Symmetry breakage in the vertebrate embryo: When does it happen and how does it work?

Asymmetric development of the vertebrate embryo has fascinated embryologists for over a century. Much has been learned since the asymmetric Nodal signaling cascade in the left lateral plate mesoderm was detected, and began to be unraveled over the past decade or two. When and how symmetry is initially broken, however, has remained a matter of debate. Two essentially mutually exclusive models prevail. Cilia-driven leftward flow of extracellular fluids occurs in mammalian, fish and amphibian embryos. A great deal of experimental evidence indicates that this flow is indeed required for symmetry breaking. An alternative model has argued, however, that flow simply acts as an amplification step for early asymmetric cues generated by ion flux during the first cleavage divisions. In this review we critically evaluate the experimental basis of both models. Although a number of open questions persist, the available evidence is best compatible with flow-based symmetry breakage as the archetypical mode of symmetry breakage.     

The GABAergic network in the suprachiasmatic nucleus as a key regulator of the biological clock: does it change during senescence?

GABA is the main neurotransmitter of the hypothalamic suprachiasmatic nucleus (SCN) and plays a key role in the function of this master circadian pacemaker. Despite the evidence that disturbances of biological rhythms are common during aging, little is known about the GABAergic network in the SCN of the aging brain. We here provide a brief overview of the GABAergic structures and the role of GABA in the SCN. We also review some age-related changes of the GABAergic system occurring in the brain outside the SCN. Finally, we present preliminary data on the GABAergic system within the SCN comparing young and aging mice. In particular, our study on age-related changes in the SCN focused on the daily expression of the alpha3 subunit of the GABA(A) receptor and on the density of GABAergic axon terminals. Interestingly, our preliminary findings point to alterations of the GABAergic network in the biological clock during senescence.     

Did biological control cause extinction of the coconut moth, Levuana iridescens, in Fiji?

In 1925, J.D. Tothill and two colleagues set out to manage Levuana iridescens, the coconut moth of Fiji, using biological control. By 1930, they had succeeded so completely that this pest of the copra crop had been reduced to almost undetectable levels by the tachinid fly, Bessa remota, introduced from Malaya, and they had summarized their campaign in a thoroughly documented and well-illustrated monograph. The example of the coconut moth is presented in the modern literature as the first and best documented extinction of a species due to scientific biological control. The program has been severely criticized because the moth was unique, beautiful, and considered endemic to Fiji. Thus, this program is also portrayed as an example of the highly controversial practice of neoclassical biological control. However, a careful reexamination of this event discloses that the moth was likely not native to Fiji, appeared to be spreading through the Fijian Archipelago, and might have spread to other island groups in the South Pacific. Also, L. iridescens is probably not extinct. Collateral damage, that is, non-target impacts, did occur as native zygaenid moths have been attacked by the tachinid, and they may be extinct. The reasons for the control campaign of L. iridescens were not primarily economic. Tothill and colleagues were trying to protect copra so that ethnic Fijian culture, so dependent on the coconut palm threatened by L. iridescens, could be sustained. Hence, this control program represents a difficult clash of values: preservation of insect biodiversity versus preservation of indigenous Pacific Islander cultures. A strategy to search for L. iridescens populations is proposed and development of biological control of B. remota, using hyperparasitoids, is possible, but would require careful evaluation since it might release L. iridescens from suppression, have non-target impacts on native tachinids, and lack an economic motivation.     

What is the time scale of magnetic field interaction in biological systems?

An experimental test constraining the intrinsic time scale of a primary physical mechanism that detects extremely-low-frequency (ELF) magnetic fields in biological systems is proposed. The suggested test postulates that a transductive mechanism operating on time scales much shorter than the period of an applied magnetic field cannot obtain any information about the exposure conditions other than the absolute magnitude of the field. By generating field exposures that differ in their vector properties but are equivalent in their time-varying absolute amplitude, it is possible to differentiate between two broad classes of mechanisms: 1) those with intrinsic time scales comparable with or longer than those of the external influence, and 2) those that are much faster than the period of the applied field. The hypothesis assumes an experimental model proven to respond to magnetic fields and sensitive to a change of about a factor of two in one of the field parameters (AC, DC amplitude or frequency). The case of general linearly polarized fields is discussed, and an analytical solution for the case of perpendicular AC/DC fields is given. Bioelectromagnetics 18:244–249, 1997 © 1997 Wiley-Liss, Inc.     

Controlled group designs in biofeedback research: Ask, “what does the control group control for?”

