bluuebunny/crossref_metadata_2025 huggingface dataset:
Stack Splinting Versus Kirschner Wire Treatment in Acute Closed Mallet Finger Doyle I
Authors: Velez Maria de los Angeles Mendoza , Medina Marco Aurelio Rendon , Lopez Ricardo Pacheco , Morales Hecly Lya Vazquez , Ordoñez Ruben Hernandez
Published: April 2021

Introduction:

Mallet injuries are common and usually treated conservatively. Various systematic reviews have found a lack of evidence regarding the best management, and it is still unclear.

Objective:

To evaluate the treatment efficacy of Stack Splinting compared to a Kirschner wire immobilization of acute closed mallet finger Doyle I.

Methods:

From March 2019 to February 2020, 41 patients with acute close mallet finger Doyle I were treated; 19 patients were treated with Kirschner wire and 22 with Stack splinting for a mean of 6 weeks. The average patient age at the time of the injury was 43 years.

Results:

Twenty-eight males and 13 females were in this study. Among them, 17 patients were injured in the little finger, 15 in the middle finger, and 9 in the ring finger. Twenty-seven of injuries suffered an aggression, 11 from falling, and 3 from sports injuries. All the fingers had typical mallet malformation. Seventeen patients treated with Kirschner wire completed the treatment with full recovery, only 7 patients treated with Stack splint completed the treatment and 15 treated with Stack splint had relapse on mallet injury.

Conclusion:

Kirschner wire treatment is a simple procedure, and proves in this study that has better results in patients with acute closed mallet finger Doyle I compared to Stack splint.
Comparison of clinical efficacy between arthroscopically assisted Tight-Rope technique and clavicular hook plate fixation in treating acute high-grade acromioclavicular joint separations
Authors: Nie Si , Lan Min
Published: April 2021

Introduction:

The purpose of this study was to compare the results of arthroscopically assisted reduction of acute acromioclavicular (AC) joint separations with the Tight-Rope technique with results of clavicular hook plate fixation.

Materials and Methods:

The 28 patients with acute high-grade AC joint dislocation were treated with arthroscopic assisted fixation using the Tight-Rope system, the arthroscopic evaluation and treatment of glenohumeral lesions were performed before AC ligament reconstruction. Each Tight-Rope technique group patient was matched with three controls that underwent clavicular hook plate fixation, and preoperation and postoperative visual analogue scale (VAS) and functional recovery (Constant Score) of the shoulder joint was assessed,. Furthermore, the demographics and clinical characteristics were compared between the two groups.

Results:

All patients had clinical and radiological results available at 2 years or greater (mean: 34; range: 24–72 months), they were statistically significant improvement in the constant score and VAS score at the end of follow-up respectively ( P < 0.001). Compared with the clavicular hook plate group, Tight-Rope system group patients were incurred significant statistically lower skin incision, hospitalization time and estimated blood loss ( P < 0.001), and the constant score and VAS score at the end of follow-up was significantly higher in the Tight-Rope group ( P < 0.001). Patients who underwent clavicular hook plate had a higher incidence of fixation failure [10 cases (11.9%) versus 2 cases (7.1%)] than those of the Tight-Rope system group.

Conclusions:

The Tight-Rope technique is advantageous for treating these patients because it is a minimally invasive procedure with low complications and superior clinical outcomes.
Resistance-associated substitutions and response to treatment in a chronic hepatitis C virus infected-patient: an unusual virological response case report
Authors: Aldunate Fabián , Echeverría Natalia , Chiodi Daniela , López Pablo , Sánchez-Cicerón Adriana , Soñora Martín , Cristina Juan , Moratorio Gonzalo , Hernández Nelia , Moreno Pilar
Published: April 2021

Background

Direct-Acting agents (DAAs) target and inhibit essential viral replication proteins. They have revolutionized the treatment of Hepatitis C virus (HCV) infection reaching high levels of sustained virologic response. However, the detection of basal resistance-associated substitutions (RASs) to DAAs in naïve patients could be important in predicting the treatment outcome in some patients exhibiting failures to DAA-based therapies. Therefore, the aim of this work was to evaluate the presence of RASs as minority variants within intra-host viral populations, and assess their relationship to response to therapy on a multiple times relapser patient infected chronically with HCV.

Case presentation

A male HCV infected-patient with a genotype 1a strain was evaluated. He had previously not responded to dual therapy (pegylated interferon-α plus ribavirin) and was going to start a direct-acting agent-based therapy (DAAs). He showed no significant liver fibrosis (F0). Viral RNA was extracted from serum samples taken prior and after therapy with DAAs (sofosbubir/ledipasvir/ribavirin). NS5A and NS5B genomic regions were PCR-amplified and the amplicons were sequenced using Sanger and next-generation sequencing (NGS) approaches. RASs were searched in in-silico translated sequences for all DAAs available and their frequencies were determined for those detected by NGS technology. Sanger sequencing did not reveal the presence of RASs in the consensus sequence neither before nor after the DAA treatment. However, several RASs were found at low frequencies, both before as well as after DAA treatment. RASs found as minority variants (particularly substitutions in position 93 within NS5A region) seem to have increased their frequency after DAA pressure. Nevertheless, these RASs did not become dominant and the patient still relapsed, despite perfect adherence to treatment and having no other complications beyond the infection (no significant fibrosis, no drug abuse).

Conclusions

This report shows that some patients might relapse after a DAA-based therapy even when RASs (pre- and post-treatment) are detected in very low frequencies (< 1%) within intra-host viral populations. Increased awareness of this association may improve detection and guide towards a personalized HCV treatment, directly improving the outcome in hard-to-treat patients.
Moving QoE for monitoring DASH video streaming: models and a study of multiple mobile clients
Authors: Kiani Mehr Sheyda , Jogalekar Prasad , Medhi Deep
Published: April 2021

Objective Quality of Experience (QoE) for Dynamic Adaptive Streaming over HTTP (DASH) video streaming has received considerable attention in recent years. While there are a number of objective QoE models, a limitation of the current models is that the QoE is provided after the entire video is delivered; also, the models are on a per client basis. For content service providers, QoE observed is important to monitor to understand ensemble performance during streaming such as for live events or concurrent streaming when multiple clients are streaming. For this purpose, we propose Moving QoE (MQoE, in short) models to measure QoE during periodically during video streaming for multiple simultaneous clients. Our first model MQoE_RF is a nonlinear model considering the bitrate gain and sensitivity from bitrate switching frequency. Our second model MQoE_SD is a linear model that focuses on capturing the standard deviation in the bitrate switching magnitude among segments along with the bitrate gain. We then study the effectiveness of both models in a multi-user mobile client environment, with the mobility patterns being based on traces from a train, a car, or a ferry. We implemented the study on the GENI testbed. Our study shows that our MQoE models are more accurate in capturing the QoE behavior during transmission than static QoE models. Furthermore, our MQoE_RF model captures the sensitivity due to bitrate switching frequency more effectively while MQoE_SD captures the sensitivity due to the magnitude of the bitrate switching. Either models are suitable for content service providers for monitoring video streaming based on their preference.
Physical activity for blood glucose control in gestational diabetes mellitus: rationale and recommendations for translational behavioral interventions
Authors: Onaade Oluwafemifola , Maples Jill M. , Rand Bethany , Fortner Kimberly B. , Zite Nikki B. , Ehrlich Samantha F.
Published: April 2021

Gestational Diabetes Mellitus (GDM) is associated with adverse health outcomes during pregnancy and beyond. Previous randomized controlled trials of exercise interventions have demonstrated that exercise, conducted primarily during supervised sessions, improves maternal glycemic control in women with GDM. However, additional research is needed to develop physical activity interventions that are easily implemented in healthcare settings (e.g., recommendations and strategies to increase non-supervised physical activity). This narrative review presents: current physical activity recommendations for pregnancy and women with GDM; the scientific literature to date on physical activity, particularly walking, and blood glucose control in GDM; rationale for physical activity interventions targeting women with GDM that are appropriate for translation to the clinical setting (e.g., lifestyle interventions that include behavioral counseling with a health coach); and the strategies employed by previous, successful lifestyle interventions for pregnant and postpartum women that were based in clinical settings.

Most previous exercise interventions for blood glucose control in women with GDM have included supervised exercise sessions, and will thus be difficult to translate to the health care system. However, lifestyle interventions for weight maintenance (i.e., healthy diet and physical activity) set in the health care system and delivered by health coaches have been successfully implemented in pregnant and postpartum populations. Therefore, we suggest that future trials examine lifestyle interventions that promote unsupervised walking with evidence-based behavioral strategies (e.g., goal setting, monitoring, and feedback) and consider incorporating the use of physical activity tracking devices to support these strategies.
How to engage patient partners in health service research: a scoping review protocol
Authors: Tscherning Sarah Cecilie , Bekker Hilary Louise , Vedelø Tina Wang , Finderup Jeanette , Rodkjær Lotte Ørneborg
Published: April 2021

Background

The patients’ and the carers’ roles in health service research has changed from being solely participants in studies to also being active partners and co-designers in the research process. Research carried out with or by patient partners is an increasingly accepted component of health service research in many countries, but how researchers can best approach engaging patient partners in the research process is still not clear. There is a need for guidance to support researchers when engaging patient partners and assess how such engagement impacts on research outputs. The aim of this paper is to present a protocol for a scoping review of published literature on how to engage patient partners effectively in the research process. Investigating this aim implies examining: a) how to engage patient partners in the research process; and b) what impact such engagement has on research outputs. This scoping review protocol is the first to examine how to engage patient partners effectively across different diseases and research areas.

