Further Expansion of the Mutational Spectrum of 3MC Syndrome: A Novel MASP1 Pathogenic Variant in a Male Patient

The 3MC syndrome is a rare autosomal recessive syndrome characterized by facial dysmorphism, multiple congenital abnormalities, and postnatal growth deficiency. Hypertelorism, blepharophimosis, blepharoptosis, high-arched eyebrows, and cleft lip/palate compose the facial gestalt, which is the key component for diagnosing the syndrome. Biallelic pathogenic variants in <i>MASP1, COLEC11</i>, and <i>COLEC10</i> are responsible for 3MC syndrome in which both genotypic and phenotypic heterogeneity is described. To date, 16 homozygous/compound heterozygous pathogenic variations in 27 patients from 22 families have been reported in the <i>MASP1</i> gene associated with 3MC syndrome. Here, we report a male patient with a novel homozygous pathogenic variant in <i>MASP1</i> in whom macrocephaly, pyloric stenosis, and prenatal findings including polyhydramnios, aortic dilatation, and intracranial cysts beside the distinctive facial features were detected. Reporting detailed clinical and molecular findings in patients is pivotal in terms of enabling the phenotypic and genotypic spectrum of this rare syndrome to be delineated.

Involvement of a FAD-linked oxidase RSc0454 for expression of the type III secretion system and pathogenicity in Ralstonia solanacearum

Ralstonia solanacearum RSc0454 is predicated as a FAD-linked oxidase based on protein homologies, while containing distinct domains of LDH and SDH. Current study demonstrates RSc0454 exhibits LDH activity and is essential for pathogenicity. Here, we characterized involvement of RSc0454 on bacterial growth and expression of the T3SS in R. solanacearum. RSc0454 mutant grew normally in rich medium but grew faintly in host plants, and failed to grow in minimal medium. Supplementary succinate, but not lactate, substantially restored some phenotypes of RSc0454 mutants, including faint growth in plants, diminished growth in minimal medium, and lost pathogenicity. The T3SS Expression is directly controlled by a master regulator HrpB, and HrpG and PrhG positively regulate hrpB expression in parallel ways. Deletion of RSc0454 substantially reduced expression levels of hrpB and T3SS both in vitro and in planta. Moreover, RSc0454 is revealed to be required for the T3SS expression via HrpG and PrhG, but through novel pathway, and impaired expression of these genes was not due to growth deficiency of RSc0454 mutants. RSc0454 is suggested to be important for redox balance inside cells and supplementary NADH partially restored diminished growth of RSc0454 mutant in minimal medium at presence of succinate at some moderate concentrations, indicating that unbalanced redox in RSc0454 mutant might be responsible for its no growth in minimal medium. All taken together, these results provide novel insights into understanding of various biological functions of this FAD-linked oxidase RSc0454 and involvement of the redox balance on expression of the T3SS in R. solanacearum.

Clinical heterogeneity of Kabuki syndrome in a cohort of Italian patients and review of the literature

Kabuki syndrome (KS) is a well-recognized disorder characterized by postnatal growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability. The syndrome is caused by KMT2D gene mutations or less frequently KDM6A gene mutations or deletions. We report a systematic evaluation of KS patients from Campania region of Italy; data were also compared with literature ones. We collected data of 15 subjects (8 males and 7 females with age range 10–26 years; mean age 16.9 years) with confirmed diagnosis of KS, representing the entire cohort of patients from Campania Region. Each patient performed biochemical testing and instrumental investigation. Neuro-intellectual development, cranio-facial dysmorphisms, and multisystem involvement data were collected retrospectively. For each category, type of defects and frequency of the anomalies were analyzed. Our observation shows that KS patients from Campania region have some particular and previously underscored, neurological and immunological findings. We found high prevalence of EEG’s abnormalities (43%) and MRI brain abnormalities (60%). Microcephaly resulted more common in our series (33%), if compared with major cohorts described in literature. Biochemical features of immunodeficiency and autoimmune diseases including thyroid autoimmunity, polyserositis, and vitiligo were observed with high prevalence (54.5%). Low immunoglobulins levels were a frequent finding. Lymphocyte class investigation showed significantly reduced CD8 levels in one patient.Conclusions: These data confirm great heterogeneity of clinical manifestations in KS and suggest to introduce further clinical diagnostic criteria in order to perform a correct and precocious diagnosis. What is Known• Kabuki syndrome is characterized by growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability• Immune dysfunction is a common finding but autoimmune diseases are rarely seen• Neurological features are common What is New• Some particular facial features could help gestalt diagnosis (hypertelorism, broad nasal bridge, micrognathia, tooth agenesis, cutaneous haemangiomas and strabismus)• Higher prevalence of autoimmune disorders than previously reported• Particular neurological features are present in this cohort (EEG and MRI brain abnormalities)