The extant literature on the specific role of biofeedback in promoting skeletal muscular relaxation is reviewed and found deficient with respect to the use of properly controlled group outcome research. The review emphasizes the failure of commonly used control procedures to adequately control a number of potentially confounding variables. Strengths and weaknesses of three types of controlled group design (attention placebo, pseudofeedback, and altered contingency) are discussed with respect to their relative usefulness in controlling certain nonspecific or placebo effects in biofeedback research. Many published biofeedback studies failed to measure the credibility of control procedures or the subject's ability to discriminate different feedback contingencies. The studies reviewed suggest that the various control procedures used are not inert and are not equivalent with respect to their effects on control group behavior. The suggestion is made that the controlled group outcome design be accepted as the minimum requirement for testing the specific effects of biofeedback, and possible methods for improving control procedures are discussed.     

The non‐existent aging program: how does it work?

Summary Aging and lifespan determination have been viewed, in the most well-accepted theories, as nonprogrammatic, and are thought to result from the evolutionary selection for early fitness at the expense of late survival. Here, recent data implicating potentially programmatic aspects of aging and lifespan determination are discussed, and analogies between programmed cell death and programmed organismal death are offered. It is hoped that the recognition of at least the possibility of a programmatic aspect, or aspects, to the determination of longevity and the process of aging will help to optimize our chances to identify appropriate therapeutic targets both for longevity enhancement and disease prevention.     

Bacteria as biological control agents of freshwater cyanobacteria: is it feasible beyond the laboratory?

Biological control of cyanobacteria is a well-researched area with a central focus on laboratory-scale studies. Numerous reports have been made on algicidal isolates, with bacteria as a major component of the antagonists. The research in this review draws a brief summary of what is currently known in the area of freshwater cyanobacteria being inhibited by bacterial isolates. Proteobacteria, Bacteroidetes and Firmicutes are among the most commonly reported phyla of bacteria associated with or employed in this research area. However, there are limited reports of upscaling these control measures beyond the laboratory scale. Lytic control agents are the most commonly reported in the literature with subsequent cyanotoxin release. From a water quality perspective, this is not feasible. Based on the available literature, temperature, pH and nutrient changes have been explored in this short review as possible contributors to less optimal bacterial performance. Moreover, the investigation into optimising some of these parameters may lead to increased bacterial performance and, therefore, viability for upscaling this biological control. Through the compilation of current research, this review offers insight to live predator-prey cell interactions between cyanobacteria and algicidal bacteria.

     

Treatment of COVID-19 with MSCs: how does it work?

Science China Life Sciences -     

Intraspecific competition in tadpoles of Rana arvalis: does it matter in nature? A field experiment

Tadpole growth and development are easily affected by intraspecific competition in tank experiments, provided treatment density is sufficiently high. Is this a phenomenon also observed in nature? A pond was divided into four tadpole-proof sections. Each year for 8 years, all spawn laid by moorfrogs (Rana arvalis) in this pond was relocated to create relative spawn and tadpole densities of 1 : 4 : 1 : 4. No direct effect of the density manipulation on survival, tadpole size, and development and metamorph timing and size could be demonstrated. However, I also measured actual tadpole density during the time of development. Apart from the experimental density manipulation, this measure included effects of between-year variation in amount of spawn, natural tadpole mortality, and pond drying (which concentrated the tadpoles by decreasing the area of the pond sections). Actual density had limited but significant effects on tadpole size and development. I suggest that density regulation, acting on the tadpole stage, may be present in the population but was of less short-term importance than abiotic factors and, possibly, adult density regulation. Consequences of the findings for conservation are discussed.     

A consistent terminology for quantifying species diversity? Yes, it does exist

The prevailing terminological confusion around the concept ‘diversity’ has hampered accurate communication and caused diversity issues to appear unnecessarily complicated. In fact, a consistent terminology for phenomena related to (species) diversity is already available. When this terminology is adhered to, diversity emerges as an easily understood concept. It is important to differentiate between diversity itself and a diversity index: an index of something is just a surrogate for the thing itself. The conceptual problem of defining diversity also has to be separated from the practical problem of deciding how to adequately quantify diversity for a community of interest. In practice, diversity can be quantified for any dataset where units of observation (such as individuals) have been classified into types (such as species). All that needs to be known is what proportion of the observed units belong to a type of mean abundance. Diversity equals the inverse of this mean, and it quantifies the effective number of the types of interest. In ecology, interest often (but not always) focuses on species diversity. If the dataset consists of (or gets divided into) subunits, then the total effective number of species (gamma diversity) can be partitioned into the effective number of compositionally distinct subunits (beta diversity) and the mean effective number of species per such subunit (alpha diversity). Species richness is related to species diversity, but they are not the same thing; richness does not take the proportional abundances into account and is therefore the actual—rather than the effective—number of types. Most of the phenomena that have been called ‘beta diversity’ in the past do not quantify an effective number of types, so they should be referred to by names other than ‘diversity’ (for example, species turnover or differentiation).     