Methods

A scoping review using a systematic process informed by Arksey and O’Malley’s framework will be carried out across six electronic databases using the terms ‘patient participation’, ‘community participation’, ‘research personnel’, ‘patient and public involvement’ and ‘patient partner’. We will include published reviews concerning engagement of patient partners in the research process in healthcare settings, and exclude studies assessing engagement in treatment and healthcare. Two reviewers will screen the titles and abstracts of articles independently for inclusion, and extract data from articles that meet the inclusion criteria. Where there is disagreement, a third reviewer will be consulted to facilitate consensus. The data elicited will include: author and study characteristics; research aims and findings; description of patient engagement in the research process; and assessment impact. Descriptive data and narrative analysis will synthesize findings.

Discussion

To understand how to engage patient partners effectively in the research process, the impact of such engagement must be taken into consideration to give a qualified suggestion for future guidance. We hope this review will raise awareness of which common elements constitute effective engagement of patient partners in the research process.
Displacement-mediated bound states in the continuum in all-dielectric superlattice metasurfaces
Authors: Shi Tan , Deng Zi-Lan , Tu Qing-An , Cao Yaoyu , Li Xiangping
Published: April 2021

Bound states in the continuum (BICs) are localized states coexisting with extended waves inside the continuous spectrum range, which have infinite lifetimes without any radiation. To extract high-Q quasi-BIC resonances from the symmetry-protected BIC for practical applications, symmetry-breaking approaches are usually exploited, either by slightly breaking the excitation field symmetry or structure symmetry. Here, we introduce an all-dielectric superlattice metasurface that can symmetry-compatibly convert BIC states into high-Q quasi-BIC modes based on the guided-mode resonance coupling by relative displacement tuning. The metasurface is composed of a superlattice of multiple nanobeams, supporting both magnetic mode and toroidal mode with large tunability. Both modes can interact with the incident continuum by mediating the displacement between nanobeams, which empowers dual asymmetric Fano resonances with high Q-factors. The bandwidth of the toroidal mode under y-polarized incidences and that of the magnetic mode under x-polarized incidences can be readily tuned by the local displacement between nanobeams in each unit cell. Such displacement-mediated BIC resonance is promising for various applications such as bio-molecule sensing and low threshold lasing.
Impact of borderline personality disorder traits on the association between age and health-related quality of life: A cohort study in the general population
Authors: Botter L. , ten Have M. , Gerritsen D. , de Graaf R. , van Dijk S. D. M. , van den Brink R. H. S. , Oude Voshaar R. C.
Published: April 2021

Background

Increasing age as well as borderline personality pathology are associated with a lower level of health-related quality of life (HR-QoL). Our objective was to investigate whether the presence of borderline personality traits modifies the association between age and HR-QoL in the general population.

Methods

Cross-sectional data from 5,303 respondents (aged 21–72 years) of the Netherlands Mental Health Survey and Incidence Study-2 were analyzed. Borderline personality traits were assessed with the International Personality Disorder Examination questionnaire. Mental and physical HR-QoL were measured with the Medical Outcomes Study Short Form Health Survey. Multiple linear regression analysis was used to examine the association of borderline personality traits, age and their interaction on mental as well as physical HR-QoL, adjusted for demographic variables as well as somatic and mental disorders.

Results

A total of 1,520 (28.7%) respondents reported one or more borderline personality traits of which 58 (1.1%) reported five or more indicative of a borderline personality disorder. A higher age was associated with lower physical HR-QoL. This negative association became significantly stronger in the presence of borderline personality traits. The association between increasing age and mental HR-QoL was positive in the absence of borderline personality traits and negative in the presence of borderline personality traits.

Conclusion

Borderline personality traits negatively interfere with the association between age and HR-QoL irrespective of somatic and mental disorders. Attention of clinicians and researchers for subthreshold borderline personality pathology is needed in middle-aged and older persons.
Cycle Development in a Mini-Freeze Dryer: Evaluation of Manometric Temperature Measurement in Small-Scale Equipment
Authors: Wenzel Tim , Gieseler Margit , Abdul-Fattah Ahmad M. , Gieseler Henning
Published: April 2021

The objective of this research was to assess the applicability of manometric temperature measurement (MTM) and SMART™ for cycle development and monitoring of critical product and process parameters in a mini-freeze dryer using a small set of seven vials. Freeze drying cycles were developed using SMART™ which automatically defines and adapts process parameters based on input data and MTM feedback information. The freeze drying behavior and product characteristics of an amorphous model system were studied at varying wall temperature control settings of the cylindrical wall surrounding the shelf in the mini-freeze dryer. Calculated product temperature profiles were similar for all different wall temperature settings during the MTM-SMART™ runs and in good agreement with the temperatures measured by thermocouples. Product resistance profiles showed uniformity in all of the runs conducted in the mini-freeze dryer, but absolute values were slightly lower compared to values determined by MTM in a LyoStar™ pilot-scale freeze dryer. The resulting cakes exhibited comparable residual moisture content and optical appearance to the products obtained in the larger freeze dryer. An increase in intra-vial heterogeneity was found for the pore morphology in the cycle with deactivated wall temperature control in the mini-freeze dryer. SMART™ cycle design and product attributes were reproducible and a minimum load of seven 10R vials was identified for more accurate MTM values. MTM-SMART™ runs suggested, that in case of the wall temperature following the product temperature of the center vial, product temperatures differ only slightly from those in the LyoStar™ freeze dryer.
Employment Instability and Fertility in Europe: A Meta-Analysis
Authors: Alderotti Giammarco , Vignoli Daniele , Baccini Michela , Matysiak Anna
Published: April 2021

