Implementing an appropriate metric for the assessment of greenhouse gas emissions from livestock production: A national case study.

Livestock farming is of major economic relevance but also severely contributes to environmental impacts, especially greenhouse gas (GHG) emissions such as methane (CH4; particularly from ruminant production) and nitrous oxide (N2O; mainly from manure management and soil cultivated for feed production). In this study, we analyse the impact of GHG emissions from Austrian livestock production, using two metrics: a) the commonly used global warming potential (GWP) over 100 years (GWP100 in CO2-equivalents, CO2-e), and b) the recently introduced metric GWP*, which describes additional warming as a function of the timeline of short-lived GHG emissions (unit CO2 warming equivalents, CO2-we). We first compiled the sectoral (i.e. only direct emissions without upstream processes) GWP100 for different livestock categories with a focus on dairy cattle, beef cattle and pigs in Austria between 1990 and 2019. We also estimated product-related (i.e. per kg carcass weight or per litre of milk) GWP100 values, including upstream processes. We then calculated the corresponding GWP* metrics, both sectoral and product-related, and compared them with the GWP100 values. Decreasing livestock numbers and improved production efficiency were found to result in strong sectoral emission reductions from dairy production (-32 % of GWP100 from 1990 to 2019) and from pigs (-32 % CO2-e). This contrasts with low reductions from other livestock categories and even increases for cattle other than dairy cows (+3 % CO2-e), mainly due to rising suckler cow numbers. Allocated results per kg milk and kg body mass show quite similar results. Using the GWP* metric, the climate impacts of Austrian livestock production are less severe. When assuming constant management and emission intensity over a period of at least 20 years, the CO2-we (GWP*) is almost 50 % less than CO2-e (GWP100) per kg Austrian raw milk due to the different impacts of the short-lived CH4. A similar trend applies to an average cattle carcass (-40 % warming impact). The emission reductions of the shrinking Austrian livestock population represent an important contribution to a climate-neutral agriculture: The CH4 reductions of livestock production during the past 20 years reduce the current total Austrian CO2-we by 16 %. Continuous CH4 reduction, as we show it here for Austrian livestock, is an effective option to tackle the climate crisis in the short term. It shall be stressed that a relatively low GWP* should not be interpreted as a concession for further CH4 emissions but as an actual reduction of (additional) warming.

Nilotinib-induced vasculopathy: identification of vascular endothelial cells as a primary target site.

The BCR/ABL1 inhibitor Nilotinib is increasingly used to treat patients with chronic myeloid leukemia (CML). Although otherwise well-tolerated, Nilotinib has been associated with the occurrence of progressive arterial occlusive disease (AOD). Our objective was to determine the exact frequency of AOD and examine in vitro and in vivo effects of Nilotinib and Imatinib on endothelial cells to explain AOD-development. In contrast to Imatinib, Nilotinib was found to upregulate pro-atherogenic adhesion-proteins (ICAM-1, E-selectin, VCAM-1) on human endothelial cells. Nilotinib also suppressed endothelial cell proliferation, migration and tube-formation and bound to a distinct set of target-kinases, relevant to angiogenesis and atherosclerosis, including angiopoietin receptor-1 TEK, ABL-2, JAK1 and MAP-kinases. Nilotinib and siRNA against ABL-2 also suppressed KDR expression. In addition, Nilotinib augmented atherosclerosis in ApoE-/- mice and blocked reperfusion and angiogenesis in a hindlimb-ischemia model of arterial occlusion, whereas Imatinib showed no comparable effects. Clinically overt AOD-events were found to accumulate over time in Nilotinib-treated patients. After a median observation-time of 2.0 years, the AOD-frequency was higher in these patients (29.4%) compared to risk factor- and age-matched controls (<5%). Together, Nilotinib exerts direct pro-atherogenic and anti-angiogenic effects on vascular endothelial cells, which may contribute to development of AOD in patients with CML.

Two novel translocation breakpoints upstream of SOX9 define borders of the proximal and distal breakpoint cluster region in campomelic dysplasia.

The semilethal skeletal malformation syndrome campomelic dysplasia (CD) with or without XY sex reversal is caused by mutations within the SOX9 gene on 17q24.3 or by chromosomal aberrations (translocations, inversions or deletions) with breakpoints outside the SOX9 coding region. The previously published CD translocation breakpoints upstream of SOX9 fall into two clusters: a proximal cluster with breakpoints between 50-300 kb and a distal cluster with breakpoints between 899-932 kb. Here, we present clinical, cytogenetic and molecular data from two novel CD translocation cases. Case 1 with karyotype 46,XY,t(1;17)(q42.1;q24.3) has characteristic symptoms of CD, including mild tibial bowing, cryptorchidism and hypospadias. By standard fluorescence in situ hybridization (FISH) and by high-resolution fiber FISH, the 17q breakpoint was mapped 375 kb from SOX9, defining the centromeric border of the proximal breakpoint cluster region. Case 2 with karyotype 46,X,t(Y;17)(q11.2;q24.3) has the acampomelic form of CD and complete XY sex reversal. By FISH and somatic cell hybrid analysis, the 17q breakpoint was mapped 789 kb from SOX9, defining the telomeric border of the distal breakpoint cluster region. We discuss the structure of the 1 Mb cis-control region upstream of SOX9 and the correlation between the position of the 14 mapped translocation breakpoints with respect to disease severity and XY sex reversal.

High-resolution mapping of the human 4q21 and the mouse 5E3 SCYB chemokine cluster by fiber-fluorescence in situ hybridization.

The CXC chemokine or small inducible cytokine B (SCYB) subfamily includes the T-cell chemoattractants MIG (CXCL9, SCYB9), IP-10 (CXCL10, SCYB10), and I-TAC (CXCL11, SCYB11). These three highly homologous chemokines lack the glutamic acid-leucine-arginine (ELR) motif and signal via the CXCR3 receptor. Previous work showed that the genes encoding these chemokines are localized in an individual mini-cluster on human Chromosome (Chr) 4 at position 4q21.2. Recently, we identified mouse Scyb11 and mapped this gene by fluorescence in situ hybridization (FISH) to mouse Chr 5E3, the orthologous locus to human 4q21 where the other two homologous mouse genes, Scyb9 and Scyb10, have also been localized. Since SCYB10 and SCYB11 are not represented in the recently published draft sequence of the human genome, we wanted to clarify exactly the order and distances of the three chemokine genes using two-color FISH on stretched DNA fiber preparations. Here, we report the simultaneous localization of all three genes and provide high-resolution visual maps of this chemokine cluster from both mouse and human. The three chemokine genes were found within a range of 32 kb on mouse and 29 kb on human DNA fiber targets. The precise physical distances were defined, and an almost identical arrangement of the human and mouse homologues was identified, indicating that this CXC chemokine mini-cluster has been completely conserved evolutionarily since the divergence of mouse and human. Our results refine previous maps of the three genes, support the hypothesis that they resulted from gene duplication that took place in a common ancestor of mouse and human, and provide complementary information on a region of the draft sequence of human Chr 4 that is not yet covered.