Involvement of Maasai Pastoralists in Participatory Rangeland Management Planning and Implementation

The pastoral Maasai lifestyle was and still is traditionally based on subsistence dairy and meat production. But with population increase, the rangelands can no longer sustainably support livestock production systems. Most of the rangelands which are used for grazing have been subdivided and partially cleared to pave way for cultivation, because of increased population pressure (Ego et al., 1999). This has led to a tendency to overgraze, thus impacting negatively on secondary production from the range. In order to effectively reverse this trend, the users of the rangeland resources were brought together to analyse constraints and opportunities for sustainable use, so that they could develop action plans for the improvement of the rangelands

Mitigation of off-target toxicity in CRISPR-Cas9 screens for essential non-coding elements.

Pooled CRISPR-Cas9 screens are a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we investigate Cas9, dCas9, and CRISPRi/a off-target activity in screens for essential regulatory elements. The sgRNAs with the largest effects in genome-scale screens for essential CTCF loop anchors in K562 cells were not single guide RNAs (sgRNAs) that disrupted gene expression near the on-target CTCF anchor. Rather, these sgRNAs had high off-target activity that, while only weakly correlated with absolute off-target site number, could be predicted by the recently developed GuideScan specificity score. Screens conducted in parallel with CRISPRi/a, which do not induce double-stranded DNA breaks, revealed that a distinct set of off-targets also cause strong confounding fitness effects with these epigenome-editing tools. Promisingly, filtering of CRISPRi libraries using GuideScan specificity scores removed these confounded sgRNAs and enabled identification of essential regulatory elements

Exciton bimolecular annihilation dynamics in supramolecular nanostructures of conjugated oligomers

We present femtosecond transient absorption measurements on $\pi$-conjugated supramolecular assemblies in a high pump fluence regime. Oligo(\emph{p}-phenylenevinylene) monofunctionalized with ureido-\emph{s}-triazine (MOPV) self-assembles into chiral stacks in dodecane solution below 75$^{\circ}$C at a concentration of $4\times 10^{-4}$ M. We observe exciton bimolecular annihilation in MOPV stacks at high excitation fluence, indicated by the fluence-dependent decay of $1^1$B$_{u}$-exciton spectral signatures, and by the sub-linear fluence dependence of time- and wavelength-integrated photoluminescence (PL) intensity. These two characteristics are much less pronounced in MOPV solution where the phase equilibrium is shifted significantly away from supramolecular assembly, slightly below the transition temperature. A mesoscopic rate-equation model is applied to extract the bimolecular annihilation rate constant from the excitation fluence dependence of transient absorption and PL signals. The results demonstrate that the bimolecular annihilation rate is very high with a square-root dependence in time. The exciton annihilation results from a combination of fast exciton diffusion and resonance energy transfer. The supramolecular nanostructures studied here have electronic properties that are intermediate between molecular aggregates and polymeric semiconductors

Effect of Oral Alendronate on Bone Mineral Density and the Incidence of Fractures in Postmenopausal Osteoporosis

BACKGROUND Postmenopausal osteoporosis is a serious health problem, and additional treatments are needed. METHODS We studied the effects of oral alendronate, an aminobisphosphonate, on bone mineral density and the incidence of fractures and height loss in 994 women with postmenopausal osteoporosis. The women were treated with placebo or alendronate (5 or 10 mg daily for three years, or 20 mg for two years followed by 5 mg for one year); all the women received 500 mg of calcium daily. Bone mineral density was measured by dual-energy x-ray absorptiometry. The occurrence of new vertebral fractures and the progression of vertebral deformities were determined by an analysis of digitized radiographs, and loss of height was determined by sequential height measurements. RESULTS The women receiving alendronate had significant, progressive increases in bone mineral density at all skeletal sites, whereas those receiving placebo had decreases in bone mineral density. At three years, the mean (±SE) differences in bone mineral density between the women receiving 10 mg of alendronate daily and those receiving placebo were 8.8±0.4 percent in the spine, 5.9±0.5 percent in the femoral neck, 7.8±0.6 percent in the trochanter, and 2.5±0.3 percent in the total body (P CONCLUSIONS Daily treatment with alendronate progressively increases the bone mass in the spine, hip, and total body and reduces the incidence of vertebral fractures, the progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis

An Outcome-based Approach for the Creation of Fetal Growth Standards: Do Singletons and Twins Need Separate Standards?

Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks’ gestation in the United States (1995–2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999–2002 vs. 1995–1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards

Neural Computation via Neural Geometry: A Place Code for Inter-whisker Timing in the Barrel Cortex?

The place theory proposed by Jeffress (1948) is still the dominant model of how the brain represents the movement of sensory stimuli between sensory receptors. According to the place theory, delays in signalling between neurons, dependent on the distances between them, compensate for time differences in the stimulation of sensory receptors. Hence the location of neurons, activated by the coincident arrival of multiple signals, reports the stimulus movement velocity. Despite its generality, most evidence for the place theory has been provided by studies of the auditory system of auditory specialists like the barn owl, but in the study of mammalian auditory systems the evidence is inconclusive. We ask to what extent the somatosensory systems of tactile specialists like rats and mice use distance dependent delays between neurons to compute the motion of tactile stimuli between the facial whiskers (or ‘vibrissae’). We present a model in which synaptic inputs evoked by whisker deflections arrive at neurons in layer 2/3 (L2/3) somatosensory ‘barrel’ cortex at different times. The timing of synaptic inputs to each neuron depends on its location relative to sources of input in layer 4 (L4) that represent stimulation of each whisker. Constrained by the geometry and timing of projections from L4 to L2/3, the model can account for a range of experimentally measured responses to two-whisker stimuli. Consistent with that data, responses of model neurons located between the barrels to paired stimulation of two whiskers are greater than the sum of the responses to either whisker input alone. The model predicts that for neurons located closer to either barrel these supralinear responses are tuned for longer inter-whisker stimulation intervals, yielding a topographic map for the inter-whisker deflection interval across the surface of L2/3. This map constitutes a neural place code for the relative timing of sensory stimuli

Finding the engram.

Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent \u27capture\u27 studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram

DNA methylation and methyl-CpG binding proteins: developmental requirements and function

DNA methylation is a major epigenetic modification in the genomes of higher eukaryotes. In vertebrates, DNA methylation occurs predominantly on the CpG dinucleotide, and approximately 60% to 90% of these dinucleotides are modified. Distinct DNA methylation patterns, which can vary between different tissues and developmental stages, exist on specific loci. Sites of DNA methylation are occupied by various proteins, including methyl-CpG binding domain (MBD) proteins which recruit the enzymatic machinery to establish silent chromatin. Mutations in the MBD family member MeCP2 are the cause of Rett syndrome, a severe neurodevelopmental disorder, whereas other MBDs are known to bind sites of hypermethylation in human cancer cell lines. Here, we review the advances in our understanding of the function of DNA methylation, DNA methyltransferases, and methyl-CpG binding proteins in vertebrate embryonic development. MBDs function in transcriptional repression and long-range interactions in chromatin and also appear to play a role in genomic stability, neural signaling, and transcriptional activation. DNA methylation makes an essential and versatile epigenetic contribution to genome integrity and function