Parading through a Circular Area Development with Arts and Sciences

In recent years, there has been increased attention toward art-science collaborations. Such collaborations encompass a broad spectrum of activities, ranging from artistic projects informed by technology and scientific research and vice versa, to novel forms of inquiry and communication at the intersection of the arts and sciences, combining diverse forms of knowledge and imagination. While such collaborations are not necessarily new, their recent manifestations allow us to gain insights into how complex societal challenges might be approached through multi-actor and disciplinary partnershi

Parading through a Circular Area Development with Arts and Sciences

In recent years, there has been increased attention toward art-science collaborations. Such collaborations encompass a broad spectrum of activities, ranging from artistic projects informed by technology and scientific research and vice versa, to novel forms of inquiry and communication at the intersection of the arts and sciences, combining diverse forms of knowledge and imagination. While such collaborations are not necessarily new, their recent manifestations allow us to gain insights into how complex societal challenges might be approached through multi-actor and disciplinary partnershi

Evaluation of two dairy herd reproductive performance indicators that are adjusted for voluntary waiting period

<p>Abstract</p> <p>Background</p> <p>Overall reproductive performance of dairy herds is monitored by various indicators. Most of them do not consider all eligible animals and do not consider different management strategies at farm level. This problem can be alleviated by measuring the proportion of pregnant cows by specific intervals after their calving date or after a fixed time period, such as the voluntary waiting period. The aim of this study was to evaluate two reproductive performance indicators that consider the voluntary waiting period at the herd. The two indicators were: percentage of pregnant cows in the herd after the voluntary waiting period plus 30 days (PV30) and percentage of inseminated cows in the herd after the voluntary waiting period plus 30 days (IV30). We wanted to assess how PV30 and IV30 perform in a simulation of herds with different reproductive management and physiology and to compare them to indicators of reproductive performance that do not consider the herd voluntary waiting period.</p> <p>Methods</p> <p>To evaluate the reproductive indicators we used the SimHerd-program, a stochastic simulation model, and 18 scenarios were simulated. The scenarios were designed by altering the reproductive management efficiency and the status of reproductive physiology of the herd. Logistic regression models, together with receiver operating characteristics (ROC), were used to examine how well the reproductive performance indicators could discriminate between herds of different levels of reproductive management efficiency or reproductive physiology.</p> <p>Results</p> <p>The logistic regression models with the ROC analysis showed that IV30 was the indicator that best discriminated between different levels of management efficiency followed by PV30, calving interval, 200-days not-in calf-rate (NotIC200), in calf rate at100-days (IC100) and a fertility index. For reproductive physiology the ROC analysis showed that the fertility index was the indicator that best discriminated between different levels, followed by PV30, NotIC200, IC100 and the calving interval. IV30 could not discriminate between the two levels.</p> <p>Conclusion</p> <p>PV30 is the single best performance indicator for estimating the level of both herd management efficiency and reproductive physiology followed by NotIC200 and IC100. This indicates that PV30 could be a potential candidate for inclusion in dairy herd improvement schemes.</p

Social responsiveness scale-aided analysis of the clinical impact of copy number variations in autism

Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient’s phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders

SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees.

The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants

Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition

Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP10-HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment. Furthermore, MTP10-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP10-HDL's favorable biodistribution and safety profile in non-human primates. In conclusion, we show that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs