Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response.

Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Recueil d'épitaphes, précédé d'un journal des principaux événements arrivés à Paris de 1557 à 1590.

Contient : 1 Journal autographe de JEHAN DE LA FOSSE, où sont notés mois par mois les principaux événements des années 1557 à 1590, arrivés en France et particulièrement à Paris, où vivait l'auteur, curé de St-Leu et de St-Barthélemy ; 2 Recueil d'épitaphes ; « Cavendish,... general Norris,... docter Story,... mylord Treasurer,... Frier Andrew,... Ellis,... earle of Essex, beheaded in the tower », Joannes Rekingale, episcopus Cicestriensis, Gulielmus de Blitz, archidiaconus Nodovicensis ; Thomas Linaerus, regis Henrici VIII medicus, Antonius Riccius Faventiae, « Mr Hofkins », Lucretia Borgia, Honorius P. M., Johannes Riberius ; Galfridus Chaucer, Corythus, filius Oenones et Paridis, Ninus, Assyriae monarcha, Pyramis, lateritia Asychis, Aegypti regis ; Bartholomaeus Platina, Petrus Pomponatius, Pompeius Magnus, Capys, Ennius, Hannibal ; Marcus Antonius Turrianus, Marcus Antonius Coccius, Marcus Antonius Casanova, Sardanapalus, Rufus, Julius Caesar, Augustus Caesar ; Petrus Ciaconius, Nicolaus Macchiavellus, Gulielmus Rondeletus, medicus, Anicia, foemina romana, Callicratea ; Johannes Coletus, Rembertus Dodonaeus, medicus Maximiliani II et Rodolphi imperatorum, Alcaeus poeta, Scipio Africanus ; Paracelsus, Gerardus Noviomagus et Andreas Hyperius, Didacus de Valdes, Albericus de Vere et Gulielmus, primus comes Oxoniensis, Robertus Buc ; Hieronymus Cagnolus Vercellensis, Johannes Stofflerus, mathematicus Tubingae, Remigius Bellaqueus, Pallas, Evandri filius, Zarmanochegas indus, de Bargosa ; Johannes Rivius Attbend, Petrus Bembus, Lucius P. M. Veronae, Gulielmus Norselez, decanus quondam ecclesiae S. Pauli Londini, Mathias Corvinus, rex Pannoniae ; Philippus Callimachus Cracoviae, in aede S. Trinitatis, Ludovicus Bologninus, Bononiae, Rachel, uxor Jacobi Bethleem, Aratus, Plato, Aeschylus ; Joannes Zonaras, Homerus, Menander, Epictetus ; Berengarius, archidiaconus Andegavensis, Andreas Fanzonius, Cyrus, Persarum monarcha, Midas ; Hugo S. Victoris Parisiensis, S. Bernardus, abbas claraevallensis, Petrus de Toledo, Psittacus, Musaeus poeta, Linus, thebanus poeta, Orpheus ; Petrus Lombardus, Petrus Comestor, Pallas, libertus Romae, Megista, Spartanus vates ; Aegidius de Roma, archiepiscopus Bituricensis, Johannes Gerson, Aristocrates, perfidus in Lycaei Jovis luco, Setho, sacerdos Vulcani et Aegypti rex, Rosamunda Cliffordensis, Petrus Aretinus ; Nicolaus de Lyra, Jacobus Pisaurus, Paphi episcopus, Cedwalla, rex Sussexiae ; Alphonsus Tostadus, hispanus, Abulensis episcopus, Albertus Pius de Sabaudia, princeps Carporum, Similis, praefectus praetorianorum, Jupiter, Osyris, Isis ; Aeneas Sylvius, Christophorus Colombus, Hermes, Apollo, Timon, Darius ; Robertus Gaguinus, Johannes de Sacro Busto, Darius, Hystaspis filius, Simandius, Aegypti rex, Idomeneus et Myrio, filii Deucalionis, Semiramis ; Alexander Piccolomineus, Justina, pulchra foemina, quam maritus zelotypus nefarie decollavit, Claudia, nobilis foemina Romae, Carolus Magnus, Carolus V, imperator ; Actius Plautus, Johannes Boccacius, Franciscus Ximenes, cardinalis Hispaniae, Federicus imperator, Sylla, Ricardus I, rex Anglorum ; Johannes Stadius, math. belga, C. Manlia camertina, Johannes de Mandeville, Patricius, Brigida et Columda in Hibernia, la reine d'Angleterre, femme de Jacques Ier ; Johannes Glandorp, Jodocus, medicus Romae, Urandus, sive Durandus, Johannes Jacobus Trivultius, Ludovicus VIII, rex Francorum ; Antonius quidam italus, Fin dal Finale, Battistina Senensis, puella elegantissima ; Chalonerus Dubliniae, Askew Lincolniensis, Christophorus Hatton, Robertus, comes Leicestriae ; Johannes Chidley, Walterus Ralegh, Arturus Gorges, Johannes Parkar, Maria Stafford, Charitas et Carolus Ho., Thomas Wals, Sylvanus Scorus, Johannes Horo et Edwardus Nymark, Edwardus Stanhop, Franciscus Wal ; Philippus Sydney, Franciscus Walsinghan, N. Marsonius, jurisconsultus, Christophorus H, Gulielmus, comes Penbrok, Angliae marescallus, Antonius Deny, frater Lubinus ; Fratislaus, dux Bohemiae, countess of Penbrok, Edward Spenser, Henry Abyngdon, Thomas Nash, N. Dobson ; Dr Hugh a price, Johannes Vitulus, Dr Bently, Hor. Pallavicin, Margaret Ratcliff ; Howlet, Elian, Henry Barron ; James Stuart, Thomas Sackville, Penelope d'Evreux, uxor domini Bar. Rich, pellicis comitis Devonshire, Robert Cecil, Ricardus Bancroft, archiepiscopus Cantuariensis ; Godefridus de Bulion, Balduinus, rex Jerusalem, Allicia, pulchra foemina anglica et forte meretrix, Theobaldus, comes Campaniae, qui vixit tempore regis Angliae Stephani ; Fernandus de Castro, hispanus in Anglia exulans et moriens ob fidem in Dominum Petrum, regem Castellae, Johannes Taylor de Colman street, usurarius, Petrus Miago Vallisoleti, in templo Sancti Stephani, Franciscus Duarte de Mendico, a proveedor de los exercitos y armadas del emperador Carlo V, Henricus, Walliae princeps ; Milo, comes de Anglera, pater Rolandi, a Mauris juxta ripam Ceae occisus, Hecuba, S. Edmundus, rex et martyr, Pindarus, poeta lyricus, Stesichorus, Anacreon, poeta vinosus, Leonidas, dux Lacedemoniorum ad Thermopylas occisus contra Persas, Timotheus, citharedus milesius ; Timocreon Rhodius, Laïs, meretrix Corinthia, sepulta in Thessalia, juxta Peneum fluvium, Acron, antiquissimus medicus Agrigentinus

Nguyêñ, Văn Thành (1757-1817). 皇越律例. Hoàng Việt luật lệ. Nguyêñ, Văn Thành (1757-1817). 皇越律例. Hoàng Việt luật lệ. Binh luật 兵律

Code de lois du Vietnam du mandarin Nguyêñ. Préface de Gialong, des tables des matières et 22 chapitres.