3D geometric morphometrics of thorax variation and allometry in Hominoidea

Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): Markus Bastir, Daniel García-Martínez, Scott A. Williams, Wolfgang Recheis, Isabel Torres-Sánchez, Francisco García Río, Motoharu Oishi, Naomichi Ogihara
Ever since the seminal papers of Keith and Schultz, hominoid primate ribcages have been described as either "funnel-" or "barrel-shaped." Following this dichotomic typology, it is currently held that Homo sapiens and hylobatids (gibbons and siamangs) share a barrel-shaped ribcage and that they are more similar to each other than to the funnel-shaped thoraces of great apes (Gorilla, Pan, and Pongo). Other researchers hypothesized that thoracic width and the invagination of the thoracic spine into the thorax are related to allometry. However, analyses that take into account the complex three-dimensional (3D) shape of the ribcage are lacking. Here, we address hypotheses about thorax shape and evolution using 3D morphometrics of thoraces in anatomical connection obtained by computed tomography scans of 23 hominoid cadavers and 10 humans and examining thorax compartments composed of seven ribs (1–7 thorax) and of 11 ribs (1–11 thorax). In the 1–7 thorax analyses, the human thorax is uniquely flat because of torsion of the upper and central ribs, differing from all non-human hominoids including hylobatids. In the 1–11 thorax analyses, humans are markedly different from African great apes, with hylobatids and orangutans intermediate. In full shape space analyses, affinities between orangutans and humans on the one hand and between hylobatids and African great apes on the other are evident. Therefore, we reject the hypothesis that humans and hylobatids bear any special affinities in overall 3D thorax shape to each other. We find that larger thoraces are wider and flatter, with a more invaginated spine, supporting the allometric hypothesis. Hominoid thorax variation shows complex interactions between allometry, rib curves, torsion, and declination, and the morphology of the costo-vertebral joint and the thoracic vertebral column. When considering functional specializations alongside phylogenetic relationships, an overly simplistic dichotomy between funnel-shaped and barrel-shaped thoraces is not supported.



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Early evolutionary diversification of mandible morphology in the New World monkeys (Primate, Platyrrhini)

Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): Guido Rocatti, Leandro Aristide, Alfred L. Rosenberger, S. Ivan Perez
New World monkeys (order Primates) are an example of a major mammalian evolutionary radiation in the Americas, with a contentious fossil record. There is evidence of an early platyrrhine occupation of this continent by the Eocene–Oligocene transition, evolving in isolation from the Old World primates from then on, and developing extensive morphological and size variation. Previous studies postulated that the platyrrhine clade arose as a local version of the Simpsonian ecospace model, with an early phase involving a rapid increase in morphological and ecological diversity driven by selection and ecological opportunity, followed by a diversification rate that slowed due to niche-filling. Under this model, variation in extant platyrrhines, in particular anatomical complexes, may resemble patterns seen among middle–late Miocene (10–14 Ma) platyrrhines as a result of evolutionary stasis. Here we examine the mandible in this regard, which may be informative about the dietary and phylogenetic history of the New World monkeys. Specifically, we test the hypothesis that the Simpsonian ecospace model applies to the platyrrhine mandible through a geometric morphometric analysis of digital images of the jaws of extant and extinct species, and we compare these results to those obtained using a phylogenetic comparative approach based on extant species. The results show a marked phylogenetic structure in the mandibular morphology of platyrrhines. Principal component analyses highlight the morphological diversity among modern forms, and reveal a similar range of variation for the clade when fossil specimens are included. Disparity-Through-Time analysis shows that most of the shape variation between platyrrhines originated early in their evolution (between 20 and 15 Ma). Our results converge with previous studies of body mass, cranial shape, the brain and the basicranium to show that platyrrhine evolution might have been shaped by an early increase in morphological variation followed by a decelerated rate of diversification and evolutionary stasis.