A microbiota–root–shoot circuit favours Arabidopsis growth over defence under suboptimal light

Bidirectional root–shoot signalling is probably key in orchestrating stress responses and ensuring plant survival. Here, we show that Arabidopsis thaliana responses to microbial root commensals and light are interconnected along a microbiota–root–shoot axis. Microbiota and light manipulation experiments in a gnotobiotic plant system reveal that low photosynthetically active radiation perceived by leaves induces long-distance modulation of root bacterial communities but not fungal or oomycete communities. Reciprocally, microbial commensals alleviate plant growth deficiency under low photosynthetically active radiation. This growth rescue was associated with reduced microbiota-induced aboveground defence responses and altered resistance to foliar pathogens compared with the control light condition. Inspection of a set of A. thaliana mutants reveals that this microbiota- and light-dependent growth–defence trade-off is directly explained by belowground bacterial community composition and requires the host transcriptional regulator MYC2. Our work indicates that aboveground stress responses in plants can be modulated by signals from microbial root commensals.

Oral findings in Coffin-Siris syndrome: A case report

This paper reports the oral health approach of a child with Coffin-Siris syndrome. This syndrome is a multisystem congenital anomaly caused by mutations in genes of BRG-1-associated factors complex. Individuals with this syndrome have been described with hypoplasia or aplasia of the fifth digit nails or phalanges. Other features include growth deficiency, developmental and intellectual delay, and other organ-system abnormalities. Clinical examination revealed gingival hyperplasia in the upper arch, dental biofilm, and dental caries on the lower deciduous and permanent molars. Guidelines on oral hygiene and dietary habits were provided to the guardians, and tooth extraction and restoration with glass-ionomer cement were performed. This case suggests that these patients require home care and periodic dental consultations for preventive and systematic dental treatment and quality of life improvement. The patient is being monitored, and her oral condition has improved.

Harnessing Escherichia coli for bio-based production of formate under pressurized H2 and CO2 gases

ABSRACTEscherichia coli is gram-negative bacterium that is a workhorse of the biotechnology industry. The organism has a flexible metabolism and can perform a mixed-acid fermentation under anaerobic conditions. Under these conditions E. coli synthesises a formate hydrogenlyase isoenzyme (FHL-1) that can generate molecular hydrogen and carbon dioxide from formic acid. The reverse reaction is hydrogen-dependent carbon dioxide reduction (HDCR), which has exciting possibilities in bio-based carbon capture and storage if it can be harnessed. In this study, an E. coli host strain was optimised for the production of formate from H2 and CO2 during bacterial growth in a pressurised batch bioreactor. A host strain was engineered that constitutively produced the FHL-1 enzyme and incorporation of tungsten in to the enzyme, in place of molybdenum, helped poise the reaction in the HDCR direction. The engineered E. coli strain showed an ability to grow under fermentative conditions while simultaneously producing formate from gaseous H2 and CO2 supplied in the bioreactor. However, while a sustained pressure of 10 bar N2 had no adverse effect on cell growth, when the culture was placed at or above 4 bar pressure of a H2:CO2 mixture then a clear growth deficiency was observed. Taken together, this work demonstrates that growing cells can be harnessed to hydrogenate carbon dioxide and provides fresh evidence that the FHL-1 enzyme may be intimately linked with bacterial energy metabolism.

Physical development of teenagers remaining without parental care

Preserving and strengthening the health of orphaned children and children left without parental care is of great medical, social and public significance. The aim of the study. Assess the health status of adolescents without parental care. Material and methods. The object of the study was teenagers left without parental care (adolescents from 10 to 18 years old). The total sample size was 2,499 adolescents. Assessment of physical development was carried out on the hardware-software complex "Health-Express". This high-tech equipment, developed by the "Kazakh-Russian Medical University". Results and discussion. The authors have shown that at the present stage, there are negative trends in the number of children with disharmonious physical development due to lack of body length. For example, the frequency of identified disharmonious physical development in the age group 10-14 years was 71.8% and in the first childhood group 28.2%. The main reason for disharmonious physical development was a growth deficiency and moderate body weight deficiency. Conclusions. The main reason for the disharmonious physical development of adolescents left without parental care was a deficit in height and a moderate deficit in body weight. Keywords: physical development, teenagers, orphans, "Health-Express", body mass index, body length.

