Identification of intramembrane hydrogen bonding between 131 keto group of bacteriochlorophyll and serine residue α27 in the LH2 light-harvesting complex

AbstractIntramembrane hydrogen bonding and its effect on the structural integrity of purple bacterial light-harvesting complex 2, LH2, have been assessed in the native membrane environment. A novel hydrogen bond has been identified by Raman resonance spectroscopy between a serine residue of the membrane-spanning region of LH2 α-subunit, and the C-131 keto carbonyl of bacteriochlorophyll (BChl) B850 bound to the β-subunit. Replacement of the serine by alanine disrupts this strong hydrogen bond, but this neither alters the strongly red-shifted absorption nor the structural arrangement of the BChls, as judged from circular dichroism. It also decreases only slightly the thermal stability of the mutated LH2 in the native membrane environment. The possibility is discussed that weak H-bonding between the C-131 keto carbonyl and a methyl hydrogen of the alanine replacing serine(−4) or the imidazole group of the nearby histidine maintains structural integrity in this very stable bacterial light-harvesting complex. A more widespread occurrence of H-bonding to C-131 not only in BChl, but also in chlorophyll proteins, is indicated by a theoretical analysis of chlorophyll/polypeptide contacts at <3.5 Å in the high-resolution structure of Photosystem I. Nearly half of the 96 chlorophylls have aa residues suitable as hydrogen bond donors to their keto groups

A20/TNFAIP3 heterozygosity predisposes to behavioral symptoms in a mouse model for neuropsychiatric lupus

Background: Neuropsychiatric lupus (NPSLE) refers to the neurological and psychiatric manifestations that are commonly observed in patients with systemic lupus erythematosus (SLE). An important question regarding the pathogenesis of NPSLE is whether the symptoms are caused primarily by CNS-intrinsic mechanisms or develop as a consequence of systemic autoimmunity. Currently used spontaneous mouse models for SLE have already contributed significantly to unraveling how systemic immunity affects the CNS. However, they are less suited when interested in CNS primary mechanisms. In addition, none of these models are based on genes that are associated with SLE. In this study, we evaluate the influence of A20, a well-known susceptibility locus for SLE, on behavior and CNS-associated changes in inflammatory markers. Furthermore, given the importance of environmental triggers for disease onset and progression, the influence of an acute immunological challenge was evaluated. Methods: Female and male A20 heterozygous mice (A20+/−) and wildtype littermates were tested in an extensive behavioral battery. This was done at the age of 10±2weeks and 24 ​± ​2 weeks to evaluate the impact of aging. To investigate the contribution of an acute immunological challenge, LPS was injected intracerebroventricularly at the age of 10±2weeks followed by behavioral analysis. Underlying molecular mechanisms were evaluated in gene expression assays on hippocampus and cortex. White blood cell count and blood-brain barrier permeability were analyzed to determine whether peripheral inflammation is a relevant factor. Results: A20 heterozygosity predisposes to cognitive symptoms that were observed at the age of 10 ​± ​2 weeks and 24 ​± ​2 weeks. Young A20+/− males and females showed a subtle cognitive phenotype (10±2weeks) with distinct neuroinflammatory phenotypes. Aging was associated with clear neuroinflammation in female A20+/− mice only. The genetic predisposition in combination with an environmental stimulus exacerbates the behavioral impairments related to anxiety, cognitive dysfunction and sensorimotor gating. This was predominantly observed in females. Furthermore, signs of neuroinflammation were solely observed in female A20+/− mice. All above observations were made in the absence of peripheral inflammation and of changes in blood-brain barrier permeability, thus consistent with the CNS-primary hypothesis. Conclusions: We show that A20 heterozygosity is a predisposing factor for NPSLE. Further mechanistic insight and possible therapeutic interventions can be studied in this mouse model that recapitulates several key hallmarks of the disease

Late Pleistocene paleosol formation in a dynamic aggradational microenvironment - A case study from the Malá nad Hronom loess succession (Slovakia)

