Activity

Among various factors, the direct environment (e.g. pH, buffer components, salts, additives, etc.…) is known to have a crucial effect on both the stability and activity of proteins. In particular, proper buffer and pH conditions can improve their stability and function significantly during purification, storage and handling, which is highly relevant for both academic and industrial applications. It can also promote data reproducibility, support the interpretation of experimental results and, finally, contribute to our general understanding of the biophysical properties of proteins. In this study, we have developed a high throughput screen of 158 different buffers/pH conditions in which we evaluated (i) the protein stability, using differential scanning fluorimetry and (ii) the protein function, using either enzymatic assays or binding activity measurements, both in an automated manner. The modular setup of the screen allows for easy implementation of other characterization methods and parameters, as well as additional test conditions. The buffer/pH screen was validated with five different proteins used as models, i.e. two active-site serine β-lactamases, two metallo-β-lactamases (one of which is only active as a tetramer) and a single-domain dromedary antibody fragment (VHH or nanobody). The formulation screen allowed automated and fast determination of optimum buffer and pH profiles for the tested proteins. Besides the determination of the optimum buffer and pH, the collection of pH profiles of many different proteins may also allow to delineate general concepts to understand and predict the relationship between pH and protein properties.

This study addresses the challenging characterisation and differentiation of CIDP versus CIDP in association with Sjögren’s syndrome to facilitate the process in clinical routine.

Patients with both CIDP and Sjögren’s syndrome and CIDP without Sjögren’s syndrome were compared concerning relevant differences in clinical, laboratory and electrophysiological findings. 154 patients who fulfilled the diagnostic EFNS/PNS criteria for CIDP were included in the analysis. 54 of these patients additionally fulfilled the ACR/EULAR classification criteria for Sjögren’s syndrome.

The frequency of female patients was higher in patients with CIDP and Sjögren’s syndrome (52%) versus CIDP patients without Sjögren’s syndrome (28%). Furthermore, the occurrence of cranial nerve impairment was significantly higher in patients with Sjögren’s syndrome (39% versus 14%). There were no significant group differences in the evaluation of initial symptoms, severity of disability judged by INCAT disability scale score, presence or distribution of sensory deficits, limb weakness and the presence of ataxia, pain or dysautonomia, CSF laboratory or electrophysiological findings.

In conclusion, our data indicate that cranial nerve impairment and female gender might represent red flags for an additional Sjögren’s syndrome in patients with CIDP. The patterns of clinical disabilities and electrophysiological findings due to peripheral nerve damage are similar in both CIDP entities.

In conclusion, our data indicate that cranial nerve impairment and female gender might represent red flags for an additional Sjögren’s syndrome in patients with CIDP. The patterns of clinical disabilities and electrophysiological findings due to peripheral nerve damage are similar in both CIDP entities.Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNFα) treatment and central nervous system (CNS) events. We described eight patients presenting with demyelinating CNS events while on treatment with anti-TNFα for autoimmune diseases and followed up for a medium period of 4 years. Four patients presented with isolated demyelinating events, three patients fulfilled the criteria for multiple sclerosis (MS), and one patient showed worsening of pre-existing MS after anti-TNF therapy initiation. All patients except one, showed a good medium-term prognosis. Our observation supports an association between anti-TNFα treatment and demyelinating events and suggests that a prompt discontinuation of the drug may lead to a favorable demyelinating disease outcome.In this study, the thermoluminescence characteristics of naturally occurring salt (NaCl) were assessed for the development of a radiation dosimeter. For this purpose, mined crystalline samples of salt were procured directly from Khewra salt mines in Pakistan. The samples were hand crushed, sieved, and compressed to pellets comparable in size to standard TLD chips, and irradiated to gamma radiation doses in the range of 5 mGy and 5000 mGy. Thermoluminescence (TL) response showed three main peaks in the glow curve around 115-130 °C, 150-170 °C, and 220-240 °C. A linear TL response was observed for the dose range of 5-100 mGy. The TL response became supra-linear for the dose ranges of 100-1000 mGy and 1000-5000 mGy. The Tm-Tstop method was applied to identify the overlapping peaks of the glow curve. Computerized glow curve deconvolution (CGCD) was then employed for the characterization of electron trap parameters such as frequency factor (s), activation energy (E), and the kinetic order (b), using General Order (GO) kinetics. selleck screening library The figure-of-merit (FOM) was found to be 1.08%, 0.94%, 0.77%, and 0.75%, at 500 mGy, 1 Gy, 2 Gy, and 5 Gy, respectively. The TL intensity faded by 20% within the first 24 h after irradiation and finally stabilized after two weeks. In addition, structural, morphological, and elemental analyses, were also performed using various analytical techniques. X-ray diffraction (XRD) showed that the salt crystallizes in a face-centered cubic structure. Scanning electron microscope (SEM) micrographs indicated that the crystallites are closely packed and cubic-shaped with non-uniform size, and mostly found in the agglomerated form. Similarly, the elemental analysis confirmed the presence of impurities such as Mg, Sr, S, K, O, and Ca, in the samples. The present study concludes that the pellets made from salt samples from Khewra mines have a potential for use as radiation dosimeters.