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Relationship between foramen magnum position and locomotion in extant and extinct hominoids

Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): Dimitri Neaux, Thibaut Bienvenu, Franck Guy, Guillaume Daver, Gabriele Sansalone, Justin A. Ledogar, Todd C. Rae, Stephen Wroe, Michel Brunet
From the Miocene Sahelanthropus tchadensis to Pleistocene Homo sapiens, hominins are characterized by a derived anterior position of the foramen magnum relative to basicranial structures. It has been previously suggested that the anterior position of the foramen magnum in hominins is related to bipedal locomotor behavior. Yet, the functional relationship between foramen magnum position and bipedal locomotion remains unclear. Recent studies, using ratios based on cranial linear measurements, have found a link between the anterior position of the foramen magnum and bipedalism in several mammalian clades: marsupials, rodents, and primates. In the present study, we compute these ratios in a sample including a more comprehensive dataset of extant hominoids and fossil hominins. First, we verify if the values of ratios can distinguish extant humans from apes. Then, we test whether extinct hominins can be distinguished from non-bipedal extant hominoids. Finally, we assess if the studied ratios are effective predictors of bipedal behavior by testing if they mainly relate to variation in foramen magnum position rather than changes in other cranial structures. Our results confirm that the ratios discriminate between extant bipeds and non-bipeds. However, the only ratio clearly discriminating between fossil hominins and other extant apes is that which only includes basicranial structures. We show that a large proportion of the interspecific variation in the other ratios relates to changes in facial, rather than basicranial, structures. In this context, we advocate the use of measurements based only on basicranial structures when assessing the relationship between foramen magnum position and bipedalism in future studies.



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Dietary traits of the ungulates from the HWK EE site at Olduvai Gorge (Tanzania): Diachronic changes and seasonality

Publication date: Available online 2 September 2017
Source:Journal of Human Evolution
Author(s): Florent Rivals, Kevin T. Uno, Faysal Bibi, Michael C. Pante, Jackson Njau, Ignacio de la Torre
The Oldowan site HWK EE (Olduvai Gorge, Tanzania) has yielded a large fossil and stone tool assemblage at the transition from Lower to Middle Bed II, ∼1.7 Ma. Integrated tooth wear and stable isotope analyses were performed on the three most abundant ungulate taxa from HWK EE, namely Alcelaphini, cf. Antidorcas recki (Antilopini) and Equus oldowayensis (Equini), to infer dietary traits in each taxon. Some paleodietary changes were observed for cf. A. recki and E. oldowayensis based on tooth wear at the transition from the Lemuta to the Lower Augitic Sandstone (LAS) interval within the HWK EE sequence. Stable carbon and oxygen isotope data show no significant changes in bulk diet or hydroclimate between the Lemuta and LAS intervals. The combined tooth wear and stable isotope data suggest similar paleoecological conditions across the two HWK EE intervals, but that differences in vegetation consumed among ungulates may have resulted in changes in dietary niches. Integrating tooth wear and stable isotope analyses permits the characterization of ungulate diets and habitats at HWK EE where C4 dominated and minor mixed C3 and C4 habitats were present. Our results provide a better understanding of the paleoenvironmental conditions of the Lemuta and LAS intervals. The LAS assemblage was mostly accumulated during relatively dry periods at Olduvai Gorge when grasses were not as readily available and grazing animals may have been more nutritionally-stressed than during the formation of the Lemuta assemblage. This helps to contextualize variations in hominin and carnivore feeding behavior observed from the faunal assemblages produced during the two main occupations of the site.



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Investigating hominin carnivory in the Okote Member of Koobi Fora, Kenya with an actualistic model of carcass consumption and traces of butchery on the elbow