The geomorphological characteristics of the loess succession at Malá nad Hronom (Slovakia) mean that it provides a valuable opportunity for the investigation of differences in soil formation in various topographic positions. Along with the semiquantitative characterization of the paleosols (on the basis of physical properties, texture, the characteristics of peds, clay films, horizon boundaries), high-resolution field magnetic susceptibility measurements and sampling were carried out along four different sections of the profile. Samples for luminescence dating were also taken, in order to establish the chronostratigraphical position of the paleosols studied. The comparison of various proxies revealed the differences in soil formation in a dynamic aggradational microenvironment for the same paleosol horizons located in various positions along the slope. Contrary to expectation, paleosols developed in local top or slope topographical positions did not display significant differences in e.g. in their degree of development, nor the characteristics of their magnetic susceptibility curves. In the case of paleosols in positions lower down the slope, signs of quasi-permanent sediment input could be recognized as being present as early as during the formation of the soil itself. This sediment input would seem to be surpassed in the case of pedogenesis strengthened by the climate of the last interglacial (marine isotope stage - MIS 5). Pedogenesis seems to be sustained by renewed intense dust accumulation in the Late Pleistocene, in MIS 3, though compared to MIS 5, the climate of MIS 3 did not favor intense pedogenesis. Despite the general belief that loess series formed in plateau positions can preserve terrestrial records without significant erosion, in the case of the Malá nad Hronom loess this is not so. Compared to the sequence affected by erosional events in the local top position, the sequence affected by quasi-continuous sediment input in the lower slope position seems to have preserved the soil horizons intact.International Visegrad Fund (project Number 11410020). The paper was also supported by a long-term conceptual development subvention available to research organizations RVO: 68145535 from the Institute of Geonics AS CR, by the Slovak Research and Development Agency under contract No. APVV-0625-11 (project “A new synthesis of the Western Carpathians landform evolution – preparation of the database for testing of key hypotheses”. B. Bradák acknowledges the financial support of project BU235P18 (Junta de Castilla y Leon, Spain) and the European Regional Development Fund (ERD), project PID2019-108753GB-C21 / AECI / 10.13039/501100011033 of the Agencia Estatal de Investigación and project PID2019-105796GB-100 / AECI / 10.13039/501100011033 of the Agencia Estatal de Investigación

Follow-up of patients with functional bowel symptoms treated with a low FODMAP diet

AIM: To investigate patient-reported outcomes from, and adherence to, a low FODMAP diet among patients suffering from irritable bowel syndrome and inflammatory bowel disease. METHODS: Consecutive patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) and co-existing IBS fulfilling the ROME. criteria, who previously attended an outpatient clinic for low FODMAP diet (LFD) dietary management and assessment by a gastroenterologist, were invited to participate in a retrospective questionnaire analysis. The questionnaires were sent and returned by regular mail and gathered information on recall of dietary treatment, efficacy, symptoms, adherence, satisfaction, change in disease course and stool type, and quality of life. Before study enrolment all patients had to sign an informed written consent. RESULTS: One hundred and eighty patients were included, 131 (73%) IBS and 49 (27%) IBD patients. Median age was 43 years (range: 18-85) and 147 (82%) were females. Median follow-up time was 16 mo (range: 2-80). Eighty-six percent reported either partial (54%) or full (32%) efficacy with greatest improvement of bloating (82%) and abdominal pain (71%). The proportion of patients with full efficacy tended to be greater in the IBD group than in the IBS group (42% vs 29%, p = 0.08). There was a significant reduction in patients with a chronic continuous disease course in both the IBS group (25%, p < 0.001) and IBD group (23%, p = 0.002) along with a significant increase in patients with a mild indolent disease course of 37% (p < 0.001) and 23% (p = 0.002), respectively. The proportion of patients having normal stools increased with 41% in the IBS group (p < 0.001) and 66% in the IBD group (p < 0.001). One-third of patients adhered to the diet and high adherence was associated with longer duration of dietary course (p < 0.001). Satisfaction with dietary management was seen in 83 (70%) IBS patients and 24 (55%) IBD patients. Eighty-four percent of patients lived on a modified LFD, where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. Wheat, dairy products, and onions were the foods most often not reintroduced by patients. CONCLUSION: These data suggest that a diet low in FODMAPs is an efficacious treatment solution in the management of functional bowel symptoms for IBS and IBD patients

Rescaled coordinate descent methods for linear programming

We propose two simple polynomial-time algorithms to find a positive solution to Ax=0Ax=0 . Both algorithms iterate between coordinate descent steps similar to von Neumann’s algorithm, and rescaling steps. In both cases, either the updating step leads to a substantial decrease in the norm, or we can infer that the condition measure is small and rescale in order to improve the geometry. We also show how the algorithms can be extended to find a solution of maximum support for the system Ax=0Ax=0 , x≥0x≥0 . This is an extended abstract. The missing proofs will be provided in the full version

Indapamide-induced transient myopia with supraciliary effusion: case report.