Pattern of Morphological Variability in Unrepaired Unilateral Clefts With and Without Cleft Palate May Suggest Intrinsic Growth Deficiency

In individuals with cleft lip and palate (CLP) an iatrogenic effect of operations on subsequent maxillary growth is well-known. Much less is known about the association between occurrence of CLP and intrinsic growth deficiency of the maxillofacial complex. The aim of this study was to compare morphological variability in subjects with unilateral cleft lip and alveolus/palate and unaffected controls using geometric morphometric methods. The research hypothesis was that if subjects with unrepaired unilateral CLP have intrinsic growth deficiency, the pattern of their craniofacial growth variation may differ from that in unaffected individuals. Lateral cephalograms were available of three groups of the same ethnic background (Proto-Malayid): (a) non-syndromic unrepaired unilateral complete cleft lip, alveolus, and palate (UCLP), N = 66, mean age 24.5 years (b) non-syndromic unrepaired unilateral complete cleft lip and alveolus (UCLA), N = 177, mean age 23.7 years, and (c) NORM (N = 50), mean age 21.2 years without a cleft. Using geometric morphometrics shape variability in groups and shape differences between groups was analyzed. Principal component analysis (PCA) was used to examine shape variability, while differences between groups and sexes were evaluated with canonical variate analysis. Sexual dimorphism was evaluated with discriminant function analysis (DA). Results showed that in comparison to NORM subjects, shape variability in UCLA and UCLP is more pronounced in the antero-posterior than in vertical direction. Pairwise comparisons of the mean shape configurations (NORM vs. UCLA, NORM vs. UCLP, and UCLA vs. UCLP) revealed significant differences between cleft and non-cleft subjects. The first canonical variate (CV1, 68.2% of variance) demonstrated that differences were associated with maxillary shape and/or position and incisor inclination, while in females, the CV1 (69.2% of variance) showed a combination of differences of “maxillary shape and/or position and incisor inclination” and inclination of the cranial base. Shape variability demonstrated considerable differences in subjects with UCLA, UCLP, and NORM. Moreover, in subjects with a cleft, within-sample variability was more pronounced in the antero-posterior direction, while in non-cleft subjects, within-sample variability was more pronounced in the vertical direction. These findings may suggest that subjects with unilateral clefts have intrinsic growth impairment affecting subsequent facial development.

Overexpression of BplERD15 Enhances Drought Tolerance in Betula platyphylla Suk.

In this study, we report the cloning and functional characterization of an early responsive gene, BplERD15, from Betula platyphylla Suk to dehydration. BplERD15 is located in the same branch as Morus indica Linnaeus ERD15 and Arabidopsis Heynh ERD15 in the phylogenetic tree built with ERD family protein sequences. The tissue-specific expression patterns of BplERD15 were characterized using qRT-PCR and the results showed that the transcript levels of BplERD15 in six tissues were ranked from the highest to the lowest levels as the following: mature leaves (ML) > young leaves (YL) > roots (R) > buds (B) > young stems (YS) > mature stems (MS). Multiple drought experiments were simulated by adding various osmotica including polyethylene glycol, mannitol, and NaCl to the growth media to decrease their water potentials, and the results showed that the expression of BplERD15 could be induced to 12, 9, and 10 folds, respectively, within a 48 h period. However, the expression level of BplERD15 was inhibited by the plant hormone abscisic acid in the early response and then restored to the level of control. The BplERD15 overexpression (OE) transgenic birch lines were developed and they did not exhibit any phenotypic anomalies and growth deficiency under normal condition. Under drought condition, BplERD15-OE1, 3, and 4 all displayed some drought tolerant characteristics and survived from the drought while the wild type (WT) plants withered and then died. Analysis showed that all BplERD15-OE lines had significant lower electrolyte leakage levels as compared to WT. Our study suggests that BplERD15 is a drought-responsive gene that can reduce mortality under stress condition.