Publication date: Available online 1 September 2017
Source:Journal of Human Evolution
Author(s): Stephen R. Merritt
Previous zooarchaeological analysis at Koobi Fora indicates that Okote Member hominins were the primary agents of bone assemblage formation, gained early access to large and small mammal flesh, and consumed both high- and low-ranked carcass parts. The discovery of additional butchered specimens prompted the re-analysis presented here of three large and well-preserved zooarchaeological assemblages from the Okote member, GaJi14, FwJj14N and FwJj14S, to revisit paleoecological hypotheses about tool-assisted carnivory. Cow and goat limb butchery documenting the skeletal location of cut marks created by skinning, defleshing, and disarticulation was used to build an actualistic model to infer hominin consumption of distinct carcass resources. Archaeological specimens were assigned to early (defleshing limbs), middle (defleshing ribs, viscera, vertebrae, and head) and late (metapodial tendon removal, element disarticulation, long bone fragmentation) carcass consumption stages, and the incidence of these butchery behaviors was examined for specimens and minimum number of element and individual aggregates. Elbow specimens, where traces of defleshing, disarticulation, and percussion co-occur, offer a sequential view of carcass consumption behaviors that is free from fragmentation bias. Classification trees populated with actualistic data were used to identify defleshing and disarticulation cut mark clusters on archaeological elbow portions by their location, cut mark count, median length, and median cross-sectional width. Actualistically-informed configurational analysis offers high-resolution behavioral reconstruction of the butchered sub-assemblage and should be integrated with assemblage-scale zooarchaeological methods. These experiments highlight the bias for detecting butchery traces of early carcass access, because defleshing cut marks are abundant and introduced to dense midshaft portions, whereas disarticulation cut marks are rare and occur on epiphyseal portions, which are often deleted by density-mediated destruction. Butchery trace interpretation across multiple analytical scales confirms a flexible carnivorous paleoecological role for Okote hominins that included primary and secondary access to carcass resources from large and small mammals.



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Pattern of Mas expression in acute and post-acute stage of nerve injury in mice

Publication date: Available online 1 September 2017
Source:Peptides
Author(s): Alex Dias Assis, Fernanda de Assis Araújo, Robson Augusto Souza Santos, Silvia Passos Andrade, Renata Graciele Zanon
Angiotensin-(1–7) (Ang [1–7]) and its receptor Mas are involved in a number of physiological processes, including control of arterial pressure and modulation of nervous system actions. However, the involvement of the Ang-(1–7)/Mas axis in peripheral nerve injury has not been investigated. Using a model of sciatic nerve injury in mice, we demonstrated opposing changes in Mas receptor expression at days 2 and 14 post-injury. Mas receptor expression was more intense 2days after the nerve lesion, compared with the intensity of the intact nerve. At this time point, the sciatic nerve functional index was −20. At day 14 after the lesion, the intensity of the immunostaining labeling in longitudinal sections of the nerve was reduced (∼30%) and the functional index increased +36 (gait improvement). In the axotomized group treated with A779 (a Mas receptor antagonist), the functional recovery index decreased in relation to the untreated axotomized group. The Mas receptor inhibitor also altered the intensity of labeling of S-100, GAP43, and IBA-1 (morphological features compatible with delayed axon growth). This study demonstrated that Ang-(1–7)/Mas axis activity was differentially modulated in the acute and post-acute stages of nerve injury.



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Isolation of new ligands for orphan receptor MRGPRX1—hemorphins LVV-H7 and VV-H7

Publication date: Available online 1 September 2017
Source:Peptides
Author(s): T. Karhu, K. Akiyama, O. Vuolteenaho, U. Bergmann, T. Naito, K. Tatemoto, K.-H. Herzig
The human MAS-related G protein-coupled receptor X1 (MRGPRX1) is a member of the GPCR family. The receptor is primate specific and expressed in the sensory neurons of dorsal root ganglion and trigeminal ganglion, where it is considered to be involved in the pain perception. The MRGPRX1 has unusual binding mechanism, as it is activated by several different ligands as well as several different fragments of precursor proteins. Thus, we hypothesize that it is activated by several unknown compounds as well. The receptor is still classified as orphan. Here, we describe the isolation of two novel endogenous ligands for the MRGPRX1 from human platelet preparation. The isolated ligands are hemoglobin β-chain fragments, known members of the hemorphin family.



