The role of urinary kininogen in the regulation of kinin generation

The role of urinary kininogen in the regulation of kinin generation. The kallikrein-kininogen-kinin system has been postulated to play a role in the regulation of blood pressure and modulation of renal salt and water transport. The activity of this system has usually been determined by measurements of urinary kallikrein excretion. However, urinary kallikrein rarely correlates with simultaneously measured urinary kinins. To further evaluate the factors influencing urinary kinin excretion, we evaluated the role of urinary kininogen in this system. Urines were analyzed from normal subjects and individuals with untreated essential hypertension and end-stage renal disease. Intact urinary kininogen was significantly correlated with urinary kinins in normal subjects (r = 0.65, P = 0.003) and essential hypertensives (r = 0.52, P = 0.026). In both essential hypertension and end-stage renal disease, urinary kinins were significantly decreased (8.00 ± 1.93, 0.90 ± 0.18, P < 0.05, respectively) compared to controls (23.73 ± 5.20). In essential hypertensives, the reduction in urinary kinins was paralleled by a reduction in intact kininogen with a normal excretion of kallikrein. In end-stage renal disease, the reduction in kinins was paralleled by a reduction in kallikrein with a normal excretion of intact kininogen. This data suggests that kininogen may be an important determinant of urinary kinin excretion in various disease states

Gendering Farmer Producer companies at the Agricultural Frontier of India: Empowerment or Burden?

Farmer Producer Companies (FPCs) are driving agricultural frontier expansions in India. Their main objectives are to mobilize small-scale farmers to collectivize and organize in order to gain collective bargaining power, in the process empowering farmers and eliminating middlemen. However, they have not established any demonstrable success in achieving these goals. This chapter seeks firstly, to draw transnational connections between agro-ecological transformations in India and larger market/capital expansions through FPCs, contextualized amidst national development goals for farmer empowerment, changing labor patterns, and ecological degradation. In doing so, it will, secondly, explore the gendered dimension of FPCs in India by analyzing how the process of establishing women-only FPCs by using mandatory inclusion as a participation tool can serve to disempower and further burden women. While mandatory involvement of women farmers on their Board of Directors as an empowerment strategy can prove crucial to enhancing women’s decision-making roles, this chapter asks whether such an inclusionary approach remains meaningful to achieve FPC success in a context where external support for women’s empowerment is not provided

A cryo-EM grid preparation device for time-resolved structural studies

Structural biology generally provides static snapshots of protein conformations that can provide information on the functional mechanisms of biological systems. Time-resolved structural biology provides a means to visualize, at near-atomic resolution, the dynamic conformational changes that macromolecules undergo as they function. X-ray free-electron-laser technology has provided a powerful tool to study enzyme mechanisms at atomic resolution, typically in the femtosecond to picosecond timeframe. Complementary to this, recent advances in the resolution obtainable by electron microscopy and the broad range of samples that can be studied make it ideally suited to time-resolved approaches in the microsecond to millisecond timeframe to study large loop and domain motions in biomolecules. Here we describe a cryo-EM grid preparation device that permits rapid mixing, voltage-assisted spraying and vitrification of samples. It is shown that the device produces grids of sufficient ice quality to enable data collection from single grids that results in a sub-4 Å reconstruction. Rapid mixing can be achieved by blot-and-spray or mix-and-spray approaches with a delay of ∼10 ms, providing greater temporal resolution than previously reported mix-and-spray approaches

Megahertz pulse trains enable multi-hit serial femtosecond crystallography experiments at X-ray free electron lasers

The European X-ray Free Electron Laser (XFEL) and Linac Coherent Light Source (LCLS) II are extremely intense sources of X-rays capable of generating Serial Femtosecond Crystallography (SFX) data at megahertz (MHz) repetition rates. Previous work has shown that it is possible to use consecutive X-ray pulses to collect diffraction patterns from individual crystals. Here, we exploit the MHz pulse structure of the European XFEL to obtain two complete datasets from the same lysozyme crystal, first hit and the second hit, before it exits the beam. The two datasets, separated by <1 µs, yield up to 2.1 Å resolution structures. Comparisons between the two structures reveal no indications of radiation damage or significant changes within the active site, consistent with the calculated dose estimates. This demonstrates MHz SFX can be used as a tool for tracking sub-microsecond structural changes in individual single crystals, a technique we refer to as multi-hit SFX

Framing smallholder inclusion in global value chains – case studies from India and West Africa

A resurrected interest in agriculture has brought in its wake growing interest in smallholders in the global South by scholars, companies, governments and development agencies alike. While non-governmental organisations and development agencies see the potential to reduce poverty, companies look upon smallholder agriculture as a widely untapped resource for the sourcing of crops and as a sales market for agricultural inputs. While the important role of large corporate buyers of agricultural produce as lead firms in value chains is often discussed and emphasised, the power of providers of technology and agricultural inputs is being rather neglected. In this paper, we analyse two case studies of technology and input providers in agricultural value chains and their role in smallholder inclusion with the aim of finding out how such companies impact the governance of the value chains. To do so we combine insights from the value chain literature with the concept of framing/overflowing

