Evaluation of English Self-Learning Modules in the Implementation of Modular Distance Learning

In response to the call that education must continue in the midst of the COVID- 19 pandemic, Self-Learning Modules (SLM) became the Department of Education’s primary learning resource in the implementation of a wide-scale Modular Distance Learning. With the educational landscape being confronted with numerous concerns that questions the quality of its SLMs,   their evaluation plays an extremely crucial role in pursuit of quality education.  The study evaluated English Self-Learning Modules used by Grade 7 students in the First Quarter and propose an enhanced learning material that will be helpful in their modular distance learning experience. The study sought to answer the following questions: (1) What are the strengths and weaknesses of the Self-Learning Modules in terms of: Intellectual Property Rights Compliance, Learning Competencies, Instructional Design and Organization, Instructional Quality, Assessment, and, Readability?; (2) What are the Alternative Interventions suggested to strengthen the identified weaknesses in the Self-Learning Modules?; and, (3) What Enhanced Self-Learning Modules may be proposed based on the strengths and weaknesses of the evaluated materials?     Using a purposive sampling, the Key Informants of the study included a total of eight (8) English teachers coming from three different secondary school locales from Legazpi City Division namely: Legazpi City National High School, Gogon High School and Cabangan High School. The study used a mixed method using a Descriptive –Evaluative Design where Key Informants answered a Survey Questionnaire and underwent Key Informants Interview to record the strengths and weaknesses of the Self-Learning Modules. Thematic analysis and percentage were used in the study to identify salient themes from qualitative and quantitative responses of the participants, respectively.   Relevant findings revealed that the strengths of Self-Learning Modules are (1) accuracy in citations, (2) copyright compliance (3) proper acknowledgement of the references, (4) accuracy in content, (5) appropriate presentation of objectives, (6) logical organization of content, (7) integration of valuable traits, (8) development of 21st century skills, (9) alignment of assessments to lesson objectives and (10) appropriateness of content and vocabulary to the learners’ level.    On the other hand,  Self-Learning Modules displayed weaknesses on the following areas: (1) rotten links, (2) missing bibliographies and references, (3) unpacking of broad competencies (4) outdated content and information, (5) grammatical errors, (6) development of lessons that allow for review, (7) providing answer keys, (8) unclear presentation of instruction and (9) seamless transitions of lessons.   To strengthen the identified weaknesses, the researchers developed a Guide Book that discusses the alternative interventions suggested by the researchers based on their insights together with the recommendations of educators.  The Guide Book aims to empower every module user to become involved in creating an improved Modular Learning experience. Moreover, the Enhanced Self-Learning Modules offshoot retained the revealed strengths and carefully applied the alternative interventions to strengthen the weaknesses. Finally, specific recommendations were suggested aimed towards the improvement of learning experiences

UHRF genes regulate programmed interdigital tissue regression and chondrogenesis in the embryonic limb

The primordium of the limb contains a number of progenitors far superior to those necessary to form the skeletal components of this appendage. During the course of development, precursors that do not follow the skeletogenic program are removed by cell senescence and apoptosis. The formation of the digits provides the most representative example of embryonic remodeling via cell degeneration. In the hand/foot regions of the embryonic vertebrate limb (autopod), the interdigital tissue and the zones of interphalangeal joint formation undergo massive degeneration that accounts for jointed and free digit morphology. Developmental senescence and caspase-dependent apoptosis are considered responsible for these remodeling processes. Our study uncovers a new upstream level of regulation of remodeling by the epigenetic regulators Uhrf1 and Uhrf2 genes. These genes are spatially and temporally expressed in the pre-apoptotic regions. UHRF1 and UHRF2 showed a nuclear localization associated with foci of methylated cytosine. Interestingly, nuclear labeling increased in cells progressing through the stages of degeneration prior to TUNEL positivity. Functional analysis in cultured limb skeletal progenitors via the overexpression of either UHRF1 or UHRF2 inhibited chondrogenesis and induced cell senescence and apoptosis accompanied with changes in global and regional DNA methylation. Uhrfs modulated canonical cell differentiation factors, such as Sox9 and Scleraxis, promoted apoptosis via up-regulation of Bak1, and induced cell senescence, by arresting progenitors at the S phase and upregulating the expression of p21. Expression of Uhrf genes in vivo was positively modulated by FGF signaling. In the micromass culture assay Uhrf1 was down-regulated as the progenitors lost stemness and differentiated into cartilage. Together, our findings emphasize the importance of tuning the balance between cell differentiation and cell stemness as a central step in the initiation of the so-called ?embryonic programmed cell death? and suggest that the structural organization of the chromatin, via epigenetic modifications, may be a precocious and critical factor in these regulatory events.Funding: We thank Montse Fernandez Calderon, Susana Dawalibi, and Sonia Perez Mantecon, for excellent technical assistance. This work was supported by a Grant (BFU2017-84046-P) from the Spanish Science and Innovation Ministry to J.A.M