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Médecins, patients et leur relation amoureuse : Erôs contre Anterôs

Publication date: Available online 1 September 2017
Source:Médecine & Droit
Author(s): Roland Chvetzoff
La relation de soin entre un médecin et son patient peut aussi se transformer en une relation amoureuse. Condamnée fermement et sans mesure par l'Ordre des médecins au titre d'un « interdit absolu », la relation amoureuse sincère entre un médecin et son patient reste un sujet tabou. Au-delà des situations condamnables d'abus d'autorité, de chantage ou de harcèlement, l'auteur tente de comprendre ce qui pourrait faire d'une relation amoureuse sincère entre un médecin et son patient une transgression, un interdit absolu ? Alors même que cet interdit n'apparaît ni dans la morale, le droit, ou le Code de déontologie médicale. La clinique confronte le médecin et son patient à l'intime et à une phantasmatique inconsciente où Erôs peut amener la relation médicale au risque d'une relation amoureuse. Seul Anterôs, le frère jumeau d'Erôs, peut permettre de rompre cette alliance interdite pour, in fine, préserver le corps médical. Mais Antigone, tout comme Créon, montrent bien que la transgression peut également prendre la forme d'une volonté ferme d'appliquer des normes, de s'abriter derrière des mobiles nobles et dignes, qu'ils soient rationnels ou pieux. C'est pourquoi l'institutionnalisation de la réflexion éthique en médecine a toute son importance afin d'échapper à la représentation d'un intolérable absolu dénuée de toute nuance.The doctor–patient relationship of care can sometimes be transformed into a relationship of love. Firmly condemned, without measure and as "absolutely prohibited" by the Medical Association, the sincere love relationship between a doctor and patient remains a taboo subject. Setting aside reprehensible circumstances such as abuse of authority, blackmail or harassment, the author here makes an attempt to understand the factors that could have led the sincere love relationship between doctor and patient to constitute a transgression and an absolute prohibition? Even though this prohibition does not appear either in morality, law, or the Code of Medical Ethics. In the clinical setting, the doctor and patient are confronted with an intimity and unconscious phantasms were Eros can lead the medical relationship towards the risk of a romantic relationship. Only Anteros, the twin brother of Eros, is permitted to sever this forbidden alliance for the ultimate preservation of the Code of Medical Ethics. But Antigone, along with Creon, clearly show that transgression can also take the form of a dogged determination to enforce guidelines and hide behind noble and dignified motives, whether it be for rational or pious reasons. This is why the formalisation of ethical reflection in medicine on these themes is of great importance, in order to escape the depiction of intolerable absolutisms that are devoid of all nuance.



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Device-assisted transdermal drug delivery

Publication date: Available online 1 September 2017
Source:Advanced Drug Delivery Reviews
Author(s): Hyunjae Lee, Changyeong Song, Seungmin Baik, Dokyoon Kim, Taeghwan Hyeon, Dae-Hyeong Kim
Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small-molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real-time analysis of physiological cues is highlighted.

Graphical abstract

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A hierarchical Bayesian approach to calibrating the linear-quadratic model from clonogenic survival assay data

Publication date: Available online 1 September 2017
Source:Radiotherapy and Oncology
Author(s): Joe Collis, Michael R. Hill, James R. Nicol, Philip J. Paine, Jonathan A. Coulter
We propose a Bayesian hierarchical model applicable to the calibration of the linear-quadratic model of radiation dose–response. Experimental data used in model calibration were taken from a clonogenic survival assay conducted on human breast cancer cells (MDA-MB-231) across a range of radiation doses (0–6Gy). Employing Markov-chain Monte Carlo methods, we calibrated the proposed Bayesian hierarchical model, computed posterior distributions for the model parameters and survival fraction dose–response probability densities. Key contributions include the proposal of a model that incorporates multiple sources of inter- and intra-experiment variability commonly neglected in the standard frequentist approach and its subsequent application to in vitro experimental data.



