Mechanochemical Synthesis and Structure of Lithium Tetrahaloaluminates, LiAlX4 (X = Cl, Br, I): A Family of Li-Ion Conducting Ternary Halides.

State-of-the-art oxides and sulfides with high Li-ion conductivity and good electrochemical stability are among the most promising candidates for solid-state electrolytes in secondary batteries. Yet emerging halides offer promising alternatives because of their intrinsic low Li+ migration energy barriers, high electrochemical oxidative stability, and beneficial mechanical properties. Mechanochemical synthesis has enabled the characterization of LiAlX4 compounds to be extended and the iodide, LiAlI4, to be synthesized for the first time (monoclinic P21/c, Z = 4; a = 8.0846(1) Å; b = 7.4369(1) Å; c = 14.8890(2) Å; ß = 93.0457(8)°). Of the tetrahaloaluminates, LiAlBr4 exhibited the highest ionic conductivity at room temperature (0.033 mS cm-1), while LiAlCl4 showed a conductivity of 0.17 mS cm-1 at 333 K, coupled with the highest thermal and oxidative stability. Modeling of the diffusion pathways suggests that the Li-ion transport mechanism in each tetrahaloaluminate is closely related and mediated by both halide polarizability and concerted complex anion motions.

Influence of Iron Sulfide Nanoparticle Sizes in Solid-State Batteries*.

Given the inherent performance limitations of intercalation-based lithium-ion batteries, solid-state conversion batteries are promising systems for future energy storage. A high specific capacity and natural abundancy make iron disulfide (FeS2 ) a promising cathode-active material. In this work, FeS2 nanoparticles were prepared solvothermally. By adjusting the synthesis conditions, samples with average particle diameters between 10 nm and 35 nm were synthesized. The electrochemical performance was evaluated in solid-state cells with a Li-argyrodite solid electrolyte. While the reduction of FeS2 was found to be irreversible in the initial discharge, a stable cycling of the reduced species was observed subsequently. A positive effect of smaller particle dimensions on FeS2 utilization was identified, which can be attributed to a higher interfacial contact area and shortened diffusion pathways inside the FeS2 particles. These results highlight the general importance of morphological design to exploit the promising theoretical capacity of conversion electrodes in solid-state batteries.

A missense mutation in the plasminogen gene, within the plasminogen kringle 3 domain, in hereditary angioedema with normal C1 inhibitor.

Hereditary angioedema (HAE) is a genetically heterogeneous disease that is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic types, HAE types I and II, are both caused by mutations in the complement C1 inhibitor (SERPING1) gene resulting either in a quantitative or a qualitative deficiency of C1 inhibitor. In so-called HAE type III, in contrast, patients show normal C1 inhibitor measurements in plasma ('HAE with normal C1 inhibitor'). As previously shown by us, one subgroup of 'HAE with normal C1 inhibitor' is caused by mutations of the coagulation factor XII (F12) gene. For the present study, following the exclusion of numerous candidate genes, we screened eight unrelated index patients representing eight 'HAE families with normal C1 inhibitor and no F12 mutation' for mutations in the plasminogen (PLG) gene. A rare non-conservative missense mutation was newly identified in exon 9 of the PLG gene. This mutation (c.1100A > G), encountered in three out of eight patients, predicts a lysine-to-glutamic acid substitution in position 311 of the mature protein (p.Lys311Glu). Using isoelectric focusing of plasma samples followed by an immunoblotting procedure we demonstrated that the presence of the mutation is associated with a dysplasminogenemia, namely the presence of an aberrant plasminogen protein. The predicted structural and functional impact of the mutation, its absence in 139 control individuals, and its co-segregation with the phenotype in three large families provide strong support that it causes disease. Extending a previously proposed gene-based alphabetic nomenclature for the various HAE types one may use the term 'HAE type C' for the HAE entity described here.

Complement factor 7 gene mutations in relation to meningococcal infection and clinical recurrence of meningococcal disease.

Meningococcal disease is caused by Neisseria meningitidis which is associated with high morbidity and mortality. Recurrences of meningococcal infection have been observed in patients with terminal complement component defects, because of the inefficient formation of the lytic membrane attack complex (MAC), C5b-9. Complement component C7 is one of the five plasma proteins to form the MAC. The gene C7 may carry mutations that cause functional abnormalities or the mere absence of the C7 protein. More than 200 patients were screened for aberrant C7 protein by isoelectric focusing (C7 IEF). These were compared with patients in whom recurrent meningococcal infection had resulted in the diagnosis of complete C7 absence (C7Q0). A higher proportion of C7 IEF variants were found in meningitis cases compared to controls (p=0.03). In contrast to C7Q0 patients, recurrent meningococcal infection was never observed in C7 IEF cases. Whereas C7Q0 sera were defective in meningococcal serogroup B and W135 killing assays, the sera of patients with C7 IEF variants were only defective in complement-mediated killing when classical pathway activation by (endogenous) anti-meningococcal antibodies was blocked. Upon sequence analysis we characterized the genetic background of the C7*6 and C7*8 IEF pattern and identified three novel C7 gene mutations in 13 C7Q0 patients. In conclusion, C7 IEF variants can determine meningococcal killing in the early stage of infection when antibody-independent killing prevails. The results endorse the lack of clinical recurrences once antibodies are present, whereas in C7Q0 patients the anti-meningococcal antibodies may not suffice to protect from recurrent meningococcal infection.