Effective role of CaO/P2O5 ratio on SiO2-CaO-P2O5 glass system

In the present work, the effect of the CaO/P2O5 ratio on the composition of sol-gel synthesized 58SiO2-(19 − x)P2O5–(23 + x)CaO (x = 0, 5, 10 and 15 mol%) glass samples was studied. Further, the effect of NBO/BO ratio on hydroxy carbonated apatite layer (HCA) forming ability based on dissolution behavior in simulated body fluid (SBF) solution was also investigated. CaO/P2O5 ratios of synthesized glass samples were 1.2, 2, 3.6, and 9.5, respectively. NBO/BO ratios were obtained using Raman spectroscopic analysis as 0.58, 1.20, 1.46, and 1.78, respectively. All samples were soaked in the SBF solution for 7 days. The calculated weight losses of these samples were 58%, 64%, 83%, and 89% for corresponding NBO/BO ratios. The increase in CaO/P2O5 ratio increases the NBO/BO ratios. However, the increase in NBO/BO ratio increases HCA forming ability of SBF treated samples. The HCA crystalline layer formation was confirmed through X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Raman and Infrared spectroscopic analysis. Higher CaO/P2O5 ratio favors the increase in HCA formation for SBF treated calcium phospho silicate glasses

Microfluidic assisted self-assembly of pH-sensitive low-molecular weight hydrogelators close to the minimum gelation concentration

The fibrillation and subsequent gelation of low molecular hydrogelators is usually triggered by external stimuli. Generally, strong acids are employed to trigger the self-assembly mechanism in pH-responsive supramolecular systems. However, the generation and design of novel stable gels with performing mechanical properties is a challenging task as a result of the uneven self-assembled networks formed. Here, we report the study of the self-assembly process of a low molecular weight hydrogelator (LMWG) in the proximity of its minimum gelation concentration (MGC = 0.3 mg/ml). At such high dilution, the generation of homogeneous gels with good mechanical properties by turning pH by strong acids is a demanding task as a result of the lack of monodisperse 1D self-assembled rod-like aggregates. A microfluidic device is employed here to gradually and homogeneously change the pH. We show that self-assembly of LMWG in well-defined structures can be enhanced by using the diffusive mixing occurring in the microfluidic reactor channel. For very short mixing times, aggregates with 2 nm cross-section are found in the region adjacent to the focused LMWG solution in contact with the low pH buffer solution streams, where the pH reaches values below the pKa of the LMWG and triggers the supramolecular self-assembly. For longer mixing times, aggregates grow in size and occupy homogeneously the micro channel. The results presented here show that better controlled self-assembly can be achieved using microfluidic mixing devices and early stages of self-assembly can be efficiently studied by coupling synchrotron SAXS with microfluidics

3D Micromachined Polyimide Mixing Devices for in Situ X-ray Imaging of Solution-Based Block Copolymer Phase Transitions

Advances in modern interface- and material sciences often rely on the understanding of a system’s structure–function relationship. Designing reproducible experiments that yield in situ time-resolved structural information at fast time scales is therefore of great interest, e.g., for better understanding the early stages of self-assembly or other phase transitions. However, it can be challenging to accurately control experimental conditions, especially when samples are only available in small amounts, prone to agglomeration, or if X-ray compatibility is required. We address these challenges by presenting a microfluidic chip for triggering dynamics via rapid diffusive mixing for in situ time-resolved X-ray investigations. This polyimide/Kapton-only-based device can be used to study the structural dynamics and phase transitions of a wide range of colloidal and soft matter samples down to millisecond time scales. The novel multiangle laser ablation three-dimensional (3D) microstructuring approach combines, for the first time, the highly desirable characteristics of Kapton (high X-ray stability with low background, organic solvent compatibility) with a 3D flow-focusing geometry that minimizes mixing dispersion and wall agglomeration. As a model system, to demonstrate the performance of these 3D Kapton microfluidic devices, we selected the non-solvent-induced self-assembly of biocompatible and amphiphilic diblock copolymers. We then followed their structural evolution in situ at millisecond time scales using on-the-chip time-resolved small-angle X-ray scattering under continuous-flow conditions. Combined with complementary results from 3D finite-element method computational fluid dynamics simulations, we find that the nonsolvent mixing is mostly complete within a few tens of milliseconds, which triggers initial spherical micelle formation, while structural transitions into micelle lattices and their deswelling only occur on the hundreds of milliseconds to second time scale. These results could have an important implication for the design and formulation of amphiphilic polymer nanoparticles for industrial applications and their use as drug-delivery systems in medicine