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Pollution characteristics, risk assessment, and source apportionment of heavy metals in road dust in Beijing, China

Publication date: 15 January 2018
Source:Science of The Total Environment, Volume 612
Author(s): Cong Men, Ruimin Liu, Fei Xu, Qingrui Wang, Lijia Guo, Zhenyao Shen
To analyze the spatial distribution patterns, risks, and sources of heavy metals (As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Zn, Fe), 36 road dust samples were collected from an urbanized area of Beijing in June 2016. The mean concentration of most metals, except As and Mn, exceeded their corresponding background values, with the mean concentration of Cd being 8 times that of its background. Spatially, for most heavy metals, except As and Mn, the high concentration areas were mainly within the 5th ring road, especially the northern area. The geo-accumulation index of Cd and Cu indicated moderate contamination at many sites. The entire study area was prone to potential ecological risks, with higher risks within the 4th ring road. Cd caused high potential ecological risk at most sites. According to the health risk assessment results, the non-carcinogenic risks that human beings suffered from heavy metals were insignificant. However, the carcinogenic risks due to Ni and Cr exceeded the acceptable level. Based on the source apportionment using positive matrix factorization, four factors were defined for the heavy metals. Factor 1, which was traffic-related exhaust, accounted for 34.47% of the concentration of heavy metals. The contributions of Factors 2 and 3 were approximately 25% each. Factor 2 was potentially related to coal combustion, while Factor 3 could be related to the manufacture and use of metal components. Factor 4, which could be related to the use of pesticides, fertilizers, and medical devices, accounted for 14.88%, which was the lowest.

Graphical abstract

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Biogeochemical controls on the speciation and aquatic toxicity of vanadium and other metals in sediments from a river reservoir

Publication date: 15 January 2018
Source:Science of The Total Environment, Volume 612
Author(s): Sara M. Nedrich, Anthony Chappaz, Michelle L. Hudson, Steven S. Brown, G. Allen Burton
Effects of hydrologic variability on reservoir biogeochemistry are relatively unknown, particularly for less studied metals like vanadium (V). Further, few studies have investigated the fate and effects of sediment-associated V to aquatic organisms in hydrologically variable systems. Our primary objective was to assess effects of hydrologic manipulation on speciation and toxicity of V (range: 635 to 1620mgkg⁻¹) and other metals to Hyalella azteca and Daphnia magna. Sediments were collected from a reservoir located in a former mining area and microcosm experiments were conducted to emulate 7-day drying and inundation periods. Despite high sediment concentrations, V bioavailability remained low with no significant effects to organism survival, growth, or reproduction. The lack of V toxicity was attributed to reduced speciation (III, IV), non-labile complexation, and sorption to Al/Fe/Mn-oxyhydroxides. Zinc (Zn) increased in surface and porewater with inundation, for some sediments exceeding the U.S. EPA threshold for chronic toxicity. While no effects of Zn to organism survival or growth were observed, Zn body concentrations were negatively correlated with H. azteca growth. Results from this study indicate that V bioavailability and environmental risk is dependent on V-speciation, and V is less influenced by hydrologic variability than more labile metals such as Zn.

Graphical abstract

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Study on evaluation of starch, dietary fiber and mineral composition of cookies developed from 12 sorghum cultivars

Publication date: 1 January 2018
Source:Food Chemistry, Volume 238
Author(s): B. Dayakar Rao, Dhanashri B. Kulkarni, Kavitha C.
The study aimed to identify best cultivars suitable for sorghum cookies accordingly nutrient and mineral compositions were evaluated. Protein and fat content of cookies were ranged from 5.89±0.04 to 8.27±0.21% and 21.03±0.01 to 23.08±0.03% respectively. The starch content of cookie ranged between 47.06±0.01 and 42.15±0.03% and dietary fiber was reported highest in CSH14 (9.27±0.01%). The highest Mg (56.24±0.03mg/100g) P (255.54±0.03mg/100g), and K (124.26±0.02mg/100g) content were found in C43 cultivar. CSV18R was reported highest iron content (1.23±0.01mg/100g). The sensory scores for overall acceptability of cookies were highest in CSH23, CSH13R and CSV18R cultivars which are rich in dietary fiber and minerals. Normally the hybrids are high yielders and the grain price/qt is 20% lower than varieties. It is implied the raw material costs of two identified cultivars (CSH23 & CSH13R) would help the industry to reduce overall cost of production and offer a better profit margins over the varieties.