The relationship between employment instability and fertility is a major topic in demographic research, with a proliferation of published papers on this matter, especially since the Great Recession. Employment instability, which most often manifests in unemployment or time-limited employment, is usually deemed to have a negative effect on fertility, although different fertility reactions are hypothesized by sociological theories, and micro-level evidence is fragmented and contradictory. We used meta-analytic techniques to synthesize European research findings, offer general conclusions about the effects of employment instability on fertility (in terms of direction and size), and rank different sources of employment instability. Our results suggest that employment instability has a nonnegligible negative effect on fertility. Men's unemployment is more detrimental for fertility than men's time-limited employment; conversely, a woman having a fixed-term contract is least likely to have a child. Next, the negative effect of employment instability on fertility has become stronger over time, and is more severe in Southern European countries, where social protection for families and the unemployed is least generous. Finally, meta-regression estimates demonstrate that failing to account for income and partner characteristics leads to an overestimation of the negative effect of employment instability on fertility. We advance the role of these two factors as potential mechanisms by which employment instability affects fertility. Overall, this meta-analysis provides the empirical foundation for new studies on the topic.
Development of a highly pulmonary metastatic orthotopic renal cell carcinoma murine model
Authors: Park Jee Soo , Lee Myung Eun , Kim Seung Hwan , Jang Won Sik , Ham Won Sik
Published: April 2021

The incidence of renal cell carcinoma (RCC) is high, and its outcomes remain poor. Mortality is attributable largely to metastatic disease and a dearth of effective therapeutic interventions. The lungs are the most common metastatic site. To elucidate the biological mechanisms underlying pulmonary metastasis and identify superior therapeutic strategies, we developed a novel and clinically relevant murine RCC model exhibiting enhanced pulmonary metastasis. Mice underwent intrarenal implantation using luciferase-expressing Renca, a murine renal adenocarcinoma cell line. Primary renal tumor progression and development of metastatic lung lesions were monitored in live mice using bioluminescent imaging, followed by post-mortem organ assessment. Cells were isolated from pulmonary metastases for reimplantation, followed by repeat monitoring and assessment. This process was repeated once more for a total of two in vivo passages to select for pulmonary metastatic Renca cell subpopulations. However, a single round of in vivo selection was sufficient to produce a near-maximally metastatic subpopulation. Relative to Renca cell-implanted mice, subpopulation-implanted mice exhibited shorter implantation-metastasis intervals (5 days), shorter implantation-moribundity intervals (sacrificed at 18.6±2.9 versus 22.3±1.1 days), a higher number of metastatic lung lesions at 23 days (183.9±39.0 versus 172.6±38.2) and poorer survival. Implantation of cells derived from the second round of in vivo selection produced no further significant differences in the above metrics. This model consistently and efficiently recapitulates RCC pulmonary metastasis while allowing in vivo monitoring of tumor progression, thereby facilitating elucidation of the molecular mechanisms underlying pulmonary metastasis and evaluation of therapeutic modalities.
The differing effects of occipital and trunk somites on neural development in the chick embryo
Authors: Lim T. M. , Lunn E. R. , Keynes R. J. , Stern C. D.
Published: April 2021

In all higher vertebrate embryos the sensory ganglia of the trunk develop adjacent to the neural tube, in the cranial halves of the somite-derived sclerotomes. It has been known for many years that ganglia do not develop in the most cranial (occipital) sclerotomes, caudal to the first somite. Here we have investigated whether this is due to craniocaudal variation in the neural tube or crest, or to an unusual property of the sclerotomes at occipital levels. Using the monoclonal antibody HNK-1 as a marker for neural crest cells in the chick embryo, we find that the crest does enter the cranial halves of the occipital sclerotomes. Further-more, staining with zinc iodide/osmium tetroxide shows that some of these crest-derived cells sprout axons within these sclerotomes. By stage 23, however, no dorsal root ganglia are present within the five occipital sclerotomes, as assessed both by haematoxy-lin/eosin and zinc iodide/osmium tetroxide staining. Moreover, despite this loss of sensory cells, motor axons grow out in these segments, many of them later fasciculating to form the hypoglossal nerve. The sclerotomes remain visible until stages 27/28, when they dissociate to form the base of the skull and the atlas and axis vertebrae.

