Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

Effect of "no added salt diet" on blood pressure control and 24 hour urinary sodium excretion in mild to moderate hypertension

<p>Abstract</p> <p>Background</p> <p>The incidence of Hypertension as a major cardiovascular threat is increasing. The best known diet for hypertensives is 'no added salt diet'.</p> <p>In this study we evaluated the effect of 'no added salt diet' on a hypertensive population with high dietary sodium intake by measuring 24 hour urinary sodium excretion.</p> <p>Methods</p> <p>In this single center randomized study 80 patients (60 cases and 20 controls) not on any drug therapy for hypertension with mild to moderate hypertension were enrolled. 24 hour holter monitoring of BP and 24 hour urinary sodium excretion were measured before and after 6 weeks of 'no added salt diet'.</p> <p>Results</p> <p>There was no statistically significant difference between age, weight, sex, Hyperlipidemia, family history of hypertension, mean systolic and diastolic BP during the day and at night and mean urinary sodium excretion in 24 hour urine of case and control groups. Seventy eight percent of all patients had moderate to high salt intake.</p> <p>After 6 week of 'no added salt diet' systolic and diastolic BP significantly decreased during the day (mean decrease: 12.1/6.8 mmhg) and at night (mean decrease: 11.1/5.9 mmhg) which is statistically significant in comparison to control group (P 0.001 and 0.01).</p> <p>Urinary sodium excretion of 24 hour urine decreased by 37.1 meq/d ± 39,67 mg/dl in case group which is statistically significant in comparison to control group (p: 0.001).</p> <p>Only 36% of the patients, after no added salt diet, reached the pretreatment goal of 24 hour urinary sodium excretion of below 100 meq/dl (P:0.001).</p> <p>Conclusion</p> <p>Despite modest effect on dietary sodium restriction, no added salt diet significantly decreased systolic and diastolic BP and so it should be advised to every hypertensive patient.</p> <p>Trial Registration</p> <p>Clinicaltrial.govnumber NCT00491881</p

Phonon-assisted radiofrequency absorption by gold nanoparticles resulting in hyperthermia

It is suggested that in gold nanoparticles (GNPs) of about 5 nm sizes used in the radiofrequency (RF) hyperthermia, an absorption of the RF photon by the Fermi electron occurs with involvement of the longitudinal acoustic vibrational mode (LAVM), the dominating one in the distribution of vibrational density of states (VDOS). This physical mechanism helps to explain two observed phenomena: the size dependence of the heating rate (HR) in GNPs and reduced heat production in aggregated GNPs. The argumentation proceeds within the one-electron approximation, taking into account the discretenesses of energies and momenta of both electrons and LAVMs. The heating of GNPs is thought to consist of two consecutive processes: first, the Fermi electron absorbs simultaneously the RF photon and the LAVM available in the GNP; hereafter the excited electron gets relaxed within the GNP's boundary, exciting a LAVM with the energy higher than that of the previously absorbed LAVM. GNPs containing the Ta and/or Fe impurities are proposed for the RF hyperthermia as promising heaters with enhanced HRs, and GNPs with rare-earth impurity atoms are also brought into consideration. It is shown why the maximum HR values should be expected in GNPs with about 5-7 nm size.Comment: proceedings at the NATO Advanced Research workshop FANEM-2015 (Minsk, May 25-27, 2015). To be published in the final form in: "Fundamental and Applied NanoElectroMagnetics" (Springer Science + Business Media B.V.

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications

The Expression of ERCC1, RRM1, and BRCA1 in Breast Cancer According to the Immunohistochemical Phenotypes

We studied the expression of BRCA1, ERCC1, and RRM1 which play an important role in DNA repair systems in breast cancer. Immunohistochemical staining for EGFR, BRCA1, ERCC1, and RRM1 were performed by using a tissue microarray made from 230 breast cancer patients. Patients were classified into luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) types according to ER, PR, and HER-2 expression. The expression of ERCC1, RRM1, and BRCA1 were correlated (P < 0.05). The expression level of ERCC1 was the lowest in TNBC type (P = 0.031), ERCC1 negativity was more prominent in TNBC and luminal B groups than luminal A and HER-2 groups (P = 0.013). Cases with EGFR overexpression showed high expression of RRM1 and BRCA1 (P = 0.046, and 0.004, respectively). In conclusion, the expression of ERCC1 is particularly lower in TNBCs than other types of breast cancers

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Feasibility and antihypertensive effect of replacing regular salt with mineral salt -rich in magnesium and potassium- in subjects with mildly elevated blood pressure

<p>Abstract</p> <p>Background</p> <p>High salt intake is linked to hypertension whereas a restriction of dietary salt lowers blood pressure (BP). Substituting potassium and/or magnesium salts for sodium chloride (NaCl) may enhance the feasibility of salt restriction and lower blood pressure beyond the sodium reduction alone. The aim of this study was to determine the feasibility and effect on blood pressure of replacing NaCl (Regular salt) with a novel mineral salt [50% sodium chloride and rich in potassium chloride (25%), magnesium ammonium potassium chloride, hydrate (25%)] (Smart Salt).</p> <p>Methods</p> <p>A randomized, double-blind, placebo-controlled study was conducted with an intervention period of 8-weeks in subjects (n = 45) with systolic (S)BP 130-159 mmHg and/or diastolic (D)BP 85-99 mmHg. During the intervention period, subjects consumed processed foods salted with either NaCl or Smart Salt. The primary endpoint was the change in SBP. Secondary endpoints were changes in DBP, daily urine excretion of sodium (24-h dU-Na), potassium (dU-K) and magnesium (dU-Mg).</p> <p>Results</p> <p>24-h dU-Na decreased significantly in the Smart Salt group (-29.8 mmol; p = 0.012) and remained unchanged in the control group: resulting in a 3.3 g difference in NaCl intake between the groups. Replacement of NaCl with Smart Salt resulted in a significant reduction in SBP over 8 weeks (-7.5 mmHg; p = 0.016). SBP increased (+3.8 mmHg, p = 0.072) slightly in the Regular salt group. The difference in the change of SBP between study groups was significant (p < 0.002).</p> <p>Conclusions</p> <p>The substitution of Smart Salt for Regular salt in subjects with high normal or mildly elevated BP resulted in a significant reduction in their daily sodium intake as well as a reduction in SBP.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN01739816">ISRCTN01739816</a></p

Population-Based Incidence of Typhoid Fever in an Urban Informal Settlement and a Rural Area in Kenya: Implications for Typhoid Vaccine Use in Africa

Background: High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene. Methods: During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated. Results: In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5–9 years old (596 per 100,000 pyo) and 2–4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2–4 and 5–9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2–4 year old urban children (2,243 per 100,000 pyo) which were.15-fold higher than rates in the rural site for the same age group