Activation of NF-��B Protein Prevents the Transition from Juvenile Ovary to Testis and Promotes Ovarian Development in Zebrafish

Testis differentiation in zebrafish involves juvenile ovary to testis transformation initiated by an apoptotic wave. The molecular regulation of this transformation process is not fully understood. NF-κB is activated at an early stage of development and has been shown to interact with steroidogenic factor-1 in mammals, leading to the suppression of anti-Müllerian hormone (Amh) gene expression. Because steroidogenic factor-1 and Amh are important for proper testis development, NF-κB-mediated induction of anti-apoptotic genes could, therefore, also play a role in zebrafish gonad differentiation. The aim of this study was to examine the potential role of NF-κB in zebrafish gonad differentiation. Exposure of juvenile zebrafish to heat-killed Escherichia coli activated the NF-κB pathways and resulted in an increased ratio of females from 30 to 85%. Microarray and quantitative real-time-PCR analysis of gonads showed elevated expression of NF-κB-regulated genes. To confirm the involvement of NF-κB-induced anti-apoptotic effects, zebrafish were treated with sodium deoxycholate, a known inducer of NF-κB or NF-κB activation inhibitor (NAI). Sodium deoxycholate treatment mimicked the effect of heat-killed bacteria and resulted in an increased proportion of females from 25 to 45%, whereas the inhibition of NF-κB using NAI resulted in a decrease in females from 45 to 20%. This study provides proof for an essential role of NF-κB in gonadal differentiation of zebrafish and represents an important step toward the complete understanding of the complicated process of sex differentiation in this species and possibly other cyprinid teleosts as well.     

Social organization and the evolution of cumulative technology in apes and hominins

Culturally supported accumulation (or ratcheting) of technological complexity is widely seen as characterizing hominin technology relative to that of the extant great apes, and thus as representing a threshold in cultural evolution. To explain this divide, we modeled the process of cultural accumulation of technology, which we defined as adding new actions to existing ones to create new functional combinations, based on a model for great ape tool use. The model shows that intraspecific and interspecific variation in the presence of simple and cumulative technology among extant orangutans and chimpanzees is largely due to variation in sociability, and hence opportunities for social learning. The model also suggests that the adoption of extensive allomaternal care (cooperative breeding) in early Pleistocene Homo, which led to an increase in sociability and to teaching, and hence increased efficiency of social learning, was enough to facilitate technological ratcheting. Hence, socioecological changes, rather than advances in cognitive abilities, can account for the cumulative cultural changes seen until the origin of the Acheulean. The consequent increase in the reliance on technology could have served as the pacemaker for increased cognitive abilities. Our results also suggest that a more important watershed in cultural evolution was the rise of donated culture (technology or concepts), in which technology or concepts was transferred to naïve individuals, allowing them to skip many learning steps, and specialization arose, which allowed individuals to learn only a subset of the population's skills.     

Structural hierarchy controls deformation behavior of collagen

The structure of collagen, the most abundant protein in mammals, consists of a triple helix composed of three helical polypeptide chains. The deformation behavior of collagen is governed by molecular mechanisms that involve the interaction between different helical hierarchies found in collagen. Here, we report results of Steered Molecular Dynamics study of the full-length collagen molecule (～290 nm). The collagen molecule is extended at various pulling rates ranging from 0.00003/ps to 0.012/ps. These simulations reveal a new level of hierarchy exhibited by collagen: helicity of the triple chain. This level of hierarchy is apparent at the 290 nm length and cannot be observed in the 7-9 nm models often described to evaluate collagen mechanics. The deformation mechanisms in collagen are governed by all three levels of hierarchy, helicity of single chain (level-1), helical triple helix (level-2), and hereby described helicity of the triple chain (level-3). The mechanics resulting from the three levels is described by an interlocking gear analogy. In addition, remarkably, the full-length collagen does not show much unwinding of triple helix unlike that exhibited by short collagen models. Further, the full-length collagen does not show significant unwinding of the triple helix, unlike that exhibited by short collagen. Also reported is that the interchain hydrogen bond energy in the full-length collagen is significantly smaller than the overall interchain nonbonded interaction energies, suggesting that the nonbonded interactions have far more important role than hydrogen bonds in the mechanics of collagen. However, hydrogen bonding is essential for the triple helical conformation of the collagen. Hence, although mechanics of collagen is controlled by nonbonded interchain interaction energies, the confirmation of collagen is attributed to the interchain hydrogen bonding.     

