A class of multivalent protein binders was designed to overcome the limitations of low-affinity therapeutic antibodies. These binders, termed "collabodies," use a triplex-forming collagen-like peptide to drive the trimerization of a heterologous target-binding domain. Different forms of collabody, consisting of the human single-chain variable fragment (scFv) fused to either the N or C terminus of the collagen-like peptide scaffold (Gly-Pro-Pro)(10), were stably expressed as soluble secretory proteins in mammalian cells. The collabody consisting of scFv fused to the N terminus of collagen scaffold is present as a homotrimer, whereas it exhibited a mixture of trimer and interchain disulfide-bonded hexamer when cysteine residues were introduced and flanked the scaffold. The collagenous motif in collabody is prolyl-hydroxylated, with remarkable thermal and serum stabilities. The collabody erb_scFv-Col bound to the extracellular domain of epidermal growth factor receptor with a binding strength approximately 20- and 1000-fold stronger than the bivalent and monovalent counterparts, respectively. The trimeric collagen scaffold does not compromise the functionality of the binding moieties of parental immunoglobulin G (IgG); therefore, it could be applied to fuse other protein molecules to acquire significantly improved targeting-binding strengths.

PurposeParanasal sinusitis is widespread and can lead to orbital complications, blindness, and death. However, the correlation between ophthalmological findings and disease staging remains unclear. This study aimed to investigate the staging, acute ophthalmological manifestations, diagnosis, management, and outcomes of orbital complications of paranasal sinusitis during a 27-year period.MethodsWe retrospectively reviewed the medical records of all patients with orbital complications of paranasal sinusitis hospitalized at the National Cheng Kung University Hospital, a medical center in Taiwan during 1988–2015. Sex, age, symptoms, history, ophthalmological findings, laboratory and imaging findings, treatments, and outcomes were analyzed by staging.ResultsEighty-three patients aged 9 days to 80 years had stage I (preseptal cellulitis, n = 39 patients), II (postseptal orbital cellulitis, n = 8), III (subperiosteal abscess, n = 16), IV (orbital abscess, n = 8), or V (intracranial involvement, n = 12) complications. Peak incidences occurred in patients aged 0–19 and 60–69 years. Chronic sinusitis and diabetes mellitus were common preexisting diseases. Extraocular movement limitation and proptosis predicted postseptal (stage II or more) involvement. The likelihood of elevated intraocular pressure increased with stage. Reduced visual acuity and presence of relative afferent pupillary defect indicated consideration of magnetic resonance imaging to investigate possible intracranial extension. Ipsilateral maxillary (81.7%) and ethmoidal (75.6%) sinuses were the most common sources of infection, and the most frequently implicated pathogens were coagulase-negative Staphylococcus spp. (25.3%) and Staphylococcus aureus (20.5%). All patients received intravenous antimicrobial therapy (multi-drug therapy in 88.0%), and 55.4% underwent surgery, most commonly endoscopic sinus surgery. One (1.2%) diabetic man with stage V complications died of fungal sinusitis with intracranial invasion. Five (6.0%) patients, all stage V, lost vision despite intensive treatment. The average length of hospital stay was 13.8 days (range 2–72 days), and significantly longer stays were associated with stages II–V as compared to stage I.ConclusionsOrbital infection originating from paranasal sinusitis can cause vision loss and death due to intracranial extension. Acute ophthalmological findings predict staging and prognosis. Cooperative consultation between ophthalmologists, otorhinolaryngologists, and neurologists is essential. Urgent diagnostic studies and aggressive antimicrobial therapy are indicated, and surgery should be considered.

Laminaripentaose-producing ␤-1,3-glucanase (LPHase), a member of glycoside hydrolase family 64, cleaves a longchain polysaccharide ␤-1,3-glucan into specific pentasaccharide oligomers. The crystal structure of LPHase from Streptomyces matensis DIC-108 was solved to 1.62 Å resolution using multiple-wavelength anomalous dispersion methods. The LPHase structure reveals a novel crescent-like fold; it consists of a barrel domain and a mixed (␣/␤) domain, forming a wide-open groove between the two domains. The liganded crystal structure was also solved to 1.

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