Abscisic acid in the xylem: where does it come from, where does it go to?

Abscisic acid is a hormonal stress signal that moves in the xylem from the root to the different parts of the shoot where it regulates transpirational water loss and leaf growth. The factors that modify the intensity of the ABA signal in the xylem are of particular interest because target cells recognize concentrations. ABA(xyl), will be decreased as radial water flow through the roots is increased, assuming that radial ABA transport occurs in the symplast only. Such dilutions of the plant hormone concentration can be compensated in different ways, which help to keep the ABA-concentrations in the xylem constant: (i) apoplastic bypass flows of ABA, (ii) ABA flows between the stem parenchyma and the xylem during transport and (iii) the action of beta-D-glucosidases that release free ABA from its conjugates to the root cortex and the leaf apoplast. The significance of reflection coefficients (sigma(ABA)), permeability coefficients of membranes (P(S)(ABA)) and apoplastic barriers for ABA is discussed.     

Sperm storage in the vertebrate female reproductive tract: How does it work so well?

The capacity for sperm storage within the female reproductive tract occurs widely across all groups of vertebrate species and is exceptionally well developed in some reptiles (maximum duration, 7 yr) and fish (maximum duration, >1 yr). Amphibians (most salamanders and one species of frog; duration approximately 5 mo), all birds examined to date and some bats, have also evolved the ability to store spermatozoa in the female reproductive tract. Although there are many reports on both the occurrence of female sperm storage and its adaptive benefits, few studies have been directed toward explaining the mechanisms involved. Phylogenetic evidence suggests that the capacity for sperm storage has evolved independently within different taxonomic groups, and it is by no means clear whether these groups have established similar or different mechanisms or whether simple and common principles have been exploited during evolution. If the process has indeed developed by the invention of numerous different and species-specific mechanisms, it is surprising that none have yet been elucidated by technologists wishing to improve the long-term storage of fresh semen. On the other hand, if there is a simple and common solution to the problem, readily accessed by diverse groups of species, it is equally logical to suppose that the mechanism should be easily discovered in the laboratory. While recognizing that studies on wild species are usually neither practically or ethically easy to undertake, it is clear that there is a huge and largely unexplored field to be investigated.     

The glyoxylate cycle: does it function in the dormant or active bear?

The presence of or induction of an active glyoxylate cycle (GC) in the dormant black bear whose sole source of energy is body fat is an attractive concept which would allow lipid (acetate) to be directed from oxidation via the tricarboxylic acid cycle to many biosynthetic pathways. However, in spite of earlier claims, the present report establishes that isocitrate lyase and malate synthetase, GC marker enzymes, could not be detected in liver or kidney of active or dormant bears; liver peroxisome numbers were similar. The absence of brown fat (by light microscopy) and of the GC enzymes in the dormant bear raises questions about the prior report.     

The NFL combine: does it predict performance in the National Football League?

The authors investigate the correlation between National Football League (NFL) combine test results and NFL success for players drafted at three different offensive positions (quarterback, running back, and wide receiver) during a recent 6-year period, 1999-2004. The combine consists of series of drills, exercises, interviews, aptitude tests, and physical exams designed to assess the skills of promising college football players and to predict their performance in the NFL. Combine measures examined in this study include 10-, 20-, and 40-yard dashes, bench press, vertical jump, broad jump, 20- and 60-yard shuttles, three-cone drill, and the Wonderlic Personnel Test. Performance criteria include 10 variables: draft order; 3 years each of salary received and games played; and position-specific data. Using correlation analysis, we find no consistent statistical relationship between combine tests and professional football performance, with the notable exception of sprint tests for running backs. We put forth possible explanations for the general lack of statistical relations detected, and, consequently, we question the overall usefulness of the combine. We also offer suggestions for improving the prediction of success in the NFL, primarily the use of more rigorous psychological tests and the examination of collegiate performance as a job sample test. Finally, from a practical standpoint, the results of the study should encourage NFL team personnel to reevaluate the usefulness of the combine's physical tests and exercises as predictors of player performance. This study should encourage team personnel to consider the weighting and importance of various combine measures and the potential benefits of overhauling the combine process, with the goal of creating a more valid system for predicting player success.     

Tackling the tumor microenvironment: what challenge does it pose to anticancer therapies?

Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stress-responsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment (TMEN). Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thorough and personalized.