After grafting occipital neural tube from quail donor embryos in place of trunk neural tube in host chick embryos, quail-derived ganglia do develop in the trunk sclerotomes. This shows that the failure of occipital ganglion development is not the result of some fixed local property of the neural crest or neural tube at occipital levels. We therefore suggest that in the chick embryo the cranial halves of the five occipi-tal sclerotomes lack factors essential for normal sen-sory ganglion development, and that these factors are correspondingly present in all the more caudal sclerotomes.
Polar asymmetry in the organization of the cortical cytokeratin system of Xenopus laevis oocytes and embryos
Authors: Klymkowsky Michael W. , Maynell Laurie A. , Polson Andrew G.
Published: April 2021

We have used whole-mount immunofluorescence mi-croscopy of late-stage Xenopus laevis oocytes and early embryos to examine the organization of their cortical cytokeratin systems. In both mature oocytes and early embryos, there is a distinct animal-vegetal polarity in cytokeratin organization. In mature (stage-VI) oocytes, the cytokeratin filaments of the vegetal region form a unique, almost geodesic net-work; in the animal region, cytokeratin organization appears much more variable and irregular. In unfer-tilized, postgerminal vesicle breakdown eggs, the cor-tical cytokeratin system is disorganized throughout both animal and vegetal hemispheres. After fertiliz-ation, cytokeratin organization reappears first in a punctate pattern that is transformed into an array of oriented filaments. These cytokeratin filaments ap-pear first in the vegetal hemisphere and are initially thin. Subsequently, they form bundles that grow thicker through the period of first to second cleavage, at which point large cytokeratin filament bundles form a loose, fishnet-like system that encompasses the vegetal portion of each blastomere. In the animal region, cytokeratin filaments do not appear to form large fibre networks, but rather appear to be organ-ized into a system of fine filaments. The animal-vegetal polarity in cytokeratin organization persists until early blastula (stage 5); in later-stage embryos, both animal and vegetal blastomeres possess qualitat-ively similar cytokeratin filament systems. The entire process of cytokeratin reorganization in the egg is initiated by prick activation. These observations indi-cate that the cortical cytoskeleton of Xenopus oocytes and early embryos is both dynamic and asymmetric.
Expression of nuclear lamins during mouse preimplantation development
Authors: Houliston Evelyn , Guilly Marie-Noëlle , Courvalin Jean-Claude , Maro Bernard
Published: April 2021

The expression of nuclear lamins during mouse preimplantation development was studied by immunofluorescence, immunoblotting and immunoprecipitation. Two sera were used, specific either for lamin B or lamins A and C. Both sera gave a positive staining of the nuclear periphery throughout preimplantation development (fertilized eggs to late blastocysts). Immunoblots revealed that the three lamins were present in eggs and blastocysts. However, lamin A from eggs was found to have a higher apparent Mr than lamin A from blastocysts and other mouse cells. Using immunoprecipitation, synthesis of lamin A was detected in eggs while synthesis of lamin B was detected in 8-cell embryos and blastocysts, indicating that at least some of the lamins used during early development do not come from a store in the egg. These results are discussed in relation to the possible role of lamins during cell differentiation.
Ultrabithorax and engrailed expression in Drosophila embryos mutant for segmentation genes of the pair-rule class
Authors: Martinez-Arias Alfonso , White Robert A. H.
Published: April 2021

Mutations in the pair-rule class of segmentation genes cause pattern deletions with a double segment periodicity in the Drosophila embryo. This phenotype is, in part, due to cell death. Using molecular probes for engrailed (en) and Ultrabithorax (Ubx) expression as markers for the body plan, we have studied the phenotype of pair-rule mutants prior to cell death. All these mutants alter the expression of en and Ubx; then-molecular phenotypes suggest a pathway whereby pair-rule gene functions construct metameric units.
The origin of spicule-forming cells in a ‘primitive’ sea urchin (Eucidaris tribuloides) which appears to lack primary mesenchyme cells
Authors: Wray Gregory A. , Mcclay David R.
Published: April 2021

The calcareous larval skeleton of euechinoid sea urchins is synthesized by primary mesenchyme cells which ingress prior to gastrulation. In embryos of the cidaroid sea urchin Eucidaris tribuloides, no mesenchyme cells ingress before gastrulation, yet larvae later contain skeletons. This apparent paradox is resolved by immunochemical, cell lineage and morphological evidence showing that spicule-forming cells of Eucidaris are homologous to primary mesenchyme cells of euechinoids. In particular, these two cell types share expression of two cell lineage-specific gene products, are derived from the same cellular precursors, the micromeres, and undergo a similar migratory phase prior to skeletogenesis. Despite these similarities, there are far fewer spicule-forming cells in Eucidaris than in typical euechinoids and they assume a different pattern during spiculogenesis. The homology between Eucidaris spicule-forming cells and euechinoid primary mesenchyme cells indicates that a heterochrony in the time of spicule-forming cell ingression has occurred since the divergence of their respective lineages.
The extracellular matrix of the developing cornea: diversity, deposition and function*
Authors: Bard J. B. L. , Bansal M. K. , Ross A. S. A.
Published: April 2021

This paper examines the role of the extracellular matrix (ECM) in the development of the cornea. After a brief summary of the corneal structure and ECM, we describe evidence suggesting that the differen-tiation of neural crest (NC) cells into endothelium and fibroblasts is under the control of ocular ECM. We then examine the role of collagen I in stromal morpho-genesis by comparing normal corneas with those of homozygous Movl3 mice which do not make collagen We report that, in spite of this absence, the cellular morphology of the Movl3 eye is indistinguishable from that of the wild type. In the 16-day mutant stroma, however, the remaining collagens form small amounts of disorganized, thin fibrils rather than orthogonally organized 20 nm-diameter fibrils; a re-sult implying that collagen I plays only a structural role and that its absence is not compensated for. It also suggests that, because these remaining collagens will not form the normal fibrils that they will in vitro, fibrillogenesis in the corneal stroma differs from that elsewhere.

