Utilizing Hydrothermal Processing to Align Structure and In Vitro Digestion Kinetics between Three Different Pulse Types

Processing results in the transformation of pulses’ structural architecture. Consequently, digestion is anticipated to emerge from the combined effect of intrinsic (matrix-dependent) and extrinsic (processed-induced) factors. In this work, we aimed to investigate the interrelated effect of intrinsic and extrinsic factors on pulses’ structural architecture and resulting digestive consequences. Three commercially relevant pulses (chickpea, pea, black bean) were selected based on reported differences in macronutrient and cell wall composition. Starch and protein digestion kinetics of hydrothermally processed whole pulses were assessed along with microstructural and physicochemical characteristics and compared to the digestion behavior of individual cotyledon cells isolated thereof. Despite different rates of hardness decay upon hydrothermal processing, the pulses reached similar residual hardness values (40 N). Aligning the pulses at the level of this macrostructural property translated into similar microstructural characteristics after mechanical disintegration (isolated cotyledon cells) with comparable yields of cotyledon cells for all pulses (41–62%). We observed that processing to equivalent microstructural properties resulted in similar starch and protein digestion kinetics, regardless of the pulse type and (prolonged) processing times. This demonstrated the capacity of (residual) hardness as a food structuring parameter in pulses. Furthermore, we illustrated that the digestive behavior of isolated cotyledon cells was representative of the digestion behavior of corresponding whole pulses, opening up perspectives for the incorporation of complete hydrothermally processed pulses as food ingredients.

Tectonostratigraphy and major structures of the Georgian Greater Caucasus: Implications for structural architecture, along-strike continuity, and orogen evolution

Although the Greater Caucasus Mountains have played a central role in absorbing late Cenozoic convergence between the Arabian and Eurasian plates, the orogenic architecture and the ways in which it accommodates modern shortening remain debated. Here, we addressed this problem using geologic mapping along two transects across the southern half of the western Greater Caucasus to reveal a suite of regionally coherent stratigraphic packages that are juxtaposed across a series of thrust faults, which we call the North Georgia fault system. From south to north within this system, stratigraphically repeated ~5–10-km-thick thrust sheets show systematically increasing bedding dip angles (<30° in the south to subvertical in the core of the range). Likewise, exhumation depth increases toward the core of the range, based on low-temperature thermochronologic data and metamorphic grade of exposed rocks. In contrast, active shortening in the modern system is accommodated, at least in part, by thrust faults along the southern margin of the orogen. Facilitated by the North Georgia fault system, the western Greater Caucasus Mountains broadly behave as an in-sequence, southward-propagating imbricate thrust fan, with older faults within the range progressively abandoned and new structures forming to accommodate shortening as the thrust propagates southward. We suggest that the single-fault-centric “Main Caucasus thrust” paradigm is no longer appropriate, as it is a system of faults, the North Georgia fault system, that dominates the architecture of the western Greater Caucasus Mountains.

Candidates for Repurposing as Anti-Virulence Agents Based on the Structural Profile Analysis of Microbial Collagenase Inhibitors

The pharmacological inhibition of the bacterial collagenases (BC) enzymes is considered a promising strategy to block the virulence of the bacteria without targeting the selection mechanism leading to drug resistance. The chemical structures of the Clostridium perfringens collagenase A (ColA) inhibitors were analyzed using Bemis–Murcko skeletons, Murcko frameworks, the type of plain rings, and docking studies. The inhibitors were classified based on their structural architecture and various scoring methods were implemented to predict the probability of new compounds to inhibit ColA and other BC. The analyses indicated that all compounds contain at least one aromatic ring, which is often a nitrobenzene fragment. 2-Nitrobenzene based compounds are, on average, more potent BC inhibitors compared to those derived from 4-nitrobenzene. The molecular descriptors MDEO-11, AATS0s, ASP-0, and MAXDN were determined as filters to identify new BC inhibitors and highlighted the necessity for a compound to contain at least three primary oxygen atoms. The DrugBank database was virtually screened using the developed methods. A total of 100 compounds were identified as potential BC inhibitors, of which, 10 are human approved drugs. Benzthiazide, entacapone, and lodoxamide were chosen as the best candidates for in vitro testing based on their pharmaco-toxicological profile.

Structural arrangement of the VH and VL domains in the COBRA™ T-cell engaging single chain diabody

Background COBRA™ (COnditional Bispecific Redirected Activation) T-cell engagers are designed to target solid tumors as a single polypeptide chain prodrug that becomes activated by proteolysis in the tumor microenvironment. One COBRA molecule comprises seven Ig domains: three single-domain antibodies (sdAbs) recognizing a tumor target or human serum albumin (HSA), and CD3ε-binding VH and VL and their inactivated counterparts, VHi and VLi. Pairing of VH and VL, and VLi and VHi, into scFvs is prevented by shortened inter-domain linkers. Instead, VH and VL are expected to interact with VLi and VHi, respectively, thus making a diabody whose binding to CD3ε on the T-cells is impaired. Methods We analyzed the structure of an EGFR COBRA in solution using negative stain electron microscopy (EM) and small-angle X-ray scattering (SAXS). Results We found that this EGFR COBRA forms stable monomers with a very dynamic interdomain arrangement. At most, only five domains at a time appeared ordered, and only one VH-VL pair was found in the Fv orientation. Non-enzymatic post-translational modifications suggest that the CDR3 loops in the VL-VHi pair are exposed but are buried in the VH-VLi pair. The MMP9 cleavage rate of the prodrug when bound to recombinant EGFR or HSA is not affected, indicating positioning of the MMP9-cleavable linker away from the EGFR and HSA binding sites. Conclusion Here we propose a model for EGFR COBRA where VH and VLi form an Fv, and VL and VHi do not, possibly interacting with other Ig domains. SAXS and MMP9 cleavage analyses suggest that all COBRA molecules tested have a similar structural architecture.

An informational sociobiological explanation of the constitution of the human body

Background: Pedro Ortiz (1933-2011), in the latest four decades of his life, developed the Informational Sociobiological Theory (IST) in a university teaching context that became the foundation of post-grade studies in neuroscience in Peru. The IST looks for a totality explanation of the phenomena of the universe proposes an explanation of the constitution of the human body. In what consist this explanation of the configuration of the human body? Methods: A bibliographical qualitative study was conducted starting from primary documental sources. It was considered among the sources, all related to the editorial project Books of Social Psychobiologic (elaborated by Ortiz during the first decade of this age). The results have been presented across a conceptual analysis, narrative and graphic, oriented to expose Ortiz’ ideas in relation to the human body’s morphology. Results: The structural architecture of the human body, and in particular in one person; shows five levels of complexity which begins in cells, the intercellular matrix, the neural system, the paleocortical psyche, and neocortical psyche. In this involve explanation, the organs of the body are essentially tissue systems, and are integrated (subsumed) at the neural level (which informationally goes through the plexuses, ganglia, and subcortical nuclei). The two levels of superior complexity to the neural system, are the space of the psychic activity, unconscious and conscious, which is suprastructurally to all bodily structures. Ortiz is settled on a different monism: that guides us to imagine and think that all psychic activity is suprastructural to the body. Conclusions: There is an original explanation of the human body within the IST. This informational morphology dialogues with the knowledge of biology, neurology, anatomy, physiology, embryology, and histology, and is proposed as a structuring element in all the conceptual architecture that represents the IST.