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Biochemical and nutritional characterization of coconut (Cocos nucifera L.) haustorium

Publication date: 1 January 2018
Source:Food Chemistry, Volume 238
Author(s): Arivalagan Manivannan, Rakesh Bhardwaj, Sugatha Padmanabhan, Poonam Suneja, K.B. Hebbar, Santosh R. Kanade
Study was conducted to determine the biochemical constituents in coconut (Cocos nucifera L.) haustorium, a spongy tissue formed during coconut germination. Results indicated that 100g of dried coconut haustorium contained 1.05±0.2% ash, 44.2±4.6% soluble sugar, 24.5±3.2% starch, 5.50±0.3% protein, 1.99±0.9% fat, 5.72±0.4% soluble dietary fibre, 20.3±1.9% insoluble dietary fibre, and 146±14.3mg phenolics. Mineral profiling showed that it contained 145±8.6, 104±9.6, 33.9±8.2, 30.9±1.9, 9.45±2.1, 0.292±0.1, 2.53±0.2 and 1.20±0.1mg of K, Mg, Ca, P, Mn, Cu, Fe and Zn, respectively. Antioxidant activity assay indicated that 100g haustorium was equivalent to 1918±173, 170±20.4, 72.8±14.7 and 860±116mg of Trolox as measured by CUPRAC, FRAP, DPPH and ABTS, respectively. Amino acid score indicated that methionine+cysteine (57.6%), phenylalanine+tyrosine (32.6%), leucine (45.7%) and isoleucine (68%) are found less in haustorium. Further studies needed in developing nutritionally balanced formulations using coconut haustorium, which will be useful for lactose intolerant children.



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New photothermal deflection technique to discriminate between heating and cooling

Publication date: January 2018
Source:Journal of Quantitative Spectroscopy and Radiative Transfer, Volume 204
Author(s): Ross S. Fontenot, Veerendra K. Mathur, John H. Barkyoumb
Photothermal deflection spectroscopy (PDS) is a highly sensitive and precise technique that is used to measure the optical absorption and thermal characteristics of a sample. While most applications of PDS utilize a heating beam, laser cooling of solids, or optical refrigeration as it is sometimes called, use this technique to determine if a laser is cooling or heating a sample. Current PDS methods for laser cooling require multiple laser wavelengths in both the Stokes and anti-Stokes region to ensure that cooling is occurring. This can cause problems if lasers must be changed or no lasers in the desired wavelength are available. Herein, we present a photothermal deflection technique that uses the deflection of the probe laser to determine if microcooling is occurring inside a sample.



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Dataset representing the effect of indirect band gap region of Cd-free AlGaAs buffer layer in Cu(In,Ga)Se photovoltaic cell

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Sadia Islam Shachi, Ali Newaz Bahar
The dataset of physical properties for the proposed CIGS solar cell with Cd-free AlGaAs buffer layer has been depicted in this data article. The cell performance outcome due to different AlGaAs buffer layer band gap is reported along with optimum solar cell performance parameters for instance, open circuit voltage (Voc), short circuit current density (Jsc), fill factor (FF), efficiency (η), as well as collection efficiency (ηc).