The latter part of the paper describes our current work on chick stromal deposition using corneal epi-thelia isolated with an intact basal lamina that lay down in vitro ∼3 /im-thick stromas of organized fibrils similar to that seen in vivo. This experimental system has yielded two unexpected results. First, the amount of collagen and proteoglycans produced by such epi-thelia is not dependent on whether its substratum is collagenous and we therefore conclude that stromal production by the intact epithelium is more auton-omous than hitherto thought. Second, chondroitin sulphate (CS), the predominant proteoglycan, appears to play no role in stromal morphogenesis: epithelia cultured in testicular hyaluronidase, which degrades CS, lay down stromas whose organization and fibril-diameter distribution are indistinguishable from con-trols. One possible role for CS, however, is as a lubricant which facilitates corneal growth: it could allow fibrils to move over one another without deform-ing their orthogonal organization. Finally, we have examined the processes of fibrillogenesis in the corneal stroma and conclude that they are different from those elsewhere in the embryo and in vitro, perhaps because there is in the primary stroma an unidentified, highly hydrated ECM macromolecule that embeds the fibrils and that may mediate their morphogenesis.
Strategies of head development: workshop report
Authors: Alberch P. , Kollar E.
Published: April 2021

We organized this workshop as an open discussion around the theme of developmental organization and evolution of the vertebrate head. To sharpen the focus of the debate initially, we, the convenors, proposed a hypothetical ‘two-step’ model of head development. The first step would be conceptually analogous to insect development, in the sense that early in embryonic development, i.e. during, or shortly after, gastrulation, a segmental pattern is specified in the neuroectoderm and/or head mesoderm. By segmentation we mean the subdivision of an embryonic field into sharply defined populations of cells linearly arranged along the anterior-posterior axis. Each population of cells would correspond to a ‘segment’ and each segment would be characterized by divergent developmental fate and potency. This initial process of regionalization by segmentation would be followed by a series of morphogenetic events, involving deformation of epithelial sheets, cell migration and epithelial-mesenchymal inductive interactions.
Expression of intermediate filament proteins during development of Xenopus laevis III. Identification of mRNAs encoding cytokeratins typical of complex epithelia
Authors: Fouquet Bernadette , Herrmann Harald , Franz Jürgen K. , Franke Werner W.
Published: April 2021

A Xenopus laevis mRNA encoding a cytokeratin of the basic (type II) subfamily that is expressed in postgastrulation embryos was cDNA-cloned and sequenced. Comparison of the deduced amino acid sequence of this polypeptide (513 residues, calculated mol. wt 55454; Mr ∼ 58 000 on SDS–PAGE) with those of other cytokeratins revealed its relationship to certain type II cytokeratins of the same and other species, but also remarkable differences. Using a subclone representing the 3′-untranslated portion of the 2·4kb mRNA encoding this cytokeratin, designated XenCK55(5development of n blot experiments, we found that it differs from the only other Xenopus type II cytokeratin known, i.e. the simple epithelium-type component XenCKl(8), in that it is absent in unfertilized eggs and pregastrulation embryos. XenCK55(5/6) mRNA was first detected at gastrulation (stage 11) and found to rapidly increase during neurulation and further development. It was also identified in Xenopus laevis cultured kidney epithelial cells of the line A6 and in the adult animal where it is a major polypeptide in the oesophageal mucosa but absent in most other tissues examined. The pattern of XenCK55(5/6) expression during embryonic development was similar to that reported for the type I polypeptides of the ‘XK81 subfamily’ previously reported to be embryo-specific and absent in adult tissues. Therefore, we used a XK81 mRNA probe representing the 3′-untranslated region in Northern blots, SI nuclease and hybrid-selection-translation assays and found the ∼ 1·6kb XK81 mRNA and the resulting protein of Mr∼ 48 000 not only in postgastrula embryos and tadpoles but also in the oesophagus of adult animals. Our results show that both these type II and type I cytokeratins are synthesized only on gastrulation and are very actively produced in early development. However, their synthesis is not restricted to developmental stages but is continued in at least one epithelium of the adult organism. These observations raise doubts on the occurrence of Xenopus cytokeratins that are strictly specific for certain embryonic or larval stages and absent in the adult. They rather suggest that embryonically expressed cytokeratins are also produced in some adult tissues, although in a restricted pattern of tissue and cell type distribution.
Organization of connective tissue patterns by dermal fibroblasts in the regenerating axolotl limb
Authors: Holder Nigel
Published: April 2021

A set of tendons, aponeurotic sheets and retinaculae, which transduce muscle action from proximal limb levels to flexion and extension of the digits, is found in limbs of many vertebrates. This set of structures, here termed the digit tendon complex, is described for the axolotl forelimb. We show that the complex forms autonomously in muscleless axolotl limb regenerates produced from a cuff of unirradiated dermis surrounding an irradiated limb stump, and persists for up to a year after amputation. The pattern of other connective tissue structures, including the skeleton, is also normal.

