The molecular toolkit pertaining to superorganisms

Our results identify Mthl5 as a new Hh signalling pathway modulator in Drosophila and suggest that many GPCRs may crosstalk with the Hh pathway in mammals.To gain a deeper understanding of pancreatic β-cell development, we used iterative weighted gene correlation network analysis to calculate a gene co-expression network (GCN) from 11 temporally and genetically defined murine cell populations. The GCN, which contained 91 distinct modules, was then used to gain three new biological insights. First, we found that the clustered protocadherin genes are differentially expressed during pancreas development. Pcdhγ genes are preferentially expressed in pancreatic endoderm, Pcdhβ genes in nascent islets, and Pcdhα genes in mature β-cells. Second, after extracting sub-networks of transcriptional regulators for each developmental stage, we identified 81 zinc finger protein (ZFP) genes that are preferentially expressed during endocrine specification and β-cell maturation. Third, we used the GCN to select three ZFPs for further analysis by CRISPR mutagenesis of mice. Zfp800 null mice exhibited early postnatal lethality, and at E18.5 their pancreata exhibited a reduced number of pancreatic endocrine cells, alterations in exocrine cell morphology, and marked changes in expression of genes involved in protein translation, hormone secretion and developmental pathways in the pancreas. Together, our results suggest that developmentally oriented GCNs have utility for gaining new insights into gene regulation during organogenesis.In humans, the combination of all sex-specific genetic, epigenetic, and hormonal influences of biologic sex produces different in vivo environments for male and female cells. We dissect how these influences of sex modify the pharmacokinetics and pharmacodynamics of multiple drugs and provide examples for common drugs acting on specific organ systems. We also discuss how gender of physicians and patients may influence the therapeutic response to drugs. We aim to highlight sex as a genetic modifier of the pharmacological response to drugs, which should be considered as a necessary step toward precision medicine that will benefit men and women. SIGNIFICANCE STATEMENT This study discusses the influences of biologic sex on the pharmacokinetics and pharmacodynamics of drugs and provides examples for common drugs acting on specific organ systems. This study also discusses how gender of physicians and patients influence the therapeutic response to drugs.An adult old cyclist presented to our hospital and was referred to the orthopaedic department with a left shoulder posterolateral acromion avulsion fracture and subacromial impingement demonstrated on X-ray and CT. This highly unusual fracture pattern was treated by open reduction and internal fixation with cannulated screws and a tension band suture technique. This fracture went onto successful union with full range of motion and good patient-reported outcome measures by the Oxford Shoulder Score at 3 months. Informed consent was taken for the following case report.A 30-year-old, multiparous widow, with postpolio residual paralysis, presented with complaints of dull aching abdominal pain for 15 days. Ultrasound showed a mixed echogenic right adnexal mass with free fluid in the pelvis and abdomen. CT abdomen and pelvis revealed partially defined peripherally enhancing collection in lower abdomen and right adnexa suggestive of tubo-ovarian abscess. There was mild ileal wall thickening and few enlarged mesenteric lymph nodes. Ascitic fluid did not show acid fast bacilli and cultures were sterile. Extensive diagnostic laboratory work was done which was inconclusive. Diagnostic laparoscopy could not be performed due to non-availability of elective operation theatre in the COVID-19 pandemic. Presumptive extrapulmonary tuberculosis was clinically and radiologically diagnosed. She was started on daily anti tuberculosis treatment. This case shows us the importance of imaging as a diagnostic tool and as an alternative for laparoscopy in COVID-19 pandemic to diagnose abdomino-pelvic tuberculosis.Cancer metastasis to the oral and maxillofacial region is uncommon, and metastasis to the mandibular condyle is considered rare. We present a case of a 56-year-old woman with a history of invasive ductal cell carcinoma of the right breast, 10 years in remission, presenting with a 6-month history of symptoms typical of temporomandibular joint (TMJ) dysfunction. Imaging revealed an osteolytic lesion of her right TMJ and subsequent open biopsy confirmed the diagnosis of metastatic breast cancer. Despite the rarity of metastatic cancer to the head and neck region, it is still important for clinicians from both medical and dental backgrounds to consider this differential diagnosis, particularly in patients with a history of hormonal positive subtype of breast cancer. Given that bony metastasis can manifest even 10 years after initial diagnosis, surveillance which includes examination of the head and neck region is important, and may include routine plain-film imaging surveillance with an orthopantomogram (OPG).We describe a case of retrovesical liposarcoma in a male patient with concurrent COVID-19. A 50-year-old man had lower urinary tract symptoms and dull pain along his right gluteus. Due to COVID-19 infection, management was delayed. During self-isolation, the patient developed urinary retention and his pain level was an eight on the Visual Analogue Scale. A urinary catheter and an epidural catheter were inserted without any difficulty. Abdominal-pelvic MRI revealed a retrovesical mass suspected of liposarcoma with clear borders from surrounding organs. Following two consecutive negative SARS-CoV-2 PCR tests, we proceeded with surgery. Histopathology was dedifferentiated liposarcoma. Postoperatively, the patient suffered reactivation of COVID-19, and he was eventually discharged after two consecutive negative results on the PCR test on Post Operative Day (POD)-10. selleck Retrovesical dedifferentiated liposarcoma is rare and considered as high-grade liposarcoma. Although surgery may exacerbate COVID-19 infection, surgical resection of symptomatic high-grade sarcoma is prioritised and performed as soon as no infection detected.