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Optomechanical devices for Deep Plasma Cancer Proteomics

Publication date: Available online 1 September 2017
Source:Seminars in Cancer Biology
Author(s): Priscila M. Kosaka, Montserrat Calleja, Javier Tamayo
Most of the cancer deaths could be avoided by early detection of the tumor when it is confined to its primary site and it has not metastasized. To this aim, one of the most promising strategies is the discovery and detection of protein biomarkers shed by the young tumor to the bloodstream. Proteomic technologies, mainly mass spectrometry and multiplexed immunoassays, have rapidly developed during last years with improved limits of detection and multiplexing capability. Unfortunately, these developments together major investments and large international efforts have not resulted into new useful protein biomarkers. Here, we analyze the potential and limitations of current proteomic technologies for detecting protein biomarkers released into circulation by the tumor. We find that these technologies can hardly probe the deepest region of the plasma proteome, at concentrations below the pg/mL level, where protein biomarkers for early cancer detection may exist. This clearly indicates the need of incorporating novel ultrasensitive techniques to the proteomic tool-box that can cover the inaccessible regions of the plasma proteome. We here propose biological detectors based on nanomechanical systems for discovery and detection of cancer protein biomarkers in plasma. We review the modes of operation of these devices, putting our focus on recent developments on nanomechanical sandwich immunoassays and nanomechanical spectrometry. The first technique enables reproducible immunodetection of proteins at concentrations well below the pg/mL level, with a limit of detection on the verge of 10 ag/mL. This technology can potentially detect low abundance tumor-associated proteins in plasma at the very early stages of the tumor. The second technique enables the identification of individual intact proteins by two physical coordinates, the mass and stiffness, instead of the mass-to-charge ratio of the protein constituents. This technology enormously simplifies the identification of proteins and it can provide useful information on interactions and posttranslational modifications, that otherwise is lost in mass spectrometry.



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Phosphatidylserine: A cancer cell targeting biomarker

Publication date: Available online 1 September 2017
Source:Seminars in Cancer Biology
Author(s): Bhupender Sharma, Shamsher S. Kanwar
Cancer is a leading cause of mortality and morbidity globally. Many prominent cancer-associated molecules have been identified over the recent years which include EGFR, CD44, TGFbRII, HER2, miR-497, NMP22, BTA, Fibrin/FDP etc. These biomarkers are often used for screening, detection, diagnosis, prognosis, prediction and monitoring of cancer development. Phosphatidylserine (PS) is an essential component in all human cells which is present on the inner leaflet of the cell membrane. The oxidative stress causes exposure of PS on the surface of the vascular endothelium in the cancer cells (lung, breast, pancreatic, bladder, skin, brain metastasis, rectal adenocarcinoma etc.) but not on the normal cells. The external PS is regulated by calcium-dependent flippase activity. Cancer cell lines with high surface PS have low flippase activity and high intracellular calcium content. Human Annexin-V, PS targeting antibodies (PGN635 and bavituximab and mch1N11), lysosomal protein, phospholipid Saposin C dioleoylphosphatidylserine (SapC–DOPS), peptide-peptoid hybrid PPS1, PS-binding 14-mer peptide (PSBP-6) and hexapeptide (E3) have been reported to target PS present on cancer cell surface. High expression of CD47 inhibits tumor cell phagocytosis by macrophages. The PS cancer biomarker has also been used to target the drugs to cancer cells specifically without affecting other healthy cells. Currently, the fusion protein (FP) consisting of L-methionase linked to human Annexin-V has been reported to target the cancer cells. The FP catalyzes the conversion of non-toxic prodrug selenomethionine into toxic methyl selenol which thus also prevents the methionine (essential amino acid) supplementation to the cancer cells.



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FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells

Publication date: October 2017
Source:Neoplasia, Volume 19, Issue 10
Author(s): Lukasz Turczyk, Kamila Kitowska, Magdalena Mieszkowska, Kamil Mieczkowski, Dominika Czaplinska, Dominika Piasecka, Radzisław Kordek, Andrzej C. Skladanowski, Piotr Potemski, Hanna M. Romanska, Rafal Sadej
Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.



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Calcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence

Publication date: October 2017
Source:Cancer Epidemiology, Volume 50, Part A
Author(s): Cameron M. Wright, Rachael E. Moorin, Enayet K. Chowdhury, Bruno H. Stricker, Christopher M. Reid, Christobel M. Saunders, Jeffery D. Hughes
Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for 'confounding by indication' was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03–1.15, I²=0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94–1.03, I²=35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We thus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712.



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