets. We finally provide a framework that may explain how PSD proteins might be useful candidates to develop new therapeutic approaches for schizophrenia and related disorders in which there is a need for new biological treatments, especially against some symptom domains, such as negative symptoms, that are poorly affected by current antipsychotics.     

HIF1α Suppresses Tumor Cell Proliferation through Inhibition of Aspartate Biosynthesis

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IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease

Background

Epidemiological studies indicate that a growing number of cirrhotic patients will develop hepatocellular carcinoma (HCC) in the next decade. Recent findings have demonstrated that Squamous cell carcinoma antigen 1 (SCCA1) and 2 (SCCA2) isoforms, now classified as serpinB3 and serpinB4, are over-expressed in HCC, but not in normal liver. As reported, high levels of circulating SCCA-IgM immunocomplexes in patients with cirrhosis are significantly associated with HCC development.

Aim

To ascertain whether IgM-linked SCCA isoforms circulate in patients with chronic liver disease, compared to total SCCA-IgM levels.

Methodology and Findings

79 patients with chronic liver disease were studied, including 17 patients with chronic hepatitis, 36 patients with cirrhosis and 26 with HCC. 28 blood donors were used as control. Monoclonal antibodies against serpinB3 and serpinB4 were used as catcher antibodies to set up specific ELISA assays, while total SCCA-IgM immunocomplexes were detected by commercially available ELISA assay. Overall, the results revealed a better diagnostic sensitivity of total SCCA-IgM assay, compared to both serpinB3 and serpinB4 IgM-linked assays. SerpinB4-IgM median values obtained with SCC103 antibody were moderately higher in patients with cirrhosis than in those with HCC, median values: 0.168 (IQR 0.140–0.427) vs. 0.140 (IQR 0.140–0.278), (p = 0.177). A trend toward decreasing serpinB4-IgM/serpinB3-IgM median ratio was observed in patients with advanced liver disease, being 1.08 in patients with HCC, 1.10 in patients with cirrhosis and 1.40 in patients with chronic hepatitis (p = 0.079).

Conclusions

IgM-linked SCCA isoforms in serum of patients with chronic liver diseases were quantified for the first time. Although the number of patients was limited, this preliminary study reveals that the relative balance of the two serpin isoforms is altered in HCC and it is characterized by a lower serpinB4-IgM/serpinB3-IgM ratio, determined by lower serpinB4 levels.