Controlled release of nutrients to mammalian cells cultured in shake flasks

Though cell culture-based protein production processes are rarely carried out under batch mode of operation, cell line and initial process development operations are usually carried out in batch mode due to simplicity of operation in widely used scale down platforms like shake flasks. Nutrient feeding, if performed, is achieved by bolus addition of concentrated feed solution at different intervals, which leads to large transient increases in nutrient concentrations. One negative consequence is increased waste metabolite production. We have developed a hydrogel-based nutrient delivery system for continuous feeding of nutrients in scale down models like shake flasks without the need for manual feed additions or any additional infrastructure. Continuous delivery also enables maintaining nutrient concentrations at low levels, if desired. The authors demonstrate the use of these systems for continuous feeding of glucose and protein hydrolysate to a suspension Chinese Hamster Ovary (CHO) culture in a shake flask. Glucose feeding achieved using the glucose-loaded hydrogel resulted in a 23% higher integral viable cell density and an 89% lower lactate concentration at the end of the culture when compared with a bolus-feed of glucose.     

Conserving small and fragmented populations of large mammals: Non-invasive genetic sampling in an isolated population of Asian elephants in Nepal

The Terai is one of the world's most spectacular landscapes, encompassing parts of Nepal and northern India. This area used to harbour large and continuous populations of charismatic species like elephants, tigers and rhinoceros. However, recent habitat fragmentation reduced these populations into small, partially or completely isolated remnants. The largest of these fragments in Nepal is the Bardia National Park. Here, the elephant population was functionally extinct in the early 1970s and -80s, but was rescued by a considerable number of immigrants in 1994. In order to assess population size, sex ratio, age structure, and levels of genetic variation, we carried out non-invasive genetic sampling, using elephant dung as the source of DNA. A capture-mark-recapture estimate of population size suggested that there were 57 individuals in the study area, which agrees well with field observations. Notably, a strongly male-biased sex ratio was evident among sub-adult individuals. This observation suggests the presence of sub-adult immigrants in the population, which was supported by formal migrant detection analysis. Genetic variation was quite high and the evidence for male immigrants suggests that there are good prospects for maintenance of genetic diversity. A decade ago a large-scale project was initiated in the Terai region to link remaining populations of large mammals through dispersal corridors. The program is basically founded on the assumption that habitat fragments are isolated with little or no migration between them. Our results indicate that this may not be the case, at least not for the Asian elephant in western Nepal, which therefore reduces the alleged extinction risk from genetic erosion and stochastic demographic events.     

Developmental phase-dependent photosynthetic responses to ultraviolet-B radiation: damage, defence, and adaptation of primary leaves of wheat seedlings

Alterations in photosynthetic capacity of primary leaves of wheat seedlings in response to ultraviolet-B (UV-B; 280–320 nm; 60 μmol m⁻² s⁻¹) exposure alone and in combination with photosynthetically active radiation (PAR; 400–800 nm; 200 μmol m⁻² s⁻¹) during different phases of leaf growth and development were assessed. UV-B exposure resulted in a phase-dependent differential loss in photosynthetic pigments, photochemical potential, photosystem 2 (PS2) quantum yield, and in vivo O₂ evolution. UV-B exposure induced maximum damage to the photosynthetic apparatus during senescence phase of development. The damages were partially alleviated when UV-B exposure was accompanied by PAR. UV-B induced an enhancement in accumulation of flavonoids during all phases of development while it caused a decline in anthocyanin content during senescence. The differential changes in these parameters demonstrated the adaptation ability of leaves to UV-B stress during all phases of development and the ability was modified in UV-B+ PAR exposed samples.     

Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task

The use of stimulants (methylphenidate and amphetamine) as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose) in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations) given with and without methylphenidate (20 mg, oral). Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less). This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate's reduction of the metabolic increases in regions from the default network (implicated in mind-wandering) was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a "focusing" of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering) or impaired (i.e., attention deficit hyperactivity disorder), but it could be detrimental when brain activity is already optimally focused. This would explain why methylphenidate has beneficial effects in some individuals and contexts and detrimental effects in others.