Interactions between Social Hierarchy and Some Udder Morphometric Traits upon Colostrum and Milk Physicochemical Characteristics in Crossbred Dairy Goats

The possible relationship between udder morphometric variables (UMVs), chemical quality (CHQ) of both colostrum (CA), and milk (MK), as affected by goat’s social rank (SR) (i.e., low-LSR, or high-HSR), was assessed. In late June, goats (Alpine–Saanen–Nubian x Criollo; n = 38; 25◦ N) were estrus-synchronized and subjected to a fixed-time artificial insemination protocol. Thereafter, in October, while a behavioral study was performed in confirmed-pregnant goats to define the SR classes (n = 15), live weight (LW), body condition (BCS), and serum glucose (GLUC) were registered on the last day of the behavioral study. The expected kidding date was 25 November. Both the UMVs (i.e., seven dates) and the CHQ (i.e., either one for CA and three times for MK) were collected across time (T). The UMVs involved udder perimeter (UDPER, cm), udder diameter (UDDIA, cm), left-teat (LTPER, cm) and right-teat perimeter (RTPER, cm), left-teat (LTLT, cm) and right-teat length (RTLT, cm), left-teat diameter (LTDIA, cm) and right-teat diameter (RTDIA, cm), and medium suspensory ligament (MSL, cm). The registered CHQ variables for both CA and MK were fat (FAT), protein (PRO), lactose (LAC), nonfat solids (NFS), freezing point (FP), and total solids (TS). The possible effect of SR, T, and the SR × T interaction upon the described response variables was tested. While LW favored the HSR goats (54.6 vs. 48.2 ± 1.7 kg; p 0.05) between SR. An SR × T interaction affected (p FAT, > PRO, and > NFS) during early lactation. Therefore, both social rank (i.e., HSR goats), as well as the temporal transition stage from the last third of pregnancy to the first phase of lactation (i.e., time), operated as important modulators upon both udder architecture and milk quality in crossbred dairy goats under a dry-semiarid production system

Mitochondrial Ca2+ Overload Underlies Aβ Oligomers Neurotoxicity Providing an Unexpected Mechanism of Neuroprotection by NSAIDs

Dysregulation of intracellular Ca2+ homeostasis may underlie amyloid β peptide (Aβ) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Aβ1–42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Aβ fibrils, induce a massive entry of Ca2+ in neurons and promote mitochondrial Ca2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Aβ oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca2+ overload, cytochrome c release and cell death induced by Aβ oligomers. Our results indicate that i) mitochondrial Ca2+ overload underlies the neurotoxicity induced by Aβ oligomers and ii) inhibition of mitochondrial Ca2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Aβ oligomers and AD

Formation and Toxicity of Soluble Polyglutamine Oligomers in Living Cells

Aggregation and cytotoxicity of mutant proteins containing an expanded number of polyglutamine (polyQ) repeats is a hallmark of several diseases, including Huntington's disease (HD). Within cells, mutant Huntingtin (mHtt) and other polyglutamine expansion mutant proteins exist as monomers, soluble oligomers, and insoluble inclusion bodies (IBs). Determining which of these forms constitute a toxic species has proven difficult. Recent studies support a role for IBs as a cellular coping mechanism to sequester levels of potentially toxic soluble monomeric and oligomeric species of mHtt.When fused to a fluorescent reporter (GFP) and expressed in cells, the soluble monomeric and oligomeric polyglutamine species are visually indistinguishable. Here, we describe two complementary biophysical fluorescence microscopy techniques to directly detect soluble polyglutamine oligomers (using Htt exon 1 or Htt(ex1)) and monitor their fates in live cells. Photobleaching analyses revealed a significant reduction in the mobilities of mHtt(ex1) variants consistent with their incorporation into soluble microcomplexes. Similarly, when fused to split-GFP constructs, both wildtype and mHtt(ex1) formed oligomers, as evidenced by the formation of a fluorescent reporter. Only the mHtt(ex1) split-GFP oligomers assembled into IBs. Both FRAP and split-GFP approaches confirmed the ability of mHtt(ex1) to bind and incorporate wildtype Htt into soluble oligomers. We exploited the irreversible binding of split-GFP fragments to forcibly increase levels of soluble oligomeric mHtt(ex1). A corresponding increase in the rate of IBs formation and the number formed was observed. Importantly, higher levels of soluble mHtt(ex1) oligomers significantly correlated with increased mutant cytotoxicity, independent of the presence of IBs.Our study describes powerful and sensitive tools for investigating soluble oligomeric forms of expanded polyglutamine proteins, and their impact on cell viability. Moreover, these methods should be applicable for the detection of soluble oligomers of a wide variety of aggregation prone proteins

Optimization in computational systems biology

Optimization aims to make a system or design as effective or functional as possible. Mathematical optimization methods are widely used in engineering, economics and science. This commentary is focused on applications of mathematical optimization in computational systems biology. Examples are given where optimization methods are used for topics ranging from model building and optimal experimental design to metabolic engineering and synthetic biology. Finally, several perspectives for future research are outlined

Diurnal and seasonal variation in root xylem embolism in neotropical savanna woody species: Impact on stomatal control of plant water status

Vulnerability to water-stress-induced embolism and variation in the degree of native embolism were measured in lateral roots of four co-occurring neotropical savanna tree species. Root embolism varied diurnally and seasonally. Late in the dry season, loss of root xylem conductivity reached 80% in the afternoon when root water potential (Ψroot) was about -2.6 MPa, and recovered to 25-40% loss of conductivity in the morning when Ψroot was about -1.0 MPa. Daily variation in Ψroot decreased, and root xylem vulnerability and capacitance increased with rooting depth. However, all species experienced seasonal minimum Ψroot close to complete hydraulic failure independent of their rooting depth or resistance to embolism. Predawn Ψroot was lower than Ψsoil when Ψsoil was relatively high (>-0.7 MPa) but became less negative than Ψsoil later in the dry season, consistent with a transition from a disequilibrium between plant and soil Ψ induced by nocturnal transpiration to one induced by hydraulic redistribution of water from deeper soil layers. Shallow longitudinal root incisions external to the xylem prevented reversal of embolism overnight, suggesting that root mechanical integrity was necessary for recovery, consistent with the hypothesis that if embolism is a function of tension, refilling may be a function of internal pressure imbalances. All species shared a common relationship in which maximum daily stomatal conductance declined linearly with increasing afternoon loss of root conductivity over the course of the dry season. Daily embolism and refilling in roots is a common occurrence and thus may be an inherent component of a hydraulic signaling mechanism enabling stomata to maintain the integrity of the hydraulic pipeline in long-lived structures such as stems. © 2006 Blackwell Publishing Ltd