Hereditary angioedema with normal C1 inhibitor: clinical symptoms and course.

PURPOSE: A new type of hereditary angioedema was described recently. It was characterized by recurrent bouts of angioedema in various organs and normal C1 inhibitor and was observed mainly in women. Our aim was to conduct a detailed study of the clinical features of this condition. METHODS: A total of 138 patients with hereditary angioedema and normal C1 inhibitor who belonged to 43 unrelated families were examined through the use of standardized questionnaires. RESULTS: A majority of patients with hereditary angioedema and normal C1 inhibitor had skin swellings (92.8%), tongue swellings (53.6%), and abdominal pain attacks (50%). Laryngeal edema (25.4%) and uvular edema (21.7%) also were frequent, whereas edema episodes of other organs were rare (3.6%). Facial swellings and tongue involvement occurred considerably more frequently compared with hereditary angioedema caused by C1 inhibitor deficiency. The number of patients with recurrent edema of only 1 organ was higher than in classic hereditary angioedema. The number of patients with disease onset in adulthood was significantly higher in hereditary angioedema with normal C1 inhibitor compared with classic hereditary angioedema. Erythema marginatum was not observed. A subgroup of patients from families with coagulation factor XII mutations showed the same symptoms as the other patients. CONCLUSIONS: Hereditary angioedema with normal C1 inhibitor levels shows a characteristic pattern of clinical symptoms. The main clinical features include skin swellings, tongue swellings, and abdominal pain attacks. There are many differences in the clinical symptoms and course of disease between this type of hereditary angioedema and classic hereditary angioedema caused by a genetic C1 inhibitor deficiency.

Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor.

Hereditary angioedema is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic types are both caused by mutations within the complement C1 inhibitor gene. A recently described new type does not show a deficiency of C1 inhibitor and affects almost exclusively women. We screened twenty unrelated index patients with this new type of hereditary angioedema for mutations in the coagulation factor XII gene. Two different missense mutations were identified in exactly the same position within exon 9 of the F12 gene. 'Mutation 1' (1032C-->A), encountered in five patients, predicts a threonine-to-lysine substitution (Thr309Lys). 'Mutation 2' (1032C-->G), observed in one patient, results in a threonine-to-arginine substitution (Thr309Arg). The predicted structural and functional impact of the mutations, their absence in 145 healthy controls, and their co-segregation with the phenotype in five families provide strong support that they cause disease.

Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin.

We have identified nonsense mutations in the gene CDSN (encoding corneodesmosin) in three families suffering from hypotrichosis simplex of the scalp (HSS; OMIM 146520). CDSN, a glycoprotein expressed in the epidermis and inner root sheath (IRS) of hair follicles, is a keratinocyte adhesion molecule. Truncated CDSN aggregates were detected in the superficial dermis and at the periphery of hair follicles. Our findings suggest that CDSN is important in normal scalp hair physiology.

Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy.

PURPOSE: Recurrent angioedema, characterized by skin swelling, colicky attacks of abdominal pain, and life-threatening laryngeal edema, can be either hereditary or acquired. According to anecdotal reports, it may be associated with use of oral contraceptives and hormone replacement therapy. We investigated potential interactions between these medications and various types of recurrent angioedema in a large cohort of women. METHODS: Women with recurrent angioedema (n = 516) underwent a thorough medical evaluation. They were then classified by type of angioedema, using standard criteria. RESULTS: Of the 516 women, 228 (44%) had used oral contraceptives or hormone replacement therapy, including 103 (45%) with urticaria-related angioedema, 50 (22%) with idiopathic angioedema, 39 (17%) with hereditary angioedema type III, 32 (14%) with hereditary angioedema type I, and 4 (2%) with angioedema induced by angiotensin-converting enzyme inhibitors. Oral contraceptives or hormone replacement therapy led to angioedema attacks in 46 women (20%), including 20 (63%) of the women with hereditary angioedema type I, 24 (62%) of those with hereditary angioedema type III, and 2 (4%) of those with idiopathic angioedema. These 46 women included 26 in whom symptoms occurred for the first time after use of these medications and 20 in whom pre-existing recurrent angioedema worsened considerably. CONCLUSION: Oral contraceptives or hormone replacement therapy can either induce or exacerbate symptoms of hereditary angioedema type I or type III, or idiopathic angioedema. However, many women with these diseases tolerate these medications without having any effects on their angioedema.