Fibroblast condensations that may represent sets of these cells normally associated with muscles in the extensor and flexor compartments of the carpal region also form in muscleless limbs. The results are discussed in terms of the importance of the dermis in pattern regulation, selforganization of connective tissues in general and autonomous development of the digit tendon complex in particular.
Isolation of potential vertebrate limb-identity genes
Authors: Tabin Clifford J.
Published: April 2021

Forelimbs and hindlimbs of tetrapods have different morphological patterns. One plausible explanation for the difference is that the cells that give rise to the limbs differentially express genes which control their pattern of development. Amphibian limb regeneration is an excellent system to test this hypothesis, since the same ultimate morphology is attained in regeneration as through embryogenesis. Using a combination of homeo-box probes and differential screening, I have isolated two newt genes which are differentially expressed in regenerating forelimbs and hindlimbs. One of these genes displays properties expected of a gene involved in controlling limb morphology, including expression in mesodermal tissue and constancy of expression upon transplantation. Based on sequence analysis, this gene appears to be homologous to a homeobox-containing gene previously isolated from frog and human libraries.
Systematic elimination of parthenogenetic cells in mouse chimeras
Authors: Fundele Reinald , Norris Michael L. , Barton Sheila C. , Reik Wolf , Surani M. Azim
Published: April 2021

The developmental potential of primitive ectoderm cells lacking paternal chromosomes was investigated by examining the distribution of parthenogenetic cells in chimeras. Using GPI-1 allozymes as marker, parthenogenetic cells were detected in most organs and tissues in adult chimeras. However, these cells were under severe selective pressure compared with cells from normal fertilized embryos. In the majority of chimeras, parthenogenetic cells in individual animals were observed in a limited number of tissues and organs and, even in these instances, their contribution was substantially reduced. Nevertheless, parthenogenetic cells were detected more consistently in some organs, especially the brain, heart, kidney and spleen. In contrast, there was apparently a systematic selection against parthenogenetic cells in some tissues, most notably in skeletal muscle, liver and pancreas. These results suggest that paternally derived genes are probably required not only for the development of extraembryonic structures but also for subsequent development of embryonic tissues derived from the primitive ectoderm lineage.
Expression of an engrailed-related protein is induced in the anterior neural ectoderm of early Xenopus embryos
Authors: Brivanlou Ali Hemmati , Harland Richard M.
Published: April 2021

We have used a monoclonal antibody directed against the C-terminus of the Drosophila inverted homeodomain to detect a nuclear protein in brain cells of Xenopus laevis embryos. We refer to this antigen as the Xenopus EN protein. The EN protein is localized at midneunda stage to a band of cells in the anterior portion of the neural plate, on each side of the neural groove. Later in development, the expression coincides with the boundary of the midbrain and hindbrain, and persists at least to the swimming tadpole stage. These properties make the EN protein an excellent molecular marker for anterior neural structures. In embryos where inductive interactions between mesodermal and ectodermal tissues have been perturbed, the expression of the EN protein is altered; in embryos that have been anterodorsalized by LiCl treatment, the region that expresses the EN protein is expanded, but still well organized. In ventralized UV-irradiated embryos, the absence of the protein is correlated with the absence of anterior neural structures. In extreme exogastrulae, where the contacts between head mesoderm and prospective neurectoderm are lost, the EN protein is not expressed.
engrailed gene expression in the abdominal segment of Oncopeltus: gradients and cell states in the insect segment
Authors: Campbell Gerard L. , Caveney Stanley
Published: April 2021

A monoclonal antibody that recognizes the product of the segmental gene, engrailed (en), of Drosophila has been used to analyse expression of the homologous gene of Oncopeltus. engrailed expression in the abdominal segment of larval Oncopeltus is confined to a narrow band of epidermal cells localized immediately anterior to the segment border. Expression varies in intensity dur-ing postembryonic development: no gene product is detectable in newly moulted larvae, but reappears soon after initiation of intermoult activities. One possible function of en in this system is revealed by a series of operations confronting cells from different anteropos-terior levels in the segment. New segment borders are generated only when en-expressing cells confront cells from the anteriormost region of the segment. All other combinations result in intercalation of intermediate intrasegmental levels. It is therefore suggested that the most important function of en is the establishment of new, and presumably the maintenance of existing, segment borders.
Collagen fibril bundles: a branching assembly unit in tendon morphogenesis
Authors: Birk David E. , Southern James F. , Zycband Emanuel I. , Fallon John T. , Trelstad Robert L.
Published: April 2021

