High levels of contact dermatitis and decreased mobility in broiler breeders, but neither have a relationship with floor eggs

Contact dermatitis, both on the foot pads and hocks, is a well-known health issue in broilers. Less is known about contact dermatitis in broiler breeders, however, although they have many risk factors for developing leg health problems in common with broilers. This study aimed to describe the prevalence and severity of contact dermatitis during the production cycle in 5 lines of broiler breeders, investigate possible causes of contact dermatitis, and study its relationship with gait, egg production, and floor egg percentage. Five commercially available genetic lines of broiler breeders were housed in 21 pens of 550 females and 50 males from 20 to 60 wk of age. Every 10 wk litter quality, leg health measurements (foot pad dermatitis, hock burn, and gait) and body weight were assessed of 50 random hens per pen. Total number of eggs, number of eggs laid outside the nest (floor eggs), and mortality were recorded daily per pen. Prevalence of foot pad dermatitis, hock burn, and gait problems increased with age. Litter quality started to decrease at 50 wk of age. Prevalence of foot pad dermatitis was affected by litter quality, whereas genetic line had little effect. One genetic line was more prone to developing hock burns, though generally the prevalence of hock burn (13%) was much lower than that of foot pad dermatitis (74%). The percentage of broiler breeders with gait problems increased up to 24% with age, but this was not related to the prevalence of contact dermatitis. The lines differed in body weight from 32 wk of age onwards, and a higher body weight was related to lower egg production and higher cumulative mortality. The percentage of floor eggs was not related to leg health parameters or genetic line. Broiler breeders thus have similar leg health problems as broilers, but these problems are not related to the percentage of floor eggs, suggesting that other factors are involved in the undesirable behavior of floor laying.</p

Anti-C2 Antibody ARGX-117 Inhibits Complement in a Disease Model for Multifocal Motor Neuropathy

BACKGROUND AND OBJECTIVES: To determine the role of complement in the disease pathology of multifocal motor neuropathy (MMN), we investigated complement activation, and inhibition, on binding of MMN patient-derived immunoglobulin M (IgM) antibodies in an induced pluripotent stem cell (iPSC)-derived motor neuron (MN) model for MMN. METHODS: iPSC-derived MNs were characterized for the expression of complement receptors and membrane-bound regulators, for the binding of circulating IgM anti-GM1 from patients with MMN, and for subsequent fixation of C4 and C3 on incubation with fresh serum. The potency of ARGX-117, a novel inhibitory monoclonal antibody targeting C2, to inhibit fixation of complement was assessed. RESULTS: iPSC-derived MNs moderately express the complement regulatory proteins CD46 and CD55 and strongly expressed CD59. Furthermore, MNs express C3aR, C5aR, and complement receptor 1. IgM anti-GM1 antibodies in serum from patients with MMN bind to MNs and induce C3 and C4 fixation on incubation with fresh serum. ARGX-117 inhibits complement activation downstream of C4 induced by patient-derived anti-GM1 antibodies bound to MNs. DISCUSSION: Binding of IgM antibodies from patients with MMN to iPSC-derived MNs induces complement activation. By expressing complement regulatory proteins, particularly CD59, MNs are protected against complement-mediated lysis. Yet, because of expressing C3aR, the function of these cells may be affected by complement activation upstream of membrane attack complex formation. ARGX-117 inhibits complement activation upstream of C3 in this disease model for MMN and therefore represents an intervention strategy to prevent harmful effects of complement in MMN

MYC is a clinically significant driver of mTOR inhibitor resistance in breast cancer

Targeting the PI3K–AKT–mTOR pathway is a promising therapeutic strategy for breast cancer treatment. However, low response rates and development of resistance to PI3K–AKT–mTOR inhibitors remain major clinical challenges. Here, we show that MYC activation drives resistance to mTOR inhibitors (mTORi) in breast cancer. Multiomic profiling of mouse invasive lobular carcinoma (ILC) tumors revealed recurrent Myc amplifications in tumors that acquired resistance to the mTORi AZD8055. MYC activation was associated with biological processes linked to mTORi response and counteracted mTORi-induced translation inhibition by promoting translation of ribosomal proteins. In vitro and in vivo induction of MYC conferred mTORi resistance in mouse and human breast cancer models. Conversely, AZD8055-resistant ILC cells depended on MYC, as demonstrated by the synergistic effects of mTORi and MYCi combination treatment. Notably, MYC status was significantly associated with poor response to everolimus therapy in metastatic breast cancer patients. Thus, MYC is a clinically relevant driver of mTORi resistance that may stratify breast cancer patients for mTOR-targeted therapies

Transcriptome Analysis of the Desert Locust Central Nervous System: Production and Annotation of a Schistocerca gregaria EST Database

) displays a fascinating type of phenotypic plasticity, designated as ‘phase polyphenism’. Depending on environmental conditions, one genome can be translated into two highly divergent phenotypes, termed the solitarious and gregarious (swarming) phase. Although many of the underlying molecular events remain elusive, the central nervous system (CNS) is expected to play a crucial role in the phase transition process. Locusts have also proven to be interesting model organisms in a physiological and neurobiological research context. However, molecular studies in locusts are hampered by the fact that genome/transcriptome sequence information available for this branch of insects is still limited. EST information is highly complementary to the existing orthopteran transcriptomic data. Since many novel transcripts encode neuronal signaling and signal transduction components, this paper includes an overview of these sequences. Furthermore, several transcripts being differentially represented in solitarious and gregarious locusts were retrieved from this EST database. The findings highlight the involvement of the CNS in the phase transition process and indicate that this novel annotated database may also add to the emerging knowledge of concomitant neuronal signaling and neuroplasticity events. EST data constitute an important new source of information that will be instrumental in further unraveling the molecular principles of phase polyphenism, in further establishing locusts as valuable research model organisms and in molecular evolutionary and comparative entomology

Alectinib en osimertinib: nieuwe generatie tyrosinekinaseremmers met betere penetratie in de hersenen bij niet-kleincellig longcarcinoom

Met de komst van alectinib en osimertinib zijn de vooruitzichten voor patiënten met niet-kleincellig longcarcinoom (NSCLC), onder de vorm van adenocarcinoom met EGFR-mutaties en ALK-translocaties, verbeterd. Zowel alectinib (Alecenca®) als osimertinib (Tagrisso®) hebben in fase 3-studies aangetoond de progressievrije overleving te verlengen. Hier staat wel een forse prijs tegenover: een behandeling van zesduizend euro per maand is geen uitzondering. De nieuwe generatie tyrosinekinaseremmers, waar alectinib en osimertinib onder vallen, penetreren de bloed-hersenbarrière beter en geven derhalve een betere intracraniële respons. Aangezien een deel van de patiënten met een EGFR-mutatie, en in het bijzonder met een ALK-translocatie, bij diagnose reeds hersenmetastasen heeft of krijgt in het beloop van hun ziekte, is de verwachting dat deze nieuwe middelen eerder in de behandeling van NSCLC worden ingezet