BACKGROUND: Ingestion of sulphonamide-derived drugs has been reported to possibly have ocular side-effects. Authors aimed to present a rare case of indapamide-induced transient myopia with ciliary body edema and supraciliary effusion. CASE PRESENTATION: A 39 years old caucasian female patient presented at the Department of Neurology with headache and sudden bilateral loss of distant vision. Neurological assessment and cranial CT scans were unremarkable. For her hypertension, twice a day bisoprolol 2.5 mg and once a day indapamide 1.5 mg tablets were prescribed several days before. At her presenting, ophthalmic findings were as follows: visual acuity 0.08-7.25Dsph = 1.0 and 0.06-7.25Dsph = 1.0; IOP 25 mmHg and 24 mmHg, anterior chamber depth (ACD) 2.32 mm and 2.49 mm, lens thickness (L) 4.02 mm and 4.09 mm in the right and the left eye, respectively. By means of ultrasound biomicroscopy (UBM), thickened (720 / 700 micron) and detached ciliary body, its forward movement (ciliary body-cornea angle 108[prime] / 114[prime]) and forward rotated ciliary processes were seen. Angle opening distance (AOD500) were 300 / 314 microns. By the following days, the myopia gradually diminished, and a week after her first symptoms, her uncorrected visual acuity was 1.0 in both eyes, IOP 13 mmHg and 17 mmHg, ACD 3.68 mm and 3.66 mm, L 3.78 mm and 3.81 mm in the right and the left eye, respectively. Ciliary body edema and detachment disappeared (ciliary body thickness 225 / 230 micron), both of the ciliary body-cornea angle 134[prime] / 140[prime] and the AOD500 (650 / 640 microns) increased. At this point, the patient admitted that she had stopped taking indapamide two days before. CONCLUSIONS: Our case report is the third one in the literature to present indapamide-induced transient myopia, and the first to employ UBM for describing the characteristics of this rare condition. According to the findings, authors suggest that both ciliary muscle contraction and ciliary body edema may play role in the pathomechanism. UBM seems to be a useful tool in the differential diagnosis of acute myopia. Further, authors wish to draw attention to one of the potential adverse effects of this drug which was not listed by its package insert

Low-FODMAP diet reduces irritable bowel symptoms in patients with inflammatory bowel disease

AIM To investigate the effect of a low-FODMAP diet on irritable bowel syndrome (IBS)-like symptoms in patients with inflammatory bowel disease (IBD). METHODS This was a randomised controlled open-label trial of patients with IBD in remission or with mild-to-moderate disease and coexisting IBS-like symptoms (Rome III) randomly assigned to a Low-FODMAP diet (LFD) or a normal diet (ND) for 6 wk between June 2012 and December 2013. Patients completed the IBS symptom severity system (IBS-SSS) and short IBD quality of life questionnaire (SIBDQ) at weeks 0 and 6. The primary end-point was response rates (at least 50-point reduction) in IBS-SSS at week 6 between groups; secondary end-point was the impact on quality of life. RESULTS Eighty-nine patients, 67 (75%) women, median age 40, range 20-70 years were randomised: 44 to LFD group and 45 to ND, from which 78 patients completed the study period and were included in the final analysis (37 LFD and 41 ND). There was a significantly larger proportion of responders in the LFD group (n = 30, 81%) than in the ND group (n = 19, 46%); (OR = 5.30; 95% CI: 1.81-15.55, P < 0.01). At week 6, the LFD group showed a significantly lower median IBS-SSS (median 115; inter-quartile range [IQR] 33-169) than ND group (median 170, IQR 91-288), P = 0.02. Furthermore, the LFD group had a significantly greater increase in SIBDQ (median 60, IQR 51-65) than the ND group (median 50, IQR 39-60), P < 0.01. CONCLUSION In a prospective study, a low-FODMAP diet reduced IBS-like symptoms and increased quality of life in patients with IBD in remission

Is Transition Experience Enough? The Donor-side Effectiveness of Czech and Polish Democracy Aid to Georgia

The paper examines the democracy aid practices of the Czech Republic and Poland in Georgia. These two countries have recently emerged as promoters of democracy, and have argued that their own transition experience puts them in a unique position to support democratization and the consolidation of democracy in the EU’s Eastern Neighbourhood. The paper evaluates how these two countries provide democracy aid to Georgia along three criteria, derived from the aid effectiveness literature: supporting locally driven change, learning from results and coordination. The results indicate that both countries have plenty of space to improve the way their democracy aid is delivered. Neither country has formal systems in place to ensure that they actually support Georgian priorities; evaluations are ad hoc and feedback loops missing; and there is significant scope to improve coordination with other donors. Nonetheless, there seems to be a general perception among stakeholders that the democracy aid provided by the Czech Republic and Poland is relevant to Georgia’s needs

Synaptic proteome changes in a DNA repair deficient Ercc1 mouse model of accelerated aging

Cognitive decline is one of the earliest hallmarks of both normal and pathological brain aging. Here we used Ercc1 mutant mice, which are impaired in multiple DNA repair systems and consequently show accelerated aging and progressive memory deficits, to identify changes in the levels of hippocampal synaptic proteins that potentially underlie these age-dependent deficits. Aged Ercc1 mutant mice show normal gross hippocampal dendritic morphology and synapse numbers, and Ercc1 mutant hippocampal neurons displayed normal outgrowth and synapse formation in vitro. However, using isobaric tag for relative and absolute quantification (iTRAQ) of hippocampal synaptic proteins at two different ages, postnatal days 28 and 112, we observed a progressive decrease in synaptic ionotropic glutamate receptor levels and increased levels of G-proteins and of cell adhesion proteins. These together may cause long-term changes in synapse function. In addition, we observed a downregulation of mitochondrial proteins and concomitant upregulation of Na,K-ATPase subunits, which might compensate for reduced mitochondrial activity. Thus, our findings show that under conditions of apparent intact neuronal connectivity, levels of specific synaptic proteins are already affected during the early stages of DNA damage-induced aging, which might contribute to age-dependent cognitive decline