The assembly, deposition and organization of collagen fibril bundles and their composite fibrils were studied during morphogenesis of the chick embryo tendon using electron microscopy, serial sections and computer-assisted three-dimensional reconstruction techniques. The 14-day chick embryo is a stage when tendon architecture is being established and rapid changes in the mechanical properties occur between days 14 and 17 of development. Tendon matrix structure develops from discrete sub-units, bundles of collagen fibrils. The bundles branch; undergo a gradual rotation over several micrometers; are intimately associated with the cellular elements of the developing tendon; and form arborizing networks within and among fascicles. The organization of discrete fibril segments into bundles, during the establishment of tendon architecture and function, where the segmental fibrillar components could interact with the interfibrillar matrix as well as with adjacent fibrils would contribute to the stabilization of this structure. The observed gradual rotation of the bundles would serve to stabilize the immature bundle through the physical twining of the composite fibrils while the extensive branching of the bundles observed at 14-days of development and their intimate association with the cellular elements would provide a higher order of structure stabilization.
The development of asymmetry: the sidedness of drug-induced limb abnormalities is reversed in situs inversus mice
Authors: Brown Nigel A. , Hoyle Christine I. , McCarthy Afshan , Wolpert Lewis
Published: April 2021

We are studying the development of handedness, in particular the relationships between handed structures with bilateral symmetry, for example the limbs, and those with lateral asymmetry, such as the heart, lungs and gut. Asymmetric (unilateral) developmental limb abnormalities can be induced by chemical treatment of mouse embryos, either in utero by acetazolamide, or in culture by misonidazole. We have examined these effects in mice homozygous for the iv gene. The development of bilateral symmetry in iv/iv mice is normal, but the control of asymmetry appears to be random, that is 50 % develop normally (situs solitus), 50 % with laterally inverted viscera (situs inversus). We find that the handedness of induced asymmetric limb defects is highly correlated with embryonic visceral situs. Right limb defects are induced in situs solitus embryos, left-sided defects in situs inversus. This suggests that the mechanism of induction of asymmetric defects is not related to any intrinsic difference between the development of left and right limbs, but is connected to visceral asymmetry. In addition, the high correlation of limb defects with situs was observed in culture as well as in utero suggesting that the maternal environment plays no role in the development of asymmetry.
The directed growth of retinal axons towards surgically transposed tecta in Xenopus; an examination of homing behaviour by retinal ganglion cell axons
Authors: Taylor J. S. H.
Published: April 2021

The growth of optic axons towards experimentally rotated tecta has been studied. In stage 24/25 embryos, a piece of the dorsal neural tube, containing the dorsal midbrain rudiment, was rotated through 180°. At later stages of development, the pathways of growing optic axons were investigated by labelling with either horseradish peroxidase or fluorescent dye. It is shown that retinal ganglion cell axons followed well-defined pathways, in spite of the abnormal structure of the brain, and were able to locate displaced tecta. This directed outgrowth of retinal axons in the optic tracts appears to be related either to the tectum or to some other component included in the graft operations. In tadpoles in which the midbrain rudiment was removed, optic axons still followed the normal course of the optic tract. This observation argues against long-range target attraction as being essential in guiding growing retinal axons towards the tectum. An alternative axon guidance mechanism, selective fasciculation, is discussed as a possible alternative to exaplain the directed axon outgrowth which occurs in both the normal and in these experimentally manipulated tadpoles.
Range and stability of cell fate determination in isolated sea urchin blastomeres
Authors: Livingston Brian T. , Wilt Fred H.
Published: April 2021

We have examined the developmental potential of blastomeres isolated from either the animal (mesomeres) or vegetal (macromeres-micromeres) half of 16-cell embryos of the sea urchin Lytechinus pictus. We have also examined the effects of two known vegetalizing agents on the development of isolated mesomeres; LiCl treatment and combination with micromeres, the small blastomeres found at the vegetal pole of the 16-cell embryo. The markers for differentiation used were both morphological (invaginations, spicules and pigment cells) and molecular (gut-specific alkaline phosphatase activity, and monoclonal antibodies against antigens specific for gut and oral ectoderm). Embryoids derived from isolated mesomeres expressed markers characteristic of vegetal differentiation only at very low levels. They did express an antigen characteristic of animal development, the oral ectoderm antigen, but with an altered pattern. Isolated macromere-micromere pairs expressed all markers characteristic of vegetal development, but did not express the marker characteristic of animal development. Increasing concentrations of LiCl caused isolated mesomeres to give rise to embryoids with an increasing tendency to express vegetal markers of differentiation, and it was found that expression of different vegetal markers begin to appear at different concentrations of LiCl. LiCl also caused the marker for oral ectoderm to be expressed in a more normal pattern. Combining micromeres with mesomeres also induced mesomere derivatives to differentiate in a vegetal manner. Micromeres were not completely effective in inducing a more normal pattern of expression of the marker for oral ectoderm. The treatment of isolated mesomeres with both LiCl and micromeres produces a synergistic effect resulting in embryoids expressing markers not induced by either treatment alone.