DNA damage precedes apoptosis during the regression of the interdigital tissue in vertebrate embryos

DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of ?H2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage. The relative distribution of cells ?H2AX-only positive, TUNEL-only positive, and cells double positive for both markers is consistent with a sequence of degenerative events starting by damage of the DNA. In support of this interpretation, the relative number of ?H2AX-only cells increases after caspase inhibition while the relative number of TUNELonly cells increases after inhibition of ATM. Furthermore, cultured interdigits survived and maintained intense chondrogenic potential, even at advanced stages of degeneration, discarding a previous commitment to die. Our findings support a new biological paradigm considering embryonic cell death secondary to genotoxic stimuli, challenging the idea that considers physiological cell death a cell suicide regulated by an internal death clock that pre-programmes degeneration

Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4-antigen electrovaccination

Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan-4 (hCSPG4)-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6-, 12-, 18- and 24-month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78–1694, 8 of 23 dogs alive] and 6-, 12-, 18- and 24-month disease-free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI 477 days, range 50–1694). Non-vaccinated dogs showed 6-, 12-, 18- and 24-month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST 200 days, range 75–1507, 1 of 19 dogs alive) and 6-, 12-, 18- and 24-month DFI rate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI 180 days, range 38–1250). Overall survival and DFI of vaccinated dogs was longer in those <20 kg. In vaccinated and non-vaccinated dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively

Transforming growth factor beta signaling: The master sculptor of fingers

Transforming growth factor beta (TGF?) constitutes a large and evolutionarily conserved superfamily of secreted factors that play essential roles in embryonic development, cancer, tissue regeneration, and human degenerative pathology. Studies of this signaling cascade in the regulation of cellular and tissue changes in the three-dimensional context of a developing embryo have notably advanced in the understanding of the action mechanism of these growth factors. In this review, we address the role of TGF? signaling in the developing limb, focusing on its essential function in the morphogenesis of the autopod. As we discuss in this work, modern mouse genetic experiments together with more classical embryological approaches in chick embryos, provided very valuable information concerning the role of TGF? and Activin family members in the morphogenesis of the digits of tetrapods, including the formation of phalanxes, digital tendons, and interphalangeal joints. We emphasize the importance of the Activin and TGF? proteins as digit inducing factors and their critical interaction with the BMP signaling to sculpt the hand and foot morphology

A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice.

Choroideremia (CHM) is a rare X-linked disease leading to progressive retinal degeneration resulting in blindness. The disorder is caused by mutations in the CHM gene encoding REP-1 protein, an essential component of the Rab geranylgeranyltransferase (GGTase) complex. In the present study, we evaluated a multi-technique analysis algorithm to describe the mutational spectrum identified in a large cohort of cases and further correlate CHM variants with phenotypic characteristics and biochemical defects of choroideremia patients. Molecular genetic testing led to the characterization of 36 out of 45 unrelated CHM families (80%), allowing the clinical reclassification of four CHM families. Haplotype reconstruction showed independent origins for the recurrent p.Arg293* and p.Lys178Argfs*5 mutations, suggesting the presence of hotspots in CHM, as well as the identification of two different unrelated events involving exon 9 deletion. No certain genotype-phenotype correlation could be established. Furthermore, all the patients´ fibroblasts analyzed presented significantly increased levels of unprenylated Rabs proteins compared to control cells; however, this was not related to the genotype. This research demonstrates the major potential of the algorithm proposed for diagnosis. Our data enhance the importance of establish a differential diagnosis with other retinal dystrophies, supporting the idea of an underestimated prevalence of choroideremia. Moreover, they suggested that the severity of the disorder cannot be exclusively explained by the genotype

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Defining the Earliest Transcriptional Steps of Chondrogenic Progenitor Specification during the Formation of the Digits in the Embryonic Limb

The characterization of genes involved in the formation of cartilage is of key importance to improve cell-based cartilage regenerative therapies. Here, we have developed a suitable experimental model to identify precocious chondrogenic events in vivo by inducing an ectopic digit in the developing embryo. In this model, only 12 hr after the implantation of a Tgfβ bead, in the absence of increased cell proliferation, cartilage forms in undifferentiated interdigital mesoderm and in the course of development, becomes a structurally and morphologically normal digit. Systematic quantitative PCR expression analysis, together with other experimental approaches allowed us to establish 3 successive periods preceding the formation of cartilage. The “pre-condensation stage”, occurring within the first 3 hr of treatment, is characterized by the activation of connective tissue identity transcriptional factors (such as Sox9 and Scleraxis) and secreted factors (such as Activin A and the matricellular proteins CCN-1 and CCN-2) and the downregulation of the galectin CG-8. Next, the “condensation stage” is characterized by intense activation of Smad 1/5/8 BMP-signaling and increased expression of extracellular matrix components. During this period, the CCN matricellular proteins promote the expression of extracellular matrix and cell adhesion components. The third period, designated the “pre-cartilage period”, precedes the formation of molecularly identifiable cartilage by 2–3 hr and is characterized by the intensification of Sox 9 gene expression, along with the stimulation of other pro-chondrogenic transcription factors, such as HifIa. In summary, this work establishes a temporal hierarchy in the regulation of pro-chondrogenic genes preceding cartilage differentiation and provides new insights into the relative roles of secreted factors and cytoskeletal regulators that direct the first steps of this process in vivo

The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken

Digits shape is sculpted by interdigital programmed cell death during limb development. Here, we show that DNA breakage in the periphery of 5-methylcytosine nuclei foci of interdigital precursors precedes cell death. These cells showed higher genome instability than the digit-forming precursors when exposed to X-ray irradiation or local bone morphogenetic protein (BMP) treatments. Regional but not global DNA methylation differences were found between both progenitors. DNA-Methyl-Transferases (DNMTs) including DNMT1, DNMT3B and, to a lesser extent, DNMT3A, exhibited well-defined expression patterns in regions destined to degenerate, as the interdigital tissue and the prospective joint regions. Dnmt3b functional experiments revealed an inverse regulation of cell death and cartilage differentiation, by transcriptional regulation of key genes including Sox9, Scleraxis, p21 and Bak1, via differential methylation of CpG islands across their promoters. Our findings point to a regulation of cell death versus chondrogenesis of limb skeletal precursors based on epigenetic mechanisms.We thank Prof. Miguel Lafarga for helpful comments and advice. We thank Dr Jose E Gomez-Arozamena for helping us with the irradiation experiments. We are grateful to Montse Fernandez Calderon, Susana Dawalibi, and Sonia Perez Mantecon, for excellent technical assistance. This work was supported by a Grant (BFU2017–84046-P) from the Spanish Science and Innovation Ministry to JAM. C.S.F is recipient of a FPI grant (BES-2015–074267)

Understanding the role of growth factors in modulating stem cell tenogenesis

Current treatments for tendon injuries often fail to fully restore joint biomechanics leading to the recurrence of symptoms, and thus resulting in a significant health problem with a relevant social impact worldwide. Cell-based approaches involving the use of stem cells might enable tailoring a successful tendon regeneration outcome. As growth factors (GFs) powerfully regulate the cell biological response, their exogenous addition can further stimulate stem cells into the tenogenic lineage, which might eventually depend on stem cells source. In the present study we investigate the tenogenic differentiation potential of human- amniotic fluid stem cells (hAFSCs) and adipose-derived stem cells (hASCs) with several GFs associated to tendon development and healing; namely, EGF, bFGF, PDGF-BB and TGF-β1. Stem cells response to biochemical stimuli was studied by screening of tendon-related genes (collagen type I, III, decorin, tenascin C and scleraxis) and proteins found in tendon extracellular matrix (ECM) (Collagen I, III, and Tenascin C). Despite the fact that GFs did not seem to influence the synthesis of tendon ECM proteins, EGF and bFGF influenced the expression of tendon-related genes in hAFSCs, while EGF and PDGF-BB stimulated the genetic expression in hASCs. Overall results on cellular alignment morphology, immunolocalization and PCR analysis indicated that both stem cell source can be biochemically induced towards tenogenic commitment, validating the potential of hASCs and hAFSCs for tendon regeneration strategies.Authors thank the Portuguese Foundation for Science and Technology (FCT) for the research project BIBS (PTDC/CVT/102972/2008) and for the post-doc fellowship grant: SFRH/BPD/86775/2012. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript