Anatomy of the antennal dorsal organ in female of Neodryinus typhlocybae (Hymenoptera: Dryinidae): A peculiar sensory structure possibly involved in perception of host vibration

Neodryinus typhlocybae (Hymenoptera: Dryinidae) is a natural enemy of the planthopper Metcalfa pruinosa, which was introduced from North America into Europe and has become established in various regions as a pest species. Vibrational signals play a crucial role in the communication of M. pruinosa, which appears to be exploited by N. typhlocybae. Scanning and transmission electron microscopy have shown that the antennae of N. typhlocybae females have peculiar and complex sensory structures: deep longitudinal grooves that house long sensilla trichodea, termed here “Antennal Dorsal Organs.” Such structures were not present on male antennae. These sensilla extend for the length of the grooves, without contact with the groove cuticle. Their hair shaft is empty and aporous, and inserted into a specialized socket, underneath which there is a cuticular ampulla‐like chamber. Each sensillum is associated with two sensory neurons: one terminates at the proximal end of the dendritic sheath; the other continues into the sensillum sinus and is enclosed in the dendritic sheath. This second sensory neuron then enters the ampulla‐like chamber through the circular opening, and then terminates with a conspicuous tubular body at the shaft base. The possible involvement of this peculiar structure in the context of host recognition mechanism is discussed. J. Morphol. 277:128–137, 2016. © 2015 Wiley Periodicals, Inc.     

Discovery of isoquinolinone and naphthyridinone-based inhibitors of poly(ADP-ribose) polymerase-1 (PARP1) as anticancer agents: Structure activity relationship and preclinical characterization

The exploitation of GLU988 and LYS903 residues in PARP1 as targets to design isoquinolinone (I & II) and naphthyridinone (III) analogues is described. Compounds of structure I have good biochemical and cellular potency but suffered from inferior PK. Constraining the linear propylene linker of structure I into a cyclopentene ring (II) offered improved PK parameters, while maintaining potency for PARP1. Finally, to avoid potential issues that may arise from the presence of an anilinic moiety, the nitrogen substituent on the isoquinolinone ring was incorporated as part of the bicyclic ring. This afforded a naphthyridinone scaffold, as shown in structure III. Further optimization of naphthyridinone series led to identification of a novel and highly potent PARP1 inhibitor 34, which was further characterized as preclinical candidate molecule. Compound 34 is orally bioavailable and displayed favorable pharmacokinetic (PK) properties. Compound 34 demonstrated remarkable antitumor efficacy both as a single-agent as well as in combination with chemotherapeutic agents in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. Additionally, compound 34 also potentiated the effect of agents such as temozolomide in breast cancer, pancreatic cancer and Ewing’s sarcoma models.     

Sensing cellular biochemistry with fluorescent chemical–genetic hybrids

Fluorescent biosensors are powerful tools for the detection of biochemical events inside cells with high spatiotemporal resolution. Biosensors based on fluorescent proteins often suffer from issues with photostability and brightness. On the other hand, hybrid, chemical–genetic systems present unique opportunities to combine the strengths of synthetic, organic chemistry with biological macromolecules to generate exquisitely tailored semisynthetic sensors.     

The structure and function of phytochrome A: the roles of the entire molecule and of its various parts

Phytochrome A is readily cleavable by proteolytic agents to yield an amino-terminal fragment of 66 kilodalton (kDa), which consists of residues 1 to approximately 600, and a dimer of the carboxy-terminal 55-kDa fragment, from residue 600 or so to the carboxyl terminus. The former domain, carrying the tetrapyrrole chromophore, has been studied extensively because of its photoactivity, while less attention has been paid to the non-chromophoric portion until quite recently. However, the evidence gathered to date suggests that this domain is also of great improtance. We present here a review of the structure and the biochemical and physiological functions of the two domains, of parts of these domains, and of the cooperation between them.     

Can dominance genetic variance be ignored in evolutionary quantitative genetic analyses of wild populations?

Accurately estimating genetic variance components is important for studying evolution in the wild. Empirical work on domesticated and wild outbred populations suggests that dominance genetic variance represents a substantial part of genetic variance, and theoretical work predicts that ignoring dominance can inflate estimates of additive genetic variance. Whether this issue is pervasive in natural systems is unknown, because we lack estimates of dominance variance in wild populations obtained in situ. Here, we estimate dominance and additive genetic variance, maternal variance, and other sources of nongenetic variance in eight traits measured in over 9000 wild nestlings linked through a genetically resolved pedigree. We find that dominance variance, when estimable, does not statistically differ from zero and represents a modest amount (2-36%) of genetic variance. Simulations show that (1) inferences of all variance components for an average trait are unbiased; (2) the power to detect dominance variance is low; (3) ignoring dominance can mildly inflate additive genetic variance and heritability estimates but such inflation becomes substantial when maternal effects are also ignored. These findings hence suggest that dominance is a small source of phenotypic variance in the wild and highlight the importance of proper model construction for accurately estimating evolutionary potential.     

Low genetic diversity and limited genetic structure across the range of the critically endangered Mexican howler monkey (Alouatta palliata mexicana)

Genetic diversity provides populations with the possibility to persist in ever-changing environments, where selective regimes change over time. Therefore, the long-term survival of a population may be affected by its level of genetic diversity. The Mexican howler monkey (Alouatta palliata mexicana) is a critically endangered primate restricted to southeast Mexico. Here, we evaluate the genetic diversity and population structure of this subspecies based on 83 individuals from 31 groups sampled across the distribution range of the subspecies, using 29 microsatellite loci. Our results revealed extremely low genetic diversity (H_O = 0.21, H_E = 0.29) compared to studies of other A. palliata populations and to other Alouatta species. Principal component analysis, a Bayesian clustering method, and analyses of molecular variance did not detect strong signatures of genetic differentiation among geographic populations of this subspecies. Although we detect small but significant F_ST values between populations, they can be explained by a pattern of isolation by distance. These results and the presence of unique alleles in different populations highlight the importance of implementing conservation efforts in multiple populations across the distribution range of A. p. mexicana to preserve its already low genetic diversity. This is especially important given current levels of population isolation due to the extreme habitat fragmentation across the distribution range of this primate.     

Unequivocal determination of sire allele origin for multiallelic microsatellites when only the sire and progeny are genotyped

The effect of a segregating economic trait locus (ETL) can be detected with the aid of a linked genetic marker, if specific alleles of each locus are in association among the individuals genotyped for the genetic marker. For dairy cattle this can be achieved by application of the ‘granddaughter design’. If only the sires and their sons are genotyped for the genetic markers, then the allele origin of sons having the same genotypes as their sires cannot be determined. Seven sires and 101 sons were genotyped for five microsatellites. The mean frequency of heterozygous sires was 77%. The mean number of alleles per locus was 8.2. Frequency of informative sons per locus ranged from 60% to 80% with a mean of 72%. With highly polymorphic microsatellites, at least 60% more grandsire families can be included in the analysis, and the number of sons assayed can be reduced by 40%, as compared to diallelic markers.