ALBERT

Description: In this work, we have used low-molecular-weight (PEG12-b-PCL6, PEG12-b-PCL9 or PEG16-b-PLA38; MW, 1.25–3.45 kDa) biodegradable block co-polymers to construct nano- and micron-scaled hybrid (polymer/lipid) vesicles, by solvent dispersion and electroformation methods, respectively. The hybrid vesicles exhibit physical properties (size, bilayer thickness and small molecule encapsulation) of a vesicular boundary, confirmed by cryogenic transmission electron microscopy, calcein leakage assay and dynamic light scattering. Importantly, we find that these low MW polymers, on their own, do not self-assemble into polymersomes at nano and micron scales. Using giant unilamellar vesicles (GUVs) model, their surface topographies are homogeneous, independent of cholesterol, suggesting more energetically favorable mixing of lipid and polymer. Despite this mixed topography with a bilayer thickness similar to that of a lipid bilayer, variation in surface topology is demonstrated using the interfacial sensitive phospholipase A2 (sPLA2). The biodegradable hybrid vesicles are less sensitive to the phospholipase digestion, reminiscent of PEGylated vesicles, and the degree of sensitivity is polymer-dependent, implying that the nano-scale surface topology can further be tuned by its chemical composition. Our results reveal and emphasize the role of phospholipids in promoting low MW polymers for spontaneous vesicular self-assembly, generating a functional hybrid lipid-polymer interface.

Description: The present study estimated muscle activation from electromyographic (EMG) recordings in patients with cerebral palsy (CP) during cycling on an ergometer. This could be used as an input to the modeling of muscle force following the neuromusculoskeletal modeling technique which can help to understand the alterations in neuromotor processes underlying disabilities in CP. EMG signals of lower extremity muscle activity from 14 adult patients with CP and 10 adult healthy participants were used here to derive muscle activation. With a self developed EMG system, signals from the following muscles were recorded: Musculus tibialis anterior, Musculus gastrocnemius, Musculus rectus femoris, and Musculus biceps femoris. Collected EMG signals were mathematically transformed into muscle activation following a parameter dependent and a nonlinear transformation. Muscle activation values from patients with CP were compared to equivalent reference values obtained from healthy controls. Muscle activation calculated at specific foot positions deviated clearly from reference values. The deviation was larger for patients with higher degree of spasticity. Observations underline the need of muscle force modeling during cycling for individualized cycling training for rehabilitation strategy.

Description: Folded proteins show a high degree of structural order and undergo (fairly constrained) collective motions related to their functions. On the other hand, intrinsically disordered proteins (IDPs), while lacking a well-defined three-dimensional structure, do exhibit some structural and dynamical ordering, but are less constrained in their motions than folded proteins. The larger structural plasticity of IDPs emphasizes the importance of entropically driven motions. Many IDPs undergo function-related disorder-to-order transitions driven by their interaction with specific binding partners. As experimental techniques become more sensitive and become better integrated with computational simulations, we are beginning to see how the modest structural ordering and large amplitude collective motions of IDPs endow them with an ability to mediate multiple interactions with different partners in the cell. To illustrate these points, here, we use Prostate-associated gene 4 (PAGE4), an IDP implicated in prostate cancer (PCa) as an example. We first review our previous efforts using molecular dynamics simulations based on atomistic AWSEM to study the conformational dynamics of PAGE4 and how its motions change in its different physiologically relevant phosphorylated forms. Our simulations quantitatively reproduced experimental observations and revealed how structural and dynamical ordering are encoded in the sequence of PAGE4 and can be modulated by different extents of phosphorylation by the kinases HIPK1 and CLK2. This ordering is reflected in changing populations of certain secondary structural elements as well as in the regularity of its collective motions. These ordered features are directly correlated with the functional interactions of WT-PAGE4, HIPK1-PAGE4 and CLK2-PAGE4 with the AP-1 signaling axis. These interactions give rise to repeated transitions between (high HIPK1-PAGE4, low CLK2-PAGE4) and (low HIPK1-PAGE4, high CLK2-PAGE4) cell phenotypes, which possess differing sensitivities to the standard PCa therapies, such as androgen deprivation therapy (ADT). We argue that, although the structural plasticity of an IDP is important in promoting promiscuous interactions, the modulation of the structural ordering is important for sculpting its interactions so as to rewire with agility biomolecular interaction networks with significant functional consequences.

Description: Vibrational spectroscopy is a powerful technique to study the molecular structure and dynamics. It has a great promise to use for medical diagnosis. It is already proved that volatile organic compound contain in breath, reflect the internal chemistry of the body. However, due to the lack of reliable investigation technique, identification and quantification of those molecules are not reached to clinically acceptable parameter. Fourier transform infrared (FTIR) based vibrational spectroscopy has been used to investigate the breath sample. Molecular identification based component analysis of breath sample is proposed.

Description: Bangladesh is one of the most climate-vulnerable countries on the globe. The country is frequently affected by numerous climatic events including floods, droughts, cyclones, etc., which damages the farm household’s livelihood and socio-economic condition. Therefore, this work intends to appraise the smallholder farmers’ perceived climate-related risk, impact, and the factors that influence their choices of adaptation strategies to cope with the adverse impact of the climatic extreme events in northern Bangladesh. Survey data were collected from 300 respondents from two drought-prone districts of northern Bangladesh in January–February 2020. The climate-related risk perception index (CRRPI) was constructed to assess the farmers’ perceived risk. The multinominal logit (MNL) model was employed to explore the factors influencing farmers’ choices of adaptation strategies. Farmers’ perceptions of climate change risk were found to be consistent with meteorological data in the research area. Results of the CRRPI revealed that flood, drought, riverbank erosion, and heat waves were the critical risks perceived by the farmers. Farmers used a variety of adaptation measures to deal with these climatic threats, including agricultural diversification, changes in fertilizer and insecticides, and crop and seed changes. The MNL model results showed that the factors that influenced a farmer’s choices of adaptation strategies were age, education level, family members, income level, year of farming experience, and the farmer’s information on climate change. This study also demonstrated that water scarcity in the dry period and the frequency of crop diseases were the major limiting factors experienced by the farmers whilst undertaking adaptation strategies. Thus, awareness and capacity building through training and support to adopt the adaptation strategies are essential to